en-usFluid ManagementOptimal salt and water balance after dialysis is a primary goal of renal replacement therapy (RRT). Inadequate fluid management leads to significant morbidity and mortality from complications of hypervolemia and hypovolemia. Fluid management is an area ripe for innovation that has a significant impact on the quality of life of people with kidney failure. It is a critical part of renal replacement therapy, and too much or too little volume can result in severe complications. Despite the unmet patient need, there are no approved devices to objectively measure volume status. There are many techniques available, yet clinicians lack technologies to accurately assess volume status. Therefore, the clinical approach to volume assessment is subjective and involves trial and error. <p></p><p> </p><p> This collection of articles from JASN and CJASN has been curated to represent the top articles published in the last two years on fluid management including blood volume measuring and monitoring, biomarkers and more.</p>Thu, 25 Apr 2024 09:20:10 GMThttp://cct.highwire.org/feeds/asn/fluid-management.rss- Healthcare resource utilization and costs of persistent severe AKI among hospitalized Stage 2/3 AKI patientsBackground: Persistent severe acute kidney injury (PS-AKI) is associated with worse clinical outcomes, but there is no data on costs of PS-AKI. We compared costs and healthcare resource utilization (HRU) for inpatients with PS-AKI vs. not-persistent severe AKI (NPS-AKI) overall and by ICU use. Methods: This retrospective observational study included 126,528 adult US inpatients in the PINC AI Healthcare Database (PHD), discharged from January 1, 2017, to December 31, 2019, with KDIGO stage 2 or 3 AKI (by serum creatinine [SCr] criteria) during hospitalization, length of stay (LOS) ≥3 days, and ≥3 SCr measurements. Patients were categorized as PS-AKI (defined as stage 3 AKI lasting ≥3 days or with death within 3 days or stage 2/3 AKI (by SCr criteria) with dialysis within 3 days), or NPS-AKI. Generalized linear model regression compared LOS and costs during index hospitalization (total cohort) and 30-days post-discharge (survivors of index hospitalization), adjusted for patient, hospital, and clinical characteristics. Results: Among 126,528 patients with stage 2/3 AKI, 30,916 developed PS-AKI. In adjusted models, compared to NPS-AKI, patients with PS-AKI had 32% longer total LOS (+3.3 days), 45% longer ICU LOS (+ 2.6 days), 46% higher total costs (+$13,143), 58% higher ICU costs (+$15,908), and during 30-days post-discharge, had 13% longer readmission LOS (+1.0 day), 22% higher readmission costs (+$4049), and 12% higher outpatient costs (+$206) (p<0.005 for all). Relative LOS and cost differences for PS-AKI vs. NPS-AKI were similar for ICU (n=57,947) and non-ICU (n=68,581) patients. Conclusions: Among hospitalized stage 2/3 AKI patients, PS-AKI was associated with significantly longer LOS and higher costs during index hospitalization and 30-days post-discharge, overall, and in ICU and non-ICU patients. Preventing PS-AKI among patients with stage 2/3 AKI may reduce hospital LOS and costs.Rachel_Mackey@premierinc.com10.34067/KID.0005552022Sun, 18 Dec 2022 09:38:34 GMT-08:00Healthcare resource utilization and costs of persistent severe AKI among hospitalized Stage 2/3 AKI patientsBackground: Persistent severe acute kidney injury (PS-AKI) is associated with worse clinical outcomes, but there is no data on costs of PS-AKI. We compared costs and healthcare resource utilization (HRU) for inpatients with PS-AKI vs. not-persistent severe AKI (NPS-AKI) overall and by ICU use. Methods: This retrospective observational study included 126,528 adult US inpatients in the PINC AI Healthcare Database (PHD), discharged from January 1, 2017, to December 31, 2019, with KDIGO stage 2 or 3 AKI (by serum creatinine [SCr] criteria) during hospitalization, length of stay (LOS) ≥3 days, and ≥3 SCr measurements. Patients were categorized as PS-AKI (defined as stage 3 AKI lasting ≥3 days or with death within 3 days or stage 2/3 AKI (by SCr criteria) with dialysis within 3 days), or NPS-AKI. Generalized linear model regression compared LOS and costs during index hospitalization (total cohort) and 30-days post-discharge (survivors of index hospitalization), adjusted for patient, hospital, and clinical characteristics. Results: Among 126,528 patients with stage 2/3 AKI, 30,916 developed PS-AKI. In adjusted models, compared to NPS-AKI, patients with PS-AKI had 32% longer total LOS (+3.3 days), 45% longer ICU LOS (+ 2.6 days), 46% higher total costs (+$13,143), 58% higher ICU costs (+$15,908), and during 30-days post-discharge, had 13% longer readmission LOS (+1.0 day), 22% higher readmission costs (+$4049), and 12% higher outpatient costs (+$206) (p<0.005 for all). Relative LOS and cost differences for PS-AKI vs. NPS-AKI were similar for ICU (n=57,947) and non-ICU (n=68,581) patients. Conclusions: Among hospitalized stage 2/3 AKI patients, PS-AKI was associated with significantly longer LOS and higher costs during index hospitalization and 30-days post-discharge, overall, and in ICU and non-ICU patients. Preventing PS-AKI among patients with stage 2/3 AKI may reduce hospital LOS and costs.Koyner, Jay L.Mackey, Rachel H.Rosenthal, Ning A.Carabuena, Leslie A.Kampf, PatrickEcheverri, JorgeMcPherson, PaulBlackowicz, Michael J.Rodriguez, ToniSanghani, Aarti R.Textoris, Julien2022-12-18T21:38:34-08:00doi:10.34067/KID.0005552022hwp:resource-id:kidney360;KID.0005552022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360costs, healthcare resource utilization, severe acute kidney injury, persistent severe acute kidney injuryOriginal InvestigationOriginal Investigationother202210.34067/KID.00055520222641-76502641-76502022-12-18T21:38:34-08:00Kidney360Original Investigation10.34067/KID.0005552022
- Zinc Deficiency: Potential Hidden Driver of the Detrimental Cycle of Chronic Kidney Disease and HypertensionGlobally, over 103 million individuals are afflicted by chronic kidney disease (CKD), a silent killer claiming the lives of 1.2 million people annually. CKD is characterized by 5 progressive stages, in which dialysis and kidney transplant are life-saving routes for patients with end-stage kidney failure. While kidney damage impairs kidney function and derails blood pressure regulation, uncontrolled hypertension accelerates the development and progression of CKD. Zinc (Zn) deficiency has emerged as a potential hidden driver within this detrimental cycle of CKD and hypertension. This review article will 1) highlight mechanisms of Zn procurement and trafficking, 2) provide evidence that urinary Zn wasting can fuel Zn deficiency in CKD, 3) discuss how Zn deficiency can accelerate the progression of hypertension and kidney damage in CKD, and 4) consider Zn supplementation as an exit strategy with the potential to rectify the course of hypertension and CKD progression.clintoria.williams@wright.edu10.34067/KID.0007812021Sun, 18 Dec 2022 09:38:34 GMT-08:00Zinc Deficiency: Potential Hidden Driver of the Detrimental Cycle of Chronic Kidney Disease and HypertensionGlobally, over 103 million individuals are afflicted by chronic kidney disease (CKD), a silent killer claiming the lives of 1.2 million people annually. CKD is characterized by 5 progressive stages, in which dialysis and kidney transplant are life-saving routes for patients with end-stage kidney failure. While kidney damage impairs kidney function and derails blood pressure regulation, uncontrolled hypertension accelerates the development and progression of CKD. Zinc (Zn) deficiency has emerged as a potential hidden driver within this detrimental cycle of CKD and hypertension. This review article will 1) highlight mechanisms of Zn procurement and trafficking, 2) provide evidence that urinary Zn wasting can fuel Zn deficiency in CKD, 3) discuss how Zn deficiency can accelerate the progression of hypertension and kidney damage in CKD, and 4) consider Zn supplementation as an exit strategy with the potential to rectify the course of hypertension and CKD progression.Ume, Adaku C.Wenegieme, Tara-YesomiAdams, Danielle N.Adesina, Sherry E.Williams, Clintoria R.2022-12-18T21:38:34-08:00doi:10.34067/KID.0007812021hwp:resource-id:kidney360;KID.0007812021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Zinc, Zinc wasting, Kidney damage, Zinc deficiency, Hypertension, Chronic Kidney Disease, Zinc supplementationBasic Science for CliniciansBasic Science for Cliniciansother202210.34067/KID.00078120212641-76502641-76502022-12-18T21:38:34-08:00Kidney360Basic Science for Clinicians10.34067/KID.0007812021
- Current Status of Renal Xenotransplantation and Next StepsRenal transplantation is the preferred treatment of ESRD, but the shortage of suitable donor kidneys from the cadaver pool means that many patients with ESRD will not receive a kidney transplant. Xenotransplantation has long represented a solution to the kidney shortage, but the occurrence of antibody-mediated rejection has precluded its clinical development. Developments in: somatic cell nuclear transfer in pigs, gene editing tools have led to the creation of new donor pigs with greatly improved crossmatches to patients. In addition, improvements in preclinical kidney xenotransplant survival using new anti-CD40/CD154 based immunosuppression, have pushed xenotransplantation to the point where it is reasonable to consider initiating a clinical trial to evaluate this potential therapy in patients.ajt135@miami.edu10.34067/KID.0007152021Sun, 18 Dec 2022 09:38:34 GMT-08:00Current Status of Renal Xenotransplantation and Next StepsRenal transplantation is the preferred treatment of ESRD, but the shortage of suitable donor kidneys from the cadaver pool means that many patients with ESRD will not receive a kidney transplant. Xenotransplantation has long represented a solution to the kidney shortage, but the occurrence of antibody-mediated rejection has precluded its clinical development. Developments in: somatic cell nuclear transfer in pigs, gene editing tools have led to the creation of new donor pigs with greatly improved crossmatches to patients. In addition, improvements in preclinical kidney xenotransplant survival using new anti-CD40/CD154 based immunosuppression, have pushed xenotransplantation to the point where it is reasonable to consider initiating a clinical trial to evaluate this potential therapy in patients.Tector, A. JosephAdams, Andrew B.Tector, Matt2022-12-18T21:38:34-08:00doi:10.34067/KID.0007152021hwp:resource-id:kidney360;KID.0007152021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Xenotransplantation, Basic ScienceReview ArticleReview Articleother202210.34067/KID.00071520212641-76502641-76502022-12-18T21:38:34-08:00Kidney360Review Article10.34067/KID.0007152021
- Risk and Timing of De Novo Sepsis in Critically Ill Children Following Acute Kidney InjuryBackground: Acute kidney injury (AKI) is common among critically ill children and is associated with an increased risk for de novo infection, however little is known about the epidemiology and temporal relationship between AKI and AKI-associated infection in this cohort. Methods: We conducted a single-center retrospective cohort study of children admitted to the pediatric and cardiac ICUs at a tertiary pediatric care center. The relationship between non-septic AKI and the development of hospital-acquired sepsis was assessed using Cox proportional-hazards models using AKI as a time-varying covariate. Results: Among the 5695 children included in the study, AKI occurred in 20.2% from ICU admission through 30 days. Hospital-acquired sepsis occurred twice as often among children with AKI compared to those without AKI (10.1% vs. 4.6%) with an adjusted hazard ratio of 1.42 (95% CI 1.12-1.81). Among the 117 children who developed sepsis following AKI, 80.3% developed sepsis within 7 days and 96.6% within 14 days of AKI onset, with a median time from AKI onset to sepsis of 2.6 days (IQR 1.5-4.7). When assessing change in risk over time, the hazard rate for sepsis remained elevated for children with stage 3 AKI compared to children without AKI at 13.5 days following AKI onset, after which the estimation of hazard rates was limited by the number of children remaining in the hospital. Conclusions: AKI is an independent risk factor for de novo sepsis. Critically ill children with stage 3 AKI remain at increased risk for sepsis at 13.5 days following AKI onset.cle34@pitt.edu10.34067/KID.0005082022Sun, 18 Dec 2022 09:38:34 GMT-08:00Risk and Timing of De Novo Sepsis in Critically Ill Children Following Acute Kidney InjuryBackground: Acute kidney injury (AKI) is common among critically ill children and is associated with an increased risk for de novo infection, however little is known about the epidemiology and temporal relationship between AKI and AKI-associated infection in this cohort. Methods: We conducted a single-center retrospective cohort study of children admitted to the pediatric and cardiac ICUs at a tertiary pediatric care center. The relationship between non-septic AKI and the development of hospital-acquired sepsis was assessed using Cox proportional-hazards models using AKI as a time-varying covariate. Results: Among the 5695 children included in the study, AKI occurred in 20.2% from ICU admission through 30 days. Hospital-acquired sepsis occurred twice as often among children with AKI compared to those without AKI (10.1% vs. 4.6%) with an adjusted hazard ratio of 1.42 (95% CI 1.12-1.81). Among the 117 children who developed sepsis following AKI, 80.3% developed sepsis within 7 days and 96.6% within 14 days of AKI onset, with a median time from AKI onset to sepsis of 2.6 days (IQR 1.5-4.7). When assessing change in risk over time, the hazard rate for sepsis remained elevated for children with stage 3 AKI compared to children without AKI at 13.5 days following AKI onset, after which the estimation of hazard rates was limited by the number of children remaining in the hospital. Conclusions: AKI is an independent risk factor for de novo sepsis. Critically ill children with stage 3 AKI remain at increased risk for sepsis at 13.5 days following AKI onset.Formeck, Cassandra L.Feldman, RobertAlthouse, Andrew D.Kellum, John A.2022-12-18T21:38:34-08:00doi:10.34067/KID.0005082022hwp:resource-id:kidney360;KID.0005082022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360acute kidney injury, hospital-acquired sepsis, critically ill childrenOriginal InvestigationOriginal Investigationother202210.34067/KID.00050820222641-76502641-76502022-12-18T21:38:34-08:00Kidney360Original Investigation10.34067/KID.0005082022
- Sex and Racial/Ethnic Differences in Home Hemodialysis MortalityBackground: Women and minorities constitute substantial portions of the prevalent population of kidney failure patients. Little is known about sex and racial/ethnic differences in mortality among patients with kidney failure on home hemodialysis in the United States. Methods: Using the United States Renal Data System, we retrospectively evaluated a cohort of 42,849 patients who started home hemodialysis between January 1, 2005, and December 31, 2015. We examined the association of sex and race/ethnicity with the outcome of all-cause mortality using adjusted Cox proportional hazard models and logistic regression models. Results: In the study cohort, 40.4% were women, and 57.4% were White. Women on home hemodialysis had higher unadjusted death rates (26.9 vs. 22.4 per 100 person-years) as compared to men. There was no difference in adjusted all-cause mortality between men and women, but women had an 8% higher adjusted risk of all-cause mortality at one-year after initiating home hemodialysis (OR 1.08, 1.01-1.15). With regards to race/ethnicity, Hispanic, White, and Blacks had higher unadjusted death rates as compared to Asians and Native Americans (25.1 vs. 24.8 vs. 23.2 vs. 17.4 vs.16.6 per 100 person-years). There was no difference in adjusted all-cause mortality in Black, Hispanic, and Native Americans as compared to Whites, while Asians had a lower risk of all-cause mortality than did Whites (HR, 0.81; CI, 0.72-0.92). There was no difference in adjusted one-year mortality for Asian, Black, Hispanic, and Native American patients, as compared to White patients. Conclusion: Among patients undergoing home hemodialysis, women have higher one-year mortality than men, and women and men have comparable survival on long-term follow-up after adjusting for other covariates. Compared to Whites, there was no difference in adjusted survival on long-term follow-up for Blacks, Hispanics, or Native Americans, while Asians had better survival. Our results suggest the need for population-wide strategies to overcome differences in home hemodialysis care.shah2sv@ucmail.uc.edu10.34067/KID.0005712022Sun, 18 Dec 2022 08:41:27 GMT-08:00Sex and Racial/Ethnic Differences in Home Hemodialysis MortalityBackground: Women and minorities constitute substantial portions of the prevalent population of kidney failure patients. Little is known about sex and racial/ethnic differences in mortality among patients with kidney failure on home hemodialysis in the United States. Methods: Using the United States Renal Data System, we retrospectively evaluated a cohort of 42,849 patients who started home hemodialysis between January 1, 2005, and December 31, 2015. We examined the association of sex and race/ethnicity with the outcome of all-cause mortality using adjusted Cox proportional hazard models and logistic regression models. Results: In the study cohort, 40.4% were women, and 57.4% were White. Women on home hemodialysis had higher unadjusted death rates (26.9 vs. 22.4 per 100 person-years) as compared to men. There was no difference in adjusted all-cause mortality between men and women, but women had an 8% higher adjusted risk of all-cause mortality at one-year after initiating home hemodialysis (OR 1.08, 1.01-1.15). With regards to race/ethnicity, Hispanic, White, and Blacks had higher unadjusted death rates as compared to Asians and Native Americans (25.1 vs. 24.8 vs. 23.2 vs. 17.4 vs.16.6 per 100 person-years). There was no difference in adjusted all-cause mortality in Black, Hispanic, and Native Americans as compared to Whites, while Asians had a lower risk of all-cause mortality than did Whites (HR, 0.81; CI, 0.72-0.92). There was no difference in adjusted one-year mortality for Asian, Black, Hispanic, and Native American patients, as compared to White patients. Conclusion: Among patients undergoing home hemodialysis, women have higher one-year mortality than men, and women and men have comparable survival on long-term follow-up after adjusting for other covariates. Compared to Whites, there was no difference in adjusted survival on long-term follow-up for Blacks, Hispanics, or Native Americans, while Asians had better survival. Our results suggest the need for population-wide strategies to overcome differences in home hemodialysis care.Shah, SilviGupta, NupurChristianson, Annette L.Meganathan, KarthikeyanLeonard, Anthony C.Thakar, Charuhas V.2022-12-18T20:41:27-08:00doi:10.34067/KID.0005712022hwp:resource-id:kidney360;KID.0005712022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360sex, home hemodialysis, mortality, race/ethnicityOriginal InvestigationOriginal Investigationother202210.34067/KID.00057120222641-76502641-76502022-12-18T20:41:27-08:00Kidney360Original Investigation10.34067/KID.0005712022
- Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKDBackground: SGLT2 inhibitors, originally developed as glucose-lowering agents for treatment of type 2 diabetes, have been shown to have cardio- and kidney protective effects among chronic kidney disease (CKD) patients with and without diabetes. However, the mechanisms remain largely unknown. Methods: DECODE-CKD is an investigator-initiated, prospective, single-center, randomized, placebo-controlled trial evaluating the effects of 6 months of treatment with 10 mg of dapagliflozin compared with placebo on cardiac structure and function in 222 adults with CKD. The primary objective is to assess whether dapagliflozin improves LV mass index. Secondary and exploratory endpoints include changes in cardiac- and kidney markers, quality of life, depressive symptoms, and cognitive function. Conclusions: This is the first study to address the effects of SGLT2 inhibitors on cardiac structure and function in patients with CKD. The results will provide valuable insights into the mechanisms underlying the cardioprotective benefits of SGLT2 inhibitors in patients with CKD.tor.biering@gmail.com10.34067/KID.0006982022Sun, 18 Dec 2022 08:41:27 GMT-08:00Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with CKDBackground: SGLT2 inhibitors, originally developed as glucose-lowering agents for treatment of type 2 diabetes, have been shown to have cardio- and kidney protective effects among chronic kidney disease (CKD) patients with and without diabetes. However, the mechanisms remain largely unknown. Methods: DECODE-CKD is an investigator-initiated, prospective, single-center, randomized, placebo-controlled trial evaluating the effects of 6 months of treatment with 10 mg of dapagliflozin compared with placebo on cardiac structure and function in 222 adults with CKD. The primary objective is to assess whether dapagliflozin improves LV mass index. Secondary and exploratory endpoints include changes in cardiac- and kidney markers, quality of life, depressive symptoms, and cognitive function. Conclusions: This is the first study to address the effects of SGLT2 inhibitors on cardiac structure and function in patients with CKD. The results will provide valuable insights into the mechanisms underlying the cardioprotective benefits of SGLT2 inhibitors in patients with CKD.Bartholdy, Katja VuJohansen, Niklas DyrbyLandler, NinoSkaarup, Kristoffer GrundtvigJensen, JesperSchou, MortenChristensen, JacobBressendorff, IainFeldt-Rasmussen, BoVaduganathan, MuthiahSolomon, ScottHaynes, RichardPersson, FrederikRossing, PeterKøber, LarsZannad, FaiezHansen, DitteBiering-Sørensen, Tor2022-12-18T20:41:27-08:00doi:10.34067/KID.0006982022hwp:resource-id:kidney360;KID.0006982022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360rct, echocardiography, cardiology, sglt2-inhibitorsOriginal InvestigationOriginal Investigationother202210.34067/KID.00069820222641-76502641-76502022-12-18T20:41:27-08:00Kidney360Original Investigation10.34067/KID.0006982022
- Extracellular Vesicles in Kidney Diseases: Moving ForwardExtracellular vesicles (EVs) are evolving as novel cell mediators, biomarkers and therapeutic targets in kidney health and disease. They are naturally deriving from cells within but also outside the kidney and carry cargo which mirrors the state of the parent cell. Thus, they are potentially more sensitive and disease specific as biomarkers and messengers in various kidney diseases. Beside their role as novel communicators within the nephron they likely communicate between different organs affected by various kidney diseases. Study of urinary EVs can help to fill current knowledge gaps in kidney diseases. However, separation and characterization are challenged by their heterogeneity in size, shape and cargo. Fortunately, more sensitive and direct EV measuring tools are in development. Many clinical syndromes in nephrology from acute to chronic kidney and glomerular to tubular diseases have been studied. Yet validation of biomarkers in larger cohorts is warranted and simpler tools are needed. Translation from in vitro to in vivo studies is also urgently needed. The therapeutic role of urinary EVs in kidney diseases has been studied extensively in rodent models of AKI. Based on the current exponential growth of EV research the field of EV diagnostics and therapeutics is moving forward.ue2u@virginia.edu10.34067/KID.0001892022Sun, 18 Dec 2022 03:21:19 GMT-08:00Extracellular Vesicles in Kidney Diseases: Moving ForwardExtracellular vesicles (EVs) are evolving as novel cell mediators, biomarkers and therapeutic targets in kidney health and disease. They are naturally deriving from cells within but also outside the kidney and carry cargo which mirrors the state of the parent cell. Thus, they are potentially more sensitive and disease specific as biomarkers and messengers in various kidney diseases. Beside their role as novel communicators within the nephron they likely communicate between different organs affected by various kidney diseases. Study of urinary EVs can help to fill current knowledge gaps in kidney diseases. However, separation and characterization are challenged by their heterogeneity in size, shape and cargo. Fortunately, more sensitive and direct EV measuring tools are in development. Many clinical syndromes in nephrology from acute to chronic kidney and glomerular to tubular diseases have been studied. Yet validation of biomarkers in larger cohorts is warranted and simpler tools are needed. Translation from in vitro to in vivo studies is also urgently needed. The therapeutic role of urinary EVs in kidney diseases has been studied extensively in rodent models of AKI. Based on the current exponential growth of EV research the field of EV diagnostics and therapeutics is moving forward.Erdbrügger, UtaHoorn, Ewout J.Le, Thu H.Blijdorp, Charles J.Burger, Dylan2022-12-18T15:21:19-08:00doi:10.34067/KID.0001892022hwp:resource-id:kidney360;KID.0001892022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360extracellular vesicles, cellular messengers, kidney biomarker, acute and chronic kidney disease, glomerular disease, tubular disease, EV biogenesis, EV detectionBasic Science for CliniciansBasic Science for Cliniciansother202210.34067/KID.00018920222641-76502641-76502022-12-18T15:21:19-08:00Kidney360Basic Science for Clinicians10.34067/KID.0001892022
- Incremental Peritoneal Dialysis - Definition, Prescription and Clinical OutcomesIncremental peritoneal dialysis (IPD) is a strategy of renal replacement therapy that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis (PD). The clearance goals are achieved through the combination of residual kidney function (RKF) and peritoneal clearance. The dialysis prescription should be increased as the RKF declines. IPD has been associated with clinical, economic, and environmental advantages. We emphasize possible better quality of life, fewer mechanical symptoms, lower costs, slight adverse metabolic effects, and lesser plastic waste and water consumption. It has also been addressed the potential benefits for RKF preservation and the lower risk of peritonitis. There are some concerns regarding this strategy, such as inadequate clearance of uremic toxins and/or severe electrolyte disturbances due to undetected loss of RKF; lower clearance of medium-sized molecules (such as beta-2-microglobulin) which mostly depends on the total PD dwell time; and patients' reluctance to dose adjustments. Current clinical evidence is based on moderate to low quality studies and suggests that the outcomes of IPD will be at least identical to those of full dose. This review aims to discuss the definition and strategies to IPD prescription, as well as its advantages and disadvantages. It'll also be reviewed the current evidence regarding this strategy.adrianafernandes@campus.ul.pt10.34067/KID.0006902022Sun, 18 Dec 2022 03:21:19 GMT-08:00Incremental Peritoneal Dialysis - Definition, Prescription and Clinical OutcomesIncremental peritoneal dialysis (IPD) is a strategy of renal replacement therapy that is based on the prescription of a lower dose rather than the standard full dose of peritoneal dialysis (PD). The clearance goals are achieved through the combination of residual kidney function (RKF) and peritoneal clearance. The dialysis prescription should be increased as the RKF declines. IPD has been associated with clinical, economic, and environmental advantages. We emphasize possible better quality of life, fewer mechanical symptoms, lower costs, slight adverse metabolic effects, and lesser plastic waste and water consumption. It has also been addressed the potential benefits for RKF preservation and the lower risk of peritonitis. There are some concerns regarding this strategy, such as inadequate clearance of uremic toxins and/or severe electrolyte disturbances due to undetected loss of RKF; lower clearance of medium-sized molecules (such as beta-2-microglobulin) which mostly depends on the total PD dwell time; and patients' reluctance to dose adjustments. Current clinical evidence is based on moderate to low quality studies and suggests that the outcomes of IPD will be at least identical to those of full dose. This review aims to discuss the definition and strategies to IPD prescription, as well as its advantages and disadvantages. It'll also be reviewed the current evidence regarding this strategy.Fernandes, AdrianaMatias, PatríciaBranco, Patrícia2022-12-18T15:21:19-08:00doi:10.34067/KID.0006902022hwp:resource-id:kidney360;KID.0006902022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360incremental peritoneal dialysis, incremental dialysis, residual kidney function, personalized medicineReview ArticleReview Articleother202210.34067/KID.00069020222641-76502641-76502022-12-18T15:21:19-08:00Kidney360Review Article10.34067/KID.0006902022
- COVID-19 Vaccination and new onset glomerular disease: Results from the IRocGN2 International registryBackground:Cases of de novo glomerular disease with various renal histologies have been reported after vaccination against SARS-CoV-2. Causality has not been established and the long-term outcomes are not known. To better characterize the glomerular diseases and clinical course/outcomes, we created the International Registry of COVID-19 vaccination and Glomerulonephritis (IRocGN2) to study in aggregate de novo glomerulonephritis cases suspected after COVID-19 vaccine exposure Methods:A RedCap survey was used for anonymized data collection. Detailed information on vaccination type and timing and glomerular disease histology were recorded in the registry. We collected serial information on laboratory values (before and after vaccination and during follow-up), treatments, and kidney-related outcomes. Results: Ninety-eight glomerular disease cases were entered into the registry over eleven months from 44 centers throughout the world. Median follow-up was 89 days after diagnosis. IgA nephropathy (IgAN) and minimal change disease (MCD) were the most the common kidney diseases reported. Recovery of kidney function and remission of proteinuria was more likely in IgAN and MCD at 4-6 months than with pauci immune glomerulonephritis /vasculitis and membranous nephropathy. Conclusions:Development of glomerular disease after vaccination against SARS-CoV-2 may be a very rare adverse event. Temporal association is present for IgAN and MCD, but causality is not firmly established. Kidney outcomes for IgAN and MCD are favorable. No changes in vaccination risk-benefit assessment is recommended based on these findings.waldmanm@niddk.nih.gov10.34067/KID.0006832022Fri, 16 Dec 2022 03:21:56 GMT-08:00COVID-19 Vaccination and new onset glomerular disease: Results from the IRocGN2 International registryBackground:Cases of de novo glomerular disease with various renal histologies have been reported after vaccination against SARS-CoV-2. Causality has not been established and the long-term outcomes are not known. To better characterize the glomerular diseases and clinical course/outcomes, we created the International Registry of COVID-19 vaccination and Glomerulonephritis (IRocGN2) to study in aggregate de novo glomerulonephritis cases suspected after COVID-19 vaccine exposure Methods:A RedCap survey was used for anonymized data collection. Detailed information on vaccination type and timing and glomerular disease histology were recorded in the registry. We collected serial information on laboratory values (before and after vaccination and during follow-up), treatments, and kidney-related outcomes. Results: Ninety-eight glomerular disease cases were entered into the registry over eleven months from 44 centers throughout the world. Median follow-up was 89 days after diagnosis. IgA nephropathy (IgAN) and minimal change disease (MCD) were the most the common kidney diseases reported. Recovery of kidney function and remission of proteinuria was more likely in IgAN and MCD at 4-6 months than with pauci immune glomerulonephritis /vasculitis and membranous nephropathy. Conclusions:Development of glomerular disease after vaccination against SARS-CoV-2 may be a very rare adverse event. Temporal association is present for IgAN and MCD, but causality is not firmly established. Kidney outcomes for IgAN and MCD are favorable. No changes in vaccination risk-benefit assessment is recommended based on these findings.Waldman, MerylSinaii, NinetLerma, Edgar V.Kurien, Anila AbrahamJhaveri, Kenar D.Uppal, Nupur N.Wanchoo, RimdaAvasare, RupaliZuckerman, Jonathan E.Liew, AdrianGallan, Alexander J.El-Meanawy, AshrafYagil, YoramLebedev, LarissaBaskaran, KrishobanVilayur, EswariWai Seung, AdrienneWeerasinghe, NethmiPetrakis, IoannisStylianou, KostasGakiopoulou, HarikleiaHamilton, Alexander J.Edney, NaomiMillner, RachelMarinaki, SmaragdiRein, Joshua L.Killen, John PaulRodríguez Chagolla, Jose ManuelBassil, ClaudeLopez del Valle, RamonEvans, JordanUrisman, AnatolyZawaideh, MonaBaxi, Pravir V.Rodby, Roger A.Vankalakunti, MaheshaMejia Vilet, Juan M.Ramirez Andrade, Silvia EuniceHoman, MalVasquez Jimenez, EnzoPerinpanayagam, NatashaVelez, Juan Carlos Q.Mohamed, Muner M.B.Mohammed, Khalid M.GSekar, ArjunOllila, LauraAron, Abraham WArellano Arteaga, Kevin JavierIslam, MahmudBerrio, Esperanza MoralMaoujoud, OmarMorales, Rebecca RufSeipp, ReganSchulze, Carl E.Yenchek, Robert H.Vancea, IrinaMuneeb, MuhammadHoward, LilianCaza, Tiffany N.2022-12-16T15:21:56-08:00doi:10.34067/KID.0006832022hwp:resource-id:kidney360;KID.0006832022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360covid-19 vaccine, glomerular, kidney, nephrotic, COVID-19, Registries, IRocGN2Original InvestigationOriginal Investigationother202210.34067/KID.00068320222641-76502641-76502022-12-16T15:21:56-08:00Kidney360Original Investigation10.34067/KID.0006832022
- Maintenance of Remission and Risk of Relapse in Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Kidney InvolvementBackground. Optimal strategy for remission-maintenance therapy in patients with MPO-ANCA associated vasculitis is not established. Defining parameters to guide maintenance therapy is required. Methods. A retrospective cohort study of all patients with MPO-ANCA associated vasculitis (microscopic with polyangiitis and granulomatosis with polyangiitis) and glomerulonephritis (GN) followed at the Mayo Clinic between 1996-2015. Relapse rate, MPO-ANCA status, and remission-maintenance therapies were reviewed. Logistic regression models, Kaplan Meier method and Cox proportional hazards regression models were applied. Results. We analyzed 159 patients with active MPO-ANCA associated vasculitis with glomerulonephritis. Sixty-six (42%) patients had at least 1 relapse, and 52 (33%) relapsed before 60 months. Patients with MPO-ANCA who became persistently negative did not relapse (HR 0.03, [95%CI, 0.002- 0.431], p=0.01). The reappearance of MPO-ANCA was associated with a higher risk of relapse (HR 1.91, [95%CI, 1.109 - 3.293], p=0.020). Immunosuppression was withdrawn in 80 (50%) patients, and this was less likely in those who received cyclophosphamide for remission-induction or in patients with persistently MPO-ANCA positive (OR 0.44, [95%CI,0.228-0.861], p=0.02; OR 0.42, [95%CI,0.213-0.820], p=0.01, respectively). Relapse frequency was not different between patients with persistently positive MPO-ANCA and patients with MPO-ANCA reappearance (44% vs. 39%, p=0.49) irrespective of remission maintenance treatment. Ear nose an and throat involvement (OR 6.10 [95%CI, 1.280-29.010], p=0.02) and MPO-ANCA reappearance (OR 9.25, [95%CI, 3.126-27.361], p<0.001), were independent associated with relapse after treatment withdrawal. Conclusions. Patients persistently MPO-ANCA negative are at low risk for relapse even without remission maintenance therapy. Persistence or subsequent reappearance of MPO-ANCA is associated with an increased risk of relapse. Serial MPO-ANCA determinations can inform the development of remission-maintenance strategies in patients with MPO-ANCA associated vasculitis with glomerulonephritis.fervenza.fernando@mayo.edu10.2215/CJN.06460622Fri, 16 Dec 2022 10:16:52 GMT-08:00Maintenance of Remission and Risk of Relapse in Myeloperoxidase Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Kidney InvolvementBackground. Optimal strategy for remission-maintenance therapy in patients with MPO-ANCA associated vasculitis is not established. Defining parameters to guide maintenance therapy is required. Methods. A retrospective cohort study of all patients with MPO-ANCA associated vasculitis (microscopic with polyangiitis and granulomatosis with polyangiitis) and glomerulonephritis (GN) followed at the Mayo Clinic between 1996-2015. Relapse rate, MPO-ANCA status, and remission-maintenance therapies were reviewed. Logistic regression models, Kaplan Meier method and Cox proportional hazards regression models were applied. Results. We analyzed 159 patients with active MPO-ANCA associated vasculitis with glomerulonephritis. Sixty-six (42%) patients had at least 1 relapse, and 52 (33%) relapsed before 60 months. Patients with MPO-ANCA who became persistently negative did not relapse (HR 0.03, [95%CI, 0.002- 0.431], p=0.01). The reappearance of MPO-ANCA was associated with a higher risk of relapse (HR 1.91, [95%CI, 1.109 - 3.293], p=0.020). Immunosuppression was withdrawn in 80 (50%) patients, and this was less likely in those who received cyclophosphamide for remission-induction or in patients with persistently MPO-ANCA positive (OR 0.44, [95%CI,0.228-0.861], p=0.02; OR 0.42, [95%CI,0.213-0.820], p=0.01, respectively). Relapse frequency was not different between patients with persistently positive MPO-ANCA and patients with MPO-ANCA reappearance (44% vs. 39%, p=0.49) irrespective of remission maintenance treatment. Ear nose an and throat involvement (OR 6.10 [95%CI, 1.280-29.010], p=0.02) and MPO-ANCA reappearance (OR 9.25, [95%CI, 3.126-27.361], p<0.001), were independent associated with relapse after treatment withdrawal. Conclusions. Patients persistently MPO-ANCA negative are at low risk for relapse even without remission maintenance therapy. Persistence or subsequent reappearance of MPO-ANCA is associated with an increased risk of relapse. Serial MPO-ANCA determinations can inform the development of remission-maintenance strategies in patients with MPO-ANCA associated vasculitis with glomerulonephritis.Moura, Marta CasalSpecks, UlrichTehranian, ShahrzadSethi, SanjeevZubidat, DaliaNardelli, Lucados Santos, FernandaSousa, CíriaLeón-Róman, JuanBobart, ShaneGreene, EddieZand, LadanFervenza, Fernando2022-12-16T10:16:52-08:00doi:10.2215/CJN.06460622hwp:resource-id:clinjasn;CJN.06460622v1American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesOriginal Articlesresearch-article202210.2215/CJN.064606221555-90411555-905X2022-12-16T10:16:52-08:00Clinical Journal of the American Society of NephrologyOriginal ArticlesCJN.06460622
- HNF1B Alters an Evolutionarily Conserved Nephrogenic Program of Target GenesBackground: Hepatocyte nuclear factor 1-beta (HNF1B) is an essential transcription factor during embryogenesis. Mutations in HNF1B are the most common monogenic causes of congenital cystic dysplastic renal malformations. The direct functional consequences of mutations in HNF1B on its transcriptional activity are unknown. Methods: Direct reprogramming of mouse fibroblasts to induced renal tubular epithelial cells (iRECs) was conducted both with wild type HNF1B and with patient mutations. HNF1B was expressed in Xenopus ectodermal explants. Transcriptomic analysis by bulk RNA-Seq identified conserved targets with differentially regulated expression by the wild type or theR295C mutant. CRISPR genome editing in Xenopus embryos evaluated transcriptional targets in vivo. Results: HNF1B is essential for reprogramming mouse fibroblasts to iRECs and induces development of ectopic renal organoids from pluripotent Xenopus cells. The mutation R295C retains reprogramming and inductive capacity but alters the expression of specific sets of downstream target genes, instead of diminishing overall transcriptional activity of HNF1B. Surprisingly, targets associated with polycystic kidney disease were less affected than genes affected in congenital renal anomalies. Cross-species conserved transcriptional targets were dysregulated in hnf1b CRISPR-depleted Xenopus embryos, confirming their dependence on hnf1b. Conclusions: HNF1B activates an evolutionarily conserved program of target genes that disease-causing mutations selectively disrupt. These findings provide insights into the renal transcriptional network that controls nephrogenesis.soeren.lienkamp@anatomy.uzh.ch10.1681/ASN.2022010076Thu, 15 Dec 2022 11:34:35 GMT-08:00HNF1B Alters an Evolutionarily Conserved Nephrogenic Program of Target GenesBackground: Hepatocyte nuclear factor 1-beta (HNF1B) is an essential transcription factor during embryogenesis. Mutations in HNF1B are the most common monogenic causes of congenital cystic dysplastic renal malformations. The direct functional consequences of mutations in HNF1B on its transcriptional activity are unknown. Methods: Direct reprogramming of mouse fibroblasts to induced renal tubular epithelial cells (iRECs) was conducted both with wild type HNF1B and with patient mutations. HNF1B was expressed in Xenopus ectodermal explants. Transcriptomic analysis by bulk RNA-Seq identified conserved targets with differentially regulated expression by the wild type or theR295C mutant. CRISPR genome editing in Xenopus embryos evaluated transcriptional targets in vivo. Results: HNF1B is essential for reprogramming mouse fibroblasts to iRECs and induces development of ectopic renal organoids from pluripotent Xenopus cells. The mutation R295C retains reprogramming and inductive capacity but alters the expression of specific sets of downstream target genes, instead of diminishing overall transcriptional activity of HNF1B. Surprisingly, targets associated with polycystic kidney disease were less affected than genes affected in congenital renal anomalies. Cross-species conserved transcriptional targets were dysregulated in hnf1b CRISPR-depleted Xenopus embryos, confirming their dependence on hnf1b. Conclusions: HNF1B activates an evolutionarily conserved program of target genes that disease-causing mutations selectively disrupt. These findings provide insights into the renal transcriptional network that controls nephrogenesis.Grand, KelliStoltz, MartineRizzo, LudovicaRöck, RuthKaminski, MichaelSalinas, GabrielaGetwan, MaikeNaert, ThomasPichler, RomanLienkamp, Soeren2022-12-15T11:34:35-08:00doi:10.1681/ASN.2022010076hwp:resource-id:jnephrol;ASN.2022010076v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220100761046-66731533-34502022-12-15T11:34:35-08:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.2022010076
- Tet2- and Tet3-Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron EndowmentBackground Nephron endowment is a key determinant of hypertension and kidney disease in later life. Epigenetic changes have been proposed to mediate fetal programming and nephron number. DNA cytosine methylation, which plays a critical role in gene regulation, is affected by proteins encoded by the 10-11 translocation (TET) DNA demethylase gene family (Tet1, Tet2, and Tet3), but the roles of TET proteins in kidney development and nephron endowment have not been characterized. Methods To study whether epigenetic changes—specifically, active DNA hydroxymethylation mediated by Tet1, Tet2, and Tet3—are necessary for nephron progenitor differentiation and nephron endowment, we generated mice with deletion of Tet1, Tet2, or Tet3 in Six2-positive nephron progenitors cells (NPCs). We then performed unbiased omics profiling, including whole-genome bisulfite sequencing on isolated Six2-positive NPCs and single-cell RNA sequencing on kidneys from newborn mice. Results We did not observe changes in kidney development or function in mice with NPCspecific deletion of Tet1, Tet2, Tet3 or Tet1/Tet2 or Tet1/Tet3. On the other hand, mice with combined Tet2 and Tet3 loss in Six2-positive NPCs failed to form nephrons, leading to kidney failure and perinatal death. Tet2 and Tet3 loss in Six2-positive NPCs resulted in defective mesenchymal to epithelial transition and renal vesicle differentiation. Whole-genome bisulfite sequencing, single-cell RNA sequencing, and gene and protein expression analysis identified a defect in expression in multiple genes, including the WNT-β-catenin signaling pathway, due to a failure in demethylation of these loci in the absence of Tet2 and Tet3. Conclusions These findings suggest that Tet2- and Tet3-mediated active cytosine hydroxymethylation in NPCs play a key role in kidney development and nephron endowment.xiujie.liang@pennmedicine.upenn.edu10.1681/ASN.2022040460Thu, 15 Dec 2022 11:34:35 GMT-08:00Tet2- and Tet3-Mediated Cytosine Hydroxymethylation in Six2 Progenitor Cells in Mice Is Critical for Nephron Progenitor Differentiation and Nephron EndowmentBackground Nephron endowment is a key determinant of hypertension and kidney disease in later life. Epigenetic changes have been proposed to mediate fetal programming and nephron number. DNA cytosine methylation, which plays a critical role in gene regulation, is affected by proteins encoded by the 10-11 translocation (TET) DNA demethylase gene family (Tet1, Tet2, and Tet3), but the roles of TET proteins in kidney development and nephron endowment have not been characterized. Methods To study whether epigenetic changes—specifically, active DNA hydroxymethylation mediated by Tet1, Tet2, and Tet3—are necessary for nephron progenitor differentiation and nephron endowment, we generated mice with deletion of Tet1, Tet2, or Tet3 in Six2-positive nephron progenitors cells (NPCs). We then performed unbiased omics profiling, including whole-genome bisulfite sequencing on isolated Six2-positive NPCs and single-cell RNA sequencing on kidneys from newborn mice. Results We did not observe changes in kidney development or function in mice with NPCspecific deletion of Tet1, Tet2, Tet3 or Tet1/Tet2 or Tet1/Tet3. On the other hand, mice with combined Tet2 and Tet3 loss in Six2-positive NPCs failed to form nephrons, leading to kidney failure and perinatal death. Tet2 and Tet3 loss in Six2-positive NPCs resulted in defective mesenchymal to epithelial transition and renal vesicle differentiation. Whole-genome bisulfite sequencing, single-cell RNA sequencing, and gene and protein expression analysis identified a defect in expression in multiple genes, including the WNT-β-catenin signaling pathway, due to a failure in demethylation of these loci in the absence of Tet2 and Tet3. Conclusions These findings suggest that Tet2- and Tet3-mediated active cytosine hydroxymethylation in NPCs play a key role in kidney development and nephron endowment.Liang, XiujieAranyi, TamasZhou, JianfuGuan, YutingHu, HailongLiu, HongboSusztak, Katalin2022-12-15T11:34:35-08:00doi:10.1681/ASN.2022040460hwp:resource-id:jnephrol;ASN.2022040460v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220404601046-66731533-34502022-12-15T11:34:35-08:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.2022040460
- Early Impact of the Circular Model of Kidney Allocation in the United StatesBackground: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system based on distance from donor hospital to transplant center within/outside a 250 nautical mile radius. Impact of this policy on kidney discards and logistics is unknown. Methods: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared to a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after COVID19 onset and KAS250 implementation were evaluated using an interrupted timeseries model. Changes in allocation practices (biopsy, machine perfusion, and virtual crossmatch) were also evaluated. Results: Post-KAS250 saw a two-fold increase in kidneys imported from non-local organ procurement organizations (OPO), a higher proportion of recipients with calculated panel reactive antibody (CPRA) 81-98% (12% vs 8%, p<0.001) and those with >5 years of pre-transplant dialysis (35% vs 33%, p<0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards post-KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased while reliance on virtual crossmatch increased, which was associated with shorter CIT. Conclusion: Early trends post-KAS250 show an increase in transplant access to patients with CPRA>80 and those with longer dialysis duration, but was accompanied by an increase in CIT and a suggestion of worsening kidney discards.puttarajappacm@upmc.edu10.1681/ASN.2022040471Thu, 27 Oct 2022 06:46:11 GMT-07:00Early Impact of the Circular Model of Kidney Allocation in the United StatesBackground: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system based on distance from donor hospital to transplant center within/outside a 250 nautical mile radius. Impact of this policy on kidney discards and logistics is unknown. Methods: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared to a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after COVID19 onset and KAS250 implementation were evaluated using an interrupted timeseries model. Changes in allocation practices (biopsy, machine perfusion, and virtual crossmatch) were also evaluated. Results: Post-KAS250 saw a two-fold increase in kidneys imported from non-local organ procurement organizations (OPO), a higher proportion of recipients with calculated panel reactive antibody (CPRA) 81-98% (12% vs 8%, p<0.001) and those with >5 years of pre-transplant dialysis (35% vs 33%, p<0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards post-KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased while reliance on virtual crossmatch increased, which was associated with shorter CIT. Conclusion: Early trends post-KAS250 show an increase in transplant access to patients with CPRA>80 and those with longer dialysis duration, but was accompanied by an increase in CIT and a suggestion of worsening kidney discards.Puttarajappa, ChethanHariharan, SundaramZhang, XingyuTevar, AmitMehta, RajilGunabushanam, VikramanSood, PuneetHoffman, WilliamMohan, Sumit2022-10-27T06:46:11-07:00doi:10.1681/ASN.2022040471hwp:resource-id:jnephrol;ASN.2022040471v2American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Clinical EpidemiologyOriginal Article - Clinical Epidemiologyresearch-article202210.1681/ASN.20220404711046-66731533-34502022-10-27T06:46:11-07:00Journal of the American Society of NephrologyOriginal Article - Clinical EpidemiologyASN.2022040471
- Genetic determinants of interleukin-6 levels and risk of end-stage renal diseaseThis is an Early Access article. Please select the PDF button, above, to view it.Adriana.Hung@vumc.org10.34067/KID.0003332022Wed, 14 Dec 2022 10:11:47 GMT-08:00Genetic determinants of interleukin-6 levels and risk of end-stage renal diseaseThis is an Early Access article. Please select the PDF button, above, to view it.Wheless, LeePike, Mindy M.Chen, Hua-ChangYu, ZhihongTao, RanBick, AlexanderChung, Cecilia P.Robinson-Cohen, CassianneHung, Adriana2022-12-14T10:11:47-08:00doi:10.34067/KID.0003332022hwp:resource-id:kidney360;KID.0003332022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360IL-6, Mendelian randomization, end-stage renal diseaseBrief CommunicationBrief Communicationother202210.34067/KID.00033320222641-76502641-76502022-12-14T10:11:47-08:00Kidney360Brief Communication10.34067/KID.0003332022
- Incidence and Risk Factors for Pruritus in Patients with Nondialysis CKDBackground: Pruritus is a common symptom experienced by patients with nondialysis CKD, but risk factors for incident pruritus in this patient population have not been evaluated. Methods: We identified 1,951 participants with CKD in the Chronic Renal Insufficiency Cohort Study without pruritus at the baseline assessment. Pruritus was assessed by the Kidney Disease Quality of Life-36 instrument, and moderate-to-severe pruritus was defined as a response of 3 or higher on a Likert scale of 1 to 5. We used time-updated multivariable joint models to evaluate the association of patient clinical characteristics, eGFR, and laboratory parameters with incident pruritus. Results: Over a median follow-up of 6 years, 660 (34%) participants developed incident moderate-to-severe pruritus, with a higher incidence rate observed among participants with more advanced CKD. In multivariable models, the hazard ratio (95% CI) for pruritus associated with a 10 mL/min/1.73 m2 lower eGFR was 1.16 (1.10 - 1.23). Older age (≥65 years), higher body mass index, diabetes, current smoking, opioid use, depressive symptoms, and serum parathyroid hormone were also associated with a higher risk of incident pruritus, while low serum calcium (<9 mg/dL) was associated with a lower risk (all p<0.05). Serum phosphate was not associated with incident pruritus in the primary analysis. Conclusions: A substantial proportion of patients with nondialysis CKD develop moderate-to-severe pruritus. While lower eGFR is associated with the risk of pruritus, other comorbidities, particularly depressive symptoms, are potential risk factors.kwulczyn@partners.org10.2215/CJN.09480822Wed, 14 Dec 2022 09:25:33 GMT-08:00Incidence and Risk Factors for Pruritus in Patients with Nondialysis CKDBackground: Pruritus is a common symptom experienced by patients with nondialysis CKD, but risk factors for incident pruritus in this patient population have not been evaluated. Methods: We identified 1,951 participants with CKD in the Chronic Renal Insufficiency Cohort Study without pruritus at the baseline assessment. Pruritus was assessed by the Kidney Disease Quality of Life-36 instrument, and moderate-to-severe pruritus was defined as a response of 3 or higher on a Likert scale of 1 to 5. We used time-updated multivariable joint models to evaluate the association of patient clinical characteristics, eGFR, and laboratory parameters with incident pruritus. Results: Over a median follow-up of 6 years, 660 (34%) participants developed incident moderate-to-severe pruritus, with a higher incidence rate observed among participants with more advanced CKD. In multivariable models, the hazard ratio (95% CI) for pruritus associated with a 10 mL/min/1.73 m2 lower eGFR was 1.16 (1.10 - 1.23). Older age (≥65 years), higher body mass index, diabetes, current smoking, opioid use, depressive symptoms, and serum parathyroid hormone were also associated with a higher risk of incident pruritus, while low serum calcium (<9 mg/dL) was associated with a lower risk (all p<0.05). Serum phosphate was not associated with incident pruritus in the primary analysis. Conclusions: A substantial proportion of patients with nondialysis CKD develop moderate-to-severe pruritus. While lower eGFR is associated with the risk of pruritus, other comorbidities, particularly depressive symptoms, are potential risk factors.Wulczyn, KendraRhee, EugeneMyint, LeslieKalim, SahirShafi, Tariq2022-12-14T09:25:33-08:00doi:10.2215/CJN.09480822hwp:resource-id:clinjasn;CJN.09480822v1American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesOriginal Articlesresearch-article202210.2215/CJN.094808221555-90411555-905X2022-12-14T09:25:33-08:00Clinical Journal of the American Society of NephrologyOriginal ArticlesCJN.09480822
- Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino PopulationBackground. Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanics/Latinos, a population with high risk for metabolic disease. Methods. We used data from 3,736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin to creatinine ratio (UACR). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites in covariate-adjusted models that accounted for the study design. 132 metabolites were available for replication in the HyperGEN study (n = 300), and 29 metabolites were available for replication in the Malmö Offspring Study (n = 999). Results. Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-Glutamine and D-Glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism. Conclusions. Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanics/Latinos.noraf@unc.edu10.2215/CJN.09070822Wed, 14 Dec 2022 09:25:33 GMT-08:00Circulating Metabolites Associated with Albuminuria in a Hispanic/Latino PopulationBackground. Albuminuria is associated with metabolic abnormalities, but these relationships are not well understood. We studied the association of metabolites with albuminuria in Hispanics/Latinos, a population with high risk for metabolic disease. Methods. We used data from 3,736 participants from the Hispanic Community Health Study/Study of Latinos, of which 16% had diabetes and 9% had an increased urine albumin to creatinine ratio (UACR). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Spot UACR was inverse normally transformed and tested for the association with each metabolite or combined, correlated metabolites in covariate-adjusted models that accounted for the study design. 132 metabolites were available for replication in the HyperGEN study (n = 300), and 29 metabolites were available for replication in the Malmö Offspring Study (n = 999). Results. Among 640 named metabolites, we identified 148 metabolites significantly associated with UACR, including 18 novel associations that replicated in independent samples. These metabolites showed enrichment for D-Glutamine and D-Glutamate metabolism and arginine biosynthesis, pathways previously reported for diabetes and insulin resistance. In correlated metabolite analyses, we identified two modules significantly associated with UACR, including a module composed of lipid metabolites related to the biosynthesis of unsaturated fatty acids and alpha linolenic acid and linoleic acid metabolism. Conclusions. Our study identified associations of albuminuria with metabolites involved in glucose dysregulation, and essential fatty acids and precursors of arachidonic acid in Hispanics/Latinos.Reynolds, KayliaLin, BridgetArmstrong, NicoleOttosson, FilipZhang, YingWilliams, AshleyYu, BingBoerwinkle, EricThyagarajan, BharatDaviglus, MarthaMuoio, DeborahQi, QibinKaplan, RobertMelander, OlleLash, JamesCai, JianwenIrvin, MargueriteNewgard, ChristopherSofer, TamarFranceschini, Nora2022-12-14T09:25:33-08:00doi:10.2215/CJN.09070822hwp:resource-id:clinjasn;CJN.09070822v1American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesOriginal Articlesresearch-article202210.2215/CJN.090708221555-90411555-905X2022-12-14T09:25:33-08:00Clinical Journal of the American Society of NephrologyOriginal ArticlesCJN.09070822
- Lived experiences of hemodialysis healthcare workers during the COVID-19 pandemic: A qualitative study from the Quebec Renal NetworkBackground: The COVID-19 pandemic has disrupted health systems and created numerous challenges in hospitals worldwide for patients and healthcare workers (HCWs). Hemodialysis centers are at risk of COVID-19 outbreaks given the difficulty of maintaining social distancing and the fact that hemodialysis patients are at higher risk of being infected with COVID-19. During the COVID-19 pandemic, HCWs have had to face many challenges and stressors. Our study was designed to gain HCWs' perspectives on their experiences of the impacts of the COVID-19 pandemic in hemodialysis units. Methods: Semi-structured interviews were conducted with 22 HCWs (nurses, nephrologists, pharmacists, social workers, patient attendants, security agents) working in five hemodialysis centers in Montreal, between November 2020 and May 2021. The content of the interviews was analyzed using thematic analysis. Results: Four themes were identified during the interviews. The first was the impact of COVID-19 on work organization, regarding which participants reported an increased workload, a need for a consistent information strategy, and positive innovations such as telemedicine. The second theme was challenges associated with communicating and caring for dialysis patients during the pandemic. The third theme was psychological distress experienced by hemodialysis staff and the psychosocial impact of COVID-19 on their personal lives. The fourth theme was recommendations made by participants for future public health emergencies, such as maintaining public health measures, ensuring an adequate supply of protective equipment and developing a consistent communication strategy. Conclusions: During the first and second waves of the COVID-19 pandemic, HCWs working in hemodialysis units faced multiple challenges that impacted their wellbeing and their work. In order to minimize challenges for HCWs in hemodialysis during a future pandemic, the healthcare system should provide an adequate supply of protective equipment, develop effective communication strategies and take into account the psychological distress related to HCWs' professional and personal lives.marie-chantal.fortin.med@ssss.gouv.qc.ca10.34067/KID.0004252022Tue, 13 Dec 2022 01:29:47 GMT-08:00Lived experiences of hemodialysis healthcare workers during the COVID-19 pandemic: A qualitative study from the Quebec Renal NetworkBackground: The COVID-19 pandemic has disrupted health systems and created numerous challenges in hospitals worldwide for patients and healthcare workers (HCWs). Hemodialysis centers are at risk of COVID-19 outbreaks given the difficulty of maintaining social distancing and the fact that hemodialysis patients are at higher risk of being infected with COVID-19. During the COVID-19 pandemic, HCWs have had to face many challenges and stressors. Our study was designed to gain HCWs' perspectives on their experiences of the impacts of the COVID-19 pandemic in hemodialysis units. Methods: Semi-structured interviews were conducted with 22 HCWs (nurses, nephrologists, pharmacists, social workers, patient attendants, security agents) working in five hemodialysis centers in Montreal, between November 2020 and May 2021. The content of the interviews was analyzed using thematic analysis. Results: Four themes were identified during the interviews. The first was the impact of COVID-19 on work organization, regarding which participants reported an increased workload, a need for a consistent information strategy, and positive innovations such as telemedicine. The second theme was challenges associated with communicating and caring for dialysis patients during the pandemic. The third theme was psychological distress experienced by hemodialysis staff and the psychosocial impact of COVID-19 on their personal lives. The fourth theme was recommendations made by participants for future public health emergencies, such as maintaining public health measures, ensuring an adequate supply of protective equipment and developing a consistent communication strategy. Conclusions: During the first and second waves of the COVID-19 pandemic, HCWs working in hemodialysis units faced multiple challenges that impacted their wellbeing and their work. In order to minimize challenges for HCWs in hemodialysis during a future pandemic, the healthcare system should provide an adequate supply of protective equipment, develop effective communication strategies and take into account the psychological distress related to HCWs' professional and personal lives.Affdal, AliyaMalo, Marie-FrançoiseBlum, DanielBallesteros Gallego, FabianBeaubien-Souligny, WilliamCaron, Marie-LineNadeau-Fredette, Annie-ClaireVasilevsky, MurrayRios, NorkaSuri, Rita S.Fortin, Marie-Chantal2022-12-13T13:29:47-08:00doi:10.34067/KID.0004252022hwp:resource-id:kidney360;KID.0004252022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360hemodialysis, healthcare providers, COVID-19 pandemic, Qualitative study, Semi-directed interviewsOriginal InvestigationOriginal Investigationother202210.34067/KID.00042520222641-76502641-76502022-12-13T13:29:47-08:00Kidney360Original Investigation10.34067/KID.0004252022
- A Microsimulation Study Of The Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis CentersBackground National guidelines recommend twice-yearly hepatitis C virus (HCV) screening for patients receiving in-center hemodialysis. However, studies examining the cost-effectiveness of HCV screening methods or frequencies are lacking. Methods We populated an HCV screening, treatment, and disease microsimulation model with a cohort representative of the US in-center hemodialysis population. Clinical outcomes, costs, and cost-effectiveness of the Kidney Disease Improving Global Outcomes (KDIGO) 2018 guidelines-endorsed HCV screening frequency (every 6 months) were compared with less frequent periodic screening (yearly, every 2 years), screening only at hemodialysis initiation, and no screening. We estimated expected quality-adjusted life-years (QALYs) and incremental costeffectiveness ratios (ICERs) between each screening strategy and the next less expensive alternative strategy, from a health care sector perspective, in 2019 US dollars. For each strategy, we modeled an HCV outbreak occurring in 1% of centers. In sensitivity analyses, we varied mortality, linkage to HCV cure, screening method (RNA versus antibody testing), test sensitivity, HCV infection rates, and outbreak frequencies. Results Screening only at hemodialysis initiation yielded HCV cure rates of 79%, with an ICER of $82,739 per QALY saved compared with no testing. Compared with screening at hemodialysis entry only, screening every 2 years increased cure rates to 88% and decreased liver-related deaths by 52%, with an ICER of $140,193. Screening every 6 months had an ICER of $934,757; in sensitivity analyses using a willingness-to-pay threshold of $150,000 per QALY gained, screening every 6 months was never cost-effective. Conclusions The KDIGO-recommended HCV screening interval (every 6 months) appears not to be a cost-effective use of health care resources, suggesting that reevaluation of less frequent screening strategies should be considered.rachel.epstein@bmc.org10.1681/ASN.2022030245Tue, 13 Dec 2022 11:13:31 GMT-08:00A Microsimulation Study Of The Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis CentersBackground National guidelines recommend twice-yearly hepatitis C virus (HCV) screening for patients receiving in-center hemodialysis. However, studies examining the cost-effectiveness of HCV screening methods or frequencies are lacking. Methods We populated an HCV screening, treatment, and disease microsimulation model with a cohort representative of the US in-center hemodialysis population. Clinical outcomes, costs, and cost-effectiveness of the Kidney Disease Improving Global Outcomes (KDIGO) 2018 guidelines-endorsed HCV screening frequency (every 6 months) were compared with less frequent periodic screening (yearly, every 2 years), screening only at hemodialysis initiation, and no screening. We estimated expected quality-adjusted life-years (QALYs) and incremental costeffectiveness ratios (ICERs) between each screening strategy and the next less expensive alternative strategy, from a health care sector perspective, in 2019 US dollars. For each strategy, we modeled an HCV outbreak occurring in 1% of centers. In sensitivity analyses, we varied mortality, linkage to HCV cure, screening method (RNA versus antibody testing), test sensitivity, HCV infection rates, and outbreak frequencies. Results Screening only at hemodialysis initiation yielded HCV cure rates of 79%, with an ICER of $82,739 per QALY saved compared with no testing. Compared with screening at hemodialysis entry only, screening every 2 years increased cure rates to 88% and decreased liver-related deaths by 52%, with an ICER of $140,193. Screening every 6 months had an ICER of $934,757; in sensitivity analyses using a willingness-to-pay threshold of $150,000 per QALY gained, screening every 6 months was never cost-effective. Conclusions The KDIGO-recommended HCV screening interval (every 6 months) appears not to be a cost-effective use of health care resources, suggesting that reevaluation of less frequent screening strategies should be considered.Epstein, RachelPramanick, TannishthaBaptiste, DimitriBuzzee, BenjaminReese, PeterLinas, BenjaminSawinski, Deirdre2022-12-13T11:13:31-08:00doi:10.1681/ASN.2022030245hwp:resource-id:jnephrol;ASN.2022030245v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Clinical EpidemiologyOriginal Article - Clinical Epidemiologyresearch-article202210.1681/ASN.20220302451046-66731533-34502022-12-13T11:13:31-08:00Journal of the American Society of NephrologyOriginal Article - Clinical EpidemiologyASN.2022030245
- Fibroblast Growth Factor-23 and Risk of Cardiovascular DiseasesBackground: Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding. Methods: SCALLOP consortium data on 19,195 participants were used to generate an FGF23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). Results: We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalties. Conclusions: Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link.will.herrington@ndph.ox.ac.uk10.2215/CJN.05080422Tue, 13 Dec 2022 08:16:57 GMT-08:00Fibroblast Growth Factor-23 and Risk of Cardiovascular DiseasesBackground: Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding. Methods: SCALLOP consortium data on 19,195 participants were used to generate an FGF23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness and left ventricular mass were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). Results: We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with carotid or cardiac abnormalties. Conclusions: Genetically predicted FGF-23 levels are not associated atherosclerotic and non-atherosclerotic cardiovascular diseases, suggesting no important causal link.Donovan, KillianHerrington, WilliamParé, GuillaumePigeyre, MarieHaynes, RichardSardell, RebeccaButterworth, AdamFolkersen, LasseGustafsson, StefanWang, QinBaigent, ColinMälarstig, AndersHolmes, MichaelStaplin, Natalie2022-12-13T08:16:57-08:00doi:10.2215/CJN.05080422hwp:resource-id:clinjasn;CJN.05080422v1American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesOriginal Articlesresearch-article202210.2215/CJN.050804221555-90411555-905X2022-12-13T08:16:57-08:00Clinical Journal of the American Society of NephrologyOriginal ArticlesCJN.05080422
- A Nationwide Comparative Analysis of Peritoneoscopic and Laparoscopic Techniques for Peritoneal Dialysis Catheter Insertion in Brunei DarussalamBackground: Brunei Darussalam introduced peritoneoscopic insertion of peritoneal dialysis catheter (PDC) as a new method in 2014. The aim of this study was to compare outcomes of PDC insertion technique in the country, using proposed standardized definitions of outcomes. Methods: This study used retrospective analysis of all PDC inserted from 1st January 2015 to 31st December 2020 in the country. Outcomes of both peritoneoscopic and laparoscopic insertion methods were analyzed. Four main categories of outcomes were assessed - 1) operative-related outcomes, 2) infective outcomes, 3) mechanical outcomes and 4) time on PD therapy. Results: During the study period, 145 PDC were inserted. 49 (33.8%) were by peritoneoscopy and 96 (66.2%) laparoscopy. The median time on PD therapy was 54.2 months. Those with a higher BMI and history of previous abdominal or pelvic surgery were more likely to undergo laparoscopic method. There was no significant difference in overall infective and mechanical outcomes between the two methods. There was however significantly more post-operative pain observed in the peritoneoscopic group than in the laparoscopic group (8.2% vs 1.0%, p = 0.045). During the study period, there were 49 dropouts to HD, about half were due to infection. However, there was no statistically significant difference observed in time on PD therapy between the two groups (HR 0.87 in laparoscopic group compared to peritoneoscopic group, 95% CI 0.49 to 1.54; p = 0.636). Conclusions: Peritoneoscopic and laparoscopic PD catheter insertions are both complementary to each other in our local setting. This study has enabled us to scrutinize our PD program, with regards to our PDC insertion experience, with the aim to sustain PD growth in the country.chiaoyuenlim905@gmail.com10.34067/KID.0006052022Mon, 12 Dec 2022 11:39:33 GMT-08:00A Nationwide Comparative Analysis of Peritoneoscopic and Laparoscopic Techniques for Peritoneal Dialysis Catheter Insertion in Brunei DarussalamBackground: Brunei Darussalam introduced peritoneoscopic insertion of peritoneal dialysis catheter (PDC) as a new method in 2014. The aim of this study was to compare outcomes of PDC insertion technique in the country, using proposed standardized definitions of outcomes. Methods: This study used retrospective analysis of all PDC inserted from 1st January 2015 to 31st December 2020 in the country. Outcomes of both peritoneoscopic and laparoscopic insertion methods were analyzed. Four main categories of outcomes were assessed - 1) operative-related outcomes, 2) infective outcomes, 3) mechanical outcomes and 4) time on PD therapy. Results: During the study period, 145 PDC were inserted. 49 (33.8%) were by peritoneoscopy and 96 (66.2%) laparoscopy. The median time on PD therapy was 54.2 months. Those with a higher BMI and history of previous abdominal or pelvic surgery were more likely to undergo laparoscopic method. There was no significant difference in overall infective and mechanical outcomes between the two methods. There was however significantly more post-operative pain observed in the peritoneoscopic group than in the laparoscopic group (8.2% vs 1.0%, p = 0.045). During the study period, there were 49 dropouts to HD, about half were due to infection. However, there was no statistically significant difference observed in time on PD therapy between the two groups (HR 0.87 in laparoscopic group compared to peritoneoscopic group, 95% CI 0.49 to 1.54; p = 0.636). Conclusions: Peritoneoscopic and laparoscopic PD catheter insertions are both complementary to each other in our local setting. This study has enabled us to scrutinize our PD program, with regards to our PDC insertion experience, with the aim to sustain PD growth in the country.Lim, Chiao YuenOo, Aung PhyoRajput, Ahmed SulemanDaiwajna, Rajendra GovindraoLim, Yee YinTan, Jackson2022-12-12T11:39:33-08:00doi:10.34067/KID.0006052022hwp:resource-id:kidney360;KID.0006052022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360kidney failure, peritoneal dialysis, peritoneal dialysis catheters, peritoneoscopy, laparoscopy, Brunei DarussalamOriginal InvestigationOriginal Investigationother202210.34067/KID.00060520222641-76502641-76502022-12-12T11:39:33-08:00Kidney360Original Investigation10.34067/KID.0006052022
- Onconephrology 2022: An UpdateOnconephrology is an upcoming and expanding subspecialty that deals with the intersections between hematology/oncology and nephrology. With the paradigm shift in the understanding of cancer immunobiology and mechanisms of onco-therapeutic drug toxicities, it is important for a nephrologist to have a sound understanding of this field. Over the last 5 years, there have been immense developments in our understanding of kidney related adverse events from various targeted, immuno and cellular-based therapies. Pathogenic mechanisms of electrolyte imbalance, hypertension (Onco-hypertension), and acute kidney injury from multiple forms of cancer therapies have been explored. Significant research has also been conducted in the field of transplant onconephrology. In this review, we have tried to assimilate the most recent updates in the last 2 years in this ever-growing and fascinating field.marco.bonilla@icloud.com10.34067/KID.0001582022Fri, 09 Dec 2022 01:39:13 GMT-08:00Onconephrology 2022: An UpdateOnconephrology is an upcoming and expanding subspecialty that deals with the intersections between hematology/oncology and nephrology. With the paradigm shift in the understanding of cancer immunobiology and mechanisms of onco-therapeutic drug toxicities, it is important for a nephrologist to have a sound understanding of this field. Over the last 5 years, there have been immense developments in our understanding of kidney related adverse events from various targeted, immuno and cellular-based therapies. Pathogenic mechanisms of electrolyte imbalance, hypertension (Onco-hypertension), and acute kidney injury from multiple forms of cancer therapies have been explored. Significant research has also been conducted in the field of transplant onconephrology. In this review, we have tried to assimilate the most recent updates in the last 2 years in this ever-growing and fascinating field.Bonilla, MarcoGudsoorkar, PrakashWanchoo, RimdaHerrmann, Sandra M.Jhaveri, Kenar D.2022-12-09T13:39:13-08:00doi:10.34067/KID.0001582022hwp:resource-id:kidney360;KID.0001582022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360onconephrology, AKI, cancer, chemotherapy, oncohypertension, transplant, immunotherapy, myeloma, amyloidosis, stem cell transplant, paraproteinemiaReview ArticleReview Articleother202210.34067/KID.00015820222641-76502641-76502022-12-09T13:39:13-08:00Kidney360Review Article10.34067/KID.0001582022
- Symptom Burden before and after Dialysis Initiation in Older Patients10.2215/CJN.09190822Thu, 10 Nov 2022 06:09:51 GMT-08:00Symptom Burden before and after Dialysis Initiation in Older Patientsde Rooij, Esther N.M.Meuleman, Yvettede Fijter, Johan W.Jager, Kitty J.Chesnaye, Nicholas C.Evans, MarieCaskey, Fergus J.Torino, ClaudiaPorto, GaetanaSzymczak, MaciejDrechsler, ChristianeWanner, ChristophDekker, Friedo W.Hoogeveen, Ellen K.,Schneider, AndreasTorp, AnkeIwig, BeatePerras, BorisMarx, ChristianDrechsler, ChristianeBlaser, ChristofWanner, ChristophEmde, ClaudiaKrieter, DetlefFuchs, DunjaIrmler, EllenPlaten, EvaSchmidt-Gürtler, HansSchlee, HendrikNaujoks, HolgerSchlee, InesCäsar, SabineBeige, JoachimRöthele, JochenMazur, JustynaHahn, KaiBlouin, KatjaNeumeier, KatrinAnding-Rost, KirstenSchramm, LotharHopf, MonikaWuttke, NadjaFrischmuth, NikolausIchtiaris, PawlosKirste, PetraSchulz, PetraAign, SabineBiribauer, SandraManan, SherinRöser, SilkeHeidenreich, StefanPalm, StephanieSchwedler, SusanneDelrieux, SylkeRenker, SylviaSchättel, SylviaStephan, TheresaSchmiedeke, ThomasWeinreich, ThomasLeimbach, TilStövesand, TorstenBahner, UdoSeeger, WolfgangCupisti, AdamascoSagliocca, AdeliaFerraro, AlbertoMele, AlessandraNaticchia, AlessandroCòsaro, AlexRanghino, AndreaStucchi, AndreaPignataro, AngeloDe Blasio, AntonellaPani, AntonelloTsalouichos, ArisAntonio, BellasiDi Iorio, Biagio RaffaeleAlessandra, ButtiAbaterusso, CataldoSomma, ChiaraD’alessandro, ClaudiaTorino, ClaudiaZullo, ClaudiaPozzi, ClaudioBergamo, DanielaCiurlino, DanieleMotta, DariaRusso, DomenicoFavaro, EnricoVigotti, FedericaAnsali, FerruccioConte, FerruccioCianciotta, FrancescaGiacchino, FrancescaCappellaio, FrancescoPizzarelli, FrancescoGreco, GaetanoPorto, GaetanaBigatti, GiadaMarinangeli, GiancarloCabiddu, GianfrancaFumagalli, GiordanoCaloro, GiorgiaPiccoli, GiorginaCapasso, GiovanbattistaGambaro, GiovanniTognarelli, GiulianaBonforte, GiuseppeConte, GiuseppeToscano, GiuseppeDel Rosso, GoffredoCapizzi, IreneBaragetti, IvanoOldrizzi, LambertoGesualdo, LoretoBiancone, LuigiMagnano, ManuelaRicardi, MarcoDi Bari, MariaLaudato, MariaSirico, Maria LuisaFerraresi, MartinaProvenzano, MicheleMalaguti, MorenoPalmieri, NicolaMurrone, PaolaCirillo, PietroDattolo, PietroAcampora, PinaNigro, RitaBoero, RobertoScarpioni, RobertoSicoli, RosaMalandra, RosellaSavoldi, SilvanaBertoli, SilvioBorrelli, SilvioMaxia, StefaniaMaffei, StefanoMangano, StefanoCicchetti, TeresaRappa, TizianaPalazzo, ValentinaDe Simone, WalterSchrander, Anitavan Dam, BastiaanSiegert, CarlGaillard, CarloBeerenhout, CharlesVerburgh, CornelisJanmaat, CynthiaHoogeveen, EllenHoorn, EwoutDekker, FriedoBoots, JohannesBoom, HenkEijgenraam, Jan-WillemKooman, JeroenRotmans, JorisJager, KittyVogt, LiffertRaasveld, MaartenVervloet, Marcvan Buren, Marjolijnvan Diepen, MerelChesnaye, NicholasLeurs, PaulVoskamp, PaulineBlankestijn, Petervan Esch, SadieBoorsma, SiskaBerger, StefanKonings, ConstantijnAydin, ZeynepMusiała, AleksandraSzymczak, AnnaOlczyk, EwelinaAugustyniak-Bartosik, HannaMiśkowiec-Wiśniewska, IlonaManitius, JacekPondel, JoannaJędrzejak, KamilaNowańska, KatarzynaNowak, ŁukaszSzymczak, MaciejDurlik, MagdalenaDorota, SzyszkowskaNieszporek, TeresaHeleniak, ZbigniewJonsson, AndreasBlom, Anna-LenaRogland, BjörnWallquist, CarinVargas, DenesDimény, EmökeSundelin, FredrikUhlin, FredrikWelander, GunillaHernandez, Isabel BascaranGröntoft, Knut-ChristianStendahl, MariaSvensson, MariaEvans, MarieHeimburger, OlofKashioulis, PavlosMelander, StefanAlmquist, ToraJensen, UlrikaWoodman, AlistairMcKeever, AnnaUllah, AsadMcLaren, BarbaraHarron, CamilleBarrett, CarlaO'Toole, CharlotteSummersgill, ChristinaGeddes, ColinGlowski, DeborahMcGlynn, DeborahSands, DympnaCaskey, FergusRoy, GeenaHirst, GillianKing, HayleyMcNally, HelenMasri-Senghor, HoudaMurtagh, HughRayner, HughTurner, JaneWilcox, JoanneBerdeprado, JocelynWong, JonathanBanda, JoyceJones, KirsteenHaydock, LesleyWilkinson, LilyCarmody, MargaretWeetman, MariaJoinson, MartinDutton, MaryMatthews, MichaelMorgan, NealBleakley, NinaCockwell, PaulRoderick, PaulMason, PhilKalra, PhilipSajith, RincyChapman, SallyNavjee, SanteeCrosbie, SarahBrown, SharonTickle, SheilaMathavakkannan, SureshKuan, Ying2022-11-10T06:09:51-08:00doi:10.2215/CJN.09190822hwp:resource-id:clinjasn;17/12/1719American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end stage kidney disease, epidemiology and outcomes, elderly, chronic kidney diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-12-01December 202210.2215/CJN.091908221555-90411555-905X2022-11-10T06:09:51-08:002022-12Clinical Journal of the American Society of NephrologyOriginal Article171217191729
- Correction: Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients10.2215/CJN.10870922Tue, 11 Oct 2022 06:28:12 GMT-07:00Correction: Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant RecipientsAmerican Society of Nephrology2022-10-11T06:28:12-07:00doi:10.2215/CJN.10870922hwp:resource-id:clinjasn;17/12/1802American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20222022-12-01December 202210.2215/CJN.108709221555-90411555-905X2022-10-11T06:28:12-07:002022-12Clinical Journal of the American Society of NephrologyErratum171712218022711804279
- Nephrology Program Director Protected Time for Program Administration in the United States10.2215/CJN.09050822Wed, 26 Oct 2022 11:06:56 GMT-07:00Nephrology Program Director Protected Time for Program Administration in the United StatesYuan, Christina M.Young, Brian Y.Watson, Maura A.Sussman, Amy N.2022-10-26T11:06:56-07:00doi:10.2215/CJN.09050822hwp:resource-id:clinjasn;17/12/1775American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, program director, fellowship program, protected time, program administration, didactic teachingOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-12-01December 202210.2215/CJN.090508221555-90411555-905X2022-10-26T11:06:56-07:002022-12Clinical Journal of the American Society of NephrologyOriginal Article171217751782
- The Immune System and Idiopathic Nephrotic SyndromeIdiopathic nephrotic syndrome often responds to immunosuppressive treatment. Nevertheless, this syndrome—and the drugs used to treat it—remain important causes of patient morbidity. Idiopathic nephrotic syndrome is usually caused by minimal change disease or FSGS, diseases that primarily affect the podocytes. In spite of decades of research, the underlying causes of both diseases remain incompletely understood. There is, however, a large body of observational and experimental data linking the immune system with both minimal change disease and FSGS, including associations with systemic infections and hematologic malignancies. Perhaps most compellingly, many different immunomodulatory drugs are effective for treating idiopathic nephrotic syndrome, including biologic agents that have well-defined immune targets. In fact, the unexpected efficacy of targeted therapeutic agents has provided important new insights into the pathogenesis of these diseases. Given the large number of drugs that are available to deplete or block specific cells and molecules within the immune system, a better understanding of the immunologic causes of idiopathic nephrotic syndrome may lead to better diagnostic and therapeutic approaches.10.2215/CJN.07180622Wed, 05 Oct 2022 09:25:09 GMT-07:00The Immune System and Idiopathic Nephrotic SyndromeIdiopathic nephrotic syndrome often responds to immunosuppressive treatment. Nevertheless, this syndrome—and the drugs used to treat it—remain important causes of patient morbidity. Idiopathic nephrotic syndrome is usually caused by minimal change disease or FSGS, diseases that primarily affect the podocytes. In spite of decades of research, the underlying causes of both diseases remain incompletely understood. There is, however, a large body of observational and experimental data linking the immune system with both minimal change disease and FSGS, including associations with systemic infections and hematologic malignancies. Perhaps most compellingly, many different immunomodulatory drugs are effective for treating idiopathic nephrotic syndrome, including biologic agents that have well-defined immune targets. In fact, the unexpected efficacy of targeted therapeutic agents has provided important new insights into the pathogenesis of these diseases. Given the large number of drugs that are available to deplete or block specific cells and molecules within the immune system, a better understanding of the immunologic causes of idiopathic nephrotic syndrome may lead to better diagnostic and therapeutic approaches.Campbell, Ruth E.Thurman, Joshua M.2022-10-05T09:25:09-07:00doi:10.2215/CJN.07180622hwp:resource-id:clinjasn;17/12/1823American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunology, focal segmental glomerulosclerosis, idiopathic nephrotic syndromeReviewReviewreview-article20222022-12-01December 202210.2215/CJN.071806221555-90411555-905X2022-10-05T09:25:09-07:002022-12Clinical Journal of the American Society of NephrologyReview171218231834
- Overview of the Medical Management of the Critically Ill PatientThe medical management of the critically ill patient focuses predominantly on treatment of the underlying condition (e.g., sepsis or respiratory failure). However, in the past decade, the importance of initiating early prophylactic treatment for complications arising from care in the intensive care unit setting has become increasingly apparent. As survival from critical illness has improved, there is an increased prevalence of postintensive care syndrome—defined as a decline in physical, cognitive, or psychologic function among survivors of critical illness. The Intensive Care Unit Liberation Bundle, a major initiative of the Society of Critical Care Medicine, is centered on facilitating the return to normal function as early as possible, with the intent of minimizing iatrogenic harm during necessary critical care. These concepts are universally applicable to patients seen by nephrologists in the intensive care unit and may have particular relevance for patients with kidney failure either on dialysis or after kidney transplant. In this article, we will briefly summarize some known organ-based consequences associated with critical illness, review the components of the ABCDEF bundle (the conceptual framework for Intensive Care Unit Liberation), highlight the role nephrologists can play in implementing and complying with the ABCDEF bundle, and briefly discuss areas for additional research.10.2215/CJN.07130622Fri, 18 Nov 2022 05:09:20 GMT-08:00Overview of the Medical Management of the Critically Ill PatientThe medical management of the critically ill patient focuses predominantly on treatment of the underlying condition (e.g., sepsis or respiratory failure). However, in the past decade, the importance of initiating early prophylactic treatment for complications arising from care in the intensive care unit setting has become increasingly apparent. As survival from critical illness has improved, there is an increased prevalence of postintensive care syndrome—defined as a decline in physical, cognitive, or psychologic function among survivors of critical illness. The Intensive Care Unit Liberation Bundle, a major initiative of the Society of Critical Care Medicine, is centered on facilitating the return to normal function as early as possible, with the intent of minimizing iatrogenic harm during necessary critical care. These concepts are universally applicable to patients seen by nephrologists in the intensive care unit and may have particular relevance for patients with kidney failure either on dialysis or after kidney transplant. In this article, we will briefly summarize some known organ-based consequences associated with critical illness, review the components of the ABCDEF bundle (the conceptual framework for Intensive Care Unit Liberation), highlight the role nephrologists can play in implementing and complying with the ABCDEF bundle, and briefly discuss areas for additional research.Martinez, Rebecca H.Liu, Kathleen D.Aldrich, J. Matthew2022-11-18T05:09:20-08:00doi:10.2215/CJN.07130622hwp:resource-id:clinjasn;17/12/1805American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, renal injury, clinical epidemiologyCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-12-01December 202210.2215/CJN.071306221555-90411555-905X2022-11-18T05:09:20-08:002022-12Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury171218051813
- How I Treat Focal Segmental Glomerulosclerosis10.2215/CJN.06850622Tue, 23 Aug 2022 07:06:41 GMT-07:00How I Treat Focal Segmental GlomerulosclerosisLiew, AdrianGibson, Keisha L.2022-08-23T07:06:41-07:00doi:10.2215/CJN.06850622hwp:resource-id:clinjasn;17/12/1814American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfocal segmental glomerulosclerosisKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-12-01December 202210.2215/CJN.068506221555-90411555-905X2022-08-23T07:06:41-07:002022-12Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat171218141816
- A Blueprint for Assessing Affordability of SGLT2 Inhibitors in the United States10.2215/CJN.09900822Wed, 02 Nov 2022 07:07:07 GMT-07:00A Blueprint for Assessing Affordability of SGLT2 Inhibitors in the United StatesKhine, AnnikaLin, Eugene2022-11-02T07:07:07-07:00doi:10.2215/CJN.09900822hwp:resource-id:clinjasn;17/12/1707American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, economic analysis, progression of chronic renal failureEditorialEditorialeditorial20222022-12-01December 202210.2215/CJN.099008221555-90411555-905X2022-11-02T07:07:07-07:002022-12Clinical Journal of the American Society of NephrologyEditorial1712121707173017091741
- Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes10.2215/CJN.08900722Tue, 22 Nov 2022 05:49:08 GMT-08:00Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without DiabetesVart, PriyaVaduganathan, MuthiahJongs, NielsRemuzzi, GiuseppeWheeler, David C.Hou, Fan FanMcCausland, FinnianChertow, Glenn M.Heerspink, Hiddo J.L.2022-11-22T05:49:08-08:00doi:10.2215/CJN.08900722hwp:resource-id:clinjasn;17/12/1754American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic kidney failure, death, treatment, ACEi/ARB, SGLT2 inhibitor, lifetime benefit, renin-angiotensin systemOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-12-01December 202210.2215/CJN.089007221555-90411555-905X2022-11-22T05:49:08-08:002022-12Clinical Journal of the American Society of NephrologyOriginal Article1712121754171017621712
- Toward Guideline-Directed Medical Therapy in Nephrology10.2215/CJN.12401022Tue, 22 Nov 2022 07:10:33 GMT-08:00Toward Guideline-Directed Medical Therapy in NephrologyZeitler, Evan M.Mottl, Amy K.2022-11-22T07:10:33-08:00doi:10.2215/CJN.12401022hwp:resource-id:clinjasn;17/12/1710American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, chronic kidney disease, ACE inhibitors, SGLT2 inhibitorsEditorialEditorialeditorial20222022-12-01December 202210.2215/CJN.124010221555-90411555-905X2022-11-22T07:10:33-08:002022-12Clinical Journal of the American Society of NephrologyEditorial1712121710175417121762
- Community Houses to Increase Access to Home Dialysis10.2215/CJN.09090822Fri, 14 Oct 2022 08:50:05 GMT-07:00Community Houses to Increase Access to Home DialysisWalker, RachaelPalmer, Suetonia2022-10-14T08:50:05-07:00doi:10.2215/CJN.09090822hwp:resource-id:clinjasn;17/12/1820American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, chronic kidney failure, dialysis, end stage kidney disease, home dialysisPerspectivePerspectiveresearch-article20222022-12-01December 202210.2215/CJN.090908221555-90411555-905X2022-10-14T08:50:05-07:002022-12Clinical Journal of the American Society of NephrologyPerspective171218201822
- Effect of Furosemide on Proximal Tubular Secretion of Organic Solutes in Patients Receiving Hemodialysis10.2215/CJN.08310722Tue, 04 Oct 2022 10:46:23 GMT-07:00Effect of Furosemide on Proximal Tubular Secretion of Organic Solutes in Patients Receiving HemodialysisSirich, Tammy L.Hostetter, Thomas H.Flythe, Jennifer E.2022-10-04T10:46:23-07:00doi:10.2215/CJN.08310722hwp:resource-id:clinjasn;17/12/1800American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiuretics, secretion, uremia, furosemideResearch LetterResearch Letterletter20222022-12-01December 202210.2215/CJN.083107221555-90411555-905X2022-10-04T10:46:23-07:002022-12Clinical Journal of the American Society of NephrologyResearch Letter171218001801
- Cost-Effectiveness of Dapagliflozin as a Treatment for Chronic Kidney Disease10.2215/CJN.03790322Wed, 02 Nov 2022 06:03:30 GMT-07:00Cost-Effectiveness of Dapagliflozin as a Treatment for Chronic Kidney DiseaseMcEwan, PhilDarlington, OliverMiller, RyanMcMurray, John J.V.Wheeler, David C.Heerspink, Hiddo J.L.Briggs, AndrewBergenheim, KlasGarcia Sanchez, Juan Jose2022-11-02T06:03:30-07:00doi:10.2215/CJN.03790322hwp:resource-id:clinjasn;17/12/1730American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydapagliflozin, SGLT2 inhibitor, chronic kidney disease, cost-effectivenessOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-12-01December 202210.2215/CJN.037903221555-90411555-905X2022-11-02T06:03:30-07:002022-12Clinical Journal of the American Society of NephrologyOriginal Article1712121730170717411709
- Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes10.2215/CJN.05020422Fri, 04 Nov 2022 07:10:25 GMT-07:00Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 DiabetesØstergaard, Helena BlekenRead, Stephanie H.Sattar, NaveedFranzén, StefanHalbesma, NynkeDorresteijn, Jannick A.N.Westerink, JanVisseren, Frank L.J.Wild, Sarah H.Eliasson, Björnvan der Leeuw, Joep2022-11-04T07:10:25-07:00doi:10.2215/CJN.05020422hwp:resource-id:clinjasn;17/12/1783American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, risk factors, diabetes mellitus, epidemiology and outcomes, epidemiology and outcomesOriginal ArticleDiabetes and the KidneyOriginal ArticleDiabetes and the Kidneyresearch-article20222022-12-01December 202210.2215/CJN.050204221555-90411555-905X2022-11-04T07:10:25-07:002022-12Clinical Journal of the American Society of NephrologyOriginal Article171217831791
- Menstrual Abnormalities and Reproductive Lifespan in Females with CKD10.2215/CJN.07100622Wed, 23 Nov 2022 05:36:35 GMT-08:00Menstrual Abnormalities and Reproductive Lifespan in Females with CKDRytz, Chantal L.Kochaksaraei, Golasa SamediSkeith, LeslieRonksley, Paul E.Dumanski, Sandra M.Robert, MagaliAhmed, Sofia B.2022-11-23T05:36:35-08:00doi:10.2215/CJN.07100622hwp:resource-id:clinjasn;17/12/1742American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, dialysis, kidney transplantation, menarche, menopause, menstruation, menstrual disturbances, menstrual irregularities, reproductive life spanOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-12-01December 202210.2215/CJN.071006221555-90411555-905X2022-11-23T05:36:35-08:002022-12Clinical Journal of the American Society of NephrologyOriginal Article1712121742171617531718
- A Survey of Environmental Sustainability Practices in Dialysis Facilities in Australia and New Zealand10.2215/CJN.08090722Fri, 11 Nov 2022 07:12:04 GMT-08:00A Survey of Environmental Sustainability Practices in Dialysis Facilities in Australia and New ZealandTalbot, BenjaminBarraclough, KatherineSypek, MatthewGois, PedroArnold, LeilaMcDonald, StephenKnight, John2022-11-11T07:12:04-08:00doi:10.2215/CJN.08090722hwp:resource-id:clinjasn;17/12/1792American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, climate change, Australia, New Zealand, environmental sustainabilityOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-12-01December 202210.2215/CJN.080907221555-90411555-905X2022-11-11T07:12:04-08:002022-12Clinical Journal of the American Society of NephrologyOriginal Article171217921799
- Bardoxolone Methyl for Alport Syndrome: Opportunities and Challenges10.2215/CJN.12491022Mon, 21 Nov 2022 11:30:28 GMT-08:00Bardoxolone Methyl for Alport Syndrome: Opportunities and ChallengesQuinlan, CatherineJayasinghe, Kushani2022-11-21T11:30:28-08:00doi:10.2215/CJN.12491022hwp:resource-id:clinjasn;17/12/1713American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, bardoxolone, therapy, genetic kidney disease, hematuria, proteinuria, clinical trialEditorialEditorialeditorial20222022-12-01December 202210.2215/CJN.124910221555-90411555-905X2022-11-21T11:30:28-08:002022-12Clinical Journal of the American Society of NephrologyEditorial1712121713176317151774
- Obesity in CKD10.2215/CJN.09150822Tue, 20 Sep 2022 06:25:15 GMT-07:00Obesity in CKDFriedman, Allon N.2022-09-20T06:25:15-07:00doi:10.2215/CJN.09150822hwp:resource-id:clinjasn;17/12/1817American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyobesity, chronic kidney disease, bariatric surgery, glucagon-like peptide-1 receptor agonist, glucose-dependent insulinotropic polypeptide, weight lossPerspectivePerspectiveresearch-article20222022-12-01December 202210.2215/CJN.091508221555-90411555-905X2022-09-20T06:25:15-07:002022-12Clinical Journal of the American Society of NephrologyPerspective171218171819
- Reproductive Health in Women with Kidney Disease10.2215/CJN.12461022Wed, 23 Nov 2022 05:36:35 GMT-08:00Reproductive Health in Women with Kidney DiseaseGumber, RamnikaShah, Silvi2022-11-23T05:36:35-08:00doi:10.2215/CJN.12461022hwp:resource-id:clinjasn;17/12/1716American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymenstrual abnormalities, reproductive healthEditorialEditorialeditorial20222022-12-01December 202210.2215/CJN.124610221555-90411555-905X2022-11-23T05:36:35-08:002022-12Clinical Journal of the American Society of NephrologyEditorial1712121716174217181753
- Effects of Bardoxolone Methyl in Alport Syndrome10.2215/CJN.02400222Mon, 21 Nov 2022 11:30:28 GMT-08:00Effects of Bardoxolone Methyl in Alport SyndromeWarady, Bradley A.Pergola, Pablo E.Agarwal, RajivAndreoli, SharonAppel, Gerald B.Bangalore, SripalBlock, Geoffrey A.Chapman, Arlene B.Chin, Melanie P.Gibson, Keisha L.Goldsberry, AngieIijima, KazumotoInker, Lesley A.Kashtan, Clifford E.Knebelmann, BertrandMariani, Laura H.Meyer, Colin J.Nozu, KandaiO’Grady, MeganRheault, Michelle N.Silva, Arnold L.Stenvinkel, PeterTorra, RoserChertow, Glenn M.2022-11-21T11:30:28-08:00doi:10.2215/CJN.02400222hwp:resource-id:clinjasn;17/12/1763American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, bardoxolone methyl, CKDOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-12-01December 202210.2215/CJN.024002221555-90411555-905X2022-11-21T11:30:28-08:002022-12Clinical Journal of the American Society of NephrologyOriginal Article1712121763171317741715
- Gout Among Dialysis Patients: Prevalence, Associated Factors, Treatment Patterns, and Outcomes; Population-Based Retrospective Cohort StudyBackground: An association between gout and non-dialysis chronic kidney disease has long been recognized, yet limited research exists regarding prevalence, treatment, anemia management, and outcomes in end-stage renal disease (ESRD) patients undergoing dialysis. Methods: Using data from US Renal Data System (USRDS), we conducted a population-based retrospective cohort study in adult patients covered by Medicare and on dialysis in 2017. Multivariate logistic regression models were used to estimate potential factors and odds of gout diagnosis. Anti-gout medications and impact on anemia management were assessed and compared between gout and non-gout dialysis patients using descriptive and regression analyses. Associations for all-cause mortality and cardiovascular-related hospitalizations during 1-year of study follow-up were compared between gout and non-gout patients using multivariate Cox regression models. Results: Of 231,841 ESRD Medicare patients in 2017 undergoing continuous dialysis, 31,300 (13.5%) had 1 or more gout diagnostic code(s). Increased odds of having a gout diagnosis were independently associated with older age, male gender, Asian race, obesity, hypertension, and cardiovascular disease. Gout diagnosis was associated with higher prevalence for anemia as indicated by increased erythropoietin-stimulating-agent (ESA) requirements (OR=1.18 for high vs. low ESA dose, 95% 1.14 to 1.22) and likelihood of blood transfusions (OR=1.34, 95% CI 1.30 to 1.38). During the 1-year study follow-up, mortality among gout vs non-gout patients was higher by 3% (95% CI: 0-6%), and a composite association of mortality and cardiovascular disease hospitalization was higher by 6% (95% CI: 3-9%) after adjusting for comorbid conditions. Conclusions: A gout diagnosis was found in 13.5% of US dialysis-dependent patients and was associated with a higher burden of comorbid cardiovascular conditions as well as an elevated incidence of hospitalization and mortality. These observations improve our current understanding of gout among the dialysis population and highlight the importance of new and better treatments to improve outcomes.bmarder@horizontherapeutics.com10.34067/KID.0004132022Tue, 06 Dec 2022 01:28:30 GMT-08:00Gout Among Dialysis Patients: Prevalence, Associated Factors, Treatment Patterns, and Outcomes; Population-Based Retrospective Cohort StudyBackground: An association between gout and non-dialysis chronic kidney disease has long been recognized, yet limited research exists regarding prevalence, treatment, anemia management, and outcomes in end-stage renal disease (ESRD) patients undergoing dialysis. Methods: Using data from US Renal Data System (USRDS), we conducted a population-based retrospective cohort study in adult patients covered by Medicare and on dialysis in 2017. Multivariate logistic regression models were used to estimate potential factors and odds of gout diagnosis. Anti-gout medications and impact on anemia management were assessed and compared between gout and non-gout dialysis patients using descriptive and regression analyses. Associations for all-cause mortality and cardiovascular-related hospitalizations during 1-year of study follow-up were compared between gout and non-gout patients using multivariate Cox regression models. Results: Of 231,841 ESRD Medicare patients in 2017 undergoing continuous dialysis, 31,300 (13.5%) had 1 or more gout diagnostic code(s). Increased odds of having a gout diagnosis were independently associated with older age, male gender, Asian race, obesity, hypertension, and cardiovascular disease. Gout diagnosis was associated with higher prevalence for anemia as indicated by increased erythropoietin-stimulating-agent (ESA) requirements (OR=1.18 for high vs. low ESA dose, 95% 1.14 to 1.22) and likelihood of blood transfusions (OR=1.34, 95% CI 1.30 to 1.38). During the 1-year study follow-up, mortality among gout vs non-gout patients was higher by 3% (95% CI: 0-6%), and a composite association of mortality and cardiovascular disease hospitalization was higher by 6% (95% CI: 3-9%) after adjusting for comorbid conditions. Conclusions: A gout diagnosis was found in 13.5% of US dialysis-dependent patients and was associated with a higher burden of comorbid cardiovascular conditions as well as an elevated incidence of hospitalization and mortality. These observations improve our current understanding of gout among the dialysis population and highlight the importance of new and better treatments to improve outcomes.Zhang, YiKshirsagar, OnkarMarder, Brad A.Cohen, Amy R.LaMoreaux, BrianBleyer, Anthony J.2022-12-06T13:28:30-08:00doi:10.34067/KID.0004132022hwp:resource-id:kidney360;KID.0004132022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Gout, ESRD, Dialysis, Risk Factors, USRDS, ESA, Anemia, Retrospective, Clinical, Outcomes, Basic ScienceOriginal InvestigationOriginal Investigationother202210.34067/KID.00041320222641-76502641-76502022-12-06T13:28:30-08:00Kidney360Original Investigation10.34067/KID.0004132022
- Dynein-mediated trafficking, a new mechanism of diabetic podocytopathyBackground: Diabetic nephropathy (DN) is characterized by increased endocytosis and degradation of nephrin, a protein that comprises the molecular sieve of the glomerular filtration barrier. While nephrin internalization has been found activated in diabetes-stressed podocytes, the post-internalization trafficking steps that lead to the eventual depletion of nephrin and the development of DN are unclear. Our work on an inherited podocytopathy uncovered that dysregulated dynein could compromise nephrin trafficking, leading us to test whether and how dynein mediates the pathogenesis of DN. Methods: We analyzed the transcription of dynein components in public DN databases, using the Nephroseq platform. We verified altered dynein transcription in diabetic podocytopathy by quantitative PCR. Dynein-mediated trafficking and degradation of nephrin was investigated using an in vitro nephrin trafficking model and was demonstrated in a mouse model with streptozotocin (STZ)-induced DN, as well as in human kidney biopsy sections. Results: Our transcription analysis revealed increased expression of dynein in human DN and diabetic mouse kidney, correlated significantly with the severity of hyperglycemia and DN. In diabetic podocytopathy, we observed that dynein-mediated post-endocytic sorting of nephrin was upregulated, resulting in accelerated nephrin degradation and disrupted nephrin recycling. In hyperglycemia-stressed podocytes, Dynll1, one of the most upregulated dynein components, is required for the recruitment of dynein complex that mediates the post-endocytic sorting of nephrin. This was corroborated by observing enhanced Dynll1-nephrin colocalization in podocytes of diabetic patients, as well as dynein-mediated trafficking and degradation of nephrin in STZ-induced diabetic mice with hyperglycemia. Knockdown of Dynll1 attenuated lysosomal degradation of nephrin and promoted its recycling, suggesting the essential role of Dynll1 in dynein-mediated mistrafficking. Conclusion: Our studies show that hyperglycemia stimulates dynein-mediated trafficking of nephrin to lysosomes by inducing its expression. The decoding of dynein-driven pathogenesis of diabetic podocytopathy offers a spectrum of new dynein-related therapeutic targets for DN.hua-sun@uiowa.edu10.34067/KID.0006852022Tue, 06 Dec 2022 01:28:30 GMT-08:00Dynein-mediated trafficking, a new mechanism of diabetic podocytopathyBackground: Diabetic nephropathy (DN) is characterized by increased endocytosis and degradation of nephrin, a protein that comprises the molecular sieve of the glomerular filtration barrier. While nephrin internalization has been found activated in diabetes-stressed podocytes, the post-internalization trafficking steps that lead to the eventual depletion of nephrin and the development of DN are unclear. Our work on an inherited podocytopathy uncovered that dysregulated dynein could compromise nephrin trafficking, leading us to test whether and how dynein mediates the pathogenesis of DN. Methods: We analyzed the transcription of dynein components in public DN databases, using the Nephroseq platform. We verified altered dynein transcription in diabetic podocytopathy by quantitative PCR. Dynein-mediated trafficking and degradation of nephrin was investigated using an in vitro nephrin trafficking model and was demonstrated in a mouse model with streptozotocin (STZ)-induced DN, as well as in human kidney biopsy sections. Results: Our transcription analysis revealed increased expression of dynein in human DN and diabetic mouse kidney, correlated significantly with the severity of hyperglycemia and DN. In diabetic podocytopathy, we observed that dynein-mediated post-endocytic sorting of nephrin was upregulated, resulting in accelerated nephrin degradation and disrupted nephrin recycling. In hyperglycemia-stressed podocytes, Dynll1, one of the most upregulated dynein components, is required for the recruitment of dynein complex that mediates the post-endocytic sorting of nephrin. This was corroborated by observing enhanced Dynll1-nephrin colocalization in podocytes of diabetic patients, as well as dynein-mediated trafficking and degradation of nephrin in STZ-induced diabetic mice with hyperglycemia. Knockdown of Dynll1 attenuated lysosomal degradation of nephrin and promoted its recycling, suggesting the essential role of Dynll1 in dynein-mediated mistrafficking. Conclusion: Our studies show that hyperglycemia stimulates dynein-mediated trafficking of nephrin to lysosomes by inducing its expression. The decoding of dynein-driven pathogenesis of diabetic podocytopathy offers a spectrum of new dynein-related therapeutic targets for DN.Sun, HuaWeidner, JillianAllamargot, ChantalPiper, RobertMisurac, Jason M.Nester, Carla2022-12-06T13:28:30-08:00doi:10.34067/KID.0006852022hwp:resource-id:kidney360;KID.0006852022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360dynein, trafficking, diabetic nephropathy, podocyte, nephrin, Basic ScienceOriginal InvestigationOriginal Investigationother202210.34067/KID.00068520222641-76502641-76502022-12-06T13:28:30-08:00Kidney360Original Investigation10.34067/KID.0006852022
- Associations of Air Pollution and Serum Biomarker Abnormalities in Individuals with Hemodialysis-Dependent Kidney FailureBackground: Ambient PM2.5 is a ubiquitous air pollutant with established adverse health consequences. While postulated to promote a systemic inflammatory response, limited studies have demonstrated changes in serum biomarkers related to PM2.5 exposure. We aim to examine associations between short-term PM2.5 exposure and commonly measured biomarkers known to be affected by inflammation among patients receiving maintenance in-center hemodialysis. Methods: We conducted a retrospective open cohort study from 1-1-2008 to 12-31-2014. Adult hemodialysis patients were identified from the United States Renal Data System and linked at the patient level to laboratory data from a large dialysis organization. Daily ambient PM2.5 was estimated on a 1 km grid and assigned to cohort patients based on the ZIP codes of dialysis clinics. Serum albumin, serum ferritin, transferrin saturation (TSAT), and serum hemoglobin were ascertained from the dialysis provider organization database. Mixed-effect models were used to assess the changes in biomarker levels associated with PM2.5 exposure. Results: The final cohort included 173,697 hemodialysis patients. Overall, the daily ZIP-level ambient PM2.5 averages were 8.4-8.5 µg/m3. A 10 µg/m3 increase in same-day ambient PM2.5 exposure was associated with higher relative risks of lower albumin (RR: 1.01, 95% CI: 1.01, 1.02) and lower hemoglobin (RR: 1.02, 95%CI: 1.01, 1.03). Associations of same-day ambient PM2.5 exposure and higher ferritin and lower TSAT did not reach statistical significance. Conclusions: Short-term PM2.5 exposure was associated with lower serum hemoglobin and albumin among patients receiving in-center hemodialysis. These findings lend support to the role of inflammation in PM2.5 exposure-outcome associations.rappold.ana@epa.gov10.34067/KID.0003822022Tue, 06 Dec 2022 10:17:15 GMT-08:00Associations of Air Pollution and Serum Biomarker Abnormalities in Individuals with Hemodialysis-Dependent Kidney FailureBackground: Ambient PM2.5 is a ubiquitous air pollutant with established adverse health consequences. While postulated to promote a systemic inflammatory response, limited studies have demonstrated changes in serum biomarkers related to PM2.5 exposure. We aim to examine associations between short-term PM2.5 exposure and commonly measured biomarkers known to be affected by inflammation among patients receiving maintenance in-center hemodialysis. Methods: We conducted a retrospective open cohort study from 1-1-2008 to 12-31-2014. Adult hemodialysis patients were identified from the United States Renal Data System and linked at the patient level to laboratory data from a large dialysis organization. Daily ambient PM2.5 was estimated on a 1 km grid and assigned to cohort patients based on the ZIP codes of dialysis clinics. Serum albumin, serum ferritin, transferrin saturation (TSAT), and serum hemoglobin were ascertained from the dialysis provider organization database. Mixed-effect models were used to assess the changes in biomarker levels associated with PM2.5 exposure. Results: The final cohort included 173,697 hemodialysis patients. Overall, the daily ZIP-level ambient PM2.5 averages were 8.4-8.5 µg/m3. A 10 µg/m3 increase in same-day ambient PM2.5 exposure was associated with higher relative risks of lower albumin (RR: 1.01, 95% CI: 1.01, 1.02) and lower hemoglobin (RR: 1.02, 95%CI: 1.01, 1.03). Associations of same-day ambient PM2.5 exposure and higher ferritin and lower TSAT did not reach statistical significance. Conclusions: Short-term PM2.5 exposure was associated with lower serum hemoglobin and albumin among patients receiving in-center hemodialysis. These findings lend support to the role of inflammation in PM2.5 exposure-outcome associations.Xi, YuzhiRichardson, DavidKshirsagar, Abhijit V.Flythe, Jennifer E.Whitsel, Eric A.Wade, Timothy J.Rappold, Ana2022-12-06T10:17:15-08:00doi:10.34067/KID.0003822022hwp:resource-id:kidney360;KID.0003822022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360inflammation, air pollution, biomarker, chronic hemodialysisOriginal InvestigationOriginal Investigationother202210.34067/KID.00038220222641-76502641-76502022-12-06T10:17:15-08:00Kidney360Original Investigation10.34067/KID.0003822022
- Incisional hernia development after live donor nephrectomy: Impact of surgical techniqueBackground: Characteristics of incisional hernia (IH) formation following live donor nephrectomy (LDN) are not well defined. The goal of this study was to describe the incidence of IH within 3 years following LDN and identify risk factors contributing to their formation. Materials and methods: We performed a single center, retrospective review of all LDN between February 2013 to October 2018. Patients with and without IH were compared based on donor and operative variables. Data were analyzed using chi square tests with column proportions. Multivariable logistic regression with backwards elimination was used to evaluate the likelihood of IH based on potential risk factors. Results: Three hundred and one individuals underwent live donor nephrectomy. Twenty-eight patients (9.3%) developed an incisional hernia with median time to development of 7 months (range: 2-24 months). Obesity [Body Mass Index (BMI) ≥30], periumbilical hand port, and vertical infraumbilical hand port were associated with increased risk of IH development on univariate analysis. On multivariate analysis, obesity and periumbilical hand port location were persistent risk factors for IH. Conclusions: The incidence of IH following LDN is prevalent and associated with obesity and operative technique. Placing the hand port infraumbilical with a transverse fascial incision may reduce the risk of IH following LDN.bernard.j.dubray@vumc.org10.34067/KID.0005262022Tue, 06 Dec 2022 10:17:15 GMT-08:00Incisional hernia development after live donor nephrectomy: Impact of surgical techniqueBackground: Characteristics of incisional hernia (IH) formation following live donor nephrectomy (LDN) are not well defined. The goal of this study was to describe the incidence of IH within 3 years following LDN and identify risk factors contributing to their formation. Materials and methods: We performed a single center, retrospective review of all LDN between February 2013 to October 2018. Patients with and without IH were compared based on donor and operative variables. Data were analyzed using chi square tests with column proportions. Multivariable logistic regression with backwards elimination was used to evaluate the likelihood of IH based on potential risk factors. Results: Three hundred and one individuals underwent live donor nephrectomy. Twenty-eight patients (9.3%) developed an incisional hernia with median time to development of 7 months (range: 2-24 months). Obesity [Body Mass Index (BMI) ≥30], periumbilical hand port, and vertical infraumbilical hand port were associated with increased risk of IH development on univariate analysis. On multivariate analysis, obesity and periumbilical hand port location were persistent risk factors for IH. Conclusions: The incidence of IH following LDN is prevalent and associated with obesity and operative technique. Placing the hand port infraumbilical with a transverse fascial incision may reduce the risk of IH following LDN.DuBray, Bernard J.Thompson, Joshua J.Shaffer, DavidHale, Doug A.Rega, Scott A.Feurer, Irene D.Forbes, Rachel C.2022-12-06T10:17:15-08:00doi:10.34067/KID.0005262022hwp:resource-id:kidney360;KID.0005262022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360living donor, hernia, nephrectomy, Laparoscopic donor nephrectomy, Kidney transplantation, Incisional herniaOriginal InvestigationOriginal Investigationother202210.34067/KID.00052620222641-76502641-76502022-12-06T10:17:15-08:00Kidney360Original Investigation10.34067/KID.0005262022
- Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis PatientsBackground: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. Methods: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5,117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol, or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with vs. without gout. Outcomes included erythropoietin resistance index (ERI = ESA dose/(hemoglobin*weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). Results: Gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9-12%). Both HD and PD patients with gout (vs. no gout) were older, more likely male, with higher BMI, and higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate lowering therapy. After propensity score matching, mean ERI was 3-6% higher for gout vs. non-gout patients, while there was minimal evidence of association with clinical outcomes or PROs. Conclusion: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely underreported. Gout was not associated with adverse clinical or patient-reported outcomes.angelo.karaboyas@arborresearch.org10.34067/KID.0005392022Mon, 05 Dec 2022 11:21:39 GMT-08:00Gout Prevalence, Practice Patterns, and Associations with Outcomes in North American Dialysis PatientsBackground: Gout occurs frequently in patients with kidney disease and can lead to a significant burden on quality of life. Gout prevalence, and its association with outcomes in hemodialysis (HD) and peritoneal dialysis (PD) populations located in North America, is unknown. Methods: We used data from North America cohorts of 70,297 HD patients (DOPPS, 2012-2020) and 5,117 PD patients (PDOPPS, 2014-2020). We used three definitions of gout for this analysis: (1) having an active prescription for colchicine or febuxostat; (2) having an active prescription for colchicine, febuxostat, or allopurinol, or (3) having an active prescription for colchicine, febuxostat, or allopurinol, or prior diagnosis of gout. Propensity score matching was used to compare outcomes among patients with vs. without gout. Outcomes included erythropoietin resistance index (ERI = ESA dose/(hemoglobin*weight)), all-cause mortality, hospitalization, and patient-reported outcomes (PROs). Results: Gout prevalence was 13% in HD and 21% in PD; it was highest among incident dialysis patients. Description of previous history of gout was rare, and identification of gout defined by colchicine (2-3%) or febuxostat (1%) prescription was less frequent than by allopurinol (9-12%). Both HD and PD patients with gout (vs. no gout) were older, more likely male, with higher BMI, and higher prevalence of cardiovascular comorbidities. About half of patients with a gout history were prescribed urate lowering therapy. After propensity score matching, mean ERI was 3-6% higher for gout vs. non-gout patients, while there was minimal evidence of association with clinical outcomes or PROs. Conclusion: In a large cohort of PD and HD patients in North America, we found that gout occurs frequently and is likely underreported. Gout was not associated with adverse clinical or patient-reported outcomes.Guedes, MuriloZhao, JunhuiLaMoreaux, BrianMarder, BradGorlitsky, BarryDomingues, ViniciusRivara, Matthew BLew, SusieRobinson, BrucePecoits-Filho, RobertoKaraboyas, Angelo2022-12-05T11:21:39-08:00doi:10.34067/KID.0005392022hwp:resource-id:kidney360;KID.0005392022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360gout, end-stage kidney disease, Hemodialysis, Peritoneal Dialysis, North America, PrevalenceOriginal InvestigationOriginal Investigationother202210.34067/KID.00053920222641-76502641-76502022-12-05T11:21:39-08:00Kidney360Original Investigation10.34067/KID.0005392022
- Use of Rituximab in Childhood Idiopathic Nephrotic SyndromeRituximab is an established therapy in children with idiopathic nephrotic syndrome to sustain short to medium term disease remission and avoid steroid toxicities. Recent trials focus on its use as a first-line agent among those with milder disease severity. Rituximab is used in multi-drug refractory nephrotic syndrome and post-transplant disease recurrence, although the evidence is much less substantial. Available data suggest that the treatment response to rituximab depends on various patient factors, dosing regimen and the concomitant use of maintenance immunosuppression. Following repeated treatments, patients are found to have an improving response overall with longer relapse-free period. The drug effect, however, is not permanent and 80% of patients eventually relapse and many will require an additional course of rituximab. This underpins the importance to understand the long-term safety profile upon repeated treatments. Although rituximab appears to be generally safe, there are concerns of long-term hypogammaglobulinaemia, especially in young children. Reliable immunophenotyping and biomarkers are yet to be discovered to predict treatment success, risk of both rare and severe side-effects, persistent hypogammaglobulinaemia and to guide on re-dosing strategy. In this review, we highlight recent advances on the use of rituximab for childhood nephrotic syndrome and how the therapeutic landscape is evolving.Kjell.Tullus@gosh.nhs.uk10.2215/CJN.08570722Thu, 01 Dec 2022 12:41:52 GMT-08:00Use of Rituximab in Childhood Idiopathic Nephrotic SyndromeRituximab is an established therapy in children with idiopathic nephrotic syndrome to sustain short to medium term disease remission and avoid steroid toxicities. Recent trials focus on its use as a first-line agent among those with milder disease severity. Rituximab is used in multi-drug refractory nephrotic syndrome and post-transplant disease recurrence, although the evidence is much less substantial. Available data suggest that the treatment response to rituximab depends on various patient factors, dosing regimen and the concomitant use of maintenance immunosuppression. Following repeated treatments, patients are found to have an improving response overall with longer relapse-free period. The drug effect, however, is not permanent and 80% of patients eventually relapse and many will require an additional course of rituximab. This underpins the importance to understand the long-term safety profile upon repeated treatments. Although rituximab appears to be generally safe, there are concerns of long-term hypogammaglobulinaemia, especially in young children. Reliable immunophenotyping and biomarkers are yet to be discovered to predict treatment success, risk of both rare and severe side-effects, persistent hypogammaglobulinaemia and to guide on re-dosing strategy. In this review, we highlight recent advances on the use of rituximab for childhood nephrotic syndrome and how the therapeutic landscape is evolving.Chan, EugeneYap, DesmondColucci, ManuelaMa, Alison Lap-takParekh, RulanTullus, Kjell2022-12-01T12:41:52-08:00doi:10.2215/CJN.08570722hwp:resource-id:clinjasn;CJN.08570722v1American Society of NephrologyClinical Journal of the American Society of NephrologyInvited FeaturesInvited Featuresresearch-article202210.2215/CJN.085707221555-90411555-905X2022-12-01T12:41:52-08:00Clinical Journal of the American Society of NephrologyInvited FeaturesCJN.08570722
- Artificial Intelligence You Can Trust: What Matters Beyond Performance When Applying Artificial Intelligence to Renal Histopathology?Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system. In the extreme, deployment of highly performant but “black box” AI is fraught with risk, and high-profile errors could damage future trust in the technology. Furthermore, a major factor determining whether new systems are adopted in clinical settings is whether they are “trusted” by clinicians. Key to unlocking trust will be designing platforms optimized for intuitive human-AI interactions and ensuring that, where judgment is required to resolve ambiguous areas of assessment, the workings of the AI image classifier are understandable to the human observer. Therefore, determining the optimal design for AI systems depends on factors beyond performance, with considerations of goals, interpretability, and safety constraining many design and engineering choices. In this article, we explore challenges that arise in the application of AI to renal histopathology, and consider areas where choices around model architecture, training strategy, and workflow design may be influenced by factors beyond the final performance metrics of the system.10.1681/ASN.2022010069Wed, 09 Nov 2022 06:42:55 GMT-08:00Artificial Intelligence You Can Trust: What Matters Beyond Performance When Applying Artificial Intelligence to Renal Histopathology?Although still in its infancy, artificial intelligence (AI) analysis of kidney biopsy images is anticipated to become an integral aspect of renal histopathology. As these systems are developed, the focus will understandably be on developing ever more accurate models, but successful translation to the clinic will also depend upon other characteristics of the system. In the extreme, deployment of highly performant but “black box” AI is fraught with risk, and high-profile errors could damage future trust in the technology. Furthermore, a major factor determining whether new systems are adopted in clinical settings is whether they are “trusted” by clinicians. Key to unlocking trust will be designing platforms optimized for intuitive human-AI interactions and ensuring that, where judgment is required to resolve ambiguous areas of assessment, the workings of the AI image classifier are understandable to the human observer. Therefore, determining the optimal design for AI systems depends on factors beyond performance, with considerations of goals, interpretability, and safety constraining many design and engineering choices. In this article, we explore challenges that arise in the application of AI to renal histopathology, and consider areas where choices around model architecture, training strategy, and workflow design may be influenced by factors beyond the final performance metrics of the system.Ayorinde, John O.O.Citterio, FedericaLandrò, MatteoPeruzzo, EliaIslam, TubaTilley, SimonTaylor, GeoffreyBardsley, VictoriaLiò, PietroSamoshkin, AlexPettigrew, Gavin J.2022-11-09T06:42:55-08:00doi:10.1681/ASN.2022010069hwp:resource-id:jnephrol;33/12/2133American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriosclerosis, glomerulosclerosis, interstitial fibrosis, kidney biopsy, renal fibrosis, renal pathology, renal transplantation, transplant pathology, artificial intelligence, AIReviewReviewreview-article20222022-12-01December 202210.1681/ASN.20220100691046-66731533-34502022-11-09T06:42:55-08:002022-12Journal of the American Society of NephrologyReview331221332140
- Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses10.1681/ASN.2022030286Mon, 24 Oct 2022 08:45:27 GMT-07:00Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory ResponsesDoan Ngoc, Tra-MyTilly, GaëlleDanger, RichardBonizec, OrianneMasset, ChristopheGuérif, PierrickBruneau, SarahGlemain, AlexandreHarb, JeanCadoux, MarionVivet, AnaïsMai, Hoa LeGarcia, AlexandraLaplaud, DavidLiblau, RolandGiral, MagaliBlandin, StéphanieFeyeux, MagalieDubreuil, LaurencePecqueur, ClaireCyr, MatthewNi, WeimingBrouard, SophieDegauque, Nicolas,Blancho, GillesBranchereau, JulienCantarovich, DiegoChapelet, AgnèsDantal, JacquesDeltombe, ClémentFigueres, LucileGarandeau, ClaireGiral, MagaliGourraud-Vercel, CarolineHourmant, MaryvonneKaram, GeorgesKerleau, ClarisseMasset, ChristopheKervela, DelphineLebot, SabineMeurette, AurélieVille, SimonKandell, ChristineMoreau, AnneRenaudin, KarineCesbron, AnneDelbos, FlorentWalencik, AlexandreDevis, Anne2022-10-24T08:45:27-07:00doi:10.1681/ASN.2022030286hwp:resource-id:jnephrol;33/12/2211American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycell adhesion, chemokine, lymphocytes, kidney transplantation, immunology, endothelium, chronic allograft rejection, cell activation, adhesion molecule, purinergic P2X4 receptorsBasic ResearchTransplantationBasic ResearchTransplantationresearch-article20222022-12-01December 202210.1681/ASN.20220302861046-66731533-34502022-10-24T08:45:27-07:002022-12Journal of the American Society of NephrologyBasic Research331222112231
- Targeting the Right Metrics for Kidney Transplantation Success10.1681/ASN.2022080872Wed, 12 Oct 2022 11:47:37 GMT-07:00Targeting the Right Metrics for Kidney Transplantation SuccessSharif, Adnan2022-10-12T11:47:37-07:00doi:10.1681/ASN.2022080872hwp:resource-id:jnephrol;33/12/2323American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, survivalLetter to the EditorLetter to the Editorletter20222022-12-01December 202210.1681/ASN.20220808721046-66731533-34502022-10-12T11:47:37-07:002022-12Journal of the American Society of NephrologyLetter to the Editor331282323161323241624
- A Step toward Understanding the Story Behind the Pictures: Molecular Diagnostics and the Banff Classification of Renal Allograft Pathology10.1681/ASN.2022070847Wed, 28 Sep 2022 09:06:46 GMT-07:00A Step toward Understanding the Story Behind the Pictures: Molecular Diagnostics and the Banff Classification of Renal Allograft PathologyBissonnette, Mei Lin Z.Riazy, MaziarCunningham, Amanda M.Gill, John S.2022-09-28T09:06:46-07:00doi:10.1681/ASN.2022070847hwp:resource-id:jnephrol;33/12/2131American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute rejection, renal biopsy, transplantationUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-12-01December 202210.1681/ASN.20220708471046-66731533-34502022-09-28T09:06:46-07:002022-12Journal of the American Society of NephrologyUp Front Matters3312122131230621322319
- Authors’ Reply: In Silico–Based Approach to the Discovery of New Antigens in Membranous Nephropathy10.1681/ASN.2022080921Thu, 29 Sep 2022 10:43:10 GMT-07:00Authors’ Reply: In Silico–Based Approach to the Discovery of New Antigens in Membranous NephropathySealfon, RachelMariani, LauraKretzler, MatthiasBeck, Laurence H.2022-09-29T10:43:10-07:00doi:10.1681/ASN.2022080921hwp:resource-id:jnephrol;33/12/2322American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, transcriptional profiling, autoantigenLetter to the EditorLetter to the Editorletter20222022-12-01December 202210.1681/ASN.20220809211046-66731533-34502022-09-29T10:43:10-07:002022-12Journal of the American Society of NephrologyLetter to the Editor3312126232223211208232323221221
- Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy10.1681/ASN.2022020189Tue, 30 Aug 2022 07:22:47 GMT-07:00Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA NephropathyZhao, JinBai, MingNing, XiaoxuanQin, YunlongWang, YuweiYu, ZixianDong, RuijuanZhang, YumengSun, Shiren2022-08-30T07:22:47-07:00doi:10.1681/ASN.2022020189hwp:resource-id:jnephrol;33/12/2276American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, gut microbiota, Escherichia-Shigella, 16S ribosomal RNA, treatment responseClinical ResearchGlomerulonephritis and Interstitial NephritisClinical ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-12-01December 202210.1681/ASN.20220201891046-66731533-34502022-08-30T07:22:47-07:002022-12Journal of the American Society of NephrologyClinical Research3312122276i2292i
- Nephrotic Syndrome Gene TBC1D8B Is Required for Endosomal Maturation and Nephrin Endocytosis in Drosophila10.1681/ASN.2022030275Thu, 22 Sep 2022 11:18:08 GMT-07:00Nephrotic Syndrome Gene TBC1D8B Is Required for Endosomal Maturation and Nephrin Endocytosis in DrosophilaMilosavljevic, JulianLempicki, CamilleLang, KonradHeinkele, HelenaKampf, Lina L.Leroy, ClaireChen, MengmengGerstner, LeaSpitz, DominikWang, MinxianKnob, Andrea U.Kayser, SéverineHelmstädter, MartinWalz, GerdPollak, Martin R.Hermle, Tobias2022-09-22T11:18:08-07:00doi:10.1681/ASN.2022030275hwp:resource-id:jnephrol;33/12/2174American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, nephrotic syndrome, genetic kidney disease, endocytosis, focal segmental glomerulosclerosis, glomerular filtration barrier, human genetics, nephrin, Drosophila, nephrocyteBasic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article20222022-12-01December 202210.1681/ASN.20220302751046-66731533-34502022-09-22T11:18:08-07:002022-12Journal of the American Society of NephrologyBasic Research3312122174212721932128
- Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance10.1681/ASN.2022030378Fri, 19 Aug 2022 10:51:51 GMT-07:00Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite ImbalanceHolle, JohannesBartolomaeus, HendrikLöber, UlrikeBehrens, FelixBartolomaeus, Theda U.P.Anandakumar, HarithaaWimmer, Moritz I.Vu, Dai LongKuhring, MathiasBrüning, UlrikeMaifeld, AndrasGeisberger, SabrinaKempa, StefanSchumacher, FabianKleuser, BurkhardBufler, PhilipQuerfeld, UweKitschke, StefanieEngler, DeniseKuhrt, Leonard D.Drechsel, OliverEckardt, Kai-UweForslund, Sofia K.Thürmer, AndreaMcParland, VictoriaKirwan, Jennifer A.Wilck, NicolaMüller, Dominik2022-08-19T10:51:51-07:00doi:10.1681/ASN.2022030378hwp:resource-id:jnephrol;33/12/2259American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, children, chronic kidney disease, hypertension, immunology, pediatric nephrology, vascular disease, chronic inflammation, dysbiosisClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-12-01December 202210.1681/ASN.20220303781046-66731533-34502022-08-19T10:51:51-07:002022-12Journal of the American Society of NephrologyClinical Research3312122259i2275i
- A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination10.1681/ASN.2022030258Fri, 04 Nov 2022 01:16:32 GMT-07:00A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 VaccinationCanney, MarkAtiquzzaman, MohammadCunningham, Amanda M.Zheng, YuyanEr, LeeHawken, StevenZhao, YinshanBarbour, Sean J.2022-11-04T13:16:32-07:00doi:10.1681/ASN.2022030258hwp:resource-id:jnephrol;33/12/2247American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical epidemiology, glomerular disease, COVID-19, vaccination, recurrence, glomerulonephritisClinical EpidemiologyGlomerulonephritis and Interstitial NephritisClinical EpidemiologyGlomerulonephritis and Interstitial Nephritisresearch-article20222022-12-01December 202210.1681/ASN.20220302581046-66731533-34502022-11-04T13:16:32-07:002022-12Journal of the American Society of NephrologyClinical Epidemiology3312122247212822572131
- mRNA COVID-19 Vaccines and Their Risk to Induce a Relapse of Glomerular Diseases10.1681/ASN.2022091078Fri, 04 Nov 2022 01:16:32 GMT-07:00mRNA COVID-19 Vaccines and Their Risk to Induce a Relapse of Glomerular DiseasesKronbichler, AndreasAnders, Hans-Joachim2022-11-04T13:16:32-07:00doi:10.1681/ASN.2022091078hwp:resource-id:jnephrol;33/12/2128American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, vasculitis, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis, membranous nephropathy, COVID-19Up Front MattersEditorialUp Front MattersEditorialeditorial20222022-12-01December 202210.1681/ASN.20220910781046-66731533-34502022-11-04T13:16:32-07:002022-12Journal of the American Society of NephrologyUp Front Matters3312122128224721312257
- This Month’s Highlights10.1681/ASN.2022101157Wed, 30 Nov 2022 10:00:30 GMT-08:00This Month’s HighlightsAmerican Society of Nephrology2022-11-30T10:00:30-08:00doi:10.1681/ASN.2022101157hwp:resource-id:jnephrol;33/12/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyhighlightsThis Month’s HighlightsThis Month’s Highlightsresearch-article20222022-12-01December 202210.1681/ASN.20221011571046-66731533-34502022-11-30T10:00:30-08:002022-12Journal of the American Society of NephrologyThis Month’s Highlights3312121212i219422762259i221022922275
- Skeletal Outcomes in Children and Young Adults with Glomerular Disease10.1681/ASN.2021101372Wed, 28 Sep 2022 07:50:27 GMT-07:00Skeletal Outcomes in Children and Young Adults with Glomerular DiseaseGoodwin Davies, Amy J.Xiao, RuiRazzaghi, HaniehBailey, L. CharlesUtidjian, LevonGluck, CarolineEckrich, DanielDixon, Bradley P.Deakyne Davies, Sara J.Flynn, Joseph T.Ranade, DakshaSmoyer, William E.Kitzmiller, MelodyDharnidharka, Vikas R.Magnusen, BriannaMitsnefes, MarkSomers, MichaelClaes, Donna J.Burrows, Evanette K.Luna, Ingrid Y.Furth, Susan L.Forrest, Christopher B.Denburg, Michelle R.2022-09-28T07:50:27-07:00doi:10.1681/ASN.2021101372hwp:resource-id:jnephrol;33/12/2233American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, fracture, avascular necrosis, osteonecrosis, slipped capital femoral epiphysis, PEDSnet, nephrotic syndrome, young adult, child, musculoskeletal systemClinical EpidemiologyGlomerulonephritis and Interstitial NephritisClinical EpidemiologyGlomerulonephritis and Interstitial Nephritisresearch-article20222022-12-01December 202210.1681/ASN.20211013721046-66731533-34502022-09-28T07:50:27-07:002022-12Journal of the American Society of NephrologyClinical Epidemiology331222332246
- Slit Diaphragms: Junctions That Never Sleep10.1681/ASN.2022101147Fri, 04 Nov 2022 07:11:15 GMT-07:00Slit Diaphragms: Junctions That Never SleepDrummond, Iain A.2022-11-04T07:11:15-07:00doi:10.1681/ASN.2022101147hwp:resource-id:jnephrol;33/12/2127American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, genetic renal disease, focal segmental glomerulosclerosisUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-12-01December 202210.1681/ASN.20221011471046-66731533-34502022-11-04T07:11:15-07:002022-12Journal of the American Society of NephrologyUp Front Matters3312122127217421282193
- Banff Human Organ Transplant Transcripts Correlate with Renal Allograft Pathology and Outcome: Importance of Capillaritis and Subpathologic Rejection10.1681/ASN.2022040444Wed, 31 Aug 2022 11:57:52 GMT-07:00Banff Human Organ Transplant Transcripts Correlate with Renal Allograft Pathology and Outcome: Importance of Capillaritis and Subpathologic RejectionRosales, Ivy A.Mahowald, Grace K.Tomaszewski, KristenHotta, KiyohikoIwahara, NaoyaOtsuka, TakuyaTsuji, TakahiroTakada, YusukeAcheampong, EllenAraujo-Medina, MilagrosBruce, AmyRios, AndreaCosimi, Anthony BenedictElias, NahelKawai, TatsuoGilligan, HannahSafa, KassemRiella, Leonardo V.Tolkoff-Rubin, Nina E.Williams, Winfred W.Smith, Rex NealColvin, Robert B.2022-08-31T11:57:52-07:00doi:10.1681/ASN.2022040444hwp:resource-id:jnephrol;33/12/2306American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant pathology, renal biopsy, molecular biology, rejection, transplantation, pathology, mRNAClinical ResearchTransplantationClinical ResearchTransplantationresearch-article20222022-12-01December 202210.1681/ASN.20220404441046-66731533-34502022-08-31T11:57:52-07:002022-12Journal of the American Society of NephrologyClinical Research3312122306213123192132
- Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases10.1681/ASN.2021101286Wed, 05 Oct 2022 09:45:00 GMT-07:00Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular DiseasesMitrofanova, AllaFontanella, AntonioTolerico, MatthewMallela, ShamroopMolina David, JudithZuo, YiqinBoulina, MarciaKim, Jin-JuSantos, JavierGe, MengyuanSloan, AlexisIssa, WadihGurumani, MargaretPressly, JeffreyIto, MarieKretzler, MatthiasEddy, SeanNelson, RobertMerscher, SandraBurke, GeorgeFornoni, Alessia2022-10-05T09:45:00-07:00doi:10.1681/ASN.2021101286hwp:resource-id:jnephrol;33/12/2153American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyAlport-s syndrome, diabetic nephropathy, STING, glomerular disease, podocyte, proteinuriaBasic ResearchChronic Kidney DiseaseBasic ResearchChronic Kidney Diseaseresearch-article20222022-12-01December 202210.1681/ASN.20211012861046-66731533-34502022-10-05T09:45:00-07:002022-12Journal of the American Society of NephrologyBasic Research331221532173
- In Silico–Based Approach to the Discovery of New Antigens in Membranous Nephropathy10.1681/ASN.2022070832Thu, 29 Sep 2022 10:43:09 GMT-07:00In Silico–Based Approach to the Discovery of New Antigens in Membranous NephropathyTakahashi-Kobayashi, MayumiUsui, JoichiKawanishi, KunioYamagata, Kunihiro2022-09-29T10:43:09-07:00doi:10.1681/ASN.2022070832hwp:resource-id:jnephrol;33/12/2321American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, antigensLetter to the EditorLetter to the Editorletter20222022-12-01December 202210.1681/ASN.20220708321046-66731533-34502022-09-29T10:43:09-07:002022-12Journal of the American Society of NephrologyLetter to the Editor3312126232123221208232223231221
- Designing Interventions Addressing Structural Racism to Reduce Kidney Health Disparities: A Report from a National Institute of Diabetes and Digestive and Kidney Diseases WorkshopStructural racism embodies the many ways in which society fosters racial discrimination through “mutually reinforcing inequitable systems” that limit access to resources and opportunities that can promote health and well being among marginalized communities. To achieve health equity, and kidney health equity more specifically, structural racism must be eliminated. In February 2022, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “Designing Interventions that Address Structural Racism to Reduce Kidney Health Disparities” workshop, which was aimed at describing the mechanisms through which structural racism contributes to health and health care disparities for people along the continuum of kidney disease and identifying actionable opportunities for interventional research focused on dismantling or addressing the effects of structural racism. Participants identified six domains as key targets for interventions and future research: (1) apply an antiracism lens, (2) promote structural interventions, (3) target multiple levels, (4) promote effective community and stakeholder engagement, (5) improve data collection, and (6) advance health equity through new health care models. There is an urgent need for research to develop, implement, and evaluate interventions that address the unjust systems, policies, and laws that generate and perpetuate inequities in kidney health.10.1681/ASN.2022080890Wed, 19 Oct 2022 12:40:55 GMT-07:00Designing Interventions Addressing Structural Racism to Reduce Kidney Health Disparities: A Report from a National Institute of Diabetes and Digestive and Kidney Diseases WorkshopStructural racism embodies the many ways in which society fosters racial discrimination through “mutually reinforcing inequitable systems” that limit access to resources and opportunities that can promote health and well being among marginalized communities. To achieve health equity, and kidney health equity more specifically, structural racism must be eliminated. In February 2022, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “Designing Interventions that Address Structural Racism to Reduce Kidney Health Disparities” workshop, which was aimed at describing the mechanisms through which structural racism contributes to health and health care disparities for people along the continuum of kidney disease and identifying actionable opportunities for interventional research focused on dismantling or addressing the effects of structural racism. Participants identified six domains as key targets for interventions and future research: (1) apply an antiracism lens, (2) promote structural interventions, (3) target multiple levels, (4) promote effective community and stakeholder engagement, (5) improve data collection, and (6) advance health equity through new health care models. There is an urgent need for research to develop, implement, and evaluate interventions that address the unjust systems, policies, and laws that generate and perpetuate inequities in kidney health.Crews, Deidra C.Patzer, Rachel E.Cervantes, LiliaKnight, RichardPurnell, Tanjala S.Powe, Neil R.Edwards, Dawn P.Norris, Keith C.2022-10-19T12:40:55-07:00doi:10.1681/ASN.2022080890hwp:resource-id:jnephrol;33/12/2141American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhealth disparities, CKD, racism, racial and ethnic disparitiesSpecial ArticleSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseaseSpecial ArticleSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-12-01December 202210.1681/ASN.20220808901046-66731533-34502022-10-19T12:40:55-07:002022-12Journal of the American Society of NephrologySpecial Article331221412152
- HLA-DQ Mismatches Lead to More Unacceptable Antigens, Greater Sensitization, and Increased Disparities in Repeat Transplant Candidates10.1681/ASN.2022030296Wed, 31 Aug 2022 11:57:52 GMT-07:00HLA-DQ Mismatches Lead to More Unacceptable Antigens, Greater Sensitization, and Increased Disparities in Repeat Transplant CandidatesIsaacson, DylanSchold, Jesse D.Gmeiner, Michael W.Copley, Hannah C.Kosmoliaptsis, VasilisTambur, Anat R.2022-08-31T11:57:52-07:00doi:10.1681/ASN.2022030296hwp:resource-id:jnephrol;33/12/2293American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycadaver organ transplantation, chronic rejection, end stage renal disease, kidney donation, kidney transplantation, organ transplant, renal transplantation, transplantation, transplant outcomes, transplant pathologyClinical ResearchTransplantationClinical ResearchTransplantationresearch-article20222022-12-01December 202210.1681/ASN.20220302961046-66731533-34502022-08-31T11:57:52-07:002022-12Journal of the American Society of NephrologyClinical Research331222932305
- Anatomical Evidence for Parasympathetic Innervation of the Renal Vasculature and Pelvis10.1681/ASN.2021111518Mon, 17 Oct 2022 07:25:15 GMT-07:00Anatomical Evidence for Parasympathetic Innervation of the Renal Vasculature and PelvisCheng, XiaofengZhang, YongshengChen, RuixiQian, ShenghuiLv, HaijunLiu, XiuliZeng, Shaoqun2022-10-17T07:25:15-07:00doi:10.1681/ASN.2021111518hwp:resource-id:jnephrol;33/12/2194American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney anatomy, arteries, acetylcholine, gene transcriptionBasic ResearchNormal Kidney Structure and FunctionBasic ResearchNormal Kidney Structure and Functionresearch-article20222022-12-01December 202210.1681/ASN.20211115181046-66731533-34502022-10-17T07:25:15-07:002022-12Journal of the American Society of NephrologyBasic Research3312122194i2210i
- Prediagnostic Appearance of THSD7A Autoantibodies in Membranous NephropathyBackground: Pathogenic autoantibodies against thrombospondin type-1 domain 7A (THSD7A) are present in approximately 3% of patients with membranous nephropathy (MN). Compared to PLA2R antibodies, less is known about THSD7A autoantibodies (AB) due to the relative rarity and lack of a commercially, available quantitative immunoassay. Methods: Here we describe the development and validation of a highly quantitative, luciferase immunoprecipitation systems (LIPS) assay for detecting THSD7A AB and used it to study dominant THSD7A epitopes, disease associations and monitoring disease activity. The Department of Defense Serum Repository (DODSR) was then used to analyze THSD7A AB in 371 longitudinal serum samples collected before clinical diagnosis of MN from 110 PLA2R-negative MN subjects. Results: LIPS analysis demonstrated that a near full-length THSD7A (amino acids 1-1656) detected robust autoantibody levels in all known seropositive MN patients with 100% sensitivity and specificity compared to ELISA and/or Western blotting. The majority of THSD7A seropositive subjects in our pilot cohort had evidence of coexisting autoimmunity or cancer. Moreover, three THSD7A seropositive cases undergoing immunosuppressive therapy showed longitudinal autoantibody levels that tracked clinical status. Additional epitope analysis of two smaller protein THSD7A fragments spanning amino acids 1-416 and 1-671 demonstrated lower sensitivity of 32% and 44%, respectively. In the DODSR cohort, THSD7A seropositivity was detected in 4.5% of PLA2R negative MN cases. In one "primary" and in one secondary MN-associated with cancer, THSD7A AB were detectable less than one month prior to biopsy-proven diagnosis. In addition, 3 cases of lupus membranous nephropathy had detectable THSD7A AB years before hypoalbuminemia and biopsy-proven diagnosis. Conclusions: While further studies are needed to explore the significance of THSD7A AB in lupus membranous nephropathy, this study describes a novel, highly sensitive LIPS immunoassay for detecting THSD7A AB and adds to the existing literature on THSD7A-associated MN.burbelop@nidcr.nih.gov10.34067/KID.0005112022Tue, 29 Nov 2022 01:46:51 GMT-08:00Prediagnostic Appearance of THSD7A Autoantibodies in Membranous NephropathyBackground: Pathogenic autoantibodies against thrombospondin type-1 domain 7A (THSD7A) are present in approximately 3% of patients with membranous nephropathy (MN). Compared to PLA2R antibodies, less is known about THSD7A autoantibodies (AB) due to the relative rarity and lack of a commercially, available quantitative immunoassay. Methods: Here we describe the development and validation of a highly quantitative, luciferase immunoprecipitation systems (LIPS) assay for detecting THSD7A AB and used it to study dominant THSD7A epitopes, disease associations and monitoring disease activity. The Department of Defense Serum Repository (DODSR) was then used to analyze THSD7A AB in 371 longitudinal serum samples collected before clinical diagnosis of MN from 110 PLA2R-negative MN subjects. Results: LIPS analysis demonstrated that a near full-length THSD7A (amino acids 1-1656) detected robust autoantibody levels in all known seropositive MN patients with 100% sensitivity and specificity compared to ELISA and/or Western blotting. The majority of THSD7A seropositive subjects in our pilot cohort had evidence of coexisting autoimmunity or cancer. Moreover, three THSD7A seropositive cases undergoing immunosuppressive therapy showed longitudinal autoantibody levels that tracked clinical status. Additional epitope analysis of two smaller protein THSD7A fragments spanning amino acids 1-416 and 1-671 demonstrated lower sensitivity of 32% and 44%, respectively. In the DODSR cohort, THSD7A seropositivity was detected in 4.5% of PLA2R negative MN cases. In one "primary" and in one secondary MN-associated with cancer, THSD7A AB were detectable less than one month prior to biopsy-proven diagnosis. In addition, 3 cases of lupus membranous nephropathy had detectable THSD7A AB years before hypoalbuminemia and biopsy-proven diagnosis. Conclusions: While further studies are needed to explore the significance of THSD7A AB in lupus membranous nephropathy, this study describes a novel, highly sensitive LIPS immunoassay for detecting THSD7A AB and adds to the existing literature on THSD7A-associated MN.Burbelo, Peter D.Olson, Stephen W.Keller, Jason M.Joshi, MeghaSchwartz, Daniella M.Chuang, Yung-JenLambeau, GérardBeck, Laurence H.Waldman, Meryl2022-11-29T13:46:51-08:00doi:10.34067/KID.0005112022hwp:resource-id:kidney360;KID.0005112022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Autoantibodies, Membranous GlomerulonephritisOriginal InvestigationOriginal Investigationother202210.34067/KID.00051120222641-76502641-76502022-11-29T13:46:51-08:00Kidney360Original Investigation10.34067/KID.0005112022
- Fetal Nephrology: A Quaternary Care Center ExperienceBackground: Congenital anomalies of kidney and urinary tract (CAKUT) represent 15-20% of prenatally diagnosed abnormalities. Maternal characteristics, the frequency of various forms of renal disease including CAKUT referred for prenatal nephrology consultation and their perinatal outcomes are less well defined. Methods: Performed a retrospective chart review of fetal CAKUT and other forms of renal disease referred for prenatal nephrology consults at Texas Children's Hospital Fetal Center from January 1st 2012 to December 31st 2018. Results: 217 prenatal nephrology consultations were performed during the study period, representing 4.7% of total Fetal Center referrals at a mean estimated gestational age of 25.2 ±5.7 weeks. Maternal characteristics: Mean age 29.3±5.6 years; 14% had advanced maternal age; 10% had a family history of CAKUT or ESKD, 5% had diabetes mellitus, and 5% of pregnancies were in vitro fertilization assisted. Fetal characteristics: 62.7% of fetuses were male, and 16% had CAKUT associated with multiple congenital anomalies. The most common prenatal diagnoses were Lower Urinary Tract Obstruction in 71 (32.7%), unilateral renal agenesis or multicystic dysplastic kidney (MCDK) in 52 (24.9%), bilateral agenesis or MCDK in 22 (10.1%), and bilateral cystic renal disease in 19 (8.8%). 76% of patients received genetic counseling. 141 (64.9%) patients had some form of prenatal genetic testing with a positivity rate of 5.7% Post-natal characteristics: 61 (28.1%) of patients were seen in prenatal consultation only, and no follow up was available. Of the remaining 156 pregnancies, 136 (86.3%) were viable and delivered at mean gestational age of 35.2± 3.8 weeks. Of these, 100 (64%) survived to discharge. Additional post-natal genetic testing was obtained on 27 infants with a positivity rate of 59%. Conclusions: Overall perinatal mortality for this cohort as a whole was high (35.8%). While prenatal genetic testing had a limited diagnostic utility, targeted post-natal genetic testing had a much higher diagnostic yield.mcbraun@texaschildrens.org10.34067/KID.0004782022Tue, 29 Nov 2022 01:46:51 GMT-08:00Fetal Nephrology: A Quaternary Care Center ExperienceBackground: Congenital anomalies of kidney and urinary tract (CAKUT) represent 15-20% of prenatally diagnosed abnormalities. Maternal characteristics, the frequency of various forms of renal disease including CAKUT referred for prenatal nephrology consultation and their perinatal outcomes are less well defined. Methods: Performed a retrospective chart review of fetal CAKUT and other forms of renal disease referred for prenatal nephrology consults at Texas Children's Hospital Fetal Center from January 1st 2012 to December 31st 2018. Results: 217 prenatal nephrology consultations were performed during the study period, representing 4.7% of total Fetal Center referrals at a mean estimated gestational age of 25.2 ±5.7 weeks. Maternal characteristics: Mean age 29.3±5.6 years; 14% had advanced maternal age; 10% had a family history of CAKUT or ESKD, 5% had diabetes mellitus, and 5% of pregnancies were in vitro fertilization assisted. Fetal characteristics: 62.7% of fetuses were male, and 16% had CAKUT associated with multiple congenital anomalies. The most common prenatal diagnoses were Lower Urinary Tract Obstruction in 71 (32.7%), unilateral renal agenesis or multicystic dysplastic kidney (MCDK) in 52 (24.9%), bilateral agenesis or MCDK in 22 (10.1%), and bilateral cystic renal disease in 19 (8.8%). 76% of patients received genetic counseling. 141 (64.9%) patients had some form of prenatal genetic testing with a positivity rate of 5.7% Post-natal characteristics: 61 (28.1%) of patients were seen in prenatal consultation only, and no follow up was available. Of the remaining 156 pregnancies, 136 (86.3%) were viable and delivered at mean gestational age of 35.2± 3.8 weeks. Of these, 100 (64%) survived to discharge. Additional post-natal genetic testing was obtained on 27 infants with a positivity rate of 59%. Conclusions: Overall perinatal mortality for this cohort as a whole was high (35.8%). While prenatal genetic testing had a limited diagnostic utility, targeted post-natal genetic testing had a much higher diagnostic yield.Plaud Gonzalez, Auda M.Joseph, CatherineStover, Samantha R.Nassr, AhmedKoh, Chester J.Angelo, Joseph R.Braun, Michael C.2022-11-29T13:46:51-08:00doi:10.34067/KID.0004782022hwp:resource-id:kidney360;KID.0004782022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Pediatrics, CAKUT, Prenatal counseling, Genetic testing, perinatal mortalityOriginal InvestigationOriginal Investigationother202210.34067/KID.00047820222641-76502641-76502022-11-29T13:46:51-08:00Kidney360Original Investigation10.34067/KID.0004782022
- Digital spatial profiling of glomerular gene expression in pauci-immune focal necrotizing glomerulonephritisIntroduction: Pauci-immune focal necrotizing glomerulonephritis (piFNGN) involves asynchronous onset and progression of injurious lesions in biopsies. Pathologists describe this heterogeneity within a biopsy, but translating the information into prognostic or expression analyses is challenging. Understanding the underlying molecular processes could improve treatment; however, bulk or single cell transcriptomic analyses of dissociated tissue disregard the heterogeneity of glomerular injury. Methods: We characterize protein and mRNA expression of individual glomeruli in 20 biopsies from 18 patients with anti-neutrophil cytoplasmic antibody-associated piFNGN using the Nanostring digital spatial profiling (DSP) platform. For this purpose, circular annotations of glomeruli were analyzed using protein, immuno-oncology RNA, and cancer transcriptome atlas panels (n=120, 72, and 48 glomeruli, respectively). Histological evaluation of glomerular patterns of injury was performed in adjacent serial sections. Expression data was processed by log2 transformation, quantile normalization and batch adjustment. Results: DSP revealed distinct but overlapping gene expression profiles relating to the morphological evolution of injurious lesions, including dynamic expression of various immune checkpoint regulators. Enrichment analysis indicated deregulated pathways that underline known and highlight novel potential mechanisms of disease. Moreover, by capturing individual glomeruli, DSP describes heterogeneity between and within biopsies. Conclusions: We demonstrate the benefit of spatial profiling for characterization of heterogeneous glomerular injury, indicating novel molecular correlates of glomerular injury in piFNGN.andre.oszwald@meduniwien.ac.at10.34067/KID.0004612022Tue, 29 Nov 2022 01:46:51 GMT-08:00Digital spatial profiling of glomerular gene expression in pauci-immune focal necrotizing glomerulonephritisIntroduction: Pauci-immune focal necrotizing glomerulonephritis (piFNGN) involves asynchronous onset and progression of injurious lesions in biopsies. Pathologists describe this heterogeneity within a biopsy, but translating the information into prognostic or expression analyses is challenging. Understanding the underlying molecular processes could improve treatment; however, bulk or single cell transcriptomic analyses of dissociated tissue disregard the heterogeneity of glomerular injury. Methods: We characterize protein and mRNA expression of individual glomeruli in 20 biopsies from 18 patients with anti-neutrophil cytoplasmic antibody-associated piFNGN using the Nanostring digital spatial profiling (DSP) platform. For this purpose, circular annotations of glomeruli were analyzed using protein, immuno-oncology RNA, and cancer transcriptome atlas panels (n=120, 72, and 48 glomeruli, respectively). Histological evaluation of glomerular patterns of injury was performed in adjacent serial sections. Expression data was processed by log2 transformation, quantile normalization and batch adjustment. Results: DSP revealed distinct but overlapping gene expression profiles relating to the morphological evolution of injurious lesions, including dynamic expression of various immune checkpoint regulators. Enrichment analysis indicated deregulated pathways that underline known and highlight novel potential mechanisms of disease. Moreover, by capturing individual glomeruli, DSP describes heterogeneity between and within biopsies. Conclusions: We demonstrate the benefit of spatial profiling for characterization of heterogeneous glomerular injury, indicating novel molecular correlates of glomerular injury in piFNGN.Oszwald, AndréMejía-Pedroza, Raúl AlejandroSchachner, HelgaAigner, ChristofRees, AndrewKain, Renate2022-11-29T13:46:51-08:00doi:10.34067/KID.0004612022hwp:resource-id:kidney360;KID.0004612022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360histopathology, glomerulus, glomerulonephritis, glomerular disease, gene expression, ANCA, vasculitis, transcriptional profiling, Renal pathology, kidney biopsy, Basic ScienceInnovative Technology and MethodologyInnovative Technology and Methodologyother202210.34067/KID.00046120222641-76502641-76502022-11-29T13:46:51-08:00Kidney360Innovative Technology and Methodology10.34067/KID.0004612022
- PPARδ agonism ameliorates renal fibrosis in an Alport syndrome mouse modelBackground: Alport syndrome is a genetic kidney disease caused by mutation in any of the COL4A3, COL4A4 or COL4A5 genes encoding the type IV collagen α3, α4, and α5 chains. Defects of type IV collagen α3α4α5 cause glomerular basement membrane abnormalities and lead to defects in glomerular filtration and end stage kidney disease. Treatment with angiotensin converting enzyme inhibitors (ACEi) dramatically slows disease progression but does not stop progression to renal failure. Therefore, novel therapeutic options with different modes of action from ACEi are needed. Peroxisome proliferator-activated receptor (PPAR) δ agonists have shown renoprotective effects in several acute kidney injury mouse models. In the present study, we investigated the effects of a potent and selective PPARδ agonist, REN001 (formerly HPP593), in a mouse model of Alport syndrome. Methods: We administered REN001 from the early stages to the late stages of disease via once daily intraperitoneal injections. Results: REN001 treatment halved proteinuria at the late stages of disease in Col4a3-/- mice. Blood urea nitrogen levels were also decreased, and histological and molecular analyses showed that REN001 ameliorated renal inflammation and fibrosis. Conclusions: These results indicate that REN001 slows kidney disease progression in Alport mice. REN001 has a different mechanism of action from ACEi, so we therefore hypothesize that combining the two treatments may show additive effects to attenuate renal injury and slow progression to renal failure.jeffminer@wustl.edu10.34067/KID.0006662022Tue, 29 Nov 2022 01:46:51 GMT-08:00PPARδ agonism ameliorates renal fibrosis in an Alport syndrome mouse modelBackground: Alport syndrome is a genetic kidney disease caused by mutation in any of the COL4A3, COL4A4 or COL4A5 genes encoding the type IV collagen α3, α4, and α5 chains. Defects of type IV collagen α3α4α5 cause glomerular basement membrane abnormalities and lead to defects in glomerular filtration and end stage kidney disease. Treatment with angiotensin converting enzyme inhibitors (ACEi) dramatically slows disease progression but does not stop progression to renal failure. Therefore, novel therapeutic options with different modes of action from ACEi are needed. Peroxisome proliferator-activated receptor (PPAR) δ agonists have shown renoprotective effects in several acute kidney injury mouse models. In the present study, we investigated the effects of a potent and selective PPARδ agonist, REN001 (formerly HPP593), in a mouse model of Alport syndrome. Methods: We administered REN001 from the early stages to the late stages of disease via once daily intraperitoneal injections. Results: REN001 treatment halved proteinuria at the late stages of disease in Col4a3-/- mice. Blood urea nitrogen levels were also decreased, and histological and molecular analyses showed that REN001 ameliorated renal inflammation and fibrosis. Conclusions: These results indicate that REN001 slows kidney disease progression in Alport mice. REN001 has a different mechanism of action from ACEi, so we therefore hypothesize that combining the two treatments may show additive effects to attenuate renal injury and slow progression to renal failure.Omachi, KoheiO'Carroll, ColinMiner, Jeffrey H.2022-11-29T13:46:51-08:00doi:10.34067/KID.0006662022hwp:resource-id:kidney360;KID.0006662022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Alport syndrome, fibrosis, PPAR agonist, kidney, Basic ScienceOriginal InvestigationOriginal Investigationother202210.34067/KID.00066620222641-76502641-76502022-11-29T13:46:51-08:00Kidney360Original Investigation10.34067/KID.0006662022
- Safety and Adequacy of Kidney Biopsy Procedure in Patients with ObesityThis is an Early Access article. Please select the PDF button, above, to view it.dennis.moledina@yale.edu10.34067/KID.0006602022Tue, 29 Nov 2022 01:46:51 GMT-08:00Safety and Adequacy of Kidney Biopsy Procedure in Patients with ObesityThis is an Early Access article. Please select the PDF button, above, to view it.Qian, LongMenez, StevenHu, DavidWeinstein, JasonMelchinger, HannahThiessen Philbrook, Heather R.Luciano, Randy L.Turner, Jeffrey M.Perazella, Mark A.Corona Villalobos, Celia PamelaShaw, Melissa M.Wilson, F. PerryParikh, Chirag R.Moledina, Dennis G.2022-11-29T13:46:51-08:00doi:10.34067/KID.0006602022hwp:resource-id:kidney360;KID.0006602022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Kidney biopsy, Obesity, PathologyBrief CommunicationBrief Communicationother202210.34067/KID.00066020222641-76502641-76502022-11-29T13:46:51-08:00Kidney360Brief Communication10.34067/KID.0006602022
- Global Dialysis Perspective: NicaraguaThis is an Early Access article. Please select the PDF button, above, to view it.cacarjimenna@gmail.com10.34067/KID.0005572022Tue, 29 Nov 2022 01:46:51 GMT-08:00Global Dialysis Perspective: NicaraguaThis is an Early Access article. Please select the PDF button, above, to view it.Cajina Aguirre, Carmen L.Strasma, Anna K.Álvarez-Novoa, Rodrigo J.2022-11-29T13:46:51-08:00doi:10.34067/KID.0005572022hwp:resource-id:kidney360;KID.0005572022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Nicaragua, Dialysis, Peritoneal dialysis, Hemodialysis, ESKD, Mesoamerican nephropathy, Latin America, Central America, nephrology, Global healthGlobal PerspectivesGlobal Perspectivesother202210.34067/KID.00055720222641-76502641-76502022-11-29T13:46:51-08:00Kidney360Global Perspectives10.34067/KID.0005572022
- Negative modulation of B cell activation by MC1R signaling protects against membranous nephropathyBackground: The pituitary neuropeptide melanocortins, and specifically ACTH, have recently emerged as a novel therapeutic modality for membranous nephropathy (MN). However, the mechanism(s) of action remains elusive. Methods: Passive Heymann nephritis (PHN), a model of MN, was induced in wild-type (WT) rats and melanocortin 1 receptor (MC1R) knockout (KO) rats generated by the CRISPR/Cas9 technology, followed by treatment with various melanocortin agents, including Repository Corticotropin Injection, the non-steroidogenic pan-MCR agonist NDP-MSH, and the selective MC1R agonist MS05. Additional rats received adoptive transfer of syngeneic bone marrow-derived cells (BMDC) beforehand. Kidney function, histology and molecular changes were evaluated. Results: MC1R KO worsened PHN, associated with increased deposition of autologous IgG and complement C5b-9 in glomeruli and higher circulating levels of autologous IgG, as evidence of a sensitized humoral immune response. Melanocortin therapy ameliorated PHN in WT rats, coinciding with reduced glomerular deposition of autologous IgG and C5b-9. The beneficial efficacy of melanocortins was blunted in KO rats but was restored by adoptive transfer of syngeneic BMDC derived from WT rats. Mechanistically, MC1R was expressed in B lymphocytes, and negatively associated with B cell activation as revealed by gene set enrichment analysis. MC1R agonism triggered MITF induction in activated B cells in a cAMP-dependent mode, and repressed the expression of IRF4, a lymphoid transcription factor essential for B cell development and maturation, resulting in suppressed plasmacytic differentiation and IgG production. Conclusion: MC1R signaling negatively modulates B cell activation and suppresses humoral immune responses in PHN, representing a novel therapeutic target for MN.rujun.gong@utoledo.edu10.1681/ASN.2022050605Tue, 29 Nov 2022 12:51:00 GMT-08:00Negative modulation of B cell activation by MC1R signaling protects against membranous nephropathyBackground: The pituitary neuropeptide melanocortins, and specifically ACTH, have recently emerged as a novel therapeutic modality for membranous nephropathy (MN). However, the mechanism(s) of action remains elusive. Methods: Passive Heymann nephritis (PHN), a model of MN, was induced in wild-type (WT) rats and melanocortin 1 receptor (MC1R) knockout (KO) rats generated by the CRISPR/Cas9 technology, followed by treatment with various melanocortin agents, including Repository Corticotropin Injection, the non-steroidogenic pan-MCR agonist NDP-MSH, and the selective MC1R agonist MS05. Additional rats received adoptive transfer of syngeneic bone marrow-derived cells (BMDC) beforehand. Kidney function, histology and molecular changes were evaluated. Results: MC1R KO worsened PHN, associated with increased deposition of autologous IgG and complement C5b-9 in glomeruli and higher circulating levels of autologous IgG, as evidence of a sensitized humoral immune response. Melanocortin therapy ameliorated PHN in WT rats, coinciding with reduced glomerular deposition of autologous IgG and C5b-9. The beneficial efficacy of melanocortins was blunted in KO rats but was restored by adoptive transfer of syngeneic BMDC derived from WT rats. Mechanistically, MC1R was expressed in B lymphocytes, and negatively associated with B cell activation as revealed by gene set enrichment analysis. MC1R agonism triggered MITF induction in activated B cells in a cAMP-dependent mode, and repressed the expression of IRF4, a lymphoid transcription factor essential for B cell development and maturation, resulting in suppressed plasmacytic differentiation and IgG production. Conclusion: MC1R signaling negatively modulates B cell activation and suppresses humoral immune responses in PHN, representing a novel therapeutic target for MN.Chen, BohanGuan, XuejingGunning, WilliamGe, YanGohara, AmiraDworkin, LanceGong, Rujun2022-11-29T12:51:00-08:00doi:10.1681/ASN.2022050605hwp:resource-id:jnephrol;ASN.2022050605v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220506051046-66731533-34502022-11-29T12:51:00-08:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.2022050605
- Risk Stratification to Predict Renal Survival in Anti-GBM DiseaseAnti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy. Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0.760. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-, moderate-, and high-risk groups, respectively (P<0.001). The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD (P<0.001, P<0.001). Considering the 129 patients initially requiring RRT, the best predictor for renal recovery was the percentage of normal glomeruli (C=0.622; P<0.001), a split either side of 10% providing good stratification. A model with the predictors RRT and normal glomeruli (N) achieved superior discrimination (C=0.840, P<0.001). Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N≥10%), 74.0% (no RRT, N<10%), 42.3% (RRT, N≥10%) and 14.1% (RRT, N<10%), respectively. In summary, we demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Here, we propose a stratification to assist in the management of anti-GBM disease.Silke.Brix@mft.nhs.uk10.1681/ASN.2022050581Tue, 29 Nov 2022 12:51:00 GMT-08:00Risk Stratification to Predict Renal Survival in Anti-GBM DiseaseAnti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy. Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0.760. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-, moderate-, and high-risk groups, respectively (P<0.001). The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD (P<0.001, P<0.001). Considering the 129 patients initially requiring RRT, the best predictor for renal recovery was the percentage of normal glomeruli (C=0.622; P<0.001), a split either side of 10% providing good stratification. A model with the predictors RRT and normal glomeruli (N) achieved superior discrimination (C=0.840, P<0.001). Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N≥10%), 74.0% (no RRT, N<10%), 42.3% (RRT, N≥10%) and 14.1% (RRT, N<10%), respectively. In summary, we demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Here, we propose a stratification to assist in the management of anti-GBM disease.Floyd, LaurenBate, SebastianKafagi, AbdulBrown, NinaScott, JenniferSrikantharajah, MukunthanMysilvecek, MarekReid, GraemeAqeel, FatenFrausova, DoubravkaKollar, MarekKieu, Phuong LeKhurshid, BilalDhaygude, AjayTesar, VladimirMcAdoo, StephenLittle, MarkGeetha, DuvuruBrix, Silke2022-11-29T12:51:00-08:00doi:10.1681/ASN.2022050581hwp:resource-id:jnephrol;ASN.2022050581v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Clinical ResearchOriginal Article - Clinical Researchresearch-article202210.1681/ASN.20220505811046-66731533-34502022-11-29T12:51:00-08:00Journal of the American Society of NephrologyOriginal Article - Clinical ResearchASN.2022050581
- Association of Shear Stress with Subsequent Lumen Remodeling in Hemodialysis Arteriovenous FistulasBackground Blood flow-induced wall shear stress (WSS) is a strong local regulator of vascular remodeling, but its effects on arteriovenous fistula (AVF) remodeling are unclear. Methods In this prospective cohort study, we used statistical mixed-effects modeling to investigate the associations between WSS and AVF remodeling in 120 participants undergoing AVF creation surgery. Postoperative magnetic resonance imaging data at 1 day, 6 weeks, and 6 months were used to derive current WSS by computational fluid dynamic simulations and to quantify subsequent changes in AVF lumen cross-sectional area at 1-mm intervals along the proximal artery and AVF vein. Results Combining artery and vein data, prior mean WSS was significantly associated with lumen area expansion. Mean WSS at day 1 was significantly associated with lumen area change from day 1 to week 6 (11% larger week-6 area per IQR increase in day-1 mean WSS, 95% CI 5%-18%; n=101), and mean WSS at 6 weeks was significantly associated with lumen area change from week 6 to month 6 (14% larger area per IQR increase, 95% CI 3%-28%; n=52). The association of mean WSS at day 1 with lumen area expansion from day 1 to week 6 differed significantly by diabetes (p=0.009): 27% (95% CI 17%-37%) larger area per IQR increase in mean WSS without diabetes, and 9% (95% CI -1-19%) with diabetes. Day-1 oscillatory shear index (OSI) was significantly associated with lumen area change from day 1 to week 6 (5% smaller area per IQR increase in OSI, 95% CI 3%-7%), and OSI at week 6 was significantly associated with lumen change from week 6 to month 6 (7% smaller area per IQR increase in OSI, 95% CI 2%-11%). WSS spatial gradient was not significantly associated with subsequent remodeling. In a joint model, WSS and OSI statistically significantly interacted in their associations with lumen area expansion in a complex nonlinear fashion. Conclusion Higher WSS and lower OSI were associated with greater lumen expansion after AVF creation surgery.Yong.He@surgery.ufl.edu10.2215/CJN.04630422Tue, 29 Nov 2022 11:05:50 GMT-08:00Association of Shear Stress with Subsequent Lumen Remodeling in Hemodialysis Arteriovenous FistulasBackground Blood flow-induced wall shear stress (WSS) is a strong local regulator of vascular remodeling, but its effects on arteriovenous fistula (AVF) remodeling are unclear. Methods In this prospective cohort study, we used statistical mixed-effects modeling to investigate the associations between WSS and AVF remodeling in 120 participants undergoing AVF creation surgery. Postoperative magnetic resonance imaging data at 1 day, 6 weeks, and 6 months were used to derive current WSS by computational fluid dynamic simulations and to quantify subsequent changes in AVF lumen cross-sectional area at 1-mm intervals along the proximal artery and AVF vein. Results Combining artery and vein data, prior mean WSS was significantly associated with lumen area expansion. Mean WSS at day 1 was significantly associated with lumen area change from day 1 to week 6 (11% larger week-6 area per IQR increase in day-1 mean WSS, 95% CI 5%-18%; n=101), and mean WSS at 6 weeks was significantly associated with lumen area change from week 6 to month 6 (14% larger area per IQR increase, 95% CI 3%-28%; n=52). The association of mean WSS at day 1 with lumen area expansion from day 1 to week 6 differed significantly by diabetes (p=0.009): 27% (95% CI 17%-37%) larger area per IQR increase in mean WSS without diabetes, and 9% (95% CI -1-19%) with diabetes. Day-1 oscillatory shear index (OSI) was significantly associated with lumen area change from day 1 to week 6 (5% smaller area per IQR increase in OSI, 95% CI 3%-7%), and OSI at week 6 was significantly associated with lumen change from week 6 to month 6 (7% smaller area per IQR increase in OSI, 95% CI 2%-11%). WSS spatial gradient was not significantly associated with subsequent remodeling. In a joint model, WSS and OSI statistically significantly interacted in their associations with lumen area expansion in a complex nonlinear fashion. Conclusion Higher WSS and lower OSI were associated with greater lumen expansion after AVF creation surgery.He, YongShiu, Yan-TingImrey, PeterRadeva, MilenaBeck, GeraldGassman, JenniferNorthrup, HannahRoy-Chaudhury, PrabirBerceli, ScottCheung, Alfred2022-11-29T11:05:50-08:00doi:10.2215/CJN.04630422hwp:resource-id:clinjasn;CJN.04630422v1American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesOriginal Articlesresearch-article202210.2215/CJN.046304221555-90411555-905X2022-11-29T11:05:50-08:00Clinical Journal of the American Society of NephrologyOriginal ArticlesCJN.04630422
- Pathophysiology of AV Fistula Maturation and Non-Maturationmaurizio.gallieni@unimi.it10.2215/CJN.13101122Tue, 29 Nov 2022 11:05:50 GMT-08:00Pathophysiology of AV Fistula Maturation and Non-MaturationGallieni, MaurizioSabiu, Gianmarco2022-11-29T11:05:50-08:00doi:10.2215/CJN.13101122hwp:resource-id:clinjasn;CJN.13101122v1American Society of NephrologyClinical Journal of the American Society of NephrologyEditorialsEditorialsresearch-article202210.2215/CJN.131011221555-90411555-905X2022-11-29T11:05:50-08:00Clinical Journal of the American Society of NephrologyEditorialsCJN.13101122
- Genomic Disorders in CKD across the Lifespan10.1681/ASN.2022060725Thu, 27 Oct 2022 11:46:36 GMT-07:00Genomic Disorders in CKD across the LifespanVerbitsky, MiguelKrishnamurthy, SarathbabuKrithivasan, PriyaHughes, DanielKhan, AtlasMarasà, MaddalenaVena, NatalieKhosla, PavanZhang, JunyingLim, Tze Y.Glessner, Joseph T.Weng, ChunhuaShang, NingShen, YufengHripcsak, GeorgeHakonarson, HakonIonita-Laza, IulianaLevy, BrynnKenny, Eimear E.Loos, Ruth J.F.Kiryluk, KrzysztofSanna-Cherchi, SimoneCrosslin, David R.Furth, SusanWarady, Bradley A.Igo, Robert P.Iyengar, Sudha K.Wong, Craig S.Parsa, AfshinFeldman, Harold I.Gharavi, Ali G.2022-10-27T11:46:36-07:00doi:10.1681/ASN.2022060725hwp:resource-id:jnephrol;ASN.2022060725v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, genetic kidney disease, genetics and development, glomerular disease, glomerulonephritis, glomerulopathyBasic ResearchChronic Kidney DiseaseBasic ResearchChronic Kidney Diseaseresearch-article202210.1681/ASN.20220607251046-66731533-34502022-10-27T11:46:36-07:00Journal of the American Society of NephrologyBasic ResearchASN.2022060725
- Reproductive Healthcare is a Key Component of Comprehensive Care for Adolescents with CKDmmoxeymims@childrensnational.org10.1681/ASN.2022101163Wed, 23 Nov 2022 10:51:15 GMT-08:00Reproductive Healthcare is a Key Component of Comprehensive Care for Adolescents with CKDReynolds, MonicaOliverio, AndreaBrunson, CelinaMoxey-Mims, Marva2022-11-23T10:51:15-08:00doi:10.1681/ASN.2022101163hwp:resource-id:jnephrol;ASN.2022101163v1American Society of NephrologyJournal of the American Society of NephrologyInvited FeatureInvited Featureresearch-article202210.1681/ASN.20221011631046-66731533-34502022-11-23T10:51:15-08:00Journal of the American Society of NephrologyInvited FeatureASN.2022101163
- Association of Bradycardia and Asystole Episodes with Dialytic Parameters: An Analysis of the Monitoring in Dialysis (MiD) Study10.34067/KID.0003142022Tue, 11 Oct 2022 12:10:49 GMT-07:00Association of Bradycardia and Asystole Episodes with Dialytic Parameters: An Analysis of the Monitoring in Dialysis (MiD) StudySoomro, Qandeel H.Bansal, NishaWinkelmayer, Wolfgang C.Koplan, Bruce A.Costea, Alexandru I.Roy-Chaudhury, PrabirTumlin, James A.Kher, VijayWilliamson, Don E.Pokhariyal, SaurabhMcClure, Candace K.Charytan, David M.2022-10-11T12:10:49-07:00doi:10.34067/KID.0003142022hwp:resource-id:kidney360;3/11/1871American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, arrhythmia, asystole, bradycardia, dialysisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-11-2410.34067/KID.00031420222641-76502022-10-11T12:10:49-07:002022-11-24Kidney360Original Investigation31118711880
- Associations of Metabolic Syndrome and Abdominal Obesity with Anion Gap Metabolic Acidosis among US Adults10.34067/KID.0002402022Wed, 13 Jul 2022 02:01:21 GMT-07:00Associations of Metabolic Syndrome and Abdominal Obesity with Anion Gap Metabolic Acidosis among US AdultsLambert, Douglas C.Kane, JamieSlaton, AnthonyAbramowitz, Matthew K.2022-07-13T14:01:21-07:00doi:10.34067/KID.0002402022hwp:resource-id:kidney360;3/11/1842American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, abdominal obesity, acid-base equilibrium, anion gap, metabolic acidosis, metabolic syndrome, obesity, waist circumferenceOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20222022-11-2410.34067/KID.00024020222641-76502022-07-13T14:01:21-07:002022-11-24Kidney360Original Investigation31118421851
- Telemonitoring for Hypertension Management: The Time Is Now10.34067/KID.0001302022Wed, 05 Oct 2022 05:56:19 GMT-07:00Telemonitoring for Hypertension Management: The Time Is NowKaram, SabineDrawz, Paul E.2022-10-05T05:56:19-07:00doi:10.34067/KID.0001302022hwp:resource-id:kidney360;3/11/1961American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hypertension, telemedicinePerspectivePerspectiveresearch-article20222022-11-2410.34067/KID.00013020222641-76502022-10-05T05:56:19-07:002022-11-24Kidney360Perspective31119611964
- In Primary Aldosteronism Acute Potassium Chloride Supplementation Suppresses Abundance and Phosphorylation of the Sodium-Chloride Cotransporter10.34067/KID.0003632022Fri, 26 Aug 2022 11:27:03 GMT-07:00In Primary Aldosteronism Acute Potassium Chloride Supplementation Suppresses Abundance and Phosphorylation of the Sodium-Chloride CotransporterWu, AihuaWolley, Martin J.Matthews, AlexandraCowley, DianeWelling, Paul A.Fenton, Robert A.Stowasser, Michael2022-08-26T11:27:03-07:00doi:10.34067/KID.0003632022hwp:resource-id:kidney360;3/11/1909American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hypertension, blood pressure, NCC, potassium, primary aldosteronism, urinary extracellular vesiclesOriginal InvestigationHypertensionOriginal InvestigationHypertensionresearch-article20222022-11-2410.34067/KID.00036320222641-76502022-08-26T11:27:03-07:002022-11-24Kidney360Original Investigation31119091923
- Patient Perspective on Xenotransplantation10.34067/KID.0003542022Wed, 12 Oct 2022 05:55:27 GMT-07:00Patient Perspective on XenotransplantationBaliker, MaryV. Roberts, Glenda2022-10-12T05:55:27-07:00doi:10.34067/KID.0003542022hwp:resource-id:kidney360;3/11/1953American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, advisory boards, clinical trials, mistrust, patient, xenotransplantationPatient PerspectivePatient Perspectiveresearch-article20222022-11-2410.34067/KID.00035420222641-76502022-10-12T05:55:27-07:002022-11-24Kidney360Patient Perspective31119531954
- An Unsuspected Histological Finding in a Patient with Cancer and AKI10.34067/KID.0002812022Wed, 23 Nov 2022 07:45:30 GMT-08:00An Unsuspected Histological Finding in a Patient with Cancer and AKIHengel, Felicitas E.Wiech, ThorstenWenzel, Ulrich2022-11-23T07:45:30-08:00doi:10.34067/KID.0002812022hwp:resource-id:kidney360;3/11/1996American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute kidney failure, glomerular micrometastasis, kidney biopsy, squamous cell carcinomaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-11-2410.34067/KID.00028120222641-76502022-11-23T07:45:30-08:002022-11-24Kidney360Clinical Images in Nephrology and Dialysis31119961997
- Delivery of Active Medical Management without Dialysis through an Embedded Kidney Palliative Care Model10.34067/KID.0001352022Tue, 19 Jul 2022 01:29:42 GMT-07:00Delivery of Active Medical Management without Dialysis through an Embedded Kidney Palliative Care ModelBursic, Alexandra E.Schell, Jane O.Ernecoff, Natalie C.Bansal, Amar D.2022-07-19T13:29:42-07:00doi:10.34067/KID.0001352022hwp:resource-id:kidney360;3/11/1881American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360geriatric and palliative nephrology, advance care planning, dialysis, hospice, palliative care, symptom managementOriginal InvestigationGeriatric and Palliative NephrologyOriginal InvestigationGeriatric and Palliative Nephrologyresearch-article20222022-11-2410.34067/KID.00013520222641-76502022-07-19T13:29:42-07:002022-11-24Kidney360Original Investigation31118811889
- In Memoriam: Jerry Yee, MD10.34067/KID.0004262022Wed, 05 Oct 2022 07:21:44 GMT-07:00In Memoriam: Jerry Yee, MDChoi, Michael J.2022-10-05T07:21:44-07:00doi:10.34067/KID.0004262022hwp:resource-id:kidney360;3/11/1942American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, memoriamReflectionReflectionother20222022-11-2410.34067/KID.00042620222641-76502022-10-05T07:21:44-07:002022-11-24Kidney360Reflection31119421943
- Point of Care Ultrasound in Cirrhosis-Associated Acute Kidney Injury: Beyond Inferior Vena Cava10.34067/KID.0005522022Wed, 05 Oct 2022 05:56:19 GMT-07:00Point of Care Ultrasound in Cirrhosis-Associated Acute Kidney Injury: Beyond Inferior Vena CavaKoratala, AbhilashReisinger, Nathaniel2022-10-05T05:56:19-07:00doi:10.34067/KID.0005522022hwp:resource-id:kidney360;3/11/1965American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, cirrhosis, hemodynamics, nephrology, POCUS, point-of-care ultrasound, VExUSPerspectivePerspectiveresearch-article20222022-11-2410.34067/KID.00055220222641-76502022-10-05T05:56:19-07:002022-11-24Kidney360Perspective31119651968
- Proinflammatory Diets and Risk of ESKD in US Adults with CKD10.34067/KID.0000442022Wed, 07 Sep 2022 01:31:55 GMT-07:00Proinflammatory Diets and Risk of ESKD in US Adults with CKDBanerjee, TanushreeMcCulloch, Charles E.Crews, Deidra C.Burrows, Nilka RiosPavkov, Meda E.Saran, RajivMorgenstern, HalBragg-Gresham, JenniferPowe, Neil R.,Powe, NeilBanerjee, TanushreeTuot, DelphineHsu, Chi-yuanMcCulloch, CharlesCrews, DeidraHsu, RaymondChu, ChiBibbins-Domingo, KirstenVelasquez, AlexandraCoresh, JosefSaran, RajivShahinian, VahaknGillespie, BrendaMorgenstern, HalHeung, MichaelHerman, WilliamBragg-Gresham, JenniferSteffick, DianeYin, MaggieRobinson, IanZivin, KaraHan, YunWyncott, AprilBurrows, Nilka RíosKoyama, AlainMondesire, JuanitaPatel, PritiPavkov, MedaRolka, DeborahSaydah, SharonWaller, Larry2022-09-07T13:31:55-07:00doi:10.34067/KID.0000442022hwp:resource-id:kidney360;3/11/1852American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, ADII, diet, end stage kidney disease, epidemiology and outcomes, inflammationOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-11-2410.34067/KID.00004420222641-76502022-09-07T13:31:55-07:002022-11-24Kidney360Original Investigation31118521860
- Minding the Gap Beyond Kidney Disease: Utility of the Anion Gap in Metabolic Syndrome10.34067/KID.0005142022Wed, 23 Nov 2022 07:45:30 GMT-08:00Minding the Gap Beyond Kidney Disease: Utility of the Anion Gap in Metabolic SyndromeTamargo, ChristinaCervantes, C. Elena2022-11-23T07:45:30-08:00doi:10.34067/KID.0005142022hwp:resource-id:kidney360;3/11/1819American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, acid-base equilibrium, acidosis, anion gap, CKD, metabolic syndrome, nonanion gapEditorialEditorialeditorial20222022-11-2410.34067/KID.00051420222641-76502022-11-23T07:45:30-08:002022-11-24Kidney360Editorial31118191822
- Short-Term Mortality Associated with Outpatient Vascular Access Restoration Procedures10.34067/KID.0004442022Wed, 12 Oct 2022 05:55:27 GMT-07:00Short-Term Mortality Associated with Outpatient Vascular Access Restoration ProceduresParatane, DeepikaDoll, Margaret K.Swain, Carol-AnnCardone, Katie E.McLaughlin, Colleen C.2022-10-12T05:55:27-07:00doi:10.34067/KID.0004442022hwp:resource-id:kidney360;3/11/1939American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, end stage kidney disease, interventional nephrology, mortality, outpatients, vascular accessBrief CommunicationDialysisBrief CommunicationDialysisresearch-article20222022-11-2410.34067/KID.00044420222641-76502022-10-12T05:55:27-07:002022-11-24Kidney360Brief Communication31119391941
- Magnetic Resonance Elastography as Surrogate Marker of Interstitial Fibrosis in Kidney Transplantation: A Prospective Study10.34067/KID.0004282022Wed, 07 Sep 2022 01:31:55 GMT-07:00Magnetic Resonance Elastography as Surrogate Marker of Interstitial Fibrosis in Kidney Transplantation: A Prospective StudyChauveau, BertrandMerville, PierreSoulabaille, BrunoTaton, BenjaminKaminski, HannahVisentin, JonathanVermorel, AgatheBouzgarrou, MounirCouzi, LionelGrenier, Nicolas2022-09-07T13:31:55-07:00doi:10.34067/KID.0004282022hwp:resource-id:kidney360;3/11/1924American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, elastography, fibrosis, histopathology, kidney transplantation, magnetic resonance imaging, prospective studiesOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-11-2410.34067/KID.00042820222641-76502022-09-07T13:31:55-07:002022-11-24Kidney360Original Investigation31119241933
- Complications Associated with Continuous RRTContinuous renal replacement therapy (CRRT) is a form of renal replacement therapy that is used in modern intensive care units (ICUs) to help manage acute kidney injury (AKI), end stage kidney disease (ESKD), poisonings, and some electrolyte disorders. CRRT has transformed the care of patients in the ICU over the past several decades. In this setting, it is important to recognize CRRT-associated complications but also up-to-date management of these complications. Some of these complications are minor, but others may be more significant and even life-threatening. Some CRRT complications may be related to dialysis factors and others to specific patient factors. Our overarching goal in this article is to review and discuss the most significant CRRT-related complications at the different stage of management of CRRT. With the advent of newer solutions, there have been newer complications as well.10.34067/KID.0000792022Mon, 12 Sep 2022 09:23:15 GMT-07:00Complications Associated with Continuous RRTContinuous renal replacement therapy (CRRT) is a form of renal replacement therapy that is used in modern intensive care units (ICUs) to help manage acute kidney injury (AKI), end stage kidney disease (ESKD), poisonings, and some electrolyte disorders. CRRT has transformed the care of patients in the ICU over the past several decades. In this setting, it is important to recognize CRRT-associated complications but also up-to-date management of these complications. Some of these complications are minor, but others may be more significant and even life-threatening. Some CRRT complications may be related to dialysis factors and others to specific patient factors. Our overarching goal in this article is to review and discuss the most significant CRRT-related complications at the different stage of management of CRRT. With the advent of newer solutions, there have been newer complications as well.Gautam, Samir C.Lim, JonathanJaar, Bernard G.2022-09-12T09:23:15-07:00doi:10.34067/KID.0000792022hwp:resource-id:kidney360;3/11/1980American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, bleeding, circuit, complications, CRRT, dialysis, drugs, electrolytes, ICU, pneumothoraxReview ArticleReview Articlereview-article20222022-11-2410.34067/KID.00007920222641-76502022-09-12T09:23:15-07:002022-11-24Kidney360Review Article31119801990
- Quality of Life in Patients with Chronic Kidney Disease Managed with or without Dialysis: An Observational Study10.34067/KID.0001602022Wed, 13 Jul 2022 10:48:31 GMT-07:00Quality of Life in Patients with Chronic Kidney Disease Managed with or without Dialysis: An Observational StudySo, SarahLi, KellyHoffman, Anna T.Josland, ElizabethBrown, Mark A.2022-07-13T10:48:31-07:00doi:10.34067/KID.0001602022hwp:resource-id:kidney360;3/11/1890American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360geriatric and palliative nephrology, chronic kidney disease, chronic renal failure, conservative kidney management, end stage kidney disease, geriatric nephrology, kidney supportive care, quality of lifeOriginal InvestigationGeriatric and Palliative NephrologyOriginal InvestigationGeriatric and Palliative Nephrologyresearch-article20222022-11-2410.34067/KID.00016020222641-76502022-07-13T10:48:31-07:002022-11-24Kidney360Original Investigation31118901898
- A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome10.34067/KID.0005472022Wed, 26 Oct 2022 02:03:07 GMT-07:00A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport SyndromeKohler, JenneferOmachi, KoheiCharu, VivekMiner, Jeffrey H.Bhalla, Vivek2022-10-26T14:03:07-07:00doi:10.34067/KID.0005472022hwp:resource-id:kidney360;3/11/1899American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, Alport syndrome, basic science, collagen, geneticsOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-11-2410.34067/KID.00054720222641-76502022-10-26T14:03:07-07:002022-11-24Kidney360Original Investigation31118991908
- Importance of Confounding Factors in the Evaluation of Surrogate Measures for Kidney Transplant Fibrosis10.34067/KID.0005852022Wed, 23 Nov 2022 07:45:30 GMT-08:00Importance of Confounding Factors in the Evaluation of Surrogate Measures for Kidney Transplant FibrosisAdam, Benjamin A.2022-11-23T07:45:30-08:00doi:10.34067/KID.0005852022hwp:resource-id:kidney360;3/11/1829American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, fibrosis, kidney transplantationEditorialEditorialeditorial20222022-11-2410.34067/KID.00058520222641-76502022-11-23T07:45:30-08:002022-11-24Kidney360Editorial31118291830
- Genital Edema in a Patient on Continuous Ambulatory Peritoneal Dialysis10.34067/KID.0003152022Wed, 23 Nov 2022 07:45:30 GMT-08:00Genital Edema in a Patient on Continuous Ambulatory Peritoneal DialysisThammathiwat, TheerachaiSirilak, SupindaSaksiriyadakun, Mayuree2022-11-23T07:45:30-08:00doi:10.34067/KID.0003152022hwp:resource-id:kidney360;3/11/1994American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, abdominal wall leakage, continuous ambulatory peritoneal dialysis, edema, ESKD, genitalia, peritoneal dialysisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-11-2410.34067/KID.00031520222641-76502022-11-23T07:45:30-08:002022-11-24Kidney360Clinical Images in Nephrology and Dialysis31119941995
- Heme Proteins and Kidney Injury: Beyond RhabdomyolysisHeme proteins, the stuff of life, represent an ingenious biologic strategy that capitalizes on the biochemical versatility of heme, and yet is one that avoids the inherent risks to cellular vitality posed by unfettered and promiscuously reactive heme. Heme proteins, however, may be a double-edged sword because they can damage the kidney in certain settings. Although such injury is often viewed mainly within the context of rhabdomyolysis and the nephrotoxicity of myoglobin, an increasing literature now attests to the fact that involvement of heme proteins in renal injury ranges well beyond the confines of this single disease (and its analog, hemolysis); indeed, through the release of the defining heme motif, destabilization of intracellular heme proteins may be a common pathway for acute kidney injury, in general, and irrespective of the underlying insult. This brief review outlines current understanding regarding processes underlying such heme protein-induced acute kidney injury (AKI) and chronic kidney disease (CKD). Topics covered include, among others, the basis for renal injury after the exposure of the kidney to and its incorporation of myoglobin and hemoglobin; auto-oxidation of myoglobin and hemoglobin; destabilization of heme proteins and the release of heme; heme/iron/oxidant pathways of renal injury; generation of reactive oxygen species and reactive nitrogen species by NOX, iNOS, and myeloperoxidase; and the role of circulating cell-free hemoglobin in AKI and CKD. Also covered are the characteristics of the kidney that render this organ uniquely vulnerable to injury after myolysis and hemolysis, and pathobiologic effects emanating from free, labile heme. Mechanisms that defend against the toxicity of heme proteins are discussed, and the review concludes by outlining the therapeutic strategies that have arisen from current understanding of mechanisms of renal injury caused by heme proteins and how such mechanisms may be interrupted.10.34067/KID.0005442022Wed, 05 Oct 2022 09:24:11 GMT-07:00Heme Proteins and Kidney Injury: Beyond RhabdomyolysisHeme proteins, the stuff of life, represent an ingenious biologic strategy that capitalizes on the biochemical versatility of heme, and yet is one that avoids the inherent risks to cellular vitality posed by unfettered and promiscuously reactive heme. Heme proteins, however, may be a double-edged sword because they can damage the kidney in certain settings. Although such injury is often viewed mainly within the context of rhabdomyolysis and the nephrotoxicity of myoglobin, an increasing literature now attests to the fact that involvement of heme proteins in renal injury ranges well beyond the confines of this single disease (and its analog, hemolysis); indeed, through the release of the defining heme motif, destabilization of intracellular heme proteins may be a common pathway for acute kidney injury, in general, and irrespective of the underlying insult. This brief review outlines current understanding regarding processes underlying such heme protein-induced acute kidney injury (AKI) and chronic kidney disease (CKD). Topics covered include, among others, the basis for renal injury after the exposure of the kidney to and its incorporation of myoglobin and hemoglobin; auto-oxidation of myoglobin and hemoglobin; destabilization of heme proteins and the release of heme; heme/iron/oxidant pathways of renal injury; generation of reactive oxygen species and reactive nitrogen species by NOX, iNOS, and myeloperoxidase; and the role of circulating cell-free hemoglobin in AKI and CKD. Also covered are the characteristics of the kidney that render this organ uniquely vulnerable to injury after myolysis and hemolysis, and pathobiologic effects emanating from free, labile heme. Mechanisms that defend against the toxicity of heme proteins are discussed, and the review concludes by outlining the therapeutic strategies that have arisen from current understanding of mechanisms of renal injury caused by heme proteins and how such mechanisms may be interrupted.Nath, Karl A.Singh, Raman DeepCroatt, Anthony J.Adams, Christopher M.2022-10-05T09:24:11-07:00doi:10.34067/KID.0005442022hwp:resource-id:kidney360;3/11/1969American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, auto-oxidation, CKD, heme, hemoglobin, hemolysis, myoglobin, rhabdomyolysisBasic Science for CliniciansBasic Science for Cliniciansresearch-article20222022-11-2410.34067/KID.00054420222641-76502022-10-05T09:24:11-07:002022-11-24Kidney360Basic Science for Clinicians31119691979
- Bardoxolone for CKD: The Paradox of Confusion and Dogma10.34067/KID.0000992022Wed, 07 Sep 2022 01:31:55 GMT-07:00Bardoxolone for CKD: The Paradox of Confusion and DogmaAvula, Uma Mahesh R.Harris, LiliiaHassanein, Mohamed2022-09-07T13:31:55-07:00doi:10.34067/KID.0000992022hwp:resource-id:kidney360;3/11/1955American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, bardoxolonePerspectivePerspectiveresearch-article20222022-11-2410.34067/KID.00009920222641-76502022-09-07T13:31:55-07:002022-11-24Kidney360Perspective31119551960
- Potassium Homeostasis and WNK Kinases in the Regulation of the Sodium-Chloride Cotransporter: Hyperaldosteronism and Its Metabolic Consequences10.34067/KID.0005752022Wed, 23 Nov 2022 07:45:30 GMT-08:00Potassium Homeostasis and WNK Kinases in the Regulation of the Sodium-Chloride Cotransporter: Hyperaldosteronism and Its Metabolic ConsequencesJohnston, Jermaine G.Wingo, Charles S.2022-11-23T07:45:30-08:00doi:10.34067/KID.0005752022hwp:resource-id:kidney360;3/11/1823American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, aldosterone, hypokalemia, K channels, potassium recycling, WNK signalingEditorialEditorialeditorial20222022-11-2410.34067/KID.00057520222641-76502022-11-23T07:45:30-08:002022-11-24Kidney360Editorial31118231828
- Efficacy of Low-Protein Rice for Dietary Protein Restriction in CKD Patients: A Multicenter, Randomized, Controlled Study10.34067/KID.0002982022Mon, 17 Oct 2022 01:50:35 GMT-07:00Efficacy of Low-Protein Rice for Dietary Protein Restriction in CKD Patients: A Multicenter, Randomized, Controlled StudyHosojima, MichihiroKabasawa, HideyukiKaseda, RyoheiIshikawa-Tanaka, TomomiObi, YoshitsuguMurayama, ToshikoKuwahara, ShojiSuzuki, YoshikiNarita, IchieiSaito, Akihiko2022-10-17T13:50:35-07:00doi:10.34067/KID.0002982022hwp:resource-id:kidney360;3/11/1861American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, chronic kidney disease, clinical trial, low protein diet, low-protein rice, protein-restricted dietOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-11-2410.34067/KID.00029820222641-76502022-10-17T13:50:35-07:002022-11-24Kidney360Original Investigation31118611870
- SARS-CoV-2 Infections among Vaccinated Patients on Maintenance Dialysis, January 1–August 31, 2021, United States10.34067/KID.0003092022Tue, 20 Sep 2022 07:33:25 GMT-07:00SARS-CoV-2 Infections among Vaccinated Patients on Maintenance Dialysis, January 1–August 31, 2021, United StatesBardossy, Ana CeciliaAngeles, JeseniaBooth, StephanieFike, LucyWadley, AshleyRha, BrianLacson, EduardoManley, Harold J.Johnson, DougApata, Ibironke W.Novosad, Shannon2022-09-20T07:33:25-07:00doi:10.34067/KID.0003092022hwp:resource-id:kidney360;3/11/1934American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, COVID-19, COVID-19 vaccine, end stage renal disease, ESKD, SARS-CoV-2, United StatesBrief CommunicationDialysisBrief CommunicationDialysisresearch-article20222022-11-2410.34067/KID.00030920222641-76502022-09-20T07:33:25-07:002022-11-24Kidney360Brief Communication31119341938
- Global Dialysis Perspective: Italy10.34067/KID.0007462021Wed, 31 Aug 2022 12:01:56 GMT-07:00Global Dialysis Perspective: ItalyPani, AntonelloCapasso, Giovambattista2022-08-31T12:01:56-07:00doi:10.34067/KID.0007462021hwp:resource-id:kidney360;3/11/1948American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, CKD, dialysis, disease related group, ESKD, ItalyGlobal PerspectiveGlobal Perspectiveresearch-article20222022-11-2410.34067/KID.00074620212641-76502022-08-31T12:01:56-07:002022-11-24Kidney360Global Perspective31119481952
- Global Dialysis Perspective: Kenya10.34067/KID.0006662021Mon, 05 Sep 2022 07:01:22 GMT-07:00Global Dialysis Perspective: KenyaMaritim, Peter K.K.Twahir, AhmedDavids, Mogamat Razeen2022-09-05T19:01:22-07:00doi:10.34067/KID.0006662021hwp:resource-id:kidney360;3/11/1944American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, funding, KenyaGlobal PerspectiveGlobal Perspectiveresearch-article20222022-11-2410.34067/KID.00066620212641-76502022-09-05T19:01:22-07:002022-11-24Kidney360Global Perspective31119441947
- Screening for Cardiovascular Disease in CKD: COMMENTARY10.34067/KID.0000742022Mon, 28 Feb 2022 06:11:13 GMT-08:00Screening for Cardiovascular Disease in CKD: COMMENTARYMcCallum, WendySarnak, Mark J.2022-02-28T18:11:13-08:00doi:10.34067/KID.0000742022hwp:resource-id:kidney360;3/11/1839American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, coronary disease, screeningModerator CommentaryModerator Commentaryarticle-commentary20222022-11-2410.34067/KID.00007420222641-76502022-02-28T18:11:13-08:002022-11-24Kidney360Moderator Commentary31118391841
- Screening for Cardiovascular Disease in CKD: PRO10.34067/KID.0005012021Mon, 28 Feb 2022 06:11:13 GMT-08:00Screening for Cardiovascular Disease in CKD: PROJain, NishankMcAdams, MeredithHedayati, S. Susan2022-02-28T18:11:13-08:00doi:10.34067/KID.0005012021hwp:resource-id:kidney360;3/11/1831American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, cardiac biomarkers, cardiac imaging, cardiovascular disease, screeningDebates in NephrologyDebates in Nephrologyresearch-article20222022-11-2410.34067/KID.00050120212641-76502022-02-28T18:11:13-08:002022-11-24Kidney360Debates in Nephrology31118311835
- Screening for Cardiovascular Disease in CKD: CON10.34067/KID.0004742021Mon, 28 Feb 2022 06:11:13 GMT-08:00Screening for Cardiovascular Disease in CKD: CONRamos, Giana K.Charytan, David M2022-02-28T18:11:13-08:00doi:10.34067/KID.0004742021hwp:resource-id:kidney360;3/11/1836American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, CKD, coronary artery disease, stress testDebates in NephrologyDebates in Nephrologyresearch-article20222022-11-2410.34067/KID.00047420212641-76502022-02-28T18:11:13-08:002022-11-24Kidney360Debates in Nephrology31118361838
- Sodium-Glucose Cotransporter 2 Inhibitors and Urinary Tract Infection: Is There Room for Real Concern?Sodium-glucose cotransporter 2 (SGLT2) inhibitors have revolutionized our armamentarium for kidney and heart protection in patients with or without diabetes. Based on early reports of a limited number of cases, a concern for increased risk of urinary tract infections arose, which has become one of the main areas of concern for some clinicians. However, data from large randomized clinical trials and real-world population-based studies have not shown a significantly increased risk of UTI in patients on SGLT2 inhibitors. The goal of this brief review article is to review the literature and provide reassurance to patients and prescribers for the broader use of these agents.10.34067/KID.0005722022Mon, 12 Sep 2022 11:24:13 GMT-07:00Sodium-Glucose Cotransporter 2 Inhibitors and Urinary Tract Infection: Is There Room for Real Concern?Sodium-glucose cotransporter 2 (SGLT2) inhibitors have revolutionized our armamentarium for kidney and heart protection in patients with or without diabetes. Based on early reports of a limited number of cases, a concern for increased risk of urinary tract infections arose, which has become one of the main areas of concern for some clinicians. However, data from large randomized clinical trials and real-world population-based studies have not shown a significantly increased risk of UTI in patients on SGLT2 inhibitors. The goal of this brief review article is to review the literature and provide reassurance to patients and prescribers for the broader use of these agents.Wiegley, NasimSo, Paolo Nikolai2022-09-12T11:24:13-07:00doi:10.34067/KID.0005722022hwp:resource-id:kidney360;3/11/1991American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, glucose, SGLT2 inhibitor, urinary tract infectionReview ArticleReview Articlereview-article20222022-11-2410.34067/KID.00057220222641-76502022-09-12T11:24:13-07:002022-11-24Kidney360Review Article31119911993
- Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2Background: Intact expression of podocyte histone deacetylases (HDAC) during development is essential for maintaining a normal glomerular filtration barrier due to its role in modulating DNA damage and preventing premature senescence. Methods: Germline podocyte-specific Hdac1 and 2 (Hdac1/2) double knockout mice were generated to examine the importance of these enzymes during development. Results: Podocyte-specific loss of Hdac1/2 in mice resulted in severe proteinuria, kidney failure, and collapsing glomerulopathy. Hdac1/2-deprived podocytes exhibited classic characteristics of senescence, such as senescence-associated β-galactosidase activity and lipofuscin aggregates. In addition, DNA damage, likely caused by epigenetic alterations such as open chromatin conformation, not only resulted in podocyte cell-cycle entry as shown in vivo by Ki67 expression and by FUCCI-2aR mice, but also in p21-mediated cell-cycle arrest. Through the senescence secretory associated phenotype, the damaged podocytes secreted proinflammatory cytokines, growth factors, and matrix metalloproteinases, resulting in subsequent podocyte detachment and loss, evidenced by senescent podocytes in urine. Conclusions: Hdac1/2 play an essential role during development. Loss of these genes in double knockout mice leads to sustained DNA damage and podocyte senescence and loss.shuta.ishibe@yale.edu10.1681/ASN.2022050598Tue, 22 Nov 2022 11:54:51 GMT-08:00Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2Background: Intact expression of podocyte histone deacetylases (HDAC) during development is essential for maintaining a normal glomerular filtration barrier due to its role in modulating DNA damage and preventing premature senescence. Methods: Germline podocyte-specific Hdac1 and 2 (Hdac1/2) double knockout mice were generated to examine the importance of these enzymes during development. Results: Podocyte-specific loss of Hdac1/2 in mice resulted in severe proteinuria, kidney failure, and collapsing glomerulopathy. Hdac1/2-deprived podocytes exhibited classic characteristics of senescence, such as senescence-associated β-galactosidase activity and lipofuscin aggregates. In addition, DNA damage, likely caused by epigenetic alterations such as open chromatin conformation, not only resulted in podocyte cell-cycle entry as shown in vivo by Ki67 expression and by FUCCI-2aR mice, but also in p21-mediated cell-cycle arrest. Through the senescence secretory associated phenotype, the damaged podocytes secreted proinflammatory cytokines, growth factors, and matrix metalloproteinases, resulting in subsequent podocyte detachment and loss, evidenced by senescent podocytes in urine. Conclusions: Hdac1/2 play an essential role during development. Loss of these genes in double knockout mice leads to sustained DNA damage and podocyte senescence and loss.Medina Rangel, PaulinaCross, ElizabethLiu, ChangPedigo, ChristopherTian, XuefeiGuitierrez-Calabres, ElenaNagata, SoichiroPriyadarshini, AnupamaLerner, GabrielBunda, PatriciaPerincheri, SudhirGu, JianleiZhao, HongyuWang, YingInoue, KazunoriIshibe, Shuta2022-11-22T11:54:51-08:00doi:10.1681/ASN.2022050598hwp:resource-id:jnephrol;ASN.2022050598v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220505981046-66731533-34502022-11-22T11:54:51-08:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.2022050598
- Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and FrogsBackground About 40 disease genes have been described to date for isolated congenital anomalies of the kidneys and urinary tract (CAKUT), the most common cause of childhood chronic kidney disease. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in such biologic processes as cell migration and focal adhesion, acts downstream of integrin linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva, leading to CAKUT in mice with this variant. Methods To identify novel genes that, when mutated, result in CAKUT, we performed exome sequencing in an international cohort of 1265 families with CAKUT. We also assessed the effects in vitro of wild-type and mutant ARHGEF6 proteins, as well as the effects of Arhgef6 deficiency in mouse and frog models. Results We detected six different hemizygous variants in the gene ARHGEF6 (which is located on the X chromosome in humans) in eight individuals from six families with CAKUT. In kidney cells, overexpression of wild-type ARHGEF6—but not proband-derived mutant ARHGEF6— increased active levels of CDC42/RAC1, induced lamellipodia formation, and stimulated PARVAdependent cell spreading. ARHGEF6 mutant proteins showed loss of interaction with PARVA. Three-dimensional MDCK cell cultures expressing ARHGEF6 mutant proteins exhibited reduced lumen formation and polarity defects. Arhgef6 deficiency in mouse and frog models recapitulated features of human CAKUT. Conclusions Deleterious variants in ARHGEF6 may cause dysregulation of integrin-parvinRAC1/CDC42 signaling, thereby leading to X-linked CAKUT.Friedhelm.Hildebrandt@childrens.harvard.edu10.1681/ASN.2022010050Tue, 22 Nov 2022 11:54:51 GMT-08:00Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and FrogsBackground About 40 disease genes have been described to date for isolated congenital anomalies of the kidneys and urinary tract (CAKUT), the most common cause of childhood chronic kidney disease. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in such biologic processes as cell migration and focal adhesion, acts downstream of integrin linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva, leading to CAKUT in mice with this variant. Methods To identify novel genes that, when mutated, result in CAKUT, we performed exome sequencing in an international cohort of 1265 families with CAKUT. We also assessed the effects in vitro of wild-type and mutant ARHGEF6 proteins, as well as the effects of Arhgef6 deficiency in mouse and frog models. Results We detected six different hemizygous variants in the gene ARHGEF6 (which is located on the X chromosome in humans) in eight individuals from six families with CAKUT. In kidney cells, overexpression of wild-type ARHGEF6—but not proband-derived mutant ARHGEF6— increased active levels of CDC42/RAC1, induced lamellipodia formation, and stimulated PARVAdependent cell spreading. ARHGEF6 mutant proteins showed loss of interaction with PARVA. Three-dimensional MDCK cell cultures expressing ARHGEF6 mutant proteins exhibited reduced lumen formation and polarity defects. Arhgef6 deficiency in mouse and frog models recapitulated features of human CAKUT. Conclusions Deleterious variants in ARHGEF6 may cause dysregulation of integrin-parvinRAC1/CDC42 signaling, thereby leading to X-linked CAKUT.Klämbt, VerenaBuerger, FlorianWang, ChunyanNaert, ThomasRichter, KarinNauth, TheresaWeiss, Anna-CarinaSieckmann, TobiasLai, EthanConnaughton, DervlaSeltzsam, SteveMann, NinaMajmundar, AmarWu, Chen-HanOnuchic-Whitford, AnaShril, ShirleeSchneider, SophiaSchierbaum, LucaDai, RufengBekheirnia, Mir RezaJoosten, MariekeShlomovitz, OmerVivante, AsafBanne, EhudMane, ShrikantLifton, Richard PKirschner, KarinKispert, AndreasRosenberger, GeorgFischer, Klaus-DieterLienkamp, SoerenZegers, MirjamHildebrandt, Friedhelm2022-11-22T11:54:51-08:00doi:10.1681/ASN.2022010050hwp:resource-id:jnephrol;ASN.2022010050v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220100501046-66731533-34502022-11-22T11:54:51-08:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.2022010050
- Changes in Glomerular Volume, Sclerosis, and Ischemia at 5 Years after Kidney Transplantation: Incidence and Correlation with Late Graft Failure10.1681/ASN.2022040418Thu, 17 Nov 2022 05:41:00 GMT-08:00Changes in Glomerular Volume, Sclerosis, and Ischemia at 5 Years after Kidney Transplantation: Incidence and Correlation with Late Graft FailureDenic, AleksandarBogojevic, MarijaSubramani, RashmiPark, Walter D.Smith, Byron H.Alexander, Mariam P.Grande, Joseph P.Kukla, AleksandraSchinstock, Carrie A.Bentall, Andrew J.Rule, Andrew D.Stegall, Mark D.2022-11-17T05:41:00-08:00doi:10.1681/ASN.2022040418hwp:resource-id:jnephrol;ASN.2022040418v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, morphometry, glomerular volume, global glomerulosclerosis, ischemic glomeruli, allograft failure, kidney transplantation, incidence, sclerosisClinical ResearchTransplantationClinical ResearchTransplantationresearch-article202210.1681/ASN.20220404181046-66731533-34502022-11-17T05:41:00-08:00Journal of the American Society of NephrologyClinical ResearchASN.2022040418
- Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial10.1681/ASN.2022050623Thu, 17 Nov 2022 05:40:59 GMT-08:00Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover TrialRefardt, JulieImber, CorneliaNobbenhuis, RianneSailer, Clara O.Haslbauer, AaronMonnerat, SophieBathelt, CemileVogt, Deborah R.Berres, ManfredWinzeler, BettinaBridenbaugh, Stephanie A.Christ-Crain, Mirjam2022-11-17T05:40:59-08:00doi:10.1681/ASN.2022050623hwp:resource-id:jnephrol;ASN.2022050623v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhyponatremia, neurocognitive deficits, gait disturbance, MoCA, treatment, sodium-glucose cotransporter 2, empagliflozin, double-blind methodClinical ResearchAcid Base and Electrolyte DisordersClinical ResearchAcid Base and Electrolyte Disordersresearch-article202210.1681/ASN.20220506231046-66731533-34502022-11-17T05:40:59-08:00Journal of the American Society of NephrologyClinical ResearchASN.2022050623
- National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations10.1681/ASN.2022070818Fri, 11 Nov 2022 07:11:15 GMT-08:00National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating EquationsDiao, James A.Wu, Gloria J.Wang, Jason K.Kohane, Isaac S.Taylor, Herman A.Tighiouart, HocineLevey, Andrew S.Inker, Lesley A.Powe, Neil R.Manrai, Arjun K.2022-11-11T07:11:15-08:00doi:10.1681/ASN.2022070818hwp:resource-id:jnephrol;ASN.2022070818v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rate, clinical epidemiology, chronic kidney diseaseClinical EpidemiologyChronic Kidney DiseaseClinical EpidemiologyChronic Kidney Diseaseresearch-article202210.1681/ASN.20220708181046-66731533-34502022-11-11T07:11:15-08:00Journal of the American Society of NephrologyClinical EpidemiologyASN.2022070818
- Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I Hyperactivation10.1681/ASN.2022040477Wed, 19 Oct 2022 10:34:21 GMT-07:00Clinical Implications of a New DDX58 Pathogenic Variant That Causes Lupus Nephritis due to RIG-I HyperactivationPeng, JiahuiWang, YushaHan, XuZhang, ChangmingChen, XiangJin, YingYang, ZhaohuiAn, YuZhang, JiahuiLiu, ZhengzhaoChen, YinghuaGao, ErzhiZhang, YangyangXu, FengZheng, ChunxiaZhou, QingLiu, Zhihong2022-10-19T10:34:21-07:00doi:10.1681/ASN.2022040477hwp:resource-id:jnephrol;ASN.2022040477v3American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologylupus nephritis, DDX58, pathogenic variant R109C, pathogenesis, targeted therapyBasic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article202210.1681/ASN.20220404771046-66731533-34502022-10-19T10:34:21-07:00Journal of the American Society of NephrologyBasic ResearchASN.2022040477
- Short-Term Effects of Potassium Chloride Supplementation on Fibroblast Growth Factor 23 and Phosphate in Chronic Kidney Diseasem.h.yeung@umcg.nl10.2215/CJN.09340822Thu, 10 Nov 2022 10:51:25 GMT-08:00Short-Term Effects of Potassium Chloride Supplementation on Fibroblast Growth Factor 23 and Phosphate in Chronic Kidney DiseaseYeung, StanleyGritter, MartinWouda, RosaBakker, Stephanvan Zanden, JelmerRotmans, JorisHoorn, EwoutVogt, Liffertde Borst, Martin2022-11-10T10:51:25-08:00doi:10.2215/CJN.09340822hwp:resource-id:clinjasn;CJN.09340822v1American Society of NephrologyClinical Journal of the American Society of NephrologyResearch LettersResearch Lettersresearch-article202210.2215/CJN.093408221555-90411555-905X2022-11-10T10:51:25-08:00Clinical Journal of the American Society of NephrologyResearch LettersCJN.09340822
- Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman Syndrome10.1681/ASN.2022050627Thu, 27 Oct 2022 11:46:36 GMT-07:00Long-Read Sequencing Identifies Novel Pathogenic Intronic Variants in Gitelman SyndromeViering, Daan H.H.M.Hureaux, MargueriteNeveling, KorneliaLatta, FemkeKwint, MichaelBlanchard, AnneKonrad, MartinBindels, René J.M.Schlingmann, Karl-PeterVargas-Poussou, Rosade Baaij, Jeroen H.F.2022-10-27T11:46:36-07:00doi:10.1681/ASN.2022050627hwp:resource-id:jnephrol;ASN.2022050627v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyepithelial sodium transport, genetic renal disease, Na reabsorption, tubulopathy, NCC, Gitelman syndromeClinical ResearchGenetic Disease of the KidneyClinical ResearchGenetic Disease of the Kidneyresearch-article202210.1681/ASN.20220506271046-66731533-34502022-10-27T11:46:36-07:00Journal of the American Society of NephrologyClinical ResearchASN.2022050627
- The Role of Platelet-Derived Growth Factor in Focal Segmental Glomerulosclerosis10.1681/ASN.2022040491Wed, 09 Nov 2022 06:42:55 GMT-08:00The Role of Platelet-Derived Growth Factor in Focal Segmental GlomerulosclerosisJia, TingXu, TongSmeets, BartBuhl, Eva MiriamMoeller, Marcus JohannesFloege, JürgenKlinkhammer, Barbara MaraBoor, Peter2022-11-09T06:42:55-08:00doi:10.1681/ASN.2022040491hwp:resource-id:jnephrol;ASN.2022040491v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyFSGS, PDGF, podocyte, parietal epithelial cell, Thy1Basic ResearchChronic Kidney DiseaseBasic ResearchChronic Kidney Diseaseresearch-article202210.1681/ASN.20220404911046-66731533-34502022-11-09T06:42:55-08:00Journal of the American Society of NephrologyBasic ResearchASN.2022040491
- Context Matters: A Qualitative Synthesis of Adherence Literature for People on HemodialysisBackground: Patients with end-stage kidney disease treated with hemodialysis in the U.S. have persistently higher rates of nonadherence compared to patients in other developed countries. Nonadherence is associated with increased risk of death and higher medical expenditure. There is an urgent need to address it with feasible, effective interventions as the prevalence of patients on hemodialysis in the U.S. continues to grow. However, published adherence interventions demonstrate limited long-term efficacy. Methods: We conducted a synthesis of qualitative studies on adherence to hemodialysis treatment, medications, and fluid and dietary restrictions to identify gaps in published adherence interventions, searching PubMed, CINAHL, PsychInfo, Embase, and Web of Science databases. We analyzed qualitative data with a priori codes derived from the World Health Organization's adherence framework and subsequent codes from thematic analysis. Results: We screened 1775 articles and extracted qualitative data from 12. The qualitative data revealed 20 factors unique to hemodialysis across the World Health Organization's five dimensions of adherence. Additionally, two overarching themes emerged from the data: (1) adherence in the context of patients' whole lives and (2) dialysis treatment as a double-edged sword. Patient-level factors reflected in the qualitative data extended beyond knowledge about hemodialysis treatment or motivation to adhere to treatment. Patients described a profound grieving process over loss of their "old self" that impacted adherence. They also navigated complex challenges that could be exacerbated by social determinants of health as they balanced treatment, life tasks, and social roles. Conclusions: This review adds to the growing evidence that one-size-fits-all approaches to improving adherence among patients on hemodialysis are inadequate. Adherence may improve when routine care incorporates patient context and provides ongoing support to patients and families as they navigate the logistical, physical, and psychological hardships of living with dialysis. New research is urgently needed to guide a change in course.ktaylo45@jhmi.edu10.34067/KID.0005582022Tue, 08 Nov 2022 01:37:17 GMT-08:00Context Matters: A Qualitative Synthesis of Adherence Literature for People on HemodialysisBackground: Patients with end-stage kidney disease treated with hemodialysis in the U.S. have persistently higher rates of nonadherence compared to patients in other developed countries. Nonadherence is associated with increased risk of death and higher medical expenditure. There is an urgent need to address it with feasible, effective interventions as the prevalence of patients on hemodialysis in the U.S. continues to grow. However, published adherence interventions demonstrate limited long-term efficacy. Methods: We conducted a synthesis of qualitative studies on adherence to hemodialysis treatment, medications, and fluid and dietary restrictions to identify gaps in published adherence interventions, searching PubMed, CINAHL, PsychInfo, Embase, and Web of Science databases. We analyzed qualitative data with a priori codes derived from the World Health Organization's adherence framework and subsequent codes from thematic analysis. Results: We screened 1775 articles and extracted qualitative data from 12. The qualitative data revealed 20 factors unique to hemodialysis across the World Health Organization's five dimensions of adherence. Additionally, two overarching themes emerged from the data: (1) adherence in the context of patients' whole lives and (2) dialysis treatment as a double-edged sword. Patient-level factors reflected in the qualitative data extended beyond knowledge about hemodialysis treatment or motivation to adhere to treatment. Patients described a profound grieving process over loss of their "old self" that impacted adherence. They also navigated complex challenges that could be exacerbated by social determinants of health as they balanced treatment, life tasks, and social roles. Conclusions: This review adds to the growing evidence that one-size-fits-all approaches to improving adherence among patients on hemodialysis are inadequate. Adherence may improve when routine care incorporates patient context and provides ongoing support to patients and families as they navigate the logistical, physical, and psychological hardships of living with dialysis. New research is urgently needed to guide a change in course.Taylor, Kathryn S.Umeukeje, Ebele M.Santos, Sydney R.McNabb, Katherine C.Crews, Deidra C.Hladek, Melissa D.2022-11-08T13:37:17-08:00doi:10.34067/KID.0005582022hwp:resource-id:kidney360;KID.0005582022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Treatment adherence, Qualitative research, Health equity, Food security, Hemodialysis, End-stage kidney disease, Patient-centered outcomesOriginal InvestigationOriginal Investigationother202210.34067/KID.00055820222641-76502641-76502022-11-08T13:37:17-08:00Kidney360Original Investigation10.34067/KID.0005582022
- Mapping the Transcriptome Underpinning Acute Corticosteroid Action within the Cortical Collecting DuctBackground Corticosteroids regulate distal nephron and collecting duct Na+ reabsorption, contributing to fluid-volume and blood pressure homeostasis. The transcriptional landscape underpinning the acute stimulation of the epithelial sodium channel (ENaC) by physiological concentrations of corticosteroids remains unclear. Methods Transcriptomic profiles underlying corticosteroid-stimulated ENaC activity in polarised mCCDcl1 cells were generated by coupling electrophysiological measurements of amiloride-sensitive currents with RNAseq. Generation of a collecting-duct specific reporter mouse line, mT/mG-Aqp2Cre, enabled isolation of primary collecting duct cells by FACS and ENaC activity was measured in cultured primary cells following acute application of corticosteroids. Expression of target genes was assessed by qRT-PCR in cultured cells or freshly isolated cells following acute elevation of steroid hormones in mT/mG-Aqp2Cre mice. Results Physiological relevance of the mCCDcl1 model was confirmed with aldosterone-specific stimulation of SGK1 and ENaC activity. Corticosterone only modulated these responses at supraphysiological concentrations or when 11βHSD2 was inhibited. When 11βHSD2 protection was intact, corticosterone caused no significant change in transcripts. We identified a small number of aldosterone-induced transcripts associated with stimulated ENaC activity in mCCDcl1 cells and a much larger number with corticosterone in the absence of 11βHSD2 activity. Cells isolated from mT/mG-Aqp2Cre mice were validated as collecting duct-specific and assessment of identified aldosterone-induced genes revealed that Sgk1, Zbtbt16, Sult1d1, Rasd1 and Gm43305 are acutely upregulated by corticosteroids both in vitro and in vivo. Conclusions This study reports the transcriptome of mCCDcl1 collecting duct cells and identifies a small number of aldosterone-induced genes associated with acute stimulation of ENaC, including 3 previously undescribed genes.mkm27@st-andrews.ac.uk10.34067/KID.0003582022Tue, 08 Nov 2022 12:15:01 GMT-08:00Mapping the Transcriptome Underpinning Acute Corticosteroid Action within the Cortical Collecting DuctBackground Corticosteroids regulate distal nephron and collecting duct Na+ reabsorption, contributing to fluid-volume and blood pressure homeostasis. The transcriptional landscape underpinning the acute stimulation of the epithelial sodium channel (ENaC) by physiological concentrations of corticosteroids remains unclear. Methods Transcriptomic profiles underlying corticosteroid-stimulated ENaC activity in polarised mCCDcl1 cells were generated by coupling electrophysiological measurements of amiloride-sensitive currents with RNAseq. Generation of a collecting-duct specific reporter mouse line, mT/mG-Aqp2Cre, enabled isolation of primary collecting duct cells by FACS and ENaC activity was measured in cultured primary cells following acute application of corticosteroids. Expression of target genes was assessed by qRT-PCR in cultured cells or freshly isolated cells following acute elevation of steroid hormones in mT/mG-Aqp2Cre mice. Results Physiological relevance of the mCCDcl1 model was confirmed with aldosterone-specific stimulation of SGK1 and ENaC activity. Corticosterone only modulated these responses at supraphysiological concentrations or when 11βHSD2 was inhibited. When 11βHSD2 protection was intact, corticosterone caused no significant change in transcripts. We identified a small number of aldosterone-induced transcripts associated with stimulated ENaC activity in mCCDcl1 cells and a much larger number with corticosterone in the absence of 11βHSD2 activity. Cells isolated from mT/mG-Aqp2Cre mice were validated as collecting duct-specific and assessment of identified aldosterone-induced genes revealed that Sgk1, Zbtbt16, Sult1d1, Rasd1 and Gm43305 are acutely upregulated by corticosteroids both in vitro and in vivo. Conclusions This study reports the transcriptome of mCCDcl1 collecting duct cells and identifies a small number of aldosterone-induced genes associated with acute stimulation of ENaC, including 3 previously undescribed genes.Loughlin, Struan R.Costello, Hannah M.Roe, Andrew J.Buckley, CharlotteWilson, Stuart M.Bailey, Matthew A.Mansley, Morag K.2022-11-08T12:15:01-08:00doi:10.34067/KID.0003582022hwp:resource-id:kidney360;KID.0003582022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360ENaC, electrophysiology, cortisol, collecting ducts, Cell & Transport Physiology, aldosterone, Transcriptome, renal epithelial cell, gene expression, epithelial sodium transport, Basic ScienceOriginal InvestigationOriginal Investigationother202210.34067/KID.00035820222641-76502641-76502022-11-08T12:15:01-08:00Kidney360Original Investigation10.34067/KID.0003582022
- A machine learning model to predict diuretic resistanceBackground: Volume overload is a common complication encountered in hospitalized patients, and the mainstay of therapy is diuresis. Unfortunately, the diuretic response in some individuals is inadequate despite a typical dose of loop diuretics, a phenomenon called diuretic resistance. An accurate prediction model that predicts diuretic resistance using pre-dosing variables could inform the right diuretic dose for a prospective patient. Methods: Two large, deidentified, publicly available and independent ICU databases from the United States were used - The Medical Information Mart for Intensive Case III (MIMIC) and the Philips eICU databases. Loop diuretic resistance was defined as less than 1400cc of urine per 40mg of diuretic dose in 24hrs. Using 24-hour windows throughout admission, commonly accessible were obtained and incorporated into the model. Data imputation was performed using a highly accurate Machine Learning method. Using XGBoost, several models were created using train and test datasets from the eICU database. These were then combined into an ensemble model optimized for increased specificity and then externally validated on the MIMIC database. Results: The final ensemble model was composed of four separate models, each using 21 commonly available variables. The ensemble model outperformed individual models during validation. Higher serum creatinine, lower systolic blood pressure, lower serum chloride, higher age, and female sex were the most important predictors of diuretic resistance (in that order). The specificity of the model on external validation was 92% yielding a positive likelihood ratio of 3.46 while maintaining overall discrimination (C-statistic 0.69). Conclusions: A diuretic resistance prediction model was created using machine learning and was externally validated in ICU populations. The model is easy to use, would provide actionable information at the bedside, and would be ready for implementation in existing electronic medical records. This study also provides a framework for the development of future Machine Learning models.jomercier@nosm.ca10.34067/KID.0005562022Tue, 08 Nov 2022 09:30:45 GMT-08:00A machine learning model to predict diuretic resistanceBackground: Volume overload is a common complication encountered in hospitalized patients, and the mainstay of therapy is diuresis. Unfortunately, the diuretic response in some individuals is inadequate despite a typical dose of loop diuretics, a phenomenon called diuretic resistance. An accurate prediction model that predicts diuretic resistance using pre-dosing variables could inform the right diuretic dose for a prospective patient. Methods: Two large, deidentified, publicly available and independent ICU databases from the United States were used - The Medical Information Mart for Intensive Case III (MIMIC) and the Philips eICU databases. Loop diuretic resistance was defined as less than 1400cc of urine per 40mg of diuretic dose in 24hrs. Using 24-hour windows throughout admission, commonly accessible were obtained and incorporated into the model. Data imputation was performed using a highly accurate Machine Learning method. Using XGBoost, several models were created using train and test datasets from the eICU database. These were then combined into an ensemble model optimized for increased specificity and then externally validated on the MIMIC database. Results: The final ensemble model was composed of four separate models, each using 21 commonly available variables. The ensemble model outperformed individual models during validation. Higher serum creatinine, lower systolic blood pressure, lower serum chloride, higher age, and female sex were the most important predictors of diuretic resistance (in that order). The specificity of the model on external validation was 92% yielding a positive likelihood ratio of 3.46 while maintaining overall discrimination (C-statistic 0.69). Conclusions: A diuretic resistance prediction model was created using machine learning and was externally validated in ICU populations. The model is easy to use, would provide actionable information at the bedside, and would be ready for implementation in existing electronic medical records. This study also provides a framework for the development of future Machine Learning models.Mercier, Joey A.Ferguson, Thomas W.Tangri, Navdeep2022-11-08T09:30:45-08:00doi:10.34067/KID.0005562022hwp:resource-id:kidney360;KID.0005562022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360prediction, machine learning, loop diuretic resistance, DiureticsOriginal InvestigationOriginal Investigationother202210.34067/KID.00055620222641-76502641-76502022-11-08T09:30:45-08:00Kidney360Original Investigation10.34067/KID.0005562022
- Intraoperative Urine Oxygen in Cardiac Surgery and 12-Month OutcomesThis is an Early Access article. Please select the PDF button, above, to view it.samuelparry10@gmail.com10.34067/KID.0003972022Tue, 08 Nov 2022 09:30:45 GMT-08:00Intraoperative Urine Oxygen in Cardiac Surgery and 12-Month OutcomesThis is an Early Access article. Please select the PDF button, above, to view it.Parry, Samuel R.Silverton, Natalie A.Hall, Isaac E.Stoddard, Gregory J.Lofgren, LarsKuck, Kai2022-11-08T09:30:45-08:00doi:10.34067/KID.0003972022hwp:resource-id:kidney360;KID.0003972022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Oxygen, Cardiac Surgical Procedures, renal injury, renal dysfunction, clinical nephrology, hypoxiaBrief CommunicationBrief Communicationother202210.34067/KID.00039720222641-76502641-76502022-11-08T09:30:45-08:00Kidney360Brief Communication10.34067/KID.0003972022
- Global Dialysis Perspective: GeorgiaThis is an Early Access article. Please select the PDF button, above, to view it.irma.tchokhonelidze@gmail.com10.34067/KID.0000772022Tue, 08 Nov 2022 08:17:36 GMT-08:00Global Dialysis Perspective: GeorgiaThis is an Early Access article. Please select the PDF button, above, to view it.Tchkhonelidze, Irma2022-11-08T08:17:36-08:00doi:10.34067/KID.0000772022hwp:resource-id:kidney360;KID.0000772022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360hemodialysis, funding, public-private partnership, recourses optimisation, access to dialysis, cost, staffing, vascular access, epidemiology of CKD, setting rpiority, GeorgiaGlobal PerspectivesGlobal Perspectivesother202210.34067/KID.00007720222641-76502641-76502022-11-08T08:17:36-08:00Kidney360Global Perspectives10.34067/KID.0000772022
- Accepting Living Kidney Donors with Preexisting Diabetes Mellitus10.2215/CJN.09460822Tue, 11 Oct 2022 09:23:53 GMT-07:00Accepting Living Kidney Donors with Preexisting Diabetes MellitusSoliman, Karim M.Daoud, AhmedPosadas Salas, Maria AuroraRice, TeresaUehara, GentaShayto, RaniFülöp, TiborDuBay, DerekCasey, Michael J.2022-10-11T09:23:53-07:00doi:10.2215/CJN.09460822hwp:resource-id:clinjasn;CJN.09460822v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, living donorsPerspectivePerspectiveresearch-article202210.2215/CJN.094608221555-90411555-905X2022-10-11T09:23:53-07:00Clinical Journal of the American Society of NephrologyPerspectiveCJN.09460822
- Decay-Accelerating Factor Expression Modulates the Severity of Experimental Focal Segmental GlomerulosclerosisThis is an Early Access article. Please select the PDF button, above, to view it.sofia.bin@mssm.edu10.34067/KID.0005312022Mon, 07 Nov 2022 01:31:15 GMT-08:00Decay-Accelerating Factor Expression Modulates the Severity of Experimental Focal Segmental GlomerulosclerosisThis is an Early Access article. Please select the PDF button, above, to view it.Bin, SofiaBudge, Kelly L.Gentile, MicaelaPodesta, Manuel AlfredoKhan, YaseenAzzi, Jamil RSanchez Russo, LuisLa Manna, GaetanoCravedi, Paolo2022-11-07T13:31:15-08:00doi:10.34067/KID.0005312022hwp:resource-id:kidney360;KID.0005312022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Focal Segmental Glomerulosclerosis, CD55 Antigens, Adriamycin, DAF, complement, C3, C3aR, Basic ScienceBrief CommunicationBrief Communicationother202210.34067/KID.00053120222641-76502641-76502022-11-07T13:31:15-08:00Kidney360Brief Communication10.34067/KID.0005312022
- Toxic Occupational Exposures and Membranous Nephropathy10.2215/CJN.02930322Tue, 25 Oct 2022 08:17:22 GMT-07:00Toxic Occupational Exposures and Membranous NephropathyCremoni, MarionAgbekodo, SophieTeisseyre, MaximeZorzi, KevinBrglez, VesnaBenzaken, SylviaEsnault, VincentPlanchard, Jo-HannaSeitz-Polski, Barbara2022-10-25T08:17:22-07:00doi:10.2215/CJN.02930322hwp:resource-id:clinjasn;17/11/1609American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, nephrotic syndrome, occupational exposureOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-11-01November 202210.2215/CJN.029303221555-90411555-905X2022-10-25T08:17:22-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article171116091619
- Processes of Care in Survivors of Acute Kidney Injury followed in Specialized Postdischarge Clinics10.2215/CJN.00160122Thu, 25 Aug 2022 10:44:55 GMT-07:00Processes of Care in Survivors of Acute Kidney Injury followed in Specialized Postdischarge ClinicsOrtiz-Soriano, VictorSingh, GurmukteshwarChang, AlexanderRuiz, Eloy F.Wald, RonSilver, Samuel A.Neyra, Javier A.2022-08-25T10:44:55-07:00doi:10.2215/CJN.00160122hwp:resource-id:clinjasn;17/11/1669American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, specialized post-discharge clinic, processes of care, kidney recovery, patient discharge, survivorsResearch LetterResearch Letterletter20222022-11-01November 202210.2215/CJN.001601221555-90411555-905X2022-08-25T10:44:55-07:002022-11Clinical Journal of the American Society of NephrologyResearch Letter171116691672
- A Qualitative Content Analysis of Comments on Press Articles on Deemed Consent for Organ Donation in Canada10.2215/CJN.04340422Wed, 26 Oct 2022 09:16:54 GMT-07:00A Qualitative Content Analysis of Comments on Press Articles on Deemed Consent for Organ Donation in CanadaFox, Danielle E.Donald, MaoliosaChong, ChristyQuinn, Robert R.Ronksley, Paul E.Elliott, Meghan J.Lam, Ngan N.2022-10-26T09:16:54-07:00doi:10.2215/CJN.04340422hwp:resource-id:clinjasn;17/11/1656American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydeemed consent, opt-out, opt-in, organ donation, transplantation, Canada, public opinionOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-11-01November 202210.2215/CJN.043404221555-90411555-905X2022-10-26T09:16:54-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article17111111165615751577166415761579
- Integrating PROMs in Routine Dialysis Care10.2215/CJN.10840922Tue, 25 Oct 2022 08:34:20 GMT-07:00Integrating PROMs in Routine Dialysis CareFlythe, Jennifer E.2022-10-25T08:34:20-07:00doi:10.2215/CJN.10840922hwp:resource-id:clinjasn;17/11/1580American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, ESRD, hemodialysis, quality of lifeEditorialEditorialeditorial20222022-11-01November 202210.2215/CJN.108409221555-90411555-905X2022-10-25T08:34:20-07:002022-11Clinical Journal of the American Society of NephrologyEditorial1711111580163115821645
- Understanding Public Perspectives on Opt-Out Deceased Donor Transplant Policy10.2215/CJN.11230922Wed, 26 Oct 2022 10:18:29 GMT-07:00Understanding Public Perspectives on Opt-Out Deceased Donor Transplant PolicyButler, Catherine R.2022-10-26T10:18:29-07:00doi:10.2215/CJN.11230922hwp:resource-id:clinjasn;17/11/1577American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, equityEditorialEditorialeditorial20222022-11-01November 202210.2215/CJN.112309221555-90411555-905X2022-10-26T10:18:29-07:002022-11Clinical Journal of the American Society of NephrologyEditorial17111111157716561575157916641576
- Can We Turn the Symptom Curve?10.2215/CJN.11240922Fri, 28 Oct 2022 06:50:05 GMT-07:00Can We Turn the Symptom Curve?Rodriguez de Sosa, GiselleUnruh, Mark2022-10-28T06:50:05-07:00doi:10.2215/CJN.11240922hwp:resource-id:clinjasn;17/11/1586American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, symptom trajectories, health-related quality of lifeEditorialEditorialeditorial20222022-11-01November 202210.2215/CJN.112409221555-90411555-905X2022-10-28T06:50:05-07:002022-11Clinical Journal of the American Society of NephrologyEditorial1711111586158815871597
- Correction: Physiology of the Aging Kidney: We Know Where We Are Going, but We Don’t Know How…10.2215/CJN.09940822Tue, 20 Sep 2022 06:25:14 GMT-07:00Correction: Physiology of the Aging Kidney: We Know Where We Are Going, but We Don’t Know How…American Society of Nephrology2022-09-20T06:25:14-07:00doi:10.2215/CJN.09940822hwp:resource-id:clinjasn;17/11/1673American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20222022-11-01November 202210.2215/CJN.099408221555-90411555-905X2022-09-20T06:25:14-07:002022-11Clinical Journal of the American Society of NephrologyErratum17171181673110716731109
- Five-Year Symptom Trajectories in Nondialysis-Dependent CKD Patients10.2215/CJN.06140522Fri, 28 Oct 2022 06:50:05 GMT-07:00Five-Year Symptom Trajectories in Nondialysis-Dependent CKD PatientsFaye, MoustaphaLegrand, KarineLe Gall, LisaLeffondre, KarenOmorou, Abdou Y.Alencar de Pinho, NataliaCombe, ChristianFouque, DenisJacquelinet, ChristianLaville, MauriceLiabeuf, SophieMassy, Ziad A.Speyer, ElodiePecoits Filho, RobertoStengel, BénédicteFrimat, LucAyav, Carole2022-10-28T06:50:05-07:00doi:10.2215/CJN.06140522hwp:resource-id:clinjasn;17/11/1588American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysymptoms, quality of life, CKD, clinical epidemiology, cohort studiesOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-11-01November 202210.2215/CJN.061405221555-90411555-905X2022-10-28T06:50:05-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article1711111588158615971587
- “Make Me a Match”10.2215/CJN.04450422Tue, 19 Jul 2022 11:18:54 GMT-07:00“Make Me a Match”Cheng, Steven C.Pivert, Kurtis A.Sozio, Stephen M.2022-07-19T11:18:54-07:00doi:10.2215/CJN.04450422hwp:resource-id:clinjasn;17/11/1691American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, training, nephrology matchPerspectivePerspectiveresearch-article20222022-11-01November 202210.2215/CJN.044504221555-90411555-905X2022-07-19T11:18:54-07:002022-11Clinical Journal of the American Society of NephrologyPerspective171116911693
- Acute Kidney Injury in Patients with Liver DiseaseAKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C–associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.10.2215/CJN.03040322Thu, 28 Jul 2022 06:55:06 GMT-07:00Acute Kidney Injury in Patients with Liver DiseaseAKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C–associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.Cullaro, GiuseppeKanduri, Swetha RaniVelez, Juan Carlos Q.2022-07-28T06:55:06-07:00doi:10.2215/CJN.03040322hwp:resource-id:clinjasn;17/11/1674American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, cirrhosis, liver failure, hepatorenal syndrome, Critical Care Nephrology and Acute Kidney Injury SeriesCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-11-01November 202210.2215/CJN.030403221555-90411555-905X2022-07-28T06:55:06-07:002022-11Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury171116741684
- How the Routine Use of Patient-Reported Outcome Measures for Hemodialysis Care Influences Patient-Clinician Communication10.2215/CJN.05940522Tue, 25 Oct 2022 08:17:23 GMT-07:00How the Routine Use of Patient-Reported Outcome Measures for Hemodialysis Care Influences Patient-Clinician CommunicationSchick-Makaroff, KaraWozniak, Lisa A.Short, HilaryDavison, Sara N.Klarenbach, ScottBuzinski, RobertWalsh, MichaelJohnson, Jeffrey A.2022-10-25T08:17:23-07:00doi:10.2215/CJN.05940522hwp:resource-id:clinjasn;17/11/1631American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, patient-reported outcome measures, PROMs, communicationOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-11-01November 202210.2215/CJN.059405221555-90411555-905X2022-10-25T08:17:23-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article1711111631158016451582
- Genome-Wide Association Study for eGFR in a Taiwanese Population10.2215/CJN.02180222Wed, 12 Oct 2022 05:31:22 GMT-07:00Genome-Wide Association Study for eGFR in a Taiwanese PopulationChen, Ying-ChunWong, Henry Sung-ChingWu, Mei-YiChou, Wan-HsuanKao, Chih-ChinChao, Ching-HsuanChang, Wei-ChiaoWu, Mai-Szu2022-10-12T05:31:22-07:00doi:10.2215/CJN.02180222hwp:resource-id:clinjasn;17/11/1598American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal function, genome-wide association study, glomerular filtration rateOriginal ArticleGeneticsOriginal ArticleGeneticsresearch-article20222022-11-01November 202210.2215/CJN.021802221555-90411555-905X2022-10-12T05:31:22-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article171115981608
- Gut Microbiome and Kidney Disease10.2215/CJN.04480422Wed, 06 Jul 2022 08:19:46 GMT-07:00Gut Microbiome and Kidney DiseaseShankaranarayanan, DivyaRaj, Dominic S.2022-07-06T08:19:46-07:00doi:10.2215/CJN.04480422hwp:resource-id:clinjasn;17/11/1694American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, microbiomePerspectivePerspectiveresearch-article20222022-11-01November 202210.2215/CJN.044804221555-90411555-905X2022-07-06T08:19:46-07:002022-11Clinical Journal of the American Society of NephrologyPerspective171116941696
- Safety and Efficacy of Belimumab in Patients with Lupus Nephritis10.2215/CJN.02520322Thu, 27 Oct 2022 06:45:15 GMT-07:00Safety and Efficacy of Belimumab in Patients with Lupus NephritisFurie, RichardRovin, Brad H.Houssiau, FrédéricContreras, GabrielTeng, Y.K. OnnoCurtis, PaulaGreen, YuliaOkily, MohamedMadan, AnuradhaRoth, David A.2022-10-27T06:45:15-07:00doi:10.2215/CJN.02520322hwp:resource-id:clinjasn;17/11/1620American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, glomerular disease, glomerulonephritis, kidney disease, lupus nephritis, proteinuria, belimumabOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-11-01November 202210.2215/CJN.025203221555-90411555-905X2022-10-27T06:45:15-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article1711111620158316301585
- The Role of Anti-B Cell Activating Factor Therapy for Treating Lupus Nephritis10.2215/CJN.11340922Thu, 27 Oct 2022 07:09:30 GMT-07:00The Role of Anti-B Cell Activating Factor Therapy for Treating Lupus NephritisWooden, BenjaminRadhakrishnan, Jai2022-10-27T07:09:30-07:00doi:10.2215/CJN.11340922hwp:resource-id:clinjasn;17/11/1583American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysystemic lupus erythematosus, immunosuppression, voclosporin, belimumabEditorialEditorialeditorial20222022-11-01November 202210.2215/CJN.113409221555-90411555-905X2022-10-27T07:09:30-07:002022-11Clinical Journal of the American Society of NephrologyEditorial1711111583162015851630
- Digenic Alport SyndromeDigenic Alport syndrome refers to the inheritance of pathogenic variants in COL4A5 plus COL4A3 or COL4A4 or in COL4A3 plus COL4A4. Where digenic Alport syndrome includes a pathogenic COL4A5 variant, the consequences depend on the sex of the affected individual, COL4A5 variant “severity,” and the nature of the COL4A3 or COL4A4 change. A man with a pathogenic COL4A5 variant has all his collagen IV α3α4α5-heterotrimers affected, and an additional COL4A3 or COL4A4 variant may not worsen disease. A woman with a pathogenic COL4A5 variant has on average 50% of her heterotrimers affected, which is increased to 75% with a further COL4A3 or COL4A4 variant and associated with a higher risk of proteinuria. In digenic Alport syndrome with pathogenic COL4A3 and COL4A4 variants, 75% of the heterotrimers are affected. The COL4A3 and COL4A4 genes occur head-to-head on chromosome 2, and inheritance is autosomal dominant when both variants affect the same chromosome (in cis) or recessive when they affect different chromosomes (in trans). This form of digenic disease results in increased proteinuria and a median age of kidney failure intermediate between autosomal dominant and autosomal recessive Alport syndrome. Previous guidelines have suggested that all pathogenic or likely pathogenic digenic variants should be identified and reported. Affected family members should be identified, treated, and discouraged from kidney donation. Inheritance within a family is easier to predict if the two variants are considered independently and if COL4A3 and COL4A4 variants are known to be inherited on the same or different chromosomes.10.2215/CJN.03120322Wed, 08 Jun 2022 05:51:16 GMT-07:00Digenic Alport SyndromeDigenic Alport syndrome refers to the inheritance of pathogenic variants in COL4A5 plus COL4A3 or COL4A4 or in COL4A3 plus COL4A4. Where digenic Alport syndrome includes a pathogenic COL4A5 variant, the consequences depend on the sex of the affected individual, COL4A5 variant “severity,” and the nature of the COL4A3 or COL4A4 change. A man with a pathogenic COL4A5 variant has all his collagen IV α3α4α5-heterotrimers affected, and an additional COL4A3 or COL4A4 variant may not worsen disease. A woman with a pathogenic COL4A5 variant has on average 50% of her heterotrimers affected, which is increased to 75% with a further COL4A3 or COL4A4 variant and associated with a higher risk of proteinuria. In digenic Alport syndrome with pathogenic COL4A3 and COL4A4 variants, 75% of the heterotrimers are affected. The COL4A3 and COL4A4 genes occur head-to-head on chromosome 2, and inheritance is autosomal dominant when both variants affect the same chromosome (in cis) or recessive when they affect different chromosomes (in trans). This form of digenic disease results in increased proteinuria and a median age of kidney failure intermediate between autosomal dominant and autosomal recessive Alport syndrome. Previous guidelines have suggested that all pathogenic or likely pathogenic digenic variants should be identified and reported. Affected family members should be identified, treated, and discouraged from kidney donation. Inheritance within a family is easier to predict if the two variants are considered independently and if COL4A3 and COL4A4 variants are known to be inherited on the same or different chromosomes.Savige, JudyRenieri, AlessandraArs, ElisabetDaga, SergioPinto, Anna MariaRothe, HansjorgGale, Daniel P.Aksenova, MarinaCerkauskaite, AgneBielska, OlgaLipska-Zietkiewicz, BeataGibson, Joel T.2022-06-08T05:51:16-07:00doi:10.2215/CJN.03120322hwp:resource-id:clinjasn;17/11/1697American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, kidney failure, genetic renal disease, proteinuria, collagen, COL4A3, COL4A4, COL4A5 genes, digenic Alport syndromeReviewReviewreview-article20222022-11-01November 202210.2215/CJN.031203221555-90411555-905X2022-06-08T05:51:16-07:002022-11Clinical Journal of the American Society of NephrologyReview171116971706
- Effects of Dapagliflozin in People without Diabetes and with Microalbuminuria10.2215/CJN.07290622Fri, 09 Sep 2022 01:31:57 GMT-07:00Effects of Dapagliflozin in People without Diabetes and with MicroalbuminuriaHeerspink, Hiddo J.L.Chertow, Glenn M.Jongs, NielsCorrea-Rotter, RicardoRossing, PeterSjöström, C. DavidLangkilde, Anna MariaWheeler, David C.2022-09-09T13:31:57-07:00doi:10.2215/CJN.07290622hwp:resource-id:clinjasn;17/11/1665American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydapagliflozin, SGLT2 inhibitor, CKD, microalbuminuriaResearch LetterResearch Letterletter20222022-11-01November 202210.2215/CJN.072906221555-90411555-905X2022-09-09T13:31:57-07:002022-11Clinical Journal of the American Society of NephrologyResearch Letter171116651668
- Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation10.2215/CJN.03840322Thu, 27 Oct 2022 06:45:14 GMT-07:00Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney TransplantationDandamudi, RajaGu, HongjieGoss, Charles W.Walther, LeslieDharnidharka, Vikas R.2022-10-27T06:45:14-07:00doi:10.2215/CJN.03840322hwp:resource-id:clinjasn;17/11/1646American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatric kidney transplantation, rejection, BK, donor-derived cell free DNAOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-11-01November 202210.2215/CJN.038403221555-90411555-905X2022-10-27T06:45:14-07:002022-11Clinical Journal of the American Society of NephrologyOriginal Article171116461655
- How I Treat Steroid-Sensitive Nephrotic Syndrome in Children10.2215/CJN.05200422Fri, 02 Sep 2022 08:49:13 GMT-07:00How I Treat Steroid-Sensitive Nephrotic Syndrome in ChildrenVivarelli, MarinaEmma, Francesco2022-09-02T08:49:13-07:00doi:10.2215/CJN.05200422hwp:resource-id:clinjasn;17/11/1685American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyidiopathic nephrotic syndrome, prednisone, children, rituximab, mycophenolate mofetil, calcineurin inhibitorKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-11-01November 202210.2215/CJN.052004221555-90411555-905X2022-09-02T08:49:13-07:002022-11Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat171116851687
- Reducing the Risks of Home Dialysis Innovation and Uptake10.2215/CJN.05100422Fri, 12 Aug 2022 11:11:52 GMT-07:00Reducing the Risks of Home Dialysis Innovation and UptakeCahill, ZacharyConway, Paul T.Lim, Mark D.2022-08-12T11:11:52-07:00doi:10.2215/CJN.05100422hwp:resource-id:clinjasn;17/11/1688American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyhemodialysisPerspectivePerspectiveresearch-article20222022-11-01November 202210.2215/CJN.051004221555-90411555-905X2022-08-12T11:11:52-07:002022-11Clinical Journal of the American Society of NephrologyPerspective171116881690
- Media Analysis of the Canadian Deemed Consent Policy10.2215/CJN.11270922Wed, 26 Oct 2022 09:16:54 GMT-07:00Media Analysis of the Canadian Deemed Consent PolicyConway, Paul T.2022-10-26T09:16:54-07:00doi:10.2215/CJN.11270922hwp:resource-id:clinjasn;17/11/1575American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydeemed consent, opt-out, opt-in, organ donation, transplant, mandated shared decision makingPatient VoicePatient Voiceresearch-article20222022-11-01November 202210.2215/CJN.112709221555-90411555-905X2022-10-26T09:16:54-07:002022-11Clinical Journal of the American Society of NephrologyPatient Voice17111111157516561577157616641579
- Characterization of Glomerular and Tubulointerstitial Proteomes in a Case of NSAID-Attributed Acute Kidney InjuryThe major goals of the Kidney Precision Medicine Project (KPMP) are to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of chronic kidney disease and acute kidney injury. In this clinical-pathological-molecular correlation, we describe the case of a 38-year-old woman without any prior history of chronic kidney disease who underwent a research kidney biopsy in the setting of acute kidney injury suspected to be due to non-steroidal anti-inflammatory use following cesarean section delivery. The participant's histopathology was consistent with mild acute tubular injury, without significant interstitial fibrosis or tubular atrophy. This diagnosis was supported by analysis of the glomerular and tubulointerstitial proteomes. The proteomic interrogation revealed a molecular landscape that demonstrated differences in kidney prostaglandin synthesis that may be in response to NSAIDs, as well as signs of intra-renal inflammation and fibrosis that were not evident by histopathology alone.samir.parikh@osumc.edu10.2215/CJN.09260822Mon, 07 Nov 2022 09:50:01 GMT-08:00Characterization of Glomerular and Tubulointerstitial Proteomes in a Case of NSAID-Attributed Acute Kidney InjuryThe major goals of the Kidney Precision Medicine Project (KPMP) are to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of chronic kidney disease and acute kidney injury. In this clinical-pathological-molecular correlation, we describe the case of a 38-year-old woman without any prior history of chronic kidney disease who underwent a research kidney biopsy in the setting of acute kidney injury suspected to be due to non-steroidal anti-inflammatory use following cesarean section delivery. The participant's histopathology was consistent with mild acute tubular injury, without significant interstitial fibrosis or tubular atrophy. This diagnosis was supported by analysis of the glomerular and tubulointerstitial proteomes. The proteomic interrogation revealed a molecular landscape that demonstrated differences in kidney prostaglandin synthesis that may be in response to NSAIDs, as well as signs of intra-renal inflammation and fibrosis that were not evident by histopathology alone.Parikh, SamirMadhavan, SethuShapiro, JohnKnight, RichardRosenberg, AviParikh, ChiragRovin, BradMenez, Steven2022-11-07T09:50:01-08:00doi:10.2215/CJN.09260822hwp:resource-id:clinjasn;CJN.09260822v1American Society of NephrologyClinical Journal of the American Society of NephrologyInvited FeaturesInvited Featuresresearch-article202210.2215/CJN.092608221555-90411555-905X2022-11-07T09:50:01-08:00Clinical Journal of the American Society of NephrologyInvited FeaturesCJN.09260822
- Global Perspectives in Acute Kidney Injury: BoliviaThis is an Early Access article. Please select the PDF button, above, to view it.rclaure@yahoo.com10.34067/KID.0002412022Mon, 07 Nov 2022 09:33:24 GMT-08:00Global Perspectives in Acute Kidney Injury: BoliviaThis is an Early Access article. Please select the PDF button, above, to view it.Claure-Del Granado, RolandoPlata-Cornejo, Raúl2022-11-07T09:33:24-08:00doi:10.34067/KID.0002412022hwp:resource-id:kidney360;KID.0002412022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Acute Kidney Injury, Bolivia, Kidney Replacement Therapies, BiomarkersGlobal PerspectivesGlobal Perspectivesother202210.34067/KID.00024120222641-76502641-76502022-11-07T09:33:24-08:00Kidney360Global Perspectives10.34067/KID.0002412022
- Organizing Nephrologists at the State Leveldroth@med.miami.edu10.2215/CJN.09430822Mon, 07 Nov 2022 08:37:58 GMT-08:00Organizing Nephrologists at the State LevelRoth, DavidSegal, MarkSastry, AshokAslam, Nabeel2022-11-07T08:37:58-08:00doi:10.2215/CJN.09430822hwp:resource-id:clinjasn;CJN.09430822v1American Society of NephrologyClinical Journal of the American Society of NephrologyInvited FeaturesInvited Featuresresearch-article202210.2215/CJN.094308221555-90411555-905X2022-11-07T08:37:58-08:00Clinical Journal of the American Society of NephrologyInvited FeaturesCJN.09430822
- Can Kidney Organoid Xenografts Accelerate Therapeutic Development for Genetic Kidney Disorders?A number of genetic kidney diseases can now be replicated experimentally, using kidney organoids generated from human pluripotent stem cells. This methodology holds great potential for drug discovery. Under in vitro conditions, however, kidney organoids remain developmentally immature, develop scarce vasculature, and may contain undesired off-target cell types. Those critical deficiencies limit their potential as disease-modeling tools. Orthotopic transplantation under the kidney capsule improves the anatomic maturity and vascularization of kidney organoids, while reducing off-target cell content. The improvements can translate into more accurate representations of disease phenotypes and mechanisms in vivo. Recent studies using kidney organoid xenografts highlighted the unique potential of this novel methodology for elucidating molecular mechanisms driving monogenic kidney disorders and for the development ofnovel pharmacotherapies.10.1681/ASN.2022080862Mon, 07 Nov 2022 05:46:13 GMT-08:00Can Kidney Organoid Xenografts Accelerate Therapeutic Development for Genetic Kidney Disorders?A number of genetic kidney diseases can now be replicated experimentally, using kidney organoids generated from human pluripotent stem cells. This methodology holds great potential for drug discovery. Under in vitro conditions, however, kidney organoids remain developmentally immature, develop scarce vasculature, and may contain undesired off-target cell types. Those critical deficiencies limit their potential as disease-modeling tools. Orthotopic transplantation under the kidney capsule improves the anatomic maturity and vascularization of kidney organoids, while reducing off-target cell content. The improvements can translate into more accurate representations of disease phenotypes and mechanisms in vivo. Recent studies using kidney organoid xenografts highlighted the unique potential of this novel methodology for elucidating molecular mechanisms driving monogenic kidney disorders and for the development ofnovel pharmacotherapies.Kuo, Ting-ChunCabrera-Barragan, Dalia NLopez-Marfil, MartaLopez-Cantu, Diana OLemos, Dario R.2022-11-07T05:46:13-08:00doi:10.1681/ASN.2022080862hwp:resource-id:jnephrol;ASN.2022080862v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic kidney disease, stem cell, organoidsReviewReviewresearch-article202210.1681/ASN.20220808621046-66731533-34502022-11-07T05:46:13-08:00Journal of the American Society of NephrologyReviewASN.2022080862
- Management of Patients with Kidney Failure and Pericarditis10.2215/CJN.07470622Thu, 03 Nov 2022 07:23:11 GMT-07:00Management of Patients with Kidney Failure and PericarditisRosen, Raphael J.Valeri, Anthony M.2022-11-03T07:23:11-07:00doi:10.2215/CJN.07470622hwp:resource-id:clinjasn;CJN.07470622v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic dialysis, pericarditis, uremiaKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article202210.2215/CJN.074706221555-90411555-905X2022-11-03T07:23:11-07:00Clinical Journal of the American Society of NephrologyKidney Case Conference: How I TreatCJN.07470622
- Nuclear Magnetic Resonance Metabolomic Profiling and Urine Chemistries in Incident Kidney Stone Formers Compared with Controls10.1681/ASN.2022040416Tue, 19 Jul 2022 11:52:26 GMT-07:00Nuclear Magnetic Resonance Metabolomic Profiling and Urine Chemistries in Incident Kidney Stone Formers Compared with ControlsThongprayoon, CharatVuckovic, IvanVaughan, Lisa E.Macura, SlobodanLarson, Nicholas B.D’Costa, Matthew R.Lieske, John C.Rule, Andrew D.Denic, Aleksandar2022-07-19T11:52:26-07:00doi:10.1681/ASN.2022040416hwp:resource-id:jnephrol;33/11/2071American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolomics, urine chemistries, nephrolithiasis, supersaturation, NMR, kidney calculiClinical ResearchAcid Base and Electrolyte DisordersClinical ResearchAcid Base and Electrolyte Disordersresearch-article20222022-11-01November 202210.1681/ASN.20220404161046-66731533-34502022-07-19T11:52:26-07:002022-11Journal of the American Society of NephrologyClinical Research331120712086
- Anti-Neu5Gc Antibodies do not Affect Response to Human or Chimeric Monoclonal Anti-CD20 Antibodies in Children with Nephrotic Syndrome10.1681/ASN.2022070755Tue, 23 Aug 2022 02:09:48 GMT-07:00Anti-Neu5Gc Antibodies do not Affect Response to Human or Chimeric Monoclonal Anti-CD20 Antibodies in Children with Nephrotic SyndromeAngeletti, AndreaBruschi, MaurizioKajana, XhulianaLugani, FrancescaCandiano, GiovanniGhiggeri, Gian Marco2022-08-23T14:09:48-07:00doi:10.1681/ASN.2022070755hwp:resource-id:jnephrol;33/11/1985American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, anti-Neu5Gc antibodies, anti-CD20 antibodies, rituximab, steroid-dependent nephrotic syndrome, pediatricsResearch LetterGlomerulonephritis and Interstitial NephritisResearch LetterGlomerulonephritis and Interstitial Nephritisletter20222022-11-01November 202210.1681/ASN.20220707551046-66731533-34502022-08-23T14:09:48-07:002022-11Journal of the American Society of NephrologyResearch Letter331119851987
- Financial Barriers to the Optimal Use of Peritoneal Dialysis in France and Europe, as in the United States10.1681/ASN.2022070839Tue, 30 Aug 2022 07:22:48 GMT-07:00Financial Barriers to the Optimal Use of Peritoneal Dialysis in France and Europe, as in the United StatesRostoker, GuyIssad, Belkacem2022-08-30T07:22:48-07:00doi:10.1681/ASN.2022070839hwp:resource-id:jnephrol;33/11/2125American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, financial cost, hemodialysis, home dialysis, financial barriers, United States, France, EuropeLetter to the EditorLetter to the Editorletter20222022-11-01November 202210.1681/ASN.20220708391046-66731533-34502022-08-30T07:22:48-07:002022-11Journal of the American Society of NephrologyLetter to the Editor331162125106321261072
- The ABCD of Kidney Allograft Pathology—The Beginning of the Beginning10.1681/ASN.2022080967Mon, 10 Oct 2022 10:09:16 GMT-07:00The ABCD of Kidney Allograft Pathology—The Beginning of the BeginningMuthukumar, ThangamaniAnglicheau, Dany2022-10-10T10:09:16-07:00doi:10.1681/ASN.2022080967hwp:resource-id:jnephrol;33/11/1960American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, rejection, renal biopsy, transplant pathologyUp Front MattersEditorialUp Front MattersEditorialresearch-article20222022-11-01November 202210.1681/ASN.20220809671046-66731533-34502022-10-10T10:09:16-07:002022-11Journal of the American Society of NephrologyUp Front Matters3311111960202619632039
- Climate and the NephrologistClimate change is upon us, and it will have a major effect on both kidney disease and the nephrology practice. But the converse is also true: our treatment of kidney disease has an effect on the climate. Much attention has focused on how rising temperatures can lead to acute and CKD and health exacerbations in patients with established kidney disease. Climate change is also associated with rising air pollution from wildfires and industrial wastes and infectious diseases associated with flooding and changing habitats, all of which heighten the risk of acute and CKD. Less well recognized or understood are the ways nephrology practices, in turn, contribute to still more climate change. Hemodialysis, although lifesaving, can be associated with marked water usage (up to 600 L per dialysis session), energy usage (with one 4-hour session averaging as much as one fifth of the total energy consumed by a household per day), and large clinical wastes (with hemodialysis accounting for one third of total clinical medicine–associated waste). Of note, >90% of dialysis occurs in highly affluent countries, whereas dialysis is much less available in the poorer countries where climate change is having the highest effect on kidney disease. We conclude that not only do nephrologists need to prepare for the rise in climate-associated kidney disease, they must also urgently develop more climate-friendly methods of managing patients with kidney disease.10.2215/CJN.08530722Tue, 01 Nov 2022 07:35:13 GMT-07:00Climate and the NephrologistClimate change is upon us, and it will have a major effect on both kidney disease and the nephrology practice. But the converse is also true: our treatment of kidney disease has an effect on the climate. Much attention has focused on how rising temperatures can lead to acute and CKD and health exacerbations in patients with established kidney disease. Climate change is also associated with rising air pollution from wildfires and industrial wastes and infectious diseases associated with flooding and changing habitats, all of which heighten the risk of acute and CKD. Less well recognized or understood are the ways nephrology practices, in turn, contribute to still more climate change. Hemodialysis, although lifesaving, can be associated with marked water usage (up to 600 L per dialysis session), energy usage (with one 4-hour session averaging as much as one fifth of the total energy consumed by a household per day), and large clinical wastes (with hemodialysis accounting for one third of total clinical medicine–associated waste). Of note, >90% of dialysis occurs in highly affluent countries, whereas dialysis is much less available in the poorer countries where climate change is having the highest effect on kidney disease. We conclude that not only do nephrologists need to prepare for the rise in climate-associated kidney disease, they must also urgently develop more climate-friendly methods of managing patients with kidney disease.Young, Sarah E.Khoshnaw, Laveen J.Johnson, Richard J.2022-11-01T07:35:13-07:00doi:10.2215/CJN.08530722hwp:resource-id:clinjasn;CJN.08530722v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, climateReviewReviewresearch-article202210.2215/CJN.085307221555-90411555-905X2022-11-01T07:35:13-07:00Clinical Journal of the American Society of NephrologyReviewCJN.08530722
- Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant Biopsies10.1681/ASN.2022030290Wed, 07 Sep 2022 10:49:37 GMT-07:00Data-Driven Chronic Allograft Phenotypes: A Novel and Validated Complement for Histologic Assessment of Kidney Transplant BiopsiesVaulet, ThibautDivard, GillianThaunat, OlivierKoshy, PriyankaLerut, EvelyneSenev, AleksandarAubert, OlivierVan Loon, ElisabetCallemeyn, JasperEmonds, Marie-PauleVan Craenenbroeck, AmaryllisDe Vusser, KatrienSprangers, BenRabeyrin, MaudDubois, ValérieKuypers, DirkDe Vos, MaartenLoupy, AlexandreDe Moor, BartNaesens, Maarten2022-09-07T10:49:37-07:00doi:10.1681/ASN.2022030290hwp:resource-id:jnephrol;33/11/2026American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, machine learning, consensus clustering, phenotyping, Banff classification, chronic allograft rejection, biopsyBasic ResearchTransplantationBasic ResearchTransplantationresearch-article20222022-11-01November 202210.1681/ASN.20220302901046-66731533-34502022-09-07T10:49:37-07:002022-11Journal of the American Society of NephrologyBasic Research3311112026196020391963
- A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal Dialysis10.1681/ASN.2022020221Thu, 18 Aug 2022 07:51:16 GMT-07:00A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal DialysisKaplan, Jennifer M.Niu, JingboHo, VivianWinkelmayer, Wolfgang C.Erickson, Kevin F.2022-08-18T07:51:16-07:00doi:10.1681/ASN.2022020221hwp:resource-id:jnephrol;33/11/2059American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical epidemiology, dialysis, economic analysis, peritoneal dialysis, United States, health expenditures, MedicareClinical EpidemiologyDialysisClinical EpidemiologyDialysisresearch-article20222022-11-01November 202210.1681/ASN.20220202211046-66731533-34502022-08-18T07:51:16-07:002022-11Journal of the American Society of NephrologyClinical Epidemiology331111112059i19632070i1965
- Centering Anti-Racism and Social Justice in Nephrology Education to Advance Kidney Health Equity10.1681/ASN.2022040432Fri, 09 Sep 2022 08:50:58 GMT-07:00Centering Anti-Racism and Social Justice in Nephrology Education to Advance Kidney Health EquityPurnell, Tanjala S.Bignall, O. N. RayNorris, Keith C.,Gadegbeku, Crystal A.Fields, KatrinaKliger, Alan S.Saunders, Milda R.Wesson, Donald E.Williams, Clintoria R.2022-09-09T08:50:58-07:00doi:10.1681/ASN.2022040432hwp:resource-id:jnephrol;33/11/1981American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyethnicity, racial and ethnic disparities, nephrology, kidney diseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-11-01November 202210.1681/ASN.20220404321046-66731533-34502022-09-09T08:50:58-07:002022-11Journal of the American Society of NephrologyPerspective331119811984
- Is Home Dialysis the Way Forward for Medicare? Assessing Potential Cost Savings Associated with Peritoneal Dialysis10.1681/ASN.2022091017Wed, 12 Oct 2022 11:47:37 GMT-07:00Is Home Dialysis the Way Forward for Medicare? Assessing Potential Cost Savings Associated with Peritoneal DialysisTummalapalli, Sri LekhaLin, Eugene2022-10-12T11:47:37-07:00doi:10.1681/ASN.2022091017hwp:resource-id:jnephrol;33/11/1963American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, health policy, health services research, costsUp Front MattersEditorialUp Front MattersEditorialresearch-article20222022-11-01November 202210.1681/ASN.20220910171046-66731533-34502022-10-12T11:47:37-07:002022-11Journal of the American Society of NephrologyUp Front Matters3311111963205919652070
- Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity10.1681/ASN.2022010125Tue, 30 Aug 2022 07:22:48 GMT-07:00Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to SeveritySun, ZeguoZhang, ZhongyangBanu, KhadijaAzzi, Yorg AlReghuvaran, AnandFredericks, SamuelPlanoutene, MarinaHartzell, SusanKim, YeslPell, JohnTietjen, GregoryAsch, WilliamKulkarni, SanjayFormica, RichardRana, MeenakshiMaltzman, Jonathan S.Zhang, WeijiaAkalin, EnverHeeger, Peter S.Cravedi, PaoloMenon, Madhav C.2022-08-30T07:22:48-07:00doi:10.1681/ASN.2022010125hwp:resource-id:jnephrol;33/11/2108American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, COVID-19, immune deficiency, SARS-CoV-2, transcriptomeClinical ResearchTransplantationClinical ResearchTransplantationresearch-article20222022-11-01November 202210.1681/ASN.20220101251046-66731533-34502022-08-30T07:22:48-07:002022-11Journal of the American Society of NephrologyClinical Research331121082122
- Early Molecular Events Mediating Loss of Aquaporin-2 during Ureteral Obstruction in Rats10.1681/ASN.2022050601Tue, 02 Aug 2022 12:56:00 GMT-07:00Early Molecular Events Mediating Loss of Aquaporin-2 during Ureteral Obstruction in RatsSung, Chih-ChienPoll, Brian G.Lin, Shih-HuaMurillo-de-Ozores, Adrian R.Chou, Chung-LinChen, LiheYang, Chin-RangChen, Min-HsiuHsu, Yu-JueiKnepper, Mark A.2022-08-02T12:56:00-07:00doi:10.1681/ASN.2022050601hwp:resource-id:jnephrol;33/11/2040American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyaquaporin-2, P-body, collecting ducts, ureteral obstruction, RNA-Seq, lipopolysaccharideBasic ResearchSystems BiologyBasic ResearchSystems Biologyresearch-article20222022-11-01November 202210.1681/ASN.20220506011046-66731533-34502022-08-02T12:56:00-07:002022-11Journal of the American Society of NephrologyBasic Research3311112040i2058i
- Differences in Phosphate and Parathyroid Hormone Concentrations over the Day among Patients on Hemodialysis10.1681/ASN.2021111493Wed, 17 Aug 2022 07:50:34 GMT-07:00Differences in Phosphate and Parathyroid Hormone Concentrations over the Day among Patients on HemodialysisGinsberg, CharlesMiller, Lindsay M.Ofsthun, NormaDalrymple, Lorien S.Ix, Joachim H.2022-08-17T07:50:34-07:00doi:10.1681/ASN.2021111493hwp:resource-id:jnephrol;33/11/2087American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, hemodialysis, calcium, parathyroid hormone, phosphate binders, mineral metabolism, clinical epidemiologyClinical ResearchCare of the Renal PatientClinical ResearchCare of the Renal Patientresearch-article20222022-11-01November 202210.1681/ASN.20211114931046-66731533-34502022-08-17T07:50:34-07:002022-11Journal of the American Society of NephrologyClinical Research331120872093
- A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb210.1681/ASN.2022010070Fri, 19 Aug 2022 10:51:52 GMT-07:00A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2Hada, IchiroShimizu, AkiraTakematsu, HiromuNishibori, YukinoKimura, ToruFukutomi, ToshiyukiKudo, AkihikoIto-Nitta, NorikoKiuchi, ZentaroPatrakka, JaakkoMikami, NaoakiLeclerc, SimonAkimoto, YoshihiroHirayama, YoshiakiMori, SatokaTakano, TomokoYan, Kunimasa2022-08-19T10:51:52-07:00doi:10.1681/ASN.2022010070hwp:resource-id:jnephrol;33/11/2008American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyPodocyte, nephrotic syndrome, Crb2, ezrin, autoimmunityBasic ResearchGlomerulonephritis and Interstitial NephritisBasic ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-11-01November 202210.1681/ASN.20220100701046-66731533-34502022-08-19T10:51:52-07:002022-11Journal of the American Society of NephrologyBasic Research3311112008195920251960
- Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True10.1681/ASN.2022070761Fri, 09 Sep 2022 08:51:00 GMT-07:00Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be TrueZhang, Ping L.Blatt, Neal B.Kanaan, Hassan D.Wickman, Larysa T.2022-09-09T08:51:00-07:00doi:10.1681/ASN.2022070761hwp:resource-id:jnephrol;33/11/2123American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, arginase, macrophagesLetter to the EditorLetter to the Editorletter20222022-11-01November 202210.1681/ASN.20220707611046-66731533-34502022-09-09T08:51:00-07:002022-11Journal of the American Society of NephrologyLetter to the Editor3311116212321241077212421251086
- Authors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be True10.1681/ASN.2022070836Fri, 09 Sep 2022 08:50:59 GMT-07:00Authors' Reply: Most Arginase-1 Positive Cells Are Likely Injured S3 Proximal Tubular Cells Carrying Upregulated Phagocytotic Capacity rather than M2 Macrophages—Too Many To Be TrueShin, Naomi S.Marlier, ArnaudXu, LeyuanDoilicho, NatnaelLinberg, DanielGuo, JiankanCantley, Lloyd G.2022-09-09T08:50:59-07:00doi:10.1681/ASN.2022070836hwp:resource-id:jnephrol;33/11/2124American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyarginase-1, macrophageLetter to the EditorLetter to the Editorletter20222022-11-01November 202210.1681/ASN.20220708361046-66731533-34502022-09-09T08:50:59-07:002022-11Journal of the American Society of NephrologyLetter to the Editor3311116212421231077212521241086
- Is it Time to Re-Evaluate Our Experimental Approach to Studying Diffuse Podocytopathies?10.1681/ASN.2022080949Thu, 22 Sep 2022 11:39:27 GMT-07:00Is it Time to Re-Evaluate Our Experimental Approach to Studying Diffuse Podocytopathies?Watts, Andrew J.B.Weins, Astrid2022-09-22T11:39:27-07:00doi:10.1681/ASN.2022080949hwp:resource-id:jnephrol;33/11/1959American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, proteinuria, nephrotic syndrome, nephrologyUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-11-01November 202210.1681/ASN.20220809491046-66731533-34502022-09-22T11:39:27-07:002022-11Journal of the American Society of NephrologyUp Front Matters3311111959200819602025
- This Month's Highlights10.1681/ASN.2022091022Mon, 31 Oct 2022 10:00:25 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2022-10-31T10:00:25-07:00doi:10.1681/ASN.2022091022hwp:resource-id:jnephrol;33/11/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsother20222022-11-01November 202210.1681/ASN.20220910221046-66731533-34502022-10-31T10:00:25-07:002022-11Journal of the American Society of NephrologyThis Month's Highlights3311111111i204020942059i205821072070
- Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKD10.1681/ASN.2022030306Wed, 17 Aug 2022 09:37:29 GMT-07:00Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKDJongs, NielsChertow, Glenn M.Greene, TomMcMurray, John J.V.Langkilde, Anna MariaCorrea-Rotter, RicardoKashihara, NaokiRossing, PeterSjöström, C. DavidStefánsson, Bergur V.Toto, Robert D.Wheeler, David C.Heerspink, Hiddo J.L.,Heerspink, Hiddo J.L.Wheeler, David C.Chertow, GlennCorrea-Rotter, RicardoGreene, TomHou, Fan FanMcMurray, JohnRossing, PeterToto, RobertStefánsson, BergurLangkilde, Anna Maria2022-08-17T09:37:29-07:00doi:10.1681/ASN.2022030306hwp:resource-id:jnephrol;33/11/2094American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, renal function, dapagliflozin, sodium-glucose transporter 2 inhibitorsClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-11-01November 202210.1681/ASN.20220303061046-66731533-34502022-08-17T09:37:29-07:002022-11Journal of the American Society of NephrologyClinical Research3311112094i2107i
- Hypoxia-Inducible Factor–Prolyl Hydroxyl Domain Inhibitors: From Theoretical Superiority to Clinical Noninferiority Compared with Current ESAs?Anemia is a common complication of chronic kidney disease; it is mainly treated with erythropoiesis-stimulating agents (ESAs) and iron. Experimental studies extensively investigated the mechanisms involved in the body’s response to hypoxia and led to the discovery of the hypoxia-inducible factor (HIF) pathway and the enzymes regulating its function. HIF-prolyl-hydroxyl domain (PHD) inhibitors are a new class of oral drugs developed to treat anemia in chronic kidney disease. By inhibiting the function of PHD enzymes, they mimic the exposure to moderate hypoxia and stimulate the production of endogenous erythropoietin and very likely increase iron availability. Some data also suggest that their efficacy and, consequently, dose needs are less influenced by inflammation than ESAs. Overall, data from phases 2 and 3 clinical development showed efficacy in anemia correction and maintenance for all of the class molecules compared with placebo (superiority) or erythropoiesis-stimulating agents (noninferiority). Three molecules, roxadustat, vadadustat, and daprodustat, underwent extensive clinical investigation to assess their safety on hard cardiovascular end points, mortality, and special interest events (including cancer and thrombosis). Aside from vadadustat in the nondialysis population, at the prespecified primary analyses, all three molecules met the noninferiority margin for the risk of major cardiovascular events compared with erythropoiesis-stimulating agents or placebo. The reason for this discrepancy is difficult to explain. Other safety signals came from secondary analyses of some of the other randomized clinical trials, including a higher incidence of thrombosis. A more extensive clinical experience with post-marketing data on hard safety issues is needed to define better when and how to use HIF-PHD inhibitors compared with already available ESAs.10.1681/ASN.2022040413Tue, 30 Aug 2022 11:12:10 GMT-07:00Hypoxia-Inducible Factor–Prolyl Hydroxyl Domain Inhibitors: From Theoretical Superiority to Clinical Noninferiority Compared with Current ESAs?Anemia is a common complication of chronic kidney disease; it is mainly treated with erythropoiesis-stimulating agents (ESAs) and iron. Experimental studies extensively investigated the mechanisms involved in the body’s response to hypoxia and led to the discovery of the hypoxia-inducible factor (HIF) pathway and the enzymes regulating its function. HIF-prolyl-hydroxyl domain (PHD) inhibitors are a new class of oral drugs developed to treat anemia in chronic kidney disease. By inhibiting the function of PHD enzymes, they mimic the exposure to moderate hypoxia and stimulate the production of endogenous erythropoietin and very likely increase iron availability. Some data also suggest that their efficacy and, consequently, dose needs are less influenced by inflammation than ESAs. Overall, data from phases 2 and 3 clinical development showed efficacy in anemia correction and maintenance for all of the class molecules compared with placebo (superiority) or erythropoiesis-stimulating agents (noninferiority). Three molecules, roxadustat, vadadustat, and daprodustat, underwent extensive clinical investigation to assess their safety on hard cardiovascular end points, mortality, and special interest events (including cancer and thrombosis). Aside from vadadustat in the nondialysis population, at the prespecified primary analyses, all three molecules met the noninferiority margin for the risk of major cardiovascular events compared with erythropoiesis-stimulating agents or placebo. The reason for this discrepancy is difficult to explain. Other safety signals came from secondary analyses of some of the other randomized clinical trials, including a higher incidence of thrombosis. A more extensive clinical experience with post-marketing data on hard safety issues is needed to define better when and how to use HIF-PHD inhibitors compared with already available ESAs.Locatelli, FrancescoDel Vecchio, Lucia2022-08-30T11:12:10-07:00doi:10.1681/ASN.2022040413hwp:resource-id:jnephrol;33/11/1966American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic kidney disease, erythropoietin, hypoxia inducible factor, HIF-PHD inhibitors, hemoglobin, major cardiovascular events, dialysis, chronic inflammation, erythropoiesis-stimulating agentsUp Front MattersReviewUp Front MattersReviewreview-article20222022-11-01November 202210.1681/ASN.20220404131046-66731533-34502022-08-30T11:12:10-07:002022-11Journal of the American Society of NephrologyUp Front Matters331119661979
- Steroid-Resistant Nephrotic Syndrome–Associated MYO1E Mutations Have Differential Effects on Myosin 1e Localization, Dynamics, and Activity10.1681/ASN.2021111505Fri, 09 Sep 2022 08:50:58 GMT-07:00Steroid-Resistant Nephrotic Syndrome–Associated MYO1E Mutations Have Differential Effects on Myosin 1e Localization, Dynamics, and ActivityLiu, Pei-JuGunther, Laura K.Garone, Michael E.Zhang, ChunlingPerez, DianaBi-Karchin, JingPellenz, Christopher D.Chase, Sharon E.Presti, Maria F.Plante, Eric L.Martin, Claire E.Lovric, SvjetlanaYengo, Christopher M.Hildebrandt, FriedhelmKrendel, Mira2022-09-09T08:50:58-07:00doi:10.1681/ASN.2021111505hwp:resource-id:jnephrol;33/11/1989American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, podocyte, actin, myosin, endocytosis, genetic renal diseaseBasic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article20222022-11-01November 202210.1681/ASN.20211115051046-66731533-34502022-09-09T08:50:58-07:002022-11Journal of the American Society of NephrologyBasic Research331119892007
- Translation Rescue by Targeting Ppp1r15a through Its Upstream Open Reading Frame in Sepsis-Induced Acute Kidney Injury in a Murine Model10.1681/ASN.2022060644Tue, 25 Oct 2022 10:46:47 GMT-07:00Translation Rescue by Targeting Ppp1r15a through Its Upstream Open Reading Frame in Sepsis-Induced Acute Kidney Injury in a Murine ModelKidwell, AshleyYadav, Shiv Pratap SinghMaier, BernhardZollman, AmyNi, KevinHalim, ArvinJanosevic, DanielleMyslinski, JeredSyed, FarooqZeng, LifanWaffo, Alain BopdaBanno, KimihikoXuei, XiaolingDoud, Emma H.Dagher, Pierre C.Hato, Takashi2022-10-25T10:46:47-07:00doi:10.1681/ASN.2022060644hwp:resource-id:jnephrol;ASN.2022060644v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, gene expression, open reading frames, sepsisOriginal ArticleBasic ResearchOriginal ArticleBasic Researchresearch-article202210.1681/ASN.20220606441046-66731533-34502022-10-25T10:46:47-07:00Journal of the American Society of NephrologyOriginal Article10.1681/ASN.2022060644
- Effects of vitamin D3 supplementation on cardiovascular and cancer outcomes by eGFR in VITALBackground: Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods: We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000IU vitamin D3 and/or 1g omega-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study endpoints were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results: Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years and 51% were female. Vitamin D3 resulted in higher serum 25(OH)D compared to placebo (difference in change 12.5 [95%CI 12.0,13.1] ng/mL), without heterogeneity by eGFR (p-interaction, continuous eGFR=0.20). Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR (p-interaction=0.048): -6.9 (95% CI -10.5,-3.4) , -5.8 (-8.3,-3.4), -4.0 (-5.9,-2.2), and -3.8 (-5.6,-2.0) pg/mL for eGFR <60, 60-74, 75-89, and >90 ml/min/1.73m2, respectively. Effects of vitamin D3 supplementation on cardiovascular events (p-interaction=0.61) and cancer (p-interaction=0.89) did not differ by eGFR: HR (95% CI) 1.14 (0.73,1.79), 1.06 (0.75,1.50), 0.92 (0.67,1.25), and 0.92 (0.66,1.27), across eGFR categories for cardiovascular events and 1.63 (1.03,2.58), 0.85 (0.64,1.11), 0.84 (0.68,1.03), and 1.11 (0.92,1.35) for cancer, respectively. Conclusions: We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D3 supplementation versus placebo on cardiovascular or cancer outcomes, despite impacts on 25(OH)D and PTH concentrations.climonte@uw.edu10.34067/KID.0006472022Mon, 31 Oct 2022 06:43:44 GMT-07:00Effects of vitamin D3 supplementation on cardiovascular and cancer outcomes by eGFR in VITALBackground: Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk. Methods: We assessed for heterogeneity by baseline eGFR of the effects of vitamin D3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000IU vitamin D3 and/or 1g omega-3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study endpoints were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined. Results: Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years and 51% were female. Vitamin D3 resulted in higher serum 25(OH)D compared to placebo (difference in change 12.5 [95%CI 12.0,13.1] ng/mL), without heterogeneity by eGFR (p-interaction, continuous eGFR=0.20). Difference in change in PTH between vitamin D3 and placebo was larger with lower eGFR (p-interaction=0.048): -6.9 (95% CI -10.5,-3.4) , -5.8 (-8.3,-3.4), -4.0 (-5.9,-2.2), and -3.8 (-5.6,-2.0) pg/mL for eGFR <60, 60-74, 75-89, and >90 ml/min/1.73m2, respectively. Effects of vitamin D3 supplementation on cardiovascular events (p-interaction=0.61) and cancer (p-interaction=0.89) did not differ by eGFR: HR (95% CI) 1.14 (0.73,1.79), 1.06 (0.75,1.50), 0.92 (0.67,1.25), and 0.92 (0.66,1.27), across eGFR categories for cardiovascular events and 1.63 (1.03,2.58), 0.85 (0.64,1.11), 0.84 (0.68,1.03), and 1.11 (0.92,1.35) for cancer, respectively. Conclusions: We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D3 supplementation versus placebo on cardiovascular or cancer outcomes, despite impacts on 25(OH)D and PTH concentrations.Limonte, Christine P.Zelnick, Leila R.Hoofnagle, Andrew N.Thadhani, RaviMelamed, Michal L.Mora, SamiaCook, Nancy R.Luttmann-Gibson, HeikeSesso, HowardLee, I-MinBuring, Julie E.Manson, JoAnn Ede Boer, Ian H.2022-10-31T06:43:44-07:00doi:10.34067/KID.0006472022hwp:resource-id:kidney360;KID.0006472022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Neoplasms, Cholecalciferol, Dietary SupplementsOriginal InvestigationOriginal Investigationother202210.34067/KID.00064720222641-76502641-76502022-10-31T06:43:44-07:00Kidney360Original Investigation3312122095209510.34067/KID.000647202221052105
- Heme Protein-Induced Acute Kidney Injury is caused by Disruption of Mitochondrial Homeostasis in Proximal Tubular CellsThis is an Early Access article. Please select the PDF button, above, to view it.christof.westenfelder@hsc.utah.edu10.34067/KID.0006372022Mon, 31 Oct 2022 06:43:44 GMT-07:00Heme Protein-Induced Acute Kidney Injury is caused by Disruption of Mitochondrial Homeostasis in Proximal Tubular CellsThis is an Early Access article. Please select the PDF button, above, to view it.Westenfelder, MD, ChristofGooch, Anna2022-10-31T06:43:44-07:00doi:10.34067/KID.0006372022hwp:resource-id:kidney360;KID.0006372022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Heme Protein, Acute Kidney Injury, Mitochondrial Dynamics, Mitochondrial QualityControl, Mitochondrial Fission and Fusin, Proximal tubular damage, Mitophagy, Ferroptosis, Necroptosis, Chronic Kidney Disease, Basic SciencePerspectivePerspectiveother202210.34067/KID.00063720222641-76502641-76502022-10-31T06:43:44-07:00Kidney360Perspective3312122140214010.34067/KID.000637202221422142
- Baroreceptor Sensitivity in Individuals with Chronic Kidney Disease and Heart FailureBackground: Heart failure is the most common cardiovascular complication of chronic kidney disease and foreshadows high morbidity and mortality. Baroreflex impairment likely contributes to the cardiovascular mortality. We aimed to study the associations between chronic kidney disease, heart failure and baroreflex sensitivity (BRS) as well as their association with cardiovascular outcomes Methods: We analyzed data from a previously recruited cohort study which included 247 individuals with moderate-to-severe HF. All subjects underwent BRS measurements after intravenous phenylephrine along with electrocardiography, echocardiography and laboratory measurements. We used logistic regression models to assess the association of CKD with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality Results: Median eGFR among individuals with CKD was 52 (IQR 44-56) mL/min/1.73m2 eGFR was lower in those with depressed BRS (65 IQR 54-76 mL/min/1.73m2) compared to those with preserved BRS (73 IQR 64-87 mL/min/1.73m2, P=<0.001). The majority of individuals with CKD had depressed BRS compared to those without CKD (60.3% vs. 29.1%, P=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared to those with preserved BRS and CKD. Conclusions: Cardiac BRS is depressed in patients with CKD and HF and may be an important contributor to cardiovascular mortality.david.charytan@nyulangone.org10.34067/KID.0004812022Fri, 28 Oct 2022 01:14:26 GMT-07:00Baroreceptor Sensitivity in Individuals with Chronic Kidney Disease and Heart FailureBackground: Heart failure is the most common cardiovascular complication of chronic kidney disease and foreshadows high morbidity and mortality. Baroreflex impairment likely contributes to the cardiovascular mortality. We aimed to study the associations between chronic kidney disease, heart failure and baroreflex sensitivity (BRS) as well as their association with cardiovascular outcomes Methods: We analyzed data from a previously recruited cohort study which included 247 individuals with moderate-to-severe HF. All subjects underwent BRS measurements after intravenous phenylephrine along with electrocardiography, echocardiography and laboratory measurements. We used logistic regression models to assess the association of CKD with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality Results: Median eGFR among individuals with CKD was 52 (IQR 44-56) mL/min/1.73m2 eGFR was lower in those with depressed BRS (65 IQR 54-76 mL/min/1.73m2) compared to those with preserved BRS (73 IQR 64-87 mL/min/1.73m2, P=<0.001). The majority of individuals with CKD had depressed BRS compared to those without CKD (60.3% vs. 29.1%, P=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared to those with preserved BRS and CKD. Conclusions: Cardiac BRS is depressed in patients with CKD and HF and may be an important contributor to cardiovascular mortality.Charytan, David M.Soomro, Qandeel H.Caporotondi, AngeloGuazzotti, GiampaoloMaestri, RobertoPinna, Gian DomenicoLa Rovere, Maria Teresa2022-10-28T13:14:26-07:00doi:10.34067/KID.0004812022hwp:resource-id:kidney360;KID.0004812022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360CKD, heart failure, baroreceptor sensitvity, autonomic dysfunction, PressoreceptorsOriginal InvestigationOriginal Investigationother202210.34067/KID.00048120222641-76502641-76502022-10-28T13:14:26-07:00Kidney360Original Investigation3312122027202710.34067/KID.000481202220352035
- In-Hospital Prescription Checking System for Hospitalized Patients with Decreased Glomerular Filtration Rate10.34067/KID.0001552022Fri, 08 Jul 2022 11:22:33 GMT-07:00In-Hospital Prescription Checking System for Hospitalized Patients with Decreased Glomerular Filtration RateSonoda, AkihiroKondo, YukiIwashita, YoshitakaNakao, ShojiIshida, KazuhisaIrie, TetsumiIshitsuka, Yoichi2022-07-08T11:22:33-07:00doi:10.34067/KID.0001552022hwp:resource-id:kidney360;3/10/1730American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephro-pharmacology, decreased glomerular filtration rate, dosage errors in renally excreted drugs, hospitals, prescription audit by hospital pharmacists, prescription check systemOriginal InvestigationNephropharmacologyOriginal InvestigationNephropharmacologyresearch-article20222022-10-2710.34067/KID.00015520222641-76502022-07-08T11:22:33-07:002022-10-27Kidney360Original Investigation31017301737
- Percutaneous Ultrasound-Guided Kidney Transplant Biopsy Outcomes: From the Nephrologist to the Radiologist Standpoint10.34067/KID.0000332022Tue, 23 Aug 2022 01:04:45 GMT-07:00Percutaneous Ultrasound-Guided Kidney Transplant Biopsy Outcomes: From the Nephrologist to the Radiologist StandpointMattiazzi, Adela D.Cortesi, Camilo A.Patil, Rhea J.Carias Martinez, Karla G.Sedki, MaiCabeza Rivera, Franco H.Ruiz, PhillipSalsamendi, Jason T.Guerra, Giselle2022-08-23T13:04:45-07:00doi:10.34067/KID.0000332022hwp:resource-id:kidney360;3/10/1746American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, biopsy complications, interventional radiology, interventional ultrasonography, kidney biopsy, transplant nephrologyOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-10-2710.34067/KID.00003320222641-76502022-08-23T13:04:45-07:002022-10-27Kidney360Original Investigation31017461753
- AKI in a Patient with Myelodysplastic Syndrome and Dark Urine10.34067/KID.0003102022Thu, 27 Oct 2022 08:30:18 GMT-07:00AKI in a Patient with Myelodysplastic Syndrome and Dark UrineIsobe, ShinsukeOhashi, NaroYasuda, Hideo2022-10-27T08:30:18-07:00doi:10.34067/KID.0003102022hwp:resource-id:kidney360;3/10/1815American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria, renal hemosiderosisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-10-2710.34067/KID.00031020222641-76502022-10-27T08:30:18-07:002022-10-27Kidney360Clinical Images in Nephrology and Dialysis31018151816
- A Pilot Randomized Controlled Trial of Integrated Palliative Care and Nephrology Care10.34067/KID.0000352022Fri, 12 Aug 2022 01:43:15 GMT-07:00A Pilot Randomized Controlled Trial of Integrated Palliative Care and Nephrology CareScherer, Jennifer S.Rau, Megan E.Krieger, AnnaXia, YuheZhong, HuaBrody, AbrahamCharytan, David M.Chodosh, Joshua2022-08-12T13:43:15-07:00doi:10.34067/KID.0000352022hwp:resource-id:kidney360;3/10/1720American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360geriatric and palliative nephrology, palliative care, pilot projects, randomized controlled trialsOriginal InvestigationGeriatric and Palliative NephrologyOriginal InvestigationGeriatric and Palliative Nephrologyresearch-article20222022-10-2710.34067/KID.00003520222641-76502022-08-12T13:43:15-07:002022-10-27Kidney360Original Investigation31017201729
- A Nomogram to Identify Hyperkalemia Risk in Patients with Advanced CKD10.34067/KID.0004752022Tue, 20 Sep 2022 06:14:45 GMT-07:00A Nomogram to Identify Hyperkalemia Risk in Patients with Advanced CKDXue, ChengZhou, ChenchenYang, BoYe, XiaofeiXu, JingLu, YunhuiHu, XiaohuaChen, JiaLuo, XiaolingZhang, LimingMei, ChanglinMao, Zhiguo2022-09-20T06:14:45-07:00doi:10.34067/KID.0004752022hwp:resource-id:kidney360;3/10/1699American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, hyperkalemia, nomogram, risk factorsOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-10-2710.34067/KID.00047520222641-76502022-09-20T06:14:45-07:002022-10-27Kidney360Original Investigation31016991709
- Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: CON10.34067/KID.0007762021Tue, 15 Feb 2022 09:28:57 GMT-08:00Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: CONRodby, Roger A.2022-02-15T09:28:57-08:00doi:10.34067/KID.0007762021hwp:resource-id:kidney360;3/10/1667American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, ABIM requirements, ACGME requirements, nephrology fellowship, percutaneous renal biopsyDebates in NephrologyDebates in Nephrologyarticle-commentary20222022-10-2710.34067/KID.00077620212641-76502022-02-15T09:28:57-08:002022-10-27Kidney360Debates in Nephrology31016671669
- Correction of Vascular Calcification and Hyperphosphatemia in CKD Rats Treated with ASARM Peptide10.34067/KID.0002782022Tue, 30 Aug 2022 09:39:36 GMT-07:00Correction of Vascular Calcification and Hyperphosphatemia in CKD Rats Treated with ASARM PeptideRowe, Peter S.McCarthy, Ellen M.Yu, Alan L.Stubbs, Jason R.2022-08-30T09:39:36-07:00doi:10.34067/KID.0002782022hwp:resource-id:kidney360;3/10/1683American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, ASARM, basic science, calciphylaxis, calciprotein particles, CKD-MBD, DMP1, FGF23, matrix vesicles, MEPE, osteopontin, vascular calcificationOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-10-2710.34067/KID.00027820222641-76502022-08-30T09:39:36-07:002022-10-27Kidney360Original Investigation31016831698
- The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort Study10.34067/KID.0003742022Tue, 28 Jun 2022 11:23:09 GMT-07:00The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort StudyVinson, Amanda J.Thanamayooran, AranKiberd, Bryce A.West, KennethSiddiqi, Ferhan S.Gunaratnam, LakshmanTennankore, Karthik K.2022-06-28T11:23:09-07:00doi:10.34067/KID.0003742022hwp:resource-id:kidney360;3/10/1738American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, C-peptide, hemoglobin A1c, hyperglycemia, kidney transplantation, nodat, obesity, post-transplant diabetes, risk factorsOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-10-2710.34067/KID.00037420222641-76502022-06-28T11:23:09-07:002022-10-27Kidney360Original Investigation31017381745
- Association of Pre-Transplant C-Peptide with Post-Transplant Diabetes: A New Approach to Identifying High-Risk Patients?10.34067/KID.0004922022Thu, 27 Oct 2022 08:30:18 GMT-07:00Association of Pre-Transplant C-Peptide with Post-Transplant Diabetes: A New Approach to Identifying High-Risk Patients?Joachim, Emily2022-10-27T08:30:18-07:00doi:10.34067/KID.0004922022hwp:resource-id:kidney360;3/10/1660American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, basic science, C-peptide, diabetes mellitus, hemoglobin A1c, kidney transplantation, post-transplant diabetesEditorialEditorialeditorial20222022-10-2710.34067/KID.00049220222641-76502022-10-27T08:30:18-07:002022-10-27Kidney360Editorial31016601661
- Clinical Decision Support Tools for Reduced and Changing Kidney Function10.34067/KID.0005242022Thu, 27 Oct 2022 08:30:18 GMT-07:00Clinical Decision Support Tools for Reduced and Changing Kidney FunctionSchreier, Diana J.Barreto, Erin F.2022-10-27T08:30:18-07:00doi:10.34067/KID.0005242022hwp:resource-id:kidney360;3/10/1657American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephro-pharmacology, CDSS, estimated glomerular filtration rate, pharmacist, quality, renal dosingEditorialEditorialeditorial20222022-10-2710.34067/KID.00052420222641-76502022-10-27T08:30:18-07:002022-10-27Kidney360Editorial31016571659
- Global Perspective on Kidney Transplantation: Ecuador10.34067/KID.0003452022Fri, 22 Jul 2022 01:35:59 GMT-07:00Global Perspective on Kidney Transplantation: EcuadorJiménez, DaríoJiménez, Fernando2022-07-22T13:35:59-07:00doi:10.34067/KID.0003452022hwp:resource-id:kidney360;3/10/1772American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, Ecuador, kidney transplantation, perspectivesGlobal PerspectiveGlobal Perspectiveresearch-article20222022-10-2710.34067/KID.00034520222641-76502022-07-22T13:35:59-07:002022-10-27Kidney360Global Perspective31017721774
- ESKD in a Young Patient with Chronic Bilateral Flank Pain10.34067/KID.0002902022Thu, 27 Oct 2022 08:30:18 GMT-07:00ESKD in a Young Patient with Chronic Bilateral Flank PainMerchant, Asad A.Attieh, Rose Mary2022-10-27T08:30:18-07:00doi:10.34067/KID.0002902022hwp:resource-id:kidney360;3/10/1817American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephrolithiasis, chronic kidney disease, dialysis, end stage renal disease, genetics, hyperoxaluria, metabolic, nephrocalcinosis, primary hyperoxaluria type 1Clinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-10-2710.34067/KID.00029020222641-76502022-10-27T08:30:18-07:002022-10-27Kidney360Clinical Images in Nephrology and Dialysis31018171818
- Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: PRO10.34067/KID.0007772021Tue, 15 Feb 2022 09:28:57 GMT-08:00Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: PROObaidi, ZainabSozio, Stephen M.2022-02-15T09:28:57-08:00doi:10.34067/KID.0007772021hwp:resource-id:kidney360;3/10/1664American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, biopsy, fellowship, nephrologyDebates in NephrologyDebates in Nephrologyarticle-commentary20222022-10-2710.34067/KID.00077720212641-76502022-02-15T09:28:57-08:002022-10-27Kidney360Debates in Nephrology31016641666
- The Transplant Kidney Biopsy: In Whose Hands?10.34067/KID.0005382022Thu, 27 Oct 2022 08:30:18 GMT-07:00The Transplant Kidney Biopsy: In Whose Hands?Virmani, SarthakKumar, Abhishek2022-10-27T08:30:18-07:00doi:10.34067/KID.0005382022hwp:resource-id:kidney360;3/10/1662American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, allograft, biopsy, procedureEditorialEditorialeditorial20222022-10-2710.34067/KID.00053820222641-76502022-10-27T08:30:18-07:002022-10-27Kidney360Editorial31016621663
- The Role of Different Lymphoid Cell Populations in Preeclampsia PathophysiologyPreeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, PE has no cure beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation; intrauterine growth restriction; uterine artery resistance; dysregulation of the renin-angiotensin system. Which contributes to renal dysfunction; and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling, resulting in decreased placental perfusion and thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in proinflammatory and anti-inflammatory cell types in women with PE and in animal models used to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases, such as cardiovascular disease, CKD, dementia during the postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.10.34067/KID.0001282022Fri, 12 Aug 2022 01:43:15 GMT-07:00The Role of Different Lymphoid Cell Populations in Preeclampsia PathophysiologyPreeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, PE has no cure beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation; intrauterine growth restriction; uterine artery resistance; dysregulation of the renin-angiotensin system. Which contributes to renal dysfunction; and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling, resulting in decreased placental perfusion and thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in proinflammatory and anti-inflammatory cell types in women with PE and in animal models used to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases, such as cardiovascular disease, CKD, dementia during the postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.Campbell, Nathan E.Deer, Evangeline M.Herrock, Owen T.LaMarca, Babbette B.2022-08-12T13:43:15-07:00doi:10.34067/KID.0001282022hwp:resource-id:kidney360;3/10/1785American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hypertension, basic science, lymphoid cells, preeclampsiaBasic Science for CliniciansBasic Science for Cliniciansresearch-article20222022-10-2710.34067/KID.00012820222641-76502022-08-12T13:43:15-07:002022-10-27Kidney360Basic Science for Clinicians31017851794
- Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with Diabetes10.34067/KID.0002152022Wed, 31 Aug 2022 12:01:56 GMT-07:00Enhanced SHP-1 Expression in Podocyturia Is Associated with Kidney Dysfunction in Patients with DiabetesLizotte, FarahRobillard, StéphanieLavoie, NicolasRousseau, MarinaDenhez, BenoitMoreau, JulieHiggins, SarahSabbagh, RobertCôté, Anne-MarieGeraldes, Pedro2022-08-31T12:01:56-07:00doi:10.34067/KID.0002152022hwp:resource-id:kidney360;3/10/1710American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, diabetic kidney disease, glomerular filtration rate, human PTPN6 protein, nephrin, podocyteOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20222022-10-2710.34067/KID.00021520222641-76502022-08-31T12:01:56-07:002022-10-27Kidney360Original Investigation31017101719
- Innate Immunity and SARS-CoV-2 Vaccine Response in Hemodialysis Patients10.34067/KID.0002542022Wed, 10 Aug 2022 01:41:42 GMT-07:00Innate Immunity and SARS-CoV-2 Vaccine Response in Hemodialysis PatientsValentini, NicolasMarchitto, LorieRaymond, MaximeGoyette, GuillaumeKaufmann, Daniel E.Finzi, AndrésSuri, Rita S.Lamarche, Caroline2022-08-10T13:41:42-07:00doi:10.34067/KID.0002542022hwp:resource-id:kidney360;3/10/1763American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, basic science, COVID-19, dendritic cell, immune response, innate immunity, monocyte, mRNA vaccine, SARS-CoV-2Brief CommunicationChronic Kidney DiseaseBrief CommunicationChronic Kidney Diseaserapid-communication20222022-10-2710.34067/KID.00025420222641-76502022-08-10T13:41:42-07:002022-10-27Kidney360Brief Communication31017631768
- International Practices on COVID-19 Vaccine Mandates for Transplant Candidates10.34067/KID.0004062022Mon, 15 Aug 2022 01:52:02 GMT-07:00International Practices on COVID-19 Vaccine Mandates for Transplant CandidatesCaliskan, YasarHippen, Benjamin E.Axelrod, David A.Schnitzler, MarkMaher, KennanAlhamad, TarekLam, Ngan N.Anwar, SiddiqKute, VivekLentine, Krista L.2022-08-15T13:52:02-07:00doi:10.34067/KID.0004062022hwp:resource-id:kidney360;3/10/1754American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, COVID-19, international practices, patient safety, solid organ transplantation, vaccines, waitlist managementOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-10-2710.34067/KID.00040620222641-76502022-08-15T13:52:02-07:002022-10-27Kidney360Original Investigation31017541762
- Advantages, Limitations, and Clinical Considerations in Using Cystatin C to Estimate GFRCystatin C has been shown to be a reliable and accurate marker of kidney function across diverse populations. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making. In the efforts to remove race from eGFR calculations in the United States, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Joint Task Force recommended increasing availability and clinical adoption of cystatin C to assess kidney function. This review summarizes the key advantages and limitations of cystatin C use in clinical practice. Our goals were to review and discuss the literature on cystatin C; understand the evidence behind the recommendations for its use as a marker of kidney function to diagnose CKD and risk stratify patients for adverse outcomes; discuss the challenges of its use in clinical practice; and guide clinicians on its interpretation.10.34067/KID.0003202022Tue, 23 Aug 2022 01:04:45 GMT-07:00Advantages, Limitations, and Clinical Considerations in Using Cystatin C to Estimate GFRCystatin C has been shown to be a reliable and accurate marker of kidney function across diverse populations. The 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommended using cystatin C to confirm the diagnosis of chronic kidney disease (CKD) determined by creatinine-based estimated glomerular filtration rate (eGFR) and to estimate kidney function when accurate eGFR estimates are needed for clinical decision-making. In the efforts to remove race from eGFR calculations in the United States, the National Kidney Foundation (NKF) and American Society of Nephrology (ASN) Joint Task Force recommended increasing availability and clinical adoption of cystatin C to assess kidney function. This review summarizes the key advantages and limitations of cystatin C use in clinical practice. Our goals were to review and discuss the literature on cystatin C; understand the evidence behind the recommendations for its use as a marker of kidney function to diagnose CKD and risk stratify patients for adverse outcomes; discuss the challenges of its use in clinical practice; and guide clinicians on its interpretation.Chen, Debbie C.Potok, O. AlisonRifkin, DenaEstrella, Michelle M.2022-08-23T13:04:45-07:00doi:10.34067/KID.0003202022hwp:resource-id:kidney360;3/10/1807American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, cystatin C, eGFRReview ArticleReview Articlereview-article20222022-10-2710.34067/KID.00032020222641-76502022-08-23T13:04:45-07:002022-10-27Kidney360Review Article31018071814
- Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: COMMENTARY10.34067/KID.0000872022Tue, 15 Feb 2022 09:28:57 GMT-08:00Kidney Biopsy Should Remain a Required Procedure for Nephrology Training Programs: COMMENTARYBrewster, Ursula C.2022-02-15T09:28:57-08:00doi:10.34067/KID.0000872022hwp:resource-id:kidney360;3/10/1670American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, biopsy, nephrologyModerator CommentaryModerator Commentaryarticle-commentary20222022-10-2710.34067/KID.00008720222641-76502022-02-15T09:28:57-08:002022-10-27Kidney360Moderator Commentary31016701671
- Peritoneal Dialysis Adequacy: Too Much of a Good Thing?10.34067/KID.0000922022Fri, 26 Aug 2022 09:06:35 GMT-07:00Peritoneal Dialysis Adequacy: Too Much of a Good Thing?Tillquist, KristenFloyd, StephanieShah, Ankur D.2022-08-26T09:06:35-07:00doi:10.34067/KID.0000922022hwp:resource-id:kidney360;3/10/1777American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, dialysis adequacy, Kt/V, peritoneal dialysisPerspectivePerspectiveresearch-article20222022-10-2710.34067/KID.00009220222641-76502022-08-26T09:06:35-07:002022-10-27Kidney360Perspective31017771779
- Biomarkers for Early Diagnosis of AKI: Could It Backfire?10.34067/KID.0001012022Thu, 08 Sep 2022 01:21:41 GMT-07:00Biomarkers for Early Diagnosis of AKI: Could It Backfire?Claure-Del Granado, RolandoMacedo, EtienneChávez-Íñiguez, Jonathan S.2022-09-08T13:21:41-07:00doi:10.34067/KID.0001012022hwp:resource-id:kidney360;3/10/1780American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, biomarkers, creatininePerspectivePerspectiveresearch-article20222022-10-2710.34067/KID.00010120222641-76502022-09-08T13:21:41-07:002022-10-27Kidney360Perspective31017801784
- Apixaban versus No Anticoagulation by P2Y12 Inhibitor Prescription Status in Dialysis Patients with Atrial Fibrillation10.34067/KID.0003002022Mon, 01 Aug 2022 01:21:41 GMT-07:00Apixaban versus No Anticoagulation by P2Y12 Inhibitor Prescription Status in Dialysis Patients with Atrial FibrillationMavrakanas, Thomas A.Charytan, David M.2022-08-01T13:21:41-07:00doi:10.34067/KID.0003002022hwp:resource-id:kidney360;3/10/1769American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, apixaban, atrial fibrillation, bleeding, dialysis, P2Y12 inhibitor, prescriptions, strokeBrief CommunicationDialysisBrief CommunicationDialysisbrief-report20222022-10-2710.34067/KID.00030020222641-76502022-08-01T13:21:41-07:002022-10-27Kidney360Brief Communication31017691771
- How to Determine Fluid Management Goals during Continuous Kidney Replacement Therapy in Patients with AKI: Focus on POCUSThe utilization of kidney replacement therapies (KRT) for fluid management of patients who are critically ill has significantly increased over the last years. Clinical studies have suggested that both fluid accumulation and high fluid removal rates are associated with adverse outcomes in the critically ill population receiving KRT. Importantly, the ideal indications and/or fluid management strategies that could favorably affect these patients are unknown; however, differentiating clinical scenarios in which effective fluid removal may provide benefit to the patient by avoiding congestive organ injury, compared with other settings in which this intervention may result in harm, is direly needed in the critical care nephrology field. In this review, we describe observational data related to fluid management with KRT, and examine the role of point-of-care ultrasonography as a potential tool that could provide physiologic insights to better individualize decisions related to fluid management through KRT.10.34067/KID.0002822022Tue, 19 Jul 2022 01:29:42 GMT-07:00How to Determine Fluid Management Goals during Continuous Kidney Replacement Therapy in Patients with AKI: Focus on POCUSThe utilization of kidney replacement therapies (KRT) for fluid management of patients who are critically ill has significantly increased over the last years. Clinical studies have suggested that both fluid accumulation and high fluid removal rates are associated with adverse outcomes in the critically ill population receiving KRT. Importantly, the ideal indications and/or fluid management strategies that could favorably affect these patients are unknown; however, differentiating clinical scenarios in which effective fluid removal may provide benefit to the patient by avoiding congestive organ injury, compared with other settings in which this intervention may result in harm, is direly needed in the critical care nephrology field. In this review, we describe observational data related to fluid management with KRT, and examine the role of point-of-care ultrasonography as a potential tool that could provide physiologic insights to better individualize decisions related to fluid management through KRT.Beaubien-Souligny, WilliamTrott, TerrenNeyra, Javier A.2022-07-19T13:29:42-07:00doi:10.34067/KID.0002822022hwp:resource-id:kidney360;3/10/1795American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, CKRT, dialysis, fluid management, fluid overload, fluid removal, POCUS, point-of-care, renal replacement therapy, ultrasonographyReview ArticleReview Articlereview-article20222022-10-2710.34067/KID.00028220222641-76502022-07-19T13:29:42-07:002022-10-27Kidney360Review Article31017951806
- When a Kidney Doctor Becomes a Kidney Donor10.34067/KID.0005092022Mon, 01 Aug 2022 01:21:41 GMT-07:00When a Kidney Doctor Becomes a Kidney DonorDjamali, Arjang2022-08-01T13:21:41-07:00doi:10.34067/KID.0005092022hwp:resource-id:kidney360;3/10/1775American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, kidney transplantation, living donorsPatient PerspectivePatient Perspectiveresearch-article20222022-10-2710.34067/KID.00050920222641-76502022-08-01T13:21:41-07:002022-10-27Kidney360Patient Perspective31017751776
- Prominent Mitochondrial Injury as an Early Event in Heme Protein-Induced Acute Kidney Injury10.34067/KID.0004832022Mon, 15 Aug 2022 01:52:02 GMT-07:00Prominent Mitochondrial Injury as an Early Event in Heme Protein-Induced Acute Kidney InjurySingh, Raman DeepCroatt, Anthony J.Ackerman, Allan W.Grande, Joseph P.Trushina, EugeniaSalisbury, Jeffrey L.Christensen, Trace A.Adams, Christopher M.Tchkonia, TamaraKirkland, James L.Nath, Karl A.2022-08-15T13:52:02-07:00doi:10.34067/KID.0004832022hwp:resource-id:kidney360;3/10/1672American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, basic science, hemeproteins, HP-AKI, mitochondria, mitochondrial dynamics, murine model, NAD, organelle biogenesisOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-10-2710.34067/KID.00048320222641-76502022-08-15T13:52:02-07:002022-10-27Kidney360Original Investigation31016721682
- The New Kidney-Focused Companies: A Privatized Approach to Value-Based Care and Addressing Social Determinants of Health10.1681/ASN.2022060716Thu, 27 Oct 2022 06:46:11 GMT-07:00The New Kidney-Focused Companies: A Privatized Approach to Value-Based Care and Addressing Social Determinants of HealthLin, EugeneDave, GauravKshirsagar, Abhijit V.2022-10-27T06:46:11-07:00doi:10.1681/ASN.2022060716hwp:resource-id:jnephrol;ASN.2022060716v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, social determinants of health, clinical nephrologyPerspectivePerspectiveresearch-article2022October 202210.1681/ASN.20220607161046-66731533-34502022-10-27T06:46:11-07:00Journal of the American Society of NephrologyPerspectiveASN.2022060716
- Platelet-Dependent Inflammatory Dysregulation in Patients with stages 4-5 Chronic Kidney Disease- A Mechanistic Clinical StudyBackground. Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stages 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT- aspirin 81 mg/d plus P2Y12 inhibitor). Methods. In a mechanistic clinical trial, we compared platelet activation markers, circulating platelet-leukocyte aggregates, leukocyte composition, and plasma cytokine profile of non-CKD controls (n=26) and CKD outpatients (n=48) with glomerular filtration rate (GFR expressed in ml/min/1.73m2) <30 on 2 weeks of DAPT. Results. Patients with CKD demonstrated reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classical monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine. There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in TNFα levels among a CKD subgroup younger than 55 years, diabetics, had GFR ≥15 or albuminuria ≥1000 mg/g; and, no change in a number of other cytokines. Correlation analysis and minimum spanning trees plot of 45-cytokine panel showed platelet-derived CD40L showed a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1β and PDGF were tightly correlated with other cytokines with IL-1β as the hub cytokine. Conclusion. Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet derived cytokines were one of the central cytokines in CKD. DAPT had multifaceted effects on thromboinflammation suggesting that there are platelet-dependent and platelet-independent inflammation in stages 4 or 5 CKD.NJain2@uams.edu10.34067/KID.0005532022Wed, 26 Oct 2022 02:03:07 GMT-07:00Platelet-Dependent Inflammatory Dysregulation in Patients with stages 4-5 Chronic Kidney Disease- A Mechanistic Clinical StudyBackground. Chronic kidney disease (CKD) is characterized by dysregulated inflammation that worsens with CKD severity. The role of platelets in modulating inflammation in stages 4 or 5 CKD remains unexplored. We investigated whether there are changes in platelet-derived thromboinflammatory markers in CKD with dual antiplatelet therapy (DAPT- aspirin 81 mg/d plus P2Y12 inhibitor). Methods. In a mechanistic clinical trial, we compared platelet activation markers, circulating platelet-leukocyte aggregates, leukocyte composition, and plasma cytokine profile of non-CKD controls (n=26) and CKD outpatients (n=48) with glomerular filtration rate (GFR expressed in ml/min/1.73m2) <30 on 2 weeks of DAPT. Results. Patients with CKD demonstrated reduced mean platelet count, elevated mean platelet volume, reduced platelet-leukocyte aggregates, reduced platelet-bound monocytes, higher total non-classical monocytes in the circulation, and higher levels of IL-1RA, VEGF, and fractalkine. There were no differences in platelet activation markers between CKD and controls. Although DAPT reduced platelet aggregation, it had multifaceted effects on thromboinflammatory markers in CKD, including a reduction in TNFα levels among a CKD subgroup younger than 55 years, diabetics, had GFR ≥15 or albuminuria ≥1000 mg/g; and, no change in a number of other cytokines. Correlation analysis and minimum spanning trees plot of 45-cytokine panel showed platelet-derived CD40L showed a large reduction in weight factor after DAPT in CKD. Additionally, platelet-derived IL-1β and PDGF were tightly correlated with other cytokines with IL-1β as the hub cytokine. Conclusion. Attenuated interactions between platelets and leukocytes in the CKD state coincided with no change in platelet activation status, an altered differentiation state of monocytes, and heightened inflammatory markers. Platelet derived cytokines were one of the central cytokines in CKD. DAPT had multifaceted effects on thromboinflammation suggesting that there are platelet-dependent and platelet-independent inflammation in stages 4 or 5 CKD.Corken, AdamWare, JerryDai, JunqiangArthur, John MSmyth, SusanDavis, Clayton L.Liu, JuanHarville, Terry O.Phadnis, Milind AMehta, Jawahar LRahmatallah, YasirJain, Nishank2022-10-26T14:03:07-07:00doi:10.34067/KID.0005532022hwp:resource-id:kidney360;KID.0005532022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360platelets, inflammation, aspirin, P2Y12 inhibitors, chronic kidney disease, leukocytes, monocytesOriginal InvestigationOriginal Investigationother202210.34067/KID.00055320222641-76502641-76502022-10-26T14:03:07-07:00Kidney360Original Investigation3312122036203610.34067/KID.000553202220472047
- Interferon Gamma contributes to the immune mechanisms of hypertensionHypertension is the leading cause of cardiovascular disease and the primary risk factor for mortality worldwide. For over half a century, researchers have demonstrated that the immunity plays an important role in the development of hypertension; however, the precise mechanisms are still under investigation. The current body of knowledge indicates that pro-inflammatory cytokines may play an important role in contributing to immune-related pathogenesis of hypertension. Interferon gamma (IFNγ), in particular, as an important cytokine that modulates immune responses, has been recently identified as an critical regulator of blood pressure by several groups including us. In this review, we focus on exploring the role of IFNγ in contributing to the pathogenesis of hypertension, outlining the various immune producers of this cytokine and described signaling mechanisms involved. We demonstrate a key role for IFNγ in hypertension through global knockout studies and related downstream signaling pathways that IFNγ production from CD8+ T cell (CD8T) in the kidney promoting CD8T-stimulated salt retention via renal tubule cells, thereby exacerbating hypertension. We discuss potential activators of these T cells described by the current literature and relay a novel hypothesis for activation.SMu@uams.edu10.34067/KID.0001292022Wed, 26 Oct 2022 02:03:07 GMT-07:00Interferon Gamma contributes to the immune mechanisms of hypertensionHypertension is the leading cause of cardiovascular disease and the primary risk factor for mortality worldwide. For over half a century, researchers have demonstrated that the immunity plays an important role in the development of hypertension; however, the precise mechanisms are still under investigation. The current body of knowledge indicates that pro-inflammatory cytokines may play an important role in contributing to immune-related pathogenesis of hypertension. Interferon gamma (IFNγ), in particular, as an important cytokine that modulates immune responses, has been recently identified as an critical regulator of blood pressure by several groups including us. In this review, we focus on exploring the role of IFNγ in contributing to the pathogenesis of hypertension, outlining the various immune producers of this cytokine and described signaling mechanisms involved. We demonstrate a key role for IFNγ in hypertension through global knockout studies and related downstream signaling pathways that IFNγ production from CD8+ T cell (CD8T) in the kidney promoting CD8T-stimulated salt retention via renal tubule cells, thereby exacerbating hypertension. We discuss potential activators of these T cells described by the current literature and relay a novel hypothesis for activation.Benson, Lance N.Liu, YunmengDeck, Katherine SMora, ChristophMu, Shengyu2022-10-26T14:03:07-07:00doi:10.34067/KID.0001292022hwp:resource-id:kidney360;KID.0001292022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360immunity and inflammation, Interferon-gamma, HypertensionBasic Science for CliniciansBasic Science for Cliniciansother202210.34067/KID.00012920222641-76502641-76502022-10-26T14:03:07-07:00Kidney360Basic Science for Clinicians3312122164216410.34067/KID.000129202221732173
- Testican-2 is Associated with Reduced Risk of Incident ESKDBackground: Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with estimated glomerular filtration rate (eGFR) and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of end stage kidney disease (ESKD) is unknown. Methods: Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK, n=703), the Chronic Renal Insufficiency Cohort (CRIC) study (n=3,196), and the Atherosclerosis Risk in Communities (ARIC) study (n=4,378). We compared baseline characteristics by testican-2 tertile and used Cox proportional hazards models to study the association of testican-2 with incident ESKD. Results: Higher testican-2 levels were associated with higher measured GFR (mGFR) in AASK, higher eGFR in the CRIC and ARIC studies, and lower albuminuria in all cohorts. Baseline testican-2 levels were significantly associated with incident ESKD in Cox proportional hazards models adjusted for age, sex, and race (Model 1) and Model 1 + mGFR or eGFR + comorbidities (Model 2). In Model 3 (Model 2 + proteinuria), the associations between testican-2 (per SD increase) and incident ESKD were: AASK (HR = 0.84 [0.72, 0.98], P = 0.023), CRIC (HR = 0.95 [0.89, 1.02], P = 0.14), ARIC (HR = 0.54 [0.36, 0.83], P = 0.0044), and meta-analysis (HR = 0.92 [0.86, 0.98], P = 0.0073). Conclusions: Across three cohorts spanning >8,000 individuals, testican-2 is associated with kidney health and prognosis, with higher levels associated with reduced risk of ESKD.dwen@bwh.harvard.edu10.1681/ASN.2022020216Wed, 26 Oct 2022 11:48:08 GMT-07:00Testican-2 is Associated with Reduced Risk of Incident ESKDBackground: Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with estimated glomerular filtration rate (eGFR) and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of end stage kidney disease (ESKD) is unknown. Methods: Aptamer-based proteomics assessed blood testican-2 levels among participants in the African American Study of Kidney Disease and Hypertension (AASK, n=703), the Chronic Renal Insufficiency Cohort (CRIC) study (n=3,196), and the Atherosclerosis Risk in Communities (ARIC) study (n=4,378). We compared baseline characteristics by testican-2 tertile and used Cox proportional hazards models to study the association of testican-2 with incident ESKD. Results: Higher testican-2 levels were associated with higher measured GFR (mGFR) in AASK, higher eGFR in the CRIC and ARIC studies, and lower albuminuria in all cohorts. Baseline testican-2 levels were significantly associated with incident ESKD in Cox proportional hazards models adjusted for age, sex, and race (Model 1) and Model 1 + mGFR or eGFR + comorbidities (Model 2). In Model 3 (Model 2 + proteinuria), the associations between testican-2 (per SD increase) and incident ESKD were: AASK (HR = 0.84 [0.72, 0.98], P = 0.023), CRIC (HR = 0.95 [0.89, 1.02], P = 0.14), ARIC (HR = 0.54 [0.36, 0.83], P = 0.0044), and meta-analysis (HR = 0.92 [0.86, 0.98], P = 0.0073). Conclusions: Across three cohorts spanning >8,000 individuals, testican-2 is associated with kidney health and prognosis, with higher levels associated with reduced risk of ESKD.Wen, DonghaiZhou, LindaZheng, ZiheSurapaneni, AdityaBallantyne, ChristieHoogeveen, RonShlipak, MichaelWaikar, SushrutVasan, RamachandraKimmel, PaulDubin, RuthDeo, RajatFeldman, HaroldGanz, PeterCoresh, JosefGrams, MorganRhee, Eugene2022-10-26T11:48:08-07:00doi:10.1681/ASN.2022020216hwp:resource-id:jnephrol;ASN.2022020216v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Clinical ResearchOriginal Article - Clinical Researchresearch-article202210.1681/ASN.20220202161046-66731533-34502022-10-26T11:48:08-07:00Journal of the American Society of NephrologyOriginal Article - Clinical ResearchASN.2022020216
- Distinguishing among HCO3−, CO3=, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters10.1681/ASN.2022030289Wed, 26 Oct 2022 08:26:35 GMT-07:00Distinguishing among HCO3−, CO3=, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” TransportersLee, Seong-KiOcchipinti, RossanaMoss, Fraser J.Parker, Mark D.Grichtchenko, Irina I.Boron, Walter F.2022-10-26T08:26:35-07:00doi:10.1681/ASN.2022030289hwp:resource-id:jnephrol;ASN.2022030289v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycell and transport physiology, chronic metabolic acidosis, electrophysiology, Na transport, proximal tubule, renal tubular acidosis, ion transport, Intracellular pH, acidosis, bicarbonatesBasic ResearchAcid Base and Electrolyte DisordersBasic ResearchAcid Base and Electrolyte Disordersresearch-article202210.1681/ASN.20220302891046-66731533-34502022-10-26T08:26:35-07:00Journal of the American Society of NephrologyBasic ResearchASN.2022030289
- Glucose/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing Receptor10.1681/ASN.2021121544Wed, 07 Sep 2022 10:49:37 GMT-07:00Glucose/Fructose Delivery to the Distal Nephron Activates the Sodium-Chloride Cotransporter via the Calcium-Sensing ReceptorBahena-Lopez, Jessica PaolaRojas-Vega, LorenaChávez-Canales, MaríaBazua-Valenti, SilvanaBautista-Pérez, RocíoLee, Ju-HyeMadero, MagdalenaVazquez-Manjarrez, NataliaAlquisiras-Burgos, IvanHernandez-Cruz, ArturoCastañeda-Bueno, MaríaEllison, David H.Gamba, Gerardo2022-09-07T10:49:37-07:00doi:10.1681/ASN.2021121544hwp:resource-id:jnephrol;ASN.2021121544v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyNCC cotransporter, SPAK, WNK4, salt transporter, diuretics, distal tubule, hypertension, sodium chloride symporters, calcium-sensing receptorsBasic ResearchAcid Base and Electrolyte DisordersBasic ResearchAcid Base and Electrolyte Disordersresearch-article202210.1681/ASN.20211215441046-66731533-34502022-09-07T10:49:37-07:00Journal of the American Society of NephrologyBasic ResearchASN.2021121544
- Sweet-Talking the Distal Nephron Calcium-Sensing Receptor10.1681/ASN.2022091054Wed, 26 Oct 2022 08:26:34 GMT-07:00Sweet-Talking the Distal Nephron Calcium-Sensing ReceptorSubramanya, Arohan R.2022-10-26T08:26:34-07:00doi:10.1681/ASN.2022091054hwp:resource-id:jnephrol;ASN.2022091054v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologySPAK, WNK4, diuretics, distal tubule, calcium-sensing receptor, sodium chloride symporters, NCC cotransporter, fructoseEditorialEditorialeditorial202210.1681/ASN.20220910541046-66731533-34502022-10-26T08:26:34-07:00Journal of the American Society of NephrologyEditorialASN.2022091054
- Basic Requirements for Improving Home Dialysis Utilization: Specialty Nephrology Care and Pre-End Stage Kidney Disease Educationashutosh.shukla@medicine.ufl.edu10.1681/ASN.2022060685Tue, 25 Oct 2022 10:46:47 GMT-07:00Basic Requirements for Improving Home Dialysis Utilization: Specialty Nephrology Care and Pre-End Stage Kidney Disease EducationShukla, AshutoshCavanaugh, KerriWadhwa, AnuradhaCrowley, SusanFried, Linda2022-10-25T10:46:47-07:00doi:10.1681/ASN.2022060685hwp:resource-id:jnephrol;ASN.2022060685v1American Society of NephrologyJournal of the American Society of NephrologyInvited FeatureInvited Featureresearch-article202210.1681/ASN.20220606851046-66731533-34502022-10-25T10:46:47-07:00Journal of the American Society of NephrologyInvited FeatureASN.2022060685
- XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in Mice10.1681/ASN.2021091180Fri, 21 Oct 2022 06:17:47 GMT-07:00XBP1 Activation Reduces Severity of Polycystic Kidney Disease due to a Nontruncating Polycystin-1 Mutation in MiceKrappitz, MatteusBhardwaj, RishiDong, KeStaudner, TobiasYilmaz, Duygu ElifPioppini, CarlottaWestergerling, ParisaRuemmele, DavidHollmann, TillNguyen, Thuy AnhCai, YiqiangGallagher, Anna-RachelSomlo, StefanFedeles, Sorin2022-10-21T06:17:47-07:00doi:10.1681/ASN.2021091180hwp:resource-id:jnephrol;ASN.2021091180v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyunfolded protein response, polycystic kidney disease, polycystin-1, Ire1α-XBP1 pathway, protein folding, chaperone, genetic renal disease, mutationOriginal ArticleBasic ResearchOriginal ArticleBasic Researchresearch-article2022October 202210.1681/ASN.20210911801046-66731533-34502022-10-21T06:17:47-07:00Journal of the American Society of NephrologyOriginal ArticleASN.2021091180
- Relationship of kidney tubule biomarkers with cognition among community-living elders in the Health ABC StudyThis is an Early Access article. Please select the PDF button, above, to view it.lmmiller@health.ucsd.edu10.34067/KID.0004022022Thu, 20 Oct 2022 11:55:33 GMT-07:00Relationship of kidney tubule biomarkers with cognition among community-living elders in the Health ABC StudyThis is an Early Access article. Please select the PDF button, above, to view it.Miller, Lindsay M.Sarnak, Mark J.Rifkin, Dena E.Potok, O. AlisonFried, Linda F.Kritchevsky, StephenDrew, DavidShlipak, Michael G.Ix, Joachim H.2022-10-20T11:55:33-07:00doi:10.34067/KID.0004022022hwp:resource-id:kidney360;KID.0004022022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Cognition, Kidney Tubules, BiomarkersBrief CommunicationBrief Communicationother202210.34067/KID.00040220222641-76502641-76502022-10-20T11:55:33-07:00Kidney360Brief Communication3312122106210610.34067/KID.000402202221092109
- Kidney-Protective Effects of SGLT2 InhibitorsThe sodium-glucose cotransporter 2 (SGLT2) inhibitors have become an integral part of clinical practice guidelines to slow the progression of CKD in patients with and without diabetes mellitus. Although initially developed as antihyperglycemic drugs, their effect on the kidney is multifactorial resulting from profuse glycosuria and natriuresis consequent to their primary site of action. Hemodynamic and metabolic changes ensue that mediate kidney-protective effects, including (1) decreased workload of proximal tubular cells and prevention of aberrant increases in glycolysis, contributing to a decreased risk of AKI; (2) lowering of intraglomerular pressure by activating tubular glomerular feedback and reductions in BP and tissue sodium content; (3) initiation of nutrient-sensing pathways reminiscent of starvation activating ketogenesis, increased autophagy, and restoration of carbon flow through the mitochondria without production of reactive oxygen species; (4) body weight loss without a reduction in basal metabolic rate due to increases in nonshivering thermogenesis; and (5) favorable changes in quantity and characteristics of perirenal fat leading to decreased release of adipokines, which adversely affect the glomerular capillary and signal increased sympathetic outflow. Additionally, these drugs stimulate phosphate and magnesium reabsorption and increase uric acid excretion. Familiarity with kidney-specific mechanisms of action, potential changes in kidney function, and/or alterations in electrolytes and volume status, which are induced by these widely prescribed drugs, will facilitate usage in the patients for whom they are indicated.10.2215/CJN.09380822Tue, 11 Oct 2022 09:23:53 GMT-07:00Kidney-Protective Effects of SGLT2 InhibitorsThe sodium-glucose cotransporter 2 (SGLT2) inhibitors have become an integral part of clinical practice guidelines to slow the progression of CKD in patients with and without diabetes mellitus. Although initially developed as antihyperglycemic drugs, their effect on the kidney is multifactorial resulting from profuse glycosuria and natriuresis consequent to their primary site of action. Hemodynamic and metabolic changes ensue that mediate kidney-protective effects, including (1) decreased workload of proximal tubular cells and prevention of aberrant increases in glycolysis, contributing to a decreased risk of AKI; (2) lowering of intraglomerular pressure by activating tubular glomerular feedback and reductions in BP and tissue sodium content; (3) initiation of nutrient-sensing pathways reminiscent of starvation activating ketogenesis, increased autophagy, and restoration of carbon flow through the mitochondria without production of reactive oxygen species; (4) body weight loss without a reduction in basal metabolic rate due to increases in nonshivering thermogenesis; and (5) favorable changes in quantity and characteristics of perirenal fat leading to decreased release of adipokines, which adversely affect the glomerular capillary and signal increased sympathetic outflow. Additionally, these drugs stimulate phosphate and magnesium reabsorption and increase uric acid excretion. Familiarity with kidney-specific mechanisms of action, potential changes in kidney function, and/or alterations in electrolytes and volume status, which are induced by these widely prescribed drugs, will facilitate usage in the patients for whom they are indicated.Palmer, Biff F.Clegg, Deborah J.2022-10-11T09:23:53-07:00doi:10.2215/CJN.09380822hwp:resource-id:clinjasn;CJN.09380822v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysodium-glucose cotransport inhibitor, tubuloglomerular feedback, metabolic flexibility, SGLT2ReviewReviewresearch-article202210.2215/CJN.093808221555-90411555-905X2022-10-11T09:23:53-07:00Clinical Journal of the American Society of NephrologyReviewCJN.09380822
- Genetic testing in nephrology: Show your pedigree!This is an Early Access article. Please select the PDF button, above, to view it.francesca.becherucci@meyer.it10.34067/KID.0002732022Wed, 19 Oct 2022 04:33:59 GMT-07:00Genetic testing in nephrology: Show your pedigree!This is an Early Access article. Please select the PDF button, above, to view it.Cirillo, LuigiBecherucci, Francesca2022-10-19T04:33:59-07:00doi:10.34067/KID.0002732022hwp:resource-id:kidney360;KID.0002732022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Genetics, Exome sequencing, Inherited kidney disease, Rare kidney disease, Gene, Next generation sequencing, Renal genetic clinic, Genetic test, Genetic in nephrology, Genetic kidney diseasePerspectivePerspectiveother202210.34067/KID.00027320222641-76502641-76502022-10-19T04:33:59-07:00Kidney360Perspective3312122148214810.34067/KID.000273202221522152
- Role of GSTM1 in hypertension, chronic kidney disease and related diseases across the lifespanOver twenty years after the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, chronic kidney disease (CKD) remains a major public health burden with very limited therapeutic options to halt or slow kidney disease progression at all ages. The general consensus is that oxidative stress contributes to CKD development and progression. Yet, to date, there is no clear evidence that broad use of antioxidant therapy provides a beneficial effect in CKD. Understanding the specific pathophysiologic mechanisms in those who are genetically most susceptible to oxidative stress is a crucial step to inform therapy in an individualized medicine approach, taking into account differing exposures and risks across the lifespan. GSTM1 (glutathione-S-transferase mu 1) is a phase II enzyme involved in inactivation of reactive oxygen species and metabolism of xenobiotics. In particular, those with the highly prevalent GSTM1 null genotype (GSTM1(0/0)) may be more susceptible to kidney disease progression due to impaired capacity to handle the increased oxidative stress burden in disease states and might specifically benefit from therapy that targets the redox imbalance mediated by loss of GSTM1 enzyme. In this review, we will discuss the studies implicating the role of GSTM1 deficiency in kidney and related diseases from experimental rodent models to humans, from the prenatal period through senescence, and the potential underlying mechanism.Thu_Le@URMC.Rochester.edu10.34067/KID.0004552022Wed, 19 Oct 2022 04:33:59 GMT-07:00Role of GSTM1 in hypertension, chronic kidney disease and related diseases across the lifespanOver twenty years after the introduction of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, chronic kidney disease (CKD) remains a major public health burden with very limited therapeutic options to halt or slow kidney disease progression at all ages. The general consensus is that oxidative stress contributes to CKD development and progression. Yet, to date, there is no clear evidence that broad use of antioxidant therapy provides a beneficial effect in CKD. Understanding the specific pathophysiologic mechanisms in those who are genetically most susceptible to oxidative stress is a crucial step to inform therapy in an individualized medicine approach, taking into account differing exposures and risks across the lifespan. GSTM1 (glutathione-S-transferase mu 1) is a phase II enzyme involved in inactivation of reactive oxygen species and metabolism of xenobiotics. In particular, those with the highly prevalent GSTM1 null genotype (GSTM1(0/0)) may be more susceptible to kidney disease progression due to impaired capacity to handle the increased oxidative stress burden in disease states and might specifically benefit from therapy that targets the redox imbalance mediated by loss of GSTM1 enzyme. In this review, we will discuss the studies implicating the role of GSTM1 deficiency in kidney and related diseases from experimental rodent models to humans, from the prenatal period through senescence, and the potential underlying mechanism.Levy, RebeccaLe, Thu H.2022-10-19T04:33:59-07:00doi:10.34067/KID.0004552022hwp:resource-id:kidney360;KID.0004552022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360GSTM1, oxidative stress, chronic kidney disease, hypertensionBasic Science for CliniciansBasic Science for Cliniciansother202210.34067/KID.00045520222641-76502641-76502022-10-19T04:33:59-07:00Kidney360Basic Science for Clinicians3312122153215310.34067/KID.000455202221632163
- The Cleveland Clinic Kidney Biopsy Epidemiological ProjectBackground: The kidney biopsy is the gold standard for the diagnosis of glomerular diseases. Large-scale, epidemiological studies describing the prevalence of kidney diseases are lacking especially in the US. We aimed to determine the spectrum of biopsy proven kidney disease across the Cleveland Clinic enterprise. Methods: We identified all patients with a native kidney biopsy performed/reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, gender, race and location to determine epidemiological trends. Results: Of over 9600 patients, we excluded transplant/donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46.2% female patients. Self-reported racial demographics included 72.9% White, 21.7% Black, 3.1% multi-racial, and 1.6% Asian background, with 5.1% Hispanic. Common diagnoses were: FSGS (n=633, 15.3%), diabetic kidney disease (DKD) (n=602, 14.6%), IgA nephropathy (n=319, 7.7%), lupus nephritis (LN) (n=289, 7.0%), pauci-immune glomerulonephritis (n=275, 6.7%), membranous nephropathy (n=211, 5.1%), and amyloidosis (n=110, 2.7%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those over 70 years were more likely to have FSGS, while those less than 45 years were more likely to have IgA Nephropathy or LN. Males were more likely to have FSGS or IgAN and less likely to have LN. Blacks were more likely to have FSGS, DKD or LN. Hispanics were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum prior to and during the COVID 19 pandemic. Conclusion: Our study catalogues the spectrum of biopsy proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States.bobarts@ccf.org10.34067/KID.0005882022Wed, 19 Oct 2022 04:33:59 GMT-07:00The Cleveland Clinic Kidney Biopsy Epidemiological ProjectBackground: The kidney biopsy is the gold standard for the diagnosis of glomerular diseases. Large-scale, epidemiological studies describing the prevalence of kidney diseases are lacking especially in the US. We aimed to determine the spectrum of biopsy proven kidney disease across the Cleveland Clinic enterprise. Methods: We identified all patients with a native kidney biopsy performed/reviewed at the Cleveland Clinic from January 2015 to September 2021. Retrospective chart review was performed to obtain clinical and demographic characteristics. Results were stratified by age, gender, race and location to determine epidemiological trends. Results: Of over 9600 patients, we excluded transplant/donor biopsies and unavailable records, and included 4128 patients with native kidney biopsy data. The median age was 60 years, with 46.2% female patients. Self-reported racial demographics included 72.9% White, 21.7% Black, 3.1% multi-racial, and 1.6% Asian background, with 5.1% Hispanic. Common diagnoses were: FSGS (n=633, 15.3%), diabetic kidney disease (DKD) (n=602, 14.6%), IgA nephropathy (n=319, 7.7%), lupus nephritis (LN) (n=289, 7.0%), pauci-immune glomerulonephritis (n=275, 6.7%), membranous nephropathy (n=211, 5.1%), and amyloidosis (n=110, 2.7%). There were 3322 patients in Ohio, with 361 patients in Florida. Using multivariate analysis, those over 70 years were more likely to have FSGS, while those less than 45 years were more likely to have IgA Nephropathy or LN. Males were more likely to have FSGS or IgAN and less likely to have LN. Blacks were more likely to have FSGS, DKD or LN. Hispanics were more likely to have DKD. Finally, patients in Florida were more likely to have LN. There was no change in the disease spectrum prior to and during the COVID 19 pandemic. Conclusion: Our study catalogues the spectrum of biopsy proven kidney disease across the Cleveland Clinic enterprise. This lays the foundation for glomerular disease clinical trials and highlights the need for a standardized national kidney biopsy registry to bolster glomerular and kidney disease research in the United States.Bobart, Shane A.Portalatin, GildaSawaf, HannyShettigar, ShrutiCarrion Rodriguez, AstridLiang, HongHerlitz, LealGebreselassie, Surafel K.2022-10-19T04:33:59-07:00doi:10.34067/KID.0005882022hwp:resource-id:kidney360;KID.0005882022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Kidney Biopsy, Glomerular Disease, Diabetes, FSGS, IgA Nephropathy, Lupus Nephritis, Registry, Database, Epidemiology, GlomerulonephritisOriginal InvestigationOriginal Investigationother202210.34067/KID.00058820222641-76502641-76502022-10-19T04:33:59-07:00Kidney360Original Investigation3312122077207710.34067/KID.000588202220852085
- Cardiac manifestations in patients with autosomal polycystic kidney disease (ADPKD) - a single-center studyBackground: ADPKD is the most common monogenetic kidney disease and results in kidney failure in over 75% of affected individuals. As a systemic disorder, ADPKD is associated with a variety of extrarenal manifestations affecting the majority of patients including cardiac manifestations. We characterized the cardiac involvement in ADPKD patients from the German AD(H)PKD registry and compared them to kidney donor candidates as controls. Methods: In this single-center cohort study, we evaluated 141 ADPKD (44.17 ± 11.23 years) patients from the German AD(H)PKD registry and 60 kidney donor candidates (55.08 ± 10.21 years). All patients underwent clinical examination, abdominal MRI, and transthoracic echocardiography. Results: 65% of ADPKD patients showed hypertrophy of the left ventricle (as defined by an end-diastolic left ventricular septal wall thickness (IVSd) greater than 10mm) compared to 55% in control patients. Mitral regurgitation was the most common finding among 53.57 % of ADPKD patients who exhibited valvular dysfunction, albeit mild in the majority of patients. Interestingly, left ventricular ejection fraction (LV-EF) differed significantly between both groups with higher values in ADPKD patients (63.53±6.38% vs. 60.21±5.72%), while other parameters including IVSd, left ventricular end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE) and pressure gradients across the aortic and tricuspid valve were similar between groups. Correlations of echocardiographic parameters with markers of disease progression revealed statistically significant associations for aortic root diameter (p = 0.014), the pressure gradient across the aortic valve (AV dPmax) (p = 0.0003) and left ventricular septal wall thickness (IVSd) (p = 0.0001), indicating that rapid kidney disease progression may also be associated with cardiac findings. Conclusion: Cardiovascular abnormalities are prevalent in ADPKD patients. Considering the importance of cardiovascular disease for outcome in CKD, early management and possibly prevention are important goals of any treatment scheme. Consequently, echocardiography should be offered to all ADPKD patients in routine management.roman-ulrich.mueller@uk-koeln.de10.34067/KID.0002942022Tue, 18 Oct 2022 02:17:49 GMT-07:00Cardiac manifestations in patients with autosomal polycystic kidney disease (ADPKD) - a single-center studyBackground: ADPKD is the most common monogenetic kidney disease and results in kidney failure in over 75% of affected individuals. As a systemic disorder, ADPKD is associated with a variety of extrarenal manifestations affecting the majority of patients including cardiac manifestations. We characterized the cardiac involvement in ADPKD patients from the German AD(H)PKD registry and compared them to kidney donor candidates as controls. Methods: In this single-center cohort study, we evaluated 141 ADPKD (44.17 ± 11.23 years) patients from the German AD(H)PKD registry and 60 kidney donor candidates (55.08 ± 10.21 years). All patients underwent clinical examination, abdominal MRI, and transthoracic echocardiography. Results: 65% of ADPKD patients showed hypertrophy of the left ventricle (as defined by an end-diastolic left ventricular septal wall thickness (IVSd) greater than 10mm) compared to 55% in control patients. Mitral regurgitation was the most common finding among 53.57 % of ADPKD patients who exhibited valvular dysfunction, albeit mild in the majority of patients. Interestingly, left ventricular ejection fraction (LV-EF) differed significantly between both groups with higher values in ADPKD patients (63.53±6.38% vs. 60.21±5.72%), while other parameters including IVSd, left ventricular end-diastolic diameter (LVEDD), tricuspid annular plane systolic excursion (TAPSE) and pressure gradients across the aortic and tricuspid valve were similar between groups. Correlations of echocardiographic parameters with markers of disease progression revealed statistically significant associations for aortic root diameter (p = 0.014), the pressure gradient across the aortic valve (AV dPmax) (p = 0.0003) and left ventricular septal wall thickness (IVSd) (p = 0.0001), indicating that rapid kidney disease progression may also be associated with cardiac findings. Conclusion: Cardiovascular abnormalities are prevalent in ADPKD patients. Considering the importance of cardiovascular disease for outcome in CKD, early management and possibly prevention are important goals of any treatment scheme. Consequently, echocardiography should be offered to all ADPKD patients in routine management.Arjune, SitaGrundmann, FranziskaTodorova, PolinaHendrix, ClaudiaPfister, Romanten Freyhaus, HenrikMüller, Roman-Ulrich2022-10-18T14:17:49-07:00doi:10.34067/KID.0002942022hwp:resource-id:kidney360;KID.0002942022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Autosomal dominant polycystic kidney disease, extrarenal manifestationss, left ventricular hypertrophy, echocardiography, cardiovascular disease, heart, cardiac valve defectOriginal InvestigationOriginal Investigationother202210.34067/KID.00029420222641-76502641-76502022-10-18T14:17:49-07:00Kidney360Original Investigation10.34067/KID.0002942022
- Urinary Citrate is Associated with Kidney Outcomes in Early Polycystic Kidney DiseaseThis is an Early Access article. Please select the PDF button, above, to view it.ita.heilberg@gmail.com10.34067/KID.0004772022Mon, 17 Oct 2022 01:50:35 GMT-07:00Urinary Citrate is Associated with Kidney Outcomes in Early Polycystic Kidney DiseaseThis is an Early Access article. Please select the PDF button, above, to view it.Ribeiro da Rocha, DanielXue, LaixiSousa, Hiago Murilo GomesMatos, Ana CristinaHoorn, Ewout JSalih, MahdiHeilberg, Ita Pfeferman2022-10-17T13:50:35-07:00doi:10.34067/KID.0004772022hwp:resource-id:kidney360;KID.0004772022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360ADPKD, Urinary Citrate, CKD, eGFR, Polycystic Kidney DiseaseBrief CommunicationBrief Communicationother202210.34067/KID.00047720222641-76502641-76502022-10-17T13:50:35-07:00Kidney360Brief Communication3312122110211010.34067/KID.000477202221152115
- Environmental Exposures and Kidney DiseasesAccumulating evidence underscores the large role played by the environment in the health of communities and individuals. We review the currently known contribution of environmental exposures and pollutants on kidney disease and its associated morbidity. We review air pollutants, such as particulate matter; water pollutants such as trace elements, per- and polyfluorooakyl substances, and pesticides; and extreme weather events and natural disasters. We also discuss gaps in the evidence which at present relies heavily on observational studies and animal models, and propose using recently developed quantitative methods to help bridge the gaps. With the expected increase in the intensity and frequency of many environmental exposures in the decades to come, an improved understanding of their potential effect on kidney disease is crucial to mitigate potential morbidity and mortality.abhijit_kshirsagar@med.unc.edu10.34067/KID.0007962021Mon, 17 Oct 2022 01:50:35 GMT-07:00Environmental Exposures and Kidney DiseasesAccumulating evidence underscores the large role played by the environment in the health of communities and individuals. We review the currently known contribution of environmental exposures and pollutants on kidney disease and its associated morbidity. We review air pollutants, such as particulate matter; water pollutants such as trace elements, per- and polyfluorooakyl substances, and pesticides; and extreme weather events and natural disasters. We also discuss gaps in the evidence which at present relies heavily on observational studies and animal models, and propose using recently developed quantitative methods to help bridge the gaps. With the expected increase in the intensity and frequency of many environmental exposures in the decades to come, an improved understanding of their potential effect on kidney disease is crucial to mitigate potential morbidity and mortality.Kshirsagar, Abhijit V.Zeitler, Evan M.Weaver, AnneFranceschini, NoraEngel, Lawrence S.2022-10-17T13:50:35-07:00doi:10.34067/KID.0007962021hwp:resource-id:kidney360;KID.0007962021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Air pollution, Water pollution, Extreme weather events, Kidney diseaseReview ArticleReview Articleother202210.34067/KID.00079620212641-76502641-76502022-10-17T13:50:35-07:00Kidney360Review Article3312122174217410.34067/KID.000796202121822182
- Ratio Profile: Physiologic Approach to Estimating Appropriate IV Fluid Rate to Manage Hyponatremia of SIADA hyponatremic patient with the syndrome of inappropriate antidiuresis (SIAD) gets normal saline (NS), and the plasma sodium decreases, paradoxically. To explain, desalination is often invoked: If urine is more concentrated than NS, the fluid's salts are excreted while some water is reabsorbed, exacerbating hyponatremia. But comparing concentrations can be deceiving. They should be converted to quantities, as mass balance is key to unlocking the paradox. The [sodium] equation can legitimately be used to track all of the sodium, potassium, and water entering and leaving the body. Each input or output "module" can be counterbalanced by a chosen IV fluid so that the plasma sodium stays stable. This equipoise is expressed in terms of the IV fluid's infusion rate, an easy calculation called the ratio profile. Knowing the infusion rate that maintains steady state, we can prescribe the IV fluid at a faster rate in order to raise the plasma sodium. Rates less than the ratio profile may risk a paradox, which essentially is caused by an IV fluid underdosing. Selecting an IV fluid that is more concentrated than urine is not enough to prevent paradoxes; even 3% saline can be underdosed. Water drinking adds to the ratio profile and is underestimated in its ability to provoke a paradox. In conclusion, the quantitative approach demystifies the paradoxical worsening of hyponatremia in SIAD and offers a prescriptive guide to keep the paradox from happening. The ratio profile method is objective and quickly deployable on rounds, where it may change patient management for the better.shelchen@yahoo.com10.34067/KID.0004882022Mon, 17 Oct 2022 05:55:39 GMT-07:00Ratio Profile: Physiologic Approach to Estimating Appropriate IV Fluid Rate to Manage Hyponatremia of SIADA hyponatremic patient with the syndrome of inappropriate antidiuresis (SIAD) gets normal saline (NS), and the plasma sodium decreases, paradoxically. To explain, desalination is often invoked: If urine is more concentrated than NS, the fluid's salts are excreted while some water is reabsorbed, exacerbating hyponatremia. But comparing concentrations can be deceiving. They should be converted to quantities, as mass balance is key to unlocking the paradox. The [sodium] equation can legitimately be used to track all of the sodium, potassium, and water entering and leaving the body. Each input or output "module" can be counterbalanced by a chosen IV fluid so that the plasma sodium stays stable. This equipoise is expressed in terms of the IV fluid's infusion rate, an easy calculation called the ratio profile. Knowing the infusion rate that maintains steady state, we can prescribe the IV fluid at a faster rate in order to raise the plasma sodium. Rates less than the ratio profile may risk a paradox, which essentially is caused by an IV fluid underdosing. Selecting an IV fluid that is more concentrated than urine is not enough to prevent paradoxes; even 3% saline can be underdosed. Water drinking adds to the ratio profile and is underestimated in its ability to provoke a paradox. In conclusion, the quantitative approach demystifies the paradoxical worsening of hyponatremia in SIAD and offers a prescriptive guide to keep the paradox from happening. The ratio profile method is objective and quickly deployable on rounds, where it may change patient management for the better.Chen, SheldonShey, JasonChiaramonte, Robert2022-10-17T05:55:39-07:00doi:10.34067/KID.0004882022hwp:resource-id:kidney360;KID.0004882022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Desalination, Normal Saline, Equation, SIADH, ParadoxReview ArticleReview Articleother202210.34067/KID.00048820222641-76502641-76502022-10-17T05:55:39-07:00Kidney360Review Article3312122183218310.34067/KID.000488202221892189
- Global Dialysis Perspectives: EcuadorThis is an Early Access article. Please select the PDF button, above, to view it.cristobalsantacruz@yahoo.com10.34067/KID.0003762022Mon, 17 Oct 2022 05:55:39 GMT-07:00Global Dialysis Perspectives: EcuadorThis is an Early Access article. Please select the PDF button, above, to view it.Santacruz Mancheno, JuanSantacruz, Angel Cristóbal2022-10-17T05:55:39-07:00doi:10.34067/KID.0003762022hwp:resource-id:kidney360;KID.0003762022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Hemodialysis, Dialysis, Latin-American, Ecuador, Perspectives, Public healthGlobal PerspectivesGlobal Perspectivesother202210.34067/KID.00037620222641-76502641-76502022-10-17T05:55:39-07:00Kidney360Global Perspectives3312122131213110.34067/KID.000376202221352135
- Implementation and Effectiveness of a Learning Collaborative to Improve Palliative Care for Seriously Ill Hemodialysis Patients10.2215/CJN.00090122Wed, 14 Sep 2022 06:12:18 GMT-07:00Implementation and Effectiveness of a Learning Collaborative to Improve Palliative Care for Seriously Ill Hemodialysis PatientsKurella Tamura, ManjulaHoldsworth, LauraStedman, MargaretAldous, AnnetteAsch, Steven M.Han, JialinHarbert, GlendaLorenz, Karl A.Malcolm, ElizabethNicklas, AmandaMoss, Alvin H.Lupu, Dale E.2022-09-14T06:12:18-07:00doi:10.2215/CJN.00090122hwp:resource-id:clinjasn;17/10/1495American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, renal dialysisOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-10-01October 202210.2215/CJN.000901221555-90411555-905X2022-09-14T06:12:18-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article1710101495143315051435
- Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems10.2215/CJN.04110422Fri, 09 Sep 2022 06:28:58 GMT-07:00Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care SystemsAn, JaejinKurella Tamura, ManjulaOdden, Michelle C.Ni, LiangThomas, I-ChunMontez-Rath, Maria E.Sim, John J.2022-09-09T06:28:58-07:00doi:10.2215/CJN.04110422hwp:resource-id:clinjasn;17/10/1457American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, prevalence, hypertension, delivery of health careOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-10-01October 202210.2215/CJN.041104221555-90411555-905X2022-09-09T06:28:58-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article1710101457143614661438
- Resistant Hypertension in Chronic Kidney Disease10.2215/CJN.09720822Fri, 09 Sep 2022 07:02:26 GMT-07:00Resistant Hypertension in Chronic Kidney DiseaseShulman, RachelCohen, Jordana B.2022-09-09T07:02:26-07:00doi:10.2215/CJN.09720822hwp:resource-id:clinjasn;17/10/1436American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, diuretics, resistant hypertension, clinician inertia, medication adherence, blood pressure measurement, mineralocorticoid receptor antagonistsEditorialEditorialeditorial20222022-10-01October 202210.2215/CJN.097208221555-90411555-905X2022-09-09T07:02:26-07:002022-10Clinical Journal of the American Society of NephrologyEditorial1710101436145714381466
- Associations of COVID-19 Outcomes with Dialysis Modalities and SettingsHow maintenance dialysis modality, dialysis setting, and residence in a nursing facility have jointly associated with coronavirus disease 2019 (COVID-19)-related outcomes in the United States is relevant to future viral outbreaks. Using Medicare claims, we determined the incidence of COVID-19–related infection, hospitalization, and death between March 15, 2020 and June 5, 2021. The exposure was one of five combinations of dialysis modality and care setting: in-facility hemodialysis without a recent history of skilled nursing facility care, in-facility hemodialysis with a recent history of skilled nursing facility care, hemodialysis in a skilled nursing facility, home hemodialysis, and (home) peritoneal dialysis. Patient-weeks were pooled to estimate the adjusted associations of event incidence with each dialysis modality/setting during four intervals in 2020–2021. Relative to in-facility hemodialysis without a recent history of skilled nursing facility care, home dialysis was associated with 36%–60% lower odds of all events during weeks 12–23 of 2020; 24%–37% lower odds of all events during weeks 24–37 of 2020; 20%–33% lower odds of infection and hospitalization during the winter of 2020–2021; and similar odds of all events thereafter. In contrast, exposure to skilled nursing facilities was associated with 570%–1140% higher odds of all events during spring of 2020, although excess risk attenuated as the pandemic transpired, especially among patients who received hemodialysis in skilled nursing facilities. In conclusion, home dialysis was associated with lower risks of COVID-19 diagnosis, hospitalization, and death until vaccines were available, whereas care in skilled nursing facilities was associated with higher risks.10.2215/CJN.03400322Thu, 08 Sep 2022 08:07:15 GMT-07:00Associations of COVID-19 Outcomes with Dialysis Modalities and SettingsHow maintenance dialysis modality, dialysis setting, and residence in a nursing facility have jointly associated with coronavirus disease 2019 (COVID-19)-related outcomes in the United States is relevant to future viral outbreaks. Using Medicare claims, we determined the incidence of COVID-19–related infection, hospitalization, and death between March 15, 2020 and June 5, 2021. The exposure was one of five combinations of dialysis modality and care setting: in-facility hemodialysis without a recent history of skilled nursing facility care, in-facility hemodialysis with a recent history of skilled nursing facility care, hemodialysis in a skilled nursing facility, home hemodialysis, and (home) peritoneal dialysis. Patient-weeks were pooled to estimate the adjusted associations of event incidence with each dialysis modality/setting during four intervals in 2020–2021. Relative to in-facility hemodialysis without a recent history of skilled nursing facility care, home dialysis was associated with 36%–60% lower odds of all events during weeks 12–23 of 2020; 24%–37% lower odds of all events during weeks 24–37 of 2020; 20%–33% lower odds of infection and hospitalization during the winter of 2020–2021; and similar odds of all events thereafter. In contrast, exposure to skilled nursing facilities was associated with 570%–1140% higher odds of all events during spring of 2020, although excess risk attenuated as the pandemic transpired, especially among patients who received hemodialysis in skilled nursing facilities. In conclusion, home dialysis was associated with lower risks of COVID-19 diagnosis, hospitalization, and death until vaccines were available, whereas care in skilled nursing facilities was associated with higher risks.Weinhandl, Eric D.Liu, JiannongGilbertson, David T.Wetmore, James B.Johansen, Kirsten L.2022-09-08T08:07:15-07:00doi:10.2215/CJN.03400322hwp:resource-id:clinjasn;17/10/1526American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUnited States Renal Data System, COVID-19, ESRDInsights from the USRDSInsights from the USRDSresearch-article20222022-10-01October 202210.2215/CJN.034003221555-90411555-905X2022-09-08T08:07:15-07:002022-10Clinical Journal of the American Society of NephrologyInsights from the USRDS171015261534
- Drug Development for Cystic Kidney Diseases10.2215/CJN.04910422Tue, 23 Aug 2022 12:00:26 GMT-07:00Drug Development for Cystic Kidney DiseasesFedeles, SorinPerrone, Ronald D.2022-08-23T12:00:26-07:00doi:10.2215/CJN.04910422hwp:resource-id:clinjasn;17/10/1549American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypolycystic kidney disease, regulatory development, drug development, clinical trialPerspectivePerspectiveresearch-article20222022-10-01October 202210.2215/CJN.049104221555-90411555-905X2022-08-23T12:00:26-07:002022-10Clinical Journal of the American Society of NephrologyPerspective171010101015491551155515591550155415581562
- Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in DialysisSkeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping–specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.10.2215/CJN.11980921Tue, 15 Mar 2022 08:22:04 GMT-07:00Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in DialysisSkeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to (1) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, (2) construct a conceptual model for developing and evaluating a skeletal muscle cramping–specific patient-reported outcome measure, and (3) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.Richardson, Michelle M.Grandinetti, AmandaHilliard-Boone, Tandrea S.Wilund, Kenneth R.Wingard, RebeccaSt. Peter, Wendy L.Logan, DilaniTentori, FrancescaKeller, SanWest, MelissaLacson, Eduardo2022-03-15T08:22:04-07:00doi:10.2215/CJN.11980921hwp:resource-id:clinjasn;17/10/1563American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymuscle cramping, dialysis, patient-reported outcome measure, literature review, focus group, Kidney Health InitiativeFeatureFeatureresearch-article20222022-10-01October 202210.2215/CJN.119809211555-90411555-905X2022-03-15T08:22:04-07:002022-10Clinical Journal of the American Society of NephrologyFeature171015631574
- Point-of-Care Ultrasound Training during Nephrology Fellowship10.2215/CJN.01850222Wed, 21 Sep 2022 10:43:19 GMT-07:00Point-of-Care Ultrasound Training during Nephrology FellowshipMoore, Catherine A.Ross, Daniel W.Pivert, Kurtis A.Lang, Valerie J.Sozio, Stephen M.O’Neill, W. Charles2022-09-21T10:43:19-07:00doi:10.2215/CJN.01850222hwp:resource-id:clinjasn;17/10/1487American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyechocardiography, dialysis access, kidney biopsy, kidney anatomy, nephrology, vascular access, fellowships and scholarships, point-of-care systemsOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-10-01October 202210.2215/CJN.018502221555-90411555-905X2022-09-21T10:43:19-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article1710101487144214941445
- Perspectives on Drug Development in Autosomal Recessive Polycystic Kidney Disease10.2215/CJN.04870422Tue, 23 Aug 2022 12:00:27 GMT-07:00Perspectives on Drug Development in Autosomal Recessive Polycystic Kidney DiseaseLiebau, Max C.Hartung, Erum A.Perrone, Ronald D.2022-08-23T12:00:27-07:00doi:10.2215/CJN.04870422hwp:resource-id:clinjasn;17/10/1551American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPKHD1, fibrocystin, ARPKD, ADPKD, PKD, genetic kidney diseases, drug developmentPerspectivePerspectiveresearch-article20222022-10-01October 202210.2215/CJN.048704221555-90411555-905X2022-08-23T12:00:27-07:002022-10Clinical Journal of the American Society of NephrologyPerspective171010101015511549155515591554155015581562
- Current Challenges and Perspectives on Developing a Clinical Trial Design for ADPKD10.2215/CJN.05360522Tue, 23 Aug 2022 11:21:43 GMT-07:00Current Challenges and Perspectives on Developing a Clinical Trial Design for ADPKDOstroff, CraigPerrone, Ronald D.Czerwiec, Frank S.2022-08-23T11:21:43-07:00doi:10.2215/CJN.05360522hwp:resource-id:clinjasn;17/10/1559American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, clinical trial, glomerular filtration rate, total kidney volume, accelerated approval, biomarkerPerspectivePerspectiveresearch-article20222022-10-01October 202210.2215/CJN.053605221555-90411555-905X2022-08-23T11:21:43-07:002022-10Clinical Journal of the American Society of NephrologyPerspective171010101015591549155115551562155015541558
- Apolipoprotein L1 Genotypes and the Association of Urinary Potassium Excretion with CKD Progression10.2215/CJN.02680322Wed, 31 Aug 2022 10:49:50 GMT-07:00Apolipoprotein L1 Genotypes and the Association of Urinary Potassium Excretion with CKD ProgressionIlori, Titilayo O.Liu, JingRodan, Aylin R.Verma, AshishMills, Katherine T.He, JiangWinkler, Cheryl A.Dupuis, JoséeAnderson, Cheryl A.M.Waikar, Sushrut S.2022-08-31T10:49:50-07:00doi:10.2215/CJN.02680322hwp:resource-id:clinjasn;17/10/1477American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypotassium, genotype, chronic kidney disease, APOL1, gene environment interactionOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-10-01October 202210.2215/CJN.026803221555-90411555-905X2022-08-31T10:49:50-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article171014771486
- The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after Angiography10.2215/CJN.02160222Thu, 25 Aug 2022 06:17:18 GMT-07:00The Relationship between Rate and Volume of Intravenous Fluid Administration and Kidney Outcomes after AngiographySoomro, Qandeel H.Anand, Sonia T.Weisbord, Steven D.Gallagher, Martin P.Ferguson, Ryan E.Palevsky, Paul M.Bhatt, Deepak L.Parikh, Chirag R.Kaufman, James S.,Brophy, MaryChertow, GlennConner, ToddFerguson, RyanFine, M.Kaufman, JamesLew, RobertMcCullough, PeterPalevsky, PaulParikh, ChiragRinger, RobertShunk, KendrickSoliva, SusanWeisbord, StevenBhatt, DeepakCass, AlanGallagher, MartinMcFalls, EdwardPirakh, ChiragWu, HongshengRatliff, MichelleKetteler, ErikaGoff, JamesSnider, RichardJones, DebraKreuch, JeannieDuvernoy, ClaireThomas, MichaelWillatt, JonathanGurm, HitinderKrishnamurthy, VenkatNallamothu, BrahmajeeSzymanski, KendraGrossman, P. MichaelMenees, DanielRose, PatriciaMavromatis, KretonKumar, GautamRaghavan, SumatiDow, JeanneMandawat, MahendraNoe, SusanAlavi, HossainCalkins, JoeMcNear, JenniferBeals, DonaldCavalieri, StuartSierzega, RenataPearson, LauraAfaq, MazharVaitkus, PaulKudryk, BruceHall, DennisNadella, NeelimaCorin, WilliamWoklu, NinaInting-Toothman, StellaWescott, LeaVentura, NicoleKinlay, ScottCroce, KevinFaxon, DavidVokonas, PantelRaffetto, JosephMcPhee, JamesGupta, NarenNava, AdriannaLy, SamanthaMy-Do, JacquelynOstrowski, SimonBundy, MariahQuinn, MargotChin, MelissaCorbelli, JohnDosluoglu, HasanLohr, JamesRivero, MarielCooke, BethGalla, AnnCloen, DeniseFernandes, ValerianDiBona, AlexanderNielsen, ChristopherIdleman, LoisLee, BerthaVidovich, MladenKibbe, MelinaGriza, DecebalRaicu, MihaiRothenberg, FlorenceThakar, CharuhasMadabhushi, AditiArif, ImranBath, JonathanHelmy, TarekUnterbrink, KendraRoss, StephanieBailey, CathyHailes, MyrtleGoldberg, JonathanJozic, JosephKang, PreetKalman, JeanieneRosenthal, NoahCatania, DeborahMarlow, JeanneKumaran, VinayKrupka, AngelaZappernick, TaissaBrilakis, EmmanouilTsai, ShirlingBanerjee, SubhashModrall, J. GregoryRoesle, MicheleHamilton, MarcieLusk, CassieCompton, JenniferWillis, CyenthiaAtwell, AmySoto-Gonzalez, MarilisaAgarwal, AjaySaklayen, MohammadWoerner, DonnaRoss, JeffreyTurner, KarenZheng-Phelan, LingRider, KamiaRao, SunilJones, W. SchuylerPovsic, ThomasKrucoff, MitchellBrennan, JamesMiller, MichaelMureebe, LeilaAristy, KathyPowell, MarilynBavry, AnthonyChoi, CalvinPark, KiCurry, TempaRobertson, DebraWright, CilaJneid, HaniPaniagua, DavidDenktas, AliLara-Smalling, AguedaPalmer, LeahMalarchick, Jo AnnBroussard, EmilyBolad, IslamBreall, JeffreyMotaganahalli, RaghunandanEnglish, BethRamkaransingh, JeffreyMukerji, RitaSubbarao, RoopaWilliams, VickiHenson, SharonKrier, ConnieParashara, DeepakCiniglio, RicardoBarua, RajatRoys, MichaelSurineni, KamalakarMendes, KimberleyOni, OlurindeUretsky, BarryAhmed, ZubairYousaf, MuhammadHakeem, AbdulChung, Hui YongMiller, KristinDishongh, KatherineRamanathan, KodangudiShah, RahmanMcGee, JesseQualls, ZoeArmstrong, AshleyJohnson, LillieGarcia, SantiagoAdabag, SelcukVakil, KairavNguyen, JenniferBerg, MatthewHerrmann, RebekahCondon, DebraMeyeraan, TacySedlis, StevenLorin, JeffreyKeary, MaryShah, BinitaMaranan, LeandroLatif, FaisalThadani, UdhoAbu-Fadel, MazenExaire, JoseRousan, TallaRamirez-Jimenez, ArleenPham, TrangGiacomini, JohnLit, YimingMassaband, PayamYong, CelinaFearon, WilliamZhou, WeiAalami, OliverPeters, TheresaBratcher, KarenMonteverde, EdgardoRahman, ArefBandi, RupalGarbelotti, KellyMulukutla, SureshOverberger, PamelaWatnick, SuzanneDavies, CrispinLarsen, GregAtkinson, TamaraWalczyk, JacquelineKenworthy-Heinige, TawniGuenther, StephaniePitts, AlexandraJovin, IonMinisi, AnthonySumption, KevinFeldman, GeorgeHa, JonathanHendrix, MackMaldonado, MaureenJeter, DeborahKlein, AndrewForsberg, MichaelRowe, CarolineNasir, AmmarMani, KartikVercher, PaulWaidmann, KristiVargo, KristinChilakapati, VenkataJarmukli, NabilTan, Shen-LiSherigar, RathnakaraBottomley, SharonCapuno, MaribethHenley, KatherineDev, DevasmitaMathew, JacobOchalek, TracyLui, CharlesSmith, BrighamHuo, EugeneFrodsham, AaronEskelson, NoniVelarde, KandiDulin, HeatherMartinez, LillianZimmet, JeffreySawhney, RajivMalik, FadyChou, TonyHuynh, CynthiaStanley, KathleenGarcia, EpifanioLehmann, KennethStadius, MichaelBeatty, AlexisNaria, SohilkumarGalvin, GeorgiaChilton, RobertPham, SonOliveros, ReneHecht, JoanThai, HoangTruong, Huu TamGoldman, StevenThal, SergioJuneman, ElizabethKapoor, DivyaTsuda, RyanKipps, JulianaMikhail, AmaniSandoval, MichaelCurrier, JesseLee, Hsin-YiChang, DonaldWalsworth, MatthewWarner, AlbertaChen, AliceLendvai, DoraJohnson, JanetLee, JoanneCoggan, SarahKumar, Namrata NathDempsey, ErikaKotwal, SradhaSmyth, BrendanYianni, AlexiaLee, Li HuiCheong, Siew YanYates, CaseyJames, EarlTalaulikar, GirishFarshid, AhmadJohnson, PatriciaTaverner, PearleChadwick, HeatherStewart, RalphBenatar, JocelyneStone, LouiseHowell, LeahAnderson, SueLehnhard, SiobhanPatten, CathrineFarouque, OmarBellomo, RinaldoHorrigan, MarkScott, PeterJones, NicolasYudi, MatiasHuq, RafiAl-Fiadh, AliBrown, LouiseBrieger, DavidHillis, GrahamCherry, JonathanAitken, SarahAnastasius, MalcomLau, JerrettLowe, HarryAyoub, ChadiJardine, MegO’Connor, JodyWong, ChristopherWu, JuneXu, KittyWebster, JulieMwaijele, LiliangHand, SamanthaChew, DerekAlyward, PhilipBalakrishnan, DeepuPrakash, RoshanPathik, BhupeshKinatra, VineetJones, DylanSingh, ArunRatib, KarimHammad, Nassser AlGunton, JamesMazhar, JawadMusameh, MuntaserO’Shea, CatherineJudd, JoRaman, BettyWollaston, FionaFelice, Kerri AnnHincks, ChristineHarrison, TimothyFawcett, MalcolmWright, ThereseHorsfall, Lee-AnneKissajukian, FrancisMurphy, DiedreBartlett, PamelaStockle, PaulWilliam, MagedElsokkari, IhabRangasamy, KarthikeyanRoy, ProbalTran, DavidHayat, Muhammed UmairMay, AustinNyakudarika, ElijahPhang, CalvinConway, BetsO’Donoghue, MichelleEllis, KatrinaKanna, RajeshHendriks, RandallForrest, NicoleTulloch, GillGreenwell, DellaGhapar, Abd KaharGhani, Abdul Raqib AbdSundaralingam, ShaminiFuah, K.Habizal, Nor HalwaniDaud, Siti RohayaHaq, Hafsah Begum binti AbdulMohammad, Masliza BintiHassan, Faizah CheHashim, HananiIsmail, OmarKong, Poi KeongMa, Soot KengWahab, Mohamed Jahangir AbdulAbdulla, Zarina BanuKader, Mohamad Ali Sheikh AbdulGoh, Chong AikAhmadsha, Shahul HamidNaser, Mohamad Nazrulhisham MadYusuf, AzizahGovindasamy, ParamesveriIbrahim, Nur Azliati BintiYahaya, NormilahJuergens, CraigFrench, JohnMussap, C.Lo, SidneyBurgess, S.Mallard, TrevorHuang, JustinKumar, ManishLee, AdamLeung, DominicBadie, TamarXu, JamesTerluk, AndrewCroucher, AlexandriaO’Brien, KelseyRaynes, SuzannePlotz, MariaHallani, HishamFernandes, ClyneFitzpatrick, DrewParikh, DevangCoulshed, DavidPathan, FarazGanda, PrashilChandrala, PavanBarry, LisaMackenzie, MicheleVanGaal, WilliamHyat, UmairTsay, It MenSubiakto, IvanCresp, DamianNelson, GregoryMau, JamesShaw, ElizabethYan, WarrenArena, FrankDanson, EdwardVernon, S.Ward, MichaelAllahwala, U.Reid, EmmaStraiton, NicolaWhitley, AlexandraLoxton, AnnieErickson, Royal Perth Hospital: MatthewIhdayid, Abdul-RhmanDias, PeterAtique, SyedBonner, MichelleVenn-Edmonds, ClarePrasan, AnanthSader, MarkRamsay, DavidFord, TomWeaver, JamesBinnekamp, MauritsBarrett, DavidRoy, JamesNg, BenYoussef, GeorgeShrestha, PrakritiVrachas, DeborahDobinson, KateTernouth, IanLumb, NickySebastian, JeffreyJackson, CarolynVickers, CathyPrideaux, JanAhmad, Wan Azman WanAbidin, Imran ZainalZuhdi, Ahmad Syadi MahmoodIsmail, Muhammad DzafirSridhar, Ganiga SrinivasaiahLim, Soo KunHadi, Moud FirdausAdnan, Wan Ahmad Hafiz Wan MdKassim, Zainab AbuMansor, Syed Mukhtar SyedLee, Vin-ZhenHarding, ScottRanchord, AnilMatsis, PhilipAitken, AndrewSimmonds, Mark BernardFairley, SarahWolbinski, MariuszPlunkett, SusanSinan, Ali AlFerrier, KatherineO’Meeghan, TimWilkins, BenAnscomise, RussellSasse, AlexanderKirby, AlyssaErshad, ShakiyaSmyth, DuncanLim, Ren YikMiddleditch, DianeDavies, Bronwyn2022-08-25T18:17:18-07:00doi:10.2215/CJN.02160222hwp:resource-id:clinjasn;17/10/1446American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, chronic kidney disease, randomized controlled trials, angiography, fluid administrationOriginal ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-10-01October 202210.2215/CJN.021602221555-90411555-905X2022-08-25T18:17:18-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article171014461456
- Rituximab in the Frail and Elderly with Severe ANCA-Associated GN10.2215/CJN.04760422Tue, 02 Aug 2022 10:19:00 GMT-07:00Rituximab in the Frail and Elderly with Severe ANCA-Associated GNBrix, Silke R.Tesař, Vladimir2022-08-02T10:19:00-07:00doi:10.2215/CJN.04760422hwp:resource-id:clinjasn;17/10/1546American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, glomerulonephritis, rituximabKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-10-01October 202210.2215/CJN.047604221555-90411555-905X2022-08-02T10:19:00-07:002022-10Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat171015461548
- Perspectives on Drug Development in Early ADPKD10.2215/CJN.05190422Tue, 23 Aug 2022 11:45:42 GMT-07:00Perspectives on Drug Development in Early ADPKDMekahli, DjalilaWomack, HayleyDahl, Neera K.2022-08-23T11:45:42-07:00doi:10.2215/CJN.05190422hwp:resource-id:clinjasn;17/10/1555American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, drug development, early stagesPerspectivePerspectiveresearch-article20222022-10-01October 202210.2215/CJN.051904221555-90411555-905X2022-08-23T11:45:42-07:002022-10Clinical Journal of the American Society of NephrologyPerspective171010101015551549155115591558155015541562
- Employment Status and Work Functioning among Kidney Transplant Recipients10.2215/CJN.05560522Mon, 26 Sep 2022 06:49:55 GMT-07:00Employment Status and Work Functioning among Kidney Transplant RecipientsKnobbe, Tim J.Kremer, DaanAbma, Femke I.Annema, CobyBerger, Stefan P.Navis, Gerjan J.van der Mei, Sijrike F.Bültmann, UteVisser, AnnemiekeBakker, Stephan J.L.,Annema-de Jong, C.Bakker, S.J.L.Berger, S.P.Blokzijl, H.Bodewes, F.A.J.A.de Boer, M.T.Damman, K.de Borst, M.H.Diepstra, A.Dijkstra, G.Douwes, R.M.Eisenga, M.F.Erasmus, M.E.Gan, C.T.Gomes Neto, A.W.Hak, E.Hepkema, B.G.Klont, F.Knobbe, T.J.Kremer, D.Leuvenink, H.G.D.Lexmond, W.S.de Meijer, V.E.Niesters, H.G.M.van Pelt, L.J.Pol, R.A.Porte, R.J.Ranchor, A.V.Sanders, J.S.F.Siebelink, M.J.Slart, R.J.H.J.A.Swarte, J.C.Touw, D.J.van den Heuvel, M.C.van Leer-Buter, C.van Londen, M.Verschuuren, E.A.M.Vos, M.J.Weersma, R.K.2022-09-26T06:49:55-07:00doi:10.2215/CJN.05560522hwp:resource-id:clinjasn;17/10/1506American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologywork functioning, side effects of immunosuppressive therapy, kidney transplantation, quality of life, employment statusOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-10-01October 202210.2215/CJN.055605221555-90411555-905X2022-09-26T06:49:55-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article1710101506143115141432
- Genome-Wide Epistatic Interaction between DEF1B and APOL1 High-Risk Genotypes for Chronic Kidney Disease10.2215/CJN.03610322Wed, 10 Aug 2022 06:32:06 GMT-07:00Genome-Wide Epistatic Interaction between DEF1B and APOL1 High-Risk Genotypes for Chronic Kidney DiseaseVy, Ha My T.Lin, Bridget M.Gulamali, Faris F.Kooperberg, CharlesGraff, MariaelisaWong, JennyCampbell, Kirk N.Matise, Tara C.Coresh, JosefThomas, FridtjofReiner, Alexander P.Nassir, RamiSchnatz, Peter F.Johns, TanyaBuyske, StevenHaiman, ChristopherCooper, RichardLoos, Ruth J.F.Horowitz, Carol R.Gutierrez, Orlando M.Do, RonFranceschini, NoraNadkarni, Girish N.2022-08-10T06:32:06-07:00doi:10.2215/CJN.03610322hwp:resource-id:clinjasn;17/10/1522American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, APOL1, human genetics, genetic variation, chronic kidney diseaseResearch LetterResearch Letterletter20222022-10-01October 202210.2215/CJN.036103221555-90411555-905X2022-08-10T06:32:06-07:002022-10Clinical Journal of the American Society of NephrologyResearch Letter171015221525
- Incorporating Training in POCUS in Nephrology Fellowship Curriculum10.2215/CJN.09580822Wed, 21 Sep 2022 10:43:19 GMT-07:00Incorporating Training in POCUS in Nephrology Fellowship CurriculumReisinger, Nathaniel C.Koratala, Abhilash2022-09-21T10:43:19-07:00doi:10.2215/CJN.09580822hwp:resource-id:clinjasn;17/10/1442American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypoint of care ultras, POCUS, volume status assessment, nephrology training program, fluid overload, VExUS, venous excess ultrasound, lung ultrasound, quantitative lung ultrasonography, FOAMedEditorialEditorialeditorial20222022-10-01October 202210.2215/CJN.095808221555-90411555-905X2022-09-21T10:43:19-07:002022-10Clinical Journal of the American Society of NephrologyEditorial1710101442148714451494
- Reducing Racial Disparities in Access to Transplant in the United States10.2215/CJN.09590822Mon, 19 Sep 2022 07:44:40 GMT-07:00Reducing Racial Disparities in Access to Transplant in the United StatesReed, Rhiannon D.Locke, Jayme E.2022-09-19T07:44:40-07:00doi:10.2215/CJN.09590822hwp:resource-id:clinjasn;17/10/1439American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, transplantationEditorialEditorialeditorial20222022-10-01October 202210.2215/CJN.095908221555-90411555-905X2022-09-19T07:44:40-07:002022-10Clinical Journal of the American Society of NephrologyEditorial1710101439151514411521
- Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney Transplantation10.2215/CJN.04850422Mon, 19 Sep 2022 06:10:48 GMT-07:00Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney TransplantationKu, ElaineAmaral, SandraMcCulloch, Charles E.Adey, Deborah B.Li, LiboJohansen, Kirsten L.2022-09-19T06:10:48-07:00doi:10.2215/CJN.04850422hwp:resource-id:clinjasn;17/10/1515American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, disparityOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-10-01October 202210.2215/CJN.048504221555-90411555-905X2022-09-19T06:10:48-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article1710101515143915211441
- Arterial Stiffness and Chronic Kidney Disease Progression in Children10.2215/CJN.02200222Thu, 25 Aug 2022 06:17:18 GMT-07:00Arterial Stiffness and Chronic Kidney Disease Progression in ChildrenAzukaitis, KarolisKirchner, MariettaDoyon, AnkeLitwin, MieczysławBayazit, AysunDuzova, AliCanpolat, NurJankauskiene, AugustinaShroff, RukshanaMelk, AnetteQuerfeld, UweSchaefer, Franz2022-08-25T18:17:18-07:00doi:10.2215/CJN.02200222hwp:resource-id:clinjasn;17/10/1467American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, chronic kidney disease, pulse wave velocity, arterial stiffness, longitudinal studies, prospective studiesOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-10-01October 202210.2215/CJN.022002221555-90411555-905X2022-08-25T18:17:18-07:002022-10Clinical Journal of the American Society of NephrologyOriginal Article171014671476
- Postoperative Acute Kidney InjuryPostoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.10.2215/CJN.16541221Thu, 16 Jun 2022 09:33:17 GMT-07:00Postoperative Acute Kidney InjuryPostoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.Boyer, NaomiEldridge, JackProwle, John R.Forni, Lui G.2022-06-16T09:33:17-07:00doi:10.2215/CJN.16541221hwp:resource-id:clinjasn;17/10/1535American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury Series, acute kidney injury, perioperative, postoperative, surgery, biomarkers, kidney replacement therapyCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-10-01October 202210.2215/CJN.165412211555-90411555-905X2022-06-16T09:33:17-07:002022-10Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury171015351545
- Palliative Care for Hemodialysis Patients?10.2215/CJN.09710822Wed, 14 Sep 2022 07:07:42 GMT-07:00Palliative Care for Hemodialysis Patients?Brennan, FrankBrown, Mark A.2022-09-14T07:07:42-07:00doi:10.2215/CJN.09710822hwp:resource-id:clinjasn;17/10/1433American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypalliative care, hemodialysisEditorialEditorialeditorial20222022-10-01October 202210.2215/CJN.097108221555-90411555-905X2022-09-14T07:07:42-07:002022-10Clinical Journal of the American Society of NephrologyEditorial1710101433149514351505
- Dialysis, Transplantation, and Work10.2215/CJN.09840822Mon, 26 Sep 2022 07:07:11 GMT-07:00Dialysis, Transplantation, and WorkFadem, Stephen Z.2022-09-26T07:07:11-07:00doi:10.2215/CJN.09840822hwp:resource-id:clinjasn;17/10/1431American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyemployment, chronic hemodialysis, kidney transplantationPatient VoicePatient Voiceresearch-article20222022-10-01October 202210.2215/CJN.098408221555-90411555-905X2022-09-26T07:07:11-07:002022-10Clinical Journal of the American Society of NephrologyPatient Voice1710101431150614321514
- Oversimplification and Misplaced Blame will Not Solve the Complex Kidney Underutilization ProblemThis is an Early Access article. Please select the PDF button, above, to view it.gaurav.gupta@vcuhealth.org10.34067/KID.0005402022Wed, 05 Oct 2022 09:24:11 GMT-07:00Oversimplification and Misplaced Blame will Not Solve the Complex Kidney Underutilization ProblemThis is an Early Access article. Please select the PDF button, above, to view it.Stewart, DarrenTanriover, BekirGupta, Gaurav2022-10-05T09:24:11-07:00doi:10.34067/KID.0005402022hwp:resource-id:kidney360;KID.0005402022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Policy, Equity, Kidney Transplantation, Organ Allocation, Organ Discard, Organ UtilizationPerspectivePerspectiveother202210.34067/KID.00054020222641-76502641-76502022-10-05T09:24:11-07:00Kidney360Perspective3312122143214310.34067/KID.000540202221472147
- Genetic Variants of the COL4A3, COL4A4, and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients10.1681/ASN.2021111447Wed, 21 Sep 2022 09:47:36 GMT-07:00Genetic Variants of the COL4A3, COL4A4, and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy PatientsYuan, XiaohanSu, QingWang, HuiShi, SufangLiu, LijunLv, JichengWang, SuxiaZhu, LiZhang, Hong2022-09-21T09:47:36-07:00doi:10.1681/ASN.2021111447hwp:resource-id:jnephrol;ASN.2021111447v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, glomerulonephritis, glomerular basement membraneClinical ResearchClinical Researchresearch-article202210.1681/ASN.20211114471046-66731533-34502022-09-21T09:47:36-07:00Journal of the American Society of NephrologyClinical ResearchASN.2021111447
- Automated Kidney and Liver Segmentation in MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease: A Multicenter StudyBackground: Imaging-based total kidney and liver volumes (TKV, TLV) are major prognostic factors in autosomal dominant polycystic kidney disease (ADPKD) and endpoints for clinical trials. However, volumetry is time-consuming and reader-dependent in clinical practice. Our aim was to develop a fully automated method for joint kidney and liver segmentation in magnetic resonance imaging (MRI) and to evaluate its performance in a multi-sequence, multicenter setting. Methods: Convolutional neural network was trained on a large multicenter dataset consisting of 992 MRI scans of 327 patients. Manual segmentation delivered ground-truth labels. The model's performance was evaluated in a separate test dataset of 93 patients (350 MRI scans), as well as a heterogeneous external dataset of 831 MRI scans from 323 patients. Results: The segmentation model yielded excellent performance, achieving a median per-study Dice coefficient of 0.92-0.97 for the kidneys and 0.96 for the liver. Automatically computed TKV correlated highly with manual measurements (intraclass correlation coefficient (ICC): 0.996-0.999) with low bias and high precision (-0.2%±4.3% for axial and 0.5%±3.5% for coronal images). TLV estimation showed an ICC of 0.999 and bias/precision of -0.5%±3.3%. For the external dataset, the automated TKV demonstrated bias and precision of -1.3±7.4%. Conclusions: Our deep learning model enabled accurate segmentation of kidneys and liver and objective assessment of TKV and TLV. Importantly, this approach was validated with axial and coronal MRI scans from 40 different scanners, making implementation in clinical routine care feasible.roman-ulrich.mueller@uk-koeln.de10.34067/KID.0003192022Wed, 05 Oct 2022 05:56:19 GMT-07:00Automated Kidney and Liver Segmentation in MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease: A Multicenter StudyBackground: Imaging-based total kidney and liver volumes (TKV, TLV) are major prognostic factors in autosomal dominant polycystic kidney disease (ADPKD) and endpoints for clinical trials. However, volumetry is time-consuming and reader-dependent in clinical practice. Our aim was to develop a fully automated method for joint kidney and liver segmentation in magnetic resonance imaging (MRI) and to evaluate its performance in a multi-sequence, multicenter setting. Methods: Convolutional neural network was trained on a large multicenter dataset consisting of 992 MRI scans of 327 patients. Manual segmentation delivered ground-truth labels. The model's performance was evaluated in a separate test dataset of 93 patients (350 MRI scans), as well as a heterogeneous external dataset of 831 MRI scans from 323 patients. Results: The segmentation model yielded excellent performance, achieving a median per-study Dice coefficient of 0.92-0.97 for the kidneys and 0.96 for the liver. Automatically computed TKV correlated highly with manual measurements (intraclass correlation coefficient (ICC): 0.996-0.999) with low bias and high precision (-0.2%±4.3% for axial and 0.5%±3.5% for coronal images). TLV estimation showed an ICC of 0.999 and bias/precision of -0.5%±3.3%. For the external dataset, the automated TKV demonstrated bias and precision of -1.3±7.4%. Conclusions: Our deep learning model enabled accurate segmentation of kidneys and liver and objective assessment of TKV and TLV. Importantly, this approach was validated with axial and coronal MRI scans from 40 different scanners, making implementation in clinical routine care feasible.Woznicki, PiotrSiedek, Florianvan Gastel, Maatje D.A.Pinto dos Santos, DanielArjune, SitaKarner, LarinaMeyer, FranziskaPersigehl, ThorstenGansevoort, Ronald T.Grundmann, FranziskaBaessler, BettinaMüller, Roman-Ulrich2022-10-05T05:56:19-07:00doi:10.34067/KID.0003192022hwp:resource-id:kidney360;KID.0003192022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360liver, kidney, polycystic kidney disease, ADPKD, volumetry, automated, deep neural network, segmentationOriginal InvestigationOriginal Investigationother202210.34067/KID.00031920222641-76502641-76502022-10-05T05:56:19-07:00Kidney360Original Investigation3312122048204810.34067/KID.000319202220582058
- Belatacept-based Maintenance Immunosuppression Controls the Post-transplant Humoral Immune Response in Highly Sensitized Non-human primatesPre-existing donor-specific antibody (DSA) to major histocompatibility complex (MHC) antigens increases the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pre-transplant desensitization with costimulation blockade and proteasome inhibition has facilitated transplantation in our pre-clinical nonhuman primate (NHP) model. However, long-term graft survival is limited by rebound of DSA after transplantation. In this study we performed kidney transplants between highly sensitized, maximally MHC-mismatched NHPs (n=14). At kidney transplantation, primates received T cell depletion with rhesus-specific antithymocyte globulin (rhATG, n=10) or monoclonal anti-CD4 and anti-CD8 antibodies (n=4). Maintenance immunosuppression consisted of belatacept and tacrolimus (n=5) or belatacept and rapamycin (n=9) with steroids. Rebound of DSA post kidney transplantation was significantly reduced compared to maintenance immunosuppression with tacrolimus, mycophenolate, and steroids. Protocol lymph node biopsies showed a decrease in germinal center activity with low frequencies of T follicular helper cells as well as class-switched B cells after kidney transplantation. Combined belatacept and rapamycin was superior in controlling viral reactivation, enabling weaning of ganciclovir prophylaxis. Tacrolimus was associated with increased morbidity that included cytomegalovirus (CMV) and parvovirus viremia and post-transplant lymphoproliferative disorder. All primates in the tacrolimus/belatacept group failed discontinuation of anti-viral therapy. Overall, belatacept-based immunosuppression increased AMR-free graft survival by controlling post-transplant humoral responses in highly sensitized NHP recipients and should be further investigated in a human clinical trial.jean.kwun@duke.edu10.34067/KID.0001732022Tue, 04 Oct 2022 01:24:08 GMT-07:00Belatacept-based Maintenance Immunosuppression Controls the Post-transplant Humoral Immune Response in Highly Sensitized Non-human primatesPre-existing donor-specific antibody (DSA) to major histocompatibility complex (MHC) antigens increases the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pre-transplant desensitization with costimulation blockade and proteasome inhibition has facilitated transplantation in our pre-clinical nonhuman primate (NHP) model. However, long-term graft survival is limited by rebound of DSA after transplantation. In this study we performed kidney transplants between highly sensitized, maximally MHC-mismatched NHPs (n=14). At kidney transplantation, primates received T cell depletion with rhesus-specific antithymocyte globulin (rhATG, n=10) or monoclonal anti-CD4 and anti-CD8 antibodies (n=4). Maintenance immunosuppression consisted of belatacept and tacrolimus (n=5) or belatacept and rapamycin (n=9) with steroids. Rebound of DSA post kidney transplantation was significantly reduced compared to maintenance immunosuppression with tacrolimus, mycophenolate, and steroids. Protocol lymph node biopsies showed a decrease in germinal center activity with low frequencies of T follicular helper cells as well as class-switched B cells after kidney transplantation. Combined belatacept and rapamycin was superior in controlling viral reactivation, enabling weaning of ganciclovir prophylaxis. Tacrolimus was associated with increased morbidity that included cytomegalovirus (CMV) and parvovirus viremia and post-transplant lymphoproliferative disorder. All primates in the tacrolimus/belatacept group failed discontinuation of anti-viral therapy. Overall, belatacept-based immunosuppression increased AMR-free graft survival by controlling post-transplant humoral responses in highly sensitized NHP recipients and should be further investigated in a human clinical trial.Schmitz, RobinFitch, Zachary W.Manook, MiriamSchroder, Paul M.Choi, Ashley Y.Olaso, DanaeYoon, JanghoonBae, YeeunShaw, Brian I.Song, MingqingKuchibhatla, MaragathaFarris, Alton B.Kirk, AllanKwun, JeanKnechtle, Stuart J.2022-10-04T13:24:08-07:00doi:10.34067/KID.0001732022hwp:resource-id:kidney360;KID.0001732022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Belatacept, Antibody-mediated rejection, kidney transplantation, immunosuppression, PTLD, Nonhuman primate, Desensitization, Sensitization, Follicular helper T cells, Basic ScienceInnovative Technology and MethodologyInnovative Technology and Methodologyother202210.34067/KID.00017320222641-76502641-76502022-10-04T13:24:08-07:00Kidney360Innovative Technology and Methodology3312122116211610.34067/KID.000173202221302130
- Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant RecipientsBackground: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates tumor necrosis factor alpha (TNF) production that amplifies allograft inflammation and may negatively impact transplant outcomes. Methods: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase II clinical trial. Two-hundred twenty-five primary transplant recipients of deceased-donor kidneys (KTx) (38.2% Black/African-American, 44% White) were randomized to receive i.v. infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated prior to \ kidney reperfusion. All subjects received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary endpoint was the difference between groups in mean 24-month estimated glomerular filtration rate (eGFR). Results: There was no difference in the primary endpoint, 24-mo eGFR between IFX (52.45 ml/min/1.73m2, 95% CI 48.38-56.52) vs. PLBO (57.35 ml/min/1.73m2, 95% CI 53.18-61.52, p=0.099). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ and day 7 post-KTx plasma analyses showed ~10-fold lower TNF (p<0.001) in IFX vs. PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) vs. PLBO (13.4% p=0.004) with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) vs. PLBO (4.9%, p=0.06). Conclusions: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peri-transplant inflammation as a strategy to improve KTx outcomes.Peter.Heeger@cshs.org10.1681/ASN.2022040454Tue, 04 Oct 2022 11:08:38 GMT-07:00Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant RecipientsBackground: Ischemia-reperfusion (IR) of a kidney transplant (KTx) upregulates tumor necrosis factor alpha (TNF) production that amplifies allograft inflammation and may negatively impact transplant outcomes. Methods: We tested the effects of blocking TNF peri-KTx via a randomized, double-blind, placebo-controlled, 15-center, phase II clinical trial. Two-hundred twenty-five primary transplant recipients of deceased-donor kidneys (KTx) (38.2% Black/African-American, 44% White) were randomized to receive i.v. infliximab (IFX) 3 mg/kg or saline placebo (PLBO) initiated prior to \ kidney reperfusion. All subjects received rabbit anti-thymocyte globulin induction and maintenance immunosuppression (IS) with tacrolimus, mycophenolate mofetil, and prednisone. The primary endpoint was the difference between groups in mean 24-month estimated glomerular filtration rate (eGFR). Results: There was no difference in the primary endpoint, 24-mo eGFR between IFX (52.45 ml/min/1.73m2, 95% CI 48.38-56.52) vs. PLBO (57.35 ml/min/1.73m2, 95% CI 53.18-61.52, p=0.099). There were no significant differences between groups in rates of delayed graft function, biopsy-proven acute rejection (BPAR), development of de novo donor-specific antibodies, or graft loss/death. Immunosuppression did not differ and day 7 post-KTx plasma analyses showed ~10-fold lower TNF (p<0.001) in IFX vs. PLBO. BK viremia requiring IS change occurred more frequently in IFX (28.9%) vs. PLBO (13.4% p=0.004) with a strong trend toward higher rates of BKV nephropathy in IFX (13.3%) vs. PLBO (4.9%, p=0.06). Conclusions: IFX induction therapy does not benefit recipients of kidney transplants from deceased donors on this IS regimen. Because the intervention unexpectedly increased rates of BK virus infections, our findings underscore the complexities of targeting peri-transplant inflammation as a strategy to improve KTx outcomes.Hricik, DonaldArmstrong, BrianAlhamad, TarekBrennan, DanielBromberg, JonathanBunnapradist, SuphamaiChandran, SindhuFairchild, RobertFoley, DavidFormica, RichardGibson, IanKesler, KarenKim, S. JosephMannon, RoslynMenon, MadhavNewell, KennethNickerson, PeterOdim, JonahPoggio, EmilioSung, RandallShapiro, RonTinckam, KathrynVincenti, FlavioHeeger, Peter2022-10-04T11:08:38-07:00doi:10.1681/ASN.2022040454hwp:resource-id:jnephrol;ASN.2022040454v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Clinical ResearchOriginal Article - Clinical Researchresearch-article202210.1681/ASN.20220404541046-66731533-34502022-10-04T11:08:38-07:00Journal of the American Society of NephrologyOriginal Article - Clinical ResearchASN.2022040454
- The Case for Prioritizing Diversity in the Transplantation Workforce to Advance Kidney Health Equity10.1681/ASN.2022040429Tue, 02 Aug 2022 12:56:00 GMT-07:00The Case for Prioritizing Diversity in the Transplantation Workforce to Advance Kidney Health EquityButler, ThomasCummings, Lee S.Purnell, Tanjala S.2022-08-02T12:56:00-07:00doi:10.1681/ASN.2022040429hwp:resource-id:jnephrol;33/10/1817American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, kidney transplantation, organ transplant, racial and ethnic disparitiesPerspectiveAddressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220404291046-66731533-34502022-08-02T12:56:00-07:002022-10Journal of the American Society of NephrologyPerspective331018171819
- Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study10.1681/ASN.2022030373Fri, 29 Jul 2022 10:32:22 GMT-07:00Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort StudySwartling, OskarYang, YuanhangClase, Catherine M.Fu, Edouard L.Hecking, ManfredHödlmoser, SebastianTrolle-Lagerros, YlvaEvans, MarieCarrero, Juan J.2022-07-29T10:32:22-07:00doi:10.1681/ASN.2022030373hwp:resource-id:jnephrol;33/10/1903American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, sex difference, epidemiology and outcomesClinical EpidemiologyChronic Kidney DiseaseClinical EpidemiologyChronic Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220303731046-66731533-34502022-07-29T10:32:22-07:002022-10Journal of the American Society of NephrologyClinical Epidemiology331010101903i18041914i1806
- Description and Outcomes of an Innovative Concurrent Hospice-Dialysis Program10.1681/ASN.2022010064Tue, 12 Jul 2022 11:22:38 GMT-07:00Description and Outcomes of an Innovative Concurrent Hospice-Dialysis ProgramErnecoff, Natalie C.Bursic, Alexandra E.Motter, Erica M.Lagnese, KeithTaylor, RobertSchell, Jane O.2022-07-12T11:22:38-07:00doi:10.1681/ASN.2022010064hwp:resource-id:jnephrol;33/10/1942American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, end stage kidney disease, end stage renal disease, geriatric nephrology, hospicesClinical ResearchDialysisClinical ResearchDialysisresearch-article20222022-10-01October 202210.1681/ASN.20220100641046-66731533-34502022-07-12T11:22:38-07:002022-10Journal of the American Society of NephrologyClinical Research3310101942180819501810
- Blocking CCL8-CCR8–Mediated Early Allograft Inflammation Improves Kidney Transplant Function10.1681/ASN.2022020139Tue, 16 Aug 2022 07:40:22 GMT-07:00Blocking CCL8-CCR8–Mediated Early Allograft Inflammation Improves Kidney Transplant FunctionDangi, AnilHusain, IrmaJordan, Collin Z.Yu, ShuangjinNatesh, NaveenShen, XilingKwun, JeanLuo, Xunrong2022-08-16T07:40:22-07:00doi:10.1681/ASN.2022020139hwp:resource-id:jnephrol;33/10/1876American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, kidney transplantation, macrophages, inflammation, allograftsBasic ResearchTransplantationBasic ResearchTransplantationresearch-article20222022-10-01October 202210.1681/ASN.20220201391046-66731533-34502022-08-16T07:40:22-07:002022-10Journal of the American Society of NephrologyBasic Research331018761890
- Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats10.1681/ASN.2022040474Fri, 19 Aug 2022 10:51:52 GMT-07:00Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in RatsBergling, KarinMartus, GiedreÖberg, Carl M.2022-08-19T10:51:52-07:00doi:10.1681/ASN.2022040474hwp:resource-id:jnephrol;33/10/1857American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologywater transport, ultrafiltration, glucose, phloretin, peritoneal dialysis, peritoneal membraneBasic ResearchDialysisBasic ResearchDialysisresearch-article20222022-10-01October 202210.1681/ASN.20220404741046-66731533-34502022-08-19T10:51:52-07:002022-10Journal of the American Society of NephrologyBasic Research3310101857180318631804
- Expression of Concern: Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy10.1681/ASN.2022080927Fri, 09 Sep 2022 08:51:00 GMT-07:00Expression of Concern: Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic CardiomyopathyAmerican Society of Nephrology2022-09-09T08:51:00-07:00doi:10.1681/ASN.2022080927hwp:resource-id:jnephrol;33/10/1957American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyExpression of ConcernExpression of Concerncorrection20222022-10-01October 202210.1681/ASN.20220809271046-66731533-34502022-09-09T08:51:00-07:002022-10Journal of the American Society of NephrologyExpression of Concern33311081957174619571760
- Authors’ Reply: Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!10.1681/ASN.2022070747Wed, 10 Aug 2022 10:14:36 GMT-07:00Authors’ Reply: Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!Segelmark, MårtenKjellman, Christian2022-08-10T10:14:36-07:00doi:10.1681/ASN.2022070747hwp:resource-id:jnephrol;33/10/1954American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, glomerulonephritisLetter to the EditorLetter to the Editorletter20222022-10-01October 202210.1681/ASN.20220707471046-66731533-34502022-08-10T10:14:36-07:002022-10Journal of the American Society of NephrologyLetter to the Editor33101041954195382919551954838
- Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney Biopsies10.1681/ASN.2022030234Wed, 03 Aug 2022 09:40:33 GMT-07:00Prognostic Implications of a Morphometric Evaluation for Chronic Changes on All Diagnostic Native Kidney BiopsiesDenic, AleksandarBogojevic, MarijaMullan, Aidan F.Sabov, MoldovanAsghar, Muhammad S.Sethi, SanjeevSmith, Maxwell L.Fervenza, Fernando C.Glassock, Richard J.Hommos, Musab S.Rule, Andrew D.2022-08-03T09:40:33-07:00doi:10.1681/ASN.2022030234hwp:resource-id:jnephrol;33/10/1927American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, end stage kidney disease, kidney biopsy, morphometry, interstitial fibrosis, renal pathologyClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220302341046-66731533-34502022-08-03T09:40:33-07:002022-10Journal of the American Society of NephrologyClinical Research3310101927i1941i
- Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy10.1681/ASN.2022050608Fri, 19 Aug 2022 10:51:51 GMT-07:00Netrin G1 Is a Novel Target Antigen in Primary Membranous NephropathyReinhard, LindaMachalitza, MayaWiech, ThorstenGröne, Hermann-JosefLassé, MoritzRinschen, Markus M.Ferru, NicolettaBräsen, Jan HinrichDrömann, FriederikeRob, Peter MariaSethi, SanjeevHoxha, ElionStahl, Rolf A.K.2022-08-19T10:51:51-07:00doi:10.1681/ASN.2022050608hwp:resource-id:jnephrol;33/10/1823American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, NTNG1 antibody, netrinsRapid CommunicationDialysisRapid CommunicationDialysisrapid-communication20222022-10-01October 202210.1681/ASN.20220506081046-66731533-34502022-08-19T10:51:51-07:002022-10Journal of the American Society of NephrologyRapid Communication3310101823i1831i
- Dapagliflozin Prevents Kidney Glycogen Accumulation and Improves Renal Proximal Tubule Cell Functions in a Mouse Model of Glycogen Storage Disease Type 1b10.1681/ASN.2021070935Tue, 12 Jul 2022 11:22:38 GMT-07:00Dapagliflozin Prevents Kidney Glycogen Accumulation and Improves Renal Proximal Tubule Cell Functions in a Mouse Model of Glycogen Storage Disease Type 1bD’Acierno, MariavittoriaResaz, RobertaIervolino, AnnaNielsen, RikkeSardella, DonatoSiccardi, SabrinaCostanzo, VincenzoD’Apolito, LucianoSuzumoto, YokoSegalerba, DanielaAstigiano, SimonettaPerna, Alessandra F.Capasso, GiovambattistaEva, AlessandraTrepiccione, Francesco2022-07-12T11:22:38-07:00doi:10.1681/ASN.2021070935hwp:resource-id:jnephrol;33/10/1864American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, SGLT-2 inhibitors, glycogen, dapagliflozin, NHE-3, Napi-2, glycogen storage disease 1b, hexokinase-1Basic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article20222022-10-01October 202210.1681/ASN.20210709351046-66731533-34502022-07-12T11:22:38-07:002022-10Journal of the American Society of NephrologyBasic Research331018641875
- Ensuring Equitable Access to Dialysis: The Medicare Secondary Payer Act in Marietta Memorial Hospital Employee Health Benefit Plan v. DaVita, Inc.10.1681/ASN.2022020224Wed, 03 Aug 2022 09:40:32 GMT-07:00Ensuring Equitable Access to Dialysis: The Medicare Secondary Payer Act in Marietta Memorial Hospital Employee Health Benefit Plan v. DaVita, Inc.Maliha, GeorgeGlickman, Joel D.McCoy, Matthew S.2022-08-03T09:40:32-07:00doi:10.1681/ASN.2022020224hwp:resource-id:jnephrol;33/10/1814American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, chronic kidney disease, chronic kidney failure, chronic renal failure, chronic renal disease, end stage kidney disease, end-stage renal disease, ESRD, hemodialysis, health statusPerspectivePerspectiveresearch-article20222022-10-01October 202210.1681/ASN.20220202241046-66731533-34502022-08-03T09:40:32-07:002022-10Journal of the American Society of NephrologyPerspective331018141816
- Policy and Kidney Community Engagement to Advance toward Greener Kidney Care10.1681/ASN.2022070741Thu, 18 Aug 2022 07:51:16 GMT-07:00Policy and Kidney Community Engagement to Advance toward Greener Kidney CareStruthers, Sarah A.Kribs, ZacharyButler, Catherine R.2022-08-18T07:51:16-07:00doi:10.1681/ASN.2022070741hwp:resource-id:jnephrol;33/10/1811American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, dialysisPerspectivePerspectiveresearch-article20222022-10-01October 202210.1681/ASN.20220707411046-66731533-34502022-08-18T07:51:16-07:002022-10Journal of the American Society of NephrologyPerspective331018111813
- Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKD10.1681/ASN.2022010013Mon, 29 Aug 2022 01:48:09 GMT-07:00Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKDBinder, VeronikaChruścicka-Smaga, BarbaraBergum, BrithJaisson, StéphaneGillery, PhilippeSivertsen, JoarHervig, TorKaminska, MartaTilvawala, RonakNemmara, Venkatesh V.Thompson, Paul R.Potempa, JanMarti, Hans-PeterMydel, Piotr2022-08-29T13:48:09-07:00doi:10.1681/ASN.2022010013hwp:resource-id:jnephrol;33/10/1841American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, chronic kidney failure, end stage renal disease, platelets, uremia, coagulation, carbamylation, protein carbamylationBasic ResearchChronic Kidney DiseaseBasic ResearchChronic Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220100131046-66731533-34502022-08-29T13:48:09-07:002022-10Journal of the American Society of NephrologyBasic Research331018411856
- Concurrent Hospice and Dialysis: Proof of Concept10.1681/ASN.2022080919Mon, 12 Sep 2022 07:24:16 GMT-07:00Concurrent Hospice and Dialysis: Proof of ConceptButler, Catherine R.Wachterman, Melissa W.O’Hare, Ann M.2022-09-12T07:24:16-07:00doi:10.1681/ASN.2022080919hwp:resource-id:jnephrol;33/10/1808American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhospice, concurrent care, dialysisEditorialEditorialeditorial20222022-10-01October 202210.1681/ASN.20220809191046-66731533-34502022-09-12T07:24:16-07:002022-10Journal of the American Society of NephrologyEditorial3310101808194218101950
- Sex Disparities in the Quality of Care for CKD10.1681/ASN.2022080939Mon, 12 Sep 2022 07:24:16 GMT-07:00Sex Disparities in the Quality of Care for CKDReaves, Allison C.Levey, Andrew S.2022-09-12T07:24:16-07:00doi:10.1681/ASN.2022080939hwp:resource-id:jnephrol;33/10/1804American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, albuminuria, quality of care, women's health, disparities in careEditorialEditorialeditorial20222022-10-01October 202210.1681/ASN.20220809391046-66731533-34502022-09-12T07:24:16-07:002022-10Journal of the American Society of NephrologyEditorial331010101804i19031806i1914
- Assessing Tubular Function, an Ignored Component of CKD, Might Be a Difference Maker!10.1681/ASN.2022080946Fri, 09 Sep 2022 08:51:00 GMT-07:00Assessing Tubular Function, an Ignored Component of CKD, Might Be a Difference Maker!Kalantari, Kambiz2022-09-09T08:51:00-07:00doi:10.1681/ASN.2022080946hwp:resource-id:jnephrol;33/10/1806American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, biomarkers, tubular functionEditorialEditorialeditorial20222022-10-01October 202210.1681/ASN.20220809461046-66731533-34502022-09-09T08:51:00-07:002022-10Journal of the American Society of NephrologyEditorial3310101806191518081926
- This Month's Highlights10.1681/ASN.2022080947Mon, 12 Sep 2022 07:24:17 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2022-09-12T07:24:17-07:00doi:10.1681/ASN.2022080947hwp:resource-id:jnephrol;33/10/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsother20222022-10-01October 202210.1681/ASN.20220809471046-66731533-34502022-09-12T07:24:17-07:002022-10Journal of the American Society of NephrologyThis Month's Highlights331010101010i1823190318041927i1831191418061941
- The Sweet Science of Glucose Transport10.1681/ASN.2022070841Fri, 09 Sep 2022 08:51:00 GMT-07:00The Sweet Science of Glucose TransportSridhar, Vikas S.Bargman, Joanne M.2022-09-09T08:51:00-07:00doi:10.1681/ASN.2022070841hwp:resource-id:jnephrol;33/10/1803American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglucose transport, ultrafiltration, GLUT, SGLTEditorialEditorialeditorial20222022-10-01October 202210.1681/ASN.20220708411046-66731533-34502022-09-09T08:51:00-07:002022-10Journal of the American Society of NephrologyEditorial3310101803185718041863
- Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!10.1681/ASN.2022050609Wed, 10 Aug 2022 10:14:36 GMT-07:00Endopeptidase Therapy for Anti-Glomerular Basement Membrane Disease: Beware of Anti-Hinge Antibodies!Borza, Dorin-BogdanManral, Pallavi2022-08-10T10:14:36-07:00doi:10.1681/ASN.2022050609hwp:resource-id:jnephrol;33/10/1953American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, endopeptidase therapy, anti-hinge antibodies, imlifidaseLetter to the EditorLetter to the Editorletter20222022-10-01October 202210.1681/ASN.20220506091046-66731533-34502022-08-10T10:14:36-07:002022-10Journal of the American Society of NephrologyLetter to the Editor33101041953195482919541955838
- Authors’ Reply: Understanding the Multiple Roles of Extracellular Histones in Mediating Endothelial Dysfunction10.1681/ASN.2022060687Wed, 03 Aug 2022 10:38:18 GMT-07:00Authors’ Reply: Understanding the Multiple Roles of Extracellular Histones in Mediating Endothelial DysfunctionZafrani, LaraArnaud, MarineMooney, Nuala2022-08-03T10:38:18-07:00doi:10.1681/ASN.2022060687hwp:resource-id:jnephrol;33/10/1952American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhistone, endothelial cellsLetter to the EditorLetter to the Editorletter20222022-10-01October 202210.1681/ASN.20220606871046-66731533-34502022-08-03T10:38:18-07:002022-10Journal of the American Society of NephrologyLetter to the Editor3310106195219511154195319521171
- Understanding the Multiple Roles of Extracellular Histones in Mediating Endothelial Dysfunction10.1681/ASN.2022060640Wed, 03 Aug 2022 10:08:29 GMT-07:00Understanding the Multiple Roles of Extracellular Histones in Mediating Endothelial DysfunctionYang, TinghangLi, YupeiSu, Baihai2022-08-03T10:08:29-07:00doi:10.1681/ASN.2022060640hwp:resource-id:jnephrol;33/10/1951American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhistones, endothelial dysfunction, VE-cadherin, Toll-like receptor 4Letter to the EditorLetter to the Editorletter20222022-10-01October 202210.1681/ASN.20220606401046-66731533-34502022-08-03T10:08:29-07:002022-10Journal of the American Society of NephrologyLetter to the Editor3310106195119521154195219531171
- SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses10.1681/ASN.2022040504Tue, 16 Aug 2022 07:40:22 GMT-07:00SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine DosesMontez-Rath, Maria E.Garcia, PabloHan, JialinCadden, LinaCelHunsader, PattiMorgan, CurtKerschmann, RussellBeyer, PaulDittrich, MaryBlock, Geoffrey A.Parsonnet, JulieChertow, Glenn M.Anand, Shuchi2022-08-16T07:40:22-07:00doi:10.1681/ASN.2022040504hwp:resource-id:jnephrol;33/10/1832American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, ESKD, immunology, clinical epidemiology, COVID-19, SARS-CoV-2Rapid CommunicationGlomerulonephritis and Interstitial NephritisRapid CommunicationGlomerulonephritis and Interstitial Nephritisresearch-article20222022-10-01October 202210.1681/ASN.20220405041046-66731533-34502022-08-16T07:40:22-07:002022-10Journal of the American Society of NephrologyRapid Communication331018321839
- Sex Differences in Age-Related Loss of Kidney Function10.1681/ASN.2022030323Wed, 17 Aug 2022 07:50:35 GMT-07:00Sex Differences in Age-Related Loss of Kidney FunctionMelsom, ToralfNorvik, Jon ViljarEnoksen, Inger ThereseStefansson, VidarMathisen, Ulla DorteFuskevåg, Ole MartinJenssen, Trond G.Solbu, Marit D.Eriksen, Bjørn O.2022-08-17T07:50:35-07:00doi:10.1681/ASN.2022030323hwp:resource-id:jnephrol;33/10/1891American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, gender difference, glomerular filtration rate, glomerular hyperfiltration, kidney failure, microalbuminuria, renal function decline, risk factors, health statusClinical EpidemiologyChronic Kidney DiseaseClinical EpidemiologyChronic Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220303231046-66731533-34502022-08-17T07:50:35-07:002022-10Journal of the American Society of NephrologyClinical Epidemiology331018911902
- Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD10.1681/ASN.2022010117Tue, 16 Aug 2022 07:40:22 GMT-07:00Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKDBullen, Alexander L.Ascher, Simon B.Scherzer, RebeccaGarimella, Pranav S.Katz, RonitHallan, Stein I.Cheung, Alfred K.Raphael, Kalani L.Estrella, Michelle M.Jotwani, Vasantha K.Malhotra, RakeshSeegmiller, Jesse C.Shlipak, Michael G.Ix, Joachim H.2022-08-16T07:40:22-07:00doi:10.1681/ASN.2022010117hwp:resource-id:jnephrol;33/10/1915American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytubular secretion, biomarker, adverse events, hypertensionClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220101171046-66731533-34502022-08-16T07:40:22-07:002022-10Journal of the American Society of NephrologyClinical Research3310101915180619261808
- Acknowledging Socioecological Systems to Address the Systemic Racial Disparities in Children with Kidney Disease10.1681/ASN.2022040428Wed, 29 Jun 2022 08:14:49 GMT-07:00Acknowledging Socioecological Systems to Address the Systemic Racial Disparities in Children with Kidney DiseaseDawson, Anne E.LaMotte, Julia E.Bignall, O. N. Ray2022-06-29T08:14:49-07:00doi:10.1681/ASN.2022040428hwp:resource-id:jnephrol;33/10/1820American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypediatric nephrology, ethnic minority, ecosystem, racial and ethnic disparitiesPerspectiveAddressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-10-01October 202210.1681/ASN.20220404281046-66731533-34502022-06-29T08:14:49-07:002022-10Journal of the American Society of NephrologyPerspective331018201822
- Renal Macrophages and Multinucleated Giant Cells: Ferrymen of the River Styx?10.34067/KID.0003992022Fri, 22 Jul 2022 01:35:59 GMT-07:00Renal Macrophages and Multinucleated Giant Cells: Ferrymen of the River Styx?Sivaguru, MayandiFouke, Bruce W.2022-07-22T13:35:59-07:00doi:10.34067/KID.0003992022hwp:resource-id:kidney360;3/9/1616American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephrolithiasis, basic science, CaP crystals, COD crystals, COM crystals, crystal aggregation, endocytosis, macrophage migration, macrophages, multinucleated giant cells, phagocytosis, stone formationPerspectivePerspectiveresearch-article20222022-09-2910.34067/KID.00039920222641-76502022-07-22T13:35:59-07:002022-09-29Kidney360Perspective3916161619
- The Integration of Diabetic Eye Screening into Hemodialysis Units in Northern Ireland10.34067/KID.0001802022Wed, 18 May 2022 01:30:25 GMT-07:00The Integration of Diabetic Eye Screening into Hemodialysis Units in Northern IrelandCushley, Laura N.Quinn, Nicola B.Blows, PeterMcKeever, EdwardPeto, Tunde2022-05-18T13:30:25-07:00doi:10.34067/KID.0001802022hwp:resource-id:kidney360;3/9/1542American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, diabetes, diabetic eye disease, diabetic retinopathy, eye screening, hemodialysis, nephrology, Northern IrelandOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20222022-09-2910.34067/KID.00018020222641-76502022-05-18T13:30:25-07:002022-09-29Kidney360Original Investigation3915421544
- Critical Role of Osteopontin in Maintaining Urinary Phosphate Solubility in CKD10.34067/KID.0007352021Thu, 23 Jun 2022 06:48:58 GMT-07:00Critical Role of Osteopontin in Maintaining Urinary Phosphate Solubility in CKDStubbs, Jason R.Zhang, ShiqinJansson, Kyle P.Fields, Timothy A.Boulanger, JosephLiu, ShiguangRowe, Peter S.2022-06-23T06:48:58-07:00doi:10.34067/KID.0007352021hwp:resource-id:kidney360;3/9/1578American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360mineral metabolism, basic science, chronic kidney disease, mineral metabolism, nephrocalcinosis, osteopontin, phosphate, solubilityOriginal InvestigationMineral MetabolismOriginal InvestigationMineral Metabolismresearch-article20222022-09-2910.34067/KID.00073520212641-76502022-06-23T06:48:58-07:002022-09-29Kidney360Original Investigation3915781589
- Continuous Long-Term Physical Activity Monitoring in Hemodialysis Patients10.34067/KID.0002082022Wed, 13 Jul 2022 11:26:13 GMT-07:00Continuous Long-Term Physical Activity Monitoring in Hemodialysis PatientsCohen, BrandonMunugoti, SamhithaKotwani, SoniaRandhawa, Lovepreet S.Dalezman, SolomonElters, Antonio C.Nam, KateIbarra, Jose S.Venkataraman, SandheepParedes, WilliamOhri, NitinAbramowitz, Matthew K.2022-07-13T11:26:13-07:00doi:10.34067/KID.0002082022hwp:resource-id:kidney360;3/9/1545American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, accelerometry, chronic renal insufficiency, data visualization, exercise, fatigue, physical activity, physical fitness, renal dialysisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-09-2910.34067/KID.00020820222641-76502022-07-13T11:26:13-07:002022-09-29Kidney360Original Investigation3915451555
- Protein Restriction for CKD: Time to Move On10.34067/KID.0001002022Thu, 23 Jun 2022 06:48:58 GMT-07:00Protein Restriction for CKD: Time to Move OnObeid, WaseemHiremath, SwapnilTopf, Joel M.2022-06-23T06:48:58-07:00doi:10.34067/KID.0001002022hwp:resource-id:kidney360;3/9/1611American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, diet, guidelines, KDOQI, nutrition, proteinPerspectivePerspectiveresearch-article20222022-09-2910.34067/KID.00010020222641-76502022-06-23T06:48:58-07:002022-09-29Kidney360Perspective3916111615
- Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD10.34067/KID.0001442022Wed, 29 Jun 2022 02:43:44 GMT-07:00Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKDPergola, Pablo E.Charytan, ChaimLittle, Dustin J.Tham, StefanSzczech, LyndaLeong, RobertFishbane, Steven2022-06-29T14:43:44-07:00doi:10.34067/KID.0001442022hwp:resource-id:kidney360;3/9/1511American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, anemia, hemoglobin, iron, roxadustatOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-09-2910.34067/KID.00014420222641-76502022-06-29T14:43:44-07:002022-09-29Kidney360Original Investigation3915111528
- Osteopontin Regulates Phosphate Solubility to Prevent Mineral Aggregates in CKD10.34067/KID.0004292022Thu, 29 Sep 2022 07:30:28 GMT-07:00Osteopontin Regulates Phosphate Solubility to Prevent Mineral Aggregates in CKDImig, John D.2022-09-29T07:30:28-07:00doi:10.34067/KID.0004292022hwp:resource-id:kidney360;3/9/1477American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, basic science, mineral aggregates, nanocrystals, nephrocalcinosis, osteopontin, phosphate, solubilityEditorialEditorialeditorial20222022-09-2910.34067/KID.00042920222641-76502022-09-29T07:30:28-07:002022-09-29Kidney360Editorial3914771479
- Dyspnea and Weight Loss following Left Internal Jugular Vein Dialysis Catheter Placement10.34067/KID.0002842022Thu, 29 Sep 2022 07:30:28 GMT-07:00Dyspnea and Weight Loss following Left Internal Jugular Vein Dialysis Catheter PlacementMhlana, NontembisoIsmail, ZaneChothia, Mogamat-Yazied2022-09-29T07:30:28-07:00doi:10.34067/KID.0002842022hwp:resource-id:kidney360;3/9/1654American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, chylothorax, dialysis catheterClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-09-2910.34067/KID.00028420222641-76502022-09-29T07:30:28-07:002022-09-29Kidney360Clinical Images in Nephrology and Dialysis3916541655
- A Practical Guide to Genetic Testing for Kidney Disorders of Unknown EtiologyGenetic testing is increasingly used in the workup and diagnosis of kidney disease and kidney-related disorders of undetermined cause. Out-of-pocket costs for clinical genetic testing have become affordable, and logistical hurdles overcome. The interest in genetic testing may stem from the need to make or confirm a diagnosis, guide management, or the patient’s desire to have a more informed explanation or prognosis. This poses a challenge for providers who do not have formal training in the selection, interpretation, and limitations of genetic tests. In this manuscript, we provide detailed discussion of relevant cases in which clinical genetic testing using a kidney gene panel was applied. The cases demonstrate identification of pathogenic variants for monogenic diseases—contrasting them from genetic risk alleles—and bring up diagnostic limitations and diagnostic utility of these tests in nephrology. This review aims to guide clinicians in formulating pretest conversations with their patients, interpreting genetic variant nomenclature, and considering follow-up investigations. Although providers are gaining experience, there is still risk of testing causing more anxiety than benefit. However, with provider education and support, clinical genetic testing applied to otherwise unexplained kidney-related disorders will increasingly serve as a valuable diagnostic tool with the potential to reshape how we consider and treat many kidney-related diagnoses.10.34067/KID.0007552021Fri, 08 Jul 2022 01:22:03 GMT-07:00A Practical Guide to Genetic Testing for Kidney Disorders of Unknown EtiologyGenetic testing is increasingly used in the workup and diagnosis of kidney disease and kidney-related disorders of undetermined cause. Out-of-pocket costs for clinical genetic testing have become affordable, and logistical hurdles overcome. The interest in genetic testing may stem from the need to make or confirm a diagnosis, guide management, or the patient’s desire to have a more informed explanation or prognosis. This poses a challenge for providers who do not have formal training in the selection, interpretation, and limitations of genetic tests. In this manuscript, we provide detailed discussion of relevant cases in which clinical genetic testing using a kidney gene panel was applied. The cases demonstrate identification of pathogenic variants for monogenic diseases—contrasting them from genetic risk alleles—and bring up diagnostic limitations and diagnostic utility of these tests in nephrology. This review aims to guide clinicians in formulating pretest conversations with their patients, interpreting genetic variant nomenclature, and considering follow-up investigations. Although providers are gaining experience, there is still risk of testing causing more anxiety than benefit. However, with provider education and support, clinical genetic testing applied to otherwise unexplained kidney-related disorders will increasingly serve as a valuable diagnostic tool with the potential to reshape how we consider and treat many kidney-related diagnoses.Aron, Abraham W.Dahl, Neera K.Besse, Whitney2022-07-08T13:22:03-07:00doi:10.34067/KID.0007552021hwp:resource-id:kidney360;3/9/1640American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360genetics, gene panel, genetic testing, genetics, next-generation sequencingReview ArticleReview Articlereview-article20222022-09-2910.34067/KID.00075520212641-76502022-07-08T13:22:03-07:002022-09-29Kidney360Review Article3916401651
- A Post Hoc Analysis of KidneyIntelX and Cardiorenal Outcomes in Diabetic Kidney Disease10.34067/KID.0002172022Thu, 19 May 2022 08:54:56 GMT-07:00A Post Hoc Analysis of KidneyIntelX and Cardiorenal Outcomes in Diabetic Kidney DiseaseNadkarni, Girish N.Takale, DiptiNeal, BruceMahaffey, Kenneth W.Yavin, YshaiHansen, Michael K.Fleming, FergusHeerspink, Hiddo J.L.Coca, Steven G.2022-05-19T08:54:56-07:00doi:10.34067/KID.0002172022hwp:resource-id:kidney360;3/9/1599American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, chronic renal disease, diabetes, diabetes mellitus, diabetic nephropathyBrief CommunicationClinical NephrologyBrief CommunicationClinical Nephrologyresearch-article20222022-09-2910.34067/KID.00021720222641-76502022-05-19T08:54:56-07:002022-09-29Kidney360Brief Communication3915991602
- FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney Disease10.34067/KID.0002192022Tue, 05 Jul 2022 11:41:45 GMT-07:00FGF23 and Cardiovascular Structure and Function in Advanced Chronic Kidney DiseaseHalim, ArvinBurney, Heather N.Li, XiaochunLi, YangTomkins, ClaudiaSiedlecki, Andrew M.Lu, Tzong-shiKalim, SahirThadhani, RaviMoe, SharonTing, Stephen M.S.Zehnder, DanielHiemstra, Thomas F.Lim, Kenneth2022-07-05T11:41:45-07:00doi:10.34067/KID.0002192022hwp:resource-id:kidney360;3/9/1529American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, cardiopulmonary exercise testing (CPET), cardiovascular functional capacity, dialysis, fibroblast growth factor 23 (FGF23), heart failure, kidney transplant, LVMI, VO2MaxOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-09-2910.34067/KID.00021920222641-76502022-07-05T11:41:45-07:002022-09-29Kidney360Original Investigation3915291541
- Global Dialysis Perspective: Sri Lanka10.34067/KID.0001592022Fri, 08 Jul 2022 11:22:33 GMT-07:00Global Dialysis Perspective: Sri LankaWijewickrama, Eranga SanjeewaHerath, Nalaka2022-07-08T11:22:33-07:00doi:10.34067/KID.0001592022hwp:resource-id:kidney360;3/9/1603American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, dialysis, end stage kidney disease, Sri LankaGlobal PerspectiveGlobal Perspectiveresearch-article20222022-09-2910.34067/KID.00015920222641-76502022-07-08T11:22:33-07:002022-09-29Kidney360Global Perspective3916031606
- Development of an Administrative Data-Based Frailty Index for Older Adults Receiving Dialysis10.34067/KID.0000032022Tue, 19 Jul 2022 01:29:42 GMT-07:00Development of an Administrative Data-Based Frailty Index for Older Adults Receiving DialysisHall, Rasheeda K.Morton, SarahWilson, JonathanKim, Dae HyunColón-Emeric, CathleenScialla, Julia J.Platt, AlyssaEphraim, Patti L.Boulware, L. EbonyPendergast, Jane2022-07-19T13:29:42-07:00doi:10.34067/KID.0000032022hwp:resource-id:kidney360;3/9/1566American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360geriatric and palliative nephrology, deficit accumulation index, geriatric nephrology, hospitalization, mortality risk, renal dialysis, United States Renal Data SystemOriginal InvestigationGeriatric and Palliative NephrologyOriginal InvestigationGeriatric and Palliative Nephrologyresearch-article20222022-09-2910.34067/KID.00000320222641-76502022-07-19T13:29:42-07:002022-09-29Kidney360Original Investigation3915661577
- The Next Frontier: Biomarkers and Artificial Intelligence Predicting Cardiorenal Outcomes in Diabetic Kidney Disease10.34067/KID.0003322022Thu, 29 Sep 2022 07:30:28 GMT-07:00The Next Frontier: Biomarkers and Artificial Intelligence Predicting Cardiorenal Outcomes in Diabetic Kidney DiseaseBraden, Gregory L.Landry, Daniel L.2022-09-29T07:30:28-07:00doi:10.34067/KID.0003322022hwp:resource-id:kidney360;3/9/1480American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, artificial intelligence, biomarkers, cardiorenal, diabetic CKDEditorialEditorialeditorial20222022-09-2910.34067/KID.00033220222641-76502022-09-29T07:30:28-07:002022-09-29Kidney360Editorial3914801483
- Urinary Neutrophil Gelatinase–Associated Lipocalin Predicts Intensive Care Unit Admission Diagnosis: A Prospective Cohort Study10.34067/KID.0001492022Wed, 13 Jul 2022 11:26:12 GMT-07:00Urinary Neutrophil Gelatinase–Associated Lipocalin Predicts Intensive Care Unit Admission Diagnosis: A Prospective Cohort StudyKatz-Greenberg, GoniMalinchoc, MichaelBroyles, Dennis L.Oxman, DavidHamrahian, Seyed M.Maarouf, Omar H.2022-07-13T11:26:12-07:00doi:10.34067/KID.0001492022hwp:resource-id:kidney360;3/9/1502American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI, cardiogenic shock, ICU nephrology, injury marker, lipocalin-2, NGAL, sepsis, shock, urine biomarkerOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-09-2910.34067/KID.00014920222641-76502022-07-13T11:26:12-07:002022-09-29Kidney360Original Investigation3915021510
- The Gut and Kidney Crosstalk in Immunoglobulin A NephropathyImmunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.10.34067/KID.0002382022Mon, 27 Jun 2022 12:01:40 GMT-07:00The Gut and Kidney Crosstalk in Immunoglobulin A NephropathyImmunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.Sanchez-Russo, LuisRajasekaran, ArunBin, SofiaFaith, JeremiahCravedi, Paolo2022-06-27T12:01:40-07:00doi:10.34067/KID.0002382022hwp:resource-id:kidney360;3/9/1630American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, gut-associated lymphoid tissue, IgA nephropathy, immunoglobulin A, inflammatory bowel disease, microbiome, Peyer’s patchesReview ArticleReview Articlereview-article20222022-09-2910.34067/KID.00023820222641-76502022-06-27T12:01:40-07:002022-09-29Kidney360Review Article3916301639
- A Machine Learning Model for Predicting Mortality within 90 Days of Dialysis Initiation10.34067/KID.0007012021Wed, 20 Jul 2022 12:46:48 GMT-07:00A Machine Learning Model for Predicting Mortality within 90 Days of Dialysis InitiationRankin, SummerHan, LucyScherzer, RebeccaTenney, SusanKeating, MatthewGenberg, KimberlyRahn, MatthewWilkins, KennethShlipak, MichaelEstrella, Michelle2022-07-20T12:46:48-07:00doi:10.34067/KID.0007012021hwp:resource-id:kidney360;3/9/1556American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, chronic kidney failure, chronic renal failure, dialysis, end stage kidney disease, ESRD, machine learning, mortality, outcomes, prediction modeling, United States Renal Data SystemOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-09-2910.34067/KID.00070120212641-76502022-07-20T12:46:48-07:002022-09-29Kidney360Original Investigation3915561565
- Development of New Equations Predicting the Mortality Risk of Patients on Continuous RRT10.34067/KID.0000862022Tue, 02 Aug 2022 01:02:04 GMT-07:00Development of New Equations Predicting the Mortality Risk of Patients on Continuous RRTKang, Min WooTangri, NavdeepKwon, SoieLi, LilinLee, HyeseungHan, Seung SeokAn, Jung NamLee, JeonghwanKim, Dong KiLim, Chun SooKim, Yon SuKim, SejoongLee, Jung Pyo,2022-08-02T13:02:04-07:00doi:10.34067/KID.0000862022hwp:resource-id:kidney360;3/9/1494American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, CRRT, mortality, predictionOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-09-2910.34067/KID.00008620222641-76502022-08-02T13:02:04-07:002022-09-29Kidney360Original Investigation3914941501
- Global Dialysis Perspective: Nigeria10.34067/KID.0002312022Thu, 14 Jul 2022 10:34:18 GMT-07:00Global Dialysis Perspective: NigeriaOkoye, OgochukwuMamven, Manmak2022-07-14T10:34:18-07:00doi:10.34067/KID.0002312022hwp:resource-id:kidney360;3/9/1607American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, CKD, dialysis, ESKD, hemodialysis, nephrology care, Nigeria, perspectivesGlobal PerspectiveGlobal Perspectiveresearch-article20222022-09-2910.34067/KID.00023120222641-76502022-07-14T10:34:18-07:002022-09-29Kidney360Global Perspective3916071610
- Seeing the Light: Improving Diabetic Retinopathy Outcomes by Bringing Screening to the Dialysis Clinic10.34067/KID.0003752022Thu, 29 Sep 2022 07:30:28 GMT-07:00Seeing the Light: Improving Diabetic Retinopathy Outcomes by Bringing Screening to the Dialysis ClinicKlein, Klara R.Flythe, Jennifer E.2022-09-29T07:30:28-07:00doi:10.34067/KID.0003752022hwp:resource-id:kidney360;3/9/1474American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, diabetes, diabetic retinopathy, dialysis, glycemia, kidney failureEditorialEditorialeditorial20222022-09-2910.34067/KID.00037520222641-76502022-09-29T07:30:28-07:002022-09-29Kidney360Editorial3914741476
- Exercising the FGF23-Cardiac Axis10.34067/KID.0004962022Thu, 29 Sep 2022 07:30:28 GMT-07:00Exercising the FGF23-Cardiac AxisMurray, Susan L.Wolf, Myles2022-09-29T07:30:28-07:00doi:10.34067/KID.0004962022hwp:resource-id:kidney360;3/9/1471American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360mineral metabolism, exercise, fibroblast growth factor 23, heart failure, kidney disease, left ventricular hypertrophyEditorialEditorialeditorial20222022-09-2910.34067/KID.00049620222641-76502022-09-29T07:30:28-07:002022-09-29Kidney360Editorial3914711473
- White Plaques on the Tongue of a Patient with Advanced CKD10.34067/KID.0002682022Thu, 29 Sep 2022 07:30:28 GMT-07:00White Plaques on the Tongue of a Patient with Advanced CKDGomes, Orlando VieiraRodrigues de Oliveira Campos, MaríliaSilva, Gyl Eanes B.2022-09-29T07:30:28-07:00doi:10.34067/KID.0002682022hwp:resource-id:kidney360;3/9/1652American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, renal insufficiency, chronic, stomatitis, uremiaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-09-2910.34067/KID.00026820222641-76502022-09-29T07:30:28-07:002022-09-29Kidney360Clinical Images in Nephrology and Dialysis3916521653
- Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney DamageSalt-sensitive hypertension is a major risk factor for cardiovascular morbidity and mortality. The pathophysiologic mechanisms leading to different individual BP responses to changes in dietary salt remain elusive. Research in the last two decades revealed that the immune system plays a critical role in the development of hypertension and related end organ damage. Moreover, sodium accumulates nonosmotically in human tissue, including the skin and muscle, shifting the dogma on body sodium balance and its regulation. Emerging evidence suggests that high concentrations of extracellular sodium can directly trigger an inflammatory response in antigen-presenting cells (APCs), leading to hypertension and vascular and renal injury. Importantly, sodium entry into APCs is mediated by the epithelial sodium channel (ENaC). Although the role of the ENaC in renal regulation of sodium excretion and BP is well established, these new findings imply that the ENaC may also exert BP modulatory effects in extrarenal tissue through an immune-dependent pathway. In this review, we discuss the recent advances in our understanding of the pathophysiology of salt-sensitive hypertension with a particular focus on the roles of APCs and the extrarenal ENaC.10.34067/KID.0001272022Mon, 27 Jun 2022 12:01:40 GMT-07:00Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney DamageSalt-sensitive hypertension is a major risk factor for cardiovascular morbidity and mortality. The pathophysiologic mechanisms leading to different individual BP responses to changes in dietary salt remain elusive. Research in the last two decades revealed that the immune system plays a critical role in the development of hypertension and related end organ damage. Moreover, sodium accumulates nonosmotically in human tissue, including the skin and muscle, shifting the dogma on body sodium balance and its regulation. Emerging evidence suggests that high concentrations of extracellular sodium can directly trigger an inflammatory response in antigen-presenting cells (APCs), leading to hypertension and vascular and renal injury. Importantly, sodium entry into APCs is mediated by the epithelial sodium channel (ENaC). Although the role of the ENaC in renal regulation of sodium excretion and BP is well established, these new findings imply that the ENaC may also exert BP modulatory effects in extrarenal tissue through an immune-dependent pathway. In this review, we discuss the recent advances in our understanding of the pathophysiology of salt-sensitive hypertension with a particular focus on the roles of APCs and the extrarenal ENaC.Ertuglu, Lale A.Kirabo, Annet2022-06-27T12:01:40-07:00doi:10.34067/KID.0001272022hwp:resource-id:kidney360;3/9/1620American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hypertension, dendritic cell, hypertension, inflammation, isolevuglandins, salt sensitivity, sodiumBasic Science for CliniciansBasic Science for Cliniciansresearch-article20222022-09-2910.34067/KID.00012720222641-76502022-06-27T12:01:40-07:002022-09-29Kidney360Basic Science for Clinicians3916201629
- Post-Traumatic Stress Disorder and Post-Traumatic Growth following Kidney Transplantation10.34067/KID.0008152021Mon, 01 Aug 2022 01:21:41 GMT-07:00Post-Traumatic Stress Disorder and Post-Traumatic Growth following Kidney TransplantationNash, Rebekah P.Loiselle, Marci M.Stahl, Jessica L.Conklin, Jamie L.Rose, Terra L.Hutto, AlissaEvon, Donna M.Flythe, Jennifer E.Burker, Eileen J.2022-08-01T13:21:41-07:00doi:10.34067/KID.0008152021hwp:resource-id:kidney360;3/9/1590American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, benefit finding, kidney transplantation, post-traumatic growth, post-traumatic stress disorder, resilienceOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-09-2910.34067/KID.00081520212641-76502022-08-01T13:21:41-07:002022-09-29Kidney360Original Investigation3915901598
- Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: COMMENTARY10.34067/KID.0008112021Wed, 26 Jan 2022 01:33:56 GMT-08:00Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: COMMENTARYPerazella, Mark A.2022-01-26T13:33:56-08:00doi:10.34067/KID.0008112021hwp:resource-id:kidney360;3/9/1491American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephro-pharmacology, acute interstitial nephritis, acute kidney injury, acute tubular injury, cast nephropathy, nephrotoxicity, vancomycinModerator CommentaryModerator Commentaryarticle-commentary20222022-09-2910.34067/KID.00081120212641-76502022-01-26T13:33:56-08:002022-09-29Kidney360Moderator Commentary3914911493
- Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: PRO10.34067/KID.0008032021Wed, 26 Jan 2022 01:33:56 GMT-08:00Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: PROMurphy, Mark E.Barreto, Erin F.2022-01-26T13:33:56-08:00doi:10.34067/KID.0008032021hwp:resource-id:kidney360;3/9/1484American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, adverse drug reaction, antibiotic, pharmacokinetic/pharmacodynamics, renal failure, toxicity, vancomycinDebates in NephrologyDebates in Nephrologyresearch-article20222022-09-2910.34067/KID.00080320212641-76502022-01-26T13:33:56-08:002022-09-29Kidney360Debates in Nephrology3914841487
- Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: CON10.34067/KID.0007932021Wed, 26 Jan 2022 01:33:56 GMT-08:00Vancomycin Should Be Considered a Nephrotoxic Antimicrobial Agent: CONMullaney, Scott R.2022-01-26T13:33:56-08:00doi:10.34067/KID.0007932021hwp:resource-id:kidney360;3/9/1488American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephro-pharmacology, acute kidney injury, AKI, anti-infective agents, vancomycinDebates in NephrologyDebates in Nephrologyresearch-article20222022-09-2910.34067/KID.00079320212641-76502022-01-26T13:33:56-08:002022-09-29Kidney360Debates in Nephrology3914881490
- Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin MistraffickingBackground: NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in >1-month-old children. Missense NPHS2 variants were reported to cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was based on overexpression in some non-podocyte cell lines. Methods: We generated a series of human induced pluripotent stem cell (iPSC) lines bearing pathogenic missense variants of NPHS2, encoding the protein changes p.G92C, p.P118L, p.R138Q, p.R168H and p.R291W, as well as control lines. iPSC lines were also generated from a patient with steroid-resistant nephrotic syndrome (p.R168H homozygote) and a healthy heterozygous parent. All lines were differentiated into kidney organoids. Immunofluorescence assessed PODOCIN expression and subcellular localization. Podocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated. Results: All variant lines revealed reduced levels of PODOCIN protein in the absence of reduced transcription. While wildtype PODOCIN localized to the membrane, distinct variant proteins displayed unique patterns of subcellular protein trafficking, some unreported. P118L and R138Q were preferentially retained in the endoplasmic reticulum (ER); R168H and R291W accumulated in the Golgi. Podocyte profiling demonstrated minimal diseaseassociated transcriptional change. All variants displayed podocyte-specific apoptosis, which was not linked to ER stress. NEPHRIN-PODOCIN co-localization elucidated the variantspecific impact on NEPHRIN association and hence NEPHRIN trafficking. Conclusion: Specific variants of endogenous NPHS2 result in distinct subcellular PODOCIN localization within organoid podocytes. Understanding the impact of each variant on protein levels and localization and impact on NEPHRIN provides additional insight into the pathobiology of NPHS2 variants.Melissa.Little@mcri.edu.au10.1681/ASN.2022060707Tue, 27 Sep 2022 09:43:06 GMT-07:00Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin MistraffickingBackground: NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in >1-month-old children. Missense NPHS2 variants were reported to cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was based on overexpression in some non-podocyte cell lines. Methods: We generated a series of human induced pluripotent stem cell (iPSC) lines bearing pathogenic missense variants of NPHS2, encoding the protein changes p.G92C, p.P118L, p.R138Q, p.R168H and p.R291W, as well as control lines. iPSC lines were also generated from a patient with steroid-resistant nephrotic syndrome (p.R168H homozygote) and a healthy heterozygous parent. All lines were differentiated into kidney organoids. Immunofluorescence assessed PODOCIN expression and subcellular localization. Podocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated. Results: All variant lines revealed reduced levels of PODOCIN protein in the absence of reduced transcription. While wildtype PODOCIN localized to the membrane, distinct variant proteins displayed unique patterns of subcellular protein trafficking, some unreported. P118L and R138Q were preferentially retained in the endoplasmic reticulum (ER); R168H and R291W accumulated in the Golgi. Podocyte profiling demonstrated minimal diseaseassociated transcriptional change. All variants displayed podocyte-specific apoptosis, which was not linked to ER stress. NEPHRIN-PODOCIN co-localization elucidated the variantspecific impact on NEPHRIN association and hence NEPHRIN trafficking. Conclusion: Specific variants of endogenous NPHS2 result in distinct subcellular PODOCIN localization within organoid podocytes. Understanding the impact of each variant on protein levels and localization and impact on NEPHRIN provides additional insight into the pathobiology of NPHS2 variants.Dorison, AudeGhobrial, IreneGraham, AlisonPeiris, ThanushiForbes, ThomasSee, MichaelDas, MithunSaleem, MoinQuinlan, CatherineLawlor, KynanRamialison, MiranaHowden, SaraLittle, Melissa2022-09-27T09:43:06-07:00doi:10.1681/ASN.2022060707hwp:resource-id:jnephrol;ASN.2022060707v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Basic ResearchOriginal Article - Basic Researchresearch-article202210.1681/ASN.20220607071046-66731533-34502022-09-27T09:43:06-07:00Journal of the American Society of NephrologyOriginal Article - Basic ResearchASN.2022060707
- Induction of Long-lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant RecipientsBackground We recently demonstrated that donor-derived modified immune cells (MICs)—PBMCs that acquire immunosuppressive properties after a brief treatment— induced specific immunosuppression against the allogeneic donor when administered prior to kidney transplantation. We found an up to 68-fold increase in CD19+CD24hiCD38hi transitional B lymphocytes compared with transplanted controls. Methods Ten patients from a phase I clinical trial who had received MIC infusions before kidney transplantation were followed to posttransplant day 1080. Results Patients treated with MICs had a favorable clinical course, showing no donor-specific HLA antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third-party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and 7-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively (P<0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets, and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients, in vitro lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiological role of regulatory B lymphocytes in donor-specific unresponsiveness. Conclusions These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population which, when administered to recipients prior to transplantation, may exert a beneficial effect on kidney transplants.christian.morath@med.uni-heidelberg.de10.1681/ASN.2022020210Thu, 22 Sep 2022 11:18:08 GMT-07:00Induction of Long-lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant RecipientsBackground We recently demonstrated that donor-derived modified immune cells (MICs)—PBMCs that acquire immunosuppressive properties after a brief treatment— induced specific immunosuppression against the allogeneic donor when administered prior to kidney transplantation. We found an up to 68-fold increase in CD19+CD24hiCD38hi transitional B lymphocytes compared with transplanted controls. Methods Ten patients from a phase I clinical trial who had received MIC infusions before kidney transplantation were followed to posttransplant day 1080. Results Patients treated with MICs had a favorable clinical course, showing no donor-specific HLA antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third-party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and 7-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively (P<0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets, and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients, in vitro lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiological role of regulatory B lymphocytes in donor-specific unresponsiveness. Conclusions These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population which, when administered to recipients prior to transplantation, may exert a beneficial effect on kidney transplants.Morath, ChristianSchaier, MatthiasIbrahim, EmanWang, LeiKleist, ChristianOpelz, GerhardSüsal, CanerPonath, GeraldAly, MostafaAlvarez, CristiamKälble, FlorianSpeer, ClaudiusBenning, LouiseNusshag, Christianda Silva, Luiza PegoSommerer, ClaudiaHückelhoven-Krauss, AngelaCzock, DavidMehrabi, ArianebSchwab, ConstantinWaldherr, RüdigerSchnitzler, PaulMerle, UtaTran, Thuong HienScherer, SabineBoehmig, GeorgMüller-Tidow, CarstenReiser, JochenSchmitt, AnitaZeier, MartinSchmitt, MichaelTerness, PeterDaniel, Volker2022-09-22T11:18:08-07:00doi:10.1681/ASN.2022020210hwp:resource-id:jnephrol;ASN.2022020210v1American Society of NephrologyJournal of the American Society of NephrologyOriginal Article - Clinical ResearchOriginal Article - Clinical Researchresearch-article202210.1681/ASN.20220202101046-66731533-34502022-09-22T11:18:08-07:00Journal of the American Society of NephrologyOriginal Article - Clinical ResearchASN.2022020210
- Continuous Glucose Monitoring to Optimize Management of Diabetes in Patients with Advanced CKDTreatment of patients with diabetes and CKD includes optimizing glycemic control using lifestyle modifications and drugs that safely control glycemia and improve clinical kidney and cardiovascular disease outcomes. However, patients with advanced CKD, defined as eGFR <30 ml/min per 1.73 m2 or kidney disease treated with dialysis, have limitations to the use of some preferred glucose-lowering medications, are often treated with insulin, and experience high rates of severe hypoglycemia. Moreover, hemoglobin A1c accuracy decreases as GFR deteriorates. Hence, there is a need for better glycemic monitoring tools. Continuous glucose monitoring allows for 24-hour glycemic monitoring to understand patterns and the effects of lifestyle and medications. Real-time continuous glucose monitoring can be used to guide the administration of insulin and noninsulin therapies. Continuous glucose monitoring can overcome the limitations of self-monitored capillary glucose testing and hemoglobin A1c and has been shown to prevent hypoglycemic excursions in some populations. More data are needed to understand whether similar benefits can be obtained for patients with diabetes and advanced CKD. This review provides an updated approach to management of glycemia in advanced CKD, focusing on the role of continuous glucose monitoring in this high-risk population.10.2215/CJN.04510422Wed, 31 Aug 2022 10:49:50 GMT-07:00Continuous Glucose Monitoring to Optimize Management of Diabetes in Patients with Advanced CKDTreatment of patients with diabetes and CKD includes optimizing glycemic control using lifestyle modifications and drugs that safely control glycemia and improve clinical kidney and cardiovascular disease outcomes. However, patients with advanced CKD, defined as eGFR <30 ml/min per 1.73 m2 or kidney disease treated with dialysis, have limitations to the use of some preferred glucose-lowering medications, are often treated with insulin, and experience high rates of severe hypoglycemia. Moreover, hemoglobin A1c accuracy decreases as GFR deteriorates. Hence, there is a need for better glycemic monitoring tools. Continuous glucose monitoring allows for 24-hour glycemic monitoring to understand patterns and the effects of lifestyle and medications. Real-time continuous glucose monitoring can be used to guide the administration of insulin and noninsulin therapies. Continuous glucose monitoring can overcome the limitations of self-monitored capillary glucose testing and hemoglobin A1c and has been shown to prevent hypoglycemic excursions in some populations. More data are needed to understand whether similar benefits can be obtained for patients with diabetes and advanced CKD. This review provides an updated approach to management of glycemia in advanced CKD, focusing on the role of continuous glucose monitoring in this high-risk population.Galindo, Rodolfo J.de Boer, Ian H.Neumiller, Joshua J.Tuttle, Katherine R.2022-08-31T10:49:50-07:00doi:10.2215/CJN.04510422hwp:resource-id:clinjasn;CJN.04510422v2American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, chronic kidney disease, diabetes, diabetes mellitus, end-stage renal disease, continuous glucose monitoring, CGMInvited FeaturesReviewInvited FeaturesReviewresearch-article202210.2215/CJN.045104221555-90411555-905X2022-08-31T10:49:50-07:00Clinical Journal of the American Society of NephrologyInvited FeaturesCJN.04510422
- Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0002492022 and the CON: 10.34067/KID.0002512022rbrown@bidmc.harvard.edu10.34067/KID.0002502022Tue, 20 Sep 2022 11:25:45 GMT-07:00Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0002492022 and the CON: 10.34067/KID.0002512022Brown, Robert S.2022-09-20T11:25:45-07:00doi:10.34067/KID.0002502022hwp:resource-id:kidney360;KID.0002502022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360FENa, FEUrea, Fractional excretion, Acute kidney injury, AKI, Prerenal, ATN, SodiumModerator CommentaryModerator Commentaryother202210.34067/KID.00025020222641-76502641-76502022-09-20T11:25:45-07:00Kidney360Moderator Commentary10.34067/KID.0002502022
- Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0002492022 and the COMMENTARY: 10.34067/KID.0002502022awaron@stanford.edu10.34067/KID.0002512022Tue, 20 Sep 2022 11:25:45 GMT-07:00Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0002492022 and the COMMENTARY: 10.34067/KID.0002502022Aron, Abraham WAmatruda, Jonathan G2022-09-20T11:25:45-07:00doi:10.34067/KID.0002512022hwp:resource-id:kidney360;KID.0002512022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Urine electrolytes, FENa, FEUrea, AKIDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00025120222641-76502641-76502022-09-20T11:25:45-07:00Kidney360Debates in Nephrology10.34067/KID.0002512022
- Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0002512022 and the COMMENTARY: 10.34067/KID.0002502022.kamelgharaibeh@gmail.com10.34067/KID.0002492022Tue, 20 Sep 2022 11:25:45 GMT-07:00Fractional Excretion of Sodium and Urea are Useful Tools in the Evaluation of AKI: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0002512022 and the COMMENTARY: 10.34067/KID.0002502022.Hamadah, AbdurrahmanGharaibeh, Kamel2022-09-20T11:25:45-07:00doi:10.34067/KID.0002492022hwp:resource-id:kidney360;KID.0002492022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Acute Kidney Injury, Urea, SodiumDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00024920222641-76502641-76502022-09-20T11:25:45-07:00Kidney360Debates in Nephrology10.34067/KID.0002492022
- Metabolomic Profiling Identifies New Endogenous Markers of Tubular Secretory ClearanceBACKGROUND: The proximal tubules eliminate protein-bound toxins and drugs via secretion. Measurements or estimates of glomerular filtration rate do not necessarily reflect the physiologically distinct process of secretion. Clinical assessment of this important intrinsic kidney function requires endogenous markers that are highly specific for secretory transport. METHODS: We used metabolomics profiling to identify candidate markers of tubular secretory clearance in 50 participants from a kidney pharmacokinetics study. We measured metabolites in three sequential plasma samples and a concurrent 10-hour timed urine sample using hydrophilic interaction liquid chromatography-high resolution mass spectrometry. We quantified the association between estimated kidney clearance and normalized plasma peak height of each candidate solute to the clearance of administered furosemide, a protein-bound, avidly secreted medication. RESULTS: We identified 528 metabolites present in plasma and urine, excluding pharmaceuticals. We found 7 highly (>50%) protein bound and 49 poorly bound solutes with clearances significantly associated with furosemide clearance, and 18 solute clearances favoring an association with furosemide clearance by the 90th percentile when compared to GFR. We also found 4 highly bound and 42 poorly bound plasma levels that were significantly associated with furosemide clearance. CONCLUSIONS: We found several candidate metabolites whose kidney clearances or relative plasma levels are highly associated with furosemide clearance, an avidly secreted tracer medication of the organic anion transporters, highlighting their potential as endogenous markers of proximal tubular secretory clearance.mlgranda@uw.edu10.34067/KID.0004172022Tue, 20 Sep 2022 07:33:25 GMT-07:00Metabolomic Profiling Identifies New Endogenous Markers of Tubular Secretory ClearanceBACKGROUND: The proximal tubules eliminate protein-bound toxins and drugs via secretion. Measurements or estimates of glomerular filtration rate do not necessarily reflect the physiologically distinct process of secretion. Clinical assessment of this important intrinsic kidney function requires endogenous markers that are highly specific for secretory transport. METHODS: We used metabolomics profiling to identify candidate markers of tubular secretory clearance in 50 participants from a kidney pharmacokinetics study. We measured metabolites in three sequential plasma samples and a concurrent 10-hour timed urine sample using hydrophilic interaction liquid chromatography-high resolution mass spectrometry. We quantified the association between estimated kidney clearance and normalized plasma peak height of each candidate solute to the clearance of administered furosemide, a protein-bound, avidly secreted medication. RESULTS: We identified 528 metabolites present in plasma and urine, excluding pharmaceuticals. We found 7 highly (>50%) protein bound and 49 poorly bound solutes with clearances significantly associated with furosemide clearance, and 18 solute clearances favoring an association with furosemide clearance by the 90th percentile when compared to GFR. We also found 4 highly bound and 42 poorly bound plasma levels that were significantly associated with furosemide clearance. CONCLUSIONS: We found several candidate metabolites whose kidney clearances or relative plasma levels are highly associated with furosemide clearance, an avidly secreted tracer medication of the organic anion transporters, highlighting their potential as endogenous markers of proximal tubular secretory clearance.Granda, Michael L.Prince, David K.Fiehn, OliverChen, YanRajabi, TanyaYeung, Catherine K.Hoofnagle, Andrew N.Kestenbaum, Bryan2022-09-20T07:33:25-07:00doi:10.34067/KID.0004172022hwp:resource-id:kidney360;KID.0004172022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360secretory clearance, uremia, renal proximal tubule cell, kidney function, diuretics, proximal tubule, metabolomics, secretion, tubular secretionOriginal InvestigationOriginal Investigationother202210.34067/KID.00041720222641-76502641-76502022-09-20T07:33:25-07:00Kidney360Original Investigation10.34067/KID.0004172022
- Acid-Base Disorders in the Critically Ill PatientAcid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed disturbances. These disorders are divided into four major categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Metabolic acidosis is subdivided into anion gap and non–gap acidosis. Distinguishing between these is helpful in establishing the cause of the acidosis. Anion gap acidosis, caused by the accumulation of organic anions from sepsis, diabetes, alcohol use, and numerous drugs and toxins, is usually present on admission to the intensive care unit. Lactic acidosis from decreased delivery or utilization of oxygen is associated with increased mortality. This is likely secondary to the disease process, as opposed to the degree of acidemia. Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin. The use of therapy to normalize the pH is controversial. Non–gap acidoses result from disorders of renal tubular H+ transport, decreased renal ammonia secretion, gastrointestinal and kidney losses of bicarbonate, dilution of serum bicarbonate from excessive intravenous fluid administration, or addition of hydrochloric acid. Metabolic alkalosis is the most common acid-base disorder found in patients who are critically ill, and most often occurs after admission to the intensive care unit. Its etiology is most often secondary to the aggressive therapeutic interventions used to treat shock, acidemia, volume overload, severe coagulopathy, respiratory failure, and AKI. Treatment consists of volume resuscitation and repletion of potassium deficits. Aggressive lowering of the pH is usually not necessary. Respiratory disorders are caused by either decreased or increased minute ventilation. The use of permissive hypercapnia to prevent barotrauma has become the standard of care. The use of bicarbonate to correct the acidemia is not recommended. In patients at the extreme, the use of extracorporeal therapies to remove CO2 can be considered.10.2215/CJN.04500422Tue, 23 Aug 2022 07:06:40 GMT-07:00Acid-Base Disorders in the Critically Ill PatientAcid-base disorders are common in the intensive care unit. By utilizing a systematic approach to their diagnosis, it is easy to identify both simple and mixed disturbances. These disorders are divided into four major categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Metabolic acidosis is subdivided into anion gap and non–gap acidosis. Distinguishing between these is helpful in establishing the cause of the acidosis. Anion gap acidosis, caused by the accumulation of organic anions from sepsis, diabetes, alcohol use, and numerous drugs and toxins, is usually present on admission to the intensive care unit. Lactic acidosis from decreased delivery or utilization of oxygen is associated with increased mortality. This is likely secondary to the disease process, as opposed to the degree of acidemia. Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin. The use of therapy to normalize the pH is controversial. Non–gap acidoses result from disorders of renal tubular H+ transport, decreased renal ammonia secretion, gastrointestinal and kidney losses of bicarbonate, dilution of serum bicarbonate from excessive intravenous fluid administration, or addition of hydrochloric acid. Metabolic alkalosis is the most common acid-base disorder found in patients who are critically ill, and most often occurs after admission to the intensive care unit. Its etiology is most often secondary to the aggressive therapeutic interventions used to treat shock, acidemia, volume overload, severe coagulopathy, respiratory failure, and AKI. Treatment consists of volume resuscitation and repletion of potassium deficits. Aggressive lowering of the pH is usually not necessary. Respiratory disorders are caused by either decreased or increased minute ventilation. The use of permissive hypercapnia to prevent barotrauma has become the standard of care. The use of bicarbonate to correct the acidemia is not recommended. In patients at the extreme, the use of extracorporeal therapies to remove CO2 can be considered.Achanti, AnandSzerlip, Harold M.2022-08-23T07:06:40-07:00doi:10.2215/CJN.04500422hwp:resource-id:clinjasn;CJN.04500422v3American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacid-base, critical illness, metabolic acidosis, metabolic alkalosis, anion gap, lactic acidosis, ketoacidosisCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article202210.2215/CJN.045004221555-90411555-905X2022-08-23T07:06:40-07:00Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney InjuryCJN.04500422
- Indications for and Timing of Initiation of KRTKRT is considered for patients with severe AKI and associated complications. The exact indications for initiating KRT have been debated for decades. There is a general consensus that KRT should be considered in patients with AKI and medically refractory complications (“urgent indications”). “Relative indications” are more common but defined with less precision. In this review, we summarize the latest evidence from recent landmark clinical trials, discuss strategies to anticipate the need for KRT in individual patients, and propose an algorithm for decision making. We emphasize that the decision to consider KRT should be made in conjunction with other forms of organ support therapies and important nonkidney factors, including the patient’s preferences and overall goals of care. We also suggest future research to differentiate patients who benefit from timely initiation of KRT from those with imminent recovery of kidney function. Until then, efforts are needed to optimize the initiation and delivery of KRT in routine clinical practice, to minimize nonessential variation, and to ensure that patients with persistent AKI or progressive organ failure affected by AKI receive KRT in a timely manner.10.2215/CJN.05450522Tue, 13 Sep 2022 05:36:59 GMT-07:00Indications for and Timing of Initiation of KRTKRT is considered for patients with severe AKI and associated complications. The exact indications for initiating KRT have been debated for decades. There is a general consensus that KRT should be considered in patients with AKI and medically refractory complications (“urgent indications”). “Relative indications” are more common but defined with less precision. In this review, we summarize the latest evidence from recent landmark clinical trials, discuss strategies to anticipate the need for KRT in individual patients, and propose an algorithm for decision making. We emphasize that the decision to consider KRT should be made in conjunction with other forms of organ support therapies and important nonkidney factors, including the patient’s preferences and overall goals of care. We also suggest future research to differentiate patients who benefit from timely initiation of KRT from those with imminent recovery of kidney function. Until then, efforts are needed to optimize the initiation and delivery of KRT in routine clinical practice, to minimize nonessential variation, and to ensure that patients with persistent AKI or progressive organ failure affected by AKI receive KRT in a timely manner.Ostermann, MarliesBagshaw, Sean M.Lumlertgul, NutthaWald, Ron2022-09-13T05:36:59-07:00doi:10.2215/CJN.05450522hwp:resource-id:clinjasn;CJN.05450522v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury Series, acute kidney injury, renal replacement therapy, critical care nephrology, CRRT, CKRTCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article202210.2215/CJN.054505221555-90411555-905X2022-09-13T05:36:59-07:00Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney InjuryCJN.05450522
- Urinary sediment microscopy and correlations with kidney biopsy: red flags not to be missedBackground: Urinary sediment is a non-invasive laboratory test that can be performed by an automated analyzer, or manually by trained personnel. Manual examination remains the diagnostic standard because it excels at differentiating isomorphic from dysmorphic red blood cells, and identifying other urinary particles such as renal tubular epithelial cells (RTECs), lipids, crystals, and the composition of casts. This study aimed to investigate the prevalence of a complete profile of urinary sediment particles and its associations with histological lesions on kidney biopsy, regardless of diagnosis. Methods: Single center, observational retrospective study of 131 patients who had contemporary manual urinary sediment evaluation and kidney biopsy. A comprehensive set of urinary particles and histological lesions were quantified, and their associations were analyzed. Results: In our samples, we found an elevated frequency of findings suggestive of proliferative kidney disease, and a low frequency of particles evoking urological damage. The association of histological lesions and urinary particles was explored with a multivariate model. We identified urinary sediment characteristics that independently correlated with the presence of some histological lesions: urinary lipids with mesangial expansion [OR 2.86 (1.30-6.30)], mesangial hypercellularity [OR 2.44 (1.06-5.58)], and wire loops and/or hyaline deposits [OR 2.89 (1.13-7.73)], and urinary renal tubular epithelial cells with endocapillary hypercellularity [OR 3.17 (1.36-7.39)], neutrophils and/or karyorrhexis [OR 4.51 (1.61-12.61)], fibrinoid necrosis [OR 4.35 (1.48-12.74)], cellular/fibrocellular crescents [OR 5.27 (1.95-14.26)] and acute tubular necrosis [OR 2.31 (1.08-4.97)]. Conclusion: In a population of patients submitted to kidney biopsy, we found that the presence of some urinary particles (renal tubular epithelial cells, lipids, and dysmorphic erythrocytes), which are seldom reported by automated analyzers, is associated with active proliferative histological lesions. In this regard, manual urinary sediment evaluation may help to shape the indications for performing a kidney biopsy.davidbnavarro@gmail.com10.34067/KID.0003082022Mon, 12 Sep 2022 11:24:13 GMT-07:00Urinary sediment microscopy and correlations with kidney biopsy: red flags not to be missedBackground: Urinary sediment is a non-invasive laboratory test that can be performed by an automated analyzer, or manually by trained personnel. Manual examination remains the diagnostic standard because it excels at differentiating isomorphic from dysmorphic red blood cells, and identifying other urinary particles such as renal tubular epithelial cells (RTECs), lipids, crystals, and the composition of casts. This study aimed to investigate the prevalence of a complete profile of urinary sediment particles and its associations with histological lesions on kidney biopsy, regardless of diagnosis. Methods: Single center, observational retrospective study of 131 patients who had contemporary manual urinary sediment evaluation and kidney biopsy. A comprehensive set of urinary particles and histological lesions were quantified, and their associations were analyzed. Results: In our samples, we found an elevated frequency of findings suggestive of proliferative kidney disease, and a low frequency of particles evoking urological damage. The association of histological lesions and urinary particles was explored with a multivariate model. We identified urinary sediment characteristics that independently correlated with the presence of some histological lesions: urinary lipids with mesangial expansion [OR 2.86 (1.30-6.30)], mesangial hypercellularity [OR 2.44 (1.06-5.58)], and wire loops and/or hyaline deposits [OR 2.89 (1.13-7.73)], and urinary renal tubular epithelial cells with endocapillary hypercellularity [OR 3.17 (1.36-7.39)], neutrophils and/or karyorrhexis [OR 4.51 (1.61-12.61)], fibrinoid necrosis [OR 4.35 (1.48-12.74)], cellular/fibrocellular crescents [OR 5.27 (1.95-14.26)] and acute tubular necrosis [OR 2.31 (1.08-4.97)]. Conclusion: In a population of patients submitted to kidney biopsy, we found that the presence of some urinary particles (renal tubular epithelial cells, lipids, and dysmorphic erythrocytes), which are seldom reported by automated analyzers, is associated with active proliferative histological lesions. In this regard, manual urinary sediment evaluation may help to shape the indications for performing a kidney biopsy.Navarro, DavidMoreira Fonseca, NunoFerreira, Ana CarinaBarata, RuiGóis, MárioSousa, HelenaNolasco, Fernando2022-09-12T11:24:13-07:00doi:10.34067/KID.0003082022hwp:resource-id:kidney360;KID.0003082022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Microscopy, proteinuria, lipids, renal tubular epithelial cells, kidney biopsy, Urinary sediment, kidney disease, hematuria, lipiduria, leukocyturiaOriginal InvestigationOriginal Investigationother202210.34067/KID.00030820222641-76502641-76502022-09-12T11:24:13-07:00Kidney360Original Investigation10.34067/KID.0003082022
- Global Perspectives in Acute Kidney Injury: EcuadorThis is an Early Access article. Please select the PDF button, above, to view it.dxjimenezmd@gmail.com10.34067/KID.0001262022Thu, 08 Sep 2022 01:21:41 GMT-07:00Global Perspectives in Acute Kidney Injury: EcuadorThis is an Early Access article. Please select the PDF button, above, to view it.Jiménez, DaríoJiménez, Jazmín2022-09-08T13:21:41-07:00doi:10.34067/KID.0001262022hwp:resource-id:kidney360;KID.0001262022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360AKI, Perspectives, Ecuador, Critically ill patientsGlobal PerspectivesGlobal Perspectivesother202210.34067/KID.00012620222641-76502641-76502022-09-08T13:21:41-07:00Kidney360Global Perspectives3312122136213610.34067/KID.000126202221392139
- The Importance of Transplant Nephrology to a Successful Kidney Transplant Program10.2215/CJN.02000222Mon, 01 Aug 2022 06:15:53 GMT-07:00The Importance of Transplant Nephrology to a Successful Kidney Transplant ProgramMoe, Sharon M.Brennan, Daniel C.Doshi, Mona D.Gaston, Robert S.Gurley, Susan B.Mujtaba, Muhammad A.Schmidt, Rebecca J.Segal, Mark S.Tucker, J. KevinWiseman, Alexander C.Josephson, Michelle A.2022-08-01T06:15:53-07:00doi:10.2215/CJN.02000222hwp:resource-id:clinjasn;17/9/1403American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, clinical nephrology, transplant nephrectomy, transplantation, end-stage renal disease, kidney transplantation, nephrectomy, organ transplant, end-stage kidney diseasePerspectivePerspectiveresearch-article20222022-09-01September 202210.2215/CJN.020002221555-90411555-905X2022-08-01T06:15:53-07:002022-09Clinical Journal of the American Society of NephrologyPerspective17999914031272137214071406127413811409
- Survey of Salary and Job Satisfaction of Transplant Nephrologists in the United States10.2215/CJN.03490322Mon, 01 Aug 2022 06:15:52 GMT-07:00Survey of Salary and Job Satisfaction of Transplant Nephrologists in the United StatesSingh, NeerajDoshi, Mona D.Schold, Jesse D.Preczewski, LukeKlein, ChristinaAkalin, EnverLeca, NicolaeNicoll, KimberlyPesavento, ToddDadhania, Darshana M.Friedewald, JohnSamaniego-Picota, MilagrosBloom, Roy D.Wiseman, Alexander C.2022-08-01T06:15:52-07:00doi:10.2215/CJN.03490322hwp:resource-id:clinjasn;17/9/1372American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, epidemiology and outcomes, lipidsOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-09-01September 202210.2215/CJN.034903221555-90411555-905X2022-08-01T06:15:52-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17999913721272140314071381127414061409
- Extracellular Vesicles as Theranostic Tools in Kidney DiseaseExtracellular vesicles are important vectors for cell-cell communication and show potential value for diagnosis and treatment of kidney diseases. The pathologic diagnosis of kidney diseases relies on kidney biopsy, whereas collection of extracellular vesicles from urine or circulating blood may constitute a less invasive diagnostic tool. In particular, urinary extracellular vesicles released mainly from resident kidney cells might provide an alternative tool for detection of kidney injury. Because extracellular vesicles mirror many features of their parent cells, cargoes of several populations of urinary extracellular vesicles are promising biomarkers for disease processes, like diabetic kidney disease, kidney transplant, and lupus nephritis. Contrarily, extracellular vesicles derived from reparative cells, such as mesenchymal stem cells, tubular epithelial progenitor cells, and human umbilical cord blood represent promising regenerative tools for treatment of kidney diseases. Furthermore, induced pluripotent stem cells–derived and engineered extracellular vesicles are being developed for specific applications for the kidney. Nevertheless, some assumptions regarding the specificity and immunogenicity of extracellular vesicles remain to be established. This review focuses on the utility of extracellular vesicles as therapeutic and diagnostic (theranostic) tools in kidney diseases and future directions for studies.10.2215/CJN.16751221Tue, 08 Mar 2022 09:14:49 GMT-08:00Extracellular Vesicles as Theranostic Tools in Kidney DiseaseExtracellular vesicles are important vectors for cell-cell communication and show potential value for diagnosis and treatment of kidney diseases. The pathologic diagnosis of kidney diseases relies on kidney biopsy, whereas collection of extracellular vesicles from urine or circulating blood may constitute a less invasive diagnostic tool. In particular, urinary extracellular vesicles released mainly from resident kidney cells might provide an alternative tool for detection of kidney injury. Because extracellular vesicles mirror many features of their parent cells, cargoes of several populations of urinary extracellular vesicles are promising biomarkers for disease processes, like diabetic kidney disease, kidney transplant, and lupus nephritis. Contrarily, extracellular vesicles derived from reparative cells, such as mesenchymal stem cells, tubular epithelial progenitor cells, and human umbilical cord blood represent promising regenerative tools for treatment of kidney diseases. Furthermore, induced pluripotent stem cells–derived and engineered extracellular vesicles are being developed for specific applications for the kidney. Nevertheless, some assumptions regarding the specificity and immunogenicity of extracellular vesicles remain to be established. This review focuses on the utility of extracellular vesicles as therapeutic and diagnostic (theranostic) tools in kidney diseases and future directions for studies.Huang, WeijunZhu, Xiang-YangLerman, AmirLerman, Lilach O.2022-03-08T09:14:49-08:00doi:10.2215/CJN.16751221hwp:resource-id:clinjasn;17/9/1418American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiagnosis, extracellular vesicles, kidney diseasesReviewReviewreview-article20222022-09-01September 202210.2215/CJN.167512211555-90411555-905X2022-03-08T09:14:49-08:002022-09Clinical Journal of the American Society of NephrologyReview17914181429
- Choosing the Right Treatment in Patients with Lupus Nephritis10.2215/CJN.04120422Fri, 29 Jul 2022 05:37:25 GMT-07:00Choosing the Right Treatment in Patients with Lupus NephritisMejia Vilet, Juan ManuelLiu, Zhi-HongChan, Tak Mao2022-07-29T05:37:25-07:00doi:10.2215/CJN.04120422hwp:resource-id:clinjasn;17/9/1399American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, systemic lupus erythematosus, acute kidney injury, chronic kidney diseaseKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-09-01September 202210.2215/CJN.041204221555-90411555-905X2022-07-29T05:37:25-07:002022-09Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat17913991402
- Implications of Accumulated Cold Time for US Kidney Transplantation Offer Acceptance10.2215/CJN.01600222Fri, 22 Jul 2022 08:54:11 GMT-07:00Implications of Accumulated Cold Time for US Kidney Transplantation Offer AcceptanceBarah, MasoudKilambi, VikramFriedewald, John J.Mehrotra, Sanjay2022-07-22T08:54:11-07:00doi:10.2215/CJN.01600222hwp:resource-id:clinjasn;17/9/1353American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, kidney transplantation, transplantation, ischemiaOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-09-01September 202210.2215/CJN.016002221555-90411555-905X2022-07-22T08:54:11-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17913531362
- Chronic Kidney Disease and Severe Mental IllnessIndividuals with severe mental illness, including conditions such as schizophrenia and bipolar disorder, are at a higher risk of developing CKD. Higher incidences of CKD in this population can be partially explained by known risk factors, such as the use of lithium treatment and higher rates of cardiovascular disease. However, this does not fully explain the higher proportion of CKD in individuals with severe mental illness, and further research investigating the factors influencing disease onset and progression is needed. Similarly, although it is well documented that mental health difficulties, such as depression and anxiety, are highly prevalent among individuals with CKD, there is a lack of published data regarding the rates of severe mental illness in individuals with CKD. Furthermore, for individuals with CKD, having severe mental illness is associated with poor health outcomes, including higher mortality rates and higher rates of hospitalizations. Evidence also suggests that individuals with severe mental illness receive suboptimal kidney care, have fewer appointments with nephrologists, and are less likely to receive a kidney transplant. Limited research suggests that care might be improved through educating kidney health care staff regarding the needs of patients with severe mental illness and by facilitating closer collaboration with psychiatry. Further research investigating the rates of severe mental illness in patients with CKD, as well as the barriers and facilitators to effective care for this population, is clearly required to inform the provision of appropriate supports and to improve health outcomes for individuals with CKD and co-occurring severe mental illness.10.2215/CJN.15691221Thu, 31 Mar 2022 06:26:06 GMT-07:00Chronic Kidney Disease and Severe Mental IllnessIndividuals with severe mental illness, including conditions such as schizophrenia and bipolar disorder, are at a higher risk of developing CKD. Higher incidences of CKD in this population can be partially explained by known risk factors, such as the use of lithium treatment and higher rates of cardiovascular disease. However, this does not fully explain the higher proportion of CKD in individuals with severe mental illness, and further research investigating the factors influencing disease onset and progression is needed. Similarly, although it is well documented that mental health difficulties, such as depression and anxiety, are highly prevalent among individuals with CKD, there is a lack of published data regarding the rates of severe mental illness in individuals with CKD. Furthermore, for individuals with CKD, having severe mental illness is associated with poor health outcomes, including higher mortality rates and higher rates of hospitalizations. Evidence also suggests that individuals with severe mental illness receive suboptimal kidney care, have fewer appointments with nephrologists, and are less likely to receive a kidney transplant. Limited research suggests that care might be improved through educating kidney health care staff regarding the needs of patients with severe mental illness and by facilitating closer collaboration with psychiatry. Further research investigating the rates of severe mental illness in patients with CKD, as well as the barriers and facilitators to effective care for this population, is clearly required to inform the provision of appropriate supports and to improve health outcomes for individuals with CKD and co-occurring severe mental illness.Cogley, ClodaghCarswell, ClaireBramham, KateChilcot, Joseph2022-03-31T06:26:06-07:00doi:10.2215/CJN.15691221hwp:resource-id:clinjasn;17/9/1413American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, depression, disparityReviewReviewreview-article20222022-09-01September 202210.2215/CJN.156912211555-90411555-905X2022-03-31T06:26:06-07:002022-09Clinical Journal of the American Society of NephrologyReview17914131417
- Music for Health10.2215/CJN.04320422Wed, 15 Jun 2022 10:07:23 GMT-07:00Music for HealthNobakht, NiloofarKamgar, MohammadBilder, Robert M.Nobakht, Ehsan2022-06-15T10:07:23-07:00doi:10.2215/CJN.04320422hwp:resource-id:clinjasn;17/9/1410American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymusic, depression, chronic kidney disease, quality of lifePerspectivePerspectiveresearch-article20222022-09-01September 202210.2215/CJN.043204221555-90411555-905X2022-06-15T10:07:23-07:002022-09Clinical Journal of the American Society of NephrologyPerspective17914101412
- Patient Preferences for Waiting Time and Kidney Quality10.2215/CJN.01480222Fri, 19 Aug 2022 06:15:27 GMT-07:00Patient Preferences for Waiting Time and Kidney QualityMehrotra, SanjayGonzalez, Juan MarcosSchantz, KarolinaYang, Jui-ChenFriedewald, John J.Knight, Richard2022-08-19T06:15:27-07:00doi:10.2215/CJN.01480222hwp:resource-id:clinjasn;17/9/1363American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, transplant outcomes, waiting lists, patient preferenceOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-09-01September 202210.2215/CJN.014802221555-90411555-905X2022-08-19T06:15:27-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17999136312671278137112681280
- Acute Kidney Injury in Critically Ill Patients with CancerAdvances in cancer therapy have significantly improved overall patient survival; however, AKI remains a common complication in patients with cancer, occurring in anywhere from 11% to 22% of patients, depending on patient-related or cancer-specific factors. Critically ill patients with cancer as well as patients with certain malignancies (e.g., leukemias, lymphomas, multiple myeloma, and renal cell carcinoma) are at highest risk of developing AKI. AKI may be a consequence of the underlying malignancy itself or from the wide array of therapies used to treat it. Cancer-associated AKI can affect virtually every compartment of the nephron and can present as subclinical AKI or as overt acute tubular injury, tubulointerstitial nephritis, or thrombotic microangiopathy, among others. AKI can have major repercussions for patients with cancer, potentially jeopardizing further eligibility for therapy and leading to greater morbidity and mortality. This review highlights the epidemiology of AKI in critically ill patients with cancer, risk factors for AKI, and common pathologies associated with certain cancer therapies, as well as the management of AKI in different clinical scenarios. It highlights gaps in our knowledge of AKI in patients with cancer, including the lack of validated biomarkers, as well as evidence-based therapies to prevent AKI and its deleterious consequences.10.2215/CJN.15681221Fri, 25 Mar 2022 07:54:20 GMT-07:00Acute Kidney Injury in Critically Ill Patients with CancerAdvances in cancer therapy have significantly improved overall patient survival; however, AKI remains a common complication in patients with cancer, occurring in anywhere from 11% to 22% of patients, depending on patient-related or cancer-specific factors. Critically ill patients with cancer as well as patients with certain malignancies (e.g., leukemias, lymphomas, multiple myeloma, and renal cell carcinoma) are at highest risk of developing AKI. AKI may be a consequence of the underlying malignancy itself or from the wide array of therapies used to treat it. Cancer-associated AKI can affect virtually every compartment of the nephron and can present as subclinical AKI or as overt acute tubular injury, tubulointerstitial nephritis, or thrombotic microangiopathy, among others. AKI can have major repercussions for patients with cancer, potentially jeopardizing further eligibility for therapy and leading to greater morbidity and mortality. This review highlights the epidemiology of AKI in critically ill patients with cancer, risk factors for AKI, and common pathologies associated with certain cancer therapies, as well as the management of AKI in different clinical scenarios. It highlights gaps in our knowledge of AKI in patients with cancer, including the lack of validated biomarkers, as well as evidence-based therapies to prevent AKI and its deleterious consequences.Gupta, ShrutiGudsoorkar, PrakashJhaveri, Kenar D.2022-03-25T07:54:20-07:00doi:10.2215/CJN.15681221hwp:resource-id:clinjasn;17/9/1385American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, onconephrology, cancer, AKI, drug nephrotoxicity, acute kidney injuryCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-09-01September 202210.2215/CJN.156812211555-90411555-905X2022-03-25T07:54:20-07:002022-09Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury17913851398
- Existing Transplant Nephrology Compensation Models and Opportunities for Equitable Pay10.2215/CJN.02010222Mon, 01 Aug 2022 06:15:52 GMT-07:00Existing Transplant Nephrology Compensation Models and Opportunities for Equitable PayJosephson, Michelle A.Wiseman, Alexander C.Tucker, J. KevinSegal, Mark S.Schmidt, Rebecca J.Mujtaba, Muhammad A.Gurley, Susan B.Gaston, Robert S.Doshi, Mona D.Brennan, Daniel C.Moe, Sharon M.2022-08-01T06:15:52-07:00doi:10.2215/CJN.02010222hwp:resource-id:clinjasn;17/9/1407American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, clinical nephrology, transplant nephrectomy, transplantation, end stage kidney disease, end-stage renal disease, kidney transplantation, nephrectomy, compensation, qualityPerspectivePerspectiveresearch-article20222022-09-01September 202210.2215/CJN.020102221555-90411555-905X2022-08-01T06:15:52-07:002022-09Clinical Journal of the American Society of NephrologyPerspective17999914071272137214031409127413811406
- Central Venous Catheter Malfunction in Children10.2215/CJN.01470222Mon, 11 Jul 2022 05:42:06 GMT-07:00Central Venous Catheter Malfunction in ChildrenBruno, ClaudiaMoumneh, RayanSauvage, EmilieStronach, LynseyWaters, KathrynSimcock, IanArthurs, OwenSchievano, SilviaCapelli, ClaudioShroff, Rukshana2022-07-11T05:42:06-07:00doi:10.2215/CJN.01470222hwp:resource-id:clinjasn;17/9/1382American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, pediatric nephrology, pediatric catheters performance, catheter design, computational fluid dynamics, dialysis access, hemodialysis access, bioengineeringResearch LetterResearch Letterletter20222022-09-01September 202210.2215/CJN.014702221555-90411555-905X2022-07-11T05:42:06-07:002022-09Clinical Journal of the American Society of NephrologyResearch Letter17913821384
- Unraveling the Mysteries of CKD of Uncertain Etiology10.2215/CJN.08430722Tue, 09 Aug 2022 05:56:25 GMT-07:00Unraveling the Mysteries of CKD of Uncertain EtiologyGarcia, PabloAnand, Shuchi2022-08-09T05:56:25-07:00doi:10.2215/CJN.08430722hwp:resource-id:clinjasn;17/9/1269American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKDuEditorialEditorialeditorial20222022-09-01September 202210.2215/CJN.084307221555-90411555-905X2022-08-09T05:56:25-07:002022-09Clinical Journal of the American Society of NephrologyEditorial17991269129312711304
- Mitigating Pain in People Undergoing Hemodialysis10.2215/CJN.08690722Wed, 24 Aug 2022 05:52:34 GMT-07:00Mitigating Pain in People Undergoing HemodialysisDavison, Sara N.2022-08-24T05:52:34-07:00doi:10.2215/CJN.08690722hwp:resource-id:clinjasn;17/9/1275American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, hemodialysis access, pain, music therapyEditorialEditorialeditorial20222022-09-01September 202210.2215/CJN.086907221555-90411555-905X2022-08-24T05:52:34-07:002022-09Clinical Journal of the American Society of NephrologyEditorial17991275133712771345
- Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis Patients10.2215/CJN.00550122Tue, 02 Aug 2022 06:41:53 GMT-07:00Three Times Weekly Dosing of Daprodustat versus Conventional Epoetin for Treatment of Anemia in Hemodialysis PatientsCoyne, Daniel W.Singh, Ajay K.Lopes, Renato D.Bailey, Christine K.DiMino, Tara L.Huang, ChunConnaire, JeffreyRastogi, AnjayKim, Sung-GyunOrias, MarceloShah, SapnaPatel, VickasCobitz, Alexander R.Wanner, Christoph2022-08-02T06:41:53-07:00doi:10.2215/CJN.00550122hwp:resource-id:clinjasn;17/9/1325American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, hemoglobin, erythropoietin, anemia, clinical trial, blood pressure, epoetin, randomized controlled trials, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), chronic kidney diseaseOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-09-01September 202210.2215/CJN.005501221555-90411555-905X2022-08-02T06:41:53-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17913251336
- Getting a Kidney: Where Is Patient Choice?10.2215/CJN.08400722Fri, 19 Aug 2022 07:58:24 GMT-07:00Getting a Kidney: Where Is Patient Choice?Lennon, Michael “Jack”2022-08-19T07:58:24-07:00doi:10.2215/CJN.08400722hwp:resource-id:clinjasn;17/9/1267American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Patient PreferencePatient VoicePatient Voiceresearch-article20222022-09-01September 202210.2215/CJN.084007221555-90411555-905X2022-08-19T07:58:24-07:002022-09Clinical Journal of the American Society of NephrologyPatient Voice17999126713631278126813711280
- Advancing Kidney Health Equity10.2215/CJN.08280722Tue, 16 Aug 2022 07:40:06 GMT-07:00Advancing Kidney Health EquityMohottige, DinushikaTuot, Delphine S.2022-08-16T07:40:06-07:00doi:10.2215/CJN.08280722hwp:resource-id:clinjasn;17/9/1281American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyequity, gender affirming care, transgender, kidney function, creatinineEditorialEditorialeditorial20222022-09-01September 202210.2215/CJN.082807221555-90411555-905X2022-08-16T07:40:06-07:002022-09Clinical Journal of the American Society of NephrologyEditorial17991281130512831315
- Improving the Utilization of Deceased Donor Kidneys by Prioritizing Patient Preferences10.2215/CJN.08500722Fri, 19 Aug 2022 07:58:25 GMT-07:00Improving the Utilization of Deceased Donor Kidneys by Prioritizing Patient PreferencesMohan, SumitHusain, S. Ali2022-08-19T07:58:25-07:00doi:10.2215/CJN.08500722hwp:resource-id:clinjasn;17/9/1278American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, kidney transplantationEditorialEditorialeditorial20222022-09-01September 202210.2215/CJN.085007221555-90411555-905X2022-08-19T07:58:25-07:002022-09Clinical Journal of the American Society of NephrologyEditorial17999127813631267128013711268
- Effect of Music in Reducing Pain during Hemodialysis Access Cannulation10.2215/CJN.00360122Wed, 24 Aug 2022 05:52:34 GMT-07:00Effect of Music in Reducing Pain during Hemodialysis Access CannulationInayama, EmiYamada, YosukeKishida, MasatsuguKitamura, MineakiNishino, TomoyaOta, KeikoTakahashi, KanaeShintani, AyumiIkenoue, Tatsuyoshi2022-08-24T05:52:34-07:00doi:10.2215/CJN.00360122hwp:resource-id:clinjasn;17/9/1337American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, hemodialysis access, single-blind method, music, painOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-09-01September 202210.2215/CJN.003601221555-90411555-905X2022-08-24T05:52:34-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17991337127513451277
- Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial Fibrosis10.2215/CJN.04360422Wed, 10 Aug 2022 06:32:06 GMT-07:00Urine Uromodulin as a Biomarker of Kidney Tubulointerstitial FibrosisMelchinger, HannahCalderon-Gutierrez, FridaObeid, WassimXu, LeyuanShaw, Melissa M.Luciano, Randy L.Kuperman, MichaelMoeckel, Gilbert W.Kashgarian, MichaelWilson, F. PerryParikh, Chirag R.Moledina, Dennis G.2022-08-10T06:32:06-07:00doi:10.2215/CJN.04360422hwp:resource-id:clinjasn;17/9/1284American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybiomarker, kidney biopsy, interstitial fibrosis, glomerulosclerosis, cross-sectional analysis, uromodulinOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-09-01September 202210.2215/CJN.043604221555-90411555-905X2022-08-10T06:32:06-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17912841292
- Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images10.2215/CJN.01760222Tue, 26 Jul 2022 08:45:14 GMT-07:00Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy ImagesTesta, FrancescaFontana, FrancescoPollastri, FedericoChester, JohannaLeonelli, MarcoGiaroni, FrancescoGualtieri, FabioBolelli, FedericoMancini, ElenaNordio, MaurizioSacco, PaoloLigabue, GiuliaGiovanella, SilviaFerri, MariaAlfano, GaetanoGesualdo, LoretoCimino, SimonettaDonati, GabrieleGrana, CostantinoMagistroni, Riccardo2022-07-26T08:45:14-07:00doi:10.2215/CJN.01760222hwp:resource-id:clinjasn;17/9/1316American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, kidney biopsy, renal insufficiency, kidney failure, artificial intelligence, Oxford classification, histopathology, MEST-C, deep learningOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-09-01September 202210.2215/CJN.017602221555-90411555-905X2022-07-26T08:45:14-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17913161324
- The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function10.2215/CJN.01890222Tue, 16 Aug 2022 07:40:06 GMT-07:00The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney FunctionKrupka, EmilyCurtis, SarahFerguson, ThomasWhitlock, ReidAskin, NicoleMillar, Adam C.Dahl, MarshallFung, RaymondAhmed, Sofia B.Tangri, NavdeepWalsh, MichaelCollister, David2022-08-16T07:40:06-07:00doi:10.2215/CJN.01890222hwp:resource-id:clinjasn;17/9/1305American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransgender, gender affirming hormone therapy, kidney function, systematic review, meta-analysis, hormonesOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-09-01September 202210.2215/CJN.018902221555-90411555-905X2022-08-16T07:40:06-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17991305128113151283
- Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology10.2215/CJN.16831221Tue, 09 Aug 2022 05:36:51 GMT-07:00Potential Mechanisms Involved in Chronic Kidney Disease of Unclear EtiologyHolliday, Michael W.Li, QingtianBustamante, Edlyn G.Niu, JingboHuang, LupingEspina, Ilse M.Dominguez, Jose R.Truong, LuanMurray, Kristy O.Fan, LeiAnumudu, Samaya J.Shah, MaulinFischer, Rebecca S.B.Vangala, ChandanMandayam, SreedharPerez, JosePan, Jenny S.Ali, SehrishAwan, Ahmed A.Sheikh-Hamad, David2022-08-09T05:36:51-07:00doi:10.2215/CJN.16831221hwp:resource-id:clinjasn;17/9/1293American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMesoamerican nephropathy, CKDu, ROS, OCT2, MATE1, agrochemicals, chronic kidney diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-09-01September 202210.2215/CJN.168312211555-90411555-905X2022-08-09T05:36:51-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17991293126913041271
- Transplant Nephrology10.2215/CJN.08710722Mon, 01 Aug 2022 09:32:31 GMT-07:00Transplant NephrologyChonchol, MichelGutierrez, Orlando M.Rahman, MahboobCharytan, David M.Rosner, Mitchell2022-08-01T09:32:31-07:00doi:10.2215/CJN.08710722hwp:resource-id:clinjasn;17/9/1272American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant nephrologyEditorialEditorialeditorial20222022-09-01September 202210.2215/CJN.087107221555-90411555-905X2022-08-01T09:32:31-07:002022-09Clinical Journal of the American Society of NephrologyEditorial17999912721372140314071274138114061409
- Incidence and Risk Factors for Dialysis Reinitiation among Patients with a History of Dialysis Dependencyelaine.ku@ucsf.edu10.2215/CJN.01870222Thu, 11 Aug 2022 06:20:03 GMT-07:00Incidence and Risk Factors for Dialysis Reinitiation among Patients with a History of Dialysis DependencyKu, ElaineHsu, Raymond K.McCulloch, Charles E.Lo, LowellCopeland, TimothySiyahian, SalpiGrimes, BarbaraJohansen, Kirsten L.2022-08-11T06:20:03-07:00doi:10.2215/CJN.01870222hwp:resource-id:clinjasn;17/9/1346American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, nephrotic syndrome, lupus nephritis, acute kidney injury, chronic kidney diseaseOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-09-01September 202210.2215/CJN.018702221555-90411555-905X2022-08-11T06:20:03-07:002022-09Clinical Journal of the American Society of NephrologyOriginal Article17913461352
- Meta-analysis and cohort study of histopathological and clinical outcomes in ANCA negative versus positive vasculitisBackground: ANCA negative pauci-immune glomerulonephritis (PIGN) represents a rare and often under-studied subgroup of the vasculitidies. This study aims to investigate differences in the clinical phenotype, renal histological features and clinical outcomes amongst patients with PIGN, with and without serum ANCA positivity. Methods: A cohort of biopsy proven PIGN with and without detectable circulating ANCA was constructed from a single centre between 2006 and 2016. Primary outcomes compared clinical presentation and histopathological features according to ANCA status, with multivariate Cox regression to compare mortality and end-stage kidney disease (ESKD). A systematic review and meta-analysis of the published literature was undertaken. Results: In our cohort of 146 patients; 21.9% (n=32) had ANCA negative disease with a comparatively younger mean age at diagnosis; 51.4 vs 65.6 years (P<0.001). Fourteen studies, inclusive of our cohort were eligible for meta-analysis, totalling 301 ANCA negative patients. Those with ANCA negative disease tended to have fewer extra-renal symptoms and a higher frequency of renal limited disease, but both failed to reach statistical significance (P=0.92 and P=0.07). The risk of ESKD was significantly higher in seronegative disease (RR 2.28 [1.42-3.65], P<0.001), reflecting our experience, with a fivefold increased risk of ESKD in ANCA negative disease (P<0.001). No significant difference in the chronicity of histopathological findings was seen and the meta-analysis showed no difference in morality (RR 1.22 [0.63-2.38], P=0.55). Conclusion: Our findings demonstrate that ANCA negative PIGN presents in younger patients, with fewer extra renal manifestations and higher ESKD risk despite a lack of difference in histopathology. This study provides the impetus for further research into the pathogenesis, treatment response and duration of immunotherapy in ANCA negative disease. We suggest that the absence of positive ANCA serology should not discourage treatment and for clinical trials to include ANCA negative patients.lauren.floyd@doctors.org.uk10.34067/KID.0003892022Mon, 05 Sep 2022 07:01:22 GMT-07:00Meta-analysis and cohort study of histopathological and clinical outcomes in ANCA negative versus positive vasculitisBackground: ANCA negative pauci-immune glomerulonephritis (PIGN) represents a rare and often under-studied subgroup of the vasculitidies. This study aims to investigate differences in the clinical phenotype, renal histological features and clinical outcomes amongst patients with PIGN, with and without serum ANCA positivity. Methods: A cohort of biopsy proven PIGN with and without detectable circulating ANCA was constructed from a single centre between 2006 and 2016. Primary outcomes compared clinical presentation and histopathological features according to ANCA status, with multivariate Cox regression to compare mortality and end-stage kidney disease (ESKD). A systematic review and meta-analysis of the published literature was undertaken. Results: In our cohort of 146 patients; 21.9% (n=32) had ANCA negative disease with a comparatively younger mean age at diagnosis; 51.4 vs 65.6 years (P<0.001). Fourteen studies, inclusive of our cohort were eligible for meta-analysis, totalling 301 ANCA negative patients. Those with ANCA negative disease tended to have fewer extra-renal symptoms and a higher frequency of renal limited disease, but both failed to reach statistical significance (P=0.92 and P=0.07). The risk of ESKD was significantly higher in seronegative disease (RR 2.28 [1.42-3.65], P<0.001), reflecting our experience, with a fivefold increased risk of ESKD in ANCA negative disease (P<0.001). No significant difference in the chronicity of histopathological findings was seen and the meta-analysis showed no difference in morality (RR 1.22 [0.63-2.38], P=0.55). Conclusion: Our findings demonstrate that ANCA negative PIGN presents in younger patients, with fewer extra renal manifestations and higher ESKD risk despite a lack of difference in histopathology. This study provides the impetus for further research into the pathogenesis, treatment response and duration of immunotherapy in ANCA negative disease. We suggest that the absence of positive ANCA serology should not discourage treatment and for clinical trials to include ANCA negative patients.Floyd, LaurenMorris, Adam D.Elsayed, Mohamed E.Shetty, AnamayBaksi, AnanyaGeetha, DuvuruDhaygude, AjayMitra, Sandip2022-09-05T19:01:22-07:00doi:10.34067/KID.0003892022hwp:resource-id:kidney360;KID.0003892022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360ANCA associated vasculitis, ANCA, pauci-immune glomerulonephritis, Renal biopsy, ANCA negative Vasculitis, glomerulonephritis, vasculitis, end stage kidney disease, Outcomes, Cohort StudiesOriginal InvestigationOriginal Investigationother202210.34067/KID.00038920222641-76502641-76502022-09-05T19:01:22-07:00Kidney360Original Investigation10.34067/KID.0003892022
- The Highs and Lows of Potassium Intake in CKD—Does One Size Fit All?10.1681/ASN.2022070743Tue, 19 Jul 2022 11:52:25 GMT-07:00The Highs and Lows of Potassium Intake in CKD—Does One Size Fit All?Terker, Andrew S.Saritas, TurgayMcDonough, Alicia A.2022-07-19T11:52:25-07:00doi:10.1681/ASN.2022070743hwp:resource-id:jnephrol;33/9/1638American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypotassium intake, chronic kidney disease, clinical trial, dietary supplementsUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20222022-09-01September 202210.1681/ASN.20220707431046-66731533-34502022-07-19T11:52:25-07:002022-09Journal of the American Society of NephrologyUp Front Matters339991638i17791640i1789
- The Advancing American Kidney Health Initiative: The Challenge of Overcoming the Status Quo10.1681/ASN.2022040510Tue, 02 Aug 2022 12:56:00 GMT-07:00The Advancing American Kidney Health Initiative: The Challenge of Overcoming the Status QuoConway, Paul T.Gedney, NieltjeRoy, ShuvoFissell, William H.2022-08-02T12:56:00-07:00doi:10.1681/ASN.2022040510hwp:resource-id:jnephrol;33/9/1797American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, kidney transplantation, nephrology, organ transplant, peritoneal dialysis, quality of life, renal dialysis, transplantation, United StatesLetter to the EditorLetter to the Editorletter20222022-09-01September 202210.1681/ASN.20220405101046-66731533-34502022-08-02T12:56:00-07:002022-09Journal of the American Society of NephrologyLetter to the Editor33996179718001060179818011062
- Emerging Insights into Glomerular Vascular Pole and MicrocirculationThe glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for >30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy1.1–induced mesangiolysis and intravital microscopy to unequivocally establish in vivo the long-suspected contractile function of mesangial cells, which have the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize the existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.10.1681/ASN.2022030354Tue, 19 Jul 2022 11:52:26 GMT-07:00Emerging Insights into Glomerular Vascular Pole and MicrocirculationThe glomerular vascular pole is the gate for the afferent and efferent arterioles and mesangial cells and a frequent location of peripolar cells with an unclear function. It has been studied in definitive detail for >30 years, and functionally interrogated in the context of signal transduction from the macula densa to the mesangial cells and afferent arteriolar smooth muscle cells from 10 to 20 years ago. Two recent discoveries shed additional light on the vascular pole, with possibly far-reaching implications. One, which uses novel serial section electron microscopy, reveals a shorter capillary pathway between the basins of the afferent and efferent arterioles. Such a pathway, when patent, may short-circuit the multitude of capillaries in the glomerular tuft. Notably, this shorter capillary route is enclosed within the glomerular mesangium. The second study used anti-Thy1.1–induced mesangiolysis and intravital microscopy to unequivocally establish in vivo the long-suspected contractile function of mesangial cells, which have the ability to change the geometry and curvature of glomerular capillaries. These studies led me to hypothesize the existence of a glomerular perfusion rheostat, in which the shorter path periodically fluctuates between being more and less patent. This action reduces or increases blood flow through the entire glomerular capillary tuft. A corollary is that the GFR is a net product of balance between the states of capillary perfusion, and that deviations from the balanced state would increase or decrease GFR. Taken together, these studies may pave the way to a more profound understanding of glomerular microcirculation under basal conditions and in progression of glomerulopathies.Goligorsky, Michael S.2022-07-19T11:52:26-07:00doi:10.1681/ASN.2022030354hwp:resource-id:jnephrol;33/9/1641American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rate, glomerulus, mesangial cells, microcirculationUp Front MattersReviewUp Front MattersReviewresearch-article20222022-09-01September 202210.1681/ASN.20220303541046-66731533-34502022-07-19T11:52:26-07:002022-09Journal of the American Society of NephrologyUp Front Matters33916411648
- Nuclear Condensation of CDYL Links Histone Crotonylation and Cystogenesis in Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2021111425Tue, 02 Aug 2022 01:10:36 GMT-07:00Nuclear Condensation of CDYL Links Histone Crotonylation and Cystogenesis in Autosomal Dominant Polycystic Kidney DiseaseDang, LinCao, XinyiZhang, TianyeSun, YongzhanTian, ShanshanGong, TianyuXiong, HuiCao, PeipeiLi, YuhaoYu, ShengqiangYang, LiZhang, LirongLiu, TongZhang, KaiLiang, JingChen, Yupeng2022-08-02T13:10:36-07:00doi:10.1681/ASN.2021111425hwp:resource-id:jnephrol;33/9/1708American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyCDYL, histone crotonylation, phase separation, ADPKDBasic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article20222022-09-01September 202210.1681/ASN.20211114251046-66731533-34502022-08-02T13:10:36-07:002022-09Journal of the American Society of NephrologyBasic Research33991708162917251630
- Systematic Review and Meta-Analysis of Plasma and Urine Biomarkers for CKD Outcomes10.1681/ASN.2022010098Wed, 20 Jul 2022 06:30:48 GMT-07:00Systematic Review and Meta-Analysis of Plasma and Urine Biomarkers for CKD OutcomesLiu, CarolineDebnath, NehaMosoyan, GoharChauhan, KinsukVasquez-Rios, GeorgeSoudant, CelineMenez, SteveParikh, Chirag R.Coca, Steven G.2022-07-20T06:30:48-07:00doi:10.1681/ASN.2022010098hwp:resource-id:jnephrol;33/9/1657American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, chronic allograft failureMeta-analysisChronic Kidney DiseaseMeta-analysisChronic Kidney Diseaseresearch-article20222022-09-01September 202210.1681/ASN.20220100981046-66731533-34502022-07-20T06:30:48-07:002022-09Journal of the American Society of NephrologyMeta-analysis33916571672
- KLC3 Regulates Ciliary Trafficking and Cyst Progression in CILK1 Deficiency–Related Polycystic Kidney Disease10.1681/ASN.2021111455Fri, 12 Aug 2022 12:00:51 GMT-07:00KLC3 Regulates Ciliary Trafficking and Cyst Progression in CILK1 Deficiency–Related Polycystic Kidney DiseaseRah, GyuyeongCha, HwayeonKim, JooheeSong, JieunKim, HyunhoOh, Yun KyuAhn, CurieKang, MinyongKim, JongminYoo, Kyung HyunKim, Min JungKo, Hyuk WanKo, Je YeongPark, Jong Hoon2022-08-12T12:00:51-07:00doi:10.1681/ASN.2021111455hwp:resource-id:jnephrol;33/9/1726American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyCILK1, KLC3, cyst, PKD, ciliaBasic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article20222022-09-01September 202210.1681/ASN.20211114551046-66731533-34502022-08-12T12:00:51-07:002022-09Journal of the American Society of NephrologyBasic Research33917261741
- Sources of Variation in the Carbon Footprint of Hemodialysis Treatment10.1681/ASN.2022010086Thu, 02 Jun 2022 10:56:36 GMT-07:00Sources of Variation in the Carbon Footprint of Hemodialysis TreatmentSehgal, Ashwini R.Slutzman, Jonathan E.Huml, Anne M.2022-06-02T10:56:36-07:00doi:10.1681/ASN.2022010086hwp:resource-id:jnephrol;33/9/1790American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, carbon footprintClinical ResearchDialysisClinical ResearchDialysisresearch-article20222022-09-01September 202210.1681/ASN.20220100861046-66731533-34502022-06-02T10:56:36-07:002022-09Journal of the American Society of NephrologyClinical Research339991790i16351795i1637
- Hurricanes and Mortality among Patients Receiving Dialysis10.1681/ASN.2021111520Thu, 14 Jul 2022 05:49:43 GMT-07:00Hurricanes and Mortality among Patients Receiving DialysisBlum, Matthew F.Feng, YijingAnderson, G. BrookeSegev, Dorry L.McAdams-DeMarco, MaraGrams, Morgan E.2022-07-14T05:49:43-07:00doi:10.1681/ASN.2021111520hwp:resource-id:jnephrol;33/9/1757American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymortality risk, extreme weather, tropical cyclones, hurricanes, climate change, dialysis, USRDSClinical EpidemiologyChronic Kidney DiseaseClinical EpidemiologyChronic Kidney Diseaseresearch-article20222022-09-01September 202210.1681/ASN.20211115201046-66731533-34502022-07-14T05:49:43-07:002022-09Journal of the American Society of NephrologyClinical Epidemiology33991757i1766i
- Association of Rosuvastatin Use with Risk of Hematuria and Proteinuria10.1681/ASN.2022020135Tue, 19 Jul 2022 10:23:57 GMT-07:00Association of Rosuvastatin Use with Risk of Hematuria and ProteinuriaShin, Jung-ImFine, Derek M.Sang, YingyingSurapaneni, AdityaDunning, Stephan C.Inker, Lesley A.Nolin, Thomas D.Chang, Alex R.Grams, Morgan E.2022-07-19T10:23:57-07:00doi:10.1681/ASN.2022020135hwp:resource-id:jnephrol;33/9/1767American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologystatins, drug nephrotoxicity, clinical epidemiology, chronic kidney disease, rosuvastatin calcium, hematuria, proteinuriaClinical EpidemiologyPharmacology and Therapeutic DevelopmentClinical EpidemiologyPharmacology and Therapeutic Developmentresearch-article20222022-09-01September 202210.1681/ASN.20220201351046-66731533-34502022-07-19T10:23:57-07:002022-09Journal of the American Society of NephrologyClinical Epidemiology33917671777
- Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous Nephropathy10.1681/ASN.2021101384Fri, 01 Jul 2022 06:03:14 GMT-07:00Complement C3a and C3a Receptor Activation Mediates Podocyte Injuries in the Mechanism of Primary Membranous NephropathyGao, ShuangCui, ZhaoZhao, Ming-hui2022-07-01T06:03:14-07:00doi:10.1681/ASN.2021101384hwp:resource-id:jnephrol;33/9/1742American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembrane nephropathy, complement, C3a receptor, podocyte, Heymann nephritisBasic ResearchGlomerulonephritis and Interstitial NephritisBasic ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-09-01September 202210.1681/ASN.20211013841046-66731533-34502022-07-01T06:03:14-07:002022-09Journal of the American Society of NephrologyBasic Research339991742i16311756i1633
- The Potential for Pragmatic Trials to Reduce Racial and Ethnic Disparities in Kidney Disease10.1681/ASN.2022030301Wed, 03 Aug 2022 09:40:32 GMT-07:00The Potential for Pragmatic Trials to Reduce Racial and Ethnic Disparities in Kidney DiseaseDember, Laura M.2022-08-03T09:40:32-07:00doi:10.1681/ASN.2022030301hwp:resource-id:jnephrol;33/9/1649American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyPerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-09-01September 202210.1681/ASN.20220303011046-66731533-34502022-08-03T09:40:32-07:002022-09Journal of the American Society of NephrologyPerspective33916491651
- Health Care Equity and Justice Scorecard To Increase Diversity in Clinical Trial Recruitment and Retention10.1681/ASN.2022040427Wed, 29 Jun 2022 08:14:50 GMT-07:00Health Care Equity and Justice Scorecard To Increase Diversity in Clinical Trial Recruitment and RetentionNicholas, Susanne B.Cervantes, Lilia2022-06-29T08:14:50-07:00doi:10.1681/ASN.2022040427hwp:resource-id:jnephrol;33/9/1652American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical trial, community engagement, patient partners, racial and ethnic disparities, chronic kidney disease, diversityPerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-09-01September 202210.1681/ASN.20220404271046-66731533-34502022-06-29T08:14:50-07:002022-09Journal of the American Society of NephrologyPerspective33916521655
- Assessing the Carbon Footprint of Hemodialysis: A First Step Toward Environmentally Sustainable Kidney Care10.1681/ASN.2022060661Fri, 15 Jul 2022 06:33:18 GMT-07:00Assessing the Carbon Footprint of Hemodialysis: A First Step Toward Environmentally Sustainable Kidney CareBarraclough, Katherine A.McAlister, Scott2022-07-15T06:33:18-07:00doi:10.1681/ASN.2022060661hwp:resource-id:jnephrol;33/9/1635American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, hemodialysis, peritoneal dialysisUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-09-01September 202210.1681/ASN.20220606611046-66731533-34502022-07-15T06:33:18-07:002022-09Journal of the American Society of NephrologyUp Front Matters339991635i17901637i1795
- Decorating Histones in Polycystic Kidney Disease10.1681/ASN.2022070750Tue, 02 Aug 2022 01:10:35 GMT-07:00Decorating Histones in Polycystic Kidney DiseaseRamalingam, HariniPatel, Vishal2022-08-02T13:10:35-07:00doi:10.1681/ASN.2022070750hwp:resource-id:jnephrol;33/9/1629American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, epigenetics, histones, crotonylation, phase separation, gene expressionUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-09-01September 202210.1681/ASN.20220707501046-66731533-34502022-08-02T13:10:35-07:002022-09Journal of the American Society of NephrologyUp Front Matters33991629170816301725
- Searching for the Risk-Benefit Profile of Higher Potassium Intake in CKD: Primum Non Nocere10.1681/ASN.2022060695Thu, 04 Aug 2022 08:12:47 GMT-07:00Searching for the Risk-Benefit Profile of Higher Potassium Intake in CKD: Primum Non NocereGuedes, MuriloPecoits-Filho, Roberto2022-08-04T08:12:47-07:00doi:10.1681/ASN.2022060695hwp:resource-id:jnephrol;33/9/1633American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypotassium, chronic kidney disease, hyperkalemiaUp Front MattersEditorialUp Front MattersEditorialresearch-article20222022-09-01September 202210.1681/ASN.20220606951046-66731533-34502022-08-04T08:12:47-07:002022-09Journal of the American Society of NephrologyUp Front Matters339991633i17791635i1789
- Complement is Complimentary in Membranous Nephropathy10.1681/ASN.2022060633Wed, 13 Jul 2022 06:34:38 GMT-07:00Complement is Complimentary in Membranous NephropathyKettritz, RalphSchreiber, Adrian2022-07-13T06:34:38-07:00doi:10.1681/ASN.2022060633hwp:resource-id:jnephrol;33/9/1631American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, complementUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-09-01September 202210.1681/ASN.20220606331046-66731533-34502022-07-13T06:34:38-07:002022-09Journal of the American Society of NephrologyUp Front Matters339991631i17421633i1756
- This Month's Highlights10.1681/ASN.2022070827Wed, 31 Aug 2022 10:00:23 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2022-08-31T10:00:23-07:00doi:10.1681/ASN.2022070827hwp:resource-id:jnephrol;33/9/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsother20222022-09-01September 202210.1681/ASN.20220708271046-66731533-34502022-08-31T10:00:23-07:002022-09Journal of the American Society of NephrologyThis Month's Highlights33999999999i17901635175717421631177916331638i17951637176617561633178916351640
- Authors’ Reply: “The Advancing American Kidney Health Initiative: The Challenge of Overcoming the Status Quo” and “The Advancing American Kidney Health Initiative: Do Not Let 80% Distract Us from the Fact that We Can Do Better”10.1681/ASN.2022050540Tue, 02 Aug 2022 12:56:01 GMT-07:00Authors’ Reply: “The Advancing American Kidney Health Initiative: The Challenge of Overcoming the Status Quo” and “The Advancing American Kidney Health Initiative: Do Not Let 80% Distract Us from the Fact that We Can Do Better”Quinn, Robert R.Lam, Ngan N.Ravani, PietroOliver, Matthew J.Blake, Peter G.Tonelli, Marcello2022-08-02T12:56:01-07:00doi:10.1681/ASN.2022050540hwp:resource-id:jnephrol;33/9/1800American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney failure, end stage kidney disease, dialysis, transplantationLetter to the EditorLetter to the Editorletter20222022-09-01September 202210.1681/ASN.20220505401046-66731533-34502022-08-02T12:56:01-07:002022-09Journal of the American Society of NephrologyLetter to the Editor33999618001797179810601801179817991062
- The Advancing American Kidney Health Initiative: Do Not Let 80% Distract Us from the Fact that We Can Do Better10.1681/ASN.2022050536Tue, 02 Aug 2022 12:56:00 GMT-07:00The Advancing American Kidney Health Initiative: Do Not Let 80% Distract Us from the Fact that We Can Do BetterMendu, Mallika L.Bieber, Scott D.Watnick, Suzanne G.Weiner, Daniel E.2022-08-02T12:56:00-07:00doi:10.1681/ASN.2022050536hwp:resource-id:jnephrol;33/9/1798American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, kidney transplantation, peritoneal dialysis, health policy, United StatesLetter to the EditorLetter to the Editorletter20222022-09-01September 202210.1681/ASN.20220505361046-66731533-34502022-08-02T12:56:00-07:002022-09Journal of the American Society of NephrologyLetter to the Editor33996179818001060179918011062
- Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD10.1681/ASN.2022020147Tue, 24 May 2022 11:35:29 GMT-07:00Effects of Short-Term Potassium Chloride Supplementation in Patients with CKDGritter, MartinWouda, Rosa D.Yeung, Stanley M.H.Wieërs, Michiel L.A.Geurts, Frankde Ridder, Maria A.J.Ramakers, Christian R.B.Vogt, Liffertde Borst, Martin H.Rotmans, Joris I.Hoorn, Ewout J.,Boom, Henkde Graaf Gasthuis, ReinierGabreëls, Bas Ah.T.F.Groeneveld, MarcJanssen, Wilbert M.T.Korte, Mario R.Laverman, Goos D.van der Lubbe, Nilsvan der Net, Jeroen B.Soonawala, DariusSwart, Reinout M.Verhoeven, Martine A.M.2022-05-24T11:35:29-07:00doi:10.1681/ASN.2022020147hwp:resource-id:jnephrol;33/9/1779American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyaldosterone, chronic kidney disease, clinical trial, electrolytes, hypertension, acidosis, potassium chloride, dietary supplementsClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-09-01September 202210.1681/ASN.20220201471046-66731533-34502022-05-24T11:35:29-07:002022-09Journal of the American Society of NephrologyClinical Research3399991779i163316381789i16351640
- Cation Channel Activity of Apolipoprotein L1 is Modulated by Haplotype Background10.1681/ASN.2022020213Fri, 15 Jul 2022 06:33:19 GMT-07:00Cation Channel Activity of Apolipoprotein L1 is Modulated by Haplotype BackgroundWinkler, Rebecca L.Bruno, JonathanBuchanan, PaulaEdwards, John C.2022-07-15T06:33:19-07:00doi:10.1681/ASN.2022020213hwp:resource-id:jnephrol;33/9/1673American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic kidney disease, chronic kidney disease, ion channel, K channels, racial disparities, apolipoprotein L1, haplotypes, cationsResearch LetterGenetic Disease of the KidneyResearch LetterGenetic Disease of the Kidneyletter20222022-09-01September 202210.1681/ASN.20220202131046-66731533-34502022-07-15T06:33:19-07:002022-09Journal of the American Society of NephrologyResearch Letter33916731675
- Kidney Failure Alters Parathyroid Pin1 Phosphorylation and Parathyroid Hormone mRNA-Binding Proteins, Leading to Secondary Hyperparathyroidism10.1681/ASN.2022020197Fri, 12 Aug 2022 12:00:52 GMT-07:00Kidney Failure Alters Parathyroid Pin1 Phosphorylation and Parathyroid Hormone mRNA-Binding Proteins, Leading to Secondary HyperparathyroidismHassan, AliaPollak, Yael E.Kilav-Levin, RachelSilver, JustinLondon, NirNechama, MorrisBen-Dov, Iddo Z.Naveh-Many, Tally2022-08-12T12:00:52-07:00doi:10.1681/ASN.2022020197hwp:resource-id:jnephrol;33/9/1677American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymineral metabolism, molecular biology, mRNA, parathyroid hormone, renal failure, hyperparathyroidism, phosphorylationBasic ResearchChronic Kidney DiseaseBasic ResearchChronic Kidney Diseaseresearch-article20222022-09-01September 202210.1681/ASN.20220201971046-66731533-34502022-08-12T12:00:52-07:002022-09Journal of the American Society of NephrologyBasic Research33916771693
- Transcription Factors YAP/TAZ and SRF Cooperate To Specify Renal Myofibroblasts in the Developing Mouse Kidney10.1681/ASN.2021121559Tue, 02 Aug 2022 12:20:32 GMT-07:00Transcription Factors YAP/TAZ and SRF Cooperate To Specify Renal Myofibroblasts in the Developing Mouse KidneyDrake, Keri A.Chaney, ChristopherPatel, MohitaDas, AmritaBittencourt, JuliaCohn, MartinCarroll, Thomas J.2022-08-02T12:20:32-07:00doi:10.1681/ASN.2021121559hwp:resource-id:jnephrol;33/9/1694American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyHippo/Warts, pericyte, fibroblast heterogeneity, stromal microenvironment, kidney development, myofibroblastsBasic ResearchDevelopment of the KidneyBasic ResearchDevelopment of the Kidneyresearch-article20222022-09-01September 202210.1681/ASN.20211215591046-66731533-34502022-08-02T12:20:32-07:002022-09Journal of the American Society of NephrologyBasic Research33916941707
- Prolonged Intermittent Kidney Replacement TherapyKidney replacement therapy (KRT) is a vital, supportive treatment for patients with critical illness and severe AKI. The optimal timing, dose, and modality of KRT have been studied extensively, but gaps in knowledge remain. With respect to modalities, continuous KRT and intermittent hemodialysis are well-established options, but prolonged intermittent KRT is becoming more prevalent worldwide, particularly in emerging countries. Compared with continuous KRT, prolonged intermittent KRT offers similar hemodynamic stability and overall cost savings, and its intermittent nature allows patients time off therapy for mobilization and procedures. When compared with intermittent hemodialysis, prolonged intermittent KRT offers more hemodynamic stability, particularly in patients who remain highly vulnerable to hypotension from aggressive ultrafiltration over a shorter duration of treatment. The prescription of prolonged intermittent KRT can be tailored to patients’ progression in their recovery from critical illness, and the frequency, flow rates, and duration of treatment can be modified to avert hemodynamic instability during de-escalation of care. Dosing of prolonged intermittent KRT can be extrapolated from urea kinetics used to calculate clearance for continuous KRT and intermittent hemodialysis. Practice variations across institutions with respect to terminology, prescription, and dosing of prolonged intermittent KRT create significant challenges, especially in creating specific drug dosing recommendations during prolonged intermittent KRT. During the coronavirus disease 2019 pandemic, prolonged intermittent KRT was rapidly implemented to meet the KRT demands during patient surges in some of the medical centers overwhelmed by sheer volume of patients with AKI. Ideally, implementation of prolonged intermittent KRT at any institution should be conducted in a timely manner, with judicious planning and collaboration among nephrology, critical care, dialysis and intensive care nursing, and pharmacy leadership. Future analyses and clinical trials with respect to prescription and delivery of prolonged intermittent KRT and clinical outcomes will help to guide standardization of practice.10.2215/CJN.04310422Mon, 29 Aug 2022 06:04:11 GMT-07:00Prolonged Intermittent Kidney Replacement TherapyKidney replacement therapy (KRT) is a vital, supportive treatment for patients with critical illness and severe AKI. The optimal timing, dose, and modality of KRT have been studied extensively, but gaps in knowledge remain. With respect to modalities, continuous KRT and intermittent hemodialysis are well-established options, but prolonged intermittent KRT is becoming more prevalent worldwide, particularly in emerging countries. Compared with continuous KRT, prolonged intermittent KRT offers similar hemodynamic stability and overall cost savings, and its intermittent nature allows patients time off therapy for mobilization and procedures. When compared with intermittent hemodialysis, prolonged intermittent KRT offers more hemodynamic stability, particularly in patients who remain highly vulnerable to hypotension from aggressive ultrafiltration over a shorter duration of treatment. The prescription of prolonged intermittent KRT can be tailored to patients’ progression in their recovery from critical illness, and the frequency, flow rates, and duration of treatment can be modified to avert hemodynamic instability during de-escalation of care. Dosing of prolonged intermittent KRT can be extrapolated from urea kinetics used to calculate clearance for continuous KRT and intermittent hemodialysis. Practice variations across institutions with respect to terminology, prescription, and dosing of prolonged intermittent KRT create significant challenges, especially in creating specific drug dosing recommendations during prolonged intermittent KRT. During the coronavirus disease 2019 pandemic, prolonged intermittent KRT was rapidly implemented to meet the KRT demands during patient surges in some of the medical centers overwhelmed by sheer volume of patients with AKI. Ideally, implementation of prolonged intermittent KRT at any institution should be conducted in a timely manner, with judicious planning and collaboration among nephrology, critical care, dialysis and intensive care nursing, and pharmacy leadership. Future analyses and clinical trials with respect to prescription and delivery of prolonged intermittent KRT and clinical outcomes will help to guide standardization of practice.Levine, ZoeyVijayan, Anitha2022-08-29T06:04:11-07:00doi:10.2215/CJN.04310422hwp:resource-id:clinjasn;CJN.04310422v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and AKI series, intermittent RRT, PIRRTCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article202210.2215/CJN.043104221555-90411555-905X2022-08-29T06:04:11-07:00Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney InjuryCJN.04310422
- Endothelial KLF11 as a Nephroprotectant in AKI10.34067/KID.0003422022Thu, 25 Aug 2022 06:30:29 GMT-07:00Endothelial KLF11 as a Nephroprotectant in AKIGhajar-Rahimi, GelareAgarwal, Anupam2022-08-25T06:30:29-07:00doi:10.34067/KID.0003422022hwp:resource-id:kidney360;3/8/1302American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, endothelium, Krüppel-like factors, nephroprotective agentsEditorialEditorialeditorial20222022-08-2510.34067/KID.00034220222641-76502022-08-25T06:30:29-07:002022-08-25Kidney360Editorial3813021305
- Guiding Kidney Transplantation Candidates for Effective Weight Loss: A Clinical Cohort Study10.34067/KID.0001682022Mon, 16 May 2022 01:21:46 GMT-07:00Guiding Kidney Transplantation Candidates for Effective Weight Loss: A Clinical Cohort StudyKukla, AleksandraDiwan, TayyabSmith, Byron H.Collazo-Clavell, Maria L.Lorenz, Elizabeth C.Clark, MatthewGrothe, KarenDenic, AleksandarPark, Walter D.Sahi, SukhdeepSchinstock, Carrie A.Amer, HatemIssa, NaimBentall, Andrew J.Dean, Patrick G.Kudva, Yogish C.Mundi, ManpreetStegall, Mark D.2022-05-16T13:21:46-07:00doi:10.34067/KID.0001682022hwp:resource-id:kidney360;3/8/1411American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, bariatric surgery, BMI, cohort studies, diabetes, dialysis, kidney transplant candidates, mortality, obesity, weight lossOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-08-2510.34067/KID.00016820222641-76502022-05-16T13:21:46-07:002022-08-25Kidney360Original Investigation3814111416
- High Ultrafiltration Rates and Mortality in Hemodialysis Patients: Current Evidence and Future Steps10.34067/KID.0003402022Thu, 25 Aug 2022 06:30:29 GMT-07:00High Ultrafiltration Rates and Mortality in Hemodialysis Patients: Current Evidence and Future StepsRavi, Katherine Scovner2022-08-25T06:30:29-07:00doi:10.34067/KID.0003402022hwp:resource-id:kidney360;3/8/1293American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, hemodialysis, hypertension, hypervolemia, ultrafiltrationEditorialEditorialeditorial20222022-08-2510.34067/KID.00034020222641-76502022-08-25T06:30:29-07:002022-08-25Kidney360Editorial3812931295
- Intensive RRT for AKI: Dial Down Your Enthusiasm!10.34067/KID.0000972022Fri, 03 Jun 2022 03:49:41 GMT-07:00Intensive RRT for AKI: Dial Down Your Enthusiasm!Clark, Edward G.Vijayan, Anitha2022-06-03T15:49:41-07:00doi:10.34067/KID.0000972022hwp:resource-id:kidney360;3/8/1439American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI, CRRT, dialysis, dose, hemodialysis, intensity, RRTPerspectivePerspectiveresearch-article20222022-08-2510.34067/KID.00009720222641-76502022-06-03T15:49:41-07:002022-08-25Kidney360Perspective3814391441
- County-Level Dialysis Facility Supply and Distance Traveled to Facilities among Incident Kidney Failure Patients10.34067/KID.0000312022Tue, 24 May 2022 01:38:02 GMT-07:00County-Level Dialysis Facility Supply and Distance Traveled to Facilities among Incident Kidney Failure PatientsVelázquez, Alexis F.Thorsness, RebeccaTrivedi, Amal N.Nguyen, Kevin H.2022-05-24T13:38:02-07:00doi:10.34067/KID.0000312022hwp:resource-id:kidney360;3/8/1367American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, health disparities, kidney failure, renal dialysis, renal insufficiency, travelOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-08-2510.34067/KID.00003120222641-76502022-05-24T13:38:02-07:002022-08-25Kidney360Original Investigation3813671373
- Proportion of Hemodialysis Treatments with High Ultrafiltration Rate and the Association with Mortality10.34067/KID.0001322022Thu, 05 May 2022 01:22:35 GMT-07:00Proportion of Hemodialysis Treatments with High Ultrafiltration Rate and the Association with MortalityNavarrete, José E.Rajabalan, AjaiCobb, JasonLea, Janice P.2022-05-05T13:22:35-07:00doi:10.34067/KID.0001322022hwp:resource-id:kidney360;3/8/1359American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, hemodialysis, mortality risk, ultrafiltration rateOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-08-2510.34067/KID.00013220222641-76502022-05-05T13:22:35-07:002022-08-25Kidney360Original Investigation3813591366
- Fundamentals of Arterial Blood Gas InterpretationAcid-base disturbances in patients with cardiopulmonary or other disorders are common and are often misinterpreted or interpreted incompletely. Treating acid-base disorders in greater detail facilitates pathophysiologic understanding and improved therapeutic planning. Understanding the ratiometric relationship between the lungs, which excrete volatile acid as carbon dioxide, and the kidneys, which contribute to maintenance of plasma bicarbonate, allows precise identification of the dominant acid-base disturbance when more than a simple disorder is present and aids in executing a measured treatment response. Concordantly, mapping paired values of the partial pressure of carbon dioxide (PCO2) and the bicarbonate concentration ([HCO3–]) on a Cartesian coordinate system visually defines an acid-base disorder and validates the ratiometric methodology. We review and demonstrate the algebraic and logarithmic methods of arterial blood gas analysis through the example of a complex acid-base disorder, emphasizing examination of the PCO2-to-[HCO3–] ratio.10.34067/KID.0008102021Fri, 03 Jun 2022 01:46:37 GMT-07:00Fundamentals of Arterial Blood Gas InterpretationAcid-base disturbances in patients with cardiopulmonary or other disorders are common and are often misinterpreted or interpreted incompletely. Treating acid-base disorders in greater detail facilitates pathophysiologic understanding and improved therapeutic planning. Understanding the ratiometric relationship between the lungs, which excrete volatile acid as carbon dioxide, and the kidneys, which contribute to maintenance of plasma bicarbonate, allows precise identification of the dominant acid-base disturbance when more than a simple disorder is present and aids in executing a measured treatment response. Concordantly, mapping paired values of the partial pressure of carbon dioxide (PCO2) and the bicarbonate concentration ([HCO3–]) on a Cartesian coordinate system visually defines an acid-base disorder and validates the ratiometric methodology. We review and demonstrate the algebraic and logarithmic methods of arterial blood gas analysis through the example of a complex acid-base disorder, emphasizing examination of the PCO2-to-[HCO3–] ratio.Yee, JerryFrinak, StanMohiuddin, NaushabaUduman, Junior2022-06-03T13:46:37-07:00doi:10.34067/KID.0008102021hwp:resource-id:kidney360;3/8/1458American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, acid-base disorders, arterial blood gas analysis, arterial blood gas interpretation, arterial blood gas measurementReview ArticleReview Articlereview-article20222022-08-2510.34067/KID.00081020212641-76502022-06-03T13:46:37-07:002022-08-25Kidney360Review Article3814581466
- Inhibitory Antibodies against PCSK9 Reduce Surface CD36 and Mitigate Diet-Induced Renal Lipotoxicity10.34067/KID.0007022021Wed, 27 Apr 2022 11:32:08 GMT-07:00Inhibitory Antibodies against PCSK9 Reduce Surface CD36 and Mitigate Diet-Induced Renal LipotoxicityByun, Jae HyunLebeau, Paul F.Platko, KhrystynaCarlisle, Rachel E.Faiyaz, MahiChen, JackMacDonald, Melissa E.Makda, YumnaYousof, TamanaLynn, Edward G.Dickhout, Jeffrey G.Krepinsky, Joan C.Weaver, FionaIgdoura, Suleiman A.Seidah, Nabil G.Austin, Richard C.2022-04-27T11:32:08-07:00doi:10.34067/KID.0007022021hwp:resource-id:kidney360;3/8/1394American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360renal physiology, basic science, cardiovascular disease, CD36, chronic kidney disease, endoplasmic reticulum stress, hypercholesterolemia, lipid accumulation, lipids, monoclonal antibodies, PCSK9, renal injuryOriginal InvestigationRenal PhysiologyOriginal InvestigationRenal Physiologyresearch-article20222022-08-2510.34067/KID.00070220212641-76502022-04-27T11:32:08-07:002022-08-25Kidney360Original Investigation3813941410
- Global Perspectives in Acute Kidney Injury: England10.34067/KID.0000052022Wed, 29 Jun 2022 04:04:15 GMT-07:00Global Perspectives in Acute Kidney Injury: EnglandLewington, AndrewBonfield, Becky2022-06-29T04:04:15-07:00doi:10.34067/KID.0000052022hwp:resource-id:kidney360;3/8/1435American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI alerts, COVID-19, England, epidemiology, guidelines, outcomesGlobal PerspectiveGlobal Perspectiveresearch-article20222022-08-2510.34067/KID.00000520222641-76502022-06-29T04:04:15-07:002022-08-25Kidney360Global Perspective3814351438
- Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-1910.34067/KID.0001632022Wed, 18 May 2022 01:30:25 GMT-07:00Refractoriness of Hyperkalemia and Hyperphosphatemia in Dialysis-Dependent AKI Associated with COVID-19Kanduri, Swetha R.Ramanand, AkankshVarghese, VipinWen, YuangMohamed, Muner M.B.Velez, Juan Carlos Q.2022-05-18T13:30:25-07:00doi:10.34067/KID.0001632022hwp:resource-id:kidney360;3/8/1317American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, coronavirus, COVID-19, CRRT, electrolyte, hyperkalemia, hyperphosphatemia, phosphorus, potassium, SLEDOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20222022-08-2510.34067/KID.00016320222641-76502022-05-18T13:30:25-07:002022-08-25Kidney360Original Investigation3813171322
- Global Dialysis Perspective: Ethiopia10.34067/KID.0006902021Tue, 24 May 2022 01:38:03 GMT-07:00Global Dialysis Perspective: EthiopiaMengistu, Yewondwossen T.Ejigu, Addisu M.2022-05-24T13:38:03-07:00doi:10.34067/KID.0006902021hwp:resource-id:kidney360;3/8/1431American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, Africa, dialysis, EthiopiaGlobal PerspectiveGlobal Perspectiveresearch-article20222022-08-2510.34067/KID.00069020212641-76502022-05-24T13:38:03-07:002022-08-25Kidney360Global Perspective3814311434
- Persistent Abdominal Pain following Peritoneal Dialysis Catheter Removal for Peritonitis10.34067/KID.0002602022Thu, 25 Aug 2022 06:30:29 GMT-07:00Persistent Abdominal Pain following Peritoneal Dialysis Catheter Removal for PeritonitisKhan, Sana F.2022-08-25T06:30:29-07:00doi:10.34067/KID.0002602022hwp:resource-id:kidney360;3/8/1469American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, abdominal abscess, peritoneal dialysis, peritonitisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-08-2510.34067/KID.00026020222641-76502022-08-25T06:30:29-07:002022-08-25Kidney360Clinical Images in Nephrology and Dialysis3814691470
- Design and Basic Characteristics of a National Patient-Powered Registry in ADPKD10.34067/KID.0002372022Fri, 20 May 2022 02:09:38 GMT-07:00Design and Basic Characteristics of a National Patient-Powered Registry in ADPKDHoover, ElisePerrone, Ronald D.Rusconi, ChrisBenson, BeverlyDahl, Neera K.Gitomer, BereniceManelli, AmyMrug, MichalPark, MeyeonSeliger, Stephen L.Phadnis, Milind A.Thewarapperuma, NadeeshaWatnick, Terry J.2022-05-20T14:09:38-07:00doi:10.34067/KID.0002372022hwp:resource-id:kidney360;3/8/1350American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, kidney disease, outcomes, polycystic kidney disease, quality of life, registriesOriginal InvestigationCystic Kidney DiseaseOriginal InvestigationCystic Kidney Diseaseresearch-article20222022-08-2510.34067/KID.00023720222641-76502022-05-20T14:09:38-07:002022-08-25Kidney360Original Investigation3813501358
- The Many Lives of PCSK9: Therapeutic Implications10.34067/KID.0003272022Thu, 25 Aug 2022 06:30:29 GMT-07:00The Many Lives of PCSK9: Therapeutic ImplicationsPressly, JeffreyFornoni, Alessia2022-08-25T06:30:29-07:00doi:10.34067/KID.0003272022hwp:resource-id:kidney360;3/8/1296American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, PCSK9, proprotein convertase 9EditorialEditorialeditorial20222022-08-2510.34067/KID.00032720222641-76502022-08-25T06:30:29-07:002022-08-25Kidney360Editorial3812961298
- KLF11 Is a Novel Endogenous Protectant against Renal Ischemia-Reperfusion Injury10.34067/KID.0002272022Fri, 06 May 2022 01:23:10 GMT-07:00KLF11 Is a Novel Endogenous Protectant against Renal Ischemia-Reperfusion InjuryNath, Karl A.Singh, Raman DeepCroatt, Anthony J.Ackerman, Allan W.Grande, Joseph P.Khazaie, KhasayarshaChen, Y. EugeneZhang, Jifeng2022-05-06T13:23:10-07:00doi:10.34067/KID.0002272022hwp:resource-id:kidney360;3/8/1417American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, basic science, endothelin-1, heme oxygenase-1, IL-6, KLF11, protectant, reperfusion injuryBrief CommunicationAcute Kidney Injury and ICU NephrologyBrief CommunicationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-08-2510.34067/KID.00022720222641-76502022-05-06T13:23:10-07:002022-08-25Kidney360Brief Communication3814171422
- Hypercalcemia and Suppressed Intact PTH in a Hemodialysis Patient10.34067/KID.0000282022Thu, 25 Aug 2022 06:30:29 GMT-07:00Hypercalcemia and Suppressed Intact PTH in a Hemodialysis PatientDonato, BeatrizRaimundo, MárioVeiga, Ricardo2022-08-25T06:30:29-07:00doi:10.34067/KID.0000282022hwp:resource-id:kidney360;3/8/1467American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360mineral metabolism, bone tissue, calciphylaxis, hemodialysis, hypercalcemia, parathyroid hormone, scintigraphyClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-08-2510.34067/KID.00002820222641-76502022-08-25T06:30:29-07:002022-08-25Kidney360Clinical Images in Nephrology and Dialysis3814671468
- Bariatric Surgery Decreases Barriers for Kidney Transplant: Are There Other Weight-Loss Options?10.34067/KID.0003622022Thu, 25 Aug 2022 06:30:29 GMT-07:00Bariatric Surgery Decreases Barriers for Kidney Transplant: Are There Other Weight-Loss Options?Lorden, Heather M.Parajuli, Sandesh2022-08-25T06:30:29-07:00doi:10.34067/KID.0003622022hwp:resource-id:kidney360;3/8/1299American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, bariatric surgery, kidney transplantation, weight lossEditorialEditorialeditorial20222022-08-2510.34067/KID.00036220222641-76502022-08-25T06:30:29-07:002022-08-25Kidney360Editorial3812991301
- Polycystic Ovary Syndrome: Insights from Preclinical ResearchPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10%. PCOS is diagnosed by the presence of at least two of these three criteria: hyperandrogenemia, oligo- or anovulation, and polycystic ovaries. The most common type (80%) of PCOS includes hyperandrogenemia. PCOS is also characterized by obesity or overweight (in 80% of US women with PCOS), insulin resistance with elevated plasma insulin but not necessarily hyperglycemia, dyslipidemia, proteinuria, and elevated BP. Although elevated compared with age-matched controls, BP may not reach levels considered treatable according to the current clinical hypertension guidelines. However, it is well known that elevated BP, even modestly so, increases the risk of cardiovascular disease. We have developed a model of hyperandrogenemia in rodents that mimics the characteristics of PCOS in women, with increases in body weight, insulin resistance, dyslipidemia, andproteinuria and elevated BP. This review discusses potential mechanisms responsible for the elevated BP in the adult and aging PCOS rat model that may be extrapolated to women with PCOS.10.34067/KID.0002052022Fri, 17 Jun 2022 01:26:06 GMT-07:00Polycystic Ovary Syndrome: Insights from Preclinical ResearchPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10%. PCOS is diagnosed by the presence of at least two of these three criteria: hyperandrogenemia, oligo- or anovulation, and polycystic ovaries. The most common type (80%) of PCOS includes hyperandrogenemia. PCOS is also characterized by obesity or overweight (in 80% of US women with PCOS), insulin resistance with elevated plasma insulin but not necessarily hyperglycemia, dyslipidemia, proteinuria, and elevated BP. Although elevated compared with age-matched controls, BP may not reach levels considered treatable according to the current clinical hypertension guidelines. However, it is well known that elevated BP, even modestly so, increases the risk of cardiovascular disease. We have developed a model of hyperandrogenemia in rodents that mimics the characteristics of PCOS in women, with increases in body weight, insulin resistance, dyslipidemia, andproteinuria and elevated BP. This review discusses potential mechanisms responsible for the elevated BP in the adult and aging PCOS rat model that may be extrapolated to women with PCOS.Reckelhoff, Jane F.Shawky, Noha M.Romero, Damian G.Yanes Cardozo, Licy L.2022-06-17T13:26:06-07:00doi:10.34067/KID.0002052022hwp:resource-id:kidney360;3/8/1449American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hypertension, aging, basic science, blood pressure, hyperandrogenemia, obesity, polycystic ovary syndrome, pregnancy, renin-angiotensin systemBasic Science for CliniciansBasic Science for Cliniciansresearch-article20222022-08-2510.34067/KID.00020520222641-76502022-06-17T13:26:06-07:002022-08-25Kidney360Basic Science for Clinicians3814491457
- Fostering Scientific Innovation to Impact AKI: A Roadmap from ASN’s AKINow Basic Science Workgroup10.34067/KID.0007472021Fri, 17 Jun 2022 03:54:12 GMT-07:00Fostering Scientific Innovation to Impact AKI: A Roadmap from ASN’s AKINow Basic Science WorkgroupParikh, Samir M.Agarwal, AnupamBajwa, AmandeepKumar, SanjeevMansour, Sherry G.Okusa, Mark D.Cerda, Jorge,Cerda, JorgeAgarwal, AnupamBarreto, ErinGoldstein, StuartLiu, KathleenKoyner, JayMansour, SherryNeyra, JavierOkusa, MarkOsterman, MarliesParikh, SamirVijayan, Anitha2022-06-17T15:54:12-07:00doi:10.34067/KID.0007472021hwp:resource-id:kidney360;3/8/1445American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKINow, basic sciencePerspectivePerspectiveresearch-article20222022-08-2510.34067/KID.00074720212641-76502022-06-17T15:54:12-07:002022-08-25Kidney360Perspective3814451448
- Associations of Anxiety during the COVID-19 Pandemic with Patient Characteristics and Behaviors in CKD Patients: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study10.34067/KID.0000222022Wed, 25 May 2022 06:56:49 GMT-07:00Associations of Anxiety during the COVID-19 Pandemic with Patient Characteristics and Behaviors in CKD Patients: Findings from the Chronic Renal Insufficiency Cohort (CRIC) StudyDorans, Kirsten S.Wright Nunes, Julie A.Schaubel, Douglas E.Sha, DaohangSchrauben, Sarah J.Nelson, Robert G.Rao, Panduranga S.Cohen, Debbie L.Appel, Lawrence J.Lash, James P.Rahman, MahboobFeldman, Harold I.,Appel, Lawrence J.Chen, JingCohen, Debbie L.Feldman, Harold I.Go, Alan S.Lash, James P.Nelson, Robert G.Rahman, MahboobRao, Panduranga S.Shah, Vallabh O.Unruh, Mark L.2022-05-25T06:56:49-07:00doi:10.34067/KID.0000222022hwp:resource-id:kidney360;3/8/1341American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, anxiety, chronic kidney disease, chronic renal disease, COVID-19, disparity, epidemiology and outcomes, SARS-CoV-2Original InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-08-2510.34067/KID.00002220222641-76502022-05-25T06:56:49-07:002022-08-25Kidney360Original Investigation3813411349
- Are Undergraduates Familiar with Nephrology as a Medical Specialty? A Single Site Survey of Undergraduate Students10.34067/KID.0002472022Thu, 02 Jun 2022 01:28:26 GMT-07:00Are Undergraduates Familiar with Nephrology as a Medical Specialty? A Single Site Survey of Undergraduate StudentsHopkins, JuliaVelez, Juan Carlos Q.Arthur, John M.Janech, Michael G.2022-06-02T13:28:26-07:00doi:10.34067/KID.0002472022hwp:resource-id:kidney360;3/8/1332American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, career, exposure, fellowship, nephrology, studentsOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-08-2510.34067/KID.00024720222641-76502022-06-02T13:28:26-07:002022-08-25Kidney360Original Investigation3813321340
- Balancing Hyperkalemia Risks with Clinical Benefits of Renin-Angiotensin-Aldosterone Inhibitors/Mineralocorticoid Receptor Antagonists Blockade: It’s Apples and Oranges10.34067/KID.0000952022Wed, 18 May 2022 11:34:09 GMT-07:00Balancing Hyperkalemia Risks with Clinical Benefits of Renin-Angiotensin-Aldosterone Inhibitors/Mineralocorticoid Receptor Antagonists Blockade: It’s Apples and OrangesLeon, Silvia J.Tangri, Navdeep2022-05-18T11:34:09-07:00doi:10.34067/KID.0000952022hwp:resource-id:kidney360;3/8/1442American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, ACE inhibitors, ARB, finerenone, hyperkalemia, MRA, potassium binders, RAAS inhibitorPerspectivePerspectiveresearch-article20222022-08-2510.34067/KID.00009520222641-76502022-05-18T11:34:09-07:002022-08-25Kidney360Perspective3814421444
- Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y12 Inhibitors in Patients Receiving Dialysis10.34067/KID.0002442022Wed, 18 May 2022 09:36:27 GMT-07:00Age Modifies Intracranial and Gastrointestinal Bleeding Risk from P2Y12 Inhibitors in Patients Receiving DialysisJain, NishankMartin, Bradley C.Dai, JunqiangPhadnis, Milind A.Al-Hindi, LaythShireman, Theresa I.Hedayati, S. SusanRasu, Rafia S.Mehta, Jawahar L.2022-05-18T09:36:27-07:00doi:10.34067/KID.0002442022hwp:resource-id:kidney360;3/8/1374American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, age, clopidogrel, dialysis, gastrointestinal bleeding, intracranial bleeding, P2Y12 inhibitors, prasugrel, ticagrelorOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-08-2510.34067/KID.00024420222641-76502022-05-18T09:36:27-07:002022-08-25Kidney360Original Investigation3813741383
- Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: PROandrew.donati@yale.edu10.34067/KID.0006642021Thu, 20 Jan 2022 12:28:46 GMT-08:00Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: PRODonati, AndrewKrishnan, Namrata2022-01-20T12:28:46-08:00doi:10.34067/KID.0006642021hwp:resource-id:kidney360;3/8/1306American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute interstitial nephritis, acute kidney injury, biopsy, drug-induced acute interstitial nephritis, glucocorticoids, steroidsDebates in NephrologyDebates in Nephrologyresearch-article20222022-08-2510.34067/KID.00066420212641-76502022-01-20T12:28:46-08:002022-08-25Kidney360Debates in Nephrology3813061309
- Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: CON10.34067/KID.0007042021Thu, 20 Jan 2022 12:28:46 GMT-08:00Should Corticosteroids Be Used to Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: CONGallagher, Martin P.Kotwal, Sradha2022-01-20T12:28:46-08:00doi:10.34067/KID.0007042021hwp:resource-id:kidney360;3/8/1310American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephro-pharmacology, acute interstitial nephritis, biopsy, corticosteroidsDebates in NephrologyDebates in Nephrologyresearch-article20222022-08-2510.34067/KID.00070420212641-76502022-01-20T12:28:46-08:002022-08-25Kidney360Debates in Nephrology3813101313
- Should Corticosteroids be Used To Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: COMMENTARY10.34067/KID.0008342021Thu, 20 Jan 2022 12:28:46 GMT-08:00Should Corticosteroids be Used To Treat Biopsy-Proven Drug-Induced Acute Interstitial Nephritis?: COMMENTARYPraga, ManuelCaravaca-Fontán, Fernando2022-01-20T12:28:46-08:00doi:10.34067/KID.0008342021hwp:resource-id:kidney360;3/8/1314American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute interstitial nephritis, biopsy, corticosteroidsModerator CommentaryModerator Commentaryarticle-commentary20222022-08-2510.34067/KID.00083420212641-76502022-01-20T12:28:46-08:002022-08-25Kidney360Moderator Commentary3813141316
- Learning Methodological Lessons from Exemplar Studies in Nephrology: PEXIVAS and Sample Size Calculation10.34067/KID.0005052021Fri, 20 May 2022 11:12:10 GMT-07:00Learning Methodological Lessons from Exemplar Studies in Nephrology: PEXIVAS and Sample Size CalculationSandys, VickiSexton, Donal J.2022-05-20T11:12:10-07:00doi:10.34067/KID.0005052021hwp:resource-id:kidney360;3/8/1427American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, PEXIVAS, plasma exchange, plasmapheresis, sample sizeClinical Research MethodsClinical Research Methodsresearch-article20222022-08-2510.34067/KID.00050520212641-76502022-05-20T11:12:10-07:002022-08-25Kidney360Clinical Research Methods3814271430
- Associations of Dysnatremia with COVID-19 Status and Mortality10.34067/KID.0001062022Fri, 03 Jun 2022 03:49:41 GMT-07:00Associations of Dysnatremia with COVID-19 Status and MortalityLiu, DianeMowrey, WenzhuFisher, MollyBasalely, AbbyMcCarthy, JohnKumar, NeeljaThakkar, JyotsanaAzzi, YorgBrogan, MaureenGolestaneh, LadanReidy, Kimberly JChen, Wei2022-06-03T15:49:41-07:00doi:10.34067/KID.0001062022hwp:resource-id:kidney360;3/8/1323American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, acute kidney injury, COVID-19, dysnatremia, hypernatremia, hyponatremia, mortality, SARS-CoV-2Original InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20222022-08-2510.34067/KID.00010620222641-76502022-06-03T15:49:41-07:002022-08-25Kidney360Original Investigation3813231331
- Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis10.34067/KID.0000812022Tue, 24 May 2022 01:38:02 GMT-07:00Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental GlomerulosclerosisNagano, ChinaHara, ShigeoYoshikawa, NorishigeTakeda, AsamiGotoh, YoshimitsuHamada, RikuMatsuoka, KentaroYamamoto, MasakiFujinaga, ShuichiroSakuraya, KojiKamei, KoichiHamasaki, YukoOguchi, HideyoAraki, YoshinoriOgawa, YayoiOkamoto, TakayukiIto, ShuichiTanaka, SeijiKaito, HiroshiAoto, YuyaIshiko, ShinyaRossanti, RiniSakakibara, NanaHorinouchi, TomokoYamamura, TomohikoNagase, HiroakiIijima, KazumotoNozu, Kandai2022-05-24T13:38:02-07:00doi:10.34067/KID.0000812022hwp:resource-id:kidney360;3/8/1384American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, Columbia classification, end stage kidney disease, focal segmental glomerulosclerosis, genetic renal disease, genotype-phenotype correlation, histopathology, nephrotic syndrome, variantOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-08-2510.34067/KID.00008120222641-76502022-05-24T13:38:02-07:002022-08-25Kidney360Original Investigation3813841393
- The Utilization of Packed Red Blood Cell Transfusion and Angiography in Pediatric Inpatients after Kidney Biopsy in the United States10.34067/KID.0000022022Wed, 18 May 2022 09:36:27 GMT-07:00The Utilization of Packed Red Blood Cell Transfusion and Angiography in Pediatric Inpatients after Kidney Biopsy in the United StatesAfolabi, HalimatO’Shaughnessy, Michelle M.Charu, Vivek2022-05-18T09:36:27-07:00doi:10.34067/KID.0000022022hwp:resource-id:kidney360;3/8/1423American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, health services research, kidney biopsyBrief CommunicationGlomerular and Tubulointerstitial DiseasesBrief CommunicationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-08-2510.34067/KID.00000220222641-76502022-05-18T09:36:27-07:002022-08-25Kidney360Brief Communication3814231426
- Continuous KRTAKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.10.2215/CJN.04350422Thu, 18 Aug 2022 10:25:48 GMT-07:00Continuous KRTAKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.Teixeira, J. PedroNeyra, Javier A.Tolwani, Ashita2022-08-18T10:25:48-07:00doi:10.2215/CJN.04350422hwp:resource-id:clinjasn;CJN.04350422v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury Series, CRRT, AKI, ICU, renal replacement therapy, continuous KRT, acute kidney injuryInvited FeaturesCritical Care Nephrology and Acute Kidney InjuryInvited FeaturesCritical Care Nephrology and Acute Kidney Injuryresearch-article202210.2215/CJN.043504221555-90411555-905X2022-08-18T10:25:48-07:00Clinical Journal of the American Society of NephrologyInvited FeaturesCJN.04350422
- How I Manage Hypertension and Proteinuria Associated with VEGF Inhibitor10.2215/CJN.05610522Wed, 17 Aug 2022 06:47:39 GMT-07:00How I Manage Hypertension and Proteinuria Associated with VEGF InhibitorRashidi, ArashWanchoo, RimdaIzzedine, Hassan2022-08-17T06:47:39-07:00doi:10.2215/CJN.05610522hwp:resource-id:clinjasn;CJN.05610522v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproteinuria, hypertensionKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article202210.2215/CJN.056105221555-90411555-905X2022-08-17T06:47:39-07:00Clinical Journal of the American Society of NephrologyKidney Case Conference: How I TreatCJN.05610522
- Soluble ACE2 is Filtered into the UrineBackground: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, ACE2 has highest levels of abundance in the kidney with expression in a number of extra-renal tissues as well. Previously, we reported an association between enhanced susceptibility to hypertension and elevated renal AngII levels in global ACE2 knockout mice. Methods: To examine the impact of ACE2 expressed in the kidney, relative to extra-renal expression, on the development of hypertension, we utilized a kidney cross-transplantation strategy with ACE2 KO and WT mice. In this model, both native kidneys are removed and renal function is provided entirely by the transplanted kidney such that 4 experimental groups with restricted ACE2 expression are generated: WT→WT (WT), KO→WT (KidneyKO), WT→KO (SystemicKO), and KO→KO (TotalKO). Additionally, we utilized nano-scale mass spectrometry-based proteomics to identify ACE2 fragments in early glomerular filtrate of mice. Result: Although significant differences in BP were not detected, a major finding of our study is that shed or soluble ACE2 (sACE2) was present in urine of KidneyKO mice which lack renal ACE2 expression. Detection of sACE2 in the urine of KidneyKO mice during AngII hypertension suggests that sACE2 originating from extra-renal tissues is able to reach the kidney and can be excreted in urine. To confirm glomerular filtration of ACE2, we used micropuncture and nano-scale proteomics to detect peptides derived from ACE2 in Bowman's space. Conclusions: Our findings suggest that both systemic and renal tissues may contribute to sACE2 in urine, identifying the kidney as a major site for ACE2 actions. Moreover, filtration of sACE2 into the lumen of the nephron may contribute to the pathophysiology of kidney diseases characterized by disruption of the glomerular flitration barrier.gurley@ohsu.edu10.34067/KID.0001622022Wed, 10 Aug 2022 01:41:42 GMT-07:00Soluble ACE2 is Filtered into the UrineBackground: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, ACE2 has highest levels of abundance in the kidney with expression in a number of extra-renal tissues as well. Previously, we reported an association between enhanced susceptibility to hypertension and elevated renal AngII levels in global ACE2 knockout mice. Methods: To examine the impact of ACE2 expressed in the kidney, relative to extra-renal expression, on the development of hypertension, we utilized a kidney cross-transplantation strategy with ACE2 KO and WT mice. In this model, both native kidneys are removed and renal function is provided entirely by the transplanted kidney such that 4 experimental groups with restricted ACE2 expression are generated: WT→WT (WT), KO→WT (KidneyKO), WT→KO (SystemicKO), and KO→KO (TotalKO). Additionally, we utilized nano-scale mass spectrometry-based proteomics to identify ACE2 fragments in early glomerular filtrate of mice. Result: Although significant differences in BP were not detected, a major finding of our study is that shed or soluble ACE2 (sACE2) was present in urine of KidneyKO mice which lack renal ACE2 expression. Detection of sACE2 in the urine of KidneyKO mice during AngII hypertension suggests that sACE2 originating from extra-renal tissues is able to reach the kidney and can be excreted in urine. To confirm glomerular filtration of ACE2, we used micropuncture and nano-scale proteomics to detect peptides derived from ACE2 in Bowman's space. Conclusions: Our findings suggest that both systemic and renal tissues may contribute to sACE2 in urine, identifying the kidney as a major site for ACE2 actions. Moreover, filtration of sACE2 into the lumen of the nephron may contribute to the pathophysiology of kidney diseases characterized by disruption of the glomerular flitration barrier.Nelson, Jonathan W.Ortiz-Melo, David I.Mattocks, Natalie K.Emathinger, Jacqueline M.Prescott, JessicaXu, KatherineGriffiths, Robert C.Wakasaki, RumiePiehowski, Paul D.Hutchens, Michael P.Coffman, Thomas M.Gurley, Susan B.2022-08-10T13:41:42-07:00doi:10.34067/KID.0001622022hwp:resource-id:kidney360;KID.0001622022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360ACE2, Soluble ACE2, Kidney, Renin Angiotensin System, Basic ScienceOriginal InvestigationOriginal Investigationother202210.34067/KID.00016220222641-76502641-76502022-08-10T13:41:42-07:00Kidney360Original Investigation3312122086208610.34067/KID.000162202220942094
- Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria10.2215/CJN.01280122Tue, 26 Jul 2022 10:31:25 GMT-07:00Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade ProteinuriaWang, ShudanSpielman, AllanGinsberg, MindyPetri, MichelleRovin, Brad H.Buyon, JillBroder, Anna2022-07-26T10:31:25-07:00doi:10.2215/CJN.01280122hwp:resource-id:clinjasn;17/8/1150American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproteinuria, systemic lupus erythematosusOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-08-01August 202210.2215/CJN.012801221555-90411555-905X2022-07-26T10:31:25-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17811501158
- Trainee Perspectives on Race, Antiracism, and the Path toward Justice in Kidney Care10.2215/CJN.02500222Tue, 07 Jun 2022 07:32:08 GMT-07:00Trainee Perspectives on Race, Antiracism, and the Path toward Justice in Kidney CareHeffron, Anna S.Khazanchi, RohanNkinsi, NaomiBervell, Joel A.Cerdeña, Jessica P.Diao, James A.Eisenstein, Leo GordonGillespie, Nali JuliaHongsermeier-Graves, NatashaKane, MaddyKaur, KarampreetSeija, Luis E.Tsai, JenniferVyas, Darshali A.Zhang, Angela Y.2022-06-07T07:32:08-07:00doi:10.2215/CJN.02500222hwp:resource-id:clinjasn;17/8/1251American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, equity, diversity, bias, ethnicityPerspectivePerspectiveresearch-article20222022-08-01August 202210.2215/CJN.025002221555-90411555-905X2022-06-07T07:32:08-07:002022-08Clinical Journal of the American Society of NephrologyPerspective17812511254
- Age and the Course of GFR in Persons Aged 70 and Above10.2215/CJN.16631221Mon, 18 Jul 2022 11:41:05 GMT-07:00Age and the Course of GFR in Persons Aged 70 and AboveSchaeffner, Elke S.Ebert, NatalieKuhlmann, Martin K.Martus, PeterMielke, NinaSchneider, Alicevan der Giet, MarkusHuscher, Dörte2022-07-18T11:41:05-07:00doi:10.2215/CJN.16631221hwp:resource-id:clinjasn;17/8/1119American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal function decline, geriatric nephrology, glomerular filtration rate, chronic kidney diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-08-01August 202210.2215/CJN.166312211555-90411555-905X2022-07-18T11:41:05-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17881119110711281109
- HIF-PHIs for Anemia Management in CKD10.2215/CJN.02440222Tue, 05 Jul 2022 05:42:16 GMT-07:00HIF-PHIs for Anemia Management in CKDMcCallum, WendyWeiner, Daniel E.2022-07-05T05:42:16-07:00doi:10.2215/CJN.02440222hwp:resource-id:clinjasn;17/8/1255American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, chronic kidney disease, dialysis, HIF-PHI, erythropoiesis stimulating agentPerspectivePerspectiveresearch-article20222022-08-01August 202210.2215/CJN.024402221555-90411555-905X2022-07-05T05:42:16-07:002022-08Clinical Journal of the American Society of NephrologyPerspective17812551258
- Short-Term Changes in Serum Potassium and the Risk of Subsequent Vascular Events and Mortality10.2215/CJN.00180122Wed, 27 Jul 2022 05:41:45 GMT-07:00Short-Term Changes in Serum Potassium and the Risk of Subsequent Vascular Events and MortalityOhkuma, ToshiakiHarris, KatieCooper, MarkGrobbee, Diederick E.Hamet, PavelHarrap, StephenMancia, GiuseppeMarre, MichelPatel, AnushkaRodgers, AnthonyWilliams, BryanWoodward, MarkChalmers, John2022-07-27T05:41:45-07:00doi:10.2215/CJN.00180122hwp:resource-id:clinjasn;17/8/1139American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyACE inhibitors, randomized controlled trials, hyperkalemia, discontinuation, renin angiotensin systemOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-08-01August 202210.2215/CJN.001801221555-90411555-905X2022-07-27T05:41:45-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17881139111611491118
- Correction: CRRT Fluid Choices: A Solution for a Common Problem?10.2215/CJN.06480622Mon, 25 Jul 2022 06:11:43 GMT-07:00Correction: CRRT Fluid Choices: A Solution for a Common Problem?American Society of Nephrology2022-07-25T06:11:43-07:00doi:10.2215/CJN.06480622hwp:resource-id:clinjasn;17/8/1219American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20222022-08-01August 202210.2215/CJN.064806221555-90411555-905X2022-07-25T06:11:43-07:002022-08Clinical Journal of the American Society of NephrologyErratum17178512196311219633
- Correction: Fractional Excretion of Sodium (FENa): An Imperfect Tool for a Flawed Question10.2215/CJN.06410522Mon, 25 Jul 2022 06:11:43 GMT-07:00Correction: Fractional Excretion of Sodium (FENa): An Imperfect Tool for a Flawed QuestionAmerican Society of Nephrology2022-07-25T06:11:43-07:00doi:10.2215/CJN.06410522hwp:resource-id:clinjasn;17/8/1218American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20222022-08-01August 202210.2215/CJN.064105221555-90411555-905X2022-07-25T06:11:43-07:002022-08Clinical Journal of the American Society of NephrologyErratum17178612187771218778
- Anxiety, Comorbid Depression, and Dialysis Symptom Burden10.2215/CJN.01210122Mon, 13 Jun 2022 05:05:30 GMT-07:00Anxiety, Comorbid Depression, and Dialysis Symptom BurdenCukor, DanielDonahue, StephanieTummalapalli, Sri LekhaBohmart, AndrewSilberzweig, Jeffrey2022-06-13T05:05:30-07:00doi:10.2215/CJN.01210122hwp:resource-id:clinjasn;17/8/1216American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepression, anxietyResearch LetterResearch Letterletter20222022-08-01August 202210.2215/CJN.012101221555-90411555-905X2022-06-13T05:05:30-07:002022-08Clinical Journal of the American Society of NephrologyResearch Letter17812161217
- Physiology of the Aging Kidney10.2215/CJN.06880622Mon, 18 Jul 2022 11:55:37 GMT-07:00Physiology of the Aging KidneyDelanaye, PierrePottel, HansMelsom, Toralf2022-07-18T11:55:37-07:00doi:10.2215/CJN.06880622hwp:resource-id:clinjasn;17/8/1107American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular filtration rateEditorialEditorialeditorial20222022-08-01August 202210.2215/CJN.068806221555-90411555-905X2022-07-18T11:55:37-07:002022-08Clinical Journal of the American Society of NephrologyEditorial17178811110711191673110911281673
- Health Care for Older Adults with Kidney Failure10.2215/CJN.07110622Thu, 28 Jul 2022 07:07:40 GMT-07:00Health Care for Older Adults with Kidney FailureFonseca-Correa, Jorge I.Jassal, S. Vanita2022-07-28T07:07:40-07:00doi:10.2215/CJN.07110622hwp:resource-id:clinjasn;17/8/1110American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, quality of lifeEditorialEditorialeditorial20222022-08-01August 202210.2215/CJN.071106221555-90411555-905X2022-07-28T07:07:40-07:002022-08Clinical Journal of the American Society of NephrologyEditorial17881110115911121167
- How I Treat IgA Nephropathy10.2215/CJN.02710322Wed, 08 Jun 2022 05:51:14 GMT-07:00How I Treat IgA NephropathyReich, Heather N.Floege, Jürgen2022-06-08T05:51:14-07:00doi:10.2215/CJN.02710322hwp:resource-id:clinjasn;17/8/1243American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathyKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-08-01August 202210.2215/CJN.027103221555-90411555-905X2022-06-08T05:51:14-07:002022-08Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat17812431246
- Calamari, Hyperkalemia, and Renin-Angiotensin System Blockade10.2215/CJN.07280622Wed, 27 Jul 2022 06:06:27 GMT-07:00Calamari, Hyperkalemia, and Renin-Angiotensin System BlockadeJanak, EmilyKramer, Holly2022-07-27T06:06:27-07:00doi:10.2215/CJN.07280622hwp:resource-id:clinjasn;17/8/1116American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, diabetes, renin angiotensin system, ACE inhibitorsEditorialEditorialeditorial20222022-08-01August 202210.2215/CJN.072806221555-90411555-905X2022-07-27T06:06:27-07:002022-08Clinical Journal of the American Society of NephrologyEditorial17881116113911181149
- Novel Approaches for the Removal of Uremic Solutes10.2215/CJN.06860622Thu, 14 Jul 2022 07:20:22 GMT-07:00Novel Approaches for the Removal of Uremic SolutesTang, MengyaoKalim, Sahir2022-07-14T07:20:22-07:00doi:10.2215/CJN.06860622hwp:resource-id:clinjasn;17/8/1113American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, uremic solutesEditorialEditorialeditorial20222022-08-01August 202210.2215/CJN.068606221555-90411555-905X2022-07-14T07:20:22-07:002022-08Clinical Journal of the American Society of NephrologyEditorial17881113116811151175
- Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKD10.2215/CJN.05270522Thu, 09 Jun 2022 09:42:01 GMT-07:00Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKDHiremath, SwapnilMcGuinty, MichaelineArgyropoulos, ChristosBrimble, K. ScottBrown, Pierre AntoineChagla, ZainCooper, RebeccaHoar, StephanieJuurlink, DavidTreleaven, DarinWalsh, MichaelYeung, AngieBlake, Peter2022-06-09T09:42:01-07:00doi:10.2215/CJN.05270522hwp:resource-id:clinjasn;17/8/1247American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, dialysis, drug metabolism, pharmacokinetics, transplantation, chronic kidney diseasePerspectivePerspectiveresearch-article20222022-08-01August 202210.2215/CJN.052705221555-90411555-905X2022-06-09T09:42:01-07:002022-08Clinical Journal of the American Society of NephrologyPerspective17812471250
- Relative Contributions of Pseudohypoxia and Inflammation to Peritoneal Alterations with Long-Term Peritoneal Dialysis PatientsLong-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.10.2215/CJN.15371121Tue, 15 Feb 2022 07:19:38 GMT-08:00Relative Contributions of Pseudohypoxia and Inflammation to Peritoneal Alterations with Long-Term Peritoneal Dialysis PatientsLong-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.Krediet, Raymond T.Parikova, Alena2022-02-15T07:19:38-08:00doi:10.2215/CJN.15371121hwp:resource-id:clinjasn;17/8/1259American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypseudohypoxia, inflammation, peritoneal dialysis, peritoneal membrane alterations, vascular endothelial growth factor, plasminogen activator inhibitor-1, connective tissue growth factor, glucose exposureReviewReviewreview-article20222022-08-01August 202210.2215/CJN.153711211555-90411555-905X2022-02-15T07:19:38-08:002022-08Clinical Journal of the American Society of NephrologyReview17812591266
- Removal of Uremic Solutes from Dialysate by Activated Carbon10.2215/CJN.01610222Thu, 14 Jul 2022 07:20:22 GMT-07:00Removal of Uremic Solutes from Dialysate by Activated CarbonLee, SeolhyunSirich, Tammy L.Blanco, Ignacio J.Plummer, Natalie S.Meyer, Timothy W.2022-07-14T07:20:22-07:00doi:10.2215/CJN.01610222hwp:resource-id:clinjasn;17/8/1168American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, uremia, urea modeling, charcoalOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-08-01August 202210.2215/CJN.016102221555-90411555-905X2022-07-14T07:20:22-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17881168111311751115
- Association of HLA Mismatches and Histology Suggestive of Antibody-Mediated Injury in the Absence of Donor-Specific Anti-HLA Antibodies10.2215/CJN.00570122Wed, 01 Jun 2022 11:56:25 GMT-07:00Association of HLA Mismatches and Histology Suggestive of Antibody-Mediated Injury in the Absence of Donor-Specific Anti-HLA AntibodiesSenev, AleksandarLerut, EvelyneCoemans, MaartenCallemeyn, JasperCopley, Hannah CharlotteClaas, FransKoshy, PriyankaKosmoliaptsis, VasilisKuypers, DirkSprangers, BenVan Craenenbroeck, AmaryllisVan Loon, ElisabetVan Sandt, VickyEmonds, Marie-PauleNaesens, Maarten2022-06-01T11:56:25-07:00doi:10.2215/CJN.00570122hwp:resource-id:clinjasn;17/8/1204American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute allograft rejection, immunology, kidney biopsy, kidney transplantation, rejection, renal biopsy, renal transplantation, antibody-mediated rejection, human leukocyte antigenOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-08-01August 202210.2215/CJN.005701221555-90411555-905X2022-06-01T11:56:25-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17812041215
- Long-Term Effect of Physical Exercise on the Risk for Hospitalization and Death in Dialysis Patients10.2215/CJN.03160322Mon, 25 Jul 2022 05:57:33 GMT-07:00Long-Term Effect of Physical Exercise on the Risk for Hospitalization and Death in Dialysis PatientsMallamaci, FrancescaD’Arrigo, GraziellaTripepi, GiovanniLamberti, NicolaTorino, ClaudiaManfredini, FabioZoccali, Carmine2022-07-25T05:57:33-07:00doi:10.2215/CJN.03160322hwp:resource-id:clinjasn;17/8/1176American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyexercise, chronic kidney failure, CKD, hospitalization, deathOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-08-01August 202210.2215/CJN.031603221555-90411555-905X2022-07-25T05:57:33-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17811761182
- Quality of Life before and after the Start of Dialysis in Older Patients10.2215/CJN.16371221Thu, 28 Jul 2022 06:55:05 GMT-07:00Quality of Life before and after the Start of Dialysis in Older Patientsde Rooij, Esther N.M.Meuleman, Yvettede Fijter, Johan W.Le Cessie, SaskiaJager, Kitty J.Chesnaye, Nicholas C.Evans, MariePagels, Agneta A.Caskey, Fergus J.Torino, ClaudiaPorto, GaetanaSzymczak, MaciejDrechsler, ChristianeWanner, ChristophDekker, Friedo W.Hoogeveen, Ellen K.2022-07-28T06:55:05-07:00doi:10.2215/CJN.16371221hwp:resource-id:clinjasn;17/8/1159American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyquality of life, dialysis, end stage kidney disease, agedOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-08-01August 202210.2215/CJN.163712211555-90411555-905X2022-07-28T06:55:05-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17881159111011671112
- Drug-Induced Acute Kidney InjuryMedications are a common cause of AKI, especially for patients admitted to hospital wards and the intensive care unit. Although drug-related kidney injury occurs through different mechanisms, this review will focus on three specific types of tubulointerstitial injury. Direct acute tubular injury develops from several medications, which are toxic to various cellular functions. Their excretory pathways through the proximal tubules contribute further to AKI. Drug-induced AKI may also develop through induction of inflammation within the tubulointerstitium. Medications can elicit a T cell–mediated immune response that promotes the development of acute interstitial nephritis leading to AKI. Although less common, a third pathway to kidney injury results from the insolubility of drugs in the urine leading to their precipitation as crystals within distal tubular lumens, causing a crystalline-related AKI. Intratubular obstruction, direct tubular injury, and localized inflammation lead to AKI. Clinicians should be familiar with the pathogenesis and clinical-pathologic manifestations of these forms of kidney injury. Prevention and treatment of AKI relies on understanding the pathogenesis and judiciously using these agents in settings where AKI risk is high.10.2215/CJN.11290821Thu, 10 Mar 2022 07:00:02 GMT-08:00Drug-Induced Acute Kidney InjuryMedications are a common cause of AKI, especially for patients admitted to hospital wards and the intensive care unit. Although drug-related kidney injury occurs through different mechanisms, this review will focus on three specific types of tubulointerstitial injury. Direct acute tubular injury develops from several medications, which are toxic to various cellular functions. Their excretory pathways through the proximal tubules contribute further to AKI. Drug-induced AKI may also develop through induction of inflammation within the tubulointerstitium. Medications can elicit a T cell–mediated immune response that promotes the development of acute interstitial nephritis leading to AKI. Although less common, a third pathway to kidney injury results from the insolubility of drugs in the urine leading to their precipitation as crystals within distal tubular lumens, causing a crystalline-related AKI. Intratubular obstruction, direct tubular injury, and localized inflammation lead to AKI. Clinicians should be familiar with the pathogenesis and clinical-pathologic manifestations of these forms of kidney injury. Prevention and treatment of AKI relies on understanding the pathogenesis and judiciously using these agents in settings where AKI risk is high.Perazella, Mark A.Rosner, Mitchell H.2022-03-10T07:00:02-08:00doi:10.2215/CJN.11290821hwp:resource-id:clinjasn;17/8/1220American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury Series, acute kidney injury, drugs, nephrotoxins, acute tubular injury, acute interstitial nephritis, crystalline nephropathy, chronic kidney disease, inflammation, apoptosisCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-08-01August 202210.2215/CJN.112908211555-90411555-905X2022-03-10T07:00:02-08:002022-08Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury17812201233
- Radiographic Contrast Media and the KidneyAKI is a potential complication of intravascular iodinated contrast exposure. Contrast-associated AKI, which typically manifests as small and transient decrements in kidney function that develop within several days of contrast administration, is associated with serious adverse outcomes, including progressive kidney dysfunction and death. However, a causal link between the small increases in serum creatinine that characteristically occur with contrast-associated AKI and serious adverse outcomes remains unproven. This is important given mounting evidence that clinically indicated, potentially lifesaving radiographic procedures are underutilized in patients with CKD. This has been hypothesized to be related to provider concern about precipitating contrast-associated AKI. Intravascular gadolinium-based contrast, an alternative to iodinated contrast that is administered with magnetic resonance imaging, has also been linked with potential serious adverse events, notably the development of nephrogenic systemic fibrosis in patients with severe impairment in kidney function. Patients hospitalized in the intensive care unit frequently have clinical indications for diagnostic and therapeutic procedures that involve the intravascular administration of contrast media. Accordingly, critical care providers and others treating critically ill patients should possess a sound understanding of the risk factors for and incidence of such outcomes, the ability to perform evidence-based risk-benefit assessments regarding intravascular contrast administration, and knowledge of empirical data on the prevention of these iatrogenic complications.10.2215/CJN.16311221Fri, 01 Jul 2022 06:35:28 GMT-07:00Radiographic Contrast Media and the KidneyAKI is a potential complication of intravascular iodinated contrast exposure. Contrast-associated AKI, which typically manifests as small and transient decrements in kidney function that develop within several days of contrast administration, is associated with serious adverse outcomes, including progressive kidney dysfunction and death. However, a causal link between the small increases in serum creatinine that characteristically occur with contrast-associated AKI and serious adverse outcomes remains unproven. This is important given mounting evidence that clinically indicated, potentially lifesaving radiographic procedures are underutilized in patients with CKD. This has been hypothesized to be related to provider concern about precipitating contrast-associated AKI. Intravascular gadolinium-based contrast, an alternative to iodinated contrast that is administered with magnetic resonance imaging, has also been linked with potential serious adverse events, notably the development of nephrogenic systemic fibrosis in patients with severe impairment in kidney function. Patients hospitalized in the intensive care unit frequently have clinical indications for diagnostic and therapeutic procedures that involve the intravascular administration of contrast media. Accordingly, critical care providers and others treating critically ill patients should possess a sound understanding of the risk factors for and incidence of such outcomes, the ability to perform evidence-based risk-benefit assessments regarding intravascular contrast administration, and knowledge of empirical data on the prevention of these iatrogenic complications.Cashion, WinnWeisbord, Steven D.2022-07-01T06:35:28-07:00doi:10.2215/CJN.16311221hwp:resource-id:clinjasn;17/8/1234American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, contrast mediaCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-08-01August 202210.2215/CJN.163112211555-90411555-905X2022-07-01T06:35:28-07:002022-08Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury17812341242
- Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature10.2215/CJN.15011121Tue, 19 Jul 2022 10:29:53 GMT-07:00Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely PrematureHingorani, SangeetaSchmicker, RobertAhmad, Kaashif A.Frantz, Ivan D.Mayock, Dennis E.La Gamma, Edmund F.Baserga, MarianaKhan, Janine Y.Gilmore, Maureen M.Robinson, TonyaBrophy, PatrickHeagerty, Patrick J.Juul, Sandra E.Goldstein, StuartAskenazi, David,Wadhawan, RajanCourtney, Sherry E.Robinson, TonyaAhmad, Kaashif A.Bendel-Stenzel, EllenBaserga, MarianaLaGamma, Edmund F.Downey, L. CorbinRao, RaghavendraFahim, NancyLampland, AndreaFrantz, Ivan D.Khan, JanineWeiss, MichaelGilmore, Maureen M.Ohls, Robin K.Lowe, JeanSrinivasan, NishantPerez, Jorge E.Thomas, Victor McKay BillyElhassan, NahedMulkey, SarahVijayamadhavan, Vivek K.Mulrooney, NeilYoder, BradleyKase, Jordan S.Check, JenniferOsterholm, ErinGeorge, ThomasGeorgieff, MichaelMartin, Camilia R.O’Reilly, DeirdredeRegnier, Raye-AnnPorta, NicolasBazacliu, CatalinaNorthington, FrancesValdez, Raul ChavezSaurabhkumar, PatelDiaz-Barbosa, MagalyRichards, ToddFeltner, John B.Esposito, IsabellaHauge, StephanieNikirk, SamanthaSilvia, AmyClopp, BaileyOtt, DebbieMora, Ariana FrancoHedrick, PamelaFlynn, VickiWyatt, AndreaLoy, EmilieSikes, NatalieMason, MelanieMcConnell, JanaBrown, TiffanyHarrison, HenryPearson, DeniseDrake, TammyWright, JocelynWalden, DebraGuy, AnnetteNason, JenniferTalbot, MorganLee, KristenPenny, SarahBoles, TerriDrummond, MelanieKohlleppel, KatyKathen, CharmaineKaletka, BrianGonzales, ShaniaWorwa, CathyFisher, MollyRichter, TylerGinder, AlexanderReich, BrixenRau, CarrieLoertscher, ManndiCole, LauraMcGrath, KandaceLewis, Kimberlee WeaverBurnett, JillSchaefer, SusanBird, KarieGiblin, ClareDaly, RitaLanier, KristiWarden, KellyWassenaar, JennaEricksen, JensinaDavern, BridgetOsborne, Mary PatTalele, NehaObregon, EvelynZiyeh, TiglathClarke, MollyWegner, Rachel E.Patel, PalakSchau, MollyRussow, AnnamarieCurry, KellyBarnhart, LisaParkinson, CharlamaineBeauman, SandraHanson, MaryKuan, ElizabethLacy, Conra BackstromGalvis, Edshelee M.Bombino, SusanaMartinez, DeniseBell, SuziLong, CorrieNefcy, ChristopherKonodi, Mark A.Hartman, Phuong T. Vu AdamO’Shea, T. MichaelBallard, RobertaO’Shea, MikeKuban, KarlLowe, JeanWidness, John2022-07-19T10:29:53-07:00doi:10.2215/CJN.15011121hwp:resource-id:clinjasn;17/8/1129American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, chronic kidney disease, hypertension, systolic blood pressure, prematurity, epidemiology and outcomes, children, blood pressureOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-08-01August 202210.2215/CJN.150111211555-90411555-905X2022-07-19T10:29:53-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17811291138
- Patterns in Tacrolimus Variability and Association with De Novo Donor-Specific Antibody Formation in Pediatric Kidney Transplant Recipients10.2215/CJN.16421221Tue, 26 Jul 2022 08:45:14 GMT-07:00Patterns in Tacrolimus Variability and Association with De Novo Donor-Specific Antibody Formation in Pediatric Kidney Transplant RecipientsPiburn, Kim H.Sigurjonsdottir, Vaka K.Indridason, Olafur S.Maestretti, LynnPatton, Mary VictoriaMcGrath, AnnePalsson, RunolfurGallo, AmyChaudhuri, AbantiGrimm, Paul C.2022-07-26T08:45:14-07:00doi:10.2215/CJN.16421221hwp:resource-id:clinjasn;17/8/1194American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatric kidney transplantation, tacrolimus, young adult, kidney transplantation, child, immunosuppression, transplant outcomesOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-08-01August 202210.2215/CJN.164212211555-90411555-905X2022-07-26T08:45:14-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17881194110512031106
- Pathophysiological Implications of Variability in Blood Tacrolimus Levels in Pediatric and Adolescent Kidney Transplant Recipients10.2215/CJN.06640622Tue, 26 Jul 2022 08:45:14 GMT-07:00Pathophysiological Implications of Variability in Blood Tacrolimus Levels in Pediatric and Adolescent Kidney Transplant RecipientsBecker-Cohen, Rachel2022-07-26T08:45:14-07:00doi:10.2215/CJN.06640622hwp:resource-id:clinjasn;17/8/1105American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, tacrolimus, kidney transplantation, adolescentEditorialEditorialeditorial20222022-08-01August 202210.2215/CJN.066406221555-90411555-905X2022-07-26T08:45:14-07:002022-08Clinical Journal of the American Society of NephrologyEditorial17881105119411061203
- Association of Genetically Predicted Fibroblast Growth Factor-23 with Heart Failure10.2215/CJN.00960122Thu, 28 Jul 2022 06:55:05 GMT-07:00Association of Genetically Predicted Fibroblast Growth Factor-23 with Heart FailureAkwo, ElvisPike, Mindy M.Ertuglu, Lale A.Vartanian, NicholasFarber-Eger, EricLipworth, LorenPerwad, FarzanaSiew, EdwardHung, AdrianaBansal, Nishade Boer, IanKestenbaum, BryanCox, Nancy J.Ikizler, T. AlpWells, QuinnRobinson-Cohen, Cassianne2022-07-28T06:55:05-07:00doi:10.2215/CJN.00960122hwp:resource-id:clinjasn;17/8/1183American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymineral metabolism, human genetics, heart failure, FGF23, Mendelian randomization analysisOriginal ArticleMineral MetabolismOriginal ArticleMineral Metabolismresearch-article20222022-08-01August 202210.2215/CJN.009601221555-90411555-905X2022-07-28T06:55:05-07:002022-08Clinical Journal of the American Society of NephrologyOriginal Article17811831193
- Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized TrialsBackground: Hyperkalemia is a common electrolyte abnormality in patients with chronic kidney disease (CKD), which is associated with worse outcomes and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi). This post hoc subgroup analysis of three clinical trials evaluated the efficacy and safety of the sodium-free, potassium-binding polymer, patiromer, for the treatment of hyperkalemia in adults with non-dialysis CKD. Methods: Data from the 4-week treatment periods of AMETHYST-DN, OPAL-HK, and TOURMALINE studies were combined. Patients had baseline diagnosis of CKD, hyperkalemia (serum potassium >5.0 mEq/L) and received patiromer 8.4-33.6 g/day. Patients were stratified by baseline estimated glomerular filtration rate (eGFR) into two subgroups: severe/end-stage CKD (Stage 3b-5; eGFR<45 mL/min/1.73m2) and mild/moderate CKD (Stage 1-3a; eGFR ≥45 mL/min/1.73m2). Efficacy was assessed by the change in serum potassium (mean±standard error [SE]) from baseline to week 4. Safety assessments included incidence and severity of adverse events (AEs). Results: Efficacy analyses (N=626; 62% male, mean age 66 years) included 417 (67%) patients with severe/end-stage CKD and 209 (33%) with mild/moderate CKD. Most patients were receiving RAASi therapy at baseline (severe/end-stage CKD: 92%; mild/moderate CKD: 98%). The mean±SE change in serum potassium (baseline to week 4) was −0.84±0.03 in the severe/end-stage CKD subgroup, and −0.60±0.04 mEq/L in the mild/moderate CKD subgroup. AEs were reported for 40% and 27% patients in the severe/end-stage and mild/moderate CKD subgroups, respectively, with 16% and 12% reporting AEs considered related to patiromer. The most frequent AEs were mild-to-moderate constipation (8% and 3%) and diarrhea (4% and 2%). AEs leading to patiromer discontinuation occurred in 6% and 2% of patients with severe/end-stage CKD, and mild/moderate CKD, respectively. Conclusions: Patiromer was effective for treatment of hyperkalemia and well tolerated in patients across stages of CKD, most of whom were receiving guideline-recommended RAASi therapy.haller.hermann@mh-hannover.de10.34067/KID.0001562022Tue, 02 Aug 2022 01:21:50 GMT-07:00Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized TrialsBackground: Hyperkalemia is a common electrolyte abnormality in patients with chronic kidney disease (CKD), which is associated with worse outcomes and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi). This post hoc subgroup analysis of three clinical trials evaluated the efficacy and safety of the sodium-free, potassium-binding polymer, patiromer, for the treatment of hyperkalemia in adults with non-dialysis CKD. Methods: Data from the 4-week treatment periods of AMETHYST-DN, OPAL-HK, and TOURMALINE studies were combined. Patients had baseline diagnosis of CKD, hyperkalemia (serum potassium >5.0 mEq/L) and received patiromer 8.4-33.6 g/day. Patients were stratified by baseline estimated glomerular filtration rate (eGFR) into two subgroups: severe/end-stage CKD (Stage 3b-5; eGFR<45 mL/min/1.73m2) and mild/moderate CKD (Stage 1-3a; eGFR ≥45 mL/min/1.73m2). Efficacy was assessed by the change in serum potassium (mean±standard error [SE]) from baseline to week 4. Safety assessments included incidence and severity of adverse events (AEs). Results: Efficacy analyses (N=626; 62% male, mean age 66 years) included 417 (67%) patients with severe/end-stage CKD and 209 (33%) with mild/moderate CKD. Most patients were receiving RAASi therapy at baseline (severe/end-stage CKD: 92%; mild/moderate CKD: 98%). The mean±SE change in serum potassium (baseline to week 4) was −0.84±0.03 in the severe/end-stage CKD subgroup, and −0.60±0.04 mEq/L in the mild/moderate CKD subgroup. AEs were reported for 40% and 27% patients in the severe/end-stage and mild/moderate CKD subgroups, respectively, with 16% and 12% reporting AEs considered related to patiromer. The most frequent AEs were mild-to-moderate constipation (8% and 3%) and diarrhea (4% and 2%). AEs leading to patiromer discontinuation occurred in 6% and 2% of patients with severe/end-stage CKD, and mild/moderate CKD, respectively. Conclusions: Patiromer was effective for treatment of hyperkalemia and well tolerated in patients across stages of CKD, most of whom were receiving guideline-recommended RAASi therapy.Haller, HermannBianchi, StefanoMcCafferty, KieranArthur, SusanQuinn, Carol MorenoBudden, JeffreyWeir, Matthew R.2022-08-02T13:21:50-07:00doi:10.34067/KID.0001562022hwp:resource-id:kidney360;KID.0001562022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360RAASi, patiromer, hyperkalaemia, chronic kidney diseaseOriginal InvestigationOriginal Investigationother202210.34067/KID.00015620222641-76502641-76502022-08-02T13:21:50-07:00Kidney360Original Investigation3312122019201910.34067/KID.000156202220262026
- Targeted Disruption of a Proximal Tubule–Specific TMEM174 Gene in Mice Causes Hyperphosphatemia and Vascular Calcification10.1681/ASN.2021121578Fri, 22 Apr 2022 10:52:49 GMT-07:00Targeted Disruption of a Proximal Tubule–Specific TMEM174 Gene in Mice Causes Hyperphosphatemia and Vascular CalcificationMiyazaki-Anzai, ShinobuKeenan, Audrey L.Blaine, JudithMiyazaki, Makoto2022-04-22T10:52:49-07:00doi:10.1681/ASN.2021121578hwp:resource-id:jnephrol;33/8/1477American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyTMEM174, NPT2A, proximal tubule, hyperphosphatemia, vascular calcificationRapid CommunicationChronic Kidney DiseaseRapid CommunicationChronic Kidney Diseaseresearch-article20222022-08-01August 202210.1681/ASN.20211215781046-66731533-34502022-04-22T10:52:49-07:002022-08Journal of the American Society of NephrologyRapid Communication33814771486
- A Composite End Point of Graft Status and eGFR at 1 Year to Improve the Scientific Registry of Transplant Recipients’ Five-Tier Rating System10.1681/ASN.2022010078Tue, 10 May 2022 08:57:24 GMT-07:00A Composite End Point of Graft Status and eGFR at 1 Year to Improve the Scientific Registry of Transplant Recipients’ Five-Tier Rating SystemWang, KaichengDeng, YanhongStewart, DarrenFormica, Richard N.2022-05-10T08:57:24-07:00doi:10.1681/ASN.2022010078hwp:resource-id:jnephrol;33/8/1613American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, outcomes, renal transplantation, survival, transplant outcomesClinical ResearchTransplantationClinical ResearchTransplantationresearch-article20222022-08-01August 202210.1681/ASN.20220100781046-66731533-34502022-05-10T08:57:24-07:002022-08Journal of the American Society of NephrologyClinical Research338121613232316242324
- High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and BioactivityFull-length parathyroid hormone (PTH 1–84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1–84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1–84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1–84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1–84, PTH fragments, and post-translationally modified PTH 1–84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.10.1681/ASN.2022010036Fri, 08 Apr 2022 08:35:43 GMT-07:00High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and BioactivityFull-length parathyroid hormone (PTH 1–84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1–84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1–84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1–84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1–84, PTH fragments, and post-translationally modified PTH 1–84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.Ulmer, Candice Z.Kritmetapak, KittraweeSingh, Ravinder J.Vesper, Hubert W.Kumar, Rajiv2022-04-08T08:35:43-07:00doi:10.1681/ASN.2022010036hwp:resource-id:jnephrol;33/8/1448American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyparathyroid hormone, mineral metabolism, mass spectrometryUp Front MattersReviewUp Front MattersReviewreview-article20222022-08-01August 202210.1681/ASN.20220100361046-66731533-34502022-04-08T08:35:43-07:002022-08Journal of the American Society of NephrologyUp Front Matters33814481458
- The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis10.1681/ASN.2021101353Fri, 01 Jul 2022 06:03:12 GMT-07:00The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during HemodialysisRicherson, Wesley T.Schmit, Brian D.Wolfgram, Dawn F.2022-07-01T06:03:12-07:00doi:10.1681/ASN.2021101353hwp:resource-id:jnephrol;33/8/1602American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, vascular disease, end stage kidney diseaseClinical ResearchDialysisClinical ResearchDialysisresearch-article20222022-08-01August 202210.1681/ASN.20211013531046-66731533-34502022-07-01T06:03:12-07:002022-08Journal of the American Society of NephrologyClinical Research33881602i1612i
- Optimizing the Design and Analysis of Future AKI TrialsAKI is a complex clinical syndrome associated with an increased risk of morbidity and mortality, particularly in critically ill and perioperative patient populations. Most AKI clinical trials have been inconclusive, failing to detect clinically important treatment effects at predetermined statistical thresholds. Heterogeneity in the pathobiology, etiology, presentation, and clinical course of AKI remains a key challenge in successfully testing new approaches for AKI prevention and treatment. This article, derived from the “AKI” session of the “Kidney Disease Clinical Trialists” virtual workshop held in October 2021, reviews barriers to and strategies for improving the design and implementation of clinical trials in patients with, or at risk of, developing AKI. The novel approaches to trial design included in this review span adaptive trial designs that increase the knowledge gained from each trial participant; pragmatic trial designs that allow for the efficient enrollment of sufficiently large numbers of patients to detect small, but clinically significant, treatment effects; and platform trial designs that use one trial infrastructure to answer multiple clinical questions simultaneously. This review also covers novel approaches to clinical trial analysis, such as Bayesian analysis and assessing heterogeneity in the response to therapies among trial participants. We also propose a road map and actionable recommendations to facilitate the adoption of the reviewed approaches. We hope that the resulting road map will help guide future clinical trial planning, maximize learning from AKI trials, and reduce the risk of missing important signals of benefit (or harm) from trial interventions.10.1681/ASN.2021121605Wed, 13 Jul 2022 06:34:39 GMT-07:00Optimizing the Design and Analysis of Future AKI TrialsAKI is a complex clinical syndrome associated with an increased risk of morbidity and mortality, particularly in critically ill and perioperative patient populations. Most AKI clinical trials have been inconclusive, failing to detect clinically important treatment effects at predetermined statistical thresholds. Heterogeneity in the pathobiology, etiology, presentation, and clinical course of AKI remains a key challenge in successfully testing new approaches for AKI prevention and treatment. This article, derived from the “AKI” session of the “Kidney Disease Clinical Trialists” virtual workshop held in October 2021, reviews barriers to and strategies for improving the design and implementation of clinical trials in patients with, or at risk of, developing AKI. The novel approaches to trial design included in this review span adaptive trial designs that increase the knowledge gained from each trial participant; pragmatic trial designs that allow for the efficient enrollment of sufficiently large numbers of patients to detect small, but clinically significant, treatment effects; and platform trial designs that use one trial infrastructure to answer multiple clinical questions simultaneously. This review also covers novel approaches to clinical trial analysis, such as Bayesian analysis and assessing heterogeneity in the response to therapies among trial participants. We also propose a road map and actionable recommendations to facilitate the adoption of the reviewed approaches. We hope that the resulting road map will help guide future clinical trial planning, maximize learning from AKI trials, and reduce the risk of missing important signals of benefit (or harm) from trial interventions.Legrand, MatthieuBagshaw, Sean M.Koyner, Jay L.Schulman, Ivonne H.Mathis, Michael R.Bernholz, JulianeCoca, StevenGallagher, MartinGaudry, StéphaneLiu, Kathleen D.Mehta, Ravindra L.Pirracchio, RomainRyan, AbigailSteubl, DominikStockbridge, NormanErlandsson, FredrikTuran, AlparslanWilson, F. PerryZarbock, AlexanderBokoch, Michael P.Casey, Jonathan D.Rossignol, PatrickHarhay, Michael O.2022-07-13T06:34:39-07:00doi:10.1681/ASN.2021121605hwp:resource-id:jnephrol;33/8/1459American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, randomized controlled trials, pragmatic, cluster, Bayesian, heterogeneityUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20222022-08-01August 202210.1681/ASN.20211216051046-66731533-34502022-07-13T06:34:39-07:002022-08Journal of the American Society of NephrologyUp Front Matters33814591470
- Channel Function of Polycystin-2 in the Endoplasmic Reticulum Protects against Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2022010053Thu, 14 Jul 2022 05:49:42 GMT-07:00Channel Function of Polycystin-2 in the Endoplasmic Reticulum Protects against Autosomal Dominant Polycystic Kidney DiseasePadhy, BiswajitXie, JianWang, RunpingLin, FangHuang, Chou-Long2022-07-14T05:49:42-07:00doi:10.1681/ASN.2022010053hwp:resource-id:jnephrol;33/8/1501American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, polycystin, endoplasmic reticulum, ion channelBasic ResearchGenetic Disease of the KidneyBasic ResearchGenetic Disease of the Kidneyresearch-article20222022-08-01August 202210.1681/ASN.20220100531046-66731533-34502022-07-14T05:49:42-07:002022-08Journal of the American Society of NephrologyBasic Research338881501i14331516i1434
- Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity10.1681/ASN.2021081142Tue, 07 Jun 2022 08:48:24 GMT-07:00Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease ActivityChen, Dhruti P.McInnis, Elizabeth A.Wu, Eveline Y.Stember, Katherine G.Hogan, Susan L.Hu, YichunHenderson, Candace D.Blazek, Lauren N.Mallal, SimonKarosiene, EditaPeters, BjoernSidney, JohnJames, Eddie A.Kwok, William W.Jennette, J. CharlesCiavatta, Dominic J.Falk, Ronald J.Free, Meghan E.2022-06-07T08:48:24-07:00doi:10.1681/ASN.2021081142hwp:resource-id:jnephrol;33/8/1517American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyHLA, ANCA, PR3, T cell, remission, HLA-DPB1 antigen, maintenanceBasic ResearchGlomerulonephritis and Interstitial NephritisBasic ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-08-01August 202210.1681/ASN.20210811421046-66731533-34502022-06-07T08:48:24-07:002022-08Journal of the American Society of NephrologyBasic Research33881517143515271437
- This Month’s Highlights10.1681/ASN.2022060694Fri, 29 Jul 2022 10:00:25 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2022-07-29T10:00:25-07:00doi:10.1681/ASN.2022060694hwp:resource-id:jnephrol;33/8/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyhighlightsThis Month’s HighlightsThis Month’s Highlightsother20222022-08-01August 202210.1681/ASN.20220606941046-66731533-34502022-07-29T10:00:25-07:002022-08Journal of the American Society of NephrologyThis Month’s Highlights3388888i1501143315691602i1516143415801612
- On the Importance of Considering Glycosylation When Evaluating Biologic Therapies10.1681/ASN.2022040461Fri, 15 Jul 2022 06:33:19 GMT-07:00On the Importance of Considering Glycosylation When Evaluating Biologic TherapiesLemaire, Mathieu2022-07-15T06:33:19-07:00doi:10.1681/ASN.2022040461hwp:resource-id:jnephrol;33/8/1625American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, recombinant antibodies, glycosylation, neuraminic acidLetter to the EditorLetter to the Editorletter20222022-08-01August 202210.1681/ASN.20220404611046-66731533-34502022-07-15T06:33:19-07:002022-08Journal of the American Society of NephrologyLetter to the Editor338810162516262652162516262663
- Serum Protein-Induced Tubular Injury10.1681/ASN.2022050568Fri, 29 Jul 2022 10:00:25 GMT-07:00Serum Protein-Induced Tubular InjuryO’Neill, W. Charles2022-07-29T10:00:25-07:00doi:10.1681/ASN.2022050568hwp:resource-id:jnephrol;33/8/1627American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyserumLetter to the EditorLetter to the Editorletter20222022-08-01August 202210.1681/ASN.20220505681046-66731533-34502022-07-29T10:00:25-07:002022-08Journal of the American Society of NephrologyLetter to the Editor338851627162794916271628965
- Collaboration between Dialysis Providers10.1681/ASN.2021111475Thu, 02 Jun 2022 10:56:36 GMT-07:00Collaboration between Dialysis ProvidersSilberzweig, JeffreyBhat, J. GaneshDittrich, Mary O.Durvasula, RaghuGiullian, JeffHymes, Jeffrey L.Johnson, DougSchiller, BrigitteSpech, RichardSpry, LeslieWalker, Geoffrey ScottWatnick, SuzanneYee, JerryFreedman, Barry I.2022-06-02T10:56:36-07:00doi:10.1681/ASN.2021111475hwp:resource-id:jnephrol;33/8/1440American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, dialysis, end stage kidney disease, outcomes, patient-centered careUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20222022-08-01August 202210.1681/ASN.20211114751046-66731533-34502022-06-02T10:56:36-07:002022-08Journal of the American Society of NephrologyUp Front Matters33814401444
- A Deep Learning Approach for Automated Segmentation of Kidneys and Exophytic Cysts in Individuals with Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2021111400Wed, 29 Jun 2022 08:14:50 GMT-07:00A Deep Learning Approach for Automated Segmentation of Kidneys and Exophytic Cysts in Individuals with Autosomal Dominant Polycystic Kidney DiseaseKim, YoungwooTao, ChengKim, HyungchanOh, Geum-YoonKo, JeongbeomBae, Kyongtae T.2022-06-29T08:14:50-07:00doi:10.1681/ASN.2021111400hwp:resource-id:jnephrol;33/8/1581American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, chronic kidney disease, chronic kidney failure, cystic kidney, kidney volume, risk factors, deep learning, exophytic cyst, image segmentationClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-08-01August 202210.1681/ASN.20211114001046-66731533-34502022-06-29T08:14:50-07:002022-08Journal of the American Society of NephrologyClinical Research33815811589
- Vaccination, Transplantation, and a Social Contract10.1681/ASN.2021111501Wed, 11 May 2022 08:24:36 GMT-07:00Vaccination, Transplantation, and a Social ContractKates, Olivia S.Limaye, Ajit P.Kaplan, Bruce2022-05-11T08:24:36-07:00doi:10.1681/ASN.2021111501hwp:resource-id:jnephrol;33/8/1445American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyvirology, transplantation, kidney transplantation, COVID-19, SARS-CoV-2, COVID-19 vaccinesUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20222022-08-01August 202210.1681/ASN.20211115011046-66731533-34502022-05-11T08:24:36-07:002022-08Journal of the American Society of NephrologyUp Front Matters33814451447
- Complementary Nck1/2 Signaling in Podocytes Controls α Actinin-4–Mediated Actin Organization, Adhesion, and Basement Membrane Composition10.1681/ASN.2021101343Fri, 29 Jul 2022 10:00:25 GMT-07:00Complementary Nck1/2 Signaling in Podocytes Controls α Actinin-4–Mediated Actin Organization, Adhesion, and Basement Membrane CompositionMartin, Claire E.Phippen, Noah J.Keyvani Chahi, AvaTilak, ManaliBanerjee, Sara L.Lu, PeihuaNew, Laura A.Williamson, Casey R.Platt, Mathew J.Simpson, Jeremy A.Krendel, MiraBisson, NicolasGingras, Anne-ClaudeJones, Nina2022-07-29T10:00:25-07:00doi:10.1681/ASN.2021101343hwp:resource-id:jnephrol;33/8/1546American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, mass spectrometry, cell adhesion, extracellular matrix, actin cytoskeleton, Nck1/2, proteomics, transcriptomics, mouse models, basement membraneBasic ResearchNormal Kidney Structure and FunctionBasic ResearchNormal Kidney Structure and Functionresearch-article20222022-08-01August 202210.1681/ASN.20211013431046-66731533-34502022-07-29T10:00:25-07:002022-08Journal of the American Society of NephrologyBasic Research33815461567
- Housing: A Critical Contributor to Kidney Disease Disparities10.1681/ASN.2022040424Wed, 11 May 2022 08:24:36 GMT-07:00Housing: A Critical Contributor to Kidney Disease DisparitiesNovick, Tessa K.Baweja, Mukta,Novick, TessaBaweja, MuktaBrowne, TeriMahooty, Stephanie J.Ng, Yue-HarnRizzolo, KatherineRobinson, LisaSekkarie, Mohamed A.Young, Bessie A.2022-05-11T08:24:36-07:00doi:10.1681/ASN.2022040424hwp:resource-id:jnephrol;33/8/1471American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologydisparities, housing, socioeconomic status, racial and ethnic disparitiesPerspectiveAddressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-08-01August 202210.1681/ASN.20220404241046-66731533-34502022-05-11T08:24:36-07:002022-08Journal of the American Society of NephrologyPerspective33814711473
- Myeloid CCR2 Promotes Atherosclerosis after AKI10.1681/ASN.2022010048Tue, 10 May 2022 08:57:25 GMT-07:00Myeloid CCR2 Promotes Atherosclerosis after AKIHüsing, Anne M.Wulfmeyer, Vera C.Gaedcke, SvenjaFleig, Susanne V.Rong, SongDeLuca, DavidHaller, HermannSchmitt, Rolandvon Vietinghoff, Sibylle2022-05-10T08:57:25-07:00doi:10.1681/ASN.2022010048hwp:resource-id:jnephrol;33/8/1487American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriosclerosis, cardiovascular disease, chronic inflammation, renal ischemia, macrophages, acute kidney injuryBasic ResearchAcute Kidney InjuryBasic ResearchAcute Kidney Injuryresearch-article20222022-08-01August 202210.1681/ASN.20220100481046-66731533-34502022-05-10T08:57:25-07:002022-08Journal of the American Society of NephrologyBasic Research33814871500
- Unfulfilled Expectations Open New Horizons: What Have We Learned about Volume-Regulated Anion Channels in the Kidney?10.1681/ASN.2022050588Fri, 15 Jul 2022 06:33:18 GMT-07:00Unfulfilled Expectations Open New Horizons: What Have We Learned about Volume-Regulated Anion Channels in the Kidney?Pochynyuk, OlehPalygin, Oleg2022-07-15T06:33:18-07:00doi:10.1681/ASN.2022050588hwp:resource-id:jnephrol;33/8/1437American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologySWELL1, LRRC8, VRAC, proximal tubule, cell volume regulation, anionsUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-08-01August 202210.1681/ASN.20220505881046-66731533-34502022-07-15T06:33:18-07:002022-08Journal of the American Society of NephrologyUp Front Matters33881437152814391545
- Authors’ Reply: Serum Protein-induced Tubular Injury10.1681/ASN.2022060657Fri, 29 Jul 2022 10:00:25 GMT-07:00Authors’ Reply: Serum Protein-induced Tubular InjuryLidberg, KevinHimmelfarb, JonathanKelly, EdwardAkilesh, Shreeram2022-07-29T10:00:25-07:00doi:10.1681/ASN.2022060657hwp:resource-id:jnephrol;33/8/1627-aAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, cell activation, cytokines, kidney dysfunction, nephrotic syndrome, proteinuria, proximal tubule, transcription regulationLetter to the EditorLetter to the Editorletter20222022-08-01August 202210.1681/ASN.20220606571046-66731533-34502022-07-29T10:00:25-07:002022-08Journal of the American Society of NephrologyLetter to the Editor338851627162794916281627965
- Polycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the Cilium10.1681/ASN.2022050557Fri, 29 Jul 2022 10:00:25 GMT-07:00Polycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the CiliumCaplan, Michael J.2022-07-29T10:00:25-07:00doi:10.1681/ASN.2022050557hwp:resource-id:jnephrol;33/8/1433American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystin-2, endoplasmic reticulum, IP3 receptor, calcium, cilium, polycystic kidney diseaseUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-08-01August 202210.1681/ASN.20220505571046-66731533-34502022-07-29T10:00:25-07:002022-08Journal of the American Society of NephrologyUp Front Matters338881433i15011434i1516
- Coronary Artery Calcification Score and the Progression of Chronic Kidney Disease10.1681/ASN.2022010080Thu, 02 Jun 2022 10:56:36 GMT-07:00Coronary Artery Calcification Score and the Progression of Chronic Kidney DiseaseYun, Hae-RyongJoo, Young SuKim, Hyung WooPark, Jung TakChang, Tae IkSon, Nak-HoonYoo, Tae-HyunKang, Shin-WookSung, SuahLee, Kyu-BeckLee, JoongyubOh, Kook-HwanHan, Seung Hyeok,Ahn, CurieOh, Kook-HwanHan, Seung SeokLee, HajeongKoh, Young OkSo, JeongokKo, SeonuiLee, AramChae, Dong WanJeong, Jong CheolCho, Hyun JinOh, Jung EunLee, Kyu JinYoo, Tae-HyunChoi, Kyu HunHan, Seung HyeokPark, Jung TakHong, Hui KyungYou, Ji YoungLee, Kyu-BeckHyun, Young YoulKim, Hyun JungKim, Yong-SooKim, YaeniKim, Sol JiChung, WookyungJung, Ji YongJin, Kwon EunSung, SuahMin, Hyang KiKu, Ja YungKim, Soo WanKwon, SeongBae, Eun HuiKim, Chang SeongKim, Ha YeonOh, Tae RyomChoi, Hong SangKim, MinahMyeong, ChanaLee, Jeong HoLee, Ji SeonKim, Yeong HoonKang, Sun WooKim, Tae HeeKim, YunmiOh, Young EunKoo, Ja RyongSeo, Jang WonBaek, Seon HaKim, Myung SunChang, Tae IkPark, Kyoung SookChoi, Aei KyungOh, Yun KyuLee, Jung PyoLee, Jeong HwanPark, Jeong MiSeong, Eun YoungHeon, Song SangRhee, HarinKim, Hyo JinWoon, Kim DaJi, Seung HeeKim, Young TaekNa, Ki RyangChoi, Dae EunHam, Young RokLee, Eu JinCha, Yoon Jung2022-06-02T10:56:36-07:00doi:10.1681/ASN.2022010080hwp:resource-id:jnephrol;33/8/1590American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycoronary calcification, coronary artery disease, chronic renal disease, clinical nephrology, vascular calcificationClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-08-01August 202210.1681/ASN.20220100801046-66731533-34502022-06-02T10:56:36-07:002022-08Journal of the American Society of NephrologyClinical Research33815901601
- Renal Deletion of LRRC8/VRAC Channels Induces Proximal Tubulopathy10.1681/ASN.2021111458Fri, 01 Jul 2022 06:03:13 GMT-07:00Renal Deletion of LRRC8/VRAC Channels Induces Proximal TubulopathyLópez-Cayuqueo, Karen I.Planells-Cases, RosaPietzke, MatthiasOliveras, AnnaKempa, StefanBachmann, SebastianJentsch, Thomas J.2022-07-01T06:03:13-07:00doi:10.1681/ASN.2021111458hwp:resource-id:jnephrol;33/8/1528American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyVSOR, RVD, transepithelial, glycosuria, chloride channel, Cl− channel, lysosome, Fanconi-like syndromeBasic ResearchNormal Kidney Structure and FunctionBasic ResearchNormal Kidney Structure and Functionresearch-article20222022-08-01August 202210.1681/ASN.20211114581046-66731533-34502022-07-01T06:03:13-07:002022-08Journal of the American Society of NephrologyBasic Research33881528143715451439
- Addressing Inequities in Kidney Care for Indigenous People in Canada10.1681/ASN.2022020215Mon, 06 Jun 2022 08:07:49 GMT-07:00Addressing Inequities in Kidney Care for Indigenous People in CanadaHarasemiw, OksanaKomenda, PaulTangri, Navdeep2022-06-06T08:07:49-07:00doi:10.1681/ASN.2022020215hwp:resource-id:jnephrol;33/8/1474American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologysocial determinants of health, health care access, health disparities, early detection, indigenous Canadians, screening, racial and ethnic disparitiesPerspectiveAddressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-08-01August 202210.1681/ASN.20220202151046-66731533-34502022-06-06T08:07:49-07:002022-08Journal of the American Society of NephrologyPerspective33814741476
- Identifying Antigen-Specific T Cells in ANCA-Associated Vasculitis: A Glimpse of the Future?10.1681/ASN.2022060668Fri, 29 Jul 2022 10:00:25 GMT-07:00Identifying Antigen-Specific T Cells in ANCA-Associated Vasculitis: A Glimpse of the Future?Shochet, LaniKitching, A. Richard2022-07-29T10:00:25-07:00doi:10.1681/ASN.2022060668hwp:resource-id:jnephrol;33/8/1435American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, vasculitis, lymphocytes, glomerulonephritisUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-08-01August 202210.1681/ASN.20220606681046-66731533-34502022-07-29T10:00:25-07:002022-08Journal of the American Society of NephrologyUp Front Matters33881435151714371527
- Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial10.1681/ASN.2022020207Tue, 19 Apr 2022 09:24:58 GMT-07:00Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical TrialProvenzano, MichelePuchades, Maria JesúsGarofalo, CarloJongs, NielsD’Marco, LuisAndreucci, MicheleDe Nicola, LucaGorriz, Jose LuisHeerspink, Hiddo J.L.,Pennino, LuigiDe Gregorio, IlariaPolese, LucioCaturano, AlfredoMinutolo, RobertoSasso, FerdinandoGagliardi, IdaZicarelli, MariateresaCrugliano, GiuseppinaCivera, Elena GimenezPanizo, NayaraSen, TahaXie, Di2022-04-19T09:24:58-07:00doi:10.1681/ASN.2022020207hwp:resource-id:jnephrol;33/8/1569American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, aldosterone, chronic kidney disease, randomized controlled trials, sodium glucose co transporter, mineralocorticoid receptor antagonist, dapagliflozin, eplerenoneClinical ResearchChronic Kidney DiseaseClinical ResearchChronic Kidney Diseaseresearch-article20222022-08-01August 202210.1681/ASN.20220202071046-66731533-34502022-04-19T09:24:58-07:002022-08Journal of the American Society of NephrologyClinical Research33881569i1580i
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- Temporal Changes in Electrolytes, Acid-Base, QTc Duration, and Point-of-Care Ultrasound during Inpatient Hemodialysis Sessions10.34067/KID.0001652022Tue, 10 May 2022 05:04:57 GMT-07:00Temporal Changes in Electrolytes, Acid-Base, QTc Duration, and Point-of-Care Ultrasound during Inpatient Hemodialysis SessionsRavi, Katherine ScovnerEspersen, CarolineCurtis, Katherine A.Cunningham, Jonathan W.Jering, Karola S.Prasad, Narayana G.Platz, ElkeMc Causland, Finnian R.2022-05-10T17:04:57-07:00doi:10.34067/KID.0001652022hwp:resource-id:kidney360;3/7/1217American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, acid-base, ECG, electrolytes, hemodialysis, inpatients, point-of-care systems, QTc, ultrasoundOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-07-2810.34067/KID.00016520222641-76502022-05-10T17:04:57-07:002022-07-28Kidney360Original Investigation3712171227
- Selonsertib Enhances Kidney Protection Beyond Standard of Care in a Hypertensive, Secondary Glomerulosclerosis CKD Model10.34067/KID.0001032022Mon, 11 Apr 2022 11:55:37 GMT-07:00Selonsertib Enhances Kidney Protection Beyond Standard of Care in a Hypertensive, Secondary Glomerulosclerosis CKD ModelBadal, Shawn S.Al Tuhaifi, TareqYu, Ya-FenLopez, DavidPlato, Craig T.Joly, KristinBreckenridge, David G.Yang, Hai-ChunLiles, John T.Fogo, Agnes B.2022-04-11T11:55:37-07:00doi:10.34067/KID.0001032022hwp:resource-id:kidney360;3/7/1169American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, angiotensin-converting enzyme inhibitor, apoptosis signal-regulating kinase 1 inhibitor, basic science, diabetic kidney disease, selonsertibOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-07-2810.34067/KID.00010320222641-76502022-04-11T11:55:37-07:002022-07-28Kidney360Original Investigation3711691182
- Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic MiceBackground: Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. Methods: Using hydrodynamic tail-vein injection, we over-express Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli. Results: In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that over-expression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease-promoting and interferon-related genes, including Ackr2 and Cxcl11. Conclusions: We demonstrate that in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select interferon signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.vbhalla@stanford.edu10.34067/KID.0001712022Tue, 19 Jul 2022 01:29:42 GMT-07:00Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic MiceBackground: Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. Methods: Using hydrodynamic tail-vein injection, we over-express Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli. Results: In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that over-expression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease-promoting and interferon-related genes, including Ackr2 and Cxcl11. Conclusions: We demonstrate that in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select interferon signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.Zheng, XiaoyiHigdon, LaurenGaudet, AlexandreShah, ManavBalistrieri, AngelaLi, Catherinede Nadai, PatriciaPalaniappan, LathaYang, XiaopingSanto, BrianaGinley, BrandonWang, Xiaoxin X.Myakala, KomuraiahNallagatla, PratimaLevi, MosheSarder, PinakiRosenberg, AviMaltzman, Jonathan S.de Freitas Caires, NathalieBhalla, Vivek2022-07-19T13:29:42-07:00doi:10.34067/KID.0001712022hwp:resource-id:kidney360;KID.0001712022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360endocan, Esm-1, diabetic nephropathy, Immunology, albuminuria, transgenic mouse, transcriptional profiling, podocyte, macrophages, glomerular disease, Basic Science, Interferon, Leukocyte infiltrationOriginal InvestigationOriginal Investigationother202210.34067/KID.00017120222641-76502641-76502022-07-19T13:29:42-07:00Kidney360Original Investigation3312122059205910.34067/KID.000171202220762076
- Management of Intermittent Hemodialysis in the Critically Ill PatientIntermittent hemodialysis remains a cornerstone of extracorporeal KRT in the intensive care unit, either as a first-line therapy for AKI or a second-line therapy when patients transition from a continuous or prolonged intermittent therapy. Intermittent hemodialysis is usually provided 3 days per week in this setting on the basis that no clinical benefits have been demonstrated with more frequent hemodialysis. This should not detract from the importance of continually assessing and refining the hemodialysis prescription (including the need for extra treatments) according to dynamic changes in extracellular volume and other parameters, and ensuring that an adequate dose of hemodialysis is being delivered to the patient. Compared with other KRT modalities, the cardinal challenge encountered during intermittent hemodialysis is hemodynamic instability. This phenomenon occurs when reductions in intravascular volume, as a consequence of ultrafiltration and/or osmotic shifts, outpace compensatory plasma refilling from the extravascular space. Myocardial stunning, triggered by intermittent hemodialysis, and independent of ultrafiltration, may also contribute. The hemodynamic effect of intermittent hemodialysis is likely magnified in patients who are critically ill due to an inability to mount sufficient compensatory physiologic responses in the context of multiorgan dysfunction. Of the many interventions that have undergone testing to mitigate hemodynamic instability related to KRT, the best evidence exists for cooling the dialysate and raising the dialysate sodium concentration. Unfortunately, the evidence supporting routine use of these and other interventions is weak owing to poor study quality and limited sample sizes. Intermittent hemodialysis will continue to be an important and commonly used KRT modality for AKI in patients with critical illness, especially in jurisdictions where resources are limited. There is an urgent need to harmonize the definition of hemodynamic instability related to KRT in clinical trials and robustly test strategies to combat it in this vulnerable patient population.10.2215/CJN.04000422Fri, 15 Jul 2022 10:44:05 GMT-07:00Management of Intermittent Hemodialysis in the Critically Ill PatientIntermittent hemodialysis remains a cornerstone of extracorporeal KRT in the intensive care unit, either as a first-line therapy for AKI or a second-line therapy when patients transition from a continuous or prolonged intermittent therapy. Intermittent hemodialysis is usually provided 3 days per week in this setting on the basis that no clinical benefits have been demonstrated with more frequent hemodialysis. This should not detract from the importance of continually assessing and refining the hemodialysis prescription (including the need for extra treatments) according to dynamic changes in extracellular volume and other parameters, and ensuring that an adequate dose of hemodialysis is being delivered to the patient. Compared with other KRT modalities, the cardinal challenge encountered during intermittent hemodialysis is hemodynamic instability. This phenomenon occurs when reductions in intravascular volume, as a consequence of ultrafiltration and/or osmotic shifts, outpace compensatory plasma refilling from the extravascular space. Myocardial stunning, triggered by intermittent hemodialysis, and independent of ultrafiltration, may also contribute. The hemodynamic effect of intermittent hemodialysis is likely magnified in patients who are critically ill due to an inability to mount sufficient compensatory physiologic responses in the context of multiorgan dysfunction. Of the many interventions that have undergone testing to mitigate hemodynamic instability related to KRT, the best evidence exists for cooling the dialysate and raising the dialysate sodium concentration. Unfortunately, the evidence supporting routine use of these and other interventions is weak owing to poor study quality and limited sample sizes. Intermittent hemodialysis will continue to be an important and commonly used KRT modality for AKI in patients with critical illness, especially in jurisdictions where resources are limited. There is an urgent need to harmonize the definition of hemodynamic instability related to KRT in clinical trials and robustly test strategies to combat it in this vulnerable patient population.Chan, Ryan J.Helmeczi, WryanCanney, MarkClark, Edward G.2022-07-15T10:44:05-07:00doi:10.2215/CJN.04000422hwp:resource-id:clinjasn;CJN.04000422v1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, hemodialysis, hypotensionInvited FeaturesCritical Care Nephrology and Acute Kidney InjuryInvited FeaturesCritical Care Nephrology and Acute Kidney Injuryresearch-article202210.2215/CJN.040004221555-90411555-905X2022-07-15T10:44:05-07:00Clinical Journal of the American Society of NephrologyInvited FeaturesCJN.04000422
- Addressing “Second Hits” in the Pursuit of Greater Equity in Health Outcomes for Individuals with ADPKD10.2215/CJN.05970522Mon, 20 Jun 2022 11:03:59 GMT-07:00Addressing “Second Hits” in the Pursuit of Greater Equity in Health Outcomes for Individuals with ADPKDMohottige, DinushikaMcElroy, Lisa M.Boulware, L. Ebony2022-06-20T11:03:59-07:00doi:10.2215/CJN.05970522hwp:resource-id:clinjasn;17/7/936American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyequity, ADPKD, health outcomesEditorialEditorialeditorial20222022-07-01July 202210.2215/CJN.059705221555-90411555-905X2022-06-20T11:03:59-07:002022-07Clinical Journal of the American Society of NephrologyEditorial17777936976934938985935
- Disentangling a Case of Glomerulonephritis with Fibrils10.2215/CJN.00630122Thu, 02 Jun 2022 08:32:55 GMT-07:00Disentangling a Case of Glomerulonephritis with FibrilsCanetta, Pietro2022-06-02T08:32:55-07:00doi:10.2215/CJN.00630122hwp:resource-id:clinjasn;17/7/1070American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), histopathology, immunohistochemistryKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20222022-07-01July 202210.2215/CJN.006301221555-90411555-905X2022-06-02T08:32:55-07:002022-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire17710701072
- Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis10.2215/CJN.05490522Fri, 01 Jul 2022 06:35:27 GMT-07:00Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative GlomerulonephritisCaravaca-Fontán, FernandoPraga, Manuel2022-07-01T06:35:27-07:00doi:10.2215/CJN.05490522hwp:resource-id:clinjasn;17/7/945American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyC3 glomerulopathy, idiopathic membranoproliferative glomerulonephritis, histological and clinical predictorsEditorialEditorialeditorial20222022-07-01July 202210.2215/CJN.054905221555-90411555-905X2022-07-01T06:35:27-07:002022-07Clinical Journal of the American Society of NephrologyEditorial17779459949481007
- Engaging Trainees by Enriching Nephrology Elective Experiences10.2215/CJN.00070122Tue, 22 Mar 2022 07:37:41 GMT-07:00Engaging Trainees by Enriching Nephrology Elective ExperiencesWilliam, Jeffrey H.Dad, TaimurHilburg, Rachel E.Jain, KoyalHusain, S. Ali2022-03-22T07:37:41-07:00doi:10.2215/CJN.00070122hwp:resource-id:clinjasn;17/7/1073American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, education, workforce and training, medical students, medical residentsPerspectivePerspectiveresearch-article20222022-07-01July 202210.2215/CJN.000701221555-90411555-905X2022-03-22T07:37:41-07:002022-07Clinical Journal of the American Society of NephrologyPerspective17710731075
- Mitochondrial DNA and Kidney Functionnephro-intensiv@charite.de10.2215/CJN.05820522Fri, 01 Jul 2022 06:35:27 GMT-07:00Mitochondrial DNA and Kidney FunctionKronenberg, FlorianEckardt, Kai-Uwe2022-07-01T06:35:27-07:00doi:10.2215/CJN.05820522hwp:resource-id:clinjasn;17/7/942American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney function, mitochondrial DNAEditorialEditorialeditorial20222022-07-01July 202210.2215/CJN.058205221555-90411555-905X2022-07-01T06:35:27-07:002022-07Clinical Journal of the American Society of NephrologyEditorial1777942966944975
- Urine or You’re Out?10.2215/CJN.06010522Tue, 28 Jun 2022 11:18:08 GMT-07:00Urine or You’re Out?Harer, Matthew W.Charlton, Jennifer R.2022-06-28T11:18:08-07:00doi:10.2215/CJN.06010522hwp:resource-id:clinjasn;17/7/939American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, urinary output thresholds, neonatalEditorialEditorialeditorial20222022-07-01July 202210.2215/CJN.060105221555-90411555-905X2022-06-28T11:18:08-07:002022-07Clinical Journal of the American Society of NephrologyEditorial1777939949941956
- Chlorthalidone and Advanced Chronic Kidney Disease10.2215/CJN.01380222Mon, 16 May 2022 08:58:35 GMT-07:00Chlorthalidone and Advanced Chronic Kidney DiseaseFurgeson, Seth B.Linas, Stuart2022-05-16T08:58:35-07:00doi:10.2215/CJN.01380222hwp:resource-id:clinjasn;17/7/1076American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, chronic kidney disease, chlorthalidonePerspectivePerspectiveresearch-article20222022-07-01July 202210.2215/CJN.013802221555-90411555-905X2022-05-16T08:58:35-07:002022-07Clinical Journal of the American Society of NephrologyPerspective17710761078
- Machine Learning–Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant Recipients10.2215/CJN.15921221Fri, 10 Jun 2022 05:55:26 GMT-07:00Machine Learning–Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant RecipientsHong, NamkiLee, JuhanKim, Hyung WooJeong, Jong JuHuh, Kyu HaRhee, Yumie2022-06-10T05:55:26-07:00doi:10.2215/CJN.15921221hwp:resource-id:clinjasn;17/7/1026American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, hyperparathyroidism, artificial intelligence, calcium, parathyroid hormone, machine learning, transplant recipientsOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-07-01July 202210.2215/CJN.159212211555-90411555-905X2022-06-10T05:55:26-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article17710261035
- Moving from Evidence to Implementation of Breakthrough Therapies for Diabetic Kidney DiseaseDiabetic kidney disease is the most frequent cause of kidney failure, accounting for half of all cases worldwide. Moreover, deaths from diabetic kidney disease increased 106% between 1990 and 2013, with most attributed to cardiovascular disease. Recommended screening and monitoring for diabetic kidney disease are conducted in less than half of patients with diabetes. Standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker is correspondingly low. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid antagonist are highly effective therapies to reduce kidney and cardiovascular risks in diabetic kidney disease. However, <20% of eligible patients are receiving these agents. Critical barriers are high out-of-pocket drug costs and low reimbursement rates. Data demonstrating clinical and cost-effectiveness of diabetic kidney disease care are needed to garner payer and health care system support. The pharmaceutical industry should collaborate on value-based care by increasing access through affordable drug prices. Additionally, multidisciplinary models and communication technologies tailored to individual health care systems are needed to support optimal diabetic kidney disease care. Community outreach efforts are also central to make care accessible and equitable. Finally, it is imperative that patient preferences and priorities shape implementation strategies. Access to care and implementation of breakthrough therapies for diabetic kidney disease can save millions of lives by preventing kidney failure, cardiovascular events, and premature death. Coalitions composed of patients, families, community groups, health care professionals, health care systems, federal agencies, and payers are essential to develop collaborative models that successfully address this major public health challenge.10.2215/CJN.02980322Wed, 01 Jun 2022 11:56:25 GMT-07:00Moving from Evidence to Implementation of Breakthrough Therapies for Diabetic Kidney DiseaseDiabetic kidney disease is the most frequent cause of kidney failure, accounting for half of all cases worldwide. Moreover, deaths from diabetic kidney disease increased 106% between 1990 and 2013, with most attributed to cardiovascular disease. Recommended screening and monitoring for diabetic kidney disease are conducted in less than half of patients with diabetes. Standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker is correspondingly low. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid antagonist are highly effective therapies to reduce kidney and cardiovascular risks in diabetic kidney disease. However, <20% of eligible patients are receiving these agents. Critical barriers are high out-of-pocket drug costs and low reimbursement rates. Data demonstrating clinical and cost-effectiveness of diabetic kidney disease care are needed to garner payer and health care system support. The pharmaceutical industry should collaborate on value-based care by increasing access through affordable drug prices. Additionally, multidisciplinary models and communication technologies tailored to individual health care systems are needed to support optimal diabetic kidney disease care. Community outreach efforts are also central to make care accessible and equitable. Finally, it is imperative that patient preferences and priorities shape implementation strategies. Access to care and implementation of breakthrough therapies for diabetic kidney disease can save millions of lives by preventing kidney failure, cardiovascular events, and premature death. Coalitions composed of patients, families, community groups, health care professionals, health care systems, federal agencies, and payers are essential to develop collaborative models that successfully address this major public health challenge.Tuttle, Katherine R.Wong, LeslieSt. Peter, WendyRoberts, GlendaRangaswami, JananiMottl, AmyKliger, Alan S.Harris, Raymond C.Gee, Patrick O.Fowler, KevinCherney, DavidBrosius, Frank C.Argyropoulos, ChristosQuaggin, Susan E.2022-06-01T11:56:25-07:00doi:10.2215/CJN.02980322hwp:resource-id:clinjasn;17/7/1092American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, ACE inhibitors, cardiovascular disease, SGLT2 inhibitors, GLP-1 receptor agonists, non-steroidal mineralocorticoid antagonist, angiotensin receptor blockers, albuminuria, disparityFeatureFeatureresearch-article20222022-07-01July 202210.2215/CJN.029803221555-90411555-905X2022-06-01T11:56:25-07:002022-07Clinical Journal of the American Society of NephrologyFeature17710921103
- Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2– Recovered Dialysis Patients10.2215/CJN.00830122Tue, 28 Jun 2022 11:05:04 GMT-07:00Immune Responses after a Third Dose of mRNA Vaccine Differ in Virus-Naive versus SARS-CoV-2– Recovered Dialysis PatientsAttias, PhilippeAzzaoui, ImaneEl Karoui, Khalilde La Selle, AndréaSokal, AurélienChappert, PascalGrimbert, PhilippeFernandez, IgnacioBouvier, MagaliSamson, ChloéDahmane, DjamalRieu, PhilippeNizard, PatriceFourati, SlimSakhi, HamzaMahévas, Matthieu,Audard, VincentBentaarit, BoutheinaBoueilh, AnnaGallien, SébastienGrimbert, PhilippeHue, SophieJoher, NizarJouan, NarindraLamriben, LarbiLelièvre, Jean-DanielLepeule, RaphaëlMahévas, MatthieuMatignon, MarieMelica, GiovannaOniszczuk, JuliePawlotsky, Jean-MichelStehlé, ThomasVindrios, WilliamWemmert, Charlotte2022-06-28T11:05:04-07:00doi:10.2215/CJN.00830122hwp:resource-id:clinjasn;17/7/1008American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, immunology, mRNA vaccine, SARS-CoV-2, COVID-19, memory B cellsOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-07-01July 202210.2215/CJN.008301221555-90411555-905X2022-06-28T11:05:04-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article17710081016
- Glomerular Exostosin as a Subtype and Activity Marker of Class 5 Lupus Nephritis10.2215/CJN.00350122Wed, 18 May 2022 10:59:11 GMT-07:00Glomerular Exostosin as a Subtype and Activity Marker of Class 5 Lupus NephritisWang, ChengyuLiu, YangZhang, MingchaoYang, FanXu, FengShi, ShaolinZeng, CaihongChen, XinMiao, YiqiLiu, ZhengzhaoHu, Weixin2022-05-18T10:59:11-07:00doi:10.2215/CJN.00350122hwp:resource-id:clinjasn;17/7/986American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, target antigen, membranous lupus nephritis, exostosinOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-07-01July 202210.2215/CJN.003501221555-90411555-905X2022-05-18T10:59:11-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article177986993
- Treatment Decision Making for Older Kidney Patients during COVID-1910.2215/CJN.13241021Tue, 07 Jun 2022 05:24:39 GMT-07:00Treatment Decision Making for Older Kidney Patients during COVID-19Porteny, ThaliaGonzales, Kristina M.Aufort, Kate E.Levine, SarahWong, John B.Isakova, TamaraRifkin, Dena E.Gordon, Elisa J.Rossi, AnaDi Perna, GaryKoch-Weser, SusanWeiner, Daniel E.Ladin, Keren,2022-06-07T05:24:39-07:00doi:10.2215/CJN.13241021hwp:resource-id:clinjasn;17/7/957American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, qualitative research, decision making, SARS-CoV-2, chronic kidney diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-07-01July 202210.2215/CJN.132410211555-90411555-905X2022-06-07T05:24:39-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article177957965
- Association of Mitochondrial DNA Copy Number with Risk of Progression of Kidney Disease10.2215/CJN.15551121Fri, 01 Jul 2022 06:35:27 GMT-07:00Association of Mitochondrial DNA Copy Number with Risk of Progression of Kidney DiseaseHe, William J.Li, ChangweiHuang, ZhijieGeng, SiyiRao, Varun S.Kelly, Tanika N.Hamm, L. LeeGrams, Morgan E.Arking, Dan E.Appel, Lawrence J.Rebholz, Casey M.,Appel, Lawrence J.Chen, JingCohen, Debbie L.Feldman, Harold I.Go, Alan S.Lash, James P.Nelson, Robert G.Rahman, MahboobRao, Panduranga S.Shah, Vallabh O.Unruh, Mark L.2022-07-01T06:35:27-07:00doi:10.2215/CJN.15551121hwp:resource-id:clinjasn;17/7/966American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage renal disease, mortality, chronic kidney disease, DNA copy number variations, disease progression, cohort studiesOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-07-01July 202210.2215/CJN.155511211555-90411555-905X2022-07-01T06:35:27-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article1777966942975944
- Low-Flow Acute Kidney InjuryAKI is a syndrome, not a disease. It results from many different primary and/or secondary etiologies and is often multifactorial, especially in the hospitalized patient. This review discusses the pathophysiology of three etiologies that cause AKI, those being kidney hypoperfusion, abdominal compartment syndrome, and urinary tract obstruction. The pathophysiology of these three causes of AKI differs but is overlapping. They all lead to a low urine flow rate and low urine sodium initially. In all three cases, with early recognition and correction of the underlying process, the resulting functional AKI can be rapidly reversed. However, with continued duration and/or increased severity, cell injury occurs within the kidney, resulting in structural AKI and a longer and more severe disease state with increased morbidity and mortality. This is why early recognition and reversal are critical.10.2215/CJN.15341121Wed, 18 May 2022 10:59:11 GMT-07:00Low-Flow Acute Kidney InjuryAKI is a syndrome, not a disease. It results from many different primary and/or secondary etiologies and is often multifactorial, especially in the hospitalized patient. This review discusses the pathophysiology of three etiologies that cause AKI, those being kidney hypoperfusion, abdominal compartment syndrome, and urinary tract obstruction. The pathophysiology of these three causes of AKI differs but is overlapping. They all lead to a low urine flow rate and low urine sodium initially. In all three cases, with early recognition and correction of the underlying process, the resulting functional AKI can be rapidly reversed. However, with continued duration and/or increased severity, cell injury occurs within the kidney, resulting in structural AKI and a longer and more severe disease state with increased morbidity and mortality. This is why early recognition and reversal are critical.Molitoris, Bruce A.2022-05-18T10:59:11-07:00doi:10.2215/CJN.15341121hwp:resource-id:clinjasn;17/7/1039American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury Series, renal hypoperfusion, intraabdominal hypertension, glomerulus, proximal tubule, renal hemodynamics, acute kidney injuryCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-07-01July 202210.2215/CJN.153411211555-90411555-905X2022-05-18T10:59:11-07:002022-07Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury17710391049
- The Pathophysiology of Sepsis-Associated AKISepsis-associated AKI is a life-threatening complication that is associated with high morbidity and mortality in patients who are critically ill. Although it is clear early supportive interventions in sepsis reduce mortality, it is less clear that they prevent or ameliorate sepsis-associated AKI. This is likely because specific mechanisms underlying AKI attributable to sepsis are not fully understood. Understanding these mechanisms will form the foundation for the development of strategies for early diagnosis and treatment of sepsis-associated AKI. Here, we summarize recent laboratory and clinical studies, focusing on critical factors in the pathophysiology of sepsis-associated AKI: microcirculatory dysfunction, inflammation, NOD-like receptor protein 3 inflammasome, microRNAs, extracellular vesicles, autophagy and efferocytosis, inflammatory reflex pathway, vitamin D, and metabolic reprogramming. Lastly, identifying these molecular targets and defining clinical subphenotypes will permit precision approaches in the prevention and treatment of sepsis-associated AKI.10.2215/CJN.00850122Tue, 28 Jun 2022 11:05:04 GMT-07:00The Pathophysiology of Sepsis-Associated AKISepsis-associated AKI is a life-threatening complication that is associated with high morbidity and mortality in patients who are critically ill. Although it is clear early supportive interventions in sepsis reduce mortality, it is less clear that they prevent or ameliorate sepsis-associated AKI. This is likely because specific mechanisms underlying AKI attributable to sepsis are not fully understood. Understanding these mechanisms will form the foundation for the development of strategies for early diagnosis and treatment of sepsis-associated AKI. Here, we summarize recent laboratory and clinical studies, focusing on critical factors in the pathophysiology of sepsis-associated AKI: microcirculatory dysfunction, inflammation, NOD-like receptor protein 3 inflammasome, microRNAs, extracellular vesicles, autophagy and efferocytosis, inflammatory reflex pathway, vitamin D, and metabolic reprogramming. Lastly, identifying these molecular targets and defining clinical subphenotypes will permit precision approaches in the prevention and treatment of sepsis-associated AKI.Kuwabara, ShuheiGoggins, EibhlinOkusa, Mark D.2022-06-28T11:05:04-07:00doi:10.2215/CJN.00850122hwp:resource-id:clinjasn;17/7/1050American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, sepsis, AKI, inflammation, microcirculatory dysfunction, metabolic reprogrammingCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-07-01July 202210.2215/CJN.008501221555-90411555-905X2022-06-28T11:05:04-07:002022-07Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury17710501069
- Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in the United States10.2215/CJN.00840122Mon, 20 Jun 2022 11:03:59 GMT-07:00Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in the United StatesMcGill, Rita L.Saunders, Milda R.Hayward, Alexandra L.Chapman, Arlene B.2022-06-20T11:03:59-07:00doi:10.2215/CJN.00840122hwp:resource-id:clinjasn;17/7/976American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyautosomal dominant polycystic kidney, disparity, equity, ethnicity, kidney transplantation, peritoneal dialysis, United States Renal Data System, epidemiology and outcomesOriginal ArticleCystic Kidney DiseaseOriginal ArticleCystic Kidney Diseaseresearch-article20222022-07-01July 202210.2215/CJN.008401221555-90411555-905X2022-06-20T11:03:59-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article17777976934936985935938
- Urine Output Monitoring for the Diagnosis of Early-Onset Acute Kidney Injury in Very Preterm Infantsaureliedemul@gmail.com10.2215/CJN.15231121Tue, 28 Jun 2022 11:18:09 GMT-07:00Urine Output Monitoring for the Diagnosis of Early-Onset Acute Kidney Injury in Very Preterm InfantsDe Mul, AurélieParvex, PalomaHéneau, AliceBiran, ValériePoncet, AntoineBaud, OlivierSaint-Faust, MarieWilhelm-Bals, Alexandra2022-06-28T11:18:09-07:00doi:10.2215/CJN.15231121hwp:resource-id:clinjasn;17/7/949American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypreterm, urine output, acute kidney injury, tubular immaturity, mortality, early diagnosis, infant, very preterm, neonatal KDIGOOriginal ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-07-01July 202210.2215/CJN.152311211555-90411555-905X2022-06-28T11:18:09-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article1777949939956941
- SARS-CoV-2 Booster Vaccine Response among Patients Receiving Dialysis10.2215/CJN.00890122Tue, 05 Apr 2022 09:51:00 GMT-07:00SARS-CoV-2 Booster Vaccine Response among Patients Receiving DialysisGarcia, PabloHan, JialinMontez-Rath, Maria E.Sun, SumiShang, TiffanyParsonnet, JulieChertow, Glenn M.Anand, ShuchiSchiller, BrigitteAbra, Graham2022-04-05T09:51:00-07:00doi:10.2215/CJN.00890122hwp:resource-id:clinjasn;17/7/1036American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, COVID-19, ESRD, SARS-CoV-2, vaccinationResearch LetterResearch Letterletter20222022-07-01July 202210.2215/CJN.008901221555-90411555-905X2022-04-05T09:51:00-07:002022-07Clinical Journal of the American Society of NephrologyResearch Letter17710361038
- Lifesaving Care for Patients with Kidney Failure during the War in Ukraine 202210.2215/CJN.04720422Tue, 10 May 2022 06:43:13 GMT-07:00Lifesaving Care for Patients with Kidney Failure during the War in Ukraine 2022Stepanova, NataliaKolesnyk, MykolaMithani, ZainAlkofair, BaneenShakour, Rebecca LaurenPetrova, AnnaNovakivskyy, VolodymyrHymes, Jeffrey L.Brzosko, SzymonGiullian, JeffEspinel, ZeldeShultz, James M.2022-05-10T06:43:13-07:00doi:10.2215/CJN.04720422hwp:resource-id:clinjasn;17/7/1079American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, hemodialysis, equity, epidemiology and outcomes, end stage kidney disease, end-stage renal disease, disparity, dialysis, COVID-19, UkrainePerspectivePerspectiveresearch-article20222022-07-01July 202210.2215/CJN.047204221555-90411555-905X2022-05-10T06:43:13-07:002022-07Clinical Journal of the American Society of NephrologyPerspective17710791081
- Keys to Driving Implementation of the New Kidney Care ModelsContemporary nephrology practice is heavily weighted toward in-center hemodialysis, reflective of decisions on infrastructure and personnel in response to decades of policy. The Advancing American Kidney Health initiative seeks to transform care for patients and providers. Under the initiative’s framework, the Center for Medicare and Medicaid Innovation has launched two new care models that align patient choice with provider incentives. The mandatory ESRD Treatment Choices model requires participation by all nephrology practices in designated Hospital Referral Regions, randomly selecting 30% of all Hospital Referral Regions across the United States for participation, with the remaining Hospital Referral Regions serving as controls. The voluntary Kidney Care Choices model offers alternative payment programs open to nephrology practices throughout the country. To help organize implementation of the models, we developed Driver Diagrams that serve as blueprints to identify structures, processes, and norms and generate intervention concepts. We focused on two goals that are directly applicable to nephrology practices and central to the incentive structure of the ESRD Treatment Choices and Kidney Care Choices: (1) increasing utilization of home dialysis, and (2) increasing the number of kidney transplants. Several recurring themes became apparent with implementation. Multiple stakeholders from assorted backgrounds are needed. Communication with primary care providers will facilitate timely referrals, education, and comanagement. Nephrology providers (nephrologists, nursing, dialysis organizations, others) must lead implementation. Patient engagement at nearly every step will help achieve the aims of the models. Advocacy with federal and state regulatory agencies will be crucial to expanding home dialysis and transplantation access. Although the models hold promise to improve choices and outcomes for many patients, we must be vigilant that they not do reinforce existing disparities in health care or widen known racial, socioeconomic, or geographic gaps. The Advancing American Kidney Health initiative has the potential to usher in a new era of value-based care for nephrology.10.2215/CJN.10880821Mon, 14 Mar 2022 05:54:39 GMT-07:00Keys to Driving Implementation of the New Kidney Care ModelsContemporary nephrology practice is heavily weighted toward in-center hemodialysis, reflective of decisions on infrastructure and personnel in response to decades of policy. The Advancing American Kidney Health initiative seeks to transform care for patients and providers. Under the initiative’s framework, the Center for Medicare and Medicaid Innovation has launched two new care models that align patient choice with provider incentives. The mandatory ESRD Treatment Choices model requires participation by all nephrology practices in designated Hospital Referral Regions, randomly selecting 30% of all Hospital Referral Regions across the United States for participation, with the remaining Hospital Referral Regions serving as controls. The voluntary Kidney Care Choices model offers alternative payment programs open to nephrology practices throughout the country. To help organize implementation of the models, we developed Driver Diagrams that serve as blueprints to identify structures, processes, and norms and generate intervention concepts. We focused on two goals that are directly applicable to nephrology practices and central to the incentive structure of the ESRD Treatment Choices and Kidney Care Choices: (1) increasing utilization of home dialysis, and (2) increasing the number of kidney transplants. Several recurring themes became apparent with implementation. Multiple stakeholders from assorted backgrounds are needed. Communication with primary care providers will facilitate timely referrals, education, and comanagement. Nephrology providers (nephrologists, nursing, dialysis organizations, others) must lead implementation. Patient engagement at nearly every step will help achieve the aims of the models. Advocacy with federal and state regulatory agencies will be crucial to expanding home dialysis and transplantation access. Although the models hold promise to improve choices and outcomes for many patients, we must be vigilant that they not do reinforce existing disparities in health care or widen known racial, socioeconomic, or geographic gaps. The Advancing American Kidney Health initiative has the potential to usher in a new era of value-based care for nephrology.Kshirsagar, Abhijit V.Weiner, Daniel E.Mendu, Mallika L.Liu, FrankLew, Susie Q.O’Neil, Terrence J.Bieber, Scott D.White, David L.Zimmerman, JonathanMohan, Sumit2022-03-14T05:54:39-07:00doi:10.2215/CJN.10880821hwp:resource-id:clinjasn;17/7/1082American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney care models, nephrology, Advancing American Kidney HealthFeatureFeatureresearch-article20222022-07-01July 202210.2215/CJN.108808211555-90411555-905X2022-03-14T05:54:39-07:002022-07Clinical Journal of the American Society of NephrologyFeature17710821091
- Changing Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD)10.2215/CJN.05790522Mon, 20 Jun 2022 10:42:35 GMT-07:00Changing Health Disparities in Autosomal Dominant Polycystic Kidney Disease (ADPKD)Ruff, Suzanne F.2022-06-20T10:42:35-07:00doi:10.2215/CJN.05790522hwp:resource-id:clinjasn;17/7/934American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, chronic renal failure, cystic kidney, kidney failure, polycystic kidney disease, transplantation, chronic kidney disease, autosomal dominant polycystic kidney disease, ADPKDPatient VoicePatient Voiceresearch-article20222022-07-01July 202210.2215/CJN.057905221555-90411555-905X2022-06-20T10:42:35-07:002022-07Clinical Journal of the American Society of NephrologyPatient Voice17777934976936935985938
- Automated Determination of Left Ventricular Function Using Electrocardiogram Data in Patients on Maintenance Hemodialysis10.2215/CJN.16481221Mon, 06 Jun 2022 09:20:13 GMT-07:00Automated Determination of Left Ventricular Function Using Electrocardiogram Data in Patients on Maintenance HemodialysisVaid, AkhilJiang, Joy J.Sawant, AshwinSingh, KarandeepKovatch, PatriciaCharney, Alexander W.Charytan, David M.Divers, JasminGlicksberg, Benjamin S.Chan, LiliNadkarni, Girish N.2022-06-06T09:20:13-07:00doi:10.2215/CJN.16481221hwp:resource-id:clinjasn;17/7/1017American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyleft ventricular function, electrocardiogram, maintenance hemodialysisOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-07-01July 202210.2215/CJN.164812211555-90411555-905X2022-06-06T09:20:13-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article17710171025
- Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis10.2215/CJN.16801221Fri, 01 Jul 2022 06:35:28 GMT-07:00Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative GlomerulonephritisLomax-Browne, Hannah J.Medjeral-Thomas, Nicholas R.Barbour, Sean J.Gisby, JackHan, HeedeokBomback, Andrew S.Fervenza, Fernando C.Cairns, Thomas H.Szydlo, RichardTan, Sven-JeanMarks, Stephen D.Waters, Aoife M.Appel, Gerald B.D’Agati, Vivette D.Sethi, SanjeevNast, Cynthia C.Bajema, IngeborgAlpers, Charles E.Fogo, Agnes B.Licht, ChristophFakhouri, FadiCattran, Daniel C.Peters, James E.Cook, H. TerencePickering, Matthew C.2022-07-01T06:35:28-07:00doi:10.2215/CJN.16801221hwp:resource-id:clinjasn;17/7/994American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulonephritis, complement, kidney biopsy, membranoproliferative glomerulonephritis (MPGN)Original ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-07-01July 202210.2215/CJN.168012211555-90411555-905X2022-07-01T06:35:28-07:002022-07Clinical Journal of the American Society of NephrologyOriginal Article17779949451007948
- United States Renal Data System Spotlight on Racial and Ethnic Health Equity: Progress, but Much Remains to Discover, Understand, and Improve10.1681/ASN.2022030283Tue, 21 Jun 2022 07:17:29 GMT-07:00United States Renal Data System Spotlight on Racial and Ethnic Health Equity: Progress, but Much Remains to Discover, Understand, and ImproveJohansen, Kirsten L.Powe, Neil R.2022-06-21T07:17:29-07:00doi:10.1681/ASN.2022030283hwp:resource-id:jnephrol;33/7/1245American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyPerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-07-01July 202210.1681/ASN.20220302831046-66731533-34502022-06-21T07:17:29-07:002022-07Journal of the American Society of NephrologyPerspective33712451248
- Hypomagnesemia, Hypocalcemia, and Tubulointerstitial Nephropathy Caused by Claudin-16 Autoantibodies10.1681/ASN.2022010060Tue, 21 Jun 2022 07:17:27 GMT-07:00Hypomagnesemia, Hypocalcemia, and Tubulointerstitial Nephropathy Caused by Claudin-16 AutoantibodiesFigueres, LucileBruneau, SarahProt-Bertoye, CarolineBrideau, GaëlleNéel, MélanieGriveau, CamilleCheval, LydieBignon, YohanDimitrov, JordanDejoie, ThomasVille, SimonKandel-Aznar, ChristineMoreau, AnneHouillier, PascalFakhouri, Fadi2022-06-21T07:17:27-07:00doi:10.1681/ASN.2022010060hwp:resource-id:jnephrol;33/7/1402American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhypomagnesemia, claudin-16, hypocalcemia, autoantibodiesClinical ResearchGlomerulonephritis and Interstitial NephritisClinical ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-07-01July 202210.1681/ASN.20220100601046-66731533-34502022-06-21T07:17:27-07:002022-07Journal of the American Society of NephrologyClinical Research33771402123114101233
- Predicting Future Outcomes from Kidney Biopsies with MCD/FSGS Lesions: Opportunities and Limitations10.1681/ASN.2022040506Tue, 21 Jun 2022 07:17:29 GMT-07:00Predicting Future Outcomes from Kidney Biopsies with MCD/FSGS Lesions: Opportunities and LimitationsAnders, Hans-JoachimBoor, Peter2022-06-21T07:17:29-07:00doi:10.1681/ASN.2022040506hwp:resource-id:jnephrol;33/7/1233American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, proteinuria, focal segmental glomerulosclerosis, human genetics, pathophysiology of kidney disease and progressionUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-07-01July 202210.1681/ASN.20220405061046-66731533-34502022-06-21T07:17:29-07:002022-07Journal of the American Society of NephrologyUp Front Matters337771233i14111235i1426
- Looking Upstream–The Role of Primary Care in Addressing US Race Inequities in Kidney Health10.1681/ASN.2021101289Tue, 21 Jun 2022 07:17:30 GMT-07:00Looking Upstream–The Role of Primary Care in Addressing US Race Inequities in Kidney HealthBoulware, L. Ebony2022-06-21T07:17:30-07:00doi:10.1681/ASN.2021101289hwp:resource-id:jnephrol;33/7/1249American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhealth inequity, race, primary care, primary health care, racial and ethnic disparitiesPerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-07-01July 202210.1681/ASN.20211012891046-66731533-34502022-06-21T07:17:30-07:002022-07Journal of the American Society of NephrologyPerspective33712491251
- Recognizing the Potential Importance of Religion and Spirituality in the Care of Black Americans with Kidney Failure10.1681/ASN.2021101367Fri, 18 Mar 2022 05:24:43 GMT-07:00Recognizing the Potential Importance of Religion and Spirituality in the Care of Black Americans with Kidney FailureGelfand, Samantha L.Fitchett, GeorgeMoss, Alvin H.2022-03-18T05:24:43-07:00doi:10.1681/ASN.2021101367hwp:resource-id:jnephrol;33/7/1255American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage kidney disease, chronic kidney disease, patient activation, spiritual needs, spiritual pain, chaplaincy, racial and ethnic disparitiesPerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseasePerspectiveSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20222022-07-01July 202210.1681/ASN.20211013671046-66731533-34502022-03-18T05:24:43-07:002022-07Journal of the American Society of NephrologyPerspective33712551257
- Kidney Health Disparities: The Goal is Elimination10.1681/ASN.2022040509Tue, 21 Jun 2022 07:17:28 GMT-07:00Kidney Health Disparities: The Goal is EliminationWesson, Donald E.2022-06-21T07:17:28-07:00doi:10.1681/ASN.2022040509hwp:resource-id:jnephrol;33/7/1237American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyracial and ethnic disparities, chronic kidney disease, ethnic minorityEditorialSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseaseEditorialSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseeditorial20222022-07-01July 202210.1681/ASN.20220405091046-66731533-34502022-06-21T07:17:28-07:002022-07Journal of the American Society of NephrologyEditorial33712371239
- Equitable Transplantation: A Modifiable Risk Factor for Disparities in Mortality in ESKD10.1681/ASN.2022030273Fri, 01 Apr 2022 05:41:05 GMT-07:00Equitable Transplantation: A Modifiable Risk Factor for Disparities in Mortality in ESKDLaster, MarcianaNorris, Keith C.2022-04-01T05:41:05-07:00doi:10.1681/ASN.2022030273hwp:resource-id:jnephrol;33/7/1240American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage kidney disease, transplantation, pediatrics, race, equity, mortality, disparities.EditorialSpecial Series on Addressing Racial and Ethnic Disparities in Kidney DiseaseEditorialSpecial Series on Addressing Racial and Ethnic Disparities in Kidney Diseaseeditorial20222022-07-01July 202210.1681/ASN.20220302731046-66731533-34502022-04-01T05:41:05-07:002022-07Journal of the American Society of NephrologyEditorial337771240i12651241i1275
- Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients10.1681/ASN.2022030248Mon, 02 May 2022 08:50:15 GMT-07:00Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis PatientsOka, YoshinariMiyazaki, MasashiTakatsu, ShigekoMatsuda, Hiroaki2022-05-02T08:50:15-07:00doi:10.1681/ASN.2022030248hwp:resource-id:jnephrol;33/7/1427American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium-based phosphate binders, cardiovascular death, dialysis, plasma oxalate concentrationLetter to the EditorLetter to the Editorletter20222022-07-01July 202210.1681/ASN.20220302481046-66731533-34502022-05-02T08:50:15-07:002022-07Journal of the American Society of NephrologyLetter to the Editor33779142714282375142714282385
- Authors’ Reply: Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients10.1681/ASN.2022030359Mon, 02 May 2022 08:35:35 GMT-07:00Authors’ Reply: Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis PatientsPfau, AnjaKnauf, Felix2022-05-02T08:35:35-07:00doi:10.1681/ASN.2022030359hwp:resource-id:jnephrol;33/7/1428-aAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic dialysis, mortality riskLetter to the EditorLetter to the Editorletter20222022-07-01July 202210.1681/ASN.20220303591046-66731533-34502022-05-02T08:35:35-07:002022-07Journal of the American Society of NephrologyLetter to the Editor33779142814272375142814272385
- Kidney Biopsy Features Most Predictive of Clinical Outcomes in the Spectrum of Minimal Change Disease and Focal Segmental Glomerulosclerosis10.1681/ASN.2021101396Tue, 17 May 2022 12:16:15 GMT-07:00Kidney Biopsy Features Most Predictive of Clinical Outcomes in the Spectrum of Minimal Change Disease and Focal Segmental GlomerulosclerosisZee, JarcyLiu, QianSmith, Abigail R.Hodgin, Jeffrey B.Rosenberg, AviGillespie, Brenda W.Holzman, Lawrence B.Barisoni, LauraMariani, Laura H.,Adler, S.Alter, G.Athavale, A.Atkinson, M.Avila-Casado, C.Bagnasco, S.Baker, S.Barisoni, L.Bidot, C.Blake, J.Bray, M.Canetta, P.Chernitskiy, V.Cooper, A.Dell, K.Dell, T.Derebail, V.Desmond, H.Eddy, S.Fermin, D.Fervenza, F.Flynn, P.Fornoni, A.Froment, A.Gadegbeku, C.Gaut, J.Gibson, K.Gillespie, B.Gipson, D.Greenbaum, L.Hewitt, S.Hingorani, S.Hladunewich, M.Hodgin, J.Hogan, M.Holzman, L.Itteera, M.Jefferson, A.Kallem, K.Kaskel, F.Klida, C.Kretzler, M.Kopp, J.Kretzler, M.Kurtz, V.Lafayette, R.LaPage, J.Larkina, M.Lemley, K.Lieske, J.Li, S.Li, S.Lienczewski, C.C.Lin, J.J.Ling, P.Liu, J.Mainieri, T.Mariani, L.Meyers, K.Modersitzki, F.Morrison, S.Nast, C.Negrey, J.Ormond-Foster, J.Palmer, M.Pao, E.Pfaiff, M.Pradhan, A.Romano, M.Rosenberg, A.Royal, V.Quinn-Boyle, S.Reich, H.Rogers, M.Ross, M.Sambandam, K.Sampson, M.Schachere, M.Sedor, J.Sethna, C.Srivastava, T.Smith, A.Swenson, A.Tang, S.Thomas, D.Trachtman, H.Tuttle, K.Vento, S.Wang, C.Wang, Z.Williams, A.Yeung, B.Yun, E.Zee, J.Zhdanova, O.Adler, S.Alter, G.Athavale, A.Atkinson, M.Avila-Casado, C.Bagnasco, S.Baker, S.Barisoni, L.Bidot, C.Blake, J.Bray, M.Canetta, P.Cassol, C.Chernitskiy, V.Cooper, A.Dell, K.Dell, T.Demeke, D.Derebail, V.Desmond, H.Eddy, S.Fermin, D.Fervenza, F.Flynn, P.Fornoni, A.Froment, A.Gadegbeku, C.Gaut, J.Gibson, K.Gillespie, B.Gipson, D.Greenbaum, L.Hewitt, S.Hingorani, S.Hladunewich, M.Hodgin, J.Hogan, M.Holanda, D.Holzman, L.Itteera, M.Jefferson, A.Kallem, K.Kaskel, F.Klida, C.Kopp, J.Kretzler, M.Kurtz, V.Lafayette, R.LaPage, J.Larkina, M.Lemley, K.Lieske, J.Li, S.Li, S.Lienczewski, C.C.Lin, J.J.Ling, P.Liu, J.Mainieri, T.Mariani, L.Messias, N.Meyers, K.Michailov, A.Modersitzki, F.Morrison, S.Nast, C.Negrey, J.Ormond-Foster, J.Palmer, M.Pao, E.Pfaiff, M.Pradhan, A.Romano, M.Rosenberg, A.Royal, V.Quinn-Boyle, S.Reich, H.Rogers, M.Ross, M.Sambandam, K.Sampson, M.Schachere, M.Sedor, J.Sethna, C.Srivastava, T.Smith, A.Swenson, A.Tang, S.Thomas, D.Trachtman, H.Tuttle, K.Vento, S.Wang, C.Wang, Z.Williams, A.Yamashita, M.Yeung, B.Yun, E.Zee, J.Zhdanova, O.Zuo, Y.2022-05-17T12:16:15-07:00doi:10.1681/ASN.2021101396hwp:resource-id:jnephrol;33/7/1411American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, nephrotic syndrome, kidney biopsy, renal morphology, outcome predictionClinical EpidemiologyGlomerulonephritis and Interstitial NephritisClinical EpidemiologyGlomerulonephritis and Interstitial Nephritisresearch-article20222022-07-01July 202210.1681/ASN.20211013961046-66731533-34502022-05-17T12:16:15-07:002022-07Journal of the American Society of NephrologyClinical Epidemiology337771411i12331426i1235
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- Authors’ Reply: Clinical Studies of Vaccine Efficacy10.1681/ASN.2022030382Tue, 21 Jun 2022 07:17:29 GMT-07:00Authors’ Reply: Clinical Studies of Vaccine EfficacyBell, SamiraCampbell, JacquelineLambourg, EmilieMark, Patrick2022-06-21T07:17:29-07:00doi:10.1681/ASN.2022030382hwp:resource-id:jnephrol;33/7/1430American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyvaccination, COVID-19, clinical epidemiology, dialysis, transplantation, kidney replacement therapyLetter to the EditorLetter to the Editorletter20222022-07-01July 202210.1681/ASN.20220303821046-66731533-34502022-06-21T07:17:29-07:002022-07Journal of the American Society of NephrologyLetter to the Editor337741430142867714311430686
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- Association of the Comprehensive ESRD Care Model with Treatment Adherence10.34067/KID.0006132021Tue, 21 Dec 2021 11:52:25 GMT-08:00Association of the Comprehensive ESRD Care Model with Treatment AdherenceHirth, Richard A.Nahra, TammieSegal, Jonathan H.Gunden, JosephMarrufo, GreciaNegrusa, BrighitaBoyer, GregoryJiao, AmySleeman, KathrynDahlerus, ClaudiaWiens, JenniferUllman, DarinBacon, KelseyStrubler, DanielBraun, RebeccaAckerman, ArianaLi, Yi2021-12-21T11:52:25-08:00doi:10.34067/KID.0006132021hwp:resource-id:kidney360;3/6/1039American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, basic science, comprehensive health care, dialysis, dialysis treatment adherence, dialysis, skipped treatment, ESKD, ESKD patients, treatment adherenceOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-06-3010.34067/KID.00061320212641-76502021-12-21T11:52:25-08:002022-06-30Kidney360Original Investigation3610391046
- Hemoconcentration of Creatinine Minimally Contributes to Changes in Creatinine during the Treatment of Decompensated Heart Failure10.34067/KID.0007582021Tue, 12 Apr 2022 07:48:45 GMT-07:00Hemoconcentration of Creatinine Minimally Contributes to Changes in Creatinine during the Treatment of Decompensated Heart FailureMaulion, ChristopherChen, SheldonRao, Veena S.Ivey-Miranda, Juan B.Cox, Zachary L.Mahoney, DevinCoca, Steven G.Negoianu, DanAsher, Jennifer L.Turner, Jeffrey M.Inker, Lesley A.Wilson, F. PerryTestani, Jeffrey M.2022-04-12T07:48:45-07:00doi:10.34067/KID.0007582021hwp:resource-id:kidney360;3/6/1003American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, creatinine, heart failure, hematologic diseasesOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-06-3010.34067/KID.00075820212641-76502022-04-12T07:48:45-07:002022-06-30Kidney360Original Investigation3610031010
- Cardiopulmonary Resuscitation in US Dialysis Clinics: Room for Improvement10.34067/KID.0002142022Thu, 30 Jun 2022 06:00:22 GMT-07:00Cardiopulmonary Resuscitation in US Dialysis Clinics: Room for ImprovementYap, ErnieGreenberg, Sheldon2022-06-30T06:00:22-07:00doi:10.34067/KID.0002142022hwp:resource-id:kidney360;3/6/986American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, cardiopulmonary resuscitation, United StatesEditorialEditorialeditorial20222022-06-3010.34067/KID.00021420222641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Editorial36986987
- Painful Leg Ulcers in an ESKD Patient10.34067/KID.0001132022Thu, 30 Jun 2022 06:00:22 GMT-07:00Painful Leg Ulcers in an ESKD PatientFernandes, SaraFalcão, LuísAlmeida, Edgar2022-06-30T06:00:22-07:00doi:10.34067/KID.0001132022hwp:resource-id:kidney360;3/6/1120American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, calcific uremic arteriolopathy, calciphylaxis, chronic kidney disease, hemodialysis, SARS-CoV-2Clinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-06-3010.34067/KID.00011320222641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Clinical Images in Nephrology and Dialysis3611201121
- Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? CON10.34067/KID.0002082021Fri, 15 Oct 2021 09:31:44 GMT-07:00Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? CONCheng, Xingxing S.2021-10-15T09:31:44-07:00doi:10.34067/KID.0002082021hwp:resource-id:kidney360;3/6/996American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, allografts, Kidney Allocation System, multiorgan transplants, organ transplantation, prioritization, simultaneous liver-kidneyDebates in NephrologyDebates in Nephrologyresearch-article20222022-06-3010.34067/KID.00020820212641-76502021-10-15T09:31:44-07:002022-06-30Kidney360Debates in Nephrology36996998
- Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? PRO10.34067/KID.0001632021Fri, 15 Oct 2021 09:31:44 GMT-07:00Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? PROTruong, Tiffany T.Nadim, Mitra K.2021-10-15T09:31:44-07:00doi:10.34067/KID.0001632021hwp:resource-id:kidney360;3/6/993American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, kidney dysfunction, kidney transplant, liver transplant, liver-kidney transplant, MELD, safety netDebates in NephrologyDebates in Nephrologyresearch-article20222022-06-3010.34067/KID.00016320212641-76502021-10-15T09:31:44-07:002022-06-30Kidney360Debates in Nephrology36993995
- The Clinical Utility of the Neutrophil-to-Lymphocyte Ratio as a Discriminatory Test among Bacterial, Mycobacterium Tuberculosis, and Nontuberculous Mycobacterium Peritoneal Dialysis–Related Peritonitis10.34067/KID.0000842022Tue, 29 Mar 2022 11:45:29 GMT-07:00The Clinical Utility of the Neutrophil-to-Lymphocyte Ratio as a Discriminatory Test among Bacterial, Mycobacterium Tuberculosis, and Nontuberculous Mycobacterium Peritoneal Dialysis–Related PeritonitisFung, Winston Wing-ShingChow, Kai-MingNg, Jack Kit-ChungChan, Gordon Chun-KauLi, Philip Kam-TaoSzeto, Cheuk-Chun2022-03-29T11:45:29-07:00doi:10.34067/KID.0000842022hwp:resource-id:kidney360;3/6/1031American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, diagnostic test, mycobacterium tuberculosis, neutrophil-to-lymphocyte ratio, nontuberculous mycobacteria, peritoneal dialysis, peritonitisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-06-3010.34067/KID.00008420222641-76502022-03-29T11:45:29-07:002022-06-30Kidney360Original Investigation3610311038
- Central Venous Catheter Versus Permanent Access: A Hemodialysis Patient Focus Group10.34067/KID.0002692022Thu, 30 Jun 2022 06:00:22 GMT-07:00Central Venous Catheter Versus Permanent Access: A Hemodialysis Patient Focus GroupDavis, Jane S.2022-06-30T06:00:22-07:00doi:10.34067/KID.0002692022hwp:resource-id:kidney360;3/6/1111American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, central venous catheter, focus group, hemodialysis, patient, permanent accessPatient PerspectivePatient Perspectiveresearch-article20222022-06-3010.34067/KID.00026920222641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Patient Perspective3611111111
- Pretransplant Dialysis and Preemptive Transplant in Living Donor Kidney Recipients10.34067/KID.0007652021Mon, 11 Apr 2022 11:55:37 GMT-07:00Pretransplant Dialysis and Preemptive Transplant in Living Donor Kidney RecipientsLai, MasonGao, YingTavakol, MehdiFreise, ChrisLee, Brian K.Park, Meyeon2022-04-11T11:55:37-07:00doi:10.34067/KID.0007652021hwp:resource-id:kidney360;3/6/1080American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, kidney transplantation, living donor, preemptive transplant, renal dialysisOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-06-3010.34067/KID.00076520212641-76502022-04-11T11:55:37-07:002022-06-30Kidney360Original Investigation3610801088
- An Unusual Kidney Lesion Presenting with Facial Edema, Hematuria, and AKI10.34067/KID.0000782022Thu, 30 Jun 2022 06:00:22 GMT-07:00An Unusual Kidney Lesion Presenting with Facial Edema, Hematuria, and AKIBond, TannerMims, AndrewDavis, Cameron2022-06-30T06:00:22-07:00doi:10.34067/KID.0000782022hwp:resource-id:kidney360;3/6/1118American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, acanthocytes, hematuria, immunoglobulin G, kappa, light chains, myeloma, PGNMID, rituximabClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-06-3010.34067/KID.00007820222641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Clinical Images in Nephrology and Dialysis3611181119
- Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? COMMENTARY10.34067/KID.0005042021Fri, 15 Oct 2021 09:31:44 GMT-07:00Is Prioritization of Kidney Allografts to Combined Liver-Kidney Recipients Appropriate? COMMENTARYAsch, William S.2021-10-15T09:31:44-07:00doi:10.34067/KID.0005042021hwp:resource-id:kidney360;3/6/999American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, allocation, criteria, eligibility, Equity, OPTN, SLKT, UNOS, waitlistModerator CommentaryModerator Commentaryarticle-commentary20222022-06-3010.34067/KID.00050420212641-76502021-10-15T09:31:44-07:002022-06-30Kidney360Moderator Commentary369991002
- Does More Serum Creatinine Really Just Mean Less Volume?10.34067/KID.0002302022Thu, 30 Jun 2022 06:00:22 GMT-07:00Does More Serum Creatinine Really Just Mean Less Volume?Kula, Alexander J.Bansal, Nisha2022-06-30T06:00:22-07:00doi:10.34067/KID.0002302022hwp:resource-id:kidney360;3/6/983American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, ADHF, creatinine, diuresis, eGFR, hemoconcentrationEditorialEditorialeditorial20222022-06-3010.34067/KID.00023020222641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Editorial36983985
- Differential Impact of Central Venous Catheters versus Arteriovenous Fistulae on Quality of Life among Irish Haemodialysis Patients10.34067/KID.0006622021Fri, 04 Mar 2022 11:28:48 GMT-08:00Differential Impact of Central Venous Catheters versus Arteriovenous Fistulae on Quality of Life among Irish Haemodialysis PatientsMaguire, I. CaoimheBrowne, Leonard D.Dawood, MinaLeahy, FionaRyan, Maria CWhite, EoinO’Sullivan, AidanO’Sullivan, LeonardStack, Austin G.2022-03-04T11:28:48-08:00doi:10.34067/KID.0006622021hwp:resource-id:kidney360;3/6/1065American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, AVF, CVC, dialysis, ESKD, health-related quality of life, SF-36, SF-VAQOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-06-3010.34067/KID.00066220212641-76502022-03-04T11:28:48-08:002022-06-30Kidney360Original Investigation3610651072
- The Forgotten Cost of Nephrotic Syndrome to Patients and Caregivers in the United States10.34067/KID.0001942022Thu, 30 Jun 2022 06:00:22 GMT-07:00The Forgotten Cost of Nephrotic Syndrome to Patients and Caregivers in the United StatesRajasekaran, ArunRizk, Dana V.2022-06-30T06:00:22-07:00doi:10.34067/KID.0001942022hwp:resource-id:kidney360;3/6/991American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, caregivers, direct cost, glomerulonephritis, health economics, indirect cost, nephrotic syndrome, United StatesEditorialEditorialeditorial20222022-06-3010.34067/KID.00019420222641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Editorial36991992
- Facility-Level Factors and Racial Disparities in Cardiopulmonary Resuscitation within US Dialysis Clinics10.34067/KID.0008092021Fri, 11 Mar 2022 08:00:09 GMT-08:00Facility-Level Factors and Racial Disparities in Cardiopulmonary Resuscitation within US Dialysis ClinicsPun, Patrick H.Svetkey, Laura P.McNally, BryanDupre, Matthew E.2022-03-11T08:00:09-08:00doi:10.34067/KID.0008092021hwp:resource-id:kidney360;3/6/1021American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, cardiopulmonary resuscitation, cardiovascular disease, chronic hemodialysis, disparity, end stage kidney disease, racial disparitiesOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-06-3010.34067/KID.00080920212641-76502022-03-11T08:00:09-08:002022-06-30Kidney360Original Investigation3610211030
- Arteriovenous Fistula or Dialysis Catheter: A Patient’s Perspective10.34067/KID.0001462022Fri, 15 Apr 2022 01:32:21 GMT-07:00Arteriovenous Fistula or Dialysis Catheter: A Patient’s PerspectiveGedney, Nieltje2022-04-15T13:32:21-07:00doi:10.34067/KID.0001462022hwp:resource-id:kidney360;3/6/1109American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, AVF, CVC, dialysis catheter, patientPatient PerspectivePatient Perspectiveresearch-article20222022-06-3010.34067/KID.00014620222641-76502022-04-15T13:32:21-07:002022-06-30Kidney360Patient Perspective3611091110
- Ongoing Lessons from the Comprehensive ESRD Care Program10.34067/KID.0008142021Thu, 30 Jun 2022 06:00:22 GMT-07:00Ongoing Lessons from the Comprehensive ESRD Care ProgramKinlaw, Alan C.Kshirsagar, Abhijit V.2022-06-30T06:00:22-07:00doi:10.34067/KID.0008142021hwp:resource-id:kidney360;3/6/988American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, alternative payment model, ESRD, value based careEditorialEditorialeditorial20222022-06-3010.34067/KID.00081420212641-76502022-06-30T06:00:22-07:002022-06-30Kidney360Editorial36988990
- Utilization of Peritoneal Dialysis in the United States: Progress in Tackling Obstacles to ExpansionTo facilitate the desired increase in home dialysis utilization in the United States, multiple factors need to be taken into consideration in order to achieve this complex task. Through policy-level facilitators such as the Advancing American Kidney Health Initiative and the expansion of telehealth utilization, adjustments to the existing payment models, providing health equity incentives, increasing number of provider education materials on home therapies, and allaying patient fears with the expansion of home dialysis education nationwide, we have taken several steps in the right direction. There is still a long way to go, and further improvements can be made while utilizing lessons learned from some of our international peers who have been successful in their implementation of large-scale home dialysis programs.10.34067/KID.0001872022Fri, 15 Apr 2022 01:32:21 GMT-07:00Utilization of Peritoneal Dialysis in the United States: Progress in Tackling Obstacles to ExpansionTo facilitate the desired increase in home dialysis utilization in the United States, multiple factors need to be taken into consideration in order to achieve this complex task. Through policy-level facilitators such as the Advancing American Kidney Health Initiative and the expansion of telehealth utilization, adjustments to the existing payment models, providing health equity incentives, increasing number of provider education materials on home therapies, and allaying patient fears with the expansion of home dialysis education nationwide, we have taken several steps in the right direction. There is still a long way to go, and further improvements can be made while utilizing lessons learned from some of our international peers who have been successful in their implementation of large-scale home dialysis programs.El Shamy, Osama2022-04-15T13:32:21-07:00doi:10.34067/KID.0001872022hwp:resource-id:kidney360;3/6/1112American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, peritoneal dialysis, policy, racial disparities, United StatesReview ArticleReview Articlereview-article20222022-06-3010.34067/KID.00018720222641-76502022-04-15T13:32:21-07:002022-06-30Kidney360Review Article3611121117
- Global Dialysis Perspective: Haiti10.34067/KID.0007592021Tue, 29 Mar 2022 02:35:44 GMT-07:00Global Dialysis Perspective: HaitiExantus, Judith2022-03-29T14:35:44-07:00doi:10.34067/KID.0007592021hwp:resource-id:kidney360;3/6/1105American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, dialysis funding, dialysis management, Haiti, low–middle-income country, noncommunicable diseaseGlobal PerspectiveGlobal Perspectiveresearch-article20222022-06-3010.34067/KID.00075920212641-76502022-03-29T14:35:44-07:002022-06-30Kidney360Global Perspective3611051108
- Exacerbation of Racial Disparities in Living Donor Kidney Transplantation During the COVID-19 Pandemic10.34067/KID.0008392021Thu, 05 May 2022 01:22:35 GMT-07:00Exacerbation of Racial Disparities in Living Donor Kidney Transplantation During the COVID-19 PandemicSingh, NeerajLi, RuixinAlhamad, TarekSchnitzler, Mark A.Mannon, Roslyn B.Doshi, Mona D.Woodside, Kenneth J.Hippen, Benjamin E.Cooper, MatthewSnyder, JonAxelrod, David A.Lentine, Krista L.2022-05-05T13:22:35-07:00doi:10.34067/KID.0008392021hwp:resource-id:kidney360;3/6/1089American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, access, COVID-19, disparities, kidney transplantation, living donor transplantation, SARS-CoV-2Brief CommunicationTransplantationBrief CommunicationTransplantationresearch-article20222022-06-3010.34067/KID.00083920212641-76502022-05-05T13:22:35-07:002022-06-30Kidney360Brief Communication3610891094
- The Impact of COVID-19 on Postdischarge Outcomes for Dialysis Patients in the United States: Evidence from Medicare Claims Data10.34067/KID.0000242022Fri, 15 Apr 2022 01:32:21 GMT-07:00The Impact of COVID-19 on Postdischarge Outcomes for Dialysis Patients in the United States: Evidence from Medicare Claims DataWu, WenboGremel, Garrett W.He, KevinMessana, Joseph M.Sen, AnandaSegal, Jonathan H.Dahlerus, ClaudiaHirth, Richard A.Kang, JianWisniewski, KarenNahra, TammiePadilla, RobinTong, LanGu, HaoyuWang, XiSlowey, MeganEckard, AshleyDing, XuemeiBorowicz, LisaDu, JuanFrye, BrandonKalbfleisch, John D.2022-04-15T13:32:21-07:00doi:10.34067/KID.0000242022hwp:resource-id:kidney360;3/6/1047American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, aftercare, COVID-19, patient discharge, SARS-CoV-2, United StatesOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-06-3010.34067/KID.00002420222641-76502022-04-15T13:32:21-07:002022-06-30Kidney360Original Investigation3610471056
- Lived Experiences of Patients Receiving Hemodialysis during the COVID-19 Pandemic: A Qualitative Study from the Quebec Renal Network10.34067/KID.0000182022Mon, 25 Apr 2022 01:37:01 GMT-07:00Lived Experiences of Patients Receiving Hemodialysis during the COVID-19 Pandemic: A Qualitative Study from the Quebec Renal NetworkMalo, Marie-FrançoiseAffdal, AliyaBlum, DanBallesteros, FabianBeaubien-Souligny, WilliamCaron, Marie-LineNadeau-Fredette, Annie-ClaireVasilevsky, MurrayRios, NorkaFortin, Marie-ChantalSuri, Rita S.2022-04-25T13:37:01-07:00doi:10.34067/KID.0000182022hwp:resource-id:kidney360;3/6/1057American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, COVID-19 pandemics, hemodialysis, patient experience, qualitative methods, Quebec, SARS-CoV-2Original InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-06-3010.34067/KID.00001820222641-76502022-04-25T13:37:01-07:002022-06-30Kidney360Original Investigation3610571064
- The Health Economic Impact of Nephrotic Syndrome in the United States10.34067/KID.0005072021Mon, 25 Apr 2022 01:37:01 GMT-07:00The Health Economic Impact of Nephrotic Syndrome in the United StatesSimon, Christine A.Salmon, EloiseDesmond, Hailey E.Massengill, Susan F.Gipson, Wilson P.Gipson, Debbie S.2022-04-25T13:37:01-07:00doi:10.34067/KID.0005072021hwp:resource-id:kidney360;3/6/1073American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, absenteeism, food selection, health economics, low sodium diet, nephrotic syndrome, patient costs, patient experience, United StatesOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-06-3010.34067/KID.00050720212641-76502022-04-25T13:37:01-07:002022-06-30Kidney360Original Investigation3610731079
- Urinary Polycyclic Aromatic Hydrocarbons in a Longitudinal Cohort of Children with CKD: A Case of Reverse Causation?10.34067/KID.0000892022Tue, 29 Mar 2022 02:35:44 GMT-07:00Urinary Polycyclic Aromatic Hydrocarbons in a Longitudinal Cohort of Children with CKD: A Case of Reverse Causation?Jacobson, Melanie H.Wu, YinxiangLiu, MenglingKannan, KurunthachalamLee, SunmiMa, JingWarady, Bradley A.Furth, SusanTrachtman, HowardTrasande, Leonardo2022-03-29T14:35:44-07:00doi:10.34067/KID.0000892022hwp:resource-id:kidney360;3/6/1011American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, children, kidney, polycyclic aromatic hydrocarbon, renal function, reverse causationOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-06-3010.34067/KID.00008920222641-76502022-03-29T14:35:44-07:002022-06-30Kidney360Original Investigation3610111020
- Global Perspectives in Acute Kidney Injury: Japan10.34067/KID.0007892021Tue, 29 Mar 2022 02:35:44 GMT-07:00Global Perspectives in Acute Kidney Injury: JapanYamada, HiroyukiYanagita, Motoko2022-03-29T14:35:44-07:00doi:10.34067/KID.0007892021hwp:resource-id:kidney360;3/6/1099American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, Japan, Japanese, onconephrologyGlobal PerspectiveGlobal Perspectiveresearch-article20222022-06-3010.34067/KID.00078920212641-76502022-03-29T14:35:44-07:002022-06-30Kidney360Global Perspective3610991104
- Global Perspectives in Acute Kidney Injury: Ireland10.34067/KID.0001342022Thu, 21 Apr 2022 10:37:49 GMT-07:00Global Perspectives in Acute Kidney Injury: IrelandRedahan, LynnMurray, Patrick2022-04-21T10:37:49-07:00doi:10.34067/KID.0001342022hwp:resource-id:kidney360;3/6/1095American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, IrelandGlobal PerspectiveGlobal Perspectiveresearch-article20222022-06-3010.34067/KID.00013420222641-76502022-04-21T10:37:49-07:002022-06-30Kidney360Global Perspective3610951098
- Diagnostic Performance of Fractional Excretion of Sodium for the Differential Diagnosis of Acute Kidney Injury10.2215/CJN.14561121Wed, 11 May 2022 01:53:24 GMT-07:00Diagnostic Performance of Fractional Excretion of Sodium for the Differential Diagnosis of Acute Kidney InjuryAbdelhafez, MohammadNayfeh, TarekAtieh, AnwarAbuShamma, OmarBabaa, BasheerBaniowda, MuathHrizat, AlaaHasan, BasharHassett, LeslieHamadah, AbdurrahmanGharaibeh, Kamel2022-05-11T13:53:24-07:00doi:10.2215/CJN.14561121hwp:resource-id:clinjasn;17/6/785American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFENa, AKI, DTA, systematic review, meta-analysis, sodiumOriginal ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-06-01June 202210.2215/CJN.145611211555-90411555-905X2022-05-11T13:53:24-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article1766785777797778
- PCSK9 and Cardiovascular Disease in Individuals with Moderately Decreased Kidney Function10.2215/CJN.01230122Wed, 06 Apr 2022 09:26:24 GMT-07:00PCSK9 and Cardiovascular Disease in Individuals with Moderately Decreased Kidney FunctionKheirkhah, AzinLamina, ClaudiaKollerits, BarbaraSchachtl-Riess, Johanna F.Schultheiss, Ulla T.Forer, LukasSekula, PeggyKotsis, FruzsinaEckardt, Kai-UweKronenberg, Florian,Eckardt, Kai-UweMeiselbach, HeikeSchneider, Markus P.Schiffer, MarioProkosch, Hans-UlrichBärthlein, BarbaraBeck, AndreasReis, AndréEkici, Arif B.Becker, SusanneBecker-Grosspitsch, DinahAlberth-Schmidt, UlrikeHausknecht, BirgitWeigel, AnkeWalz, GerdKöttgen, AnnaSchultheiß, Ulla T.Kotsis, FruzsinaMeder, SimoneMitsch, ErnaReinhard, UrsulaFloege, JürgenSaritas, TurgaySchaeffner, ElkeBaid-Agrawal, SeemaTheisen, KerstinHaller, HermannMenne, JanZeier, MartinSommerer, ClaudiaTheilinger, JohannaWolf, GunterBusch, MartinPaul, RainerSitter, ThomasWanner, ChristophKrane, VeraBörner-Klein, AntjeBauer, BrittaKronenberg, FlorianRaschenberger, JuliaKollerits, BarbaraForer, LukasSchönherr, SebastianWeissensteiner, HansiOefner, PeterGronwald, WolframSchmid, MatthiasNadal, Jennifer2022-04-06T09:26:24-07:00doi:10.2215/CJN.01230122hwp:resource-id:clinjasn;17/6/809American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, PCSK9, prospectiveOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-06-01June 202210.2215/CJN.012301221555-90411555-905X2022-04-06T09:26:24-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article176809818
- Evaluation of Conflicts of Interest among Participants of the Japanese Nephrology Clinical Practice Guideline10.2215/CJN.14661121Fri, 27 May 2022 10:37:42 GMT-07:00Evaluation of Conflicts of Interest among Participants of the Japanese Nephrology Clinical Practice GuidelineMurayama, AnjuYamada, KohkiYoshida, MakotoKaneda, YudaiSaito, HiroakiSawano, ToyoakiShrestha, SunilShrestha, RajeevTanimoto, TetsuyaOzaki, Akihiko2022-05-27T10:37:42-07:00doi:10.2215/CJN.14661121hwp:resource-id:clinjasn;17/6/819American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, conflict of interest, JapanOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-06-01June 202210.2215/CJN.146611211555-90411555-905X2022-05-27T10:37:42-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article1766819771826773
- Medicare Bundled Payment Policy on Anemia Care, Major Adverse Cardiovascular Events, and Mortality among Adults Undergoing Hemodialysis10.2215/CJN.14361121Thu, 19 May 2022 11:31:15 GMT-07:00Medicare Bundled Payment Policy on Anemia Care, Major Adverse Cardiovascular Events, and Mortality among Adults Undergoing HemodialysisPark, HaesukDesai, RajLiu, XinyueSmith, Steven M.Hincapie-Castillo, JuanHenry, LindaGoodin, AmieGopal, SaraswathiPepine, Carl J.Mohandas, Raj2022-05-19T11:31:15-07:00doi:10.2215/CJN.14361121hwp:resource-id:clinjasn;17/6/851American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, anemia, Medicare bundled payment, erythropoietin-stimulating agents, major adverse cardiovascular event, hemoglobinOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-06-01June 202210.2215/CJN.143611211555-90411555-905X2022-05-19T11:31:15-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article1766851769860770
- Variation in Peritoneal Dialysis Time on Therapy by Country10.2215/CJN.16341221Tue, 31 May 2022 12:48:45 GMT-07:00Variation in Peritoneal Dialysis Time on Therapy by CountryLambie, MarkZhao, JunhuiMcCullough, KeithDavies, Simon J.Kawanishi, HidekiJohnson, David W.Sloand, James A.Sanabria, MauricioKanjanabuch, TalerngsakKim, Yong-LimShen, Jenny I.Pisoni, Ronald L.Robinson, Bruce M.Perl, Jeffrey,,Johnson, DavidPerl, JeffreyKawanishi, HidekiKim, Yong-LimKanjanabuch, TalerngsakDavies, SimonBernardo, AngelitoPisoni, RonRobinson, BruceShen, JennyBadve, SunilBoudville, NeilBrown, FionaChow, JosephineCollins, JohnMorton, RachaelWilson, ScottVychytil, AndreasVan Biesen, WimFigueiredo, Anade Moraes, ThyagoBrunier, GillianJain, ArshJassal, VanitaNessim, SharonOliver, MatthewPrice, ValerieQuinn, RobFang, WeiSzeto, CCWang, AngelaFukasawa, MizuyaIto, YasuhikoRyuzaki, MunekazuTomo, TadashiManzano, Alfonso CuetoMarshall, MarkLjungman, SusanneBoongird, SarinyaBoonyakrai, ChanchanaCheawchanwattana, AreewanHalue, GuttigaSritippayawan, SuchaiTatiyanupanwong, SajjaTungsanga, KriangBowes, ElaineBrown, EdwinaFluck, RichardGoh, Bak LeongHurst, HelenWilkie, MartinWoodrow, GrahamBender, FilitsaBernardini, JudithChatoth, DineshCrabtree, JohnFinkelstein, FredGhaffari, ArshiaMehrotra, RajnishPiraino, BethSchreiber, MartinTeitelbaum, Isaac2022-05-31T12:48:45-07:00doi:10.2215/CJN.16341221hwp:resource-id:clinjasn;17/6/861American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hemodialysis, kidney transplantationOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-06-01June 202210.2215/CJN.163412211555-90411555-905X2022-05-31T12:48:45-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article1766861782871784
- Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations10.2215/CJN.14321121Mon, 16 May 2022 08:58:36 GMT-07:00Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African PopulationsBrandenburg, Jean-TristanGovender, Melanie A.Winkler, Cheryl A.Boua, Palwende RomualdAgongo, GodfredFabian, JuneRamsay, Michèle2022-05-16T08:58:36-07:00doi:10.2215/CJN.14321121hwp:resource-id:clinjasn;17/6/798American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, glomerular filtration rate, molecular genetics, chronic kidney disease, apolipoprotein L1Original ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-06-01June 202210.2215/CJN.143211211555-90411555-905X2022-05-16T08:58:36-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article176798808
- Electrolyte and Acid-Base Disorders Associated with Cancer ImmunotherapyNovel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all types of cancers. Immune-related adverse events have been associated with immunotherapies. AKI has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations, including immune checkpoint inhibitor–induced parathyroid hormone–related peptide production, sarcoid-like granulomas, and hyperprogression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor–induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy–associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.10.2215/CJN.14671121Fri, 21 Jan 2022 07:16:21 GMT-08:00Electrolyte and Acid-Base Disorders Associated with Cancer ImmunotherapyNovel immunotherapy drugs have changed the landscape of cancer medicine. Immune checkpoint inhibitors and chimeric antigen receptor T cells are being used and investigated in almost all types of cancers. Immune-related adverse events have been associated with immunotherapies. AKI has been the most commonly associated kidney adverse event. In this review, we showcase the several associated electrolyte disorders seen with immunotherapy. Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common. Endocrine causes of hyponatremia are rare. Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis. Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations, including immune checkpoint inhibitor–induced parathyroid hormone–related peptide production, sarcoid-like granulomas, and hyperprogression of the disease. Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor–induced tumor lysis syndrome. Chimeric antigen receptor T cell therapy–associated electrolyte disorders are also common. This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur. Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.Uppal, Nupur N.Workeneh, Biruh T.Rondon-Berrios, HelbertJhaveri, Kenar D.2022-01-21T07:16:21-08:00doi:10.2215/CJN.14671121hwp:resource-id:clinjasn;17/6/922American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunotherapy, hyponatremia, hypokalemia, hypercalcemia, cancerReviewReviewreview-article20222022-06-01June 202210.2215/CJN.146711211555-90411555-905X2022-01-21T07:16:21-08:002022-06Clinical Journal of the American Society of NephrologyReview176922933
- Mechanical Circulatory SupportMechanical life support therapies exist in many forms to temporarily replace the function of vital organs. Generally speaking, these tools are supportive therapy to allow for organ recovery but, at times, require transition to long-term mechanical support. This review will examine nonrenal extracorporeal life support for cardiac and pulmonary support as well as other mechanical circulatory support options. This is intended as a general primer and overview to assist nephrologist consultants participating in the care of these critically ill patients who often experience acute renal injury as a result of cardiopulmonary shock and from their exposure to mechanical circulatory support.10.2215/CJN.13341021Fri, 20 May 2022 09:56:38 GMT-07:00Mechanical Circulatory SupportMechanical life support therapies exist in many forms to temporarily replace the function of vital organs. Generally speaking, these tools are supportive therapy to allow for organ recovery but, at times, require transition to long-term mechanical support. This review will examine nonrenal extracorporeal life support for cardiac and pulmonary support as well as other mechanical circulatory support options. This is intended as a general primer and overview to assist nephrologist consultants participating in the care of these critically ill patients who often experience acute renal injury as a result of cardiopulmonary shock and from their exposure to mechanical circulatory support.Tam, Christopher W.Shen, LiangZeidman, Amanda DijanicSrivastava, AnkurIvascu, Natalia S.2022-05-20T09:56:38-07:00doi:10.2215/CJN.13341021hwp:resource-id:clinjasn;17/6/890American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, cardiovascular, cardiovascular disease, heart failureCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-06-01June 202210.2215/CJN.133410211555-90411555-905X2022-05-20T09:56:38-07:002022-06Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury176890901
- Endothelin Receptor Antagonists for Kidney Protection10.2215/CJN.00560122Thu, 28 Apr 2022 09:27:02 GMT-07:00Endothelin Receptor Antagonists for Kidney ProtectionHeerspink, Hiddo J.L.de Zeeuw, Dick2022-04-28T09:27:02-07:00doi:10.2215/CJN.00560122hwp:resource-id:clinjasn;17/6/908American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, diabetic nephropathy, endothelin receptor antagonistsPerspectivePerspectiveresearch-article20222022-06-01June 202210.2215/CJN.005601221555-90411555-905X2022-04-28T09:27:02-07:002022-06Clinical Journal of the American Society of NephrologyPerspective176908910
- Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison with Magnetic Resonance Imaging10.2215/CJN.14931121Tue, 05 Apr 2022 09:51:00 GMT-07:00Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison with Magnetic Resonance ImagingAkbari, PedramNasri, FatemahDeng, Shirley X.Khowaja, SaimaLee, Seung H.Warnica, WilliamLu, HuaRattansingh, AnandAtri, MostafaKhalili, KoroshYork, Pei2022-04-05T09:51:00-07:00doi:10.2215/CJN.14931121hwp:resource-id:clinjasn;17/6/827American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypolycystic kidney disease, kidney volume, ultrasonography, ADPKDOriginal ArticleCystic Kidney DiseaseOriginal ArticleCystic Kidney Diseaseresearch-article20222022-06-01June 202210.2215/CJN.149311211555-90411555-905X2022-04-05T09:51:00-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article176827834
- Sepsis Management for the NephrologistThe definition of sepsis has evolved significantly over the past three decades. Today, sepsis is defined as a dysregulated host immune response to microbial invasion leading to end organ dysfunction. Septic shock is characterized by hypotension requiring vasopressors after adequate fluid resuscitation with elevated lactate. Early recognition and intervention remain hallmarks for sepsis management. We addressed the current literature and assimilated thought regarding optimum initial resuscitation of the patient with sepsis. A nuanced understanding of the physiology of lactate is provided in our review. Physiologic and practical knowledge of steroid and vasopressor therapy for sepsis is crucial and addressed. As blood purification may interest the nephrologist treating sepsis, we have also added a brief discussion of its status.10.2215/CJN.14381121Thu, 12 May 2022 08:19:26 GMT-07:00Sepsis Management for the NephrologistThe definition of sepsis has evolved significantly over the past three decades. Today, sepsis is defined as a dysregulated host immune response to microbial invasion leading to end organ dysfunction. Septic shock is characterized by hypotension requiring vasopressors after adequate fluid resuscitation with elevated lactate. Early recognition and intervention remain hallmarks for sepsis management. We addressed the current literature and assimilated thought regarding optimum initial resuscitation of the patient with sepsis. A nuanced understanding of the physiology of lactate is provided in our review. Physiologic and practical knowledge of steroid and vasopressor therapy for sepsis is crucial and addressed. As blood purification may interest the nephrologist treating sepsis, we have also added a brief discussion of its status.Patel, SharadPuri, NitinDellinger, R. Phillip2022-05-12T08:19:26-07:00doi:10.2215/CJN.14381121hwp:resource-id:clinjasn;17/6/880American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, sepsis, acute kidney injury, septic shockCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-06-01June 202210.2215/CJN.143811211555-90411555-905X2022-05-12T08:19:26-07:002022-06Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury176880889
- Conflicts of Interest and the Trustworthiness of Clinical Practice Guidelines10.2215/CJN.04640422Fri, 27 May 2022 10:37:42 GMT-07:00Conflicts of Interest and the Trustworthiness of Clinical Practice GuidelinesMathew, AnnaClase, Catherine M.2022-05-27T10:37:42-07:00doi:10.2215/CJN.04640422hwp:resource-id:clinjasn;17/6/771American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyguidelines, integrity, trustworthiness, conflict of interest, finance biasEditorialEditorialeditorial20222022-06-01June 202210.2215/CJN.046404221555-90411555-905X2022-05-27T10:37:42-07:002022-06Clinical Journal of the American Society of NephrologyEditorial1766771819773826
- Cannabinoids for Symptom Management in Patients with Kidney FailurePeople with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, antiemetic, analgesic, and anti-inflammatory effects. Considering their known physiologic actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, although these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.10.2215/CJN.11560821Wed, 05 Jan 2022 10:13:41 GMT-08:00Cannabinoids for Symptom Management in Patients with Kidney FailurePeople with kidney failure can experience a range of symptoms that lead to suffering and poor quality of life. Available therapies are limited, and evidence for new treatment options is sparse, often resulting in incomplete relief of symptoms. There is growing interest in the potential for cannabinoids, including cannabidiol and tetrahydrocannabinol, to treat symptoms across a wide range of chronic diseases. As legal prohibitions are withdrawn or minimized in many jurisdictions, patients are increasingly able to access these agents. Cannabinoid receptors, CB1 and CB2, are widely expressed in the body, including within the nervous and immune systems, and exogenous cannabinoids can have anxiolytic, antiemetic, analgesic, and anti-inflammatory effects. Considering their known physiologic actions and successful studies in other patient populations, cannabinoids may be viewed as potential therapies for a variety of common symptoms affecting those with kidney failure, including pruritus, nausea, insomnia, chronic neuropathic pain, anorexia, and restless legs syndrome. In this review, we summarize the pharmacology and pharmacokinetics of cannabinoids, along with what is known about the use of cannabinoids for symptom relief in those with kidney disease, and the evidence available concerning their role in management of common symptoms. Presently, although these agents show varying efficacy with a reasonable safety profile in other patient populations, evidence-based prescribing of cannabinoids for people with symptomatic kidney failure is not possible. Given the symptom burden experienced by individuals with kidney failure, there is an urgent need to understand the tolerability and safety of these agents in this population, which must ultimately be followed by robust, randomized controlled trials to determine if they are effective for symptom relief.Worth, HayleyO’Hara, Daniel V.Agarwal, NeeruCollister, DavidBrennan, FrankSmyth, Brendan2022-01-05T10:13:41-08:00doi:10.2215/CJN.11560821hwp:resource-id:clinjasn;17/6/911American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, pharmacokinetics, cannabinoidsFeatureFeatureresearch-article20222022-06-01June 202210.2215/CJN.115608211555-90411555-905X2022-01-05T10:13:41-08:002022-06Clinical Journal of the American Society of NephrologyFeature176911921
- Statement of Clarification: Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug Use10.2215/CJN.04080422Wed, 18 May 2022 10:59:11 GMT-07:00Statement of Clarification: Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug UseAmerican Society of Nephrology2022-05-18T10:59:11-07:00doi:10.2215/CJN.04080422hwp:resource-id:clinjasn;17/6/879American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyStatement of ClarificationErratumStatement of ClarificationErratumcorrection20222022-06-01June 202210.2215/CJN.040804221555-90411555-905X2022-05-18T10:59:11-07:002022-06Clinical Journal of the American Society of NephrologyStatement of Clarification171764879518879526
- Hypertension with Kidney Failure10.2215/CJN.00520122Mon, 28 Mar 2022 05:07:18 GMT-07:00Hypertension with Kidney FailureRivara, Matthew B.Bansal, Nisha2022-03-28T05:07:18-07:00doi:10.2215/CJN.00520122hwp:resource-id:clinjasn;17/6/902American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal replacement therapyKidney Case Conference: Nephrology Quiz & QuestionnaireKidney Case Conference: Nephrology Quiz & Questionnaireresearch-article20222022-06-01June 202210.2215/CJN.005201221555-90411555-905X2022-03-28T05:07:18-07:002022-06Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz & Questionnaire176902904
- Medicare Bundled Payment Policy and Anemia Care10.2215/CJN.03540322Thu, 19 May 2022 11:31:15 GMT-07:00Medicare Bundled Payment Policy and Anemia CareThomas, Cher2022-05-19T11:31:15-07:00doi:10.2215/CJN.03540322hwp:resource-id:clinjasn;17/6/769American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, MedicarePatient VoicePatient Voiceresearch-article20222022-06-01June 202210.2215/CJN.035403221555-90411555-905X2022-05-19T11:31:15-07:002022-06Clinical Journal of the American Society of NephrologyPatient Voice17666769851843770860850
- Fractional Excretion of Sodium (FENa)10.2215/CJN.04750422Wed, 25 May 2022 11:01:49 GMT-07:00Fractional Excretion of Sodium (FENa)Seethapathy, HarishFenves, Andrew Z.2022-05-25T11:01:49-07:00doi:10.2215/CJN.04750422hwp:resource-id:clinjasn;17/6/777American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFENa, AKI, AT N, prerenal azotemiaEditorialEditorialeditorial20222022-06-01June 202210.2215/CJN.047504221555-90411555-905X2022-05-25T11:01:49-07:002022-06Clinical Journal of the American Society of NephrologyEditorial171766877778512187787971218
- International Variation in Time on Peritoneal Dialysis10.2215/CJN.04800422Tue, 31 May 2022 12:48:45 GMT-07:00International Variation in Time on Peritoneal DialysisRivara, Matthew B.2022-05-31T12:48:45-07:00doi:10.2215/CJN.04800422hwp:resource-id:clinjasn;17/6/782American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hemodialysis, transplantation, epidemiology and outcomesEditorialEditorialeditorial20222022-06-01June 202210.2215/CJN.048004221555-90411555-905X2022-05-31T12:48:45-07:002022-06Clinical Journal of the American Society of NephrologyEditorial1766782861784871
- Safety of SGLT2 Inhibitors in CKD10.2215/CJN.04900422Thu, 26 May 2022 07:04:51 GMT-07:00Safety of SGLT2 Inhibitors in CKDDobre, Mirela2022-05-26T07:04:51-07:00doi:10.2215/CJN.04900422hwp:resource-id:clinjasn;17/6/774American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysodium-glucose transporter 2 inhibitors, SGLT2, chronic kidney diseaseEditorialEditorialeditorial20222022-06-01June 202210.2215/CJN.049004221555-90411555-905X2022-05-26T07:04:51-07:002022-06Clinical Journal of the American Society of NephrologyEditorial1766774835776842
- Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease10.2215/CJN.16171221Thu, 26 May 2022 07:04:52 GMT-07:00Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney DiseaseCowan, AndreaJeyakumar, NivethikaKang, YuguangDixon, Stephanie N.Garg, Amit X.Naylor, KylaWeir, Matthew A.Clemens, Kristin K.2022-05-26T07:04:52-07:00doi:10.2215/CJN.16171221hwp:resource-id:clinjasn;17/6/835American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, renal osteodystrophy, epidemiology and outcomes, sodium-glucose transporter 2 inhibitors, chronic kidney diseaseOriginal ArticleDiabetes and the KidneyOriginal ArticleDiabetes and the Kidneyresearch-article20222022-06-01June 202210.2215/CJN.161712211555-90411555-905X2022-05-26T07:04:52-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article1766835774842776
- COVID-19 Vaccination for Patients Undergoing Long-Term Hemodialysis10.2215/CJN.04460422Wed, 01 Jun 2022 11:44:27 GMT-07:00COVID-19 Vaccination for Patients Undergoing Long-Term HemodialysisKorst, Uwe K.H.2022-06-01T11:44:27-07:00doi:10.2215/CJN.04460422hwp:resource-id:clinjasn;17/6/767American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, vaccination, hemodialysisPatient VoicePatient Voiceresearch-article20222022-06-01June 202210.2215/CJN.044604221555-90411555-905X2022-06-01T11:44:27-07:002022-06Clinical Journal of the American Society of NephrologyPatient Voice17666767843779768850781
- Humoral Response to Third Dose of SARS-CoV-2 Vaccines in the CKD Spectrum10.2215/CJN.01770222Thu, 12 May 2022 08:19:26 GMT-07:00Humoral Response to Third Dose of SARS-CoV-2 Vaccines in the CKD SpectrumQuiroga, BorjaSoler, María JoséOrtiz, AlbertoOrero, EstherTejedor, SandraMantecón, Carlos Jesús JaravaGómez Pérez, Virginia OlindaMarín Franco, Antonio JoséAlfaro Sánchez, ChristianPuerta Carretero, MartaJaldo Rodríguez, María TeresaCarnerero Di Riso, Manuel AntonioMartínez, ShairaGonzález, Carmen CalderónCervienka, MichalMacías Carmona, NicolásArroyo, DavidPérez del Valle, Katia M.de Arriba, GabrielMazuecos, AuxiliadoraCazorla, Juan ManuelPereira, MónicaGonzález Parra, EmilioSánchez Márquez, María GabrielaLancho Novillo, CarolinaToyos Ruiz, CarmenAguilar Cervera, María CintaMuñoz Ramos, PatriciaSánchez Horrillo, AnaJimeno Martín, IsabelToapanta, NéstorCigarrán Guldris, SecundinoFolgueiras López, MontserratValero San Cecilio, RosalíaVillacorta Linaza, BlancaMinguela Pesquera, IgnacioSantana Estupiñán, RaquelZamora, RocíoSoriano, SagrarioMuñoz de Bustillo, EduardoPizarro Sánchez, María SoledadMartínez Puerto, Ana IsabelYugueros, AlejandraMuñiz Pacios, LauraLeyva, AlbaRojas, JoséGansevoort, Ron T.de Sequera, Patricia2022-05-12T08:19:26-07:00doi:10.2215/CJN.01770222hwp:resource-id:clinjasn;17/6/872American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, vaccination, anti-Spike, chronic kidney disease, hemodialysis, peritoneal dialysis, kidney transplantation, SARS-CoV-2Research LetterResearch Letterletter20222022-06-01June 202210.2215/CJN.017702221555-90411555-905X2022-05-12T08:19:26-07:002022-06Clinical Journal of the American Society of NephrologyResearch Letter176872876
- Clinical Utility of COVID-19 Vaccination in Patients Undergoing Hemodialysis10.2215/CJN.04930422Wed, 01 Jun 2022 11:44:27 GMT-07:00Clinical Utility of COVID-19 Vaccination in Patients Undergoing HemodialysisOliver, Matthew J.Blake, Peter G.2022-06-01T11:44:27-07:00doi:10.2215/CJN.04930422hwp:resource-id:clinjasn;17/6/779American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, chronic hemodialysis, vaccinationEditorialEditorialeditorial20222022-06-01June 202210.2215/CJN.049304221555-90411555-905X2022-06-01T11:44:27-07:002022-06Clinical Journal of the American Society of NephrologyEditorial17666779843767781850768
- Severity of COVID-19 after Vaccination among Hemodialysis Patients10.2215/CJN.16621221Wed, 01 Jun 2022 11:44:27 GMT-07:00Severity of COVID-19 after Vaccination among Hemodialysis PatientsAshby, Damien R.Caplin, BenCorbett, Richard W.Asgari, ElhamKumar, NicolaSarnowski, AlexanderHull, RichardMakanjuola, DavidCole, NicholasChen, JianNyberg, SofiaMcCafferty, KieranZaman, FaryalCairns, HughSharpe, ClaireBramham, KateMotallebzadeh, RezaAnwari, Kashif JamilSalama, Alan D.Banerjee, Debasish,Ashby, Damien R.Caplin, BenCorbett, Richard W.Asgari, ElhamKumar, NicolaSarnowski, AlexanderHull, RichardMakanjuola, DavidCole, NicholasChen, JianNyberg, SofiaMcCafferty, KieranZaman, FaryalCairns, HughSharpe, ClaireBramham, KateMotallebzadeh, RezaAnwari, Kashif JamilSalama, Alan D.Banerjee, DebasishAli, OmerAntonelou, MarilinaBennet-Richards, KatyBlunden, MarkBooth, JohnCharif, RawyaChaudhury, SaurabhCove-Smith, AndreaDobbie, HamishDodd, PhillippaDreyer, GavinDuncan, NeillForbes, SuzanneGoodlad, CatrionaGriffith, MeganHassan, SevdaHemmilla, UllaHendra, HeidyHill, PeterJames, AjithJones, DanielLaurence, AnilaLoucaidou, MarinaLucisano, GaetanoMahalingasivam, ViyaasanManson, BethiaMcGuiness, DanielMcLean, AdamMontero, RosaMuthuppalaniappan, VasanthaOates, TomPalmer, AndrewRajakariar, RaviSalisbury, EmmaSamad, NasreenSandhu, EleanorStern, EdwardTandaric, DamirTomlinson, JamesVajgel, GiseleWebster, PhilWhite, WilliamWiles, KateWright, DavidYousef, Sajeda2022-06-01T11:44:27-07:00doi:10.2215/CJN.16621221hwp:resource-id:clinjasn;17/6/843American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, COVID-19, vaccination, hemodialysisOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-06-01June 202210.2215/CJN.166212211555-90411555-905X2022-06-01T11:44:27-07:002022-06Clinical Journal of the American Society of NephrologyOriginal Article176666843767779769850768781770
- Correction: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial10.2215/CJN.03710322Fri, 20 May 2022 09:56:37 GMT-07:00Correction: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled TrialAmerican Society of Nephrology2022-05-20T09:56:37-07:00doi:10.2215/CJN.03710322hwp:resource-id:clinjasn;17/6/877American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, arterial stiffness, children, clinical trial, endothelium, pediatric nephrology, polyphenol, pulse wave velocity, vascular, CurcuminErratumErratumcorrection20222022-06-01June 202210.2215/CJN.037103221555-90411555-905X2022-05-20T09:56:37-07:002022-06Clinical Journal of the American Society of NephrologyErratum171762877240878250
- The Role of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists in the Prevention and Treatment of Diabetic Kidney Disease10.2215/CJN.00020122Fri, 08 Apr 2022 07:31:44 GMT-07:00The Role of Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists in the Prevention and Treatment of Diabetic Kidney DiseaseTommerdahl, Kalie L.Kendrick, JessicaBjornstad, Petter2022-04-08T07:31:44-07:00doi:10.2215/CJN.00020122hwp:resource-id:clinjasn;17/6/905American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, albuminuria, clinical trial, cardiovascular disease, diabetes mellitusPerspectivePerspectiveresearch-article20222022-06-01June 202210.2215/CJN.000201221555-90411555-905X2022-04-08T07:31:44-07:002022-06Clinical Journal of the American Society of NephrologyPerspective176905907
- Cerebral salt wasting is a real cause of hyponatremia: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001422022 and the COMMENTARY: 10.34067/KID.0001452022rondonberriosh@upmc.edu10.34067/KID.0001412022Thu, 02 Jun 2022 10:04:41 GMT-07:00Cerebral salt wasting is a real cause of hyponatremia: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001422022 and the COMMENTARY: 10.34067/KID.0001452022Sterns, Richard H.Rondon-Berrios, Helbert2022-06-02T10:04:41-07:00doi:10.34067/KID.0001412022hwp:resource-id:kidney360;KID.0001412022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Hyponatremia, SIADH, Cerebral Salt WastingDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00014120222641-76502641-76502022-06-02T10:04:41-07:00Kidney360Debates in Nephrology10.34067/KID.0001412022
- Cerebral salt wasting is a real cause of hyponatremia: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0001412022 and the COMMENTARY: 10.34067/KID.0001452022John.Maesaka@nyulangone.org10.34067/KID.0001422022Thu, 02 Jun 2022 10:04:41 GMT-07:00Cerebral salt wasting is a real cause of hyponatremia: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0001412022 and the COMMENTARY: 10.34067/KID.0001452022Maesaka, John K.Imbriano, Louis J.2022-06-02T10:04:41-07:00doi:10.34067/KID.0001422022hwp:resource-id:kidney360;KID.0001422022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360cerebral salt wasting, HyponatremiaDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00014220222641-76502641-76502022-06-02T10:04:41-07:00Kidney360Debates in Nephrology10.34067/KID.0001422022
- Cerebral salt wasting is a real cause of hyponatremia: CommentaryThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001422022 and the CON: 10.34067/KID.0001412022biff.palmer@utsouthwestern.edu10.34067/KID.0001452022Thu, 02 Jun 2022 10:04:41 GMT-07:00Cerebral salt wasting is a real cause of hyponatremia: CommentaryThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0001422022 and the CON: 10.34067/KID.0001412022Palmer, Biff F.Clegg, Deborah J.2022-06-02T10:04:41-07:00doi:10.34067/KID.0001452022hwp:resource-id:kidney360;KID.0001452022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360hyponatremia, cerebral salt wasting, natriuretic peptides, brain natriuretic peptide, SIADH, vasopressin, syndrome of antidiuretic hormone secretionModerator CommentaryModerator Commentaryother202210.34067/KID.00014520222641-76502641-76502022-06-02T10:04:41-07:00Kidney360Moderator Commentary10.34067/KID.0001452022
- More than a Marker: Arginase-1 in Kidney Repair10.1681/ASN.2022020161Mon, 16 May 2022 11:58:01 GMT-07:00More than a Marker: Arginase-1 in Kidney Repairvon Vietinghoff, SibylleSchmitt, Roland2022-05-16T11:58:01-07:00doi:10.1681/ASN.2022020161hwp:resource-id:jnephrol;33/6/1051American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cell signaling, macrophages, renal proximal tubule cell, proliferationUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-06-01June 202210.1681/ASN.20220201611046-66731533-34502022-05-16T11:58:01-07:002022-06Journal of the American Society of NephrologyUp Front Matters336661051i10771053i1086
- Crystals or His(stones): Rethinking AKI in Tumor Lysis Syndrome10.1681/ASN.2022040425Tue, 31 May 2022 10:00:28 GMT-07:00Crystals or His(stones): Rethinking AKI in Tumor Lysis SyndromeBasile, David P.2022-05-31T10:00:28-07:00doi:10.1681/ASN.2022040425hwp:resource-id:jnephrol;33/6/1055American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-06-01June 202210.1681/ASN.20220404251046-66731533-34502022-05-31T10:00:28-07:002022-06Journal of the American Society of NephrologyUp Front Matters336661055i11541057i1171
- This Month's Highlights10.1681/ASN.2022040473Tue, 31 May 2022 10:00:28 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2022-05-31T10:00:28-07:00doi:10.1681/ASN.2022040473hwp:resource-id:jnephrol;33/6/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsother20222022-06-01June 202210.1681/ASN.20220404731046-66731533-34502022-05-31T10:00:28-07:002022-06Journal of the American Society of NephrologyThis Month's Highlights336666666i107710511105105311541055i108610531119105511711057
- Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma Exchange10.1681/ASN.2022020164Mon, 11 Apr 2022 11:45:23 GMT-07:00Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma ExchangeCasal Moura, MartaSoler, Maria JoséSethi, SanjeevFervenza, Fernando C.Specks, Ulrich2022-04-11T11:45:23-07:00doi:10.1681/ASN.2022020164hwp:resource-id:jnephrol;33/6/1223American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, glomerulonephritis, plasma exchange, anti-neutrophil cytoplasmic antibody-associated vasculitis, acute kidney injuryLetter to the EditorLetter to the Editorletter20222022-06-01June 202210.1681/ASN.20220201641046-66731533-34502022-04-11T11:45:23-07:002022-06Journal of the American Society of NephrologyLetter to the Editor336631223122462812241225637
- Factor H–Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 Glomerulopathy10.1681/ASN.2021101318Wed, 11 May 2022 01:54:29 GMT-07:00Factor H–Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 GlomerulopathyMárquez-Tirado, BárbaraGutiérrez-Tenorio, JosuéTortajada, AgustínLucientes Continente, LauraCaravaca-Fontán, FernandoMalik, Talat H.Roldán Montero, RaquelElías, SandraSaiz Gonzalez, AnaFernández-Juarez, GemaSánchez-Corral, PilarPickering, Matthew C.Praga, ManuelRodríguez de Córdoba, SantiagoGoicoechea de Jorge, Elena2022-05-11T13:54:29-07:00doi:10.1681/ASN.2021101318hwp:resource-id:jnephrol;33/6/1137American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyC3 glomerulopathy, complement, factor H-related protein 1, glomerular disease, disease susceptibility, prognosis, genetic renal diseaseBasic ResearchGlomerulonephritis and Interstitial NephritisBasic ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-06-01June 202210.1681/ASN.20211013181046-66731533-34502022-05-11T13:54:29-07:002022-06Journal of the American Society of NephrologyBasic Research33611371153
- Acute Kidney Injury Associates with Long-Term Increases in Plasma TNFR1, TNFR2, and KIM-1: Findings from the CRIC Study10.1681/ASN.2021111453Wed, 16 Mar 2022 08:07:05 GMT-07:00Acute Kidney Injury Associates with Long-Term Increases in Plasma TNFR1, TNFR2, and KIM-1: Findings from the CRIC StudyMcCoy, Ian E.Hsu, Jesse Y.Bonventre, Joseph V.Parikh, Chirag R.Go, Alan S.Liu, Kathleen D.Ricardo, Ana C.Srivastava, AnandCohen, Debbie L.He, JiangChen, JingRao, Panduranga S.Hsu, Chi-yuan,Appel, Lawrence J.Feldman, Harold J.Lash, James P.Nelson, Robert G.Rahman, MahboobShah, Vallabh O.Unruh, Mark L.2022-03-16T08:07:05-07:00doi:10.1681/ASN.2021111453hwp:resource-id:jnephrol;33/6/1173American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, chronic kidney disease, hospitalization, renal injury, acute kidney injury, biomarkers, plasmaClinical ResearchAcute Kidney InjuryClinical ResearchAcute Kidney Injuryresearch-article20222022-06-01June 202210.1681/ASN.20211114531046-66731533-34502022-03-16T08:07:05-07:002022-06Journal of the American Society of NephrologyClinical Research33611731181
- Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study10.1681/ASN.2021121642Wed, 23 Mar 2022 10:18:25 GMT-07:00Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort StudyKnoll, GregCampbell, PatriciaChassé, MichaëlFergusson, DeanRamsay, TimKarnabi, PriscillaPerl, JeffreyHouse, Andrew A.Kim, JosephJohnston, OlwynMainra, RahulHoude, IsabelleBaran, DanaTreleaven, Darin J.Senecal, LynneTibbles, Lee AnneHébert, Marie-JoséeWhite, ChristineKarpinski, MartinGill, John S.2022-03-23T10:18:25-07:00doi:10.1681/ASN.2021121642hwp:resource-id:jnephrol;33/6/1182American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, rejection, survival, transplant nephrectomyClinical ResearchTransplantationClinical ResearchTransplantationresearch-article20222022-06-01June 202210.1681/ASN.20211216421046-66731533-34502022-03-23T10:18:25-07:002022-06Journal of the American Society of NephrologyClinical Research33611821192
- Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United StatesThe United States Department of Health and Human Services launched the Advancing American Kidney Health Initiative in 2019, which included a goal of transforming dialysis care from an in-center to a largely home-based dialysis program. A substantial motivator for this transition is the potential to reduce costs of ESKD care with peritoneal dialysis. Studies demonstrating that peritoneal dialysis is less costly than in-center hemodialysis have often focused on the perspective of the payer, whereas less consideration has been given to the costs of those who are more directly involved in treatment decision making, including patients, caregivers, physicians, and dialysis facilities. We review comparisons of peritoneal dialysis and in-center hemodialysis costs, focusing on costs incurred by the people and organizations making decisions about dialysis modality, to highlight the financial barriers toward increased adoption of peritoneal dialysis. We specifically address misaligned economic incentives, underappreciated costs for key stakeholders involved in peritoneal dialysis delivery, differences in provider costs, and transition costs. We conclude by offering policy suggestions that include improving data collection to better understand costs in peritoneal dialysis, and sharing potential savings among all stakeholders, to incentivize a transition to peritoneal dialysis.10.1681/ASN.2021060854Mon, 21 Mar 2022 08:02:49 GMT-07:00Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United StatesThe United States Department of Health and Human Services launched the Advancing American Kidney Health Initiative in 2019, which included a goal of transforming dialysis care from an in-center to a largely home-based dialysis program. A substantial motivator for this transition is the potential to reduce costs of ESKD care with peritoneal dialysis. Studies demonstrating that peritoneal dialysis is less costly than in-center hemodialysis have often focused on the perspective of the payer, whereas less consideration has been given to the costs of those who are more directly involved in treatment decision making, including patients, caregivers, physicians, and dialysis facilities. We review comparisons of peritoneal dialysis and in-center hemodialysis costs, focusing on costs incurred by the people and organizations making decisions about dialysis modality, to highlight the financial barriers toward increased adoption of peritoneal dialysis. We specifically address misaligned economic incentives, underappreciated costs for key stakeholders involved in peritoneal dialysis delivery, differences in provider costs, and transition costs. We conclude by offering policy suggestions that include improving data collection to better understand costs in peritoneal dialysis, and sharing potential savings among all stakeholders, to incentivize a transition to peritoneal dialysis.Baerman, Elliot A.Kaplan, JenniferShen, Jenny I.Winkelmayer, Wolfgang C.Erickson, Kevin F.2022-03-21T08:02:49-07:00doi:10.1681/ASN.2021060854hwp:resource-id:jnephrol;33/6/1063American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, economic analysis, ESKD, peritoneal dialysis, United StatesUp Front MattersReviewUp Front MattersReviewreview-article20222022-06-01June 202210.1681/ASN.20210608541046-66731533-34502022-03-21T08:02:49-07:002022-06Journal of the American Society of NephrologyUp Front Matters336111063212510722126
- The Advancing American Kidney Health Initiative: The Challenge of Measuring Success10.1681/ASN.2021121619Tue, 29 Mar 2022 08:10:44 GMT-07:00The Advancing American Kidney Health Initiative: The Challenge of Measuring SuccessQuinn, Robert R.Lam, Ngan N.Ravani, PietroOliver, Matthew J.Blake, Peter G.Tonelli, Marcello2022-03-29T08:10:44-07:00doi:10.1681/ASN.2021121619hwp:resource-id:jnephrol;33/6/1060American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhome dialysis, Advancing American Kidney Health Initiative, conservative kidney management, policy, United StatesUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20222022-06-01June 202210.1681/ASN.20211216191046-66731533-34502022-03-29T08:10:44-07:002022-06Journal of the American Society of NephrologyUp Front Matters33699910601797179818001062179817991801
- Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study10.1681/ASN.2021111472Wed, 30 Mar 2022 10:11:26 GMT-07:00Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International StudyChan, Eugene Yu-hinYu, Ellen L.M.Angeletti, AndreaArslan, ZainabBasu, BiswanathBoyer, OliviaChan, Chang-YienColucci, ManuelaDorval, GuillaumeDossier, ClaireDrovandi, StefaniaGhiggeri, Gian MarcoGipson, Debbie S.Hamada, RikuHogan, JulienIshikura, KenjiKamei, KoichiKemper, Markus J.Ma, Alison Lap-takParekh, Rulan S.Radhakrishnan, SeethaSaini, PriyaShen, QianSinha, RajivSubun, ChantidaTeo, SharonVivarelli, MarinaWebb, HazelXu, HongYap, Hui KimTullus, Kjell2022-03-30T10:11:26-07:00doi:10.1681/ASN.2021111472hwp:resource-id:jnephrol;33/6/1193American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyrituximab, nephrotic syndrome, hypogammaglobulinemia, neutropenia, children, biologicsClinical ResearchGlomerulonephritis and Interstitial NephritisClinical ResearchGlomerulonephritis and Interstitial Nephritisresearch-article20222022-06-01June 202210.1681/ASN.20211114721046-66731533-34502022-03-30T10:11:26-07:002022-06Journal of the American Society of NephrologyClinical Research33611931207
- Authors’ Reply: Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma Exchange10.1681/ASN.2022030269Mon, 11 Apr 2022 11:29:40 GMT-07:00Authors’ Reply: Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma ExchangeNezam, DorianPorcher, RaphaëlGrolleau, FrançoisTerrier, Benjamin,Cottin, VincentFaguer, StanislasGuillevin, LoïcJourde-Chiche, NoémieKarras, AlexandreMouthon, LucNéel, AntoinePuéchal, XavierPugnet, GrégorySamson, MaximeTaillé, CamilleTerrier, Benjamin2022-04-11T11:29:40-07:00doi:10.1681/ASN.2022030269hwp:resource-id:jnephrol;33/6/1224American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, kidney failure, histopathology, plasma exchangeLetter to the EditorLetter to the Editorletter20222022-06-01June 202210.1681/ASN.20220302691046-66731533-34502022-04-11T11:29:40-07:002022-06Journal of the American Society of NephrologyLetter to the Editor336631224122362812251224637
- Tumor Lysis Syndrome and AKI: Beyond Crystal Mechanisms10.1681/ASN.2021070997Fri, 06 May 2022 11:20:43 GMT-07:00Tumor Lysis Syndrome and AKI: Beyond Crystal MechanismsArnaud, MarineLoiselle, MaudVaganay, CamillePons, StéphanieLetavernier, EmmanuelDemonchy, JordaneFodil, SofianeNouacer, ManalPlacier, SandrineFrère, PerrineArrii, EdenLion, JulienMooney, NualaItzykson, RaphaelDjediat, ChakibPuissant, AlexandreZafrani, Lara2022-05-06T11:20:43-07:00doi:10.1681/ASN.2021070997hwp:resource-id:jnephrol;33/6/1154American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, endothelium, histones, tumor lysis syndromeBasic ResearchAcute Kidney InjuryBasic ResearchAcute Kidney Injuryresearch-article20222022-06-01June 202210.1681/ASN.20210709971046-66731533-34502022-05-06T11:20:43-07:002022-06Journal of the American Society of NephrologyBasic Research3366610101154i1055195119521171i105719521953
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- International Icodextrin Use and Association with Peritoneal Membrane Function, Fluid Removal, Patient and Technique Survival10.34067/KID.0006922021Tue, 01 Mar 2022 11:54:15 GMT-08:00International Icodextrin Use and Association with Peritoneal Membrane Function, Fluid Removal, Patient and Technique SurvivalDavies, SimonZhao, JunhuiMcCullough, Keith P.Kim, Yong-LimWang, Angela Yee-MoonBadve, Sunil V.Mehrotra, RajnishKanjanabuch, TalerngsakKawanishi, HidekiRobinson, BrucePisoni, RonaldPerl, Jeffrey,2022-03-01T11:54:15-08:00doi:10.34067/KID.0006922021hwp:resource-id:kidney360;3/5/872American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, dialysis modality transfer, icodextrin, patient survival, peritoneal dialysis, peritoneal membrane functionOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20222022-05-2610.34067/KID.00069220212641-76502022-03-01T11:54:15-08:002022-05-26Kidney360Original Investigation35872882
- Measurement of Urinary Ammonium Using a Commercially Available Plasma Ammonium Assay10.34067/KID.0000262022Fri, 11 Feb 2022 05:52:12 GMT-08:00Measurement of Urinary Ammonium Using a Commercially Available Plasma Ammonium AssayGruzdys, ValentinasCahoon, KennethPearson, LaurenRaphael, Kalani L.2022-02-11T05:52:12-08:00doi:10.34067/KID.0000262022hwp:resource-id:kidney360;3/5/926American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, ammonium, chronic kidney disease, metabolic acidosisInnovative Technology and MethodologyAcid/Base and Electrolyte DisordersInnovative Technology and MethodologyAcid/Base and Electrolyte Disordersresearch-article20222022-05-2610.34067/KID.00002620222641-76502022-02-11T05:52:12-08:002022-05-26Kidney360Innovative Technology and Methodology35926932
- Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal SyndromeDespite the incompletely understood multiple etiologies and underlying mechanisms, cardiorenal syndrome is characterized by decreased glomerular filtration and sodium avidity. The underlying level of renal sodium avidity is of primary importance in driving a congested heart failure phenotype and ultimately determining the response to diuretic therapy. Historically, mechanisms of kidney sodium avidity and resultant diuretic resistance were primarily extrapolated to cardiorenal syndrome from non–heart failure populations. Yet, the mechanisms appear to differ between these populations. Recent literature in acute decompensated heart failure has refuted several classically accepted diuretic resistance mechanisms and reshaped how we conceptualize diuretic resistance mechanisms in cardiorenal syndrome. Herein, we propose an anatomically based categorization of diuretic resistance mechanisms to establish the relative importance of specific transporters and translate findings toward therapeutic strategies. Within this categorical structure, we discuss classic and novel mechanisms of diuretic resistance.10.34067/KID.0006372021Tue, 01 Mar 2022 01:34:06 GMT-08:00Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal SyndromeDespite the incompletely understood multiple etiologies and underlying mechanisms, cardiorenal syndrome is characterized by decreased glomerular filtration and sodium avidity. The underlying level of renal sodium avidity is of primary importance in driving a congested heart failure phenotype and ultimately determining the response to diuretic therapy. Historically, mechanisms of kidney sodium avidity and resultant diuretic resistance were primarily extrapolated to cardiorenal syndrome from non–heart failure populations. Yet, the mechanisms appear to differ between these populations. Recent literature in acute decompensated heart failure has refuted several classically accepted diuretic resistance mechanisms and reshaped how we conceptualize diuretic resistance mechanisms in cardiorenal syndrome. Herein, we propose an anatomically based categorization of diuretic resistance mechanisms to establish the relative importance of specific transporters and translate findings toward therapeutic strategies. Within this categorical structure, we discuss classic and novel mechanisms of diuretic resistance.Cox, Zachary L.Rao, Veena S.Testani, Jeffrey M.2022-03-01T13:34:06-08:00doi:10.34067/KID.0006372021hwp:resource-id:kidney360;3/5/954American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephropharmacology, acute heart failure, cardiorenal syndrome, diuretic resistance, diuretics, loop diureticReview ArticleNephro-PharmacologyReview ArticleNephro-Pharmacologyreview-article20222022-05-2610.34067/KID.00063720212641-76502022-03-01T13:34:06-08:002022-05-26Kidney360Review Article35954967
- Profiling Immune Cells in the Kidney Using Tissue Cytometry and Machine LearningThe immune system governs key functions that maintain renal homeostasis through various effector cells that reside in or infiltrate the kidney. These immune cells play an important role in shaping adaptive or maladaptive responses to local or systemic stress and injury. We increasingly recognize that microenvironments within the kidney are characterized by a unique distribution of immune cells, the function of which depends on this unique spatial localization. Therefore, quantitative profiling of immune cells in intact kidney tissue becomes essential, particularly at a scale and resolution that allow the detection of differences between the various “nephro-ecosystems” in health and disease. In this review, we discuss advancements in tissue cytometry of the kidney, performed through multiplexed confocal imaging and analysis using the Volumetric Tissue Exploration and Analysis (VTEA) software. We highlight how this tool has improved our understanding of the role of the immune system in the kidney and its relevance in the pathobiology of renal disease. We also discuss how the field is increasingly incorporating machine learning to enhance the analytic potential of imaging data and provide unbiased methods to explore and visualize multidimensional data. Such novel analytic methods could be particularly relevant when applied to profiling immune cells. Furthermore, machine-learning approaches applied to cytometry could present venues for nonexhaustive exploration and classification of cells from existing data and improving tissue economy. Therefore, tissue cytometry is transforming what used to be a qualitative assessment of the kidney into a highly quantitative, imaging-based “omics” assessment that complements other advanced molecular interrogation technologies.telachka@iu.edu10.34067/KID.0006802020Thu, 11 Feb 2021 09:46:02 GMT-08:00Profiling Immune Cells in the Kidney Using Tissue Cytometry and Machine LearningThe immune system governs key functions that maintain renal homeostasis through various effector cells that reside in or infiltrate the kidney. These immune cells play an important role in shaping adaptive or maladaptive responses to local or systemic stress and injury. We increasingly recognize that microenvironments within the kidney are characterized by a unique distribution of immune cells, the function of which depends on this unique spatial localization. Therefore, quantitative profiling of immune cells in intact kidney tissue becomes essential, particularly at a scale and resolution that allow the detection of differences between the various “nephro-ecosystems” in health and disease. In this review, we discuss advancements in tissue cytometry of the kidney, performed through multiplexed confocal imaging and analysis using the Volumetric Tissue Exploration and Analysis (VTEA) software. We highlight how this tool has improved our understanding of the role of the immune system in the kidney and its relevance in the pathobiology of renal disease. We also discuss how the field is increasingly incorporating machine learning to enhance the analytic potential of imaging data and provide unbiased methods to explore and visualize multidimensional data. Such novel analytic methods could be particularly relevant when applied to profiling immune cells. Furthermore, machine-learning approaches applied to cytometry could present venues for nonexhaustive exploration and classification of cells from existing data and improving tissue economy. Therefore, tissue cytometry is transforming what used to be a qualitative assessment of the kidney into a highly quantitative, imaging-based “omics” assessment that complements other advanced molecular interrogation technologies.Winfree, SethAl Hasan, MohammadEl-Achkar, Tarek M.2021-02-11T09:46:02-08:00doi:10.34067/KID.0006802020hwp:resource-id:kidney360;3/5/968American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360renal physiology, AKI, basic science, CKD, imaging, immunology, inflammation, machine learning, pathologyReview ArticleRenal PhysiologyReview ArticleRenal Physiologyreview-article20222022-05-2610.34067/KID.00068020202641-76502021-02-11T09:46:02-08:002022-05-26Kidney360Review Article35968978
- The KIDNEYCODE Program: Diagnostic Yield and Clinical Features of Individuals with CKD10.34067/KID.0004162021Thu, 10 Mar 2022 09:27:38 GMT-08:00The KIDNEYCODE Program: Diagnostic Yield and Clinical Features of Individuals with CKDLieberman, Kenneth V.Chang, Alexander R.Block, Geoffrey A.Robinson, KristinaBristow, Sara L.Morales, AnaMitchell, AsiaMcCalley, StephenMcKay, JimPollak, Martin R.Aradhya, SwaroopWarady, Bradley A.2022-03-10T09:27:38-08:00doi:10.34067/KID.0004162021hwp:resource-id:kidney360;3/5/900American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360genetics, Alport syndrome, CKD, eGFR, FSGS, genetic testing, genetics, hematuria, kidney biopsy, PKDOriginal InvestigationGeneticsOriginal InvestigationGeneticsresearch-article20222022-05-2610.34067/KID.00041620212641-76502022-03-10T09:27:38-08:002022-05-26Kidney360Original Investigation35900909
- Rates of Cardiovascular Disease and CKD Progression in Young Adults with CKD across Racial and Ethnic Groups10.34067/KID.0006712021Thu, 17 Feb 2022 11:48:22 GMT-08:00Rates of Cardiovascular Disease and CKD Progression in Young Adults with CKD across Racial and Ethnic GroupsKula, Alexander J.Prince, David K.Limonte, Christine P.Young, Bessie A.Bansal, Nisha2022-02-17T11:48:22-08:00doi:10.34067/KID.0006712021hwp:resource-id:kidney360;3/5/834American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, cardiovascular disease, disparities, ethnic groups, hypertension, young adultOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-05-2610.34067/KID.00067120212641-76502022-02-17T11:48:22-08:002022-05-26Kidney360Original Investigation35834842
- Iron Supplementation Improves Skeletal Muscle Contractile Properties in Mice with CKD10.34067/KID.0004412021Fri, 25 Mar 2022 11:44:50 GMT-07:00Iron Supplementation Improves Skeletal Muscle Contractile Properties in Mice with CKDMomb, Brent A.Patino, EdwinAkchurin, Oleh M.Miller, Mark S.2022-03-25T11:44:50-07:00doi:10.34067/KID.0004412021hwp:resource-id:kidney360;3/5/843American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, basic science, frailty, iron, kidney, mice, myosin, physical functionOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-05-2610.34067/KID.00044120212641-76502022-03-25T11:44:50-07:002022-05-26Kidney360Original Investigation35843858
- Novel Function for Bilirubin as a Metabolic Signaling Molecule: Implications for Kidney DiseasesBilirubin is the end product of the catabolism of heme via the heme oxygenase pathway. Heme oxygenase generates carbon monoxide (CO) and biliverdin from the breakdown of heme, and biliverdin is rapidly reduced to bilirubin by the enzyme biliverdin reductase (BVR). Bilirubin has long been thought of as a toxic product that is only relevant to health when blood levels are severely elevated, such as in clinical jaundice. The physiologic functions of bilirubin correlate with the growing body of evidence demonstrating the protective effects of serum bilirubin against cardiovascular and metabolic diseases. Although the correlative evidence suggests a protective effect of serum bilirubin against many diseases, the mechanism by which bilirubin offers protection against cardiovascular and metabolic diseases remains unanswered. We recently discovered a novel function for bilirubin as a signaling molecule capable of activating the peroxisome proliferator-activated receptor α (PPARα) transcription factor. This review summarizes the new finding of bilirubin as a signaling molecule and proposes several mechanisms by which this novel action of bilirubin may protect against cardiovascular and kidney diseases.10.34067/KID.0000062022Fri, 25 Mar 2022 01:37:16 GMT-07:00Novel Function for Bilirubin as a Metabolic Signaling Molecule: Implications for Kidney DiseasesBilirubin is the end product of the catabolism of heme via the heme oxygenase pathway. Heme oxygenase generates carbon monoxide (CO) and biliverdin from the breakdown of heme, and biliverdin is rapidly reduced to bilirubin by the enzyme biliverdin reductase (BVR). Bilirubin has long been thought of as a toxic product that is only relevant to health when blood levels are severely elevated, such as in clinical jaundice. The physiologic functions of bilirubin correlate with the growing body of evidence demonstrating the protective effects of serum bilirubin against cardiovascular and metabolic diseases. Although the correlative evidence suggests a protective effect of serum bilirubin against many diseases, the mechanism by which bilirubin offers protection against cardiovascular and metabolic diseases remains unanswered. We recently discovered a novel function for bilirubin as a signaling molecule capable of activating the peroxisome proliferator-activated receptor α (PPARα) transcription factor. This review summarizes the new finding of bilirubin as a signaling molecule and proposes several mechanisms by which this novel action of bilirubin may protect against cardiovascular and kidney diseases.Stec, David E.Tiribelli, ClaudioBadmus, Olufunto O.Hinds, Terry D.2022-03-25T13:37:16-07:00doi:10.34067/KID.0000062022hwp:resource-id:kidney360;3/5/945American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360renal physiology, acute kidney injury, basic science, bilirubin, biliverdin reductase-A, cardiovascular disease, heme oxygenase, hormone, hypertension, kidney disease, peroxisome proliferator-activated receptor, PPARαBasic Science for CliniciansRenal PhysiologyBasic Science for CliniciansRenal Physiologyresearch-article20222022-05-2610.34067/KID.00000620222641-76502022-03-25T13:37:16-07:002022-05-26Kidney360Basic Science for Clinicians35945953
- Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: COMMENTARY10.34067/KID.0005592021Fri, 17 Sep 2021 11:21:16 GMT-07:00Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: COMMENTARYShirali, Anushree C.2021-09-17T11:21:16-07:00doi:10.34067/KID.0005592021hwp:resource-id:kidney360;3/5/806American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, drug toxicity, immune checkpoint inhibitors, immunotherapy, onco-nephrologyModerator CommentaryModerator Commentaryarticle-commentary20222022-05-2610.34067/KID.00055920212641-76502021-09-17T11:21:16-07:002022-05-26Kidney360Moderator Commentary35806808
- Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: PRO10.34067/KID.0003962021Fri, 17 Sep 2021 11:21:16 GMT-07:00Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: PROHerrmann, Sandra M.2021-09-17T11:21:16-07:00doi:10.34067/KID.0003962021hwp:resource-id:kidney360;3/5/799American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, debates, immune checkpoint inhibitor, rechallengeDebates in NephrologyDebates in Nephrologyresearch-article20222022-05-2610.34067/KID.00039620212641-76502021-09-17T11:21:16-07:002022-05-26Kidney360Debates in Nephrology35799802
- Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: CON10.34067/KID.0003902021Fri, 17 Sep 2021 11:21:16 GMT-07:00Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: CONKanduri, Swetha RaniVelez, Juan Carlos Q.2021-09-17T11:21:16-07:00doi:10.34067/KID.0003902021hwp:resource-id:kidney360;3/5/803American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute interstitial nephritis, acute kidney injury, causality, CONS, debates, immune checkpoint inhibitors, immune-related adverse effects, rechallengeDebates in NephrologyDebates in Nephrologyarticle-commentary20222022-05-2610.34067/KID.00039020212641-76502021-09-17T11:21:16-07:002022-05-26Kidney360Debates in Nephrology35803805
- Midodrine is an effective therapy for resistant intradialytic hypotension: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007432021 and the CON: 10.34067/KID.0007422021tichang@stanford.edu10.34067/KID.0007442021Wed, 11 May 2022 01:40:23 GMT-07:00Midodrine is an effective therapy for resistant intradialytic hypotension: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007432021 and the CON: 10.34067/KID.0007422021Kim, Jackson P.Chang, Tara I.2022-05-11T13:40:23-07:00doi:10.34067/KID.0007442021hwp:resource-id:kidney360;KID.0007442021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Midodrine, intradialytic hypotension, Hemodynamics and Vascular Regulation, NephropharmacologyModerator CommentaryModerator Commentaryother202210.34067/KID.00074420212641-76502641-76502022-05-11T13:40:23-07:00Kidney360Moderator Commentary10.34067/KID.0007442021
- Midodrine is an effective therapy for resistant intradialytic hypotension: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007422021 and the COMMENTARY: 10.34067/KID.0007442021Andrew.House@lhsc.on.ca10.34067/KID.0007432021Wed, 11 May 2022 01:40:23 GMT-07:00Midodrine is an effective therapy for resistant intradialytic hypotension: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007422021 and the COMMENTARY: 10.34067/KID.0007442021House, Andrew A.McIntyre, Christopher W.2022-05-11T13:40:23-07:00doi:10.34067/KID.0007432021hwp:resource-id:kidney360;KID.0007432021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360midodrine, intradialytic hypotensionDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00074320212641-76502641-76502022-05-11T13:40:23-07:00Kidney360Debates in Nephrology10.34067/KID.0007432021
- Midodrine is an effective therapy for resistant intradialytic hypotension: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007432021 and the COMMENTARY: 10.34067/KID.0007442021steven.brunelli@davita.com10.34067/KID.0007422021Wed, 11 May 2022 01:40:23 GMT-07:00Midodrine is an effective therapy for resistant intradialytic hypotension: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007432021 and the COMMENTARY: 10.34067/KID.0007442021Husarek, KathrynBrunelli, Steven M.2022-05-11T13:40:23-07:00doi:10.34067/KID.0007422021hwp:resource-id:kidney360;KID.0007422021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Midodrine, HypotensionDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00074220212641-76502641-76502022-05-11T13:40:23-07:00Kidney360Debates in Nephrology10.34067/KID.0007422021
- Detecting and Treating Lung Congestion with Kidney FailureFluid overload is a common complication in patients with CKD, particularly patients with kidney failure, a population with a very high risk for pulmonary edema. Lung ultrasound is now a well-validated technique that allows for reliable estimates of lung water in clinical practice. Several studies in patients with kidney failure documented a high prevalence of asymptomatic lung congestion of moderate to severe degree in this population, and this alteration was only weakly related with fluid excess as measured by bioimpedance spectroscopy. Furthermore, in these studies, lung congestion correlated in a dose-dependent fashion with death risk. In the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk Kidney Failure Patients with Cardiomyopathy (LUST) trial, a treatment strategy guided by lung ultrasound safely relieved lung congestion but failed to significantly reduce the risk for a combined end point including death, nonfatal myocardial infarction, and decompensated heart failure. However, in line with three trials in patients with heart failure, a post hoc analysis of the LUST trial showed that the use of lung ultrasound reduces the risk for repeated episodes of acute heart failure and repeated cardiovascular events. Given the high cardiovascular risk of pulmonary edema in patients with predialysis CKD, defining the epidemiology of lung congestion in this population is a public health priority. Specific trials in this population and additional trials in patients with kidney failure will establish whether targeting lung congestion at an asymptomatic phase may improve the severe cardiovascular prognosis of both patients predialysis and patients on dialysis.10.2215/CJN.14591121Wed, 09 Feb 2022 08:21:03 GMT-08:00Detecting and Treating Lung Congestion with Kidney FailureFluid overload is a common complication in patients with CKD, particularly patients with kidney failure, a population with a very high risk for pulmonary edema. Lung ultrasound is now a well-validated technique that allows for reliable estimates of lung water in clinical practice. Several studies in patients with kidney failure documented a high prevalence of asymptomatic lung congestion of moderate to severe degree in this population, and this alteration was only weakly related with fluid excess as measured by bioimpedance spectroscopy. Furthermore, in these studies, lung congestion correlated in a dose-dependent fashion with death risk. In the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk Kidney Failure Patients with Cardiomyopathy (LUST) trial, a treatment strategy guided by lung ultrasound safely relieved lung congestion but failed to significantly reduce the risk for a combined end point including death, nonfatal myocardial infarction, and decompensated heart failure. However, in line with three trials in patients with heart failure, a post hoc analysis of the LUST trial showed that the use of lung ultrasound reduces the risk for repeated episodes of acute heart failure and repeated cardiovascular events. Given the high cardiovascular risk of pulmonary edema in patients with predialysis CKD, defining the epidemiology of lung congestion in this population is a public health priority. Specific trials in this population and additional trials in patients with kidney failure will establish whether targeting lung congestion at an asymptomatic phase may improve the severe cardiovascular prognosis of both patients predialysis and patients on dialysis.Zoccali, CarmineMallamaci, FrancescaPicano, Eugenio2022-02-09T08:21:03-08:00doi:10.2215/CJN.14591121hwp:resource-id:clinjasn;17/5/757American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteries, arteriosclerosis, blood pressure, cardiovascular, cardiovascular diseaseReviewReviewreview-article20222022-05-01May 202210.2215/CJN.145911211555-90411555-905X2022-02-09T08:21:03-08:002022-05Clinical Journal of the American Society of NephrologyReview175757765
- Changing the Trajectory of Heart Failure and Kidney Disease10.2215/CJN.00470122Tue, 01 Mar 2022 07:47:45 GMT-08:00Changing the Trajectory of Heart Failure and Kidney DiseaseRangaswami, JananiBhalla, VivekChertow, Glenn M.Harrington, Robert A.Staruschenko, AlexanderTuttle, KatherineBraunwald, Eugene2022-03-01T07:47:45-08:00doi:10.2215/CJN.00470122hwp:resource-id:clinjasn;17/5/742American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiorenal, SGLT2 inhibitors, multidisciplinary, heart failurePerspectivePerspectiveresearch-article20222022-05-01May 202210.2215/CJN.004701221555-90411555-905X2022-03-01T07:47:45-08:002022-05Clinical Journal of the American Society of NephrologyPerspective175742745
- Implementation of a Staff-Assisted Peritoneal Dialysis Program in the United States10.2215/CJN.00940122Tue, 05 Apr 2022 05:52:56 GMT-07:00Implementation of a Staff-Assisted Peritoneal Dialysis Program in the United StatesHussein, Wael F.Bennett, Paul N.Anwaar, AyeshaAtwal, JugjeetLegg, VeronicaAbra, GrahamZheng, SijiePravoverov, LeoSchiller, Brigitte2022-04-05T05:52:56-07:00doi:10.2215/CJN.00940122hwp:resource-id:clinjasn;17/5/703American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhome dialysis, peritoneal dialysis, assisted peritoneal dialysis, Advancing American Kidney Health, assisted home dialysis, United States, feasibility studiesResearch LetterResearch Letterletter20222022-05-01May 202210.2215/CJN.009401221555-90411555-905X2022-04-05T05:52:56-07:002022-05Clinical Journal of the American Society of NephrologyResearch Letter175703705
- Mass Transport in High-Flux HemodialysisAn understanding of the processes underlying mass transfer is paramount for the attainment of adequate solute removal in the dialytic treatment of patients with kidney failure. In this review, engineering principles are applied to characterize the physical mechanisms behind the two major modes of mass transfer during hemodialysis, namely diffusion and convection. The manner in which flow rate, dialyzer geometry, and membrane microstructure affect these processes is discussed, with concepts such as boundary layers, effective membrane diffusivity, and sieving coefficients highlighted as critical considerations. The objective is to improve clinicians’ understanding of these concepts as important factors influencing the prescription and delivery of hemodialysis therapy.10.2215/CJN.09410721Fri, 11 Mar 2022 06:56:02 GMT-08:00Mass Transport in High-Flux HemodialysisAn understanding of the processes underlying mass transfer is paramount for the attainment of adequate solute removal in the dialytic treatment of patients with kidney failure. In this review, engineering principles are applied to characterize the physical mechanisms behind the two major modes of mass transfer during hemodialysis, namely diffusion and convection. The manner in which flow rate, dialyzer geometry, and membrane microstructure affect these processes is discussed, with concepts such as boundary layers, effective membrane diffusivity, and sieving coefficients highlighted as critical considerations. The objective is to improve clinicians’ understanding of these concepts as important factors influencing the prescription and delivery of hemodialysis therapy.Mohajerani, FarzadClark, William R.Ronco, ClaudioNarsimhan, Vivek2022-03-11T06:56:02-08:00doi:10.2215/CJN.09410721hwp:resource-id:clinjasn;17/5/749American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymass transfer, membrane, diffusion, convection, ultrafiltration, uremic toxin, hemodialysisReviewReviewreview-article20222022-05-01May 202210.2215/CJN.094107211555-90411555-905X2022-03-11T06:56:02-08:002022-05Clinical Journal of the American Society of NephrologyReview175749756
- GWAS of Hematuria10.2215/CJN.13711021Tue, 26 Apr 2022 07:42:22 GMT-07:00GWAS of HematuriaGagliano Taliun, Sarah A.Sulem, PatrickSveinbjornsson, GardarGudbjartsson, Daniel F.Stefansson, KariPaterson, Andrew D.Barua, Moumita2022-04-26T07:42:22-07:00doi:10.2215/CJN.13711021hwp:resource-id:clinjasn;17/5/672American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGWAS, Alport syndrome, IgA nephropathy, collagen type IV, hematuria, United KingdomOriginal ArticleGeneticsOriginal ArticleGeneticsresearch-article20222022-05-01May 202210.2215/CJN.137110211555-90411555-905X2022-04-26T07:42:22-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article175672683
- Association of Phosphate-Containing versus Phosphate-Free Solutions on Ventilator Days in Patients Requiring Continuous Kidney Replacement Therapy10.2215/CJN.12410921Wed, 27 Apr 2022 11:03:42 GMT-07:00Association of Phosphate-Containing versus Phosphate-Free Solutions on Ventilator Days in Patients Requiring Continuous Kidney Replacement TherapyThompson Bastin, Melissa L.Stromberg, Arnold J.Nerusu, Sethabhisha N.Liu, Lucas J.Mayer, Kirby P.Liu, Kathleen D.Bagshaw, Sean M.Wald, RonMorris, Peter E.Neyra, Javier A.2022-04-27T11:03:42-07:00doi:10.2215/CJN.12410921hwp:resource-id:clinjasn;17/5/634American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycontinuous renal replacement therapy, CRRT, hypophosphatemia, critical illness, ICU, mechanical ventilation, phosphatesOriginal ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-05-01May 202210.2215/CJN.124109211555-90411555-905X2022-04-27T11:03:42-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article1755634631642633
- Functional Assessment of High-Risk APOL1 Genetic Variants10.2215/CJN.03470322Tue, 26 Apr 2022 08:49:45 GMT-07:00Functional Assessment of High-Risk APOL1 Genetic VariantsRobinson-Cohen, Cassianne2022-04-26T08:49:45-07:00doi:10.2215/CJN.03470322hwp:resource-id:clinjasn;17/5/626American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproteomics, APOL1EditorialEditorialeditorial20222022-05-01May 202210.2215/CJN.034703221555-90411555-905X2022-04-26T08:49:45-07:002022-05Clinical Journal of the American Society of NephrologyEditorial1755626684627692
- Recurrent Podocytopathy after Kidney Transplantation10.2215/CJN.15891221Fri, 25 Mar 2022 07:54:19 GMT-07:00Recurrent Podocytopathy after Kidney TransplantationGarg, NeetikaDjamali, Arjang2022-03-25T07:54:19-07:00doi:10.2215/CJN.15891221hwp:resource-id:clinjasn;17/5/739American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, focal segmental glomerulosclerosis, recurrent podocytopathy, recurrent proteinuriaKidney Case Conference: Nephrology Quiz & QuestionnaireKidney Case Conference: Nephrology Quiz & Questionnaireresearch-article20222022-05-01May 202210.2215/CJN.158912211555-90411555-905X2022-03-25T07:54:19-07:002022-05Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz & Questionnaire175739741
- Treatment Options for Venous Thromboembolism in Patients Receiving Dialysis10.2215/CJN.03410322Mon, 25 Apr 2022 11:37:13 GMT-07:00Treatment Options for Venous Thromboembolism in Patients Receiving DialysisMavrakanas, Thomas A.2022-04-25T11:37:13-07:00doi:10.2215/CJN.03410322hwp:resource-id:clinjasn;17/5/623American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvenous thromboembolism, dialysis, apixaban, warfarin, major bleedingEditorialEditorialeditorial20222022-05-01May 202210.2215/CJN.034103221555-90411555-905X2022-04-25T11:37:13-07:002022-05Clinical Journal of the American Society of NephrologyEditorial1755623693625702
- CRRT Fluid Choices10.2215/CJN.03390322Wed, 27 Apr 2022 11:42:51 GMT-07:00CRRT Fluid ChoicesVijayan, Anitha2022-04-27T11:42:51-07:00doi:10.2215/CJN.03390322hwp:resource-id:clinjasn;17/5/631American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypophosphatemia, respiratory failure, continuous renal replacement therapy, CRRTEditorialEditorialeditorial20222022-05-01May 202210.2215/CJN.033903221555-90411555-905X2022-04-27T11:42:51-07:002022-05Clinical Journal of the American Society of NephrologyEditorial171755863163412196336421219
- APOL1 Kidney Risk Variants and Proteomics10.2215/CJN.14701121Tue, 26 Apr 2022 08:36:07 GMT-07:00APOL1 Kidney Risk Variants and ProteomicsChen, Teresa K.Surapaneni, Aditya L.Arking, Dan E.Ballantyne, Christie M.Boerwinkle, EricChen, JingshaCoresh, JosefKöttgen, AnnaSusztak, KatalinTin, AdrienneYu, BingGrams, Morgan E.2022-04-26T08:36:07-07:00doi:10.2215/CJN.14701121hwp:resource-id:clinjasn;17/5/684American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, end stage kidney disease, epidemiology and outcomes, genetic renal disease, renal function decline, proteomics, apolipoprotein L1Original ArticleGeneticsOriginal ArticleGeneticsresearch-article20222022-05-01May 202210.2215/CJN.147011211555-90411555-905X2022-04-26T08:36:07-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article1755684626692627
- Provider Perspectives and Clinical Outcomes with Inpatient Telenephrology10.2215/CJN.13441021Wed, 23 Mar 2022 08:31:11 GMT-07:00Provider Perspectives and Clinical Outcomes with Inpatient TelenephrologyAndroga, Lagu A.Zoghby, ZiadRamar, PriyaAmundson, Rachel H.d’Uscio, MargaretPhilpot, Lindsey M.Thorsteinsdottir, BjoergKattah, Andrea G.Albright, Robert C.2022-03-23T08:31:11-07:00doi:10.2215/CJN.13441021hwp:resource-id:clinjasn;17/5/655American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytelenephrology, telehealth, inpatient nephrology, outcomes, patient perspectives, prospective studiesOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-05-01May 202210.2215/CJN.134410211555-90411555-905X2022-03-23T08:31:11-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article175655662
- Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term Dialysis10.2215/CJN.14021021Mon, 25 Apr 2022 11:23:36 GMT-07:00Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term DialysisWetmore, James B.Herzog, Charles A.Yan, HengReyes, Jorge L.Weinhandl, Eric D.Roetker, Nicholas S.2022-04-25T11:23:36-07:00doi:10.2215/CJN.14021021hwp:resource-id:clinjasn;17/5/693American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyapixaban, direct oral anticoagulants, warfarin, deep vein thrombosis, ESKD, end stage kidney disease, dialysisOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-05-01May 202210.2215/CJN.140210211555-90411555-905X2022-04-25T11:23:36-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article1755693623702625
- Learnings from Throwing Paint at the Wall for COVID-19 with an SGLT2 Inhibitor10.2215/CJN.03250322Thu, 28 Apr 2022 05:35:08 GMT-07:00Learnings from Throwing Paint at the Wall for COVID-19 with an SGLT2 InhibitorTuttle, Katherine R.2022-04-28T05:35:08-07:00doi:10.2215/CJN.03250322hwp:resource-id:clinjasn;17/5/628American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologySARS-CoV-2, acute kidney injury, pandemic, dapagliflozin, GFR, safety, COVID-19, sodium-glucose cotransporter 2, SGLT2EditorialEditorialeditorial20222022-05-01May 202210.2215/CJN.032503221555-90411555-905X2022-04-28T05:35:08-07:002022-05Clinical Journal of the American Society of NephrologyEditorial1755628643630654
- SARS-CoV-2 Vaccine Mandates for Patients on the Kidney Transplant Waitlist10.2215/CJN.15611121Wed, 02 Mar 2022 09:43:50 GMT-08:00SARS-CoV-2 Vaccine Mandates for Patients on the Kidney Transplant WaitlistTallaa, FaissalGunaratnam, LakshmanSuri, Rita S.2022-03-02T09:43:50-08:00doi:10.2215/CJN.15611121hwp:resource-id:clinjasn;17/5/746American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, vaccination, ethics, dialysis, COVID-19PerspectivePerspectiveresearch-article20222022-05-01May 202210.2215/CJN.156111211555-90411555-905X2022-03-02T09:43:50-08:002022-05Clinical Journal of the American Society of NephrologyPerspective175746748
- Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection10.2215/CJN.14231021Thu, 28 Apr 2022 05:03:06 GMT-07:00Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 InfectionHeerspink, Hiddo J.L.Furtado, Remo H.M.Berwanger, OtavioKoch, Gary G.Martinez, FelipeMukhtar, OmarVerma, SubodhGasparyan, Samvel B.Tang, FengmingWindsor, Sheryl L.de Souza-Dantas, Vicente Césdel Sueldo, MildrenFrankel, RobertJavaheri, AliMaldonado, Rafael A.Morse, CarynMota-Gomes, MarcoShemin, DouglasSilva, Osvaldo LourençoTognon, Alexandre PereiraTwahirwa, MarcelBuenconsejo, JoanEsterline, RussellOscarsson, JanAmbery, PhilipLangkilde, Anna MariaKosiborod, Mikhail N.2022-04-28T05:03:06-07:00doi:10.2215/CJN.14231021hwp:resource-id:clinjasn;17/5/643American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, chronic kidney disease, COVID-19, diabetes, heart failure, hospitalization, mortality risk, outcomes, randomized controlled trials, cardiovascular diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-05-01May 202210.2215/CJN.142310211555-90411555-905X2022-04-28T05:03:06-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article1755643628654630
- Overview of Diagnostic Criteria and Epidemiology of Acute Kidney Injury and Acute Kidney Disease in the Critically Ill PatientSince the description ischuria renalis by William Heberden (1), AKI has remained a prominent complication of critical illness. Beyond KRT, treatment has been limited by the capacity to phenotype this condition. Here, we chronicle the evolution of attempts to classify AKI, including the adoption of consensus definitions, the expansion of diagnosis and prognosis with novel biomarkers, and emerging tools such as artificial intelligence (AI).10.2215/CJN.14181021Tue, 15 Mar 2022 08:22:04 GMT-07:00Overview of Diagnostic Criteria and Epidemiology of Acute Kidney Injury and Acute Kidney Disease in the Critically Ill PatientSince the description ischuria renalis by William Heberden (1), AKI has remained a prominent complication of critical illness. Beyond KRT, treatment has been limited by the capacity to phenotype this condition. Here, we chronicle the evolution of attempts to classify AKI, including the adoption of consensus definitions, the expansion of diagnosis and prognosis with novel biomarkers, and emerging tools such as artificial intelligence (AI).Birkelo, Bethany C.Pannu, NeeshSiew, Edward D.2022-03-15T08:22:04-07:00doi:10.2215/CJN.14181021hwp:resource-id:clinjasn;17/5/717American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury Series, acute kidney injury, epidemiologyCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-05-01May 202210.2215/CJN.141810211555-90411555-905X2022-03-15T08:22:04-07:002022-05Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury175717735
- The Intensivist's Perspective of Shock, Volume Management, and Hemodynamic MonitoringOne of the primary reasons for intensive care admission is shock. Identifying the underlying cause of shock (hypovolemic, distributive, cardiogenic, and obstructive) may lead to entirely different clinical pathways for management. Among patients with hypovolemic and distributive shock, fluid therapy is one of the leading management strategies. Although an appropriate amount of fluid administration might save a patient's life, inadequate (or excessive) fluid use could lead to more complications, including organ failure and mortality due to either hypovolemia or volume overload. Currently, intensivists have access to a wide variety of information sources and tools to monitor the underlying hemodynamic status, including medical history, physical examination, and specific hemodynamic monitoring devices. Although appropriate and timely assessment and interpretation of this information can promote adequate fluid resuscitation, misinterpretation of these data can also lead to additional mortality and morbidity. This article provides a narrative review of the most commonly used hemodynamic monitoring approaches to assessing fluid responsiveness and fluid tolerance. In addition, we describe the benefits and disadvantages of these tools.10.2215/CJN.14191021Mon, 04 Apr 2022 07:46:06 GMT-07:00The Intensivist's Perspective of Shock, Volume Management, and Hemodynamic MonitoringOne of the primary reasons for intensive care admission is shock. Identifying the underlying cause of shock (hypovolemic, distributive, cardiogenic, and obstructive) may lead to entirely different clinical pathways for management. Among patients with hypovolemic and distributive shock, fluid therapy is one of the leading management strategies. Although an appropriate amount of fluid administration might save a patient's life, inadequate (or excessive) fluid use could lead to more complications, including organ failure and mortality due to either hypovolemia or volume overload. Currently, intensivists have access to a wide variety of information sources and tools to monitor the underlying hemodynamic status, including medical history, physical examination, and specific hemodynamic monitoring devices. Although appropriate and timely assessment and interpretation of this information can promote adequate fluid resuscitation, misinterpretation of these data can also lead to additional mortality and morbidity. This article provides a narrative review of the most commonly used hemodynamic monitoring approaches to assessing fluid responsiveness and fluid tolerance. In addition, we describe the benefits and disadvantages of these tools.Kashani, KianoushOmer, TarigShaw, Andrew D.2022-04-04T07:46:06-07:00doi:10.2215/CJN.14191021hwp:resource-id:clinjasn;17/5/706American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, hemodynamic monitoring, shock, fluid therapy, fluid responsiveness, POCUSCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-05-01May 202210.2215/CJN.141910211555-90411555-905X2022-04-04T07:46:06-07:002022-05Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury175706716
- SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function10.2215/CJN.11480821Wed, 23 Mar 2022 08:31:11 GMT-07:00SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney FunctionSuijk, Danii L.S.van Baar, Michaël J.B.van Bommel, Erik J.M.Iqbal, ZainabKrebber, Merle M.Vallon, VolkerTouw, DaanHoorn, Ewout J.Nieuwdorp, MaxKramer, Mark M.H.Joles, Jaap A.Bjornstad, Pettervan Raalte, Daniël H.2022-03-23T08:31:11-07:00doi:10.2215/CJN.11480821hwp:resource-id:clinjasn;17/5/663American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologySGLT-2 inhibition, type 2 diabetes, URAT-1, kidney, uric acidOriginal ArticleDiabetes and the KidneyOriginal ArticleDiabetes and the Kidneyresearch-article20222022-05-01May 202210.2215/CJN.114808211555-90411555-905X2022-03-23T08:31:11-07:002022-05Clinical Journal of the American Society of NephrologyOriginal Article175663671
- The Transition of a Pediatric Kidney Transplant Recipient from Childhood to Adult Care10.2215/CJN.14991121Fri, 11 Mar 2022 06:56:03 GMT-08:00The Transition of a Pediatric Kidney Transplant Recipient from Childhood to Adult CareBell, Lorraine E.2022-03-11T06:56:03-08:00doi:10.2215/CJN.14991121hwp:resource-id:clinjasn;17/5/736American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransition to adult care, young adult, adolescent, patient transfer, pediatric kidney transplantation, kidney transplantation, chronic kidney diseaseKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-05-01May 202210.2215/CJN.149911211555-90411555-905X2022-03-11T06:56:03-08:002022-05Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat175736738
- Author’s Reply: The Subcellular Localization of RRAGD10.1681/ASN.2022030252Thu, 31 Mar 2022 08:11:18 GMT-07:00Author’s Reply: The Subcellular Localization of RRAGDSchlingmann, Karl P.Jouret, FrançoisKnoers, Nine V.A.M.de Baaij, Jeroen H.F.2022-03-31T08:11:18-07:00doi:10.1681/ASN.2022030252hwp:resource-id:jnephrol;33/5/1048American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyRagD, RRAGD, immunohistochemistry, distal convoluted tubule, thick ascending limbLetter to the EditorLetter to the Editorletter20222022-05-01May 202210.1681/ASN.20220302521046-66731533-34502022-03-31T08:11:18-07:002022-05Journal of the American Society of NephrologyLetter to the Editor335511104810462885104910482899
- Enabling Patient Choice: The “Deciding Not to Decide” Option for Older Adults Facing Dialysis Decisions10.1681/ASN.2021081143Tue, 15 Feb 2022 07:08:22 GMT-08:00Enabling Patient Choice: The “Deciding Not to Decide” Option for Older Adults Facing Dialysis DecisionsSaeed, FahadMoss, Alvin H.Duberstein, Paul R.Fiscella, Kevin A.2022-02-15T07:08:22-08:00doi:10.1681/ASN.2021081143hwp:resource-id:jnephrol;33/5/880American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyinformed decision making, patient preference, dialysis decision-making, active medical management without dialysis, patient-centered care, biomedical ethics, suicideUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20222022-05-01May 202210.1681/ASN.20210811431046-66731533-34502022-02-15T07:08:22-08:002022-05Journal of the American Society of NephrologyUp Front Matters335880882
- Authors’ Reply: More Research is Still Needed to Support the Real-World Generalizability of the Benefits of Lifestyle Interventions for Chronic Kidney Disease10.1681/ASN.2022030244Wed, 30 Mar 2022 08:09:48 GMT-07:00Authors’ Reply: More Research is Still Needed to Support the Real-World Generalizability of the Benefits of Lifestyle Interventions for Chronic Kidney DiseaseBeetham, Kassia S.Coombes, Jeff S.Howden, Erin J.2022-03-30T08:09:48-07:00doi:10.1681/ASN.2022030244hwp:resource-id:jnephrol;33/5/1045-aAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologylifestyle, randomized controlled trials, exerciseLetter to the EditorLetter to the Editorletter20222022-05-01May 202210.1681/ASN.20220302441046-66731533-34502022-03-30T08:09:48-07:002022-05Journal of the American Society of NephrologyLetter to the Editor335521045104543110461045441
- Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-D10.1681/ASN.2021060735Mon, 21 Mar 2022 08:02:50 GMT-07:00Longitudinal TNFR1 and TNFR2 and Kidney Outcomes: Results from AASK and VA NEPHRON-DChen, Teresa K.Coca, Steven G.Estrella, Michelle M.Appel, Lawrence J.Coresh, JosefThiessen Philbrook, HeatherObeid, WassimFried, Linda F.Heerspink, Hiddo J.L.Ix, Joachim H.Shlipak, Michael G.Kimmel, Paul L.Parikh, Chirag R.Grams, Morgan E.,Ramachandran, Vasan S.Massaro, JosephClish, ClarySchelling, JeffreyDenburg, MichelleFurth, SusanWarady, BradleyBonventre, JosephWaikar, SushrutMcMahon, GearoidSabbisetti, VenkataCoresh, JosefGrams, MorganRebholz, CaseyAbraham, AlisonTin, AdrienneParikh, ChiragKlein, JonCoca, StevenFerket, Bart SNadkarni, Girish N.Rhee, EugeneKimmel, Paul L.Gossett, DanielRovin, BradShlipak, Michael G.Sarnak, MLevey, Andrew S.Inker, Lesley A.Foster, MeredithGutiérrez, Orlando M.Ix, JoachimDubin, RuthSeegmiller, JesseHostetter, TomDeo, RajatFeldman, Harold I.Anderson, AmandaMifflin, TheodoreXie, DaweiShou, HaochangBallard, ShawnWhitehead, KristaCollins, HeatherGreenberg, JasonGanz, Peter2022-03-21T08:02:50-07:00doi:10.1681/ASN.2021060735hwp:resource-id:jnephrol;33/5/996American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, diabetes mellitus, end-stage kidney disease, renal function decline, chronic inflammationClinical EpidemiologyClinical Epidemiologyresearch-article20222022-05-01May 202210.1681/ASN.20210607351046-66731533-34502022-03-21T08:02:50-07:002022-05Journal of the American Society of NephrologyClinical Epidemiology3355996i1010i
- Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors10.1681/ASN.2021081086Thu, 03 Feb 2022 02:12:09 GMT-08:00Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing ReceptorsZachova, KaterinaJemelkova, JanaKosztyu, PetrOhyama, YukakoTakahashi, KazuoZadrazil, JosefOrsag, JiriMatousovic, KarelGaluszkova, DanaPetejova, NadezdaMestecky, JiriRaska, Milan2022-02-03T14:12:09-08:00doi:10.1681/ASN.2021081086hwp:resource-id:jnephrol;33/5/908American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, galactose, immunoglobulin A, B lymphocytes, galactose-deficient IgA1, immunology, immunoglobulin lambda chainsBasic ResearchBasic Researchresearch-article20222022-05-01May 202210.1681/ASN.20210810861046-66731533-34502022-02-03T14:12:09-08:002022-05Journal of the American Society of NephrologyBasic Research3355908873917875
- Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease10.1681/ASN.2021060774Wed, 23 Feb 2022 08:47:01 GMT-08:00Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney DiseaseVlasschaert, CaitlynMcNaughton, Amy J.M.Chong, MichaelCook, Elina K.Hopman, WilmaKestenbaum, BryanRobinson-Cohen, CassianneGarland, JocelynMoran, Sarah M.Paré, GuillaumeClase, Catherine M.Tang, MilaLevin, AdeeraHolden, RachelRauh, Michael J.Lanktree, Matthew B.2022-02-23T08:47:01-08:00doi:10.1681/ASN.2021060774hwp:resource-id:jnephrol;33/5/985American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic inflammation, anemia, macrophages, clonal hematopoiesis, clone cells, hematopoiesis, cohort studies, chronic renal insufficiencyClinical EpidemiologyClinical Epidemiologyresearch-article20222022-05-01May 202210.1681/ASN.20210607741046-66731533-34502022-02-23T08:47:01-08:002022-05Journal of the American Society of NephrologyClinical Epidemiology33555985i878995i879
- This Month's Highlights10.1681/ASN.2022030346Fri, 29 Apr 2022 10:00:31 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2022-04-29T10:00:31-07:00doi:10.1681/ASN.2022030346hwp:resource-id:jnephrol;33/5/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsother20222022-05-01May 202210.1681/ASN.20220303461046-66731533-34502022-04-29T10:00:31-07:002022-05Journal of the American Society of NephrologyThis Month's Highlights33555555i889985878966996i9079958799841010
- Clonal Hematopoiesis and CKD Progression10.1681/ASN.2022030262Wed, 06 Apr 2022 09:16:38 GMT-07:00Clonal Hematopoiesis and CKD ProgressionNiroula, AbhishekBelizaire, Roger2022-04-06T09:16:38-07:00doi:10.1681/ASN.2022030262hwp:resource-id:jnephrol;33/5/878American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clonal hematopoiesis of indeterminate potentialUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-05-01May 202210.1681/ASN.20220302621046-66731533-34502022-04-06T09:16:38-07:002022-05Journal of the American Society of NephrologyUp Front Matters33555878i985879i995
- Correction: Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome10.1681/ASN.2022020134Fri, 29 Apr 2022 10:00:31 GMT-07:00Correction: Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic SyndromeAmerican Society of Nephrology2022-04-29T10:00:31-07:00doi:10.1681/ASN.2022020134hwp:resource-id:jnephrol;33/5/1050American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymycophenolate mofetil, rituximab, childhood-onset, complicated frequently-relapsing/steroid-dependent nephrotic syndrome, clinical trialErrataErratacorrection20222022-05-01May 202210.1681/ASN.20220201341046-66731533-34502022-04-29T10:00:31-07:002022-05Journal of the American Society of NephrologyErrata33335210504011050419
- Interleukin-33 Exacerbates IgA Glomerulonephritis in Transgenic Mice Overexpressing B Cell Activating Factor10.1681/ASN.2021081145Wed, 06 Apr 2022 08:47:58 GMT-07:00Interleukin-33 Exacerbates IgA Glomerulonephritis in Transgenic Mice Overexpressing B Cell Activating FactorWang, Yuan MinShaw, KarliZhang, Geoff YuChung, Edmund Y.M.Hu, MinCao, QiWang, YipingZheng, GuopingWu, HuilingChadban, Steven J.McCarthy, Hugh J.Harris, David C.H.Mackay, FabienneGrey, Shane T.Alexander, Stephen I.2022-04-06T08:47:58-07:00doi:10.1681/ASN.2021081145hwp:resource-id:jnephrol;33/5/966American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyB cell activating factor, IgA glomerulonephritis, innate lymphoid cells 2, IL-33, mice, transgenic, suppression of tumorigenicity 2 (ST2)Basic ResearchBasic Researchresearch-article20222022-05-01May 202210.1681/ASN.20210811451046-66731533-34502022-04-06T08:47:58-07:002022-05Journal of the American Society of NephrologyBasic Research3355966i984i
- Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury10.1681/ASN.2021060751Wed, 23 Feb 2022 08:47:02 GMT-08:00Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule InjuryLidberg, Kevin A.Muthusamy, SelvarajAdil, MohamedMahadeo, AnishYang, JadePatel, Ranita S.Wang, LuBammler, Theo K.Reichel, JonathanYeung, Catherine K.Himmelfarb, JonathanKelly, Edward J.Akilesh, Shreeram2022-02-23T08:47:02-08:00doi:10.1681/ASN.2021060751hwp:resource-id:jnephrol;33/5/949American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, albuminuria, proteinuria, renal tubular epithelial cells, gene transcription, gene expression, nephrotic syndrome, proximal tubule, transcription regulation, blood proteinsBasic ResearchBasic Researchresearch-article20222022-05-01May 202210.1681/ASN.20210607511046-66731533-34502022-02-23T08:47:02-08:002022-05Journal of the American Society of NephrologyBasic Research335889491627162796516271628
- Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA Nephropathy10.1681/ASN.2021030372Wed, 16 Feb 2022 08:42:15 GMT-08:00Chimeric Fusion between Clostridium Ramosum IgA Protease and IgG Fc Provides Long-Lasting Clearance of IgA Deposits in Mouse Models of IgA NephropathyXie, XinfangLi, JingyiLiu, PanWang, ManliuGao, LiWan, FengLv, JichengZhang, HongJin, Jing2022-02-16T08:42:15-08:00doi:10.1681/ASN.2021030372hwp:resource-id:jnephrol;33/5/918American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, IgA protease, AK183, Clostridium ramosum, Fc-fusion protein, neonatal Fc receptor/FcRn, recombinant biologicsBasic ResearchBasic Researchresearch-article20222022-05-01May 202210.1681/ASN.20210303721046-66731533-34502022-02-16T08:42:15-08:002022-05Journal of the American Society of NephrologyBasic Research335918935
- The Subcellular Localization of RRAGD10.1681/ASN.2022010006Thu, 31 Mar 2022 08:29:33 GMT-07:00The Subcellular Localization of RRAGDMa, TiantianZhang, LeiChen, Limeng2022-03-31T08:29:33-07:00doi:10.1681/ASN.2022010006hwp:resource-id:jnephrol;33/5/1046American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyRRAGD, immunofluorescence stainingLetter to the EditorLetter to the Editorletter20222022-05-01May 202210.1681/ASN.20220100061046-66731533-34502022-03-31T08:29:33-07:002022-05Journal of the American Society of NephrologyLetter to the Editor335511104610482885104810492899
- More Research is Still Needed To Support The Real-world Generalizability of The Benefits of Lifestyle Interventions for CKD10.1681/ASN.2022020172Wed, 30 Mar 2022 08:26:10 GMT-07:00More Research is Still Needed To Support The Real-world Generalizability of The Benefits of Lifestyle Interventions for CKDHuang, LiuyanZhang, Fan2022-03-30T08:26:10-07:00doi:10.1681/ASN.2022020172hwp:resource-id:jnephrol;33/5/1045American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, randomized controlled trials, lifestyleLetter to the EditorLetter to the Editorletter20222022-05-01May 202210.1681/ASN.20220201721046-66731533-34502022-03-30T08:26:10-07:002022-05Journal of the American Society of NephrologyLetter to the Editor335521045104543110451046441
- DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk Variants10.1681/ASN.2021050723Tue, 01 Mar 2022 07:48:04 GMT-08:00DGAT2 Inhibition Potentiates Lipid Droplet Formation To Reduce Cytotoxicity in APOL1 Kidney Risk VariantsChun, JustinRiella, Cristian V.Chung, HyunjaeShah, Shrijal S.Wang, MinxianMagraner, Jose M.Ribas, Guilherme T.Ribas, Hennrique T.Zhang, Jia-YueAlper, Seth. L.Friedman, David J.Pollak, Martin R.2022-03-01T07:48:04-08:00doi:10.1681/ASN.2021050723hwp:resource-id:jnephrol;33/5/889American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyFSGS, APOL1, chronic kidney disease, lipid droplet, organoids, DGAT1, DGAT2, lipid metabolism, CRISPRBasic ResearchBasic Researchresearch-article20222022-05-01May 202210.1681/ASN.20210507231046-66731533-34502022-03-01T07:48:04-08:002022-05Journal of the American Society of NephrologyBasic Research3355889i907i
- Targeting Cathepsin C in PR3-ANCA Vasculitis10.1681/ASN.2021081112Tue, 15 Mar 2022 08:38:01 GMT-07:00Targeting Cathepsin C in PR3-ANCA VasculitisJerke, UweEulenberg-Gustavus, ClaudiaRousselle, AnthonyNicklin, PaulKreideweiss, StefanGrundl, Marc A.Eickholz, PeterNickles, KatrinSchreiber, AdrianKorkmaz, BriceKettritz, Ralph2022-03-15T08:38:01-07:00doi:10.1681/ASN.2021081112hwp:resource-id:jnephrol;33/5/936American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, endothelial cells, immunology, cathepsin C, vasculitisBasic ResearchBasic Researchresearch-article20222022-05-01May 202210.1681/ASN.20210811121046-66731533-34502022-03-15T08:38:01-07:002022-05Journal of the American Society of NephrologyBasic Research3355936875947878
- Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials10.1681/ASN.2021101327Tue, 01 Mar 2022 07:48:04 GMT-08:00Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical TrialsXu, ChelseaSmith, Edward R.Tiong, Mark K.Ruderman, IreneToussaint, Nigel D.2022-03-01T07:48:04-08:00doi:10.1681/ASN.2021101327hwp:resource-id:jnephrol;33/5/1011American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyvascular calcification, cardiovascular disease, CKD-MBD, phosphate bindersClinical ResearchClinical Researchresearch-article20222022-05-01May 202210.1681/ASN.20211013271046-66731533-34502022-03-01T07:48:04-08:002022-05Journal of the American Society of NephrologyClinical Research33510111032
- Hematopoietic Stem Cell Transplant-Membranous Nephropathy Is Associated with Protocadherin FAT110.1681/ASN.2021111488Wed, 23 Mar 2022 10:18:24 GMT-07:00Hematopoietic Stem Cell Transplant-Membranous Nephropathy Is Associated with Protocadherin FAT1Sethi, SanjeevMadden, BenjaminCasal Moura, MartaNasr, Samih H.Klomjit, NattawatGross, LouAnnNegron, VivianCharlesworth, M. CristineAlexander, Mariam P.Leung, NelsonSpecks, UlrichFervenza, Fernando C.Haas, Mark2022-03-23T10:18:24-07:00doi:10.1681/ASN.2021111488hwp:resource-id:jnephrol;33/5/1033American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, nephrotic syndrome, kidney biopsy, immunology and pathology, hematopoietic stem cell transplantationClinical ResearchClinical Researchresearch-article20222022-05-01May 202210.1681/ASN.20211114881046-66731533-34502022-03-23T10:18:24-07:002022-05Journal of the American Society of NephrologyClinical Research33510331044
- Further Evidence for the Mucosal Origin of Pathogenic IgA in IgA Nephropathy10.1681/ASN.2022020201Thu, 07 Apr 2022 08:25:23 GMT-07:00Further Evidence for the Mucosal Origin of Pathogenic IgA in IgA NephropathyCheung, Chee KayBarratt, Jonathan2022-04-07T08:25:23-07:00doi:10.1681/ASN.2022020201hwp:resource-id:jnephrol;33/5/873American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, immunoglobulin A, IgA, galactose-deficient IgA1, B cells, immunology, lambda light chainsUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-05-01May 202210.1681/ASN.20220202011046-66731533-34502022-04-07T08:25:23-07:002022-05Journal of the American Society of NephrologyUp Front Matters3355873908875917
- A View on Cathepsin C as a Target for Therapy in AAV10.1681/ASN.2022030309Fri, 08 Apr 2022 07:49:33 GMT-07:00A View on Cathepsin C as a Target for Therapy in AAVKain, RenateNackenhorst, Maja C.2022-04-08T07:49:33-07:00doi:10.1681/ASN.2022030309hwp:resource-id:jnephrol;33/5/875American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycathepsin C, ANCA, vasculitis, proteinase 3, neutrophil serine proteasesUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-05-01May 202210.1681/ASN.20220303091046-66731533-34502022-04-08T07:49:33-07:002022-05Journal of the American Society of NephrologyUp Front Matters3355875936878947
- SARS-CoV-2-Specific T Cell Responses Are Not Associated with Protection against Reinfection in Hemodialysis Patients10.1681/ASN.2021121587Thu, 31 Mar 2022 07:50:52 GMT-07:00SARS-CoV-2-Specific T Cell Responses Are Not Associated with Protection against Reinfection in Hemodialysis PatientsShankar, SushmaBeckett, JosephTipton, TomOgbe, AneKasanyinga, MwilaDold, ChristinaLumley, SheilaDengu, FungaiRompianesi, GianlucaElgilani, FaysalLonget, StephanieDeeks, AlexandraPayne, Rebecca P.Duncan, Christopher J.A.Richter, Alexde Silva, Thushan I.Turtle, LanceBull, KatherineBarnardo, MartinFriend, Peter J.Dunachie, Susanna J.Hester, JoannaIssa, FadiBarnes, EleanorCarroll, Miles W.Klenerman, Paul2022-03-31T07:50:52-07:00doi:10.1681/ASN.2021121587hwp:resource-id:jnephrol;33/5/883American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, SARS-CoV-2, reinfection, T cells, protection, COVID-19Research LetterResearch Letterletter20222022-05-01May 202210.1681/ASN.20211215871046-66731533-34502022-03-31T07:50:52-07:002022-05Journal of the American Society of NephrologyResearch Letter335883887
- Dissipating the Fog at the Crossroad: Predicting Survival after the Initiation of Kidney Replacement Therapy10.34067/KID.0001122022Thu, 28 Apr 2022 06:00:32 GMT-07:00Dissipating the Fog at the Crossroad: Predicting Survival after the Initiation of Kidney Replacement TherapyCôté, Jean-MaximeBeaubien-Souligny, William2022-04-28T06:00:32-07:00doi:10.34067/KID.0001122022hwp:resource-id:kidney360;3/4/586American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, kidney replacement therapy, predictive model, research methods, statisticsEditorialEditorialeditorial20222022-04-2810.34067/KID.00011220222641-76502022-04-28T06:00:32-07:002022-04-28Kidney360Editorial34586589
- AKI in a Patient with Urinary Tract Infection, Urinary Crystals, and a Bladder Stone10.34067/KID.0006112021Thu, 28 Apr 2022 06:00:32 GMT-07:00AKI in a Patient with Urinary Tract Infection, Urinary Crystals, and a Bladder StoneSchretlen, Claire F.Jaar, Bernard G.Hanouneh, Mohamad2022-04-28T06:00:32-07:00doi:10.34067/KID.0006112021hwp:resource-id:kidney360;3/4/790American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephrolithiasis, triple phosphate crystals, urinary tract infectionClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-04-2810.34067/KID.00061120212641-76502022-04-28T06:00:32-07:002022-04-28Kidney360Clinical Images in Nephrology and Dialysis34790792
- The Implementation of a Virtual Home Dialysis Mentoring Program for Nephrologists10.34067/KID.0000202022Wed, 26 Jan 2022 01:33:56 GMT-08:00The Implementation of a Virtual Home Dialysis Mentoring Program for NephrologistsAbra, GrahamPoyan Mehr, AliChan, Christopher T.Schiller, Brigitte2022-01-26T13:33:56-08:00doi:10.34067/KID.0000202022hwp:resource-id:kidney360;3/4/734American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, home dialysis, home hemodialysis, mentorship, nephrologists, peritoneal dialysis, virtual physicianBrief CommunicationDialysisBrief CommunicationDialysisresearch-article20222022-04-2810.34067/KID.00002020222641-76502022-01-26T13:33:56-08:002022-04-28Kidney360Brief Communication34734736
- Mind the Cast: FENa versus Microscopy in AKI10.34067/KID.0001212022Thu, 28 Apr 2022 06:00:32 GMT-07:00Mind the Cast: FENa versus Microscopy in AKIHoenig, Melanie P.Parikh, Samir M.2022-04-28T06:00:32-07:00doi:10.34067/KID.0001212022hwp:resource-id:kidney360;3/4/583American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, acute tubular injury, granular casts, prerenal azotemia, urinary sodium, urine microscopyEditorialEditorialeditorial20222022-04-2810.34067/KID.00012120222641-76502022-04-28T06:00:32-07:002022-04-28Kidney360Editorial34583585
- Novel Keap1-Nrf2 Protein-Protein Interaction Inhibitor UBE-1099 Ameliorates Progressive Phenotype in Alport Syndrome Mouse Model10.34067/KID.0004572021Fri, 03 Dec 2021 08:09:40 GMT-08:00Novel Keap1-Nrf2 Protein-Protein Interaction Inhibitor UBE-1099 Ameliorates Progressive Phenotype in Alport Syndrome Mouse ModelKaseda, ShotaSannomiya, YuyaHorizono, JunKuwazuru, JunSuico, Mary AnnOgi, SayakaSasaki, RyokoSunamoto, HidetoshiFukiya, HirohikoNishiyama, HayatoKamura, MisatoNiinou, SakiKoyama, YuimiNara, FutoshiShuto, TsuyoshiOnuma, KazuhiroKai, Hirofumi2021-12-03T08:09:40-08:00doi:10.34067/KID.0004572021hwp:resource-id:kidney360;3/4/687American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360CKD, Alport syndrome, bardoxolone methyl, GA-binding protein transcription factor, Keap1-Nrf2 protein-protein interaction inhibitor, Kelch-like ECH-associated protein 1, mice, nephritis, hereditary, NF-E2-related factor 2, phenotype, proteinuriaOriginal InvestigationGeneticsOriginal InvestigationGeneticsresearch-article20222022-04-2810.34067/KID.00045720212641-76502021-12-03T08:09:40-08:002022-04-28Kidney360Original Investigation34687699
- Modifiable Lifestyle Behaviors and CKD Progression: A Narrative ReviewLiving a healthy lifestyle is one of the safest and most cost-effective ways to improve one’s quality of life and prevent and/or manage chronic disease. As such, current CKD management guidelines recommend that patients adhere to a healthy diet, perform ≥150 minutes per week of physical activity, manage their body weight, abstain from tobacco use, and limit alcohol. However, there are limited studies that investigate the relationship between these lifestyle factors and the progression of CKD among people with established CKD. In this narrative review, we examine the reported frequencies of health lifestyle behavior engagement among individuals with non–dialysis-dependent CKD and the existing literature that examines the influences of diet, physical activity, weight management, alcohol consumption, and tobacco use on the progression of CKD, as measured by decline in GFR, incident ESKD, or elevated proteinuria or albuminuria in individuals with CKD. Many of the available studies are limited by length of follow-up and small sample sizes, and meta-analyses were limited because the studies were sparse and had heterogeneous classifications of behaviors and/or referent groups and of CKD progression. Further research should be done to determine optimal methods to assess behaviors to better understand the levels at which healthy lifestyle behaviors are needed to slow CKD progression, to investigate the effect of combining multiple lifestyle behaviors on important clinical outcomes in CKD, and to develop effective techniques for behavior change. Despite the lack of evidence of efficacy from large trials on the ability of lifestyle behaviors to slow CKD progression, maintaining a healthy lifestyle remains a cornerstone of CKD management given the undisputed benefits of healthy lifestyle behaviors on cardiovascular health, BP control, and survival.10.34067/KID.0003122021Tue, 18 Jan 2022 06:23:56 GMT-08:00Modifiable Lifestyle Behaviors and CKD Progression: A Narrative ReviewLiving a healthy lifestyle is one of the safest and most cost-effective ways to improve one’s quality of life and prevent and/or manage chronic disease. As such, current CKD management guidelines recommend that patients adhere to a healthy diet, perform ≥150 minutes per week of physical activity, manage their body weight, abstain from tobacco use, and limit alcohol. However, there are limited studies that investigate the relationship between these lifestyle factors and the progression of CKD among people with established CKD. In this narrative review, we examine the reported frequencies of health lifestyle behavior engagement among individuals with non–dialysis-dependent CKD and the existing literature that examines the influences of diet, physical activity, weight management, alcohol consumption, and tobacco use on the progression of CKD, as measured by decline in GFR, incident ESKD, or elevated proteinuria or albuminuria in individuals with CKD. Many of the available studies are limited by length of follow-up and small sample sizes, and meta-analyses were limited because the studies were sparse and had heterogeneous classifications of behaviors and/or referent groups and of CKD progression. Further research should be done to determine optimal methods to assess behaviors to better understand the levels at which healthy lifestyle behaviors are needed to slow CKD progression, to investigate the effect of combining multiple lifestyle behaviors on important clinical outcomes in CKD, and to develop effective techniques for behavior change. Despite the lack of evidence of efficacy from large trials on the ability of lifestyle behaviors to slow CKD progression, maintaining a healthy lifestyle remains a cornerstone of CKD management given the undisputed benefits of healthy lifestyle behaviors on cardiovascular health, BP control, and survival.Schrauben, Sarah J.Apple, Benjamin J.Chang, Alex R.2022-01-18T06:23:56-08:00doi:10.34067/KID.0003122021hwp:resource-id:kidney360;3/4/752American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, CKD, diet, ESKD, ESRD, exercise, kidney disease, lifestyle, obesity, physical activity, smokingReview ArticleReview Articlereview-article20222022-04-2810.34067/KID.00031220212641-76502022-01-18T06:23:56-08:002022-04-28Kidney360Review Article34752778
- Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: PRO10.34067/KID.0004872021Fri, 10 Sep 2021 06:41:11 GMT-07:00Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: PROCavanaugh, Corey2021-09-10T06:41:11-07:00doi:10.34067/KID.0004872021hwp:resource-id:kidney360;3/4/597American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, acute kidney injury, biomarker, casts, debate, hematuria, urine sediment examinationDebates in NephrologyDebates in Nephrologyresearch-article20222022-04-2810.34067/KID.00048720212641-76502021-09-10T06:41:11-07:002022-04-28Kidney360Debates in Nephrology34597599
- Blood Flow Regulates Glomerular Capillary Formation in Zebrafish Pronephros10.34067/KID.0005962021Wed, 19 Jan 2022 11:33:25 GMT-08:00Blood Flow Regulates Glomerular Capillary Formation in Zebrafish PronephrosNishimura, YusukeIshii, TomohiroAndo, KojiYuge, ShinyaNakajima, HiroyukiZhou, WeibinMochizuki, NaokiFukuhara, Shigetomo2022-01-19T11:33:25-08:00doi:10.34067/KID.0005962021hwp:resource-id:kidney360;3/4/700American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hemodynamics and vascular regulation, basic science, cardiovascular, cell biology and structure, genetics and development, glomerular endothelial cells, glomerulus, hemodynamics, organogenesis, pronephros, vascular endothelial growth factor, zebrafishOriginal InvestigationHemodynamics and Vascular RegulationOriginal InvestigationHemodynamics and Vascular Regulationresearch-article20222022-04-2810.34067/KID.00059620212641-76502022-01-19T11:33:25-08:002022-04-28Kidney360Original Investigation34700713
- Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell Disease10.34067/KID.0006802021Thu, 03 Feb 2022 11:47:22 GMT-08:00Hyperkalemia and Metabolic Acidosis Occur at a Higher eGFR in Sickle Cell DiseaseSaraf, Santosh L.Derebail, Vimal K.Zhang, XuMachado, Roberto F.Gordeuk, Victor R.Lash, James P.Little, Jane2022-02-03T11:47:22-08:00doi:10.34067/KID.0006802021hwp:resource-id:kidney360;3/4/608American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, acidosis, bicarbonate, estimated glomerular filtration rate, hyperkalemia, kidney disease, potassium, sickle cell diseaseOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20222022-04-2810.34067/KID.00068020212641-76502022-02-03T11:47:22-08:002022-04-28Kidney360Original Investigation34608614
- Mission and 1-Year Outcomes of a Cardiorenal Subspecialty Consultation Service10.34067/KID.0000602022Wed, 26 Jan 2022 09:42:05 GMT-08:00Mission and 1-Year Outcomes of a Cardiorenal Subspecialty Consultation ServiceBansal, NishaArora, NayanMariuma, DavidJefferson, Jonathan AshleyO’Brien, KevinShankland, Stuart2022-01-26T09:42:05-08:00doi:10.34067/KID.0000602022hwp:resource-id:kidney360;3/4/749American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, cardiorenal, referral and consultationPerspectivePerspectiveresearch-article20222022-04-2810.34067/KID.00006020222641-76502022-01-26T09:42:05-08:002022-04-28Kidney360Perspective34749751
- Delayed Graft Function Complicated by Anuria in a Kidney Transplant Patient10.34067/KID.0007392021Thu, 28 Apr 2022 06:00:32 GMT-07:00Delayed Graft Function Complicated by Anuria in a Kidney Transplant PatientEtta, Praveen Kumar2022-04-28T06:00:32-07:00doi:10.34067/KID.0007392021hwp:resource-id:kidney360;3/4/788American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, allograft, cortical necrosis, deceased-donor, delayed graft functionClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-04-2810.34067/KID.00073920212641-76502022-04-28T06:00:32-07:002022-04-28Kidney360Clinical Images in Nephrology and Dialysis34788789
- Association of Monocyte Count and Monocyte/Lymphocyte Ratio with the Risk of Cardiovascular Outcomes in Patients with CKD10.34067/KID.0007922021Thu, 03 Feb 2022 01:57:02 GMT-08:00Association of Monocyte Count and Monocyte/Lymphocyte Ratio with the Risk of Cardiovascular Outcomes in Patients with CKDOh, Ester S.You, ZhiyingNowak, Kristen L.Jovanovich, Anna J.2022-02-03T13:57:02-08:00doi:10.34067/KID.0007922021hwp:resource-id:kidney360;3/4/657American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, cardiovascular disease, inflammation, lymphocytes, monocyte, mortalityOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-04-2810.34067/KID.00079220212641-76502022-02-03T13:57:02-08:002022-04-28Kidney360Original Investigation34657665
- A Novel Predictive Model for Hospital Survival in Patients who are Critically Ill with Dialysis-Dependent AKI: A Retrospective Single-Center Exploratory Study10.34067/KID.0007272021Tue, 25 Jan 2022 05:38:45 GMT-08:00A Novel Predictive Model for Hospital Survival in Patients who are Critically Ill with Dialysis-Dependent AKI: A Retrospective Single-Center Exploratory StudyGanguli, AnirbanFarooq, SaadDesai, NeerjaAdhikari, ShreedharShah, VatsalSherman, Michael J.Veis, Judith H.Moore, Jack2022-01-25T17:38:45-08:00doi:10.34067/KID.0007272021hwp:resource-id:kidney360;3/4/636American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, critical care, dialysis, prognostic model, survivalOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-04-2810.34067/KID.00072720212641-76502022-01-25T17:38:45-08:002022-04-28Kidney360Original Investigation34636646
- Systemic Profile of Cytokines in Arteriovenous Fistula Patients and Their Associations with Maturation Failure10.34067/KID.0006022021Fri, 14 Jan 2022 09:46:31 GMT-08:00Systemic Profile of Cytokines in Arteriovenous Fistula Patients and Their Associations with Maturation FailureMartinez, LaiselPerla, MikaelTabbara, MarwanDuque, Juan C.Rojas, Miguel G.Falcon, Nieves SantosPereira-Simon, SimoneSalman, Loay H.Vazquez-Padron, Roberto I.2022-01-14T09:46:31-08:00doi:10.34067/KID.0006022021hwp:resource-id:kidney360;3/4/677American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, chronic kidney disease, cytokine, dialysis, inflammationOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-04-2810.34067/KID.00060220212641-76502022-01-14T09:46:31-08:002022-04-28Kidney360Original Investigation34677686
- Association of Contrast-Enhanced Ultrasound–Derived Kidney Cortical Microvascular Perfusion with Kidney Function10.34067/KID.0005452021Wed, 26 Jan 2022 01:33:56 GMT-08:00Association of Contrast-Enhanced Ultrasound–Derived Kidney Cortical Microvascular Perfusion with Kidney FunctionSrivastava, AnandSridharan, AnushWalmer, Rachel W.Kasoji, Sandeep K.Burke, Lauren M.B.Dayton, Paul A.Johnson, Kennita A.Chang, Emily H.2022-01-26T13:33:56-08:00doi:10.34067/KID.0005452021hwp:resource-id:kidney360;3/4/647American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, contrast-enhanced ultrasound, end stage kidney disease, noninvasive imaging, perfusion, ultrasonography, vascular diseaseOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-04-2810.34067/KID.00054520212641-76502022-01-26T13:33:56-08:002022-04-28Kidney360Original Investigation34647656
- Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI10.34067/KID.0005692021Wed, 19 Jan 2022 01:30:01 GMT-08:00Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKIVarghese, VipinRivera, Maria S.Alalwan, AliAlghamdi, Ayman M.Ramanand, AkankshKhan, Sumayyah M.Najul-Seda, Jose E.Velez, Juan Carlos Q.2022-01-19T13:30:01-08:00doi:10.34067/KID.0005692021hwp:resource-id:kidney360;3/4/627American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, acute tubular injury, acute tubular necrosis, fractional excretion of sodium, muddy brown granular cast, urinary casts, urine microscopy, urine sedimentOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-04-2810.34067/KID.00056920212641-76502022-01-19T13:30:01-08:002022-04-28Kidney360Original Investigation34627635
- Challenges of Conducting Clinical Trials during the SARS-CoV-2 Pandemic: The ASCEND Global Program Experience10.34067/KID.0006212021Thu, 10 Feb 2022 01:27:49 GMT-08:00Challenges of Conducting Clinical Trials during the SARS-CoV-2 Pandemic: The ASCEND Global Program ExperienceJohansen, Kirsten L.Acharya, AnjaliCizman, BorutCobitz, Alexander R.Correa-Rotter, RicardoDasgupta, IndranilKher, VijayLopes, Renato D.Matsumoto, LeonardoMeadowcroft, Amy M.Merege Vieira Neto, OsvaldoOkabe, MariluRayner, BrianSilva, ArnoldThomas, HilarySingh, Ajay K.2022-02-10T13:27:49-08:00doi:10.34067/KID.0006212021hwp:resource-id:kidney360;3/4/728American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, clinical trial, COVID-19, dialysis, pandemics, SARS-CoV-2Brief CommunicationChronic Kidney DiseaseBrief CommunicationChronic Kidney Diseaseresearch-article20222022-04-2810.34067/KID.00062120212641-76502022-02-10T13:27:49-08:002022-04-28Kidney360Brief Communication34728733
- Global Perspectives in Acute Kidney Injury: Mexico10.34067/KID.0006592021Tue, 25 Jan 2022 09:34:10 GMT-08:00Global Perspectives in Acute Kidney Injury: MexicoChávez-Íñiguez, Jonathan S.Madero, Magdalena2022-01-25T09:34:10-08:00doi:10.34067/KID.0006592021hwp:resource-id:kidney360;3/4/737American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, MexicoGlobal PerspectiveGlobal Perspectiveresearch-article20222022-04-2810.34067/KID.00065920212641-76502022-01-25T09:34:10-08:002022-04-28Kidney360Global Perspective34737739
- The Role of Peritoneal Dialysis in Different Phases of Kidney TransplantationThe utilization of peritoneal dialysis (PD) has been increasing in the past decade owing to various government initiatives and recognition of benefits such as better preservation of residual renal function, quality of life, and lower cost. The Advancing American Kidney Health initiative aims to increase the utilization of home therapies such as PD and kidney transplantation to treat end stage kidney disease (ESKD). A natural consequence of this development is that more patients will receive PD, and many will eventually undergo kidney transplantation. Therefore, it is important to understand the effect of pretransplant PD on posttransplant outcomes such as delayed graft function (DGF), rejection, thrombosis, graft, and patient survival. Furthermore, some of these patients may develop DGF, which raises the question of the utility of PD during DGF and its risks. Although transplant is the best renal replacement therapy option, it is not everlasting, and many transplant recipients must go on dialysis after allograft failure. Can PD be a good option for these patients? This is another critical question. Furthermore, a significant proportion of nonrenal solid organ transplant recipients develop ESKD. Is PD feasible in this group? In this review, we try to address all of these questions in the light of available evidence.10.34067/KID.0000482022Mon, 28 Feb 2022 06:11:13 GMT-08:00The Role of Peritoneal Dialysis in Different Phases of Kidney TransplantationThe utilization of peritoneal dialysis (PD) has been increasing in the past decade owing to various government initiatives and recognition of benefits such as better preservation of residual renal function, quality of life, and lower cost. The Advancing American Kidney Health initiative aims to increase the utilization of home therapies such as PD and kidney transplantation to treat end stage kidney disease (ESKD). A natural consequence of this development is that more patients will receive PD, and many will eventually undergo kidney transplantation. Therefore, it is important to understand the effect of pretransplant PD on posttransplant outcomes such as delayed graft function (DGF), rejection, thrombosis, graft, and patient survival. Furthermore, some of these patients may develop DGF, which raises the question of the utility of PD during DGF and its risks. Although transplant is the best renal replacement therapy option, it is not everlasting, and many transplant recipients must go on dialysis after allograft failure. Can PD be a good option for these patients? This is another critical question. Furthermore, a significant proportion of nonrenal solid organ transplant recipients develop ESKD. Is PD feasible in this group? In this review, we try to address all of these questions in the light of available evidence.Gardezi, Ali I.Aziz, FahadParajuli, Sandesh2022-02-28T18:11:13-08:00doi:10.34067/KID.0000482022hwp:resource-id:kidney360;3/4/779American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, allograft failure, delayed graft function, graft survival, hemodialysis, kidney transplantation, nonrenal solid organ transplantation, patient survival, peritoneal dialysis, residual renal functionReview ArticleReview Articlereview-article20222022-04-2810.34067/KID.00004820222641-76502022-02-28T18:11:13-08:002022-04-28Kidney360Review Article34779787
- Predictors of Hyperkalemia among Patients on Maintenance Hemodialysis Transported to the Emergency Department by Ambulance10.34067/KID.0008132021Wed, 09 Feb 2022 10:18:39 GMT-08:00Predictors of Hyperkalemia among Patients on Maintenance Hemodialysis Transported to the Emergency Department by AmbulanceVinson, Amanda J.Zanjir, WayelNallbani, MegiGoldstein, JudahSwain, JanelClark, David A.More, Keigan M.Manderville, John R.Fok, Patrick T.Wiemer, HanaTennankore, Karthik K.2022-02-09T10:18:39-08:00doi:10.34067/KID.0008132021hwp:resource-id:kidney360;3/4/615American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, ambulance, emergency health services, end stage kidney disease, hyperkalemia, paramedic, risk prediction, transportOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20222022-04-2810.34067/KID.00081320212641-76502022-02-09T10:18:39-08:002022-04-28Kidney360Original Investigation34615626
- Clinical Events and Renal Function in the First Year Predict Long-Term Kidney Transplant Survival10.34067/KID.0007342021Tue, 25 Jan 2022 05:38:45 GMT-08:00Clinical Events and Renal Function in the First Year Predict Long-Term Kidney Transplant SurvivalSchold, Jesse D.Nordyke, Robert J.Wu, ZhengCorvino, FrankWang, WeiyingMohan, Sumit2022-01-25T17:38:45-08:00doi:10.34067/KID.0007342021hwp:resource-id:kidney360;3/4/714American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, acute rejection, cardiovascular disease, epidemiology and outcomes, glomerular filtration rate, kidney transplantation, transplant outcomesOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-04-2810.34067/KID.00073420212641-76502022-01-25T17:38:45-08:002022-04-28Kidney360Original Investigation34714727
- Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: CON10.34067/KID.0004582021Fri, 10 Sep 2021 06:41:12 GMT-07:00Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: CONLa, AshleyKoyner, Jay L.2021-09-10T06:41:12-07:00doi:10.34067/KID.0004582021hwp:resource-id:kidney360;3/4/600American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, biomarkers, debate, dialysis, outcomes, urinalysisDebates in NephrologyDebates in Nephrologyresearch-article20222022-04-2810.34067/KID.00045820212641-76502021-09-10T06:41:12-07:002022-04-28Kidney360Debates in Nephrology34600603
- Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: COMMENTARY10.34067/KID.0005562021Fri, 10 Sep 2021 06:41:12 GMT-07:00Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: COMMENTARYUduman, JuniorYee, Jerry2021-09-10T06:41:12-07:00doi:10.34067/KID.0005562021hwp:resource-id:kidney360;3/4/604American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, biomarkers, debate, urine sedimentModerator CommentaryModerator Commentaryarticle-commentary20222022-04-2810.34067/KID.00055620212641-76502021-09-10T06:41:12-07:002022-04-28Kidney360Moderator Commentary34604607
- Perspective on Nonsteroidal Mineralocorticoid Receptor Antagonism in Diabetic Kidney Disease10.34067/KID.0007072021Wed, 19 Jan 2022 01:30:01 GMT-08:00Perspective on Nonsteroidal Mineralocorticoid Receptor Antagonism in Diabetic Kidney DiseaseGhuman, Jasleen K.Tuttle, Katherine R.2022-01-19T13:30:01-08:00doi:10.34067/KID.0007072021hwp:resource-id:kidney360;3/4/744American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, chronic kidney disease prevention, diabetic kidney disease, kidney health, nonsteroidal mineralocorticoid receptor antagonistPerspectivePerspectiveresearch-article20222022-04-2810.34067/KID.00070720212641-76502022-01-19T13:30:01-08:002022-04-28Kidney360Perspective34744748
- Impact of Metabolic Acidosis and Alkali Therapy on Linear Growth in Children with Chronic Kidney Disease: What Is the Current Evidence?10.34067/KID.0000072022Thu, 28 Apr 2022 06:00:32 GMT-07:00Impact of Metabolic Acidosis and Alkali Therapy on Linear Growth in Children with Chronic Kidney Disease: What Is the Current Evidence?Ulrich, Emma H.Chanchlani, Rahul2022-04-28T06:00:32-07:00doi:10.34067/KID.0000072022hwp:resource-id:kidney360;3/4/590American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, acidosis, alkali, children, end stage kidney disease, growth, heightEditorialEditorialeditorial20222022-04-2810.34067/KID.00000720222641-76502022-04-28T06:00:32-07:002022-04-28Kidney360Editorial34590596
- Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKD10.34067/KID.0005402021Wed, 09 Feb 2022 10:18:39 GMT-08:00Longitudinal Associations between Low Serum Bicarbonate and Linear Growth in Children with CKDBrown, Denver D.Carroll, MeganNg, Derek K.Levy, Rebecca V.Greenbaum, Larry A.Kaskel, Frederick J.Furth, Susan L.Warady, Bradley A.Melamed, Michal L.Dauber, Andrew2022-02-09T10:18:39-08:00doi:10.34067/KID.0005402021hwp:resource-id:kidney360;3/4/666American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, child, growth, serum bicarbonateOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-04-2810.34067/KID.00054020212641-76502022-02-09T10:18:39-08:002022-04-28Kidney360Original Investigation34666676
- A Brief Introduction to Competing Risks in the Context of Kidney Disease Epidemiology10.34067/KID.0007382021Thu, 17 Feb 2022 11:48:22 GMT-08:00A Brief Introduction to Competing Risks in the Context of Kidney Disease EpidemiologyRoetker, Nicholas S.Gilbertson, David T.Weinhandl, Eric D.2022-02-17T11:48:22-08:00doi:10.34067/KID.0007382021hwp:resource-id:kidney360;3/4/740American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, competing risk analysis, epidemiology, kidney diseaseClinical Research MethodsClinical Research Methodsresearch-article20222022-04-2810.34067/KID.00073820212641-76502022-02-17T11:48:22-08:002022-04-28Kidney360Clinical Research Methods34740743
- Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007822021 and the COMMENTARY: 10.34067/KID.0002342022ghaffari@usc.edu10.34067/KID.0007782021Tue, 12 Apr 2022 01:16:11 GMT-07:00Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007822021 and the COMMENTARY: 10.34067/KID.0002342022Ghaffari, ArshiaDoria Medina Sanchez, Jorge2022-04-12T13:16:11-07:00doi:10.34067/KID.0007782021hwp:resource-id:kidney360;KID.0007782021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360urgent dialysis, urgent-start peritoneal dialysis, Urgent-start PD, PD, Initial dialysis option, acute-start dialysis, acute-start PDDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00077820212641-76502641-76502022-04-12T13:16:11-07:00Kidney360Debates in Nephrology10.34067/KID.0007782021
- Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007782021 and the CON: 10.34067/KID.0007822021mhr9r@virginia.edu10.34067/KID.0002342022Tue, 12 Apr 2022 01:16:11 GMT-07:00Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007782021 and the CON: 10.34067/KID.0007822021Rosner, Mitchell H.2022-04-12T13:16:11-07:00doi:10.34067/KID.0002342022hwp:resource-id:kidney360;KID.0002342022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Peritoneal DialysisModerator CommentaryModerator Commentaryother202210.34067/KID.00023420222641-76502641-76502022-04-12T13:16:11-07:00Kidney360Moderator Commentary10.34067/KID.0002342022
- Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007782021 and the COMMENTARY: 10.34067/KID.0002342022randy.luciano@yale.edu10.34067/KID.0007822021Tue, 12 Apr 2022 01:16:11 GMT-07:00Peritoneal Dialysis Should Be Considered the First Option for Patients Requiring Urgent Start Dialysis: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007782021 and the COMMENTARY: 10.34067/KID.0002342022Luciano, Randy L.2022-04-12T13:16:11-07:00doi:10.34067/KID.0007822021hwp:resource-id:kidney360;KID.0007822021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Peritoneal Dialysis, CKD, Urgent Start DialysisDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00078220212641-76502641-76502022-04-12T13:16:11-07:00Kidney360Debates in Nephrology10.34067/KID.0007822021
- Is There an Ideal Recipe to Increase Home Dialysis Use?10.2215/CJN.02150222Mon, 21 Mar 2022 11:23:06 GMT-07:00Is There an Ideal Recipe to Increase Home Dialysis Use?Shen, Jenny I.Perl, Jeffrey2022-03-21T11:23:06-07:00doi:10.2215/CJN.02150222hwp:resource-id:clinjasn;17/4/484American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhome dialysisEditorialEditorialeditorial20222022-04-01April 202210.2215/CJN.021502221555-90411555-905X2022-03-21T11:23:06-07:002022-04Clinical Journal of the American Society of NephrologyEditorial1744484535486545
- Measuring Disease and Transplant Knowledge among Patients with Advanced CKD10.2215/CJN.02140222Thu, 24 Mar 2022 07:14:57 GMT-07:00Measuring Disease and Transplant Knowledge among Patients with Advanced CKDUrbanski, Megan A.Patzer, Rachel E.2022-03-24T07:14:57-07:00doi:10.2215/CJN.02140222hwp:resource-id:clinjasn;17/4/481American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymeasurement, advanced CKD, knowledge, kidney transplantation, equityEditorialEditorialeditorial20222022-04-01April 202210.2215/CJN.021402221555-90411555-905X2022-03-24T07:14:57-07:002022-04Clinical Journal of the American Society of NephrologyEditorial17444481555473483564474
- Symptoms with or because of Kidney Failure?10.2215/CJN.02050222Fri, 04 Mar 2022 10:13:51 GMT-08:00Symptoms with or because of Kidney Failure?Abdel-Kader, Khaled2022-03-04T10:13:51-08:00doi:10.2215/CJN.02050222hwp:resource-id:clinjasn;17/4/475American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, chronic kidney failure, kidney failure, uremia, symptoms, quality of lifeEditorialEditorialeditorial20222022-04-01April 202210.2215/CJN.020502221555-90411555-905X2022-03-04T10:13:51-08:002022-04Clinical Journal of the American Society of NephrologyEditorial1744475496477506
- Could Phosphate Provide a Second Chance for Statin Therapy in Kidney Failure?10.2215/CJN.02210222Wed, 02 Mar 2022 09:43:50 GMT-08:00Could Phosphate Provide a Second Chance for Statin Therapy in Kidney Failure?Gutiérrez, Orlando M.2022-03-02T09:43:50-08:00doi:10.2215/CJN.02210222hwp:resource-id:clinjasn;17/4/478American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyphosphorus, statin therapyEditorialEditorialeditorial20222022-04-01April 202210.2215/CJN.022102221555-90411555-905X2022-03-02T09:43:50-08:002022-04Clinical Journal of the American Society of NephrologyEditorial1744478546480554
- Syndromes of Pseudo-Hyperaldosteronism10.2215/CJN.14201021Tue, 08 Feb 2022 07:59:53 GMT-08:00Syndromes of Pseudo-HyperaldosteronismRizzolo, KatherineBeck, Natalie M.Ambruso, Sophia L.2022-02-08T07:59:53-08:00doi:10.2215/CJN.14201021hwp:resource-id:clinjasn;17/4/581American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, hypokalemia, aldosteroneKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-04-01April 202210.2215/CJN.142010211555-90411555-905X2022-02-08T07:59:53-08:002022-04Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat174581584
- Pattern Recognition versus Pathogenesis10.2215/CJN.16061221Thu, 03 Mar 2022 05:05:39 GMT-08:00Pattern Recognition versus PathogenesisHoenig, Melanie P.Lecker, Stewart H.2022-03-03T05:05:39-08:00doi:10.2215/CJN.16061221hwp:resource-id:clinjasn;17/4/585American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyponatremia, hypoaldosteronism, potassium channels, adrenal insufficiencyKidney Case Conference: Nephrology Quiz & QuestionnaireKidney Case Conference: Nephrology Quiz & Questionnaireresearch-article20222022-04-01April 202210.2215/CJN.160612211555-90411555-905X2022-03-03T05:05:39-08:002022-04Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz & Questionnaire174585587
- Correction: Prevention of Bloodstream Infections in Patients Undergoing Hemodialysis10.2215/CJN.01840222Fri, 04 Mar 2022 09:45:00 GMT-08:00Correction: Prevention of Bloodstream Infections in Patients Undergoing HemodialysisAmerican Society of Nephrology2022-03-04T09:45:00-08:00doi:10.2215/CJN.01840222hwp:resource-id:clinjasn;17/4/568American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20222022-04-01April 202210.2215/CJN.018402221555-90411555-905X2022-03-04T09:45:00-08:002022-04Clinical Journal of the American Society of NephrologyErratum1715411568132132569151151
- Variations in Deceased Donor Terminal Creatinine Values Reported in the OPTN Data Registry10.2215/CJN.15511121Wed, 23 Feb 2022 08:47:22 GMT-08:00Variations in Deceased Donor Terminal Creatinine Values Reported in the OPTN Data RegistryYu, KathleenKing, KristenHusain, Syed AliMohan, Sumit2022-02-23T08:47:22-08:00doi:10.2215/CJN.15511121hwp:resource-id:clinjasn;17/4/565American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, acute renal failure, kidney donation, kidney transplantation, renal transplantation, transplantation, transplant outcomes, creatinine, tissue donorsResearch LetterResearch Letterletter20222022-04-01April 202210.2215/CJN.155111211555-90411555-905X2022-02-23T08:47:22-08:002022-04Clinical Journal of the American Society of NephrologyResearch Letter174565567
- Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD10.2215/CJN.11260821Mon, 21 Mar 2022 10:25:27 GMT-07:00Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKDKramers, Bart J.Koorevaar, Iris W.van Gastel, Maatje D.A.van Goor, HarryHallows, Kenneth R.Heerspink, Hiddo L.Li, HuiLeonhard, Wouter N.Peters, Dorien J.M.Qiu, JiedongTouw, Daan J.Gansevoort, Ron T.Meijer, Esther2022-03-21T10:25:27-07:00doi:10.2215/CJN.11260821hwp:resource-id:clinjasn;17/4/507American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, clinical trial, diabetes insipidus, diuretics, receptors, vasopressin, hydrochlorothiazide, metforminOriginal ArticleCystic Kidney DiseaseOriginal ArticleCystic Kidney Diseaseresearch-article20222022-04-01April 202210.2215/CJN.112608211555-90411555-905X2022-03-21T10:25:27-07:002022-04Clinical Journal of the American Society of NephrologyOriginal Article174507517
- Introduction to Critical Care Nephrology and Acute Kidney Injury10.2215/CJN.01400222Thu, 10 Mar 2022 07:00:01 GMT-08:00Introduction to Critical Care Nephrology and Acute Kidney InjuryLiu, Kathleen D.Palevsky, Paul M.2022-03-10T07:00:01-08:00doi:10.2215/CJN.01400222hwp:resource-id:clinjasn;17/4/570American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury SeriesCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-04-01April 202210.2215/CJN.014002221555-90411555-905X2022-03-10T07:00:01-08:002022-04Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury174570571
- The Knowledge Assessment of Renal Transplantation (KART) 2.010.2215/CJN.11490821Thu, 24 Mar 2022 07:14:57 GMT-07:00The Knowledge Assessment of Renal Transplantation (KART) 2.0Waterman, Amy D.Nair, DevikaPurnajo, IntanCavanaugh, Kerri L.Mittman, Brian S.Peipert, John Devin2022-03-24T07:14:57-07:00doi:10.2215/CJN.11490821hwp:resource-id:clinjasn;17/4/555American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, transplantation, knowledge, education, transplantsOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-04-01April 202210.2215/CJN.114908211555-90411555-905X2022-03-24T07:14:57-07:002022-04Clinical Journal of the American Society of NephrologyOriginal Article17444555473481564474483
- Kidney Histopathologic Spectrum and Clinical Indicators Associated with MGRS10.2215/CJN.12890921Thu, 24 Feb 2022 06:00:46 GMT-08:00Kidney Histopathologic Spectrum and Clinical Indicators Associated with MGRSYong, Zi-haoYu, Xiao-juanLiu, Jing-xiaZhou, Fu-deWang, Su-xiaZhao, Ming-hui2022-02-24T06:00:46-08:00doi:10.2215/CJN.12890921hwp:resource-id:clinjasn;17/4/527American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymonoclonal gammopathy, MGRS, kidney biopsy, cohort studies, ChinaOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-04-01April 202210.2215/CJN.128909211555-90411555-905X2022-02-24T06:00:46-08:002022-04Clinical Journal of the American Society of NephrologyOriginal Article174527534
- Knowledge Measurement Can Point to Opportunities, but Has Limits10.2215/CJN.02240222Thu, 24 Mar 2022 07:14:56 GMT-07:00Knowledge Measurement Can Point to Opportunities, but Has LimitsFranks, Karol A.2022-03-24T07:14:56-07:00doi:10.2215/CJN.02240222hwp:resource-id:clinjasn;17/4/473American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney, renal dialysis, kidney transplantation, chronic kidney diseasePatient VoicePatient Voiceresearch-article20222022-04-01April 202210.2215/CJN.022402221555-90411555-905X2022-03-24T07:14:56-07:002022-04Clinical Journal of the American Society of NephrologyPatient Voice17444473555481474564483
- Association of Serum Phosphate with Efficacy of Statin Therapy in Hemodialysis Patients10.2215/CJN.12620921Wed, 02 Mar 2022 09:43:50 GMT-08:00Association of Serum Phosphate with Efficacy of Statin Therapy in Hemodialysis PatientsMassy, Ziad A.Merkling, ThomasWagner, SandraGirerd, NicolasEssig, MarieWanner, ChristophFellstrom, Bengt C.Rossignol, PatrickZannad, Faiez2022-03-02T09:43:50-08:00doi:10.2215/CJN.12620921hwp:resource-id:clinjasn;17/4/546American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyphosphate, dialysis, statins, hyperphosphatemia, cholesterolOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-04-01April 202210.2215/CJN.126209211555-90411555-905X2022-03-02T09:43:50-08:002022-04Clinical Journal of the American Society of NephrologyOriginal Article1744546478554480
- Management of Respiratory FailureMechanical ventilation is a lifesaving therapy for critically ill patients with respiratory failure, but like all treatments, it has the potential to cause harm if not administered appropriately. This review aims to give an overview of the basic principles of invasive and noninvasive mechanical ventilation. Topics covered include modes of mechanical ventilation, respiratory mechanics and ventilator waveform interpretation, strategies for initial ventilator settings, indications and contraindications for noninvasive ventilation, and the effect of the ventilator on kidney function.10.2215/CJN.13091021Thu, 10 Mar 2022 07:00:01 GMT-08:00Management of Respiratory FailureMechanical ventilation is a lifesaving therapy for critically ill patients with respiratory failure, but like all treatments, it has the potential to cause harm if not administered appropriately. This review aims to give an overview of the basic principles of invasive and noninvasive mechanical ventilation. Topics covered include modes of mechanical ventilation, respiratory mechanics and ventilator waveform interpretation, strategies for initial ventilator settings, indications and contraindications for noninvasive ventilation, and the effect of the ventilator on kidney function.Pearson, Steven D.Koyner, Jay L.Patel, Bhakti K.2022-03-10T07:00:01-08:00doi:10.2215/CJN.13091021hwp:resource-id:clinjasn;17/4/572American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care nephrology and acute kidney injury series, respiratory failure, mechanical ventilationCritical Care Nephrology and Acute Kidney InjuryCritical Care Nephrology and Acute Kidney Injuryresearch-article20222022-04-01April 202210.2215/CJN.130910211555-90411555-905X2022-03-10T07:00:01-08:002022-04Clinical Journal of the American Society of NephrologyCritical Care Nephrology and Acute Kidney Injury174572580
- Multifaceted Intervention to Increase the Use of Home Dialysis10.2215/CJN.13191021Mon, 21 Mar 2022 11:07:36 GMT-07:00Multifaceted Intervention to Increase the Use of Home DialysisManns, Braden J.Garg, Amit X.Sood, Manish M.Ferguson, ThomasKim, S. JosephNaimark, DavidNesrallah, Gihad E.Soroka, Steven D.Beaulieu, MonicaDixon, Stephanie N.Alam, AhsanAllu, SelinaTangri, Navdeep2022-03-21T11:07:36-07:00doi:10.2215/CJN.13191021hwp:resource-id:clinjasn;17/4/535American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, randomized controlled trials, end stage kidney disease, peritoneal dialysis, home hemodialysisOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-04-01April 202210.2215/CJN.131910211555-90411555-905X2022-03-21T11:07:36-07:002022-04Clinical Journal of the American Society of NephrologyOriginal Article1744535484545486
- Trajectories of Uremic Symptom Severity and Kidney Function in Patients with Chronic Kidney Disease10.2215/CJN.13010921Fri, 04 Mar 2022 10:26:00 GMT-08:00Trajectories of Uremic Symptom Severity and Kidney Function in Patients with Chronic Kidney DiseaseWulczyn, Kendra E.Zhao, Sophia H.Rhee, Eugene P.Kalim, SahirShafi, Tariq2022-03-04T10:26:00-08:00doi:10.2215/CJN.13010921hwp:resource-id:clinjasn;17/4/496American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuremia, quality of life, depression, clinical epidemiology, chronic kidney diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-04-01April 202210.2215/CJN.130109211555-90411555-905X2022-03-04T10:26:00-08:002022-04Clinical Journal of the American Society of NephrologyOriginal Article1744496475506477
- Breaking the Barriers to Innovation in Kidney Care10.2215/CJN.15721221Tue, 15 Feb 2022 07:19:38 GMT-08:00Breaking the Barriers to Innovation in Kidney CareNissenson, Allen R.Chertow, Glenn M.Conway, Paul T.2022-02-15T07:19:38-08:00doi:10.2215/CJN.15721221hwp:resource-id:clinjasn;17/4/591American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, kidney care, innovation, KidneyX, KHIPerspectivePerspectiveresearch-article20222022-04-01April 202210.2215/CJN.157212211555-90411555-905X2022-02-15T07:19:38-08:002022-04Clinical Journal of the American Society of NephrologyPerspective174591593
- Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug Use10.2215/CJN.13681021Wed, 16 Mar 2022 08:35:00 GMT-07:00Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug UseStalund, Ida V.Grønseth, HeidiReinholt, Finn P.Svarstad, EinarMarti, Hans-PeterLeh, Sabine2022-03-16T08:35:00-07:00doi:10.2215/CJN.13681021hwp:resource-id:clinjasn;17/4/518American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyopioid addiction, intravenous drug use, IVDU, methadone, chronic kidney disease, tubular atrophy, macrophage storage, foreign materialOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-04-01April 202210.2215/CJN.136810211555-90411555-905X2022-03-16T08:35:00-07:002022-04Clinical Journal of the American Society of NephrologyOriginal Article171746518879526879
- Patient-Reported Symptoms and Subsequent Risk of Myocardial Infarction in Chronic Kidney Disease10.2215/CJN.12080921Thu, 17 Mar 2022 07:42:34 GMT-07:00Patient-Reported Symptoms and Subsequent Risk of Myocardial Infarction in Chronic Kidney DiseaseLidgard, BenjaminZelnick, Leila R.O’Brien, Kevin D.Bansal, Nisha2022-03-17T07:42:34-07:00doi:10.2215/CJN.12080921hwp:resource-id:clinjasn;17/4/487American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, myocardial infarction, patient reported outcome measuresOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-04-01April 202210.2215/CJN.120809211555-90411555-905X2022-03-17T07:42:34-07:002022-04Clinical Journal of the American Society of NephrologyOriginal Article174487495
- Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney DiseaseThe Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of CKD and AKI. Herein, we describe the case of a 66-year-old woman with CKD who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient’s histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease. Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures that were uncovered revealed evidence of early diabetic kidney disease adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of diabetic kidney disease was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.10.2215/CJN.10350721Wed, 15 Dec 2021 10:07:40 GMT-08:00Molecular Signatures of Diabetic Kidney Disease Hiding in a Patient with Hypertension-Related Kidney DiseaseThe Kidney Precision Medicine Project (KPMP) seeks to establish a molecular atlas of the kidney in health and disease and improve our understanding of the molecular drivers of CKD and AKI. Herein, we describe the case of a 66-year-old woman with CKD who underwent a protocol KPMP kidney biopsy. Her clinical history included well-controlled diabetes mellitus, hypertension, and proteinuria. The patient’s histopathology was consistent with modest hypertension-related kidney injury, without overt diabetic kidney disease. Transcriptomic signatures of the glomerulus, interstitium, and tubular subsegments were obtained from laser microdissected tissue. The molecular signatures that were uncovered revealed evidence of early diabetic kidney disease adaptation and ongoing active tubular injury with enriched pathways related to mesangial cell hypertrophy, glycosaminoglycan biosynthesis, and apoptosis. Molecular evidence of diabetic kidney disease was found across the nephron. Novel molecular assays can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.Patel, JitenTorrealba, Jose R.Poggio, Emilio D.Bebiak, JackAlpers, Charles E.Grewenow, Stephanie M.Toto, Robert D.Eadon, Michael T.2021-12-15T10:07:40-08:00doi:10.2215/CJN.10350721hwp:resource-id:clinjasn;17/4/594American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymolecular biology, pathology, clinical nephrologyFeatureFeatureresearch-article20222022-04-01April 202210.2215/CJN.103507211555-90411555-905X2021-12-15T10:07:40-08:002022-04Clinical Journal of the American Society of NephrologyFeature174594601
- In Defense of Normal Saline10.2215/CJN.10400821Wed, 09 Feb 2022 08:21:01 GMT-08:00In Defense of Normal SalineMikhael, BassemSteele, David J.R.Fenves, Andrew Z.2022-02-09T08:21:01-08:00doi:10.2215/CJN.10400821hwp:resource-id:clinjasn;17/4/588American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyelectrolytes, acidosis, clinical nephrologyPerspectivePerspectiveresearch-article20222022-04-01April 202210.2215/CJN.104008211555-90411555-905X2022-02-09T08:21:01-08:002022-04Clinical Journal of the American Society of NephrologyPerspective174588590
- Extracorporeal Treatment for Methotrexate PoisoningMethotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.10.2215/CJN.08030621Wed, 02 Mar 2022 09:43:50 GMT-08:00Extracorporeal Treatment for Methotrexate PoisoningMethotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.Ghannoum, MarcRoberts, Darren M.Goldfarb, David S.Heldrup, JesperAnseeuw, KurtGalvao, Tais F.Nolin, Thomas D.Hoffman, Robert S.Lavergne, ValeryMeyers, PaulGosselin, SophieBotnaru, TudorMardini, KarineWood, David M.2022-03-02T09:43:50-08:00doi:10.2215/CJN.08030621hwp:resource-id:clinjasn;17/4/602American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymethotrexate, extracorporeal treatment, EXTRIP, glucarpidase, hemodialysis, toxicity, nephrotoxicityFeatureFeatureresearch-article20222022-04-01April 202210.2215/CJN.080306211555-90411555-905X2022-03-02T09:43:50-08:002022-04Clinical Journal of the American Society of NephrologyFeature174602622
- Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada10.1681/ASN.2021091262Wed, 09 Mar 2022 07:40:59 GMT-08:00Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, CanadaOliver, Matthew J.Thomas, DonealBalamchi, ShabnamIp, JaneNaylor, KylaDixon, Stephanie N.McArthur, EricKwong, JeffPerl, JeffreyAtiquzzaman, MohammadSinger, JoelYeung, AngieHladunewich, MichelleYau, KevinGarg, Amit X.Leis, Jerome A.Levin, AdeeraKrajden, MelBlake, Peter G.2022-03-09T07:40:59-08:00doi:10.1681/ASN.2021091262hwp:resource-id:jnephrol;33/4/839American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, hospitalization, mortality, COVID-19, SARS-CoV-2, Ontario, maintenanceClinical ResearchClinical Researchresearch-article20222022-04-01April 202210.1681/ASN.20210912621046-66731533-34502022-03-09T07:40:59-08:002022-04Journal of the American Society of NephrologyClinical Research334839849
- Endocytosis Begins inside the Cell10.1681/ASN.2022020155Mon, 07 Mar 2022 07:48:29 GMT-08:00Endocytosis Begins inside the CellBeenken, Andrew2022-03-07T07:48:29-08:00doi:10.1681/ASN.2022020155hwp:resource-id:jnephrol;33/4/661American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyendocytosisUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-04-01April 202210.1681/ASN.20220201551046-66731533-34502022-03-07T07:48:29-08:002022-04Journal of the American Society of NephrologyUp Front Matters3344661732662745
- Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector–Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients10.1681/ASN.2021101395Tue, 08 Feb 2022 08:27:07 GMT-08:00Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector–Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis PatientsBrunelli, Steven M.Sibbel, ScottKarpinski, StephMarlowe, GilbertWalker, Adam G.Giullian, JeffreyVan Wyck, DavidKelley, TaraLazar, RachaelZywno, Meredith L.Connaire, Jeffrey J.Young, AmyTentori, Francesca2022-02-08T08:27:07-08:00doi:10.1681/ASN.2021101395hwp:resource-id:jnephrol;33/4/688American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, SARS-CoV-2, vaccine, dialysis, comparative effectiveness, BNT162 vaccineRapid CommunicationsRapid Communicationsresearch-article20222022-04-01April 202210.1681/ASN.20211013951046-66731533-34502022-02-08T08:27:07-08:002022-04Journal of the American Society of NephrologyRapid Communications334688697
- A Founder Mutation in EHD1 Presents with Tubular Proteinuria and Deafness10.1681/ASN.2021101312Fri, 11 Feb 2022 07:10:15 GMT-08:00A Founder Mutation in EHD1 Presents with Tubular Proteinuria and DeafnessIssler, NaomiAfonso, SaraWeissman, IrithJordan, KatrinCebrian-Serrano, AlbertoMeindl, KatrinDahlke, EileenTziridis, KonstantinYan, GuanhuaRobles-López, José M.Tabernero, LydiaPatel, VakshaKesselheim, AnneKlootwijk, Enriko D.Stanescu, Horia C.Dumitriu, SimonaIancu, DanielaTekman, MehmetMozere, MonikaJaureguiberry, GracianaOuttandy, PriyaRussell, ClaireForst, Anna-LenaSterner, ChristinaHeinl, Elena-SofiaOthmen, HelgaTegtmeier, InesReichold, MarkusSchiessl, Ina MariaLimm, KatharinaOefner, PeterWitzgall, RalphFu, LifeiTheilig, FranziskaSchilling, AchimShuster Biton, EfratKalfon, LimorFedida, AyallaArnon-Sheleg, EliteBen Izhak, OferMagen, DaniellaAnikster, YairSchulze, HolgerZiegler, ChristineLowe, MartinDavies, BenjaminBöckenhauer, DetlefKleta, RobertFalik Zaccai, Tzipora C.Warth, Richard2022-02-11T07:10:15-08:00doi:10.1681/ASN.2021101312hwp:resource-id:jnephrol;33/4/732American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyepithelial transport physiology, infertility, megalin, Eps15 homology domain, proximal tubule, genetic renal disease, mutationBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20211013121046-66731533-34502022-02-11T07:10:15-08:002022-04Journal of the American Society of NephrologyBasic Research3344732661745662
- Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease10.1681/ASN.2021050680Thu, 10 Mar 2022 07:04:49 GMT-08:00Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney DiseaseVerissimo, ThomasFaivre, AnnaRinaldi, AnnaLindenmeyer, MajaDelitsikou, VasilikiVeyrat-Durebex, ChristelleHeckenmeyer, CarolynFernandez, MaryliseBerchtold, LenaDalga, DelalCohen, ClemensNaesens, MaartenRicksten, Sven-ErikMartin, Pierre-YvesPugin, JérômeMerlier, FranckHaupt, KarstenRutkowski, Joseph M.Moll, SolangeCippà, Pietro E.Legouis, Davidde Seigneux, Sophie2022-03-10T07:04:49-08:00doi:10.1681/ASN.2021050680hwp:resource-id:jnephrol;33/4/810American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, metabolism, gluconeogenesisBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20210506801046-66731533-34502022-03-10T07:04:49-08:002022-04Journal of the American Society of NephrologyBasic Research334810827
- The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in Scotland10.1681/ASN.2022010046Wed, 02 Feb 2022 09:35:54 GMT-08:00The Impact of Vaccination on Incidence and Outcomes of SARS-CoV-2 Infection in Patients with Kidney Failure in ScotlandBell, SamiraCampbell, JacquelineLambourg, EmilieWatters, ChrissieO’Neil, MartinAlmond, AlisonBuck, KatharineCarr, Edward J.Clark, LauraCousland, ZoeFindlay, MarkJoss, NicolaMetcalfe, WendyPetrie, MichaelaSpalding, ElaineTraynor, Jamie P.Sanu, VinodThomson, PeterMethven, ShonaMark, Patrick B.2022-02-02T09:35:54-08:00doi:10.1681/ASN.2022010046hwp:resource-id:jnephrol;33/4/677American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical epidemiology, vaccination, COVID-19, dialysis, transplantation, kidney replacement therapyRapid CommunicationsRapid Communicationsresearch-article20222022-04-01April 202210.1681/ASN.20220100461046-66731533-34502022-02-02T09:35:54-08:002022-04Journal of the American Society of NephrologyRapid Communications33334677677122814281430686122814301431
- Authors’ Reply: Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cells10.1681/ASN.2021121588Thu, 03 Feb 2022 09:51:58 GMT-08:00Authors’ Reply: Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B CellsSato, YukiLee, Yu HoTaniguchi, KeisukeYoshikawa, TakahisaBoor, PeterFloege, JürgenYanagita, Motoko2022-02-03T09:51:58-08:00doi:10.1681/ASN.2021121588hwp:resource-id:jnephrol;33/4/868American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, tertiary lymphoid tissuesLetter to the EditorLetter to the Editorletter20222022-04-01April 202210.1681/ASN.20211215881046-66731533-34502022-02-03T09:51:58-08:002022-04Journal of the American Society of NephrologyLetter to the Editor33441868867186869867200
- Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cells10.1681/ASN.2021111509Thu, 03 Feb 2022 10:21:39 GMT-08:00Advanced Tertiary Lymphoid Tissues in Protocol Biopsies in Kidney Transplant Recipients: Addressing Additional Methods To Detect Intragraft B Cellsdu Long, RomyFlorquin, SandrineKers, Jesper2022-02-03T10:21:39-08:00doi:10.1681/ASN.2021111509hwp:resource-id:jnephrol;33/4/867American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, immunohistochemistry, B lymphocytes, biopsyLetter to the EditorLetter to the Editorletter20222022-04-01April 202210.1681/ASN.20211115091046-66731533-34502022-02-03T10:21:39-08:002022-04Journal of the American Society of NephrologyLetter to the Editor33441867868186867869200
- Correction: Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity10.1681/ASN.2022010083Thu, 31 Mar 2022 10:00:34 GMT-07:00Correction: Megalin Blockade with Cilastatin Suppresses Drug-Induced NephrotoxicityAmerican Society of Nephrology2022-03-31T10:00:34-07:00doi:10.1681/ASN.2022010083hwp:resource-id:jnephrol;33/4/872American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, colistin, drug nephrotoxicity, gentamicin, megalin, vancomycinErrataErratacorrection20222022-04-01April 202210.1681/ASN.20220100831046-66731533-34502022-03-31T10:00:34-07:002022-04Journal of the American Society of NephrologyErrata33284668721783178387217911791
- New Insights into the Pivotal Roles of Claudins in Proximal Tubule Electrolyte Reabsorption10.1681/ASN.2022020157Wed, 09 Mar 2022 08:33:17 GMT-08:00New Insights into the Pivotal Roles of Claudins in Proximal Tubule Electrolyte ReabsorptionAronson, Peter S.2022-03-09T08:33:17-08:00doi:10.1681/ASN.2022020157hwp:resource-id:jnephrol;33/4/659American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, claudinsUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-04-01April 202210.1681/ASN.20220201571046-66731533-34502022-03-09T08:33:17-08:002022-04Journal of the American Society of NephrologyUp Front Matters3344659699661717
- Lipopolysaccharide Pretreatment Prevents Medullary Vascular Congestion following Renal Ischemia by Limiting Early Reperfusion of the Medullary Circulation10.1681/ASN.2021081089Thu, 03 Feb 2022 02:12:09 GMT-08:00Lipopolysaccharide Pretreatment Prevents Medullary Vascular Congestion following Renal Ischemia by Limiting Early Reperfusion of the Medullary CirculationMcLarnon, Sarah R.Wilson, KatiePatel, BansariSun, JingpingSartain, Christina L.Mejias, Christopher D.Musall, Jacqueline B.Sullivan, Jennifer C.Wei, QingqingChen, Jian-KangHyndman, Kelly A.Marshall, BrendanYang, HaichunFogo, Agnes B.O’Connor, Paul M.2022-02-03T14:12:09-08:00doi:10.1681/ASN.2021081089hwp:resource-id:jnephrol;33/4/769American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperemia, inflammation, preconditioning, rouleaux, red cell trapping, vasa recta, acute renal failureBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20210810891046-66731533-34502022-02-03T14:12:09-08:002022-04Journal of the American Society of NephrologyBasic Research334769785
- The Search for the Perfect Agent for Anemia Management in Chronic Kidney Disease10.1681/ASN.2022020173Thu, 31 Mar 2022 10:00:34 GMT-07:00The Search for the Perfect Agent for Anemia Management in Chronic Kidney DiseaseLocatelli, FrancescoDel Vecchio, Lucia2022-03-31T10:00:34-07:00doi:10.1681/ASN.2022020173hwp:resource-id:jnephrol;33/4/662American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, erythropoietin, chronic kidney disease, dialysis, roxadustat, HIF PH inihibitors, erythropoiesis stimulating agentsUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-04-01April 202210.1681/ASN.20220201731046-66731533-34502022-03-31T10:00:34-07:002022-04Journal of the American Society of NephrologyUp Front Matters3344662850664866
- Authors’ Reply: SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?10.1681/ASN.2022010033Mon, 14 Feb 2022 09:17:25 GMT-08:00Authors’ Reply: SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?Schrezenmeier, EvaSattler, ArneHalleck, FabianBudde, Klemens2022-02-14T09:17:25-08:00doi:10.1681/ASN.2022010033hwp:resource-id:jnephrol;33/4/870American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, vaccination, transplantationLetter to the EditorLetter to the Editorletter20222022-04-01April 202210.1681/ASN.20220100331046-66731533-34502022-02-14T09:17:25-08:002022-04Journal of the American Society of NephrologyLetter to the Editor33441287086930278718693033
- Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study10.1681/ASN.2021111460Tue, 08 Mar 2022 07:47:25 GMT-08:00Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a StudyUhlin, FredrikSzpirt, WladimirKronbichler, AndreasBruchfeld, AnnetteSoveri, IngaRostaing, LionelDaugas, EricLionet, ArnaudKamar, NassimRafat, CédricMysliveček, MarekTesař, VladimírFernström, AndersKjellman, ChristianElfving, CharlotteMcAdoo, StephenMölne, JohanBajema, IngeborgSonesson, ElisabethSegelmark, Mårten2022-03-08T07:47:25-08:00doi:10.1681/ASN.2021111460hwp:resource-id:jnephrol;33/4/829American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, endopeptidases, clinical trial, glomerulonephritis, Goodpasture syndromeClinical ResearchClinical Researchresearch-article20222022-04-01April 202210.1681/ASN.20211114601046-66731533-34502022-03-08T07:47:25-08:002022-04Journal of the American Society of NephrologyClinical Research33410108291953195483819541955
- α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration Barrier10.1681/ASN.2021101319Tue, 08 Mar 2022 07:47:24 GMT-08:00α-Parvin Defines a Specific Integrin Adhesome to Maintain the Glomerular Filtration BarrierRogg, ManuelMaier, Jasmin I.Van Wymersch, ClaraHelmstädter, MartinSammarco, AlenaLindenmeyer, MajaZareba, PaulinaMontanez, EloiWalz, GerdWerner, MartinEndlich, NicoleBenzing, ThomasHuber, Tobias B.Schell, Christoph2022-03-08T07:47:24-08:00doi:10.1681/ASN.2021101319hwp:resource-id:jnephrol;33/4/786American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, glomerular epithelial cells, podocyte, proteinuria, integrin adhesion complex, IPP complex, PARVA, glomerular filtration barrier, PARVB, focal adhesionBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20211013191046-66731533-34502022-03-08T07:47:24-08:002022-04Journal of the American Society of NephrologyBasic Research334786808
- Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES Study10.1681/ASN.2020111638Thu, 31 Mar 2022 10:00:34 GMT-07:00Roxadustat Versus Epoetin Alfa for Treating Anemia in Patients with Chronic Kidney Disease on Dialysis: Results from the Randomized Phase 3 ROCKIES StudyFishbane, StevenPollock, Carol A.El-Shahawy, MohamedEscudero, Elizabeth T.Rastogi, AnjayVan, Bui PhamFrison, LarsHouser, MarkPola, MaksymLittle, Dustin J.Guzman, NicolasPergola, Pablo E.2022-03-31T10:00:34-07:00doi:10.1681/ASN.2020111638hwp:resource-id:jnephrol;33/4/850American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic kidney disease, dialysis, roxadustat, HIF-PH inhibitorClinical ResearchClinical Researchresearch-article20222022-04-01April 202210.1681/ASN.20201116381046-66731533-34502022-03-31T10:00:34-07:002022-04Journal of the American Society of NephrologyClinical Research33444850662674866664676
- Premature Death in Kidney Transplant Recipients: The Time for Trials is Now10.1681/ASN.2021111517Tue, 15 Mar 2022 08:38:02 GMT-07:00Premature Death in Kidney Transplant Recipients: The Time for Trials is NowVinson, Amanda J.Singh, SunitaChadban, StevenCherney, DavidGaber, OsamaGill, John S.Helgeson, ErikaHerzog, Charles A.Jardine, MegJha, VivekanandKasiske, Bertram L.Mannon, Roslyn B.Michos, Erin D.Mottl, Amy K.Newby, KristinRoy-Chaudhury, PrabirSawinski, DeirdreSharif, AdnanSridhar, Vikas S.Tuttle, Katherine R.Vock, David M.Matas, Arthur2022-03-15T08:38:02-07:00doi:10.1681/ASN.2021111517hwp:resource-id:jnephrol;33/4/665American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymortality, cardiovascular disease, evidence, death with graft function, death despite kidney function, kidney transplantation, transplant recipients, premature mortalityPerspectivePerspectiveresearch-article20222022-04-01April 202210.1681/ASN.20211115171046-66731533-34502022-03-15T08:38:02-07:002022-04Journal of the American Society of NephrologyPerspective334665673
- Claudin-10a Deficiency Shifts Proximal Tubular Cl- Permeability to Cation Selectivity via Claudin-2 Redistribution10.1681/ASN.2021030286Fri, 14 Jan 2022 08:48:18 GMT-08:00Claudin-10a Deficiency Shifts Proximal Tubular Cl- Permeability to Cation Selectivity via Claudin-2 RedistributionBreiderhoff, TilmanHimmerkus, NinaMeoli, LucaFromm, AnjaSewerin, SebastianKriuchkova, NataliaNagel, OliverLadilov, YuryKrug, Susanne M.Quintanova, CatarinaStumpp, MeikeGarbe-Schönberg, DieterWesternströer, UlrikeMerkel, CosimaBrinkhus, Merle AnnetteAltmüller, JanineSchweiger, Michal R.Müller, DominikMutig, KerimMorawski, MarkusHalbritter, JanMilatz, SusanneBleich, MarkusGünzel, Dorothee2022-01-14T08:48:18-08:00doi:10.1681/ASN.2021030286hwp:resource-id:jnephrol;33/4/699American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypathophysiology of kidney disease and progression, ion transport, calciumBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20210302861046-66731533-34502022-01-14T08:48:18-08:002022-04Journal of the American Society of NephrologyBasic Research3344699659717661
- A Neutralizing IL-11 Antibody Improves Renal Function and Increases Lifespan in a Mouse Model of Alport Syndrome10.1681/ASN.2021040577Wed, 09 Feb 2022 11:23:10 GMT-08:00A Neutralizing IL-11 Antibody Improves Renal Function and Increases Lifespan in a Mouse Model of Alport SyndromeWidjaja, Anissa A.Shekeran, Shamini G.Adami, EleonoraTing, Joyce G WeiTan, JessieViswanathan, SivakumarLim, Sze YunTan, Puay HoonHübner, NorbertCoffman, ThomasCook, Stuart A.2022-02-09T11:23:10-08:00doi:10.1681/ASN.2021040577hwp:resource-id:jnephrol;33/4/718American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyAlport syndrome, fibrosis, interleukin 11, podocyte, therapy, glomerular disease, glomerulosclerosis, chronic kidney diseaseBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20210405771046-66731533-34502022-02-09T11:23:10-08:002022-04Journal of the American Society of NephrologyBasic Research334718730
- SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?10.1681/ASN.2021121566Mon, 14 Feb 2022 10:29:21 GMT-08:00SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Should We Consider Intradermal Vaccination?Wijtvliet, VeerleWissing, Karl MartinAbramowicz, DanielLedeganck, Kristien J.2022-02-14T10:29:21-08:00doi:10.1681/ASN.2021121566hwp:resource-id:jnephrol;33/4/869American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyintradermal vaccination, kidney transplant recipients, SARS-CoV-2, third dose, T lymphocytes, COVID-19 vaccines, COVID-19Letter to the EditorLetter to the Editorletter20222022-04-01April 202210.1681/ASN.20211215661046-66731533-34502022-02-14T10:29:21-08:002022-04Journal of the American Society of NephrologyLetter to the Editor33441286987030278708713033
- The Non-Inferiority Complex: What Do Non-Inferiority Trials Tell Us?10.1681/ASN.2021050681Thu, 31 Mar 2022 10:00:34 GMT-07:00The Non-Inferiority Complex: What Do Non-Inferiority Trials Tell Us?Assimon, Magdalene M.Cutter, Gary R.Bargman, Joanne M.2022-03-31T10:00:34-07:00doi:10.1681/ASN.2021050681hwp:resource-id:jnephrol;33/4/674American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynoninferiority trials, study design, nephrologyPerspectivePerspectiveresearch-article20222022-04-01April 202210.1681/ASN.20210506811046-66731533-34502022-03-31T10:00:34-07:002022-04Journal of the American Society of NephrologyPerspective3344674850676866
- This Month's Highlights10.1681/ASN.2022020203Thu, 31 Mar 2022 10:00:34 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2022-03-31T10:00:34-07:00doi:10.1681/ASN.2022020203hwp:resource-id:jnephrol;33/4/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20222022-04-01April 202210.1681/ASN.20220202031046-66731533-34502022-03-31T10:00:34-07:002022-04Journal of the American Society of NephrologyThis Month’s Highlights334ii
- A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in Mice10.1681/ASN.2021030278Wed, 02 Feb 2022 09:35:54 GMT-08:00A Comprehensive Immune Cell Atlas of Cystic Kidney Disease Reveals the Involvement of Adaptive Immune Cells in Injury-Mediated Cyst Progression in MiceSong, Cheng J.Li, ZhangAhmed, Ummey Khalecha BinthaBland, Sarah J.Yashchenko, AlexLiu, ShanrunAloria, Ernald J.Lever, Jeremie M.Gonzalez, Nancy M.Bickel, Marisa A.Giles, Cory B.Georgescu, ConstantinWren, Jonathan D.Lang, Mark L.Benveniste, Etty N.Harrington, Laurie E.Tsiokas, LeoGeorge, James F.Jones, Kenneth L.Crossman, David K.Agarwal, AnupamMrug, MichalYoder, Bradley K.Hopp, KatharinaZimmerman, Kurt A.2022-02-02T09:35:54-08:00doi:10.1681/ASN.2021030278hwp:resource-id:jnephrol;33/4/747American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycystic kidney, immunology, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20222022-04-01April 202210.1681/ASN.20210302781046-66731533-34502022-02-02T09:35:54-08:002022-04Journal of the American Society of NephrologyBasic Research334747768
- How Whole Slide Imaging and Machine Learning Can Partner with Renal Pathology10.34067/KID.0007982021Thu, 31 Mar 2022 06:30:32 GMT-07:00How Whole Slide Imaging and Machine Learning Can Partner with Renal PathologyWilson, Parker C.Messias, Nidia2022-03-31T06:30:32-07:00doi:10.34067/KID.0007982021hwp:resource-id:kidney360;3/3/413American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, basic science, digital image analysis, machine learning, membranous nephropathy, minimal change disease, renal pathology, thin basement membrane disease, whole slide imagingEditorialEditorialeditorial20222022-03-3110.34067/KID.00079820212641-76502022-03-31T06:30:32-07:002022-03-31Kidney360Editorial33413415
- Is There a Role for More Intense Immunosuppression in IgA Nephropathy?10.34067/KID.0000512022Thu, 31 Mar 2022 06:30:32 GMT-07:00Is There a Role for More Intense Immunosuppression in IgA Nephropathy?Aron, Abraham W.2022-03-31T06:30:32-07:00doi:10.34067/KID.0000512022hwp:resource-id:kidney360;3/3/410American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, cyclophosphamide, IgA nephropathy, immunosuppressionEditorialEditorialeditorial20222022-03-3110.34067/KID.00005120222641-76502022-03-31T06:30:32-07:002022-03-31Kidney360Editorial33410412
- Explainable Biomarkers for Automated Glomerular and Patient-Level Disease ClassificationPathologists use multiple microscopy modalities to assess renal biopsy specimens. Besides usual diagnostic features, some changes are too subtle to be properly defined. Computational approaches have the potential to systematically quantitate subvisual clues, provide pathogenetic insight, and link to clinical outcomes. To this end, a proof-of-principle study is presented demonstrating that explainable biomarkers through machine learning can distinguish between glomerular disorders at the light-microscopy level. The proposed system used image analysis techniques and extracted 233 explainable biomarkers related to color, morphology, and microstructural texture. Traditional machine learning was then used to classify minimal change disease (MCD), membranous nephropathy (MN), and thin basement membrane nephropathy (TBMN) diseases on a glomerular and patient-level basis. The final model combined the Gini feature importance set and linear discriminant analysis classifier. Six morphologic (nuclei-to-glomerular tuft area, nuclei-to-glomerular area, glomerular tuft thickness greater than ten, glomerular tuft thickness greater than three, total glomerular tuft thickness, and glomerular circularity) and four microstructural texture features (luminal contrast using wavelets, nuclei energy using wavelets, nuclei variance using color vector LBP, and glomerular correlation using GLCM) were, together, the best performing biomarkers. Accuracies of 77% and 87% were obtained for glomerular and patient-level classification, respectively. Computational methods, using explainable glomerular biomarkers, have diagnostic value and are compatible with our existing knowledge of disease pathogenesis. Furthermore, this algorithm can be applied to clinical datasets for novel prognostic and mechanistic biomarker discovery.10.34067/KID.0005102021Thu, 09 Dec 2021 07:34:46 GMT-08:00Explainable Biomarkers for Automated Glomerular and Patient-Level Disease ClassificationPathologists use multiple microscopy modalities to assess renal biopsy specimens. Besides usual diagnostic features, some changes are too subtle to be properly defined. Computational approaches have the potential to systematically quantitate subvisual clues, provide pathogenetic insight, and link to clinical outcomes. To this end, a proof-of-principle study is presented demonstrating that explainable biomarkers through machine learning can distinguish between glomerular disorders at the light-microscopy level. The proposed system used image analysis techniques and extracted 233 explainable biomarkers related to color, morphology, and microstructural texture. Traditional machine learning was then used to classify minimal change disease (MCD), membranous nephropathy (MN), and thin basement membrane nephropathy (TBMN) diseases on a glomerular and patient-level basis. The final model combined the Gini feature importance set and linear discriminant analysis classifier. Six morphologic (nuclei-to-glomerular tuft area, nuclei-to-glomerular area, glomerular tuft thickness greater than ten, glomerular tuft thickness greater than three, total glomerular tuft thickness, and glomerular circularity) and four microstructural texture features (luminal contrast using wavelets, nuclei energy using wavelets, nuclei variance using color vector LBP, and glomerular correlation using GLCM) were, together, the best performing biomarkers. Accuracies of 77% and 87% were obtained for glomerular and patient-level classification, respectively. Computational methods, using explainable glomerular biomarkers, have diagnostic value and are compatible with our existing knowledge of disease pathogenesis. Furthermore, this algorithm can be applied to clinical datasets for novel prognostic and mechanistic biomarker discovery.Basso, Matthew NicholasBarua, MoumitaJohn, RohanKhademi, April2021-12-09T07:34:46-08:00doi:10.34067/KID.0005102021hwp:resource-id:kidney360;3/3/534American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, basic science, computational pathology, explainable biomarkers, machine learning, membranous nephropathy, minimal change disease, thin-basement membrane nephropathyInnovative Technology and MethodologyGlomerular and Tubulointerstitial DiseasesInnovative Technology and MethodologyGlomerular and Tubulointerstitial Diseasesresearch-article20222022-03-3110.34067/KID.00051020212641-76502021-12-09T07:34:46-08:002022-03-31Kidney360Innovative Technology and Methodology33534545
- How the University of Washington Implemented a Change in eGFR Reporting10.34067/KID.0006522021Wed, 26 Jan 2022 09:42:05 GMT-08:00How the University of Washington Implemented a Change in eGFR ReportingNkinsi, Naomi T.Young, Bessie A.2022-01-26T09:42:05-08:00doi:10.34067/KID.0006522021hwp:resource-id:kidney360;3/3/557American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, eGFR, kidney disease, kidney function, race, student advocacyPerspectivePerspectiveresearch-article20222022-03-3110.34067/KID.00065220212641-76502022-01-26T09:42:05-08:002022-03-31Kidney360Perspective33557560
- Extrarenal Effects of Aldosterone on Potassium HomeostasisThe role of aldosterone in regulating K+ excretion in the distal nephron is well established in kidney physiology. In addition to effects on the kidney, aldosterone modulates K+ and Na+ transport in salivary fluid, sweat, airway epithelia, and colonic fluid. More controversial and less well defined is the role of aldosterone in determining the internal distribution of K+ across cell membranes in nontransporting epithelia. In vivo studies have been limited by the difficulty in accurately measuring overall K+ balance and factoring in both variability and secondary changes in acid-base balance, systemic hemodynamics, and other K+-regulatory factors such as hormones and adrenergic activity. Despite these limitations, the aggregate data support a contributory role of aldosterone along with insulin and catecholamines in the normal physiologic regulation of internal K+ distribution. The authors speculate differences in tissue sensitivity to aldosterone may also contribute to differential tissue response of cardiac and skeletal muscle to conditions of total body K+ depletion.10.34067/KID.0006762021Fri, 14 Jan 2022 01:30:12 GMT-08:00Extrarenal Effects of Aldosterone on Potassium HomeostasisThe role of aldosterone in regulating K+ excretion in the distal nephron is well established in kidney physiology. In addition to effects on the kidney, aldosterone modulates K+ and Na+ transport in salivary fluid, sweat, airway epithelia, and colonic fluid. More controversial and less well defined is the role of aldosterone in determining the internal distribution of K+ across cell membranes in nontransporting epithelia. In vivo studies have been limited by the difficulty in accurately measuring overall K+ balance and factoring in both variability and secondary changes in acid-base balance, systemic hemodynamics, and other K+-regulatory factors such as hormones and adrenergic activity. Despite these limitations, the aggregate data support a contributory role of aldosterone along with insulin and catecholamines in the normal physiologic regulation of internal K+ distribution. The authors speculate differences in tissue sensitivity to aldosterone may also contribute to differential tissue response of cardiac and skeletal muscle to conditions of total body K+ depletion.Palmer, Biff F.Clegg, Deborah J.2022-01-14T13:30:12-08:00doi:10.34067/KID.0006762021hwp:resource-id:kidney360;3/3/561American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, aldosterone, catecholamines, extrarenal K homeostasis, hyperkalemia, hypokalemia, insulin, internal K distribution, potassium, potassium homeostasisReview ArticleReview Articlereview-article20222022-03-3110.34067/KID.00067620212641-76502022-01-14T13:30:12-08:002022-03-31Kidney360Review Article33561568
- Nephrology Considerations in the Management of Durable and Temporary Mechanical Circulatory SupportDurable and temporary mechanical circulatory support (MCS) use is growing for a range of cardiovascular indications. Kidney dysfunction is common in people evaluated for or receiving durable or temporary MCS and portends worse outcomes. This kidney dysfunction can be due to preexisting kidney chronic kidney disease (CKD), acute kidney injury (AKI) related to acute cardiovascular disease necessitating MCS, AKI due to cardiac procedures, and acute and chronic MCS effects and complications. Durable MCS, with implantable continuous flow pumps, is used for long-term support in advanced heart failure refractory to guideline-directed medical and device therapy, either permanently or as a bridge to heart transplantation. Temporary MCS—encompassing in this review intra-aortic balloon pumps (IABP), axial flow pumps, centrifugal flow pumps, and venoarterial ECMO—is used for diverse situations: high-risk percutaneous coronary interventions (PCI), acute decompensated heart failure, cardiogenic shock, and resuscitation after cardiac arrest. The wide adoption of MCS makes it imperative to improve understanding of the effects of MCS on kidney health/function and of kidney health/function on MCS outcomes. The complex structure and functions of the kidney, and the complex health states of individuals receiving MCS, makes investigations in this area challenging, and current knowledge is limited. Fortunately, the increasing nephrology toolbox of noninvasive kidney health/function assessments may enable development and testing of individualized management strategies and therapeutics in the future. We review technology, epidemiology, pathophysiology, clinical considerations, and future directions in MCS and nephrology.10.34067/KID.0003382021Fri, 14 Jan 2022 01:30:12 GMT-08:00Nephrology Considerations in the Management of Durable and Temporary Mechanical Circulatory SupportDurable and temporary mechanical circulatory support (MCS) use is growing for a range of cardiovascular indications. Kidney dysfunction is common in people evaluated for or receiving durable or temporary MCS and portends worse outcomes. This kidney dysfunction can be due to preexisting kidney chronic kidney disease (CKD), acute kidney injury (AKI) related to acute cardiovascular disease necessitating MCS, AKI due to cardiac procedures, and acute and chronic MCS effects and complications. Durable MCS, with implantable continuous flow pumps, is used for long-term support in advanced heart failure refractory to guideline-directed medical and device therapy, either permanently or as a bridge to heart transplantation. Temporary MCS—encompassing in this review intra-aortic balloon pumps (IABP), axial flow pumps, centrifugal flow pumps, and venoarterial ECMO—is used for diverse situations: high-risk percutaneous coronary interventions (PCI), acute decompensated heart failure, cardiogenic shock, and resuscitation after cardiac arrest. The wide adoption of MCS makes it imperative to improve understanding of the effects of MCS on kidney health/function and of kidney health/function on MCS outcomes. The complex structure and functions of the kidney, and the complex health states of individuals receiving MCS, makes investigations in this area challenging, and current knowledge is limited. Fortunately, the increasing nephrology toolbox of noninvasive kidney health/function assessments may enable development and testing of individualized management strategies and therapeutics in the future. We review technology, epidemiology, pathophysiology, clinical considerations, and future directions in MCS and nephrology.Walther, Carl P.Civitello, Andrew B.Liao, Kenneth K.Navaneethan, Sankar D.2022-01-14T13:30:12-08:00doi:10.34067/KID.0003382021hwp:resource-id:kidney360;3/3/569American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, dialysis, durable, kidney, LVAD, mechanical circulatory support, nephrology, temporaryReview ArticleReview Articlereview-article20222022-03-3110.34067/KID.00033820212641-76502022-01-14T13:30:12-08:002022-03-31Kidney360Review Article33569579
- Kidney Injury in Patients Treated with Immune Checkpoint Inhibitors Does Not Meet KDIGO-AKI Criteria10.34067/KID.0006752021Tue, 21 Dec 2021 11:52:25 GMT-08:00Kidney Injury in Patients Treated with Immune Checkpoint Inhibitors Does Not Meet KDIGO-AKI CriteriaVerploegen, Maartje F.A.Boers-Sonderen, Marye J.Piet, BerberWetzels, Jack F.M.2021-12-21T11:52:25-08:00doi:10.34067/KID.0006752021hwp:resource-id:kidney360;3/3/524American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, immune checkpoint inhibitors, KDIGOBrief CommunicationAcute Kidney Injury and ICU NephrologyBrief CommunicationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-03-3110.34067/KID.00067520212641-76502021-12-21T11:52:25-08:002022-03-31Kidney360Brief Communication33524529
- Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: PRO10.34067/KID.0006632020Thu, 19 Aug 2021 01:30:39 GMT-07:00Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: PROChung, Kevin K.Olson, Stephen W.2021-08-19T13:30:39-07:00doi:10.34067/KID.0006632020hwp:resource-id:kidney360;3/3/416American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, blood purification, COVID-19, cytokine storm, debates, extracorporeal, pathogen removal, sepsis, viremiaDebates in NephrologyDebates in Nephrologyresearch-article20222022-03-3110.34067/KID.00066320202641-76502021-08-19T13:30:39-07:002022-03-31Kidney360Debates in Nephrology33416418
- The Role of Kidney Biopsy in Immune Checkpoint Inhibitor-Associated AKI10.34067/KID.0000232022Thu, 13 Jan 2022 10:48:21 GMT-08:00The Role of Kidney Biopsy in Immune Checkpoint Inhibitor-Associated AKIRashidi, ArashShah, ChintanSekulic, Miroslav2022-01-13T10:48:21-08:00doi:10.34067/KID.0000232022hwp:resource-id:kidney360;3/3/530American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, biopsy, immune checkpoint inhibitorsBrief CommunicationAcute Kidney Injury and ICU NephrologyBrief CommunicationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-03-3110.34067/KID.00002320222641-76502022-01-13T10:48:21-08:002022-03-31Kidney360Brief Communication33530533
- Dark Urine in a Dialysis Patient Treated for a Bloodstream Infection10.34067/KID.0007232021Thu, 31 Mar 2022 06:30:32 GMT-07:00Dark Urine in a Dialysis Patient Treated for a Bloodstream InfectionKento, FuruyaNaoya, Itoh2022-03-31T06:30:32-07:00doi:10.34067/KID.0007232021hwp:resource-id:kidney360;3/3/582American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, cefozopran, CKD, dark urine, side effectClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-03-3110.34067/KID.00072320212641-76502022-03-31T06:30:32-07:002022-03-31Kidney360Clinical Images in Nephrology and Dialysis33582583
- Trends in Coronary Artery Disease Screening before Kidney Transplantation10.34067/KID.0005282021Thu, 09 Dec 2021 09:46:05 GMT-08:00Trends in Coronary Artery Disease Screening before Kidney TransplantationCheng, Xingxing S.Liu, SaiHan, JialinStedman, Margaret R.Chertow, Glenn M.Tan, Jane C.Fearon, William F.2021-12-09T09:46:05-08:00doi:10.34067/KID.0005282021hwp:resource-id:kidney360;3/3/516American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, cardiovascular disease, coronary artery disease, epidemiology and outcomes, mass screening, transplantationOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-03-3110.34067/KID.00052820212641-76502021-12-09T09:46:05-08:002022-03-31Kidney360Original Investigation33516523
- Feeding the Kidney Researcher Pipeline through R25-NIDDK Funded Summer Undergraduate Research Fellowships: A Student Perspective10.34067/KID.0001272021Fri, 22 Oct 2021 07:36:31 GMT-07:00Feeding the Kidney Researcher Pipeline through R25-NIDDK Funded Summer Undergraduate Research Fellowships: A Student PerspectiveWilson, Elena M.Lipp, Sarah N.Brady, Clayton T.Ishibe, ShutaRomero, Michael F.2021-10-22T07:36:31-07:00doi:10.34067/KID.0001272021hwp:resource-id:kidney360;3/3/546American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, basic science, clinical, fellowships, nephrology, student, undergraduatePerspectivePerspectiveresearch-article20222022-03-3110.34067/KID.00012720212641-76502021-10-22T07:36:31-07:002022-03-31Kidney360Perspective33546549
- Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: CON10.34067/KID.0007382020Thu, 19 Aug 2021 01:30:39 GMT-07:00Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: CONKashani, KianoushForni, Lui G.2021-08-19T13:30:39-07:00doi:10.34067/KID.0007382020hwp:resource-id:kidney360;3/3/419American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, cytokine storm, debates, extracorporeal purificationDebates in NephrologyDebates in Nephrologyresearch-article20222022-03-3110.34067/KID.00073820202641-76502021-08-19T13:30:39-07:002022-03-31Kidney360Debates in Nephrology33419422
- Artificial Intelligence in the Identification, Management, and Follow-Up of CKD10.34067/KID.0007572021Tue, 18 Jan 2022 06:23:56 GMT-08:00Artificial Intelligence in the Identification, Management, and Follow-Up of CKDTangri, NavdeepFerguson, Thomas W.2022-01-18T06:23:56-08:00doi:10.34067/KID.0007572021hwp:resource-id:kidney360;3/3/554American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, artificial, chronic, intelligence, kidney, learning, machine, statisticsPerspectivePerspectiveresearch-article20222022-03-3110.34067/KID.00075720212641-76502022-01-18T06:23:56-08:002022-03-31Kidney360Perspective33554556
- Effect of Cyclophosphamide and Glucocorticoid Therapy in IgA Nephropathy: A Single-Center Retrospective Analysis10.34067/KID.0006702021Wed, 19 Jan 2022 11:33:25 GMT-08:00Effect of Cyclophosphamide and Glucocorticoid Therapy in IgA Nephropathy: A Single-Center Retrospective AnalysisBeck, NicolasWalz, GerdSchneider, Johanna2022-01-19T11:33:25-08:00doi:10.34067/KID.0006702021hwp:resource-id:kidney360;3/3/506American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, cyclophosphamide, glucocorticoid, hematuria, IgA nephropathy, immunosuppressive therapy, proteinuria, retrospective studiesOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-03-3110.34067/KID.00067020212641-76502022-01-19T11:33:25-08:002022-03-31Kidney360Original Investigation33506515
- Urinary Podocyte Biomarkers and Glomerular Histologic Change10.34067/KID.0008212021Thu, 31 Mar 2022 06:30:32 GMT-07:00Urinary Podocyte Biomarkers and Glomerular Histologic ChangeInoue, Kazunori2022-03-31T06:30:32-07:00doi:10.34067/KID.0008212021hwp:resource-id:kidney360;3/3/407American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, glomerular disease, podocytes, urinary biomarkerEditorialEditorialeditorial20222022-03-3110.34067/KID.00082120212641-76502022-03-31T06:30:32-07:002022-03-31Kidney360Editorial33407409
- CKD Biomarkers, Cognitive Impairment, and Incident Dementia in an Older Healthy Cohort10.34067/KID.0005672021Tue, 07 Dec 2021 11:30:16 GMT-08:00CKD Biomarkers, Cognitive Impairment, and Incident Dementia in an Older Healthy CohortMurray, Anne M.Thao, Le Thi PhuongRyan, JoanneWolfe, RoryWetmore, James B.Woods, Robyn L.Polkinghorne, Kevan R.2021-12-07T11:30:16-08:00doi:10.34067/KID.0005672021hwp:resource-id:kidney360;3/3/435American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, albuminuria, cognitive impairment, cognitive screening, dementia, proteinuriaOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-03-3110.34067/KID.00056720212641-76502021-12-07T11:30:16-08:002022-03-31Kidney360Original Investigation33435445
- Patient-Reported Experiences after Acute Kidney Injury across Multiple Health-Related Quality-of-Life Domains10.34067/KID.0002782021Wed, 08 Dec 2021 02:00:13 GMT-08:00Patient-Reported Experiences after Acute Kidney Injury across Multiple Health-Related Quality-of-Life DomainsSwitzer, Galen E.Puttarajappa, Chethan M.Kane-Gill, Sandra L.Fried, Linda F.Abebe, Kaleab Z.Kellum, John A.Jhamb, ManishaBruce, Jessica G.Kuniyil, VidyaConway, Paul T.Knight, RichardMurphy, JohnPalevsky, Paul M.2021-12-08T14:00:13-08:00doi:10.34067/KID.0002782021hwp:resource-id:kidney360;3/3/426American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, kidney disease, Patient Reported Outcome Measures, quality of lifeOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-03-3110.34067/KID.00027820212641-76502021-12-08T14:00:13-08:002022-03-31Kidney360Original Investigation33426434
- Initial Home Dialysis Is Increased for Rural Patients by Accessing Urban Facilities10.34067/KID.0006932021Tue, 04 Jan 2022 05:02:17 GMT-08:00Initial Home Dialysis Is Increased for Rural Patients by Accessing Urban FacilitiesAdler, Joel T.Husain, S. AliXiang, LingweiRodrigue, James R.Waikar, Sushrut S.2022-01-04T17:02:17-08:00doi:10.34067/KID.0006932021hwp:resource-id:kidney360;3/3/488American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, clinical nephrology, home dialysis, mortality gap, rural population, urban facilitiesOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-03-3110.34067/KID.00069320212641-76502022-01-04T17:02:17-08:002022-03-31Kidney360Original Investigation33488496
- Unexpected Kidney Finding in a Patient with Anemia10.34067/KID.0006262021Thu, 31 Mar 2022 06:30:32 GMT-07:00Unexpected Kidney Finding in a Patient with AnemiaUzu, TakashiMizumoto, AyaMitsumoto, Kensuke2022-03-31T06:30:32-07:00doi:10.34067/KID.0006262021hwp:resource-id:kidney360;3/3/580American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, anemia, biopsy, lymphoma, renal tumorClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-03-3110.34067/KID.00062620212641-76502022-03-31T06:30:32-07:002022-03-31Kidney360Clinical Images in Nephrology and Dialysis33580581
- Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: COMMENTARY10.34067/KID.0005242021Thu, 19 Aug 2021 01:30:39 GMT-07:00Extracorporeal Blood Purification Is Appropriate in Critically Ill Patients with COVID-19 and Multiorgan Failure: COMMENTARYOstermann, MarliesKoyner, Jay L.2021-08-19T13:30:39-07:00doi:10.34067/KID.0005242021hwp:resource-id:kidney360;3/3/423American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, blood purification, COVID-19, debatesModerator CommentaryModerator Commentaryarticle-commentary20222022-03-3110.34067/KID.00052420212641-76502021-08-19T13:30:39-07:002022-03-31Kidney360Moderator Commentary33423425
- Prescribing Patterns of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD: A Cross-Sectional Registry Analysis10.34067/KID.0007862021Wed, 19 Jan 2022 01:30:01 GMT-08:00Prescribing Patterns of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD: A Cross-Sectional Registry AnalysisZhuo, MinLi, JiahuaBuckley, Leo F.Tummalapalli, Sri LekhaMount, David B.Steele, David J.R.Lucier, David J.Mendu, Mallika L.2022-01-19T13:30:01-08:00doi:10.34067/KID.0007862021hwp:resource-id:kidney360;3/3/455American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease (CKD), diabetes, prescribing patterns, registry analysis, sodium-glucose cotransporter-2 inhibitors (SGLT-2i)Original InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-03-3110.34067/KID.00078620212641-76502022-01-19T13:30:01-08:002022-03-31Kidney360Original Investigation33455464
- Drug-Induced Osmotic Nephropathy: Add SGLT2-Inhibitors to the List?10.34067/KID.0007882021Tue, 21 Dec 2021 01:32:50 GMT-08:00Drug-Induced Osmotic Nephropathy: Add SGLT2-Inhibitors to the List?Perazella, Mark A.Juncos, Luis A.2021-12-21T13:32:50-08:00doi:10.34067/KID.0007882021hwp:resource-id:kidney360;3/3/550American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, contrast, dextran, hydroxyethyl starch, mannitol, osmotic nephropathy, renal tubular epithelial cells, SGLT2 inhibitors, sucrosePerspectivePerspectiveresearch-article20222022-03-3110.34067/KID.00078820212641-76502021-12-21T13:32:50-08:002022-03-31Kidney360Perspective33550553
- Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials10.34067/KID.0006672021Wed, 19 Jan 2022 11:33:25 GMT-08:00Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Serum Electrolyte Levels in Patients with Type 2 Diabetes: A Pairwise and Network Meta-Analysis of Randomized Controlled TrialsZhang, JingjingHuan, YonghongLeibensperger, MarkSeo, BojungSong, Yiqing2022-01-19T11:33:25-08:00doi:10.34067/KID.0006672021hwp:resource-id:kidney360;3/3/477American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360diabetes and the kidney, calcium, diabetes mellitus, electrolytes, magnesium, meta-analysis, phosphate, potassium, SGLT2 inhibitor, sodium, type 2 diabetesOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20222022-03-3110.34067/KID.00066720212641-76502022-01-19T11:33:25-08:002022-03-31Kidney360Original Investigation33477487
- Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney Disease10.34067/KID.0004292021Wed, 08 Dec 2021 05:27:57 GMT-08:00Asymptomatic Pyuria as a Prognostic Biomarker in Autosomal Dominant Polycystic Kidney DiseaseJones, Brian E.Mkhaimer, Yaman G.Rangel, Laureano J.Chedid, MarounSchulte, Phillip J.Mohamed, Alaa K.Neal, Reem M.Zubidat, DaliaRandhawa, Amarjyot K.Hanna, ChristianGregory, Adriana V.Kline, Timothy L.Zoghby, Ziad M.Senum, Sarah R.Harris, Peter C.Torres, Vicente E.Chebib, Fouad T.2021-12-08T05:27:57-08:00doi:10.34067/KID.0004292021hwp:resource-id:kidney360;3/3/465American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, biomarkers, chronic inflammation, disease stratification, glomerular filtration rate, polycystic kidney disease, prognosis, pyuria, rapid progressionOriginal InvestigationCystic Kidney DiseaseOriginal InvestigationCystic Kidney Diseaseresearch-article20222022-03-3110.34067/KID.00042920212641-76502021-12-08T05:27:57-08:002022-03-31Kidney360Original Investigation33465476
- Three-Dimensional Super-Resolved Imaging of Paraffin-Embedded Kidney Samples10.34067/KID.0005882021Fri, 03 Dec 2021 08:09:40 GMT-08:00Three-Dimensional Super-Resolved Imaging of Paraffin-Embedded Kidney SamplesUnnersjö-Jess, DavidRamdedovic, AmerHöhne, MartinButt, LinusKoehler, Felix C.Müller, Roman-UlrichHoyer, Peter F.Blom, HansSchermer, BernhardBenzing, Thomas2021-12-03T08:09:40-08:00doi:10.34067/KID.0005882021hwp:resource-id:kidney360;3/3/446American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360CKD, diagnostic imaging, foot processes, microscopy, paraffin embedding, renal pathology routine diagnostic testsOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-03-3110.34067/KID.00058820212641-76502021-12-03T08:09:40-08:002022-03-31Kidney360Original Investigation33446454
- Evaluation of Suspected Autosomal Alport Syndrome Synonymous Variants10.34067/KID.0005252021Thu, 14 Oct 2021 09:25:28 GMT-07:00Evaluation of Suspected Autosomal Alport Syndrome Synonymous VariantsRossanti, RiniHorinouchi, TomokoYamamura, TomohikoNagano, ChinaSakakibara, NanaIshiko, ShinyaAoto, YuyaKondo, AtsushiNagai, SadayukiOkada, EriIshimori, ShingoNagase, HiroakiMatsui, SatoshiTamagaki, KeiichiUbara, YoshifumiNagahama, MasahikoShima, YukoNakanishi, KoichiNinchoji, TakeshiMatsuo, MasafumiIijima, KazumotoNozu, Kandai2021-10-14T09:25:28-07:00doi:10.34067/KID.0005252021hwp:resource-id:kidney360;3/3/497American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360genetics, Alport syndrome, basic science, COL4A3, COL4A4, silent mutation, splicing assay, synonymous variantOriginal InvestigationGeneticsOriginal InvestigationGeneticsresearch-article20222022-03-3110.34067/KID.00052520212641-76502021-10-14T09:25:28-07:002022-03-31Kidney360Original Investigation33497505
- Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0000622022 and the CON: 10.34067/KID.0000092022atolwani@uabmc.edu10.34067/KID.0002002022Fri, 25 Mar 2022 01:37:16 GMT-07:00Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0000622022 and the CON: 10.34067/KID.0000092022Neyra, Javier A.Tolwani, Ashita2022-03-25T13:37:16-07:00doi:10.34067/KID.0002002022hwp:resource-id:kidney360;KID.0002002022v2American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Nephrologists, Intensive Care Units, Renal Replacement TherapyModerator CommentaryModerator Commentaryother202210.34067/KID.00020020222641-76502641-76502022-03-25T13:37:16-07:00Kidney360Moderator Commentary10.34067/KID.0002002022
- Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0000622022 and the COMMENTARY: 10.34067/KID.0002002022bagshaw@ualberta.ca10.34067/KID.0000092022Fri, 25 Mar 2022 01:37:16 GMT-07:00Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0000622022 and the COMMENTARY: 10.34067/KID.0002002022Bagshaw, Sean M.2022-03-25T13:37:16-07:00doi:10.34067/KID.0000092022hwp:resource-id:kidney360;KID.0000092022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Nephrologists, Intensive Care Units, Renal Replacement TherapyDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00000920222641-76502641-76502022-03-25T13:37:16-07:00Kidney360Debates in Nephrology10.34067/KID.0000092022
- Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0000092022 and the COMMENTARY: 10.34067/KID.0002002022palevsky@pitt.edu10.34067/KID.0000622022Fri, 25 Mar 2022 01:37:16 GMT-07:00Nephrologists rather than intensivists should manage kidney replacement therapy in the ICU: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0000092022 and the COMMENTARY: 10.34067/KID.0002002022Palevsky, Paul M.Wald, Ron2022-03-25T13:37:16-07:00doi:10.34067/KID.0000622022hwp:resource-id:kidney360;KID.0000622022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360critical care nephrology, acute kidney injury, continuous kidney replacement therapy, hemodialysis, dialysis, critical care, Nephrologists, Intensive Care UnitsDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00006220222641-76502641-76502022-03-25T13:37:16-07:00Kidney360Debates in Nephrology10.34067/KID.0000622022
- Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007162021 and the COMMENTARY: 10.34067/KID.0001692022Adnan.Sharif@uhb.nhs.uk10.34067/KID.0007592020Tue, 08 Mar 2022 01:04:13 GMT-08:00Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: PROThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the CON: 10.34067/KID.0007162021 and the COMMENTARY: 10.34067/KID.0001692022Sharif, Adnan2022-03-08T13:04:13-08:00doi:10.34067/KID.0007592020hwp:resource-id:kidney360;KID.0007592020v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360Cardiac, Screening, Kidney transplant, Assessment, Mortality, Cardiovascular disease, RevascularizationDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00075920202641-76502641-76502022-03-08T13:04:13-08:00Kidney360Debates in Nephrology3312122008200810.34067/KID.000759202020122012
- Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007592020 and the COMMENTARY: 10.34067/KID.0001692022jiun-ruey.hu@yale.edu10.34067/KID.0007162021Tue, 08 Mar 2022 01:04:13 GMT-08:00Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: CONThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007592020 and the COMMENTARY: 10.34067/KID.0001692022Hu, Jiun-RueySugeng, Lissa2022-03-08T13:04:13-08:00doi:10.34067/KID.0007162021hwp:resource-id:kidney360;KID.0007162021v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360cardiology, stress testing, transplant candidates, risk stratification, angina, symptomsDebates in NephrologyDebates in Nephrologyother202210.34067/KID.00071620212641-76502641-76502022-03-08T13:04:13-08:00Kidney360Debates in Nephrology3312122013201310.34067/KID.000716202120162016
- Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007592020 and the CON: 10.34067/KID.0007162021hart1044@umn.edu10.34067/KID.0001692022Tue, 08 Mar 2022 01:04:13 GMT-08:00Routine cardiac stress testing in kidney transplant candidates is only appropriate in symptomatic individuals: COMMENTARYThis is an Early Access article. Please select the PDF button, above, to view it. Be sure to also read the PRO: 10.34067/KID.0007592020 and the CON: 10.34067/KID.0007162021Hart, AllysonWang, Jeffrey H.2022-03-08T13:04:13-08:00doi:10.34067/KID.0001692022hwp:resource-id:kidney360;KID.0001692022v1American Society of NephrologyCopyright © 2022 American Society of NephrologyKidney360cardiac screening, Kidney TransplantationModerator CommentaryModerator Commentaryother202210.34067/KID.00016920222641-76502641-76502022-03-08T13:04:13-08:00Kidney360Moderator Commentary3312122017201710.34067/KID.000169202220182018
- How I Treat Complement-Mediated TMA10.2215/CJN.13581021Mon, 24 Jan 2022 08:05:29 GMT-08:00How I Treat Complement-Mediated TMASperati, C. John2022-01-24T08:05:29-08:00doi:10.2215/CJN.13581021hwp:resource-id:clinjasn;17/3/452American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycomplement, hemolytic uremic syndrome, glomerulonephritisKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-03-01March 202210.2215/CJN.135810211555-90411555-905X2022-01-24T08:05:29-08:002022-03Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat173452454
- Will New Treatment Options for Lupus Nephritis Be Affordable?10.2215/CJN.00690122Fri, 04 Feb 2022 11:09:02 GMT-08:00Will New Treatment Options for Lupus Nephritis Be Affordable?Teng, Y.K. OnnoRabelink, Ton J.2022-02-04T11:09:02-08:00doi:10.2215/CJN.00690122hwp:resource-id:clinjasn;17/3/340American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, glomerulonephritis, belimumab, voclosporinEditorialEditorialeditorial20222022-03-01March 202210.2215/CJN.006901221555-90411555-905X2022-02-04T11:09:02-08:002022-03Clinical Journal of the American Society of NephrologyEditorial1733340385341394
- Can Novel Potassium Binders Liberate People with Chronic Kidney Disease from the Low-Potassium Diet?The advent of new potassium binders provides an important breakthrough in the chronic management of hyperkalemia for people with CKD. In addition to the direct benefits of managing hyperkalemia, many researchers and clinicians view these new medications as a possible means to safely transition patients away from the low-potassium diet to a more healthful eating pattern. In this review, we examine the mechanisms of potassium binders in the context of hyperkalemia risk related to dietary potassium intake in people with CKD. We note that whereas these medications target hyperkalemia caused by potassium bioaccumulation, the primary evidence for restricting dietary potassium is risk of postprandial hyperkalemia. The majority of ingested potassium is absorbed alongside endogenously secreted potassium in the small intestines, but the action of these novel medications is predominantly constrained to the large intestine. As a result and despite their effectiveness in lowering basal potassium levels, it remains unclear whether potassium binders would provide protection against hyperkalemia caused by excessive dietary potassium intake in people with CKD. Until this knowledge gap is bridged, clinicians should consider postprandial hyperkalemia risk when removing restrictions on dietary potassium intake in people with CKD on potassium binders.10.2215/CJN.09660721Wed, 20 Oct 2021 07:26:37 GMT-07:00Can Novel Potassium Binders Liberate People with Chronic Kidney Disease from the Low-Potassium Diet?The advent of new potassium binders provides an important breakthrough in the chronic management of hyperkalemia for people with CKD. In addition to the direct benefits of managing hyperkalemia, many researchers and clinicians view these new medications as a possible means to safely transition patients away from the low-potassium diet to a more healthful eating pattern. In this review, we examine the mechanisms of potassium binders in the context of hyperkalemia risk related to dietary potassium intake in people with CKD. We note that whereas these medications target hyperkalemia caused by potassium bioaccumulation, the primary evidence for restricting dietary potassium is risk of postprandial hyperkalemia. The majority of ingested potassium is absorbed alongside endogenously secreted potassium in the small intestines, but the action of these novel medications is predominantly constrained to the large intestine. As a result and despite their effectiveness in lowering basal potassium levels, it remains unclear whether potassium binders would provide protection against hyperkalemia caused by excessive dietary potassium intake in people with CKD. Until this knowledge gap is bridged, clinicians should consider postprandial hyperkalemia risk when removing restrictions on dietary potassium intake in people with CKD on potassium binders.St-Jules, David E.Clegg, Deborah J.Palmer, Biff F.Carrero, Juan-Jesus2021-10-20T07:26:37-07:00doi:10.2215/CJN.09660721hwp:resource-id:clinjasn;17/3/467American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycation exchange resins, diet, potassium, chronic renal insufficiency, chronic kidney diseaseReviewReviewreview-article20222022-03-01March 202210.2215/CJN.096607211555-90411555-905X2021-10-20T07:26:37-07:002022-03Clinical Journal of the American Society of NephrologyReview173467472
- Functional Reserve of the KidneyAn exploration of the normal limits of physiologic responses and how these responses are lost when the kidney is injured rarely occurs in clinical practice. However, the differences between “resting” and “stressed” responses identify an adaptive reactiveness that is diminished before baseline function is impaired. This functional reserve is important in the evaluation of prognosis and progression of kidney disease. Here, we discuss stress tests that examine protein-induced hyperfiltration, proximal tubular secretion, urea-selective concentration defects, and acid retention. We discuss diseases in which these tests have been used to diagnose subclinical injury. The study and follow-up of abnormal functional reserve may add considerable understanding to the natural history of CKD.10.2215/CJN.11070821Wed, 10 Nov 2021 09:47:59 GMT-08:00Functional Reserve of the KidneyAn exploration of the normal limits of physiologic responses and how these responses are lost when the kidney is injured rarely occurs in clinical practice. However, the differences between “resting” and “stressed” responses identify an adaptive reactiveness that is diminished before baseline function is impaired. This functional reserve is important in the evaluation of prognosis and progression of kidney disease. Here, we discuss stress tests that examine protein-induced hyperfiltration, proximal tubular secretion, urea-selective concentration defects, and acid retention. We discuss diseases in which these tests have been used to diagnose subclinical injury. The study and follow-up of abnormal functional reserve may add considerable understanding to the natural history of CKD.Armenta, ArmandoMadero, MagdalenaRodriguez-Iturbe, Bernardo2021-11-10T09:47:59-08:00doi:10.2215/CJN.11070821hwp:resource-id:clinjasn;17/3/458American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney diseaseReviewReviewreview-article20222022-03-01March 202210.2215/CJN.110708211555-90411555-905X2021-11-10T09:47:59-08:002022-03Clinical Journal of the American Society of NephrologyReview173458466
- Hyperkalemia with Mineralocorticoid Receptor Antagonist Use in People with CKD10.2215/CJN.13541021Wed, 01 Dec 2021 10:38:50 GMT-08:00Hyperkalemia with Mineralocorticoid Receptor Antagonist Use in People with CKDEpstein, MurrayPecoits-Filho, RobertoClase, Catherine M.Sood, Manish M.Kovesdy, Csaba P.2021-12-01T10:38:50-08:00doi:10.2215/CJN.13541021hwp:resource-id:clinjasn;17/3/455American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyaldosterone, chronic kidney disease, diabetic nephropathy, hyperkalemiaPerspectivePerspectiveresearch-article20222022-03-01March 202210.2215/CJN.135410211555-90411555-905X2021-12-01T10:38:50-08:002022-03Clinical Journal of the American Society of NephrologyPerspective173455457
- Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial10.2215/CJN.08980621Fri, 21 Jan 2022 01:53:52 GMT-08:00Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE TrialCharytan, David M.Yu, JieJardine, Meg J.Cannon, Christopher P.Agarwal, RajivBakris, GeorgeGreene, TomLevin, AdeeraPollock, CarolPowe, Neil R.Arnott, ClareMahaffey, Kenneth W.2022-01-21T13:53:52-08:00doi:10.2215/CJN.08980621hwp:resource-id:clinjasn;17/3/361American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycanagliflozin, estimated glomerular filtration rate (eGFR), clinical trial, diabetes mellitus, chronic kidney disease, race, disparityOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-03-01March 202210.2215/CJN.089806211555-90411555-905X2022-01-21T13:53:52-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article173361373
- Comparison of Aptamer-Based and Antibody-Based Assays for Protein Quantification in Chronic Kidney Disease10.2215/CJN.11700921Wed, 23 Feb 2022 06:47:04 GMT-08:00Comparison of Aptamer-Based and Antibody-Based Assays for Protein Quantification in Chronic Kidney DiseaseLopez-Silva, CarolinaSurapaneni, AdityaCoresh, JosefReiser, JochenParikh, Chirag R.Obeid, WassimGrams, Morgan E.Chen, Teresa K.2022-02-23T06:47:04-08:00doi:10.2215/CJN.11700921hwp:resource-id:clinjasn;17/3/350American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, end-stage renal disease, mortality, chronic inflammation, antibodies, biological assayOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-03-01March 202210.2215/CJN.117009211555-90411555-905X2022-02-23T06:47:04-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article173350360
- The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States10.2215/CJN.13030921Thu, 03 Feb 2022 02:12:26 GMT-08:00The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United StatesMandrik, OlenaFotheringham, JamesRen, ShijieTice, Jeffrey A.Chapman, Richard H.Stevenson, Matthew D.Pearson, Steven D.Herron-Smith, SerinaAgboola, FolusoThokala, Praveen2022-02-03T14:12:26-08:00doi:10.2215/CJN.13030921hwp:resource-id:clinjasn;17/3/385American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, economic analysis, United States, voclosporin, belimumab, cyclophosphamide, mycophenolate, cost-effectiveness analysisOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-03-01March 202210.2215/CJN.130309211555-90411555-905X2022-02-03T14:12:26-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article1733385340394341
- Volume Progression and Imaging Classification of Polycystic Liver in Early Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.08660621Fri, 25 Feb 2022 07:38:43 GMT-08:00Volume Progression and Imaging Classification of Polycystic Liver in Early Autosomal Dominant Polycystic Kidney DiseaseBae, Kyongtae T.Tao, ChengFeldman, RobertYu, Alan S.L.Torres, Vicente E.Perrone, Ronald D.Chapman, Arlene B.Brosnahan, GodelaSteinman, Theodore I.Braun, William E.Mrug, MichalBennett, William M.Harris, Peter C.Srivastava, AvantikaLandsittel, Douglas P.Abebe, Kaleab Z.,2022-02-25T07:38:43-08:00doi:10.2215/CJN.08660621hwp:resource-id:clinjasn;17/3/374American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, genetic renal disease, kidney volume, liver cysts, polycystic kidney disease, diagnostic imaging, disease progression, liverOriginal ArticleCystic Kidney DiseaseOriginal ArticleCystic Kidney Diseaseresearch-article20222022-03-01March 202210.2215/CJN.086606211555-90411555-905X2022-02-25T07:38:43-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article173374384
- Inflammatory Cells in Nephrectomy Tissue from Patients without and with a History of Urinary Stone Disease10.2215/CJN.11730921Tue, 25 Jan 2022 09:43:06 GMT-08:00Inflammatory Cells in Nephrectomy Tissue from Patients without and with a History of Urinary Stone DiseaseDejban, PegahWilson, Elena M.Jayachandran, MuthuvelHerrera Hernandez, Loren P.Haskic, ZejfaWellik, Linda E.Sinha, SutapaRule, Andrew D.Denic, AleksandarKoo, KevinPotretzke, Aaron M.Lieske, John C.2022-01-25T09:43:06-08:00doi:10.2215/CJN.11730921hwp:resource-id:clinjasn;17/3/414American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycalcification, inflammation, macrophage, medulla, nephrolithiasis, nephrectomy, urologic diseasesOriginal ArticleNephrolithiasisOriginal ArticleNephrolithiasisresearch-article20222022-03-01March 202210.2215/CJN.117309211555-90411555-905X2022-01-25T09:43:06-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article1733414338422339
- Effect of the Refitted Race-Free eGFR Formula on the CKD Prevalence and Mortality in the Danish Population10.2215/CJN.14491121Tue, 11 Jan 2022 09:40:48 GMT-08:00Effect of the Refitted Race-Free eGFR Formula on the CKD Prevalence and Mortality in the Danish PopulationVestergaard, Søren ViborgHeide-Jørgensen, UffeBirn, HenrikChristiansen, Christian Fynbo2022-01-11T09:40:48-08:00doi:10.2215/CJN.14491121hwp:resource-id:clinjasn;17/3/426American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, clinical epidemiology, algorithms, prevalence, mortality, DenmarkResearch LetterResearch Letterletter20222022-03-01March 202210.2215/CJN.144911211555-90411555-905X2022-01-11T09:40:48-08:002022-03Clinical Journal of the American Society of NephrologyResearch Letter173426428
- Exploring the Role of Inflammation toward the Pathogenesis of Calcium Nephrolithiasis10.2215/CJN.00510122Tue, 25 Jan 2022 09:43:06 GMT-08:00Exploring the Role of Inflammation toward the Pathogenesis of Calcium NephrolithiasisSakhaee, Khashayar2022-01-25T09:43:06-08:00doi:10.2215/CJN.00510122hwp:resource-id:clinjasn;17/3/338American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymacrophages, chronic inflammation, calcium nephrolithiasisEditorialEditorialeditorial20222022-03-01March 202210.2215/CJN.005101221555-90411555-905X2022-01-25T09:43:06-08:002022-03Clinical Journal of the American Society of NephrologyEditorial1733338414339422
- De Novo Malignancies after Kidney TransplantationCancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.10.2215/CJN.14570920Mon, 29 Mar 2021 10:58:19 GMT-07:00De Novo Malignancies after Kidney TransplantationCancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.Al-Adra, DavidAl-Qaoud, TalalFowler, KevinWong, Germaine2021-03-29T10:58:19-07:00doi:10.2215/CJN.14570920hwp:resource-id:clinjasn;17/3/434American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, kidney transplantation, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-03-01March 202210.2215/CJN.145709201555-90411555-905X2021-03-29T10:58:19-07:002022-03Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges173434443
- Managing Patients with Failing Kidney AllograftPatients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.10.2215/CJN.14620920Wed, 10 Mar 2021 08:40:38 GMT-08:00Managing Patients with Failing Kidney AllograftPatients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.Davis, ScottMohan, Sumit2021-03-10T08:40:38-08:00doi:10.2215/CJN.14620920hwp:resource-id:clinjasn;17/3/444American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, chronic graft deterioration, transplant nephrectomy, transplant outcomes, allografts, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-03-01March 202210.2215/CJN.146209201555-90411555-905X2021-03-10T08:40:38-08:002022-03Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges173444451
- Utilization of Palliative Care for Patients with COVID-19 and Acute Kidney Injury during a COVID-19 Surge10.2215/CJN.11030821Thu, 24 Feb 2022 06:51:23 GMT-08:00Utilization of Palliative Care for Patients with COVID-19 and Acute Kidney Injury during a COVID-19 SurgeScherer, Jennifer S.Qian, YingzhiRau, Megan E.Soomro, Qandeel H.Sullivan, RyanLinton, JanelleZhong, JudyChodosh, JoshuaCharytan, David M.2022-02-24T06:51:23-08:00doi:10.2215/CJN.11030821hwp:resource-id:clinjasn;17/3/342American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, palliative care, COVID-19, hospice and palliative care nursing, SARS-CoV-2Original ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-03-01March 202210.2215/CJN.110308211555-90411555-905X2022-02-24T06:51:23-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article1733342333349334
- Growing Understanding of the Clinical and Serologic Effects of COVID-19 Vaccines in Patients Undergoing Long-Term Dialysis10.2215/CJN.00320122Thu, 10 Feb 2022 07:07:48 GMT-08:00Growing Understanding of the Clinical and Serologic Effects of COVID-19 Vaccines in Patients Undergoing Long-Term DialysisHundemer, Gregory L.Sood, Manish M.2022-02-10T07:07:48-08:00doi:10.2215/CJN.00320122hwp:resource-id:clinjasn;17/3/335American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19 dialysis, vaccinesEditorialEditorialeditorial20222022-03-01March 202210.2215/CJN.003201221555-90411555-905X2022-02-10T07:07:48-08:002022-03Clinical Journal of the American Society of NephrologyEditorial17333335395403337402413
- Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months10.2215/CJN.12250921Thu, 10 Feb 2022 07:07:49 GMT-08:00Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 MonthsHsu, Caroline M.Weiner, Daniel E.Manley, Harold J.Aweh, Gideon N.Ladik, VladimirFrament, JillMiskulin, DanaArgyropoulos, ChristosAbreo, KennethChin, AndrewGladish, ReginaldSalman, LoayJohnson, DougLacson, Eduardo K.2022-02-10T07:07:49-08:00doi:10.2215/CJN.12250921hwp:resource-id:clinjasn;17/3/403American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, end-stage renal disease, peritoneal dialysis, COVID-19, COVID-19 vaccines, maintenance, SARS-CoV-2Original ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-03-01March 202210.2215/CJN.122509211555-90411555-905X2022-02-10T07:07:49-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article1733403335413337
- Vaccination and COVID-19 Dynamics in Dialysis Patients10.2215/CJN.10300721Thu, 10 Feb 2022 07:07:48 GMT-08:00Vaccination and COVID-19 Dynamics in Dialysis PatientsEl Karoui, KhalilHourmant, MaryvonneAyav, CaroleGlowacki, FrançoisCouchoud, CécileLapidus, Nathanaël,2022-02-10T07:07:48-08:00doi:10.2215/CJN.10300721hwp:resource-id:clinjasn;17/3/395American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, COVID-19, immunology, vaccination, SARS-CoV-2, hospitalization, hemodialysisOriginal ArticleMaintenance DialysisOriginal ArticleMaintenance Dialysisresearch-article20222022-03-01March 202210.2215/CJN.103007211555-90411555-905X2022-02-10T07:07:48-08:002022-03Clinical Journal of the American Society of NephrologyOriginal Article1733395335402337
- Renin-Angiotensin-Aldosterone System Inhibitors and the Risk of AKI in COVID-19 Compared with Influenza10.2215/CJN.11190821Wed, 02 Feb 2022 06:42:04 GMT-08:00Renin-Angiotensin-Aldosterone System Inhibitors and the Risk of AKI in COVID-19 Compared with InfluenzaBirkelo, Bethany C.Parr, Sharidan K.Perkins, Amy M.Greevy, Robert A.Arroyo, Juan PabloHung, Adriana M.Vincz, Andrew J.Shah, Shailja C.Kapoor, TarunMatheny, Michael E.Siew, Edward D.2022-02-02T06:42:04-08:00doi:10.2215/CJN.11190821hwp:resource-id:clinjasn;17/3/423American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyACE inhibitors, acute kidney injury, COVID-19, renin-angiotensin systemResearch LetterResearch Letterletter20222022-03-01March 202210.2215/CJN.111908211555-90411555-905X2022-02-02T06:42:04-08:002022-03Clinical Journal of the American Society of NephrologyResearch Letter173423425
- Catheter-Associated Bloodstream Infections among Patients on HemodialysisMeasures implemented to prevent transmission of severe acute respiratory syndrome coronavirus 2 in outpatient dialysis facilities may also help to prevent catheter-associated bloodstream infections in patients receiving hemodialysis. We used United States Renal Data System data to examine rates of antibiotic administration within dialysis facilities and rates of hospital admission for catheter-associated bloodstream infection from March 2018 through November 2020, and rates of hospitalization for sepsis, to address overall changes in hospitalization during the coronavirus disease 2019 (COVID-19) pandemic. Using logistic regression, we estimated year-over-year adjusted odds ratios of these events in 3-month intervals. During the first 6 months of the pandemic, rates of antibiotic administration were between 20% and 21% lower, and rates of hospitalization for catheter-associated bloodstream infection were between 17% and 24% lower than during corresponding periods in 2019, without significant changes in rates of hospitalization for sepsis. However, rates of catheter-associated events also decreased between 2018 and 2019, driven by reductions in facilities operated by a large dialysis provider. These data suggest that significant reductions in catheter-associated infections occurred during the pandemic, superimposed on nonpandemic-related reductions in some facilities before the pandemic. Even after the pandemic, it may be prudent to continue some COVID-19 mitigation measures to prevent catheter-associated bloodstream infections.10.2215/CJN.11360821Wed, 02 Feb 2022 06:42:04 GMT-08:00Catheter-Associated Bloodstream Infections among Patients on HemodialysisMeasures implemented to prevent transmission of severe acute respiratory syndrome coronavirus 2 in outpatient dialysis facilities may also help to prevent catheter-associated bloodstream infections in patients receiving hemodialysis. We used United States Renal Data System data to examine rates of antibiotic administration within dialysis facilities and rates of hospital admission for catheter-associated bloodstream infection from March 2018 through November 2020, and rates of hospitalization for sepsis, to address overall changes in hospitalization during the coronavirus disease 2019 (COVID-19) pandemic. Using logistic regression, we estimated year-over-year adjusted odds ratios of these events in 3-month intervals. During the first 6 months of the pandemic, rates of antibiotic administration were between 20% and 21% lower, and rates of hospitalization for catheter-associated bloodstream infection were between 17% and 24% lower than during corresponding periods in 2019, without significant changes in rates of hospitalization for sepsis. However, rates of catheter-associated events also decreased between 2018 and 2019, driven by reductions in facilities operated by a large dialysis provider. These data suggest that significant reductions in catheter-associated infections occurred during the pandemic, superimposed on nonpandemic-related reductions in some facilities before the pandemic. Even after the pandemic, it may be prudent to continue some COVID-19 mitigation measures to prevent catheter-associated bloodstream infections.Johansen, Kirsten L.Gilbertson, David T.Wetmore, James B.Peng, YiLiu, JiannongWeinhandl, Eric D.2022-02-02T06:42:04-08:00doi:10.2215/CJN.11360821hwp:resource-id:clinjasn;17/3/429American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUnited States Renal Data System, hemodialysis, vascular access, COVID-19Insights from the USRDSInsights from the USRDSresearch-article20222022-03-01March 202210.2215/CJN.113608211555-90411555-905X2022-02-02T06:42:04-08:002022-03Clinical Journal of the American Society of NephrologyInsights from the USRDS173429433
- COVID-19 and Palliative Care10.2215/CJN.01090122Thu, 24 Feb 2022 07:07:11 GMT-08:00COVID-19 and Palliative CareHickey, Edward V.Conway, Paul T.2022-02-24T07:07:11-08:00doi:10.2215/CJN.01090122hwp:resource-id:clinjasn;17/3/333American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, palliative care, patient insights, patient burden, end of life, dialysis, immunocompromised, immunosuppressedPatient VoicePatient Voiceresearch-article20222022-03-01March 202210.2215/CJN.010901221555-90411555-905X2022-02-24T07:07:11-08:002022-03Clinical Journal of the American Society of NephrologyPatient Voice1733333342334349
- Extracellular Vesicles as Novel Players in Kidney Disease10.1681/ASN.2021091232Mon, 07 Feb 2022 07:20:55 GMT-08:00Extracellular Vesicles as Novel Players in Kidney DiseaseBlijdorp, Charles J.Burger, DylanLlorente, AliciaMartens-Uzunova, Elena S.Erdbrügger, Uta2022-02-07T07:20:55-08:00doi:10.1681/ASN.2021091232hwp:resource-id:jnephrol;33/3/467American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyexosomes, extracellular vesicles, biomarkers, regeneration, Cell SignalingPerspectivePerspectiveresearch-article20222022-03-01March 202210.1681/ASN.20210912321046-66731533-34502022-02-07T07:20:55-08:002022-03Journal of the American Society of NephrologyPerspective333467471
- This Month's Highlights10.1681/ASN.2022010077Mon, 28 Feb 2022 10:00:24 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2022-02-28T10:00:24-08:00doi:10.1681/ASN.2022010077hwp:resource-id:jnephrol;33/3/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20222022-03-01March 202210.1681/ASN.20220100771046-66731533-34502022-02-28T10:00:24-08:002022-03Journal of the American Society of NephrologyThis Month’s Highlights333ii
- Risk Prediction Models for Atherosclerotic Cardiovascular Disease in Patients with Chronic Kidney Disease: The CRIC Study10.1681/ASN.2021060747Thu, 10 Feb 2022 07:47:36 GMT-08:00Risk Prediction Models for Atherosclerotic Cardiovascular Disease in Patients with Chronic Kidney Disease: The CRIC StudyBundy, Joshua D.Rahman, MahboobMatsushita, KunihiroJaeger, Byron C.Cohen, Jordana B.Chen, JingDeo, RajatDobre, Mirela A.Feldman, Harold I.Flack, JohnKallem, Radhakrishna R.Lash, James P.Seliger, StephenShafi, TariqWeiner, Shoshana J.Wolf, MylesYang, WeiAllen, Norrina B.Bansal, NishaHe, Jiang,2022-02-10T07:47:36-08:00doi:10.1681/ASN.2021060747hwp:resource-id:jnephrol;33/3/601American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, clinical epidemiology, risk factors, atherosclerosisClinical EpidemiologyClinical Epidemiologyresearch-article20222022-03-01March 202210.1681/ASN.20210607471046-66731533-34502022-02-10T07:47:36-08:002022-03Journal of the American Society of NephrologyClinical Epidemiology3333601462611464
- Urine Uromodulin and Genetics of its Variation10.1681/ASN.2022010027Mon, 28 Feb 2022 10:00:24 GMT-08:00Urine Uromodulin and Genetics of its VariationFranceschini, NoraLe, Thu H.2022-02-28T10:00:24-08:00doi:10.1681/ASN.2022010027hwp:resource-id:jnephrol;33/3/461American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhuman geneticsUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-03-01March 202210.1681/ASN.20220100271046-66731533-34502022-02-28T10:00:24-08:002022-03Journal of the American Society of NephrologyUp Front Matters3333461511462529
- Natural History of Bone Disease following Kidney Transplantation10.1681/ASN.2021081081Wed, 19 Jan 2022 11:58:37 GMT-08:00Natural History of Bone Disease following Kidney TransplantationJørgensen, Hanne SkouBehets, GeertBammens, BertClaes, KathleenMeijers, BjornNaesens, MaartenSprangers, BenKuypers, Dirk R.J.Cavalier, EtienneD’Haese, PatrickEvenepoel, Pieter2022-01-19T11:58:37-08:00doi:10.1681/ASN.2021081081hwp:resource-id:jnephrol;33/3/638American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymineral metabolism, kidney transplantation, hyperparathyroidism, bone diseases, clinical nephrologyClinical ResearchClinical Researchresearch-article20222022-03-01March 202210.1681/ASN.20210810811046-66731533-34502022-01-19T11:58:37-08:002022-03Journal of the American Society of NephrologyClinical Research333638652
- Autoimmune Podocytopathies: A Novel Sub-Group of Diseases from Childhood Idiopathic Nephrotic Syndrome10.1681/ASN.2021111469Fri, 21 Jan 2022 06:07:08 GMT-08:00Autoimmune Podocytopathies: A Novel Sub-Group of Diseases from Childhood Idiopathic Nephrotic SyndromeYe, QingChen, AnqunLai, En YinMao, Jianhua2022-01-21T06:07:08-08:00doi:10.1681/ASN.2021111469hwp:resource-id:jnephrol;33/3/653American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, clinical nephrology, idiopathic nephrotic syndromeLetter to the EditorLetter to the Editorletter20222022-03-01March 202210.1681/ASN.20211114691046-66731533-34502022-01-21T06:07:08-08:002022-03Journal of the American Society of NephrologyLetter to the Editor33331653654238654654252
- Integrin α5 Is Regulated by miR-218-5p in Endothelial Progenitor Cells10.1681/ASN.2021020140Fri, 28 Jan 2022 10:45:04 GMT-08:00Integrin α5 Is Regulated by miR-218-5p in Endothelial Progenitor CellsLiu, JialingLi, YiLyu, LingnaXiao, LiangMemon, Aliza A.Yu, XinHalim, ArvinPatel, ShivaniOsman, AbdikheyreYin, WenqingJiang, JieNaini, SaidLim, KennethZhang, AifengWilliams, Jonathan D.Koester, RuthQi, Kevin Z.Fucci, Quynh-AnhDing, LaiChang, StevenPatel, AnkitMori, YutaroChaudhari, AdvikaBao, AaronLiu, JiaLu, Tzong-ShiSiedlecki, Andrew2022-01-28T10:45:04-08:00doi:10.1681/ASN.2021020140hwp:resource-id:jnephrol;33/3/565American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyendothelial cells, renal ischemiaBasic ResearchBasic Researchresearch-article20222022-03-01March 202210.1681/ASN.20210201401046-66731533-34502022-01-28T10:45:04-08:002022-03Journal of the American Society of NephrologyBasic Research333565582
- Cardiovascular Risk Prediction Scores in CKD: What Are We Missing?10.1681/ASN.2022010039Thu, 10 Feb 2022 07:23:01 GMT-08:00Cardiovascular Risk Prediction Scores in CKD: What Are We Missing?Soomro, Qandeel H.Charytan, David M.2022-02-10T07:23:01-08:00doi:10.1681/ASN.2022010039hwp:resource-id:jnephrol;33/3/462American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyrisk factors, cardiovascular, CKDUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-03-01March 202210.1681/ASN.20220100391046-66731533-34502022-02-10T07:23:01-08:002022-03Journal of the American Society of NephrologyUp Front Matters3333462601464611
- Authors’ Reply10.1681/ASN.2021111504Wed, 19 Jan 2022 08:51:42 GMT-08:00Authors’ ReplyGuedes, MuriloRobinson, BruceBieber, BrianPecoits-Filho, Roberto2022-01-19T08:51:42-08:00doi:10.1681/ASN.2021111504hwp:resource-id:jnephrol;33/3/655American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyiron deficiencyLetter to the EditorLetter to the Editorletter20222022-03-01March 202210.1681/ASN.20211115041046-66731533-34502022-01-19T08:51:42-08:002022-03Journal of the American Society of NephrologyLetter to the Editor3333865565420206566552030
- Plasma Exchange in ANCA-Associated Vasculitis: For Whom (If Any)?10.1681/ASN.2021121550Mon, 24 Jan 2022 11:41:24 GMT-08:00Plasma Exchange in ANCA-Associated Vasculitis: For Whom (If Any)?Walsh, Michael2022-01-24T11:41:24-08:00doi:10.1681/ASN.2021121550hwp:resource-id:jnephrol;33/3/465American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyapheresis, randomized controlled trials, shared decision making, guidelinesUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-03-01March 202210.1681/ASN.20211215501046-66731533-34502022-01-24T11:41:24-08:002022-03Journal of the American Society of NephrologyUp Front Matters3333465628466637
- Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney Injury10.1681/ASN.2021060757Tue, 11 Jan 2022 09:52:07 GMT-08:00Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events after Acute Kidney InjuryMansour, Sherry G.Bhatraju, Pavan K.Coca, Steven G.Obeid, WassimWilson, Francis P.Stanaway, Ian B.Jia, YaqiThiessen-Philbrook, HeatherGo, Alan S.Ikizler, T. AlpSiew, Edward D.Chinchilli, Vernon M.Hsu, Chi-yuanGarg, Amit X.Reeves, W. BrianLiu, Kathleen D.Kimmel, Paul L.Kaufman, James S.Wurfel, Mark M.Himmelfarb, JonathanParikh, Samir M.Parikh, Chirag R.,2022-01-11T09:52:07-08:00doi:10.1681/ASN.2021060757hwp:resource-id:jnephrol;33/3/613American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyangiopoietin-1, angiopoietin-2, acute kidney injury, chronic kidney disease, heart failure, mortalityClinical ResearchClinical Researchresearch-article20222022-03-01March 202210.1681/ASN.20210607571046-66731533-34502022-01-11T09:52:07-08:002022-03Journal of the American Society of NephrologyClinical Research333333613657627657
- Tissue Culture Models of AKI: From Tubule Cells to Human Kidney OrganoidsAKI affects approximately 13.3 million people around the world each year, causing CKD and/or mortality. The mammalian kidney cannot generate new nephrons after postnatal renal damage and regenerative therapies for AKI are not available. Human kidney tissue culture systems can complement animal models of AKI and/or address some of their limitations. Donor-derived somatic cells, such as renal tubule epithelial cells or cell lines (RPTEC/hTERT, ciPTEC, HK-2, Nki-2, and CIHP-1), have been used for decades to permit drug toxicity screening and studies into potential AKI mechanisms. However, tubule cell lines do not fully recapitulate tubular epithelial cell properties in situ when grown under classic tissue culture conditions. Improving tissue culture models of AKI would increase our understanding of the mechanisms, leading to new therapeutics. Human pluripotent stem cells (hPSCs) can be differentiated into kidney organoids and various renal cell types. Injury to human kidney organoids results in renal cell-type crosstalk and upregulation of kidney injury biomarkers that are difficult to induce in primary tubule cell cultures. However, current protocols produce kidney organoids that are not mature and contain off-target cell types. Promising bioengineering techniques, such as bioprinting and “kidney-on-a-chip” methods, as applied to kidney nephrotoxicity modeling advantages and limitations are discussed. This review explores the mechanisms and detection of AKI in tissue culture, with an emphasis on bioengineered approaches such as human kidney organoid models.10.1681/ASN.2021050693Fri, 14 Jan 2022 08:48:18 GMT-08:00Tissue Culture Models of AKI: From Tubule Cells to Human Kidney OrganoidsAKI affects approximately 13.3 million people around the world each year, causing CKD and/or mortality. The mammalian kidney cannot generate new nephrons after postnatal renal damage and regenerative therapies for AKI are not available. Human kidney tissue culture systems can complement animal models of AKI and/or address some of their limitations. Donor-derived somatic cells, such as renal tubule epithelial cells or cell lines (RPTEC/hTERT, ciPTEC, HK-2, Nki-2, and CIHP-1), have been used for decades to permit drug toxicity screening and studies into potential AKI mechanisms. However, tubule cell lines do not fully recapitulate tubular epithelial cell properties in situ when grown under classic tissue culture conditions. Improving tissue culture models of AKI would increase our understanding of the mechanisms, leading to new therapeutics. Human pluripotent stem cells (hPSCs) can be differentiated into kidney organoids and various renal cell types. Injury to human kidney organoids results in renal cell-type crosstalk and upregulation of kidney injury biomarkers that are difficult to induce in primary tubule cell cultures. However, current protocols produce kidney organoids that are not mature and contain off-target cell types. Promising bioengineering techniques, such as bioprinting and “kidney-on-a-chip” methods, as applied to kidney nephrotoxicity modeling advantages and limitations are discussed. This review explores the mechanisms and detection of AKI in tissue culture, with an emphasis on bioengineered approaches such as human kidney organoid models.Bejoy, JulieQian, Eddie S.Woodard, Lauren E.2022-01-14T08:48:18-08:00doi:10.1681/ASN.2021050693hwp:resource-id:jnephrol;33/3/487American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cisplatin, cisplatin nephrotoxicity, tubule cells, renal proximal tubule cell, podocyte, kidney organoids, kidney-on-a-chip, nephrotoxicity, renal cell biologyReviewReviewreview-article20222022-03-01March 202210.1681/ASN.20210506931046-66731533-34502022-01-14T08:48:18-08:002022-03Journal of the American Society of NephrologyReview333487501
- Mechanisms and Models of Kidney Tubular Necrosis and Nephron LossUnderstanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during AKI, the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. Although mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration versus nephron loss. Unraveling the details of this “switch” must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform the discussion of therapeutic options.10.1681/ASN.2021101293Wed, 12 Jan 2022 09:56:46 GMT-08:00Mechanisms and Models of Kidney Tubular Necrosis and Nephron LossUnderstanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during AKI, the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. Although mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration versus nephron loss. Unraveling the details of this “switch” must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform the discussion of therapeutic options.Maremonti, FrancescaMeyer, ClaudiaLinkermann, Andreas2022-01-12T09:56:46-08:00doi:10.1681/ASN.2021101293hwp:resource-id:jnephrol;33/3/472American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, ferroptosis, necroptosis, cell death, necroinflammation, acute tubular necrosis, nephron lossReviewReviewreview-article20222022-03-01March 202210.1681/ASN.20211012931046-66731533-34502022-01-12T09:56:46-08:002022-03Journal of the American Society of NephrologyReview333472486
- Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD Patients10.1681/ASN.2021081044Wed, 19 Jan 2022 09:24:20 GMT-08:00Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD PatientsRostoker, GuyLepeytre, FannyRottembourg, Jacques2022-01-19T09:24:20-08:00doi:10.1681/ASN.2021081044hwp:resource-id:jnephrol;33/3/654American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynon-dialysis CKD, ferritin, transferrin saturation, mortality, cardiovascular events, inflammationLetter to the EditorLetter to the Editorletter20222022-03-01March 202210.1681/ASN.20210810441046-66731533-34502022-01-19T09:24:20-08:002022-03Journal of the American Society of NephrologyLetter to the Editor3333865465520206556562030
- Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges10.1681/ASN.2021060771Mon, 24 Jan 2022 12:05:46 GMT-08:00Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma ExchangesNezam, DorianPorcher, RaphaëlGrolleau, FrançoisMorel, PaulineTiteca-Beauport, DimitriFaguer, StanislasKarras, AlexandreSolignac, JustineJourde-Chiche, NoémieMaurier, FrançoisSakhi, HamzaEl Karoui, KhalilMesbah, RafikCarron, Pierre LouisAudard, VincentDucloux, DidierPaule, RomainAugusto, Jean-FrançoisAniort, JulienTiple, AurélienRafat, CédricBeaudreuil, SéverinePuéchal, XavierGobert, PierreMassy, ZiadHanrotel, CatherineBally, StéphaneMartis, NihalDurel, Cécile-AudreyDesbuissons, GeoffroyGodmer, PascalHummel, AuréliePerrin, FrançoisNéel, AntoineDe Moreuil, ClaireGoulenok, TiphaineGuerrot, DominiqueGrange, StevenFoucher, AurélieDeroux, AlbanCordonnier, CaroleGuilbeau-Frugier, CélineModesto-Segonds, AnneNochy, DominiqueDaniel, LaurentMoktefi, AnissaRabant, MarionGuillevin, LoïcRégent, AlexisTerrier, Benjamin,2022-01-24T12:05:46-08:00doi:10.1681/ASN.2021060771hwp:resource-id:jnephrol;33/3/628American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyplasma exchange, anti-neutrophil cytoplasmic antibody-associated vasculitis, kidney biopsy, acute kidney injuryClinical ResearchClinical Researchresearch-article20222022-03-01March 202210.1681/ASN.20210607711046-66731533-34502022-01-24T12:05:46-08:002022-03Journal of the American Society of NephrologyClinical Research3333666284651223122463746612241225
- Correction: Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKI10.1681/ASN.2021111482Mon, 28 Feb 2022 10:00:24 GMT-08:00Correction: Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKIAmerican Society of Nephrology2022-02-28T10:00:24-08:00doi:10.1681/ASN.2021111482hwp:resource-id:jnephrol;33/3/657American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin nephrotoxicity, myo-inositol oxygenase, oxidative stress, reactive oxygen species, renal injuryErrataErratacorrection20222022-03-01March 202210.1681/ASN.20211114821046-66731533-34502022-02-28T10:00:24-08:002022-03Journal of the American Society of NephrologyErrata333333657613657627
- Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in Mice10.1681/ASN.2021081099Fri, 21 Jan 2022 09:41:50 GMT-08:00Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in MiceMaeoka, YujiroFerdaus, Mohammed Z.Cornelius, Ryan J.Sharma, AvikaSu, Xiao-TongMiller, Lauren N.Robertson, Joshua A.Gurley, Susan B.Yang, Chao-LingEllison, David H.McCormick, James A.2022-01-21T09:41:50-08:00doi:10.1681/ASN.2021081099hwp:resource-id:jnephrol;33/3/584American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyWNK4, NaCl cotransporter, familial hyperkalemic hypertension, Cullin 3, Kelch-like 3, hypertension, ion transportBasic ResearchBasic Researchresearch-article20222022-03-01March 202210.1681/ASN.20210810991046-66731533-34502022-01-21T09:41:50-08:002022-03Journal of the American Society of NephrologyBasic Research333584600
- Authors’ Reply10.1681/ASN.2021121540Fri, 21 Jan 2022 05:36:13 GMT-08:00Authors’ ReplyWatts, Andrew J.B.Keller, Keith H.Weins, Astrid2022-01-21T05:36:13-08:00doi:10.1681/ASN.2021121540hwp:resource-id:jnephrol;33/3/654-aAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, renal pathology, podocyte, glomerulopathy, chronic kidney disease, nephrotic syndromeLetters to the EditorLetters to the Editorletter20222022-03-01March 202210.1681/ASN.20211215401046-66731533-34502022-01-21T05:36:13-08:002022-03Journal of the American Society of NephrologyLetters to the Editor33331654653238654654252
- Vitamin C Deficiency Causes Cell Type–Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse Model10.1681/ASN.2021070881Tue, 04 Jan 2022 09:36:13 GMT-08:00Vitamin C Deficiency Causes Cell Type–Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse ModelYu, ZihuiXu, ZiyingLiang, YuanYin, PengbinShi, YueYu, JiayiHao, JunfengWang, TingCi, Weimin2022-01-04T09:36:13-08:00doi:10.1681/ASN.2021070881hwp:resource-id:jnephrol;33/3/531American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyvitamin C, DNA methylation, N6-methyladenosine, acute tubular necrosis, renal homeostasis, single-cell RNA sequencing, ascorbic acid deficiency, epigenomicsBasic ResearchBasic Researchresearch-article20222022-03-01March 202210.1681/ASN.20210708811046-66731533-34502022-01-04T09:36:13-08:002022-03Journal of the American Society of NephrologyBasic Research333531546
- Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor–Claudin-14 Pathway10.1681/ASN.2021030392Wed, 12 Jan 2022 09:56:46 GMT-08:00Gentamicin Inhibits Ca2+ Channel TRPV5 and Induces Calciuresis Independent of the Calcium-Sensing Receptor–Claudin-14 Pathwayvan Megen, Wouter H.Beggs, Megan R.An, Sung-WanFerreira, Patrícia G.Lee, Justin J.Wolf, Matthias T.Alexander, R. ToddDimke, Henrik2022-01-12T09:56:46-08:00doi:10.1681/ASN.2021030392hwp:resource-id:jnephrol;33/3/547American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium-sensing receptor, hypercalciuria, gentamicin, kidney tubuleBasic ResearchBasic Researchresearch-article20222022-03-01March 202210.1681/ASN.20210303921046-66731533-34502022-01-12T09:56:46-08:002022-03Journal of the American Society of NephrologyBasic Research333547564
- Recurrence of Anti-Semaphorin 3B–Mediated Membranous Nephropathy after Kidney Transplantation10.1681/ASN.2021101323Tue, 11 Jan 2022 09:52:07 GMT-08:00Recurrence of Anti-Semaphorin 3B–Mediated Membranous Nephropathy after Kidney TransplantationFila, MarcDebiec, HannaPerrochia, HélèneDjouadi, NabilaVerpont, Marie-ChristineBuob, DavidRonco, Pierre2022-01-11T09:52:07-08:00doi:10.1681/ASN.2021101323hwp:resource-id:jnephrol;33/3/503American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulopathy, immunology and pathology, membranous nephropathy, antibodies, semaphorin 3B, pediatric, kidney transplantation, recurrenceRapid CommunicationsRapid Communicationsresearch-article20222022-03-01March 202210.1681/ASN.20211013231046-66731533-34502022-01-11T09:52:07-08:002022-03Journal of the American Society of NephrologyRapid Communications333503509
- Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin10.1681/ASN.2021040491Mon, 28 Feb 2022 10:00:24 GMT-08:00Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of UromodulinJoseph, Christina B.Mariniello, MartaYoshifuji, AyumiSchiano, GuglielmoLake, JenniferMarten, JonathanRichmond, AnneHuffman, Jennifer E.Campbell, ArchieHarris, Sarah E.Troyanov, StephanCocca, MassimilianoRobino, AntoniettaThériault, SébastienEckardt, Kai-UweWuttke, MatthiasCheng, YurongCorre, TanguyKolcic, IvanaBlack, CorrindaBruat, VanessaConcas, Maria PinaSala, CinziaAeschbacher, StefanieSchaefer, FranzBergmann, SvenCampbell, HarryOlden, MatthiasPolasek, OzrenPorteous, David J.Deary, Ian J.Madore, FrancoisAwadalla, PhilipGirotto, GiorgiaUlivi, SheilaConen, DavidWuehl, ElkeOlinger, EricWilson, James F.Bochud, MurielleKöttgen, AnnaHayward, CarolineDevuyst, Olivier2022-02-28T10:00:24-08:00doi:10.1681/ASN.2021040491hwp:resource-id:jnephrol;33/3/511American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycytokeratin, thick ascending limb, Tamm-Horsfall protein, loop of Henle, KRT40, WDR72Meta-AnalysisMeta-Analysisresearch-article20222022-03-01March 202210.1681/ASN.20210404911046-66731533-34502022-02-28T10:00:24-08:002022-03Journal of the American Society of NephrologyMeta-Analysis3333511461529462
- Modelling and Prevention of Acute Kidney Injury through Ischemia and Reperfusion in a Combined Human Renal Proximal Tubule/Blood Vessel-on-a-Chip10.34067/KID.0003622021Thu, 04 Nov 2021 09:28:39 GMT-07:00Modelling and Prevention of Acute Kidney Injury through Ischemia and Reperfusion in a Combined Human Renal Proximal Tubule/Blood Vessel-on-a-ChipVormann, Marianne K.Tool, Laura M.Ohbuchi, MasatoGijzen, Lindavan Vught, RemkoHankemeier, ThomasKiyonaga, FumikoKawabe, TetsuhiroGoto, TakayukiFujimori, AkiraVulto, PaulLanz, Henriette L.Tetsuka, Kazuhiro2021-11-04T09:28:39-07:00doi:10.34067/KID.0003622021hwp:resource-id:kidney360;3/2/217American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360AKI and ICU nephrology, AKI, basic science, coculture, in vitro, kidney-on-a-chip, prevention of renal ischemia damage, proximal tubule, renal ischemiaOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-02-2410.34067/KID.00036220212641-76502021-11-04T09:28:39-07:002022-02-24Kidney360Original Investigation32217231
- Practice What you Preach: The Kidney Diet Challenge10.34067/KID.0006892021Thu, 24 Feb 2022 06:30:37 GMT-08:00Practice What you Preach: The Kidney Diet ChallengePerez, Luis M.Kendrick, Jessica2022-02-24T06:30:37-08:00doi:10.34067/KID.0006892021hwp:resource-id:kidney360;3/2/199American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, diet, kidneyEditorialEditorialeditorial20222022-02-2410.34067/KID.00068920212641-76502022-02-24T06:30:37-08:002022-02-24Kidney360Editorial32199200
- Short- and Long-Term Recovery after Moderate/Severe AKI in Patients with and without COVID-19Farrukh.Koraishy@stonybrookmedicine.edu10.34067/KID.0005342021Mon, 29 Nov 2021 01:32:55 GMT-08:00Short- and Long-Term Recovery after Moderate/Severe AKI in Patients with and without COVID-19Sun, SiaoAnnadi, Raji R.Chaudhri, ImranMunir, KiranHajagos, JanosSaltz, JoelHoai, MinhMallipattu, Sandeep K.Moffitt, RichardKoraishy, Farrukh M.2021-11-29T13:32:55-08:00doi:10.34067/KID.0005342021hwp:resource-id:kidney360;3/2/242American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360AKI and ICU nephrology, AKI, CKD, COVID-19, Machine Learning, mortality, recoveryOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-02-2410.34067/KID.00053420212641-76502021-11-29T13:32:55-08:002022-02-24Kidney360Original Investigation32242257
- Fever, Dysuria, and AKI in a Kidney Transplant Patient10.34067/KID.0003422021Thu, 24 Feb 2022 06:30:37 GMT-08:00Fever, Dysuria, and AKI in a Kidney Transplant PatientAkcasu, EgeSafak, SedaTurkmen, Aydin2022-02-24T06:30:37-08:00doi:10.34067/KID.0003422021hwp:resource-id:kidney360;3/2/403American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, hernia, hydronephrosis, internal hernia, pyelonephritis, renal, supravesical, transplantClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-02-2410.34067/KID.00034220212641-76502022-02-24T06:30:37-08:002022-02-24Kidney360Clinical Images in Nephrology and Dialysis32403404
- Collateral Effects and Mortality of Kidney Transplant Recipients during the COVID-19 Pandemic10.34067/KID.0006472021Thu, 18 Nov 2021 09:22:57 GMT-08:00Collateral Effects and Mortality of Kidney Transplant Recipients during the COVID-19 PandemicSchmidt-Lauber, ChristianGünster, ChristianHuber, Tobias B.Spoden, MelissaGrahammer, Florian2021-11-18T09:22:57-08:00doi:10.34067/KID.0006472021hwp:resource-id:kidney360;3/2/325American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, acute allograft rejection, clinical epidemiology, COVID-19, epidemiology and outcomes, immunosuppression, kidney transplantation, mortality, transplant recipients, transplantationOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-02-2410.34067/KID.00064720212641-76502021-11-18T09:22:57-08:002022-02-24Kidney360Original Investigation32325336
- COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry10.34067/KID.0006612021Fri, 03 Dec 2021 01:28:10 GMT-08:00COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International RegistryWaldman, MerylSoler, Maria JoseGarcía-Carro, ClaraLightstone, LizTurner-Stokes, TabithaGriffith, MeganTorras, JoanMartinez Valenzuela, LauraBestard, OriolGeddes, ColinFlossmann, OliverBudge, Kelly L.Cantarelli, ChiaraFiaccadori, EnricoDelsante, MarcoMorales, EnriqueGutierrez, EduardoNiño-Cruz, Jose A.Martinez-Rueda, Armando J.Comai, GiorgiaBini, ClaudiaLa Manna, GaetanoSlon, Maria F.Manrique, JoaquinAvello, AlejandroFernandez-Prado, RaulOrtiz, AlbertoMarinaki, SmaragdiMartin Varas, Carmen RitaRabasco Ruiz, CristinaSierra-Carpio, MilagrosGarcía-Agudo, RebecaFernández Juárez, GemaHamilton, Alexander J.Bruchfeld, AnnetteChrysochou, ConstantinaHoward, LilianSinha, SmeetaLeach, TimAgraz Pamplona, IreneMaggiore, UmbertoCravedi, Paolo2021-12-03T13:28:10-08:00doi:10.34067/KID.0006612021hwp:resource-id:kidney360;3/2/293American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, COVID-19, follow-up studies, glomerular disease, kidney glomerulus, registriesOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-02-2410.34067/KID.00066120212641-76502021-12-03T13:28:10-08:002022-02-24Kidney360Original Investigation32293306
- Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial10.34067/KID.0005022021Thu, 18 Nov 2021 01:33:14 GMT-08:00Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE TrialWang, Ann A.Cai, XuanSrivastava, AnandPrasad, Pottumarthi V.Sprague, Stuart M.Carr, JamesWolf, MylesIx, Joachim H.Block, Geoffrey A.Chonchol, MichelRaphael, Kalani L.Cheung, Alfred K.Raj, Dominic S.Gassman, Jennifer J.Rahsepar, Amir AliMiddleton, John P.Fried, Linda F.Sarnari, RobertoIsakova, TamaraMehta, Rupal2021-11-18T13:33:14-08:00doi:10.34067/KID.0005022021hwp:resource-id:kidney360;3/2/258American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, albuminuria, cardiac MRI, diastolic dysfunction, mineral metabolismOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-02-2410.34067/KID.00050220212641-76502021-11-18T13:33:14-08:002022-02-24Kidney360Original Investigation32258268
- Left Atrial Appendage Closure: An Alternative to Anticoagulation for Stroke Prevention in Patients with Kidney DiseaseAnticoagulation to reduce thromboembolic stroke risk due to nonvalvular atrial fibrillation in ESKD is associated with increased bleeding. There is an existing debate in ESKD centers around the pros and cons of anticoagulation. We propose percutaneous left atrial appendage occlusion as a third alternative to balance thrombosis and bleeding risks in this high-risk population.srivallurupalli@gmail.com10.34067/KID.0004082021Wed, 08 Dec 2021 01:27:25 GMT-08:00Left Atrial Appendage Closure: An Alternative to Anticoagulation for Stroke Prevention in Patients with Kidney DiseaseAnticoagulation to reduce thromboembolic stroke risk due to nonvalvular atrial fibrillation in ESKD is associated with increased bleeding. There is an existing debate in ESKD centers around the pros and cons of anticoagulation. We propose percutaneous left atrial appendage occlusion as a third alternative to balance thrombosis and bleeding risks in this high-risk population.Vallurupalli, SrikanthSharma, TanyaAl’Aref, SubhiDevabhaktuni, Subodh R.Dhar, Gaurav2021-12-08T13:27:25-08:00doi:10.34067/KID.0004082021hwp:resource-id:kidney360;3/2/396American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, anticoagulants, atrial fibrillation, blood coagulation, left atrial appendage occlusion, strokeReview ArticleReview Articlereview-article20222022-02-2410.34067/KID.00040820212641-76502021-12-08T13:27:25-08:002022-02-24Kidney360Review Article32396402
- Defining Baseline Creatinine for Identification of AKI in Population-Based Laboratory Databases: A Danish Nationwide Cohort Study10.34067/KID.0006082021Mon, 15 Nov 2021 11:52:37 GMT-08:00Defining Baseline Creatinine for Identification of AKI in Population-Based Laboratory Databases: A Danish Nationwide Cohort StudyGraversen, Henriette V.Jensen, Simon K.Vestergaard, Søren V.Heide-Jørgensen, UffeChristiansen, Christian F.2021-11-15T11:52:37-08:00doi:10.34067/KID.0006082021hwp:resource-id:kidney360;3/2/232American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360AKI and ICU nephrology, AKI, creatinine, data management, laboratoriesOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-02-2410.34067/KID.00060820212641-76502021-11-15T11:52:37-08:002022-02-24Kidney360Original Investigation32232241
- Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study10.34067/KID.0005362021Thu, 09 Dec 2021 06:12:34 GMT-08:00Pharmacogenomics of Hypertension in CKD: The CKD-PGX StudyEadon, Michael T.Maddatu, JudithMoe, Sharon M.Sinha, Arjun D.Melo Ferreira, RicardoMiller, Brent W.Sher, S. JawadSu, JingPratt, Victoria M.Chapman, Arlene B.Skaar, Todd C.Moorthi, Ranjani N.Friedman, Allon N.Collins, Kimberly S.Sheth, Nehal A.Spiech, Katherine M.Sharfuddin, Asif A.Gupta, NupurHallab, AymanDoshi, SimitDollins, Matthew D.Tillman, Emma M.Rowe, ElizabethShugg, TylerZarse, Chad A.Bazeley, Jonathan W.Wish, Jay B.Hains, David S.Khalid, MydaSchwantes-An, Tae-HwiMedeiros, Elizabeth B.2021-12-09T06:12:34-08:00doi:10.34067/KID.0005362021hwp:resource-id:kidney360;3/2/307American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360hypertension, blood pressure, CKD-PGX, CYP2C9, CYP2D6, genotype, hypertension, pharmacogenomicsOriginal InvestigationHypertensionOriginal InvestigationHypertensionresearch-article20222022-02-2410.34067/KID.00053620212641-76502021-12-09T06:12:34-08:002022-02-24Kidney360Original Investigation32307316
- Hypertension Pharmacogenomics in CKD: The Clinical Relevance and Public Health Implications10.34067/KID.0007792021Thu, 24 Feb 2022 06:30:37 GMT-08:00Hypertension Pharmacogenomics in CKD: The Clinical Relevance and Public Health ImplicationsGeng, Ting-TingJafar, Tazeen H.2022-02-24T06:30:37-08:00doi:10.34067/KID.0007792021hwp:resource-id:kidney360;3/2/204American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, hypertension, pharmacogenomics, public healthEditorialEditorialeditorial20222022-02-2410.34067/KID.00077920212641-76502022-02-24T06:30:37-08:002022-02-24Kidney360Editorial32204207
- Functional Drug Screening using Kidney Cells On-A-Chip: Advances in Disease Modeling and Development of Biomarkers10.34067/KID.0007172021Thu, 24 Feb 2022 06:30:37 GMT-08:00Functional Drug Screening using Kidney Cells On-A-Chip: Advances in Disease Modeling and Development of BiomarkersAjay, Amrendra K.2022-02-24T06:30:37-08:00doi:10.34067/KID.0007172021hwp:resource-id:kidney360;3/2/194American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, acute kidney injury, biomarker, drug screening, fibrosis, kidney on-chipEditorialEditorialeditorial20222022-02-2410.34067/KID.00071720212641-76502022-02-24T06:30:37-08:002022-02-24Kidney360Editorial32194198
- The Kidney Diet Challenge: An Experiential Educational Experience10.34067/KID.0001162021Tue, 30 Nov 2021 06:13:18 GMT-08:00The Kidney Diet Challenge: An Experiential Educational ExperienceNorouzi, SaynaLiu, Kyle S.Bustamante, EdlynLa, TonMitch, William E.Pivert, KurtisStaggers, Kristen A.Shusterman, BlakeYuan, Christina M.Raghavan, Rajeev2021-11-30T06:13:18-08:00doi:10.34067/KID.0001162021hwp:resource-id:kidney360;3/2/279American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, chronic kidney disease, education, kidney diet, nephrology fellows, problem-based learningOriginal InvestigationClinical NephrologyOriginal InvestigationClinical Nephrologyresearch-article20222022-02-2410.34067/KID.00011620212641-76502021-11-30T06:13:18-08:002022-02-24Kidney360Original Investigation32279286
- Vascular Suitability for an Endovascular Arteriovenous Fistula: Getting Beyond the Velvet Rope10.34067/KID.0008012021Thu, 24 Feb 2022 06:30:37 GMT-08:00Vascular Suitability for an Endovascular Arteriovenous Fistula: Getting Beyond the Velvet RopeWasse, Haimanot2022-02-24T06:30:37-08:00doi:10.34067/KID.0008012021hwp:resource-id:kidney360;3/2/201American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, AVF, dialysis access, endoAVF, ESKD, ESRD, percutaneous fistulaEditorialEditorialeditorial20222022-02-2410.34067/KID.00080120212641-76502022-02-24T06:30:37-08:002022-02-24Kidney360Editorial32201203
- Feasibility of Creation of an Endovascular Arteriovenous Fistula in Patients Undergoing Preoperative Vascular Mapping10.34067/KID.0004242021Wed, 20 Oct 2021 11:46:20 GMT-07:00Feasibility of Creation of an Endovascular Arteriovenous Fistula in Patients Undergoing Preoperative Vascular MappingAl-Balas, AlianVarma, RakeshSharbidre, KedarAl-Balas, HassanAlmehmi, AmmarAbdel Aal, Ahmed KamelRobbin, Michelle L.Allon, Michael2021-10-20T11:46:20-07:00doi:10.34067/KID.0004242021hwp:resource-id:kidney360;3/2/287American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, AVF, dialysis access, endoAVF, feasibility studies, venous mappingOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-02-2410.34067/KID.00042420212641-76502021-10-20T11:46:20-07:002022-02-24Kidney360Original Investigation32287292
- Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic TherapyHepatorenal syndrome type 1 (HRS-1) is a serious form of AKI that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. Although the diagnostic criteria dictated by the International Club of Ascites provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of acute tubular injury, distinguishing these two causes of AKI has direct implications in management. Therefore, the use of the International Club of Ascites criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1, but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacologic therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible, and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors, and their use should be determined by availability, ease of administration, and attention to optimal risk-benefit balance for each clinical scenario.10.34067/KID.0006722021Fri, 03 Dec 2021 01:28:10 GMT-08:00Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic TherapyHepatorenal syndrome type 1 (HRS-1) is a serious form of AKI that affects individuals with advanced cirrhosis with ascites. Prompt and accurate diagnosis is essential for effective implementation of therapeutic measures that can favorably alter its clinical course. Despite decades of investigation, HRS-1 continues to be primarily a diagnosis of exclusion. Although the diagnostic criteria dictated by the International Club of Ascites provide a useful framework to approach the diagnosis of HRS-1, they do not fully reflect the complexity of clinical scenarios that is often encountered in patients with cirrhosis and AKI. Thus, diagnostic uncertainty is often faced. In particular, the distinction between HRS-1 and acute tubular injury is challenging with the currently available clinical tools. Because treatment of HRS-1 differs from that of acute tubular injury, distinguishing these two causes of AKI has direct implications in management. Therefore, the use of the International Club of Ascites criteria should be enhanced with a more individualized approach and attention to the other phenotypic aspects of HRS-1 and other types of AKI. Liver transplantation is the most effective treatment for HRS-1, but it is only available to a small fraction of the affected patients worldwide. Thus, pharmacologic therapy is necessary. Vasoconstrictors aimed to increase mean arterial pressure constitute the most effective approach. Administration of intravenous albumin is an established co-adjuvant therapy. However, the risk for fluid overload in patients with cirrhosis with AKI is not negligible, and interventions intended to expand or remove volume should be tailored to the specific needs of the patient. Norepinephrine and terlipressin are the most effective vasoconstrictors, and their use should be determined by availability, ease of administration, and attention to optimal risk-benefit balance for each clinical scenario.Velez, Juan Carlos Q.2021-12-03T13:28:10-08:00doi:10.34067/KID.0006722021hwp:resource-id:kidney360;3/2/382American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, cirrhosis, ESLD, hepatorenal syndrome, HRS, HRS-1, HRS-AKI, kidney failure, MAP, vasoconstrictorReview ArticleReview Articlereview-article20222022-02-2410.34067/KID.00067220212641-76502021-12-03T13:28:10-08:002022-02-24Kidney360Review Article32382395
- The Relationship of Kidney Tubule Biomarkers with Brain Imaging in CKD Patients in SPRINTLmmiller@health.ucsd.edu10.34067/KID.0007702021Wed, 08 Dec 2021 09:27:44 GMT-08:00The Relationship of Kidney Tubule Biomarkers with Brain Imaging in CKD Patients in SPRINTMiller, Lindsay M.Kurella Tamura, ManjulaPajewski, Nicholas M.Rifkin, DenaWeiner, DanielMarquine, MariaShlipak, Michael G.Ix, Joachim H.2021-12-08T09:27:44-08:00doi:10.34067/KID.0007702021hwp:resource-id:kidney360;3/2/337American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, biomarkers, brain, kidney tubules, neuroimagingBrief CommunicationChronic Kidney DiseaseBrief CommunicationChronic Kidney Diseaserapid-communication20222022-02-2410.34067/KID.00077020212641-76502021-12-08T09:27:44-08:002022-02-24Kidney360Brief Communication32337340
- Severe AKI in a Patient on Multiple Antimicrobial Agents for Leg Infection10.34067/KID.0006102021Thu, 24 Feb 2022 06:30:37 GMT-08:00Severe AKI in a Patient on Multiple Antimicrobial Agents for Leg InfectionRehan, AnamMoeckel, Gilbert W.Perazella, Mark A.2022-02-24T06:30:37-08:00doi:10.34067/KID.0006102021hwp:resource-id:kidney360;3/2/405American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, acute tubular injury, cast nephropathy, nephrotoxicity, uromodulin, vancomycinClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-02-2410.34067/KID.00061020212641-76502022-02-24T06:30:37-08:002022-02-24Kidney360Clinical Images in Nephrology and Dialysis32405406
- Artificial Intelligence for AKI!Now: Let’s Not Await Plato’s Utopian Republic10.34067/KID.0003472021Thu, 18 Nov 2021 01:33:14 GMT-08:00Artificial Intelligence for AKI!Now: Let’s Not Await Plato’s Utopian RepublicSoranno, Danielle E.Bihorac, AzraGoldstein, Stuart L.Kashani, Kianoush B.Menon, ShinaNadkarni, Girish N.Neyra, Javier A.Pannu, Neesh I.Singh, KarandeepCerda, JorgeKoyner, Jay L.2021-11-18T13:33:14-08:00doi:10.34067/KID.0003472021hwp:resource-id:kidney360;3/2/376American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, artificial intelligence, clinical nephrology, decision support, mortality, patient-centered outcomes, quality of care, risk predictionSpecial ArticleSpecial Articleresearch-article20222022-02-2410.34067/KID.00034720212641-76502021-11-18T13:33:14-08:002022-02-24Kidney360Special Article32376381
- Vancomycin-Associated Cast Nephropathy: Reality or Fantasy?10.34067/KID.0007282021Fri, 03 Dec 2021 08:09:40 GMT-08:00Vancomycin-Associated Cast Nephropathy: Reality or Fantasy?Stokes, Michael B.Stevens, Jacob S.2021-12-03T08:09:40-08:00doi:10.34067/KID.0007282021hwp:resource-id:kidney360;3/2/372American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, acute, cast, injury, kidney, vancomycinPerspectivePerspectiveresearch-article20222022-02-2410.34067/KID.00072820212641-76502021-12-03T08:09:40-08:002022-02-24Kidney360Perspective32372375
- Evaluation of Renal Biomarkers, Including Symmetric Dimethylarginine, following Gentamicin-Induced Proximal Tubular Injury in the RatSymmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and to provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation, including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney, were performed. Before biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed, including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function, SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50- and 100- mg/kg dose levels in the four- and ten-dose treatment groups compared with controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with microalbumin being most responsive and osteopontin least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA compared with other excretory renal function markers in a rat gentamicin acute toxicity model. In this study, serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.10.34067/KID.0006542020Tue, 07 Dec 2021 11:30:16 GMT-08:00Evaluation of Renal Biomarkers, Including Symmetric Dimethylarginine, following Gentamicin-Induced Proximal Tubular Injury in the RatSymmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and to provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days. Serum and urine renal biomarker evaluation, including serum SDMA, hematologic and serum biochemical analysis, urinalysis, and histologic examination of kidney, were performed. Before biologic validation, analytic validation of the SDMA immunoassay for rat serum was performed, including assessment of assay accuracy, precision, analytical sensitivity, linearity, analyte stability, and interference testing. Among markers of excretory renal function, SDMA and serum creatinine increased earliest and at the lowest gentamicin concentrations and were significantly increased in both the 50- and 100- mg/kg dose levels in the four- and ten-dose treatment groups compared with controls. Time- and dose-dependent increases were noted for all urinary biomarkers investigated in this study, with microalbumin being most responsive and osteopontin least responsive for detection of gentamicin-induced injury across dose levels and schedules investigated. The SDMA immunoassay met all set quality requirements assessed in analytical validation. This study is the first to investigate performance of serum SDMA compared with other excretory renal function markers in a rat gentamicin acute toxicity model. In this study, serum SDMA was an earlier biomarker for detection of gentamicin-induced toxicity than serum cystatin C, BUN, and creatinine clearance. The SDMA immunoassay provides a reliable commercially available assay for future renal investigations in rat models.Hamlin, Diane M.Schultze, A. EricCoyne, Michael J.McCrann, Donald J.Mack, RebekahDrake, CorieMurphy, Rachel E.Cross, JulieStrong-Townsend, MarilynYerramilli, MahaLeissinger, Mary K.2021-12-07T11:30:16-08:00doi:10.34067/KID.0006542020hwp:resource-id:kidney360;3/2/341American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, glomerular filtration rate, LC-MS/MS, renal biomarker, Sprague Dawley ratInnovative Technology and MethodologyAcute Kidney Injury and ICU NephrologyInnovative Technology and MethodologyAcute Kidney Injury and ICU Nephrologyresearch-article20222022-02-2410.34067/KID.00065420202641-76502021-12-07T11:30:16-08:002022-02-24Kidney360Innovative Technology and Methodology32341356
- Association of Urine Findings with Metabolic Syndrome Traits in a Population of Patients with Nephrolithiasis10.34067/KID.0002292021Tue, 30 Nov 2021 11:37:53 GMT-08:00Association of Urine Findings with Metabolic Syndrome Traits in a Population of Patients with NephrolithiasisHood, Virginia L.Sternberg, Kevan M.de Waal, DesireeAsplin, John R.Mulligan, CarleyCallas, Peter W.2021-11-30T11:37:53-08:00doi:10.34067/KID.0002292021hwp:resource-id:kidney360;3/2/317American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360nephrolithiasis, kidney calculi, metabolic syndrome, phenotypeOriginal InvestigationNephrolithiasisOriginal InvestigationNephrolithiasisresearch-article20222022-02-2410.34067/KID.00022920212641-76502021-11-30T11:37:53-08:002022-02-24Kidney360Original Investigation32317324
- Assessment of Measurement of Salivary Urea by ATR-FTIR Spectroscopy to Screen for CKDStages of CKD are currently defined by eGFR and require measurement of serum creatinine concentrations. Previous studies have shown a good correlation between salivary and serum urea levels and the stage of CKD. However, quantitative salivary urea assays in current clinical use require costly and labor-intensive commercial kits, which restricts the advantage of using saliva and limits wider applicability as a quick and easy means of assessing renal function. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has been shown to provide a potentially straightforward, reagent-free method for the identification of a range of disease-related biomarkers and is in current clinical use for analyses of the chemical composition of kidney stones. We assessed the feasibility of ATR-FTIR spectroscopy as an alternative method to measure salivary urea in patients with different stages of CKD. The ATR-FTIR spectra of dried saliva samples from six healthy controls and 20 patients with CKD (stages 1–5) were analyzed to provide their urea concentrations. The lower limit of detection of salivary urea by the ATR-FTIR spectroscopy method was 1–2 mM, at the lower end of the clinically relevant range. Statistically significant differences in salivary urea concentrations were demonstrated between healthy subjects (4.1±0.5 mM) and patients with CKD stages 3–5 (CKD stage 3, 6.8±0.7 mM; CKD stage 4, 9.1±1 mM; CKD stage 5, 14.8±1.6 mM). These salivary urea concentrations correlated well with serum urea levels in the same patients measured by an automated analyzer (Spearman rank correlation coefficient of 0.71; P<0.001). The ability of the method to detect and stage CKD was assessed from the sensitivity and specificity parameters of a receiver operating characteristics (ROC) curve analysis. This proof-of-concept study demonstrates that quantitation of salivary urea by ATR-FTIR spectroscopy could provide a viable tool for rapid and cost-effective diagnosis of stages 3–5 CKD.10.34067/KID.0004362021Tue, 21 Dec 2021 09:31:25 GMT-08:00Assessment of Measurement of Salivary Urea by ATR-FTIR Spectroscopy to Screen for CKDStages of CKD are currently defined by eGFR and require measurement of serum creatinine concentrations. Previous studies have shown a good correlation between salivary and serum urea levels and the stage of CKD. However, quantitative salivary urea assays in current clinical use require costly and labor-intensive commercial kits, which restricts the advantage of using saliva and limits wider applicability as a quick and easy means of assessing renal function. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy has been shown to provide a potentially straightforward, reagent-free method for the identification of a range of disease-related biomarkers and is in current clinical use for analyses of the chemical composition of kidney stones. We assessed the feasibility of ATR-FTIR spectroscopy as an alternative method to measure salivary urea in patients with different stages of CKD. The ATR-FTIR spectra of dried saliva samples from six healthy controls and 20 patients with CKD (stages 1–5) were analyzed to provide their urea concentrations. The lower limit of detection of salivary urea by the ATR-FTIR spectroscopy method was 1–2 mM, at the lower end of the clinically relevant range. Statistically significant differences in salivary urea concentrations were demonstrated between healthy subjects (4.1±0.5 mM) and patients with CKD stages 3–5 (CKD stage 3, 6.8±0.7 mM; CKD stage 4, 9.1±1 mM; CKD stage 5, 14.8±1.6 mM). These salivary urea concentrations correlated well with serum urea levels in the same patients measured by an automated analyzer (Spearman rank correlation coefficient of 0.71; P<0.001). The ability of the method to detect and stage CKD was assessed from the sensitivity and specificity parameters of a receiver operating characteristics (ROC) curve analysis. This proof-of-concept study demonstrates that quantitation of salivary urea by ATR-FTIR spectroscopy could provide a viable tool for rapid and cost-effective diagnosis of stages 3–5 CKD.Lin, Tzu-LingEvans, Rhys D.R.Unwin, Robert J.Norman, Jill T.Rich, Peter R.2021-12-21T09:31:25-08:00doi:10.34067/KID.0004362021hwp:resource-id:kidney360;3/2/357American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, basic science, biomarker, CKD, infrared spectroscopy, saliva, spectroscopy, Fourier transform infrared, ureaInnovative Technology and MethodologyChronic Kidney DiseaseInnovative Technology and MethodologyChronic Kidney Diseaseresearch-article20222022-02-2410.34067/KID.00043620212641-76502021-12-21T09:31:25-08:002022-02-24Kidney360Innovative Technology and Methodology32357363
- A Propensity Score–Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease10.34067/KID.0006152021Fri, 03 Dec 2021 01:28:10 GMT-08:00A Propensity Score–Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney DiseaseSeethapathy, RituvanthikaaZhao, SophiaLong, Joshua D.Strohbehn, Ian A.Sise, Meghan E.2021-12-03T13:28:10-08:00doi:10.34067/KID.0006152021hwp:resource-id:kidney360;3/2/269American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, acute kidney injury, antiviral, COVID-19, dialysis, propensity score, remdesivir, SARS-CoV-2Original InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-02-2410.34067/KID.00061520212641-76502021-12-03T13:28:10-08:002022-02-24Kidney360Original Investigation32269278
- Global Perspective on Kidney Transplantation: China10.34067/KID.0003302021Mon, 15 Nov 2021 11:52:37 GMT-08:00Global Perspective on Kidney Transplantation: ChinaZhang, ZijianLiu, ZhijiaShi, Bingyi2021-11-15T11:52:37-08:00doi:10.34067/KID.0003302021hwp:resource-id:kidney360;3/2/364American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, China, kidney transplantationGlobal PerspectiveGlobal Perspectiveresearch-article20212022-02-2410.34067/KID.00033020212641-76502021-11-15T11:52:37-08:002022-02-24Kidney360Global Perspective32364367
- Global Perspective on Kidney Transplantation: Argentina10.34067/KID.0002632021Fri, 10 Sep 2021 01:26:01 GMT-07:00Global Perspective on Kidney Transplantation: ArgentinaMaldonado, Rafael AlbertoBisigniano, Liliana2021-09-10T13:26:01-07:00doi:10.34067/KID.0002632021hwp:resource-id:kidney360;3/2/368American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, Argentina, delay graft function, graft survival, INCUCAI, kidney transplantation, living donation, LLDN, patient survival, SINTRA, transplantation barriersGlobal PerspectiveGlobal Perspectiveresearch-article20222022-02-2410.34067/KID.00026320212641-76502021-09-10T13:26:01-07:002022-02-24Kidney360Global Perspective32368371
- Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: CON10.34067/KID.0007152020Fri, 06 Aug 2021 01:32:05 GMT-07:00Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: CONKshirsagar, Abhijit V.Li, Xiaojuan2021-08-06T13:32:05-07:00doi:10.34067/KID.0007152020hwp:resource-id:kidney360;3/2/211American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, debate, hemodialysis, ironDebates in NephrologyDebates in Nephrologyresearch-article20212022-02-2410.34067/KID.00071520202641-76502021-08-06T13:32:05-07:002022-02-24Kidney360Debates in Nephrology32211213
- Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: COMMENTARY10.34067/KID.0004892021Fri, 06 Aug 2021 01:32:05 GMT-07:00Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: COMMENTARYLiu, Frank2021-08-06T13:32:05-07:00doi:10.34067/KID.0004892021hwp:resource-id:kidney360;3/2/214American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, anemia, chronic kidney disease, debate, ironModerator CommentaryModerator Commentaryarticle-commentary20222022-02-2410.34067/KID.00048920212641-76502021-08-06T13:32:05-07:002022-02-24Kidney360Moderator Commentary32214216
- Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: PRO10.34067/KID.0002442021Fri, 06 Aug 2021 01:32:05 GMT-07:00Proactive High-Dose IV Iron Is Preferred Therapy in ESKD Patients: PROCoyne, Daniel W.2021-08-06T13:32:05-07:00doi:10.34067/KID.0002442021hwp:resource-id:kidney360;3/2/208American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, debate, ferryl iron, hemodialysis, iron, mortalityDebates in NephrologyDebates in Nephrologyresearch-article20222022-02-2410.34067/KID.00024420212641-76502021-08-06T13:32:05-07:002022-02-24Kidney360Debates in Nephrology32208210
- What Patients Teach Us About Patient Engagement in Research10.2215/CJN.16561221Mon, 07 Feb 2022 10:00:33 GMT-08:00What Patients Teach Us About Patient Engagement in ResearchDember, Laura M.2022-02-07T10:00:33-08:00doi:10.2215/CJN.16561221hwp:resource-id:clinjasn;17/2/176American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient engagementEditorialEditorialeditorial20222022-02-01February 202210.2215/CJN.165612211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyEditorial17222176215171178227172
- Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure10.2215/CJN.03720321Mon, 07 Feb 2022 10:00:33 GMT-08:00Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart FailureEmmens, Johanna E.de Borst, Martin H.Boorsma, Eva M.Damman, KevinNavis, Gerjanvan Veldhuisen, Dirk J.Dickstein, KennethAnker, Stefan D.Lang, Chim C.Filippatos, GerasimosMetra, MarcoSamani, Nilesh J.Ponikowski, PiotrNg, Leong L.Voors, Adriaan A.ter Maaten, Jozine M.2022-02-07T10:00:33-08:00doi:10.2215/CJN.03720321hwp:resource-id:clinjasn;17/2/228American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproximal tubule, heart failure, outcomes, renal dysfunctionOriginal ArticleClinical NephrologyOriginal ArticleClinical Nephrologyresearch-article20222022-02-01February 202210.2215/CJN.037203211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article1722228182239183
- Effects of the 2021 CKD-EPI Creatinine eGFR Equation among a National US Veteran Cohort10.2215/CJN.10000721Fri, 19 Nov 2021 08:38:56 GMT-08:00Effects of the 2021 CKD-EPI Creatinine eGFR Equation among a National US Veteran CohortGregg, L. ParkerRichardson, Peter A.Akeroyd, JuliaMatheny, Michael E.Virani, Salim S.Navaneethan, Sankar D.2021-11-19T08:38:56-08:00doi:10.2215/CJN.10000721hwp:resource-id:clinjasn;17/2/283American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrace, eGFR, kidney disease, United States, veterans, glomerular filtration rate, cohort studies, disparityResearch LetterResearch Letterletter20222022-02-01February 202210.2215/CJN.100007211555-90411555-905X2021-11-19T08:38:56-08:002022-02Clinical Journal of the American Society of NephrologyResearch Letter172283285
- Kidney Disease Prevalence in Transgender Individuals10.2215/CJN.04660421Mon, 06 Dec 2021 08:39:14 GMT-08:00Kidney Disease Prevalence in Transgender IndividualsEckenrode, Han E.Gutierrez, Orlando M.Osis, GunarsAgarwal, AnupamCurtis, Lisa M.2021-12-06T08:39:14-08:00doi:10.2215/CJN.04660421hwp:resource-id:clinjasn;17/2/280American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney, transgender, acute kidney injury, chronic kidney diseaseResearch LetterResearch Letterletter20222022-02-01February 202210.2215/CJN.046604211555-90411555-905X2021-12-06T08:39:14-08:002022-02Clinical Journal of the American Society of NephrologyResearch Letter172280282
- Improved Survival after Acute Kidney Injury10.2215/CJN.16351221Mon, 07 Feb 2022 10:00:33 GMT-08:00Improved Survival after Acute Kidney InjuryKashani, KianoushRule, Andrew D.2022-02-07T10:00:33-08:00doi:10.2215/CJN.16351221hwp:resource-id:clinjasn;17/2/179American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, acute renal failure, epidemiology and outcomes, mortalityEditorialEditorialeditorial20222022-02-01February 202210.2215/CJN.163512211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyEditorial1722179184181193
- Induction Therapy in Immunologically Well-Matched Recipients10.2215/CJN.16591221Mon, 07 Feb 2022 10:00:33 GMT-08:00Induction Therapy in Immunologically Well-Matched RecipientsPotluri, Vishnu S.Bloom, Roy D.2022-02-07T10:00:33-08:00doi:10.2215/CJN.16591221hwp:resource-id:clinjasn;17/2/173American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinduction therapyEditorialEditorialeditorial20222022-02-01February 202210.2215/CJN.165912211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyEditorial1722173271175279
- Blood Pressure Management in the Patient with Chronic Kidney Disease10.2215/CJN.13040921Wed, 05 Jan 2022 10:13:41 GMT-08:00Blood Pressure Management in the Patient with Chronic Kidney DiseaseMuntner, PaulCushman, William C.Lerma, Edgar V.2022-01-05T10:13:41-08:00doi:10.2215/CJN.13040921hwp:resource-id:clinjasn;17/2/308American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, chronic kidney diseaseKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-02-01February 202210.2215/CJN.130409211555-90411555-905X2022-01-05T10:13:41-08:002022-02Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat172308310
- Controlled Study of Decision-Making Algorithms for Kidney Replacement Therapy Initiation in Acute Kidney Injury10.2215/CJN.02060221Wed, 15 Dec 2021 10:07:40 GMT-08:00Controlled Study of Decision-Making Algorithms for Kidney Replacement Therapy Initiation in Acute Kidney InjuryKelly, Yvelynne P.Mistry, KavitaAhmed, SalmanShaykevich, ShimonDesai, SonaliLipsitz, Stuart R.Leaf, David E.Mandel, Ernest I.Robinson, EmilyMcMahon, GearoidCzarnecki, Peter G.Charytan, David M.Waikar, Sushrut S.Mendu, Mallika L.2021-12-15T10:07:40-08:00doi:10.2215/CJN.02060221hwp:resource-id:clinjasn;17/2/194American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, renal replacement therapy, biochemical phenomena, algorithmsOriginal ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-02-01February 202210.2215/CJN.020602211555-90411555-905X2021-12-15T10:07:40-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article172194204
- Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients10.2215/CJN.09170721Mon, 07 Feb 2022 10:00:33 GMT-08:00Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant RecipientsEvans, Rhys D.R.Lan, James H.Kadatz, MatthewBrar, SandeepChang, Doris T.McMichael, LachlanGill, JagbirGill, John S.2022-02-07T10:00:33-08:00doi:10.2215/CJN.09170721hwp:resource-id:clinjasn;17/2/271American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute rejection, immunosuppression, kidney transplantation, organ transplant, United States Renal Data SystemOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-02-01February 202210.2215/CJN.091707211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article1717221227117318022791751804
- Introducing Nephrocardiology10.2215/CJN.10940821Fri, 10 Dec 2021 07:07:23 GMT-08:00Introducing NephrocardiologyHatamizadeh, Parta2021-12-10T07:07:23-08:00doi:10.2215/CJN.10940821hwp:resource-id:clinjasn;17/2/311American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, coronary artery disease, electrolytes, heart failure, hemodynamics and vascular regulation, kidney disease, mineral metabolism, risk factors, vascular disease, water-electrolyte balancePerspectivePerspectiveresearch-article20222022-02-01February 202210.2215/CJN.109408211555-90411555-905X2021-12-10T07:07:23-08:002022-02Clinical Journal of the American Society of NephrologyPerspective172311313
- Advancing Patient-Centered Research: Enabling the Patient Voice to Be Heard10.2215/CJN.16401221Mon, 07 Feb 2022 10:00:33 GMT-08:00Advancing Patient-Centered Research: Enabling the Patient Voice to Be HeardFowler, Kevin John2022-02-07T10:00:33-08:00doi:10.2215/CJN.16401221hwp:resource-id:clinjasn;17/2/171American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-centered, patient voice, kidney diseases, patient advocacyPatient VoicePatient Voiceother20222022-02-01February 202210.2215/CJN.164012211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyPatient Voice17222171215176172227178
- Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney Disease10.2215/CJN.08780621Tue, 07 Dec 2021 07:23:50 GMT-08:00Association between TNF Receptors and KIM-1 with Kidney Outcomes in Early-Stage Diabetic Kidney DiseaseWaijer, Simke W.Sen, TahaArnott, ClareNeal, BruceKosterink, Jos G.W.Mahaffey, Kenneth W.Parikh, Chirag R.de Zeeuw, DickPerkovic, VladoNeuen, Brendon L.Coca, Steven G.Hansen, Michael K.Gansevoort, Ron T.Heerspink, Hiddo J.L.2021-12-07T07:23:50-08:00doi:10.2215/CJN.08780621hwp:resource-id:clinjasn;17/2/251American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTNFR-1, TNFR-2, KIM-1, biomarkers, clinical trial design, risk prediction, normoalbuminuria, kidney outcomes, prognosis, hepatitis a virus cellular receptor 1Original ArticleDiabetes and the KidneyOriginal ArticleDiabetes and the Kidneyresearch-article20222022-02-01February 202210.2215/CJN.087806211555-90411555-905X2021-12-07T07:23:50-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article172251259
- Patient and Caregiver Experiences and Attitudes about Their Involvement in Research in Chronic Kidney Disease10.2215/CJN.05960521Mon, 07 Feb 2022 10:00:33 GMT-08:00Patient and Caregiver Experiences and Attitudes about Their Involvement in Research in Chronic Kidney DiseaseGutman, TaliaKelly, AyanoScholes-Robertson, NicoleCraig, Jonathan C.Jesudason, ShilpanjaliTong, Allison2022-02-07T10:00:33-08:00doi:10.2215/CJN.05960521hwp:resource-id:clinjasn;17/2/215American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyconsumer involvement, consumer engagement, patient involvement, patient engagement, patient partnership, chronic kidney diseaseOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-02-01February 202210.2215/CJN.059605211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article17222215171176227172178
- In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury10.2215/CJN.01730221Mon, 07 Feb 2022 10:00:33 GMT-08:00In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney InjurySohaney, RyannYin, HuiyingShahinian, VahaknSaran, RajivBurrows, Nilka RíosPavkov, Meda E.Banerjee, TanushreeHsu, Chi-yuanPowe, NeilSteffick, DianeZivin, KaraHeung, Michael,Saran, RajivShahinian, VahaknHeung, MichaelGillespie, BrendaMorgenstern, HalHerman, WilliamZivin, KaraGipson, DebModi, ZubinBragg-Gresham, JenniferSteffick, DianeHan, YunZhang, XiaosongWyncott, AprilPowe, NeilBanerjee, TanushreeTuot, DelphineHsu, Chi-yuanCoresh, JoeMcCulloch, CharlesCrews, DeidraBurrows, Nilka RíosEberhardt, MarkKoyama, AlainMondesire, JuanitaPavkov, Meda E.Rolka, DeborahSaydah, Sharon2022-02-07T10:00:33-08:00doi:10.2215/CJN.01730221hwp:resource-id:clinjasn;17/2/184American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, mortality, epidemiology and outcomes, veterans, cohort studiesOriginal ArticleAcute Kidney Injury and ICU NephrologyOriginal ArticleAcute Kidney Injury and ICU Nephrologyresearch-article20222022-02-01February 202210.2215/CJN.017302211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article1722184179193181
- The Myeloid-Kidney Interface in Health and DiseaseKidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident proinflammatory and profibrotic macrophages leads to kidney structural damage and scarring after kidney injury. Fibrosis throughout the kidney parenchyma contributes to the progressive functional decline observed in CKD, independent of the etiology. Circulating myeloid cells bearing intrinsic defects also affect the kidney substructures, such as neutrophils activated by autoantibodies that cause GN in ANCA-associated vasculitis. The kidney can also be affected by disorders of myelopoiesis, including myeloid leukemias (acute and chronic myeloid leukemias) and myelodysplastic syndromes. Clonal hematopoiesis of indeterminate potential is a common, newly recognized premalignant clinical entity characterized by clonal expansion of hyperinflammatory myeloid lineage cells that may have significant kidney sequelae. A number of existing therapies in CKD target myeloid cells and inflammation, including glucocorticoid receptor agonists and mineralocorticoid receptor antagonists. The therapeutic indications for these and other myeloid cell-targeted treatments is poised to expand as our understanding of the myeloid-kidney interface evolves.10.2215/CJN.04120321Fri, 10 Sep 2021 07:40:18 GMT-07:00The Myeloid-Kidney Interface in Health and DiseaseKidney homeostasis is highly dependent upon the correct functioning of myeloid cells. These cells form a distributed surveillance network throughout the kidney, where they play an integral role in the response to organ threat. Dysregulation of resident proinflammatory and profibrotic macrophages leads to kidney structural damage and scarring after kidney injury. Fibrosis throughout the kidney parenchyma contributes to the progressive functional decline observed in CKD, independent of the etiology. Circulating myeloid cells bearing intrinsic defects also affect the kidney substructures, such as neutrophils activated by autoantibodies that cause GN in ANCA-associated vasculitis. The kidney can also be affected by disorders of myelopoiesis, including myeloid leukemias (acute and chronic myeloid leukemias) and myelodysplastic syndromes. Clonal hematopoiesis of indeterminate potential is a common, newly recognized premalignant clinical entity characterized by clonal expansion of hyperinflammatory myeloid lineage cells that may have significant kidney sequelae. A number of existing therapies in CKD target myeloid cells and inflammation, including glucocorticoid receptor agonists and mineralocorticoid receptor antagonists. The therapeutic indications for these and other myeloid cell-targeted treatments is poised to expand as our understanding of the myeloid-kidney interface evolves.Vlasschaert, CaitlynMoran, Sarah M.Rauh, Michael J.2021-09-10T07:40:18-07:00doi:10.2215/CJN.04120321hwp:resource-id:clinjasn;17/2/323American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, macrophages, chronic inflammation, fibrosisReviewReviewreview-article20222022-02-01February 202210.2215/CJN.041203211555-90411555-905X2021-09-10T07:40:18-07:002022-02Clinical Journal of the American Society of NephrologyReview172323331
- Use of Race in Kidney Research and MedicineBlack Americans and other racially and ethnically minoritized individuals are disproportionately burdened by higher morbidity and mortality from kidney disease when compared with their White peers. Yet, kidney researchers and clinicians have struggled to fully explain or rectify causes of these inequalities. Many studies have sought to identify hypothesized genetic and/or ancestral origins of biologic or behavioral deficits as singular explanations for racial and ethnic inequalities in kidney health. However, these approaches reinforce essentialist beliefs that racial groups are inherently biologically and behaviorally different. These approaches also often conflate the complex interactions of individual-level biologic differences with aggregated population-level disparities that are due to structural racism (i.e., sociopolitical policies and practices that created and perpetuate harmful health outcomes through inequities of opportunities and resources). We review foundational misconceptions about race, racism, genetics, and ancestry that shape research and clinical practice with a focus on kidney disease and related health outcomes. We also provide recommendations on how to embed key equity-enhancing concepts, terms, and principles into research, clinical practice, and medical publishing standards.10.2215/CJN.04890421Wed, 17 Nov 2021 07:41:13 GMT-08:00Use of Race in Kidney Research and MedicineBlack Americans and other racially and ethnically minoritized individuals are disproportionately burdened by higher morbidity and mortality from kidney disease when compared with their White peers. Yet, kidney researchers and clinicians have struggled to fully explain or rectify causes of these inequalities. Many studies have sought to identify hypothesized genetic and/or ancestral origins of biologic or behavioral deficits as singular explanations for racial and ethnic inequalities in kidney health. However, these approaches reinforce essentialist beliefs that racial groups are inherently biologically and behaviorally different. These approaches also often conflate the complex interactions of individual-level biologic differences with aggregated population-level disparities that are due to structural racism (i.e., sociopolitical policies and practices that created and perpetuate harmful health outcomes through inequities of opportunities and resources). We review foundational misconceptions about race, racism, genetics, and ancestry that shape research and clinical practice with a focus on kidney disease and related health outcomes. We also provide recommendations on how to embed key equity-enhancing concepts, terms, and principles into research, clinical practice, and medical publishing standards.Mohottige, DinushikaBoulware, L. EbonyFord, Chandra L.Jones, CamaraNorris, Keith C.2021-11-17T07:41:13-08:00doi:10.2215/CJN.04890421hwp:resource-id:clinjasn;17/2/314American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrace, racism, ancestry, research, race-consciousness, disparity, equityFeatureFeatureresearch-article20222022-02-01February 202210.2215/CJN.048904211555-90411555-905X2021-11-17T07:41:13-08:002022-02Clinical Journal of the American Society of NephrologyFeature172314322
- A Heartwarming Role of the Proximal Tubules10.2215/CJN.16241221Mon, 07 Feb 2022 10:00:33 GMT-08:00A Heartwarming Role of the Proximal TubulesGranda, Michael L.Kestenbaum, Bryan2022-02-07T10:00:33-08:00doi:10.2215/CJN.16241221hwp:resource-id:clinjasn;17/2/182American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproximal kidney tubulesEditorialEditorialeditorial20222022-02-01February 202210.2215/CJN.162412211555-90411555-905X2022-02-07T10:00:33-08:002022-02Clinical Journal of the American Society of NephrologyEditorial1722182228183239
- The Use of Serological Tests in the Care of Patients with Lupus Nephritis10.2215/CJN.13431021Wed, 01 Dec 2021 10:38:50 GMT-08:00The Use of Serological Tests in the Care of Patients with Lupus NephritisAyoub, IsabelleRovin, Brad H.2021-12-01T10:38:50-08:00doi:10.2215/CJN.13431021hwp:resource-id:clinjasn;17/2/305American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyserologies, auto-antibodies, complement system, lupus nephritisKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-02-01February 202210.2215/CJN.134310211555-90411555-905X2021-12-01T10:38:50-08:002022-02Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat172305307
- Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney Samples10.2215/CJN.07830621Fri, 03 Dec 2021 09:06:28 GMT-08:00Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney SamplesMarechal, EliseJaugey, AdrienTarris, GeorgesPaindavoine, MichelSeibel, JeanMartin, LaurentFunes de la Vega, MathildeCrepin, ThomasDucloux, DidierZanetta, GilbertFelix, SophieBonnot, Pierre HenriBardet, FlorianCormier, LucRebibou, Jean-MichelLegendre, Mathieu2021-12-03T09:06:28-08:00doi:10.2215/CJN.07830621hwp:resource-id:clinjasn;17/2/260American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal pathology, deep learning, prognosis, neural networks, computerOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-02-01February 202210.2215/CJN.078306211555-90411555-905X2021-12-03T09:06:28-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article172260270
- Health-Related Quality-of-Life Trajectories over Time in Older Men and Women with Advanced Chronic Kidney Disease10.2215/CJN.08730621Mon, 24 Jan 2022 08:05:28 GMT-08:00Health-Related Quality-of-Life Trajectories over Time in Older Men and Women with Advanced Chronic Kidney DiseaseChesnaye, Nicholas C.Meuleman, Yvettede Rooij, Esther N.M.Hoogeveen, Ellen K.Dekker, Friedo W.Evans, MariePagels, Agneta A.Caskey, Fergus J.Torino, ClaudiaPorto, GaetanaSzymczak, MaciejDrechsler, ChristianeWanner, ChristophJager, Kitty J.,2022-01-24T08:05:28-08:00doi:10.2215/CJN.08730621hwp:resource-id:clinjasn;17/2/205American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, sex differences, quality of life, agedOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-02-01February 202210.2215/CJN.087306211555-90411555-905X2022-01-24T08:05:28-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article172205214
- Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD10.2215/CJN.08950621Tue, 14 Dec 2021 08:04:44 GMT-08:00Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKDNowak, Kristen L.Farmer-Bailey, HeatherWang, WeiYou, ZhiyingSteele, CortneyCadnapaphornchai, Melissa A.Klawitter, JelenaPatel, NayanaGeorge, DianaJovanovich, AnnaSoranno, Danielle E.Gitomer, BereniceChonchol, Michel2021-12-14T08:04:44-08:00doi:10.2215/CJN.08950621hwp:resource-id:clinjasn;17/2/240American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyoxidative stress, pulse wave velocity, aging, endothelial cells, ADPKDOriginal ArticleCystic Kidney DiseaseOriginal ArticleCystic Kidney Diseaseresearch-article20222022-02-01February 202210.2215/CJN.089506211555-90411555-905X2021-12-14T08:04:44-08:002022-02Clinical Journal of the American Society of NephrologyOriginal Article171726240877250877
- Long-Term Infectious Complications of Kidney TransplantationInfections remain a common complication of solid-organ transplantation. Most infections in the first month after transplant are typically health care–associated infections, whereas late infections, beyond 6–12 months, are community-acquired infections. Opportunistic infections most frequently present in the first 12 months post-transplant and can be modulated on prior exposures and use of prophylaxis. In this review, we summarize the current epidemiology of postkidney transplant infections with a focus on key viral (BK polyomavirus, cytomegalovirus, Epstein-Barr virus, and norovirus), bacterial (urinary tract infections and Clostridioides difficile colitis), and fungal infections. Current guidelines for safe living post-transplant are also summarized. Literature supporting prophylaxis and vaccination is also provided.10.2215/CJN.15971020Tue, 20 Apr 2021 11:01:50 GMT-07:00Long-Term Infectious Complications of Kidney TransplantationInfections remain a common complication of solid-organ transplantation. Most infections in the first month after transplant are typically health care–associated infections, whereas late infections, beyond 6–12 months, are community-acquired infections. Opportunistic infections most frequently present in the first 12 months post-transplant and can be modulated on prior exposures and use of prophylaxis. In this review, we summarize the current epidemiology of postkidney transplant infections with a focus on key viral (BK polyomavirus, cytomegalovirus, Epstein-Barr virus, and norovirus), bacterial (urinary tract infections and Clostridioides difficile colitis), and fungal infections. Current guidelines for safe living post-transplant are also summarized. Literature supporting prophylaxis and vaccination is also provided.Agrawal, AkanshaIson, Michael G.Danziger-Isakov, Lara2021-04-20T11:01:50-07:00doi:10.2215/CJN.15971020hwp:resource-id:clinjasn;17/2/286American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycytomegalovirus, polyomavirus, norovirus, urinary tract infection, histoplasmosis, blastomycosis, coccidioidomycosis, vaccination, kidney transplantation, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-02-01February 202210.2215/CJN.159710201555-90411555-905X2021-04-20T11:01:50-07:002022-02Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges172286295
- Long-Term Care of the Pediatric Kidney Transplant RecipientPediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize the transition to adult-oriented transplant care and long-term outcomes.10.2215/CJN.16891020Wed, 12 May 2021 07:36:09 GMT-07:00Long-Term Care of the Pediatric Kidney Transplant RecipientPediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize the transition to adult-oriented transplant care and long-term outcomes.Fernandez, Hilda E.Foster, Bethany J.2021-05-12T07:36:09-07:00doi:10.2215/CJN.16891020hwp:resource-id:clinjasn;17/2/296American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatric kidney transplantation, transition of care, adherence, risk factors, long-term care, children, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-02-01February 202210.2215/CJN.168910201555-90411555-905X2021-05-12T07:36:09-07:002022-02Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges172296304
- Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD10.1681/ASN.2021060744Fri, 17 Dec 2021 11:42:38 GMT-08:00Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKDBansal, NishaZelnick, Leila R.Reynolds, KristiHarrison, Teresa N.Lee, Ming-SumSinger, Daniel E.Sung, Sue HeeFan, DongjieGo, Alan S.2021-12-17T11:42:38-08:00doi:10.1681/ASN.2021060744hwp:resource-id:jnephrol;33/2/442American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular, chronic renal insufficiency, atrial fibrillationClinical ResearchClinical Researchresearch-article20222022-02-01February 202210.1681/ASN.20210607441046-66731533-34502021-12-17T11:42:38-08:002022-02Journal of the American Society of NephrologyClinical Research332442453
- Automated Segmentation of Kidney Cortex and Medulla in CT Images: A Multisite Evaluation Study10.1681/ASN.2021030404Tue, 07 Dec 2021 07:24:09 GMT-08:00Automated Segmentation of Kidney Cortex and Medulla in CT Images: A Multisite Evaluation StudyKorfiatis, PanagiotisDenic, AleksandarEdwards, Marie E.Gregory, Adriana V.Wright, Darryl E.Mullan, AidanAugustine, JoshuaRule, Andrew D.Kline, Timothy L.2021-12-07T07:24:09-08:00doi:10.1681/ASN.2021030404hwp:resource-id:jnephrol;33/2/420American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney cortex, kidney medulla, kidney volume, deep learning, segmentation, computed tomography, machine learning collectionClinical ResearchClinical Researchresearch-article20222022-02-01February 202210.1681/ASN.20210304041046-66731533-34502021-12-07T07:24:09-08:002022-02Journal of the American Society of NephrologyClinical Research332420430
- Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney Injury10.1681/ASN.2021030383Wed, 19 Jan 2022 09:39:06 GMT-08:00Bone Marrow–Derived RIPK3 Mediates Kidney Inflammation in Acute Kidney InjuryMartin-Sanchez, DiegoGuerrero-Mauvecin, JuanFontecha-Barriuso, MiguelMendez-Barbero, NereaSaiz, Maria LauraLopez-Diaz, Ana M.Sanchez-Niño, Maria D.Carrasco, SusanaCannata-Ortiz, PabloRuiz-Ortega, MartaOrtiz, AlbertoSanz, Ana B.2022-01-19T09:39:06-08:00doi:10.1681/ASN.2021030383hwp:resource-id:jnephrol;33/2/357American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, kidney, inflammation, bone marrow-derived leukocytes, RIPK3, TWEAK, NLRP3Basic ResearchBasic Researchresearch-article20222022-02-01February 202210.1681/ASN.20210303831046-66731533-34502022-01-19T09:39:06-08:002022-02Journal of the American Society of NephrologyBasic Research332357373
- The Trifecta Study: Comparing Plasma Levels of Donor-derived Cell-Free DNA with the Molecular Phenotype of Kidney Transplant Biopsies10.1681/ASN.2021091191Thu, 20 Jan 2022 07:40:42 GMT-08:00The Trifecta Study: Comparing Plasma Levels of Donor-derived Cell-Free DNA with the Molecular Phenotype of Kidney Transplant BiopsiesHalloran, Philip F.Reeve, JeffMadill-Thomsen, Katelynn S.Demko, ZacharyPrewett, AdamBillings, Paul,2022-01-20T07:40:42-08:00doi:10.1681/ASN.2021091191hwp:resource-id:jnephrol;33/2/387American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycell-free DNA, rejection, transplantation, microarrays, genomics, biopsy, blood donors, phenotypeClinical ResearchClinical Researchresearch-article20222022-02-01February 202210.1681/ASN.20210911911046-66731533-34502022-01-20T07:40:42-08:002022-02Journal of the American Society of NephrologyClinical Research3322387256400258
- Cisplatin-Induced Kidney Injury: Delivering the Goods10.1681/ASN.2021121591Mon, 31 Jan 2022 10:00:27 GMT-08:00Cisplatin-Induced Kidney Injury: Delivering the GoodsCurry, Joshua N.McCormick, James A.2022-01-31T10:00:27-08:00doi:10.1681/ASN.2021121591hwp:resource-id:jnephrol;33/2/255American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin nephrotoxicity, renalase, chronic kidney disease, acute kidney injuryUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-02-01February 202210.1681/ASN.20211215911046-66731533-34502022-01-31T10:00:27-08:002022-02Journal of the American Society of NephrologyUp Front Matters3322255342256356
- Arteritis Status and Renal Involvement in ANCA-Associated Vasculitis10.1681/ASN.2021091236Mon, 31 Jan 2022 10:00:27 GMT-08:00Arteritis Status and Renal Involvement in ANCA-Associated VasculitisAendekerk, Joop P.Timmermans, Sjoerd A.M.E.G.Busch, Matthias H.van Paassen, Pieter,2022-01-31T10:00:27-08:00doi:10.1681/ASN.2021091236hwp:resource-id:jnephrol;33/2/457American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, vasculitis, renal pathology, ESRD, survival, anti-neutrophil cytoplasmic antibody-associated vasculitisLetter to the EditorLetter to the Editorletter20222022-02-01February 202210.1681/ASN.20210912361046-66731533-34502022-01-31T10:00:27-08:002022-02Journal of the American Society of NephrologyLetter to the Editor3322945745823624584592374
- Authors’ Reply10.1681/ASN.2021111417Mon, 31 Jan 2022 10:00:27 GMT-08:00Authors’ ReplyWetmore, James B.Johansen, Kirsten L.Weinhandl, Eric D.2022-01-31T10:00:27-08:00doi:10.1681/ASN.2021111417hwp:resource-id:jnephrol;33/2/455-aAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, dialysis, end stage kidney diseaseLetter to the EditorLetter to the Editorletter20222022-02-01February 202210.1681/ASN.20211114171046-66731533-34502022-01-31T10:00:27-08:002022-02Journal of the American Society of NephrologyLetter to the Editor33221145545529484574552957
- This Month's Highlights10.1681/ASN.2021121604Mon, 31 Jan 2022 10:00:27 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2022-01-31T10:00:27-08:00doi:10.1681/ASN.2021121604hwp:resource-id:jnephrol;33/2/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20222022-02-01February 202210.1681/ASN.20211216041046-66731533-34502022-01-31T10:00:27-08:002022-02Journal of the American Society of NephrologyThis Month’s Highlights332ii
- Confirmed Drop in Treatment of Patients with Incident End-Stage Kidney Disease During the Novel Coronavirus Disease 2019 Pandemic10.1681/ASN.2021101296Mon, 31 Jan 2022 10:00:27 GMT-08:00Confirmed Drop in Treatment of Patients with Incident End-Stage Kidney Disease During the Novel Coronavirus Disease 2019 PandemicJacobs, LucasDevresse, ArnaudBaudoux, ThomasCollart, Frédéric2022-01-31T10:00:27-08:00doi:10.1681/ASN.2021101296hwp:resource-id:jnephrol;33/2/455American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, epidemiology and outcomes, hemodialysis, peritoneal dialysis, transplantation, COVID-19, SARS-CoV-2Letter to the EditorLetter to the Editorletter20222022-02-01February 202210.1681/ASN.20211012961046-66731533-34502022-01-31T10:00:27-08:002022-02Journal of the American Society of NephrologyLetter to the Editor33221145545529484554572957
- Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression10.1681/ASN.2021070948Fri, 03 Dec 2021 08:58:49 GMT-08:00Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease ProgressionNeuen, Brendon L.Tighiouart, HocineHeerspink, Hiddo J.L.Vonesh, Edward F.Chaudhari, JuhiMiao, ShiyuanChan, Tak MaoFervenza, Fernando C.Floege, JürgenGoicoechea, MarianHerrington, William G.Imai, EnyuJafar, Tazeen H.Lewis, Julia B.Li, Philip Kam-TaoLocatelli, FrancescoMaes, Bart D.Perrone, Ronald D.Praga, ManuelPerna, AnnalisaSchena, Francesco P.Wanner, ChristophWetzels, Jack F.M.Woodward, MarkXie, DiGreene, TomInker, Lesley A.,2021-12-03T08:58:49-08:00doi:10.1681/ASN.2021070948hwp:resource-id:jnephrol;33/2/291American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, acute decline in GFR, randomized controlled trialsMeta-AnalysisMeta-Analysisresearch-article20222022-02-01February 202210.1681/ASN.20210709481046-66731533-34502021-12-03T08:58:49-08:002022-02Journal of the American Society of NephrologyMeta-Analysis332291303
- Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1-Uox Double Knockout Mice10.1681/ASN.2021050616Fri, 19 Nov 2021 08:22:41 GMT-08:00Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1-Uox Double Knockout MiceHosoya, TakujiUchida, ShunyaShibata, ShigeruTomioka, Naoko H.Matsumoto, KojiHosoyamada, Makoto2021-11-19T08:22:41-08:00doi:10.1681/ASN.2021050616hwp:resource-id:jnephrol;33/2/326American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal hypouricemia (RHUC), urate transporter 1 (URAT1), exercise-induced acute kidney injury (EIAKI), hypoxanthine phosphoribosyltransferase (HPRT), xanthine oxidoreductase inhibitor (XOI), mice, knockout, renal tubular transport, inborn errors, urolithiasisBasic ResearchBasic Researchresearch-article20222022-02-01February 202210.1681/ASN.20210506161046-66731533-34502021-11-19T08:22:41-08:002022-02Journal of the American Society of NephrologyBasic Research332326341
- Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and MechanismsKidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.10.1681/ASN.2021091257Tue, 14 Dec 2021 07:50:01 GMT-08:00Secondary Immunodeficiency Related to Kidney Disease (SIDKD)—Definition, Unmet Need, and MechanismsKidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.Steiger, StefanieRossaint, JanZarbock, AlexanderAnders, Hans-Joachim2021-12-14T07:50:01-08:00doi:10.1681/ASN.2021091257hwp:resource-id:jnephrol;33/2/259American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, immunodeficiency, infection, chronic inflammationReviewReviewreview-article20222022-02-01February 202210.1681/ASN.20210912571046-66731533-34502021-12-14T07:50:01-08:002022-02Journal of the American Society of NephrologyReview332259278
- Effect of a 3-Year Lifestyle Intervention in Patients with Chronic Kidney Disease: A Randomized Clinical Trial10.1681/ASN.2021050668Fri, 10 Dec 2021 07:22:40 GMT-08:00Effect of a 3-Year Lifestyle Intervention in Patients with Chronic Kidney Disease: A Randomized Clinical TrialBeetham, Kassia S.Krishnasamy, RathikaStanton, TonySacre, Julian W.Douglas, BettinaIsbel, Nicole M.Coombes, Jeff S.Howden, Erin J.2021-12-10T07:22:40-08:00doi:10.1681/ASN.2021050668hwp:resource-id:jnephrol;33/2/431American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyexercise training, prevention, physical activity, cardiovascular risk, multidisciplinary team, nurse-ledClinical ResearchClinical Researchresearch-article20222022-02-01February 202210.1681/ASN.20210506681046-66731533-34502021-12-10T07:22:40-08:002022-02Journal of the American Society of NephrologyClinical Research332554311045104544110451046
- Authors’ Reply10.1681/ASN.2021111413Mon, 31 Jan 2022 10:00:27 GMT-08:00Authors’ ReplyBoudhabhay, IdrisCoutance, GuillaumeKarras, AlexandreDuong Van Huyen, Jean Paul2022-01-31T10:00:27-08:00doi:10.1681/ASN.2021111413hwp:resource-id:jnephrol;33/2/458American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyANCALetter to the EditorLetter to the Editorletter20222022-02-01February 202210.1681/ASN.20211114131046-66731533-34502022-01-31T10:00:27-08:002022-02Journal of the American Society of NephrologyLetter to the Editor3322945845723624594582374
- Comparing Plasma Donor-Derived Cell-free DNA to Indication Kidney Biopsy Tissue Gene Expression: Toward Understanding the Molecular Equivalents of Non-Invasive Tests10.1681/ASN.2021121595Thu, 20 Jan 2022 07:24:45 GMT-08:00Comparing Plasma Donor-Derived Cell-free DNA to Indication Kidney Biopsy Tissue Gene Expression: Toward Understanding the Molecular Equivalents of Non-Invasive TestsKurian, SunilFriedewald, John2022-01-20T07:24:45-08:00doi:10.1681/ASN.2021121595hwp:resource-id:jnephrol;33/2/256American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologygene expression, acute allograft rejection, cell free DNA, biomarkersUp Front MattersEditorialUp Front MattersEditorialeditorial20222022-02-01February 202210.1681/ASN.20211215951046-66731533-34502022-01-20T07:24:45-08:002022-02Journal of the American Society of NephrologyUp Front Matters3322256387258400
- Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation10.1681/ASN.2021040439Fri, 17 Dec 2021 11:42:38 GMT-08:00Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and InflammationGuo, XiaojiaXu, LeyuanVelazquez, HeinoChen, Tian-MinWilliams, Ryan M.Heller, Daniel A.Burtness, BarbaraSafirstein, RobertDesir, Gary V.2021-12-17T11:42:38-08:00doi:10.1681/ASN.2021040439hwp:resource-id:jnephrol;33/2/342American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, cisplatin nephrotoxicity, chronic renal disease, cytokines, macrophages, mitochondria, oxidative stress, proximal tubule, renal protection, cell deathBasic ResearchBasic Researchresearch-article20222022-02-01February 202210.1681/ASN.20210404391046-66731533-34502021-12-17T11:42:38-08:002022-02Journal of the American Society of NephrologyBasic Research3322342255356256
- Spatially Resolved Transcriptomic Analysis of Acute Kidney Injury in a Female Murine Model10.1681/ASN.2021081150Wed, 01 Dec 2021 09:28:12 GMT-08:00Spatially Resolved Transcriptomic Analysis of Acute Kidney Injury in a Female Murine ModelDixon, Eryn E.Wu, HaojiaMuto, YoshiharuWilson, Parker C.Humphreys, Benjamin D.2021-12-01T09:28:12-08:00doi:10.1681/ASN.2021081150hwp:resource-id:jnephrol;33/2/279American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytranscriptomics, AKI, spatialRapid CommunicationsRapid Communicationsresearch-article20222022-02-01February 202210.1681/ASN.20210811501046-66731533-34502021-12-01T09:28:12-08:002022-02Journal of the American Society of NephrologyRapid Communications332279289
- Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA10.1681/ASN.2021050596Mon, 04 Oct 2021 12:36:06 GMT-07:00Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNAViering, DaanSchlingmann, Karl P.Hureaux, MargueriteNijenhuis, TomMallett, AndrewChan, Melanie M.Y.van Beek, Andrévan Eerde, Albertien M.Coulibaly, Jean-MarieVallet, MarionDecramer, StéphanePelletier, SolenneKlaus, GünterKömhoff, MartinBeetz, RolfPatel, ChiragShenoy, MohanSteenbergen, Eric J.Anderson, GlennBongers, Ernie M.H.F.Bergmann, CarstenPanneman, DaanRodenburg, Richard J.Kleta, RobertHouillier, PascalKonrad, MartinVargas-Poussou, RosaKnoers, Nine V.A.M.Bockenhauer, Detlefde Baaij, Jeroen H.F.,2021-10-04T12:36:06-07:00doi:10.1681/ASN.2021050596hwp:resource-id:jnephrol;33/2/305American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyepithelial sodium transport, genetic renal disease, human genetics, Na transport, ion transport, mitochondria, Gitelman-s syndrome, blood pressure, chronic kidney disease, chronic kidney failureBasic ResearchBasic Researchresearch-article20222022-02-01February 202210.1681/ASN.20210505961046-66731533-34502021-10-04T12:36:06-07:002022-02Journal of the American Society of NephrologyBasic Research332305325
- Using Machine Learning to Identify Metabolomic Signatures of Pediatric Chronic Kidney Disease Etiology10.1681/ASN.2021040538Tue, 11 Jan 2022 09:52:05 GMT-08:00Using Machine Learning to Identify Metabolomic Signatures of Pediatric Chronic Kidney Disease EtiologyLee, Arthur M.Hu, JianXu, YunwenAbraham, Alison G.Xiao, RuiCoresh, JosefRebholz, CaseyChen, JingshaRhee, Eugene P.Feldman, Harold I.Ramachandran, Vasan S.Kimmel, Paul L.Warady, Bradley A.Furth, Susan L.Denburg, Michelle R.,2022-01-11T09:52:05-08:00doi:10.1681/ASN.2021040538hwp:resource-id:jnephrol;33/2/375American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolomics, pediatric nephrology, chronic kidney disease, machine learning, machine learning collectionClinical ResearchClinical Researchresearch-article20222022-02-01February 202210.1681/ASN.20210405381046-66731533-34502022-01-11T09:52:05-08:002022-02Journal of the American Society of NephrologyClinical Research332375386
- Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic Syndrome10.1681/ASN.2021050643Wed, 08 Dec 2021 01:55:07 GMT-08:00Mycophenolate Mofetil after Rituximab for Childhood-Onset Complicated Frequently-Relapsing or Steroid-Dependent Nephrotic SyndromeIijima, KazumotoSako, MayumiOba, MariTanaka, SeijiHamada, RikuSakai, TomoyukiOhwada, YokoNinchoji, TakeshiYamamura, TomohikoMachida, HiroyukiShima, YukoTanaka, RyojiroKaito, HiroshiAraki, YoshinoriMorohashi, TamakiKumagai, NaonoriGotoh, YoshimitsuIkezumi, YoheiKubota, TakuoKamei, KoichiFujita, NaoyaOhtsuka, YasufumiOkamoto, TakayukiYamada, TakeshiTanaka, ErikoShimizu, MasakiHorinochi, TomokoKonishi, AkihideOmori, TakashiNakanishi, KoichiIshikura, KenjiIto, ShuichiNakamura, HidefumiNozu, Kandai,2021-12-08T13:55:07-08:00doi:10.1681/ASN.2021050643hwp:resource-id:jnephrol;33/2/401American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologymycophenolate mofetil, rituximab, childhood-onset, complicated frequently-relapsing/steroid-dependent nephrotic syndrome, clinical trialClinical ResearchClinical Researchresearch-article20222022-02-01February 202210.1681/ASN.20210506431046-66731533-34502021-12-08T13:55:07-08:002022-02Journal of the American Society of NephrologyClinical Research33332540110504191050
- Global Dialysis Perspective: France10.34067/KID.0003722021Mon, 25 Oct 2021 07:29:09 GMT-07:00Global Dialysis Perspective: FranceCanaud, BernardCouchoud, Cecile2021-10-25T07:29:09-07:00doi:10.34067/KID.0003722021hwp:resource-id:kidney360;3/1/168American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, dialysis funding, end stage kidney disease, ESKD network, France, hemodialysis, kidney replacement therapy, kidney transplant, renal dialysisGlobal PerspectiveGlobal Perspectiveresearch-article20222022-01-2710.34067/KID.00037220212641-76502021-10-25T07:29:09-07:002022-01-27Kidney360Global Perspective31168175
- Global Dialysis Perspective: Fiji10.34067/KID.0005652021Wed, 27 Oct 2021 05:48:31 GMT-07:00Global Dialysis Perspective: FijiTalbot, Benjamin,,Chandra, YogeshniGallagher, MartinKotwal, SradhaKrishnan, AmrishMalani, JojiNand, JasmialRitchie, AngusTa’eed, Anis2021-10-27T05:48:31-07:00doi:10.34067/KID.0005652021hwp:resource-id:kidney360;3/1/164American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, Fiji, kidney replacement therapy, registry, resource allocationGlobal PerspectiveGlobal Perspectiveresearch-article20222022-01-2710.34067/KID.00056520212641-76502021-10-27T05:48:31-07:002022-01-27Kidney360Global Perspective31164167
- Unusual Ultrasound Findings in a Difficult to Cannulate Arteriovenous Graft10.34067/KID.0003952021Thu, 27 Jan 2022 08:00:35 GMT-08:00Unusual Ultrasound Findings in a Difficult to Cannulate Arteriovenous GraftGossett, Christy L.Kattah, Andrea G.Qureshi, Fawad2022-01-27T08:00:35-08:00doi:10.34067/KID.0003952021hwp:resource-id:kidney360;3/1/192American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, access, axillary vein, graft, renal dialysisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-01-2710.34067/KID.00039520212641-76502022-01-27T08:00:35-08:002022-01-27Kidney360Clinical Images in Nephrology and Dialysis31192193
- The Downside of Telephone Health Visits in a Kidney Transplant Patient during the COVID-19 Pandemic10.34067/KID.0004562021Thu, 27 Jan 2022 08:00:35 GMT-08:00The Downside of Telephone Health Visits in a Kidney Transplant Patient during the COVID-19 PandemicRoss-Smith, Maree S.Wallace, Hannah E.2022-01-27T08:00:35-08:00doi:10.34067/KID.0004562021hwp:resource-id:kidney360;3/1/190American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, dialysis, fistula, telehealth, transplantationClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20222022-01-2710.34067/KID.00045620212641-76502022-01-27T08:00:35-08:002022-01-27Kidney360Clinical Images in Nephrology and Dialysis31190191
- Dissemination and Implementation Science: A Primer and Applications in Nephrology10.34067/KID.0005662021Fri, 15 Oct 2021 12:51:19 GMT-07:00Dissemination and Implementation Science: A Primer and Applications in NephrologyUrbanski, Megan A.Wilk, Adam S.Escoffery, CamPatzer, Rachel E.2021-10-15T12:51:19-07:00doi:10.34067/KID.0005662021hwp:resource-id:kidney360;3/1/185American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, dissemination, implementation, methodology, quality improvementClinical Research MethodsClinical Research Methodsresearch-article20222022-01-2710.34067/KID.00056620212641-76502021-10-15T12:51:19-07:002022-01-27Kidney360Clinical Research Methods31185189
- Quantitative Lung Ultrasonography for the Nephrologist: Applications in Dialysis and Heart FailureVolume overload, and its attendant increase in acute care utilization and cardiovascular morbidity and mortality, represents a critical challenge for the practicing nephrologist. This is particularly true among patients with ESKD on HD, where predialysis volume overload and intradialytic and postdialytic hypovolemia account for almost a third of all cost for the Medicare dialysis benefit. Quantitative lung ultrasound is a tool for assessing the extent of extravascular lung water that outperforms physical exam and plain chest radiography. B-lines are vertical hyperechoic artifacts present in patients with increased extravascular lung water. B-lines have been shown to decrease dynamically during the hemodialysis treatment in proportion to ultrafiltration volume. Among patients with chronic heart failure, titration of diuretics on the basis of the extent of pulmonary congestion noted on lung ultrasonography has been shown to decrease recurrent acute care utilization. Early data from randomized controlled trials of lung ultrasound–guided ultrafiltration therapy among patients with ESKD on HD have shown promise for potential reduction in recurrent episodes of decompensated heart failure and cardiovascular events. Ultimately, lung ultrasound may predict those who are ultrafiltration tolerant and could be used to decrease acute care utilization and, thus, cost in this population.10.34067/KID.0003972021Thu, 11 Nov 2021 09:42:47 GMT-08:00Quantitative Lung Ultrasonography for the Nephrologist: Applications in Dialysis and Heart FailureVolume overload, and its attendant increase in acute care utilization and cardiovascular morbidity and mortality, represents a critical challenge for the practicing nephrologist. This is particularly true among patients with ESKD on HD, where predialysis volume overload and intradialytic and postdialytic hypovolemia account for almost a third of all cost for the Medicare dialysis benefit. Quantitative lung ultrasound is a tool for assessing the extent of extravascular lung water that outperforms physical exam and plain chest radiography. B-lines are vertical hyperechoic artifacts present in patients with increased extravascular lung water. B-lines have been shown to decrease dynamically during the hemodialysis treatment in proportion to ultrafiltration volume. Among patients with chronic heart failure, titration of diuretics on the basis of the extent of pulmonary congestion noted on lung ultrasonography has been shown to decrease recurrent acute care utilization. Early data from randomized controlled trials of lung ultrasound–guided ultrafiltration therapy among patients with ESKD on HD have shown promise for potential reduction in recurrent episodes of decompensated heart failure and cardiovascular events. Ultimately, lung ultrasound may predict those who are ultrafiltration tolerant and could be used to decrease acute care utilization and, thus, cost in this population.Reisinger, NathanielKoratala, Abhilash2021-11-11T09:42:47-08:00doi:10.34067/KID.0003972021hwp:resource-id:kidney360;3/1/176American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, cardiovascular outcomes, ESKD, heart failure, hemodialysis, intradialytic hypotension, POCUS, point-of-care ultrasound, pulmonary edema, quantitative lung ultrasonographyReview ArticleReview Articlereview-article20222022-01-2710.34067/KID.00039720212641-76502021-11-11T09:42:47-08:002022-01-27Kidney360Review Article31176184
- TRPM2 Plays a Minor Role in AKI and Kidney Fibrosis10.34067/KID.0005492021Sat, 23 Oct 2021 06:07:33 GMT-07:00TRPM2 Plays a Minor Role in AKI and Kidney FibrosisKurata, YuTanaka, TetsuhiroCernecka, HanaEitner, FrankNangaku, Masaomi2021-10-23T06:07:33-07:00doi:10.34067/KID.0005492021hwp:resource-id:kidney360;3/1/153American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, basic science, chronic kidney disease, fibrosis, ischemia-reperfusion injury, TRPM2Brief CommunicationAcute Kidney Injury and ICU NephrologyBrief CommunicationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-01-2710.34067/KID.00054920212641-76502021-10-23T06:07:33-07:002022-01-27Kidney360Brief Communication31153157
- Disparities in Discussions about Kidney Replacement Therapy in CKD Care10.34067/KID.0004752021Sat, 23 Oct 2021 06:07:33 GMT-07:00Disparities in Discussions about Kidney Replacement Therapy in CKD CareBarrett, Tyler M.Davenport, Clemontina A.Ephraim, Patti L.Peskoe, SarahMohottige, DinushikaDePasquale, NicoleMcElroy, LisaBoulware, L. Ebony2021-10-23T06:07:33-07:00doi:10.34067/KID.0004752021hwp:resource-id:kidney360;3/1/158American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, chronic kidney disease, dialysis, renal replacement therapy, transplantBrief CommunicationTransplantationBrief CommunicationTransplantationresearch-article20222022-01-2710.34067/KID.00047520212641-76502021-10-23T06:07:33-07:002022-01-27Kidney360Brief Communication31158163
- Obesity Related Glomerulopathy in Adolescent Women: The Effect of Body Surface Area10.34067/KID.0005312021Thu, 11 Nov 2021 01:45:22 GMT-08:00Obesity Related Glomerulopathy in Adolescent Women: The Effect of Body Surface AreaBielopolski, DanaSingh, NehaBentur, Ohad S.Renert-Yuval, YaelMacArthur, RobertVasquez, Kimberly S.Moftah, Dena S.Vaughan, Roger D.Charytan, David M.Kost, Rhonda G.Tobin, Jonathan N.2021-11-11T13:45:22-08:00doi:10.34067/KID.0005312021hwp:resource-id:kidney360;3/1/113American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, adolescence, body measures, hyperfiltration, obesityOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-01-2710.34067/KID.00053120212641-76502021-11-11T13:45:22-08:002022-01-27Kidney360Original Investigation31113121
- Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19–Associated AKI10.34067/KID.0005522021Fri, 05 Nov 2021 09:54:32 GMT-07:00Single-Cell RNA Sequencing of Urinary Cells Reveals Distinct Cellular Diversity in COVID-19–Associated AKICheung, Matthew D.Erman, Elise N.Liu, ShanrunErdmann, Nathaniel B.Ghajar-Rahimi, GelareMoore, Kyle H.Edberg, Jeffrey C.George, James F.Agarwal, Anupam2021-11-05T09:54:32-07:00doi:10.34067/KID.0005522021hwp:resource-id:kidney360;3/1/28American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, basic science, COVID-19, SARS-CoV-2, single-cell RNA sequencing, urineOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-01-2710.34067/KID.00055220212641-76502021-11-05T09:54:32-07:002022-01-27Kidney360Original Investigation312836
- Albuminuria within the Normal Range Can Predict All-Cause Mortality and Cardiovascular Mortality10.34067/KID.0003912021Fri, 05 Nov 2021 02:03:36 GMT-07:00Albuminuria within the Normal Range Can Predict All-Cause Mortality and Cardiovascular MortalityKang, MinjungKwon, SoieLee, JeonghwanShin, Jung-ImKim, Yong ChulPark, Jae YoonBae, EunjinKim, Eun YoungKim, Dong KiLim, Chun SooLee, Jung Pyo2021-11-05T14:03:36-07:00doi:10.34067/KID.0003912021hwp:resource-id:kidney360;3/1/74American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, albuminuria, cardiovascular diseases, cardiovascular system, mortality, normoalbuminuria, reference valuesOriginal InvestigationClinical NephrologyOriginal InvestigationClinical Nephrologyresearch-article20222022-01-2710.34067/KID.00039120212641-76502021-11-05T14:03:36-07:002022-01-27Kidney360Original Investigation317482
- Shroom3, a Gene Associated with CKD, Modulates Epithelial Recovery after AKI10.34067/KID.0003802021Wed, 03 Nov 2021 01:29:00 GMT-07:00Shroom3, a Gene Associated with CKD, Modulates Epithelial Recovery after AKILi, AihuaCunanan, JoannaKhalili, HadisehPlageman, TimothyAsk, KjetilKhan, AhsanHunjan, AshmeetDrysdale, ThomasBridgewater, Darren2021-11-03T13:29:00-07:00doi:10.34067/KID.0003802021hwp:resource-id:kidney360;3/1/51American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, acute kidney injury, renal tubular epithelial cells, Shroom3Original InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-01-2710.34067/KID.00038020212641-76502021-11-03T13:29:00-07:002022-01-27Kidney360Original Investigation315162
- Bile Acids Are Important Contributors to AKI Associated with Liver Disease: CON10.34067/KID.0006512020Tue, 04 May 2021 02:13:17 GMT-07:00Bile Acids Are Important Contributors to AKI Associated with Liver Disease: CONAllegretti, Andrew S.Belcher, Justin M.2021-05-04T14:13:17-07:00doi:10.34067/KID.0006512020hwp:resource-id:kidney360;3/1/21American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, bile cast nephropathy, cholemic nephropathy, cirrhosisDebates in NephrologyDebates in Nephrologyresearch-article20222022-01-2710.34067/KID.00065120202641-76502021-05-04T14:13:17-07:002022-01-27Kidney360Debates in Nephrology312124
- De Novo Central Vein Stenosis in Hemodialysis Patients Following Initial Tunneled Central Vein Catheter Placement10.34067/KID.0005202021Thu, 21 Oct 2021 09:44:27 GMT-07:00De Novo Central Vein Stenosis in Hemodialysis Patients Following Initial Tunneled Central Vein Catheter PlacementAl-Balas, AlianAlmehmi, AmmarVarma, RakeshAl-Balas, HassanAllon, Michael2021-10-21T09:44:27-07:00doi:10.34067/KID.0005202021hwp:resource-id:kidney360;3/1/99American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, central venous catheters, central venous stenosis, pathologic constriction, renal dialysis, tunneled catheterOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-01-2710.34067/KID.00052020212641-76502021-10-21T09:44:27-07:002022-01-27Kidney360Original Investigation3199102
- Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney Survival10.34067/KID.0005512021Fri, 05 Nov 2021 09:54:32 GMT-07:00Beyond ISN/RPS Lupus Nephritis Classification: Adding Chronicity Index to Clinical Variables Predicts Kidney SurvivalMoroni, GabriellaPorata, GiuliaRaffiotta, FrancescaQuaglini, SilvanaFrontini, GiuliaSacchi, LuciaBinda, ValentinaCalatroni, MartaReggiani, FrancescoBanfi, GiovanniPonticelli, Claudio2021-11-05T09:54:32-07:00doi:10.34067/KID.0005512021hwp:resource-id:kidney360;3/1/122American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, lupus nephritis, systemic lupus erythematosusOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20222022-01-2710.34067/KID.00055120212641-76502021-11-05T09:54:32-07:002022-01-27Kidney360Original Investigation31122132
- Durable Protection after Anti–SARS-CoV-2 Monoclonal Antibody Therapy10.34067/KID.0007722021Thu, 27 Jan 2022 08:00:34 GMT-08:00Durable Protection after Anti–SARS-CoV-2 Monoclonal Antibody TherapyMisch, Elizabeth A.2022-01-27T08:00:34-08:00doi:10.34067/KID.0007722021hwp:resource-id:kidney360;3/1/8American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, COVID-19, kidney transplantation, monoclonal antibody therapy, SARS-CoV-2EditorialEditorialeditorial20222022-01-2710.34067/KID.00077220212641-76502022-01-27T08:00:34-08:002022-01-27Kidney360Editorial31810
- Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD10.34067/KID.0004772021Fri, 05 Nov 2021 09:54:32 GMT-07:00Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKDFukuda, AkihiroMinakawa, AkihiroSato, YujiShibata, HirotakaHara, MasanoriFujimoto, Shouichi2021-11-05T09:54:32-07:00doi:10.34067/KID.0004772021hwp:resource-id:kidney360;3/1/63American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, podocyte, proteinuria, urinary sediment podocyte mRNA, urinary supernatant podocyte proteinOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20222022-01-2710.34067/KID.00047720212641-76502021-11-05T09:54:32-07:002022-01-27Kidney360Original Investigation316373
- Predicting Kidney Survival in Lupus Nephritis by Adding Clinical Data to Pathologic Features10.34067/KID.0007082021Thu, 27 Jan 2022 08:00:34 GMT-08:00Predicting Kidney Survival in Lupus Nephritis by Adding Clinical Data to Pathologic FeaturesSaxena, Ramesh2022-01-27T08:00:34-08:00doi:10.34067/KID.0007082021hwp:resource-id:kidney360;3/1/5American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, lupus nephritis, systemic lupus erythematosusEditorialEditorialeditorial20222022-01-2710.34067/KID.00070820212641-76502022-01-27T08:00:34-08:002022-01-27Kidney360Editorial3157
- Artificial Intelligence Assessment of Renal Scarring (AIRS Study)10.34067/KID.0003662021Thu, 11 Nov 2021 01:45:21 GMT-08:00Artificial Intelligence Assessment of Renal Scarring (AIRS Study)Chantaduly, ChanonTroutt, Hayden R.Perez Reyes, Karla A.Zuckerman, Jonathan E.Chang, Peter D.Lau, Wei Ling2021-11-11T13:45:21-08:00doi:10.34067/KID.0003662021hwp:resource-id:kidney360;3/1/83American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360clinical nephrology, artificial intelligence, convoluted neural networks, CT imaging, kidney biopsy, kidney fibrosis, machine learning, renal fibrosisOriginal InvestigationClinical NephrologyOriginal InvestigationClinical Nephrologyresearch-article20222022-01-2710.34067/KID.00036620212641-76502021-11-11T13:45:21-08:002022-01-27Kidney360Original Investigation318390
- Bile Acids Are Important Contributors to AKI Associated with Liver Disease: PRO10.34067/KID.0005932020Tue, 04 May 2021 02:13:17 GMT-07:00Bile Acids Are Important Contributors to AKI Associated with Liver Disease: PROFickert, PeterRosenkranz, Alexander R.2021-05-04T14:13:17-07:00doi:10.34067/KID.0005932020hwp:resource-id:kidney360;3/1/17American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, bile acids, hepatorenal syndrome, liver failureDebates in NephrologyDebates in Nephrologyresearch-article20222022-01-2710.34067/KID.00059320202641-76502021-05-04T14:13:17-07:002022-01-27Kidney360Debates in Nephrology311720
- A Second Chance at Transplant First: Preemptive Repeat Kidney Transplantation10.34067/KID.0007502021Thu, 27 Jan 2022 08:00:34 GMT-08:00A Second Chance at Transplant First: Preemptive Repeat Kidney TransplantationHuml, Anne M.Schold, Jesse D.2022-01-27T08:00:34-08:00doi:10.34067/KID.0007502021hwp:resource-id:kidney360;3/1/11American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, access to care, disparities, preemptive, transplant centers, transplantationEditorialEditorialeditorial20222022-01-2710.34067/KID.00075020212641-76502022-01-27T08:00:34-08:002022-01-27Kidney360Editorial311113
- Bile Acids are Important Contributors of AKI Associated with Liver Disease: COMMENTARY10.34067/KID.0002422021Tue, 04 May 2021 02:13:17 GMT-07:00Bile Acids are Important Contributors of AKI Associated with Liver Disease: COMMENTARYLopez-Ruiz, ArnaldoJuncos, Luis A.2021-05-04T14:13:17-07:00doi:10.34067/KID.0002422021hwp:resource-id:kidney360;3/1/25American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, bile acids, cirrhosis, debates in nephrology, hepatorenal syndrome, liver diseaseModerator CommentaryModerator Commentaryresearch-article20222022-01-2710.34067/KID.00024220212641-76502021-05-04T14:13:17-07:002022-01-27Kidney360Moderator Commentary312527
- SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients10.34067/KID.0005732021Wed, 20 Oct 2021 01:24:47 GMT-07:00SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant RecipientsWang, Aileen X.Busque, StephanKuo, JamieSingh, UpinderRöeltgen, KatharinaPinsky, Benjamin A.Chertow, Glenn M.Scandling, John D.Lenihan, Colin R.2021-10-20T13:24:47-07:00doi:10.34067/KID.0005732021hwp:resource-id:kidney360;3/1/133American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, COVID-19, immunosuppression, kidney transplant, monoclonal antibodies, SARS-CoV-2Original InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-01-2710.34067/KID.00057320212641-76502021-10-20T13:24:47-07:002022-01-27Kidney360Original Investigation31133143
- Home versus In-Center Dialysis and Day of the Week Hospitalization: A Cohort Study10.34067/KID.0003552021Fri, 22 Oct 2021 11:35:11 GMT-07:00Home versus In-Center Dialysis and Day of the Week Hospitalization: A Cohort StudyTennankore, Karthik K.Nadeau-Fredette, Annie-ClaireMatheson, KaraChan, Christopher T.Trinh, EmiliePerl, Jeffrey2021-10-22T11:35:11-07:00doi:10.34067/KID.0003552021hwp:resource-id:kidney360;3/1/103American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, cohort study, daily hemodialysis, day of week, home hemodialysis, hospitalization, nocturnal dialysis, peritoneal dialysisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-01-2710.34067/KID.00035520212641-76502021-10-22T11:35:11-07:002022-01-27Kidney360Original Investigation31103112
- Kidney Disease Education Services: A Good Foundation, but More Is Needed!10.34067/KID.0007632021Thu, 27 Jan 2022 08:00:34 GMT-08:00Kidney Disease Education Services: A Good Foundation, but More Is Needed!Hafeez, Muhammad SaadYuo, Theodore H.2022-01-27T08:00:34-08:00doi:10.34067/KID.0007632021hwp:resource-id:kidney360;3/1/3American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, education, kidney diseasesEditorialEditorialeditorial20222022-01-2710.34067/KID.00076320212641-76502022-01-27T08:00:34-08:002022-01-27Kidney360Editorial3134
- Kidney Fibrosis Assessment by CT Using Machine Learning10.34067/KID.0007262021Thu, 27 Jan 2022 08:00:34 GMT-08:00Kidney Fibrosis Assessment by CT Using Machine LearningLemley, Kevin V.2022-01-27T08:00:34-08:00doi:10.34067/KID.0007262021hwp:resource-id:kidney360;3/1/1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360chronic kidney disease, fibrosis, kidney diseases, machine learning, x-ray computed tomographyEditorialEditorialeditorial20222022-01-2710.34067/KID.00072620212641-76502022-01-27T08:00:34-08:002022-01-27Kidney360Editorial3112
- Disparities in Access to Preemptive Repeat Kidney Transplant: Still Missing the Mark?10.34067/KID.0003162021Thu, 21 Oct 2021 05:56:55 GMT-07:00Disparities in Access to Preemptive Repeat Kidney Transplant: Still Missing the Mark?Vinson, Amanda J.Kiberd, Bryce A.West, KennethMannon, Roslyn B.Foster, Bethany J.Tennankore, Karthik K.2021-10-21T05:56:55-07:00doi:10.34067/KID.0003162021hwp:resource-id:kidney360;3/1/144American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, deceased donor, disparity, kidney, living donors, predictors, preemptive, repeat transplant, transplantationOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20222022-01-2710.34067/KID.00031620212641-76502021-10-21T05:56:55-07:002022-01-27Kidney360Original Investigation31144152
- A Critical Role for Shared Decision-Making about Referral and Evaluation for Kidney Transplant10.34067/KID.0007642021Thu, 27 Jan 2022 08:00:34 GMT-08:00A Critical Role for Shared Decision-Making about Referral and Evaluation for Kidney TransplantButler, Catherine R.2022-01-27T08:00:34-08:00doi:10.34067/KID.0007642021hwp:resource-id:kidney360;3/1/14American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360transplantation, equity, kidney transplant, person-centered, referral and consultation, shared decision makingEditorialEditorialeditorial20222022-01-2710.34067/KID.00076420212641-76502022-01-27T08:00:34-08:002022-01-27Kidney360Editorial311416
- Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury10.34067/KID.0004802021Wed, 03 Nov 2021 01:29:00 GMT-07:00Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney InjuryMcMahon, Kelly R.Chui, HaytonRassekh, Shahrad RodSchultz, Kirk R.Blydt-Hansen, Tom D.Mammen, CherryPinsk, MauryCuvelier, Geoffrey D. E.Carleton, Bruce C.Tsuyuki, Ross T.Ross, Colin J.D.Devarajan, PrasadHuynh, LouisYordanova, MariyaCrépeau-Hubert, FrédérikWang, StellaCockovski, VedranPalijan, AnaZappitelli, Michael2021-11-03T13:29:00-07:00doi:10.34067/KID.0004802021hwp:resource-id:kidney360;3/1/37American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, chemotherapy, cisplatin nephrotoxicity, cohort studies, diagnostic testing, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, pediatric hematology/oncology, pediatric nephrology, urine biomarkersOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20222022-01-2710.34067/KID.00048020212641-76502021-11-03T13:29:00-07:002022-01-27Kidney360Original Investigation313750
- Provision of Kidney Disease Education Service Is Associated with Improved Vascular Access Outcomes among US Incident Hemodialysis Patients10.34067/KID.0004502021Tue, 28 Sep 2021 01:12:16 GMT-07:00Provision of Kidney Disease Education Service Is Associated with Improved Vascular Access Outcomes among US Incident Hemodialysis PatientsRuchi, RupamBozorgmehri, ShahabChamarthi, GajapathirajuOrozco, TatianaMohandas, RajeshOzrazgat-Baslanti, TezcanSegal, Mark S.Shukla, Ashutosh M.2021-09-28T13:12:16-07:00doi:10.34067/KID.0004502021hwp:resource-id:kidney360;3/1/91American Society of NephrologyCopyright © 2022 by the American Society of NephrologyKidney360dialysis, arteriovenous access, arteriovenous fistula, arteriovenous graft, chronic dialysis, chronic hemodialysis, CKD, clinical nephrology, dialysis access, ESKD, hemodialysis accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20222022-01-2710.34067/KID.00045020212641-76502021-09-28T13:12:16-07:002022-01-27Kidney360Original Investigation319198
- Assessing Risk of Progression in ADPKD10.2215/CJN.13071021Thu, 09 Dec 2021 08:43:16 GMT-08:00Assessing Risk of Progression in ADPKDGordon, Craig E.Miskulin, Dana C.Perrone, Ronald D.2021-12-09T08:43:16-08:00doi:10.2215/CJN.13071021hwp:resource-id:clinjasn;17/1/134American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypolycystic kidney disease, chronic kidney disease, clinical nephrology, genetic renal disease, randomized controlled trials, autosomal dominant polycystic kidney diseaseKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-01-01January 202210.2215/CJN.130710211555-90411555-905X2021-12-09T08:43:16-08:002022-01Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat171134136
- Platelet Abnormalities in CKD and Their Implications for Antiplatelet TherapyPatients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.10.2215/CJN.04100321Mon, 08 Nov 2021 08:50:47 GMT-08:00Platelet Abnormalities in CKD and Their Implications for Antiplatelet TherapyPatients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.Baaten, Constance C.F.M.J.Schröer, Jonas R.Floege, JürgenMarx, NikolausJankowski, JoachimBerger, MartinNoels, Heidi2021-11-08T08:50:47-08:00doi:10.2215/CJN.04100321hwp:resource-id:clinjasn;17/1/155American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, thrombosis, platelets, platelet aggregation inhibitors, blood platelet disordersReviewReviewreview-article20222022-01-01January 202210.2215/CJN.041003211555-90411555-905X2021-11-08T08:50:47-08:002022-01Clinical Journal of the American Society of NephrologyReview171155170
- Temporal Trends of Dietary Risk Factors after a Diagnosis of Kidney Stones10.2215/CJN.09200721Fri, 19 Nov 2021 08:38:56 GMT-08:00Temporal Trends of Dietary Risk Factors after a Diagnosis of Kidney StonesFerraro, Pietro ManuelCunha, Tamara Da SilvaTaylor, Eric N.Curhan, Gary C.2021-11-19T08:38:56-08:00doi:10.2215/CJN.09200721hwp:resource-id:clinjasn;17/1/83American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, nephrolithiasis, cohort studies, epidemiology, nutrition, risk factors, dietOriginal ArticleNephrolithiasisOriginal ArticleNephrolithiasisresearch-article20222022-01-01January 202210.2215/CJN.092007211555-90411555-905X2021-11-19T08:38:56-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article1718389
- A Core Outcome Set for Trials in Glomerular Disease10.2215/CJN.07840621Thu, 30 Dec 2021 09:39:23 GMT-08:00A Core Outcome Set for Trials in Glomerular DiseaseCarter, Simon A.Lightstone, LizCattran, DanTong, AllisonBagga, ArvindBarbour, Sean J.Barratt, JonathanBoletis, JohnCaster, Dawn J.Coppo, RosannaFervenza, Fernando C.Floege, JürgenHladunewich, Michelle A.Hogan, Jonathan J.Kitching, A. RichardLafayette, Richard A.Malvar, AnaRadhakrishnan, JaiRovin, Brad H.Scholes-Robertson, NicoleTrimarchi, HernánZhang, HongAnumudu, SamayaCho, YeoungjeeGutman, TaliaO’Lone, EmmaViecelli, Andrea K.Au, EricAzukaitis, KarolisBaumgart, AmandaBernier-Jean, AmelieDunn, LoueseHowell, MartinJu, AngelaLogeman, CharlotteNataatmadja, MelissaSautenet, BenedicteSharma, AnkitCraig, Jonathan C.2021-12-30T09:39:23-08:00doi:10.2215/CJN.07840621hwp:resource-id:clinjasn;17/1/53American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrandomized controlled trials, quality of life, outcomes, nephrotic syndrome, mortality, glomerulonephritis, glomerular disease, epidemiology and outcomes, cardiovascular diseaseOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-01-01January 202210.2215/CJN.078406211555-90411555-905X2021-12-30T09:39:23-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article171153116413
- Neutralization of SARS-CoV-2 Variants of Concern in Kidney Transplant Recipients after Standard COVID-19 Vaccination10.2215/CJN.11820921Wed, 22 Dec 2021 11:26:04 GMT-08:00Neutralization of SARS-CoV-2 Variants of Concern in Kidney Transplant Recipients after Standard COVID-19 VaccinationBenning, LouiseMorath, ChristianBartenschlager, MarieNusshag, ChristianKälble, FlorianBuylaert, MirabelSchaier, MatthiasBeimler, JörgKlein, KatrinGrenz, JuliaReichel, PaulaHidmark, AsaPonath, GeraldTöllner, MaximilianReineke, MarvinRieger, SusanneTönshoff, BurkhardSchnitzler, PaulZeier, MartinSüsal, CanerBartenschlager, RalfSpeer, Claudius2021-12-22T11:26:04-08:00doi:10.2215/CJN.11820921hwp:resource-id:clinjasn;17/1/98American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, SARS-CoV-2, kidney transplantation, variants of concern, vaccinationOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-01-01January 202210.2215/CJN.118209211555-90411555-905X2021-12-22T11:26:04-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article17111981310625
- Value-Based Care in Chronic Kidney Disease10.2215/CJN.15031121Thu, 30 Dec 2021 11:35:47 GMT-08:00Value-Based Care in Chronic Kidney DiseaseReaves, Allison C.Weiner, Daniel E.2021-12-30T11:35:47-08:00doi:10.2215/CJN.15031121hwp:resource-id:clinjasn;17/1/14American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyeconomic impact, albuminuria, health policy, chronic kidney diseaseEditorialEditorialeditorial20222022-01-01January 202210.2215/CJN.150311211555-90411555-905X2021-12-30T11:35:47-08:002022-01Clinical Journal of the American Society of NephrologyEditorial171114171626
- Cerebrovascular Response during Acute Exercise in Kidney Transplant Recipients10.2215/CJN.08410621Wed, 06 Oct 2021 11:36:40 GMT-07:00Cerebrovascular Response during Acute Exercise in Kidney Transplant RecipientsWard, Jaimie L.Ramakrishnan, MadhuriJurgensen, AndrewBillinger, SandraGupta, Aditi2021-10-06T11:36:40-07:00doi:10.2215/CJN.08410621hwp:resource-id:clinjasn;17/1/111American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, kidney transplantation, chronic kidney disease, dementia, hypertension, exerciseResearch LetterResearch Letterletter20222022-01-01January 202210.2215/CJN.084106211555-90411555-905X2021-10-06T11:36:40-07:002022-01Clinical Journal of the American Society of NephrologyResearch Letter171111113
- Monitoring Daily Ultrafiltration in Automated Peritoneal Dialysis10.2215/CJN.08180621Fri, 10 Dec 2021 07:07:23 GMT-08:00Monitoring Daily Ultrafiltration in Automated Peritoneal DialysisEibensteiner, FabianFlores, Krystell OviedoUnterwurzacher, MarkusHerzog, RebeccaKratochwill, KlausAlper, Seth L.Aufricht, ChristophKönig, FranzVychytil, Andreas2021-12-10T07:07:23-08:00doi:10.2215/CJN.08180621hwp:resource-id:clinjasn;17/1/107American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyultrafiltration, peritoneal dialysis, peritoneal membrane, chronic dialysisResearch LetterResearch Letterletter20222022-01-01January 202210.2215/CJN.081806211555-90411555-905X2021-12-10T07:07:23-08:002022-01Clinical Journal of the American Society of NephrologyResearch Letter171107110
- Trial Outcomes in Glomerular Diseases10.2215/CJN.15001121Thu, 30 Dec 2021 10:19:16 GMT-08:00Trial Outcomes in Glomerular DiseasesTroost, Jonathan P.2021-12-30T10:19:16-08:00doi:10.2215/CJN.15001121hwp:resource-id:clinjasn;17/1/11American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, clinical trialEditorialEditorialeditorial20222022-01-01January 202210.2215/CJN.150011211555-90411555-905X2021-12-30T10:19:16-08:002022-01Clinical Journal of the American Society of NephrologyEditorial171111531364
- Waitlist Mortality for Second Kidney Transplants10.2215/CJN.15021121Wed, 29 Dec 2021 02:53:31 GMT-08:00Waitlist Mortality for Second Kidney TransplantsFallahzadeh, Mohammad KazemBirdwell, Kelly A.2021-12-29T14:53:31-08:00doi:10.2215/CJN.15021121hwp:resource-id:clinjasn;17/1/6American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, mortality, transplant outcomesEditorialEditorialeditorial20222022-01-01January 202210.2215/CJN.150211211555-90411555-905X2021-12-29T14:53:31-08:002022-01Clinical Journal of the American Society of NephrologyEditorial1711690797
- Accessibility of Nutrition Care for Kidney Disease Worldwide10.2215/CJN.14861121Mon, 03 Jan 2022 02:49:53 GMT-08:00Accessibility of Nutrition Care for Kidney Disease WorldwideIyengar, ArpanaLuyckx, Valerie A.2022-01-03T14:49:53-08:00doi:10.2215/CJN.14861121hwp:resource-id:clinjasn;17/1/8American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, chronic kidney disease, dialysisEditorialEditorialeditorial20222022-01-01January 202210.2215/CJN.148611211555-90411555-905X2022-01-03T14:49:53-08:002022-01Clinical Journal of the American Society of NephrologyEditorial17118381052
- Optimizing Renin-Angiotensin System Inhibitor Use in CKD10.2215/CJN.12950921Wed, 17 Nov 2021 07:41:13 GMT-08:00Optimizing Renin-Angiotensin System Inhibitor Use in CKDChang, Tara I.Lerma, Edgar V.2021-11-17T07:41:13-08:00doi:10.2215/CJN.12950921hwp:resource-id:clinjasn;17/1/131American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyantihypertensive agents, chronic kidney diseaseKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20222022-01-01January 202210.2215/CJN.129509211555-90411555-905X2021-11-17T07:41:13-08:002022-01Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat171131133
- The Kidney in Normal Aging10.2215/CJN.10580821Wed, 20 Oct 2021 07:26:37 GMT-07:00The Kidney in Normal AgingDenic, AleksandarGlassock, Richard J.Rule, Andrew D.2021-10-20T07:26:37-07:00doi:10.2215/CJN.10580821hwp:resource-id:clinjasn;17/1/137American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, nephron loss, normal agingPerspectivePerspectiveresearch-article20222022-01-01January 202210.2215/CJN.105808211555-90411555-905X2021-10-20T07:26:37-07:002022-01Clinical Journal of the American Society of NephrologyPerspective171137139
- Assessing Global Kidney Nutrition Care10.2215/CJN.07800621Mon, 03 Jan 2022 01:48:20 GMT-08:00Assessing Global Kidney Nutrition CareWang, Angela Yee-MoonOkpechi, Ikechi G.Ye, FengKovesdy, Csaba P.Brunori, GiulianoBurrowes, Jerrilynn D.Campbell, KatrinaDamster, SandrineFouque, DenisFriedman, Allon N.Garibotto, GiacomoGuebre-Egziabher, FitsumHarris, DavidIseki, KunitoshiJha, VivekanandJindal, KailashKalantar-Zadeh, KamyarKistler, BrandonKopple, Joel D.Kuhlmann, MartinLunney, MeaghanMafra, DeniseMalik, CharuMoore, Linda W.Price, S. RussSteiber, AlisonWanner, Christophter Wee, PieterLevin, AdeeraJohnson, David W.Bello, Aminu K.2022-01-03T13:48:20-08:00doi:10.2215/CJN.07800621hwp:resource-id:clinjasn;17/1/38American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, kidney nutrition care, global, dietitians, nutrition supplement, renal nutrition, global health, nutritional statusOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-01-01January 202210.2215/CJN.078006211555-90411555-905X2022-01-03T13:48:20-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article17113885210
- Guidelines for Genetic Testing and Management of Alport SyndromeGenetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3–COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.10.2215/CJN.04230321Mon, 20 Dec 2021 06:22:07 GMT-08:00Guidelines for Genetic Testing and Management of Alport SyndromeGenetic testing for pathogenic COL4A3–5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3–COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.Savige, JudyLipska-Zietkiewicz, Beata S.Watson, ElizabethHertz, Jens MichaelDeltas, ConstantinosMari, FrancescaHilbert, PascalePlevova, PavlinaByers, PeterCerkauskaite, AgneGregory, MartinCerkauskiene, RimanteLjubanovic, Danica GalesicBecherucci, FrancescaErrichiello, CarmelaMassella, LauraAiello, ValeriaLennon, RachelHopkinson, LouiseKoziell, AniaLungu, AdrianRothe, Hansjorg MartinHoefele, JuliaZacchia, MiriamMartic, Tamara NikusevaGupta, Asheetavan Eerde, AlbertienGear, SusieLandini, SamuelaPalazzo, Vivianaal-Rabadi, LaithClaes, KathleenCorveleyn, AnniekVan Hoof, Evelienvan Geel, MicheelWilliams, MaggieAshton, EmmaBelge, HendicaArs, ElisabetBierzynska, AgnieszkaGangemi, ConcettaRenieri, AlessandraStorey, HelenFlinter, Frances2021-12-20T18:22:07-08:00doi:10.2215/CJN.04230321hwp:resource-id:clinjasn;17/1/143American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, genetic testing, COL4A5, thin basement membrane nephropathy, collagen IV, COL4A3, COL4A4, digenic Alport syndrome, FSGS, kidney cystsFeatureFeatureresearch-article20222022-01-01January 202210.2215/CJN.042303211555-90411555-905X2021-12-20T18:22:07-08:002022-01Clinical Journal of the American Society of NephrologyFeature171143154
- Terlipressin: Hopes Fulfilled or Dashed?10.2215/CJN.06710521Wed, 17 Nov 2021 10:25:50 GMT-08:00Terlipressin: Hopes Fulfilled or Dashed?Pichler, Raimund H.Swenson, Erik R.Leary, Peter J.Paine, Cary H.2021-11-17T10:25:50-08:00doi:10.2215/CJN.06710521hwp:resource-id:clinjasn;17/1/140American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyterlipressin, hepatorenal syndrome, HRS-AKI, respiratory failure, pulmonary edema, norepinephrinePerspectivePerspectiveresearch-article20222022-01-01January 202210.2215/CJN.067105211555-90411555-905X2021-11-17T10:25:50-08:002022-01Clinical Journal of the American Society of NephrologyPerspective171140142
- Waiting Time for Second Kidney Transplantation and Mortality10.2215/CJN.07620621Wed, 29 Dec 2021 08:17:49 GMT-08:00Waiting Time for Second Kidney Transplantation and MortalityKainz, AlexanderKammer, MichaelReindl-Schwaighofer, RomanStrohmaier, SusannePetr, VojtěchViklicky, OndrejAbramowicz, DanielNaik, MarcelMayer, GertOberbauer, Rainer2021-12-29T08:17:49-08:00doi:10.2215/CJN.07620621hwp:resource-id:clinjasn;17/1/90American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysecond kidney transplantation, patient survival, target trial emulation, restricted mean survival time, kidney transplantation, waiting listsOriginal ArticleTransplantationOriginal ArticleTransplantationresearch-article20222022-01-01January 202210.2215/CJN.076206211555-90411555-905X2021-12-29T08:17:49-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article1711906977
- Protection against SARS-CoV-2 Variants with COVID-19 Vaccination in Kidney Transplant Recipients10.2215/CJN.14881121Wed, 22 Dec 2021 11:26:04 GMT-08:00Protection against SARS-CoV-2 Variants with COVID-19 Vaccination in Kidney Transplant RecipientsBertrand, DominiqueCandon, Sophie2021-12-22T11:26:04-08:00doi:10.2215/CJN.14881121hwp:resource-id:clinjasn;17/1/3American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of NephrologySARS-CoV-2, COVID-19, vaccination, kidney transplantationEditorialEditorialeditorial20222022-01-01January 202210.2215/CJN.148811211555-90411555-905X2021-12-22T11:26:04-08:002022-01Clinical Journal of the American Society of NephrologyEditorial17111398151062
- Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease10.2215/CJN.09380721Wed, 10 Nov 2021 09:47:59 GMT-08:00Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney DiseaseSchmidt, Insa M.Sarvode Mothi, SurajWilson, Parker C.Palsson, RagnarSrivastava, AnandOnul, Ingrid F.Kibbelaar, Zoe A.Zhuo, MinAmodu, AfolarinStillman, Isaac E.Rennke, Helmut G.Humphreys, Benjamin D.Waikar, Sushrut S.2021-11-10T09:47:59-08:00doi:10.2215/CJN.09380721hwp:resource-id:clinjasn;17/1/27American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, proteomics, kidney biopsy, histopathology, Boston, cohort studies, biomarkers, nephrectomy, causality, plasmaOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-01-01January 202210.2215/CJN.093807211555-90411555-905X2021-11-10T09:47:59-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article1712737
- An Honorable and Ongoing Fight10.2215/CJN.15071121Wed, 22 Dec 2021 11:26:05 GMT-08:00An Honorable and Ongoing FightConway, Paul T.2021-12-22T11:26:05-08:00doi:10.2215/CJN.15071121hwp:resource-id:clinjasn;17/1/1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, nephrology, COVID-19, immunosuppressed, vaccines, vaccination, monoclonal antibodies, Delta variant, Kidney Health InitiativePatient VoicePatient Voiceeditorial20222022-01-01January 202210.2215/CJN.150711211555-90411555-905X2021-12-22T11:26:05-08:002022-01Clinical Journal of the American Society of NephrologyPatient Voice17111198321065
- Kidney Failure Risk Equation and Cost of Care in Patients with Chronic Kidney Disease10.2215/CJN.06770521Thu, 30 Dec 2021 10:48:48 GMT-08:00Kidney Failure Risk Equation and Cost of Care in Patients with Chronic Kidney DiseasePrasad, BhanuOsman, MericJafari, MaryamGordon, LexisTangri, NavdeepFerguson, Thomas W.Jin, ShanKappel, JoanneKozakewycz, Diane2021-12-30T10:48:48-08:00doi:10.2215/CJN.06770521hwp:resource-id:clinjasn;17/1/17American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, economic analysis, renal insufficiencyOriginal ArticleChronic Kidney DiseaseOriginal ArticleChronic Kidney Diseaseresearch-article20222022-01-01January 202210.2215/CJN.067705211555-90411555-905X2021-12-30T10:48:48-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article171117142616
- Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis10.2215/CJN.07810621Wed, 03 Nov 2021 09:34:38 GMT-07:00Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus NephritisWenderfer, Scott E.Chang, Joyce C.Goodwin Davies, AmyLuna, Ingrid Y.Scobell, RebeccaSears, CoraMagella, BlissMitsnefes, MarkStotter, Brian R.Dharnidharka, Vikas R.Nowicki, Katherine D.Dixon, Bradley P.Kelton, MeganFlynn, Joseph T.Gluck, CarolineKallash, MahmoudSmoyer, William E.Knight, AndreaSule, SangeetaRazzaghi, HaniehBailey, L. CharlesFurth, Susan L.Forrest, Christopher B.Denburg, Michelle R.Atkinson, Meredith A.2021-11-03T09:34:38-07:00doi:10.2215/CJN.07810621hwp:resource-id:clinjasn;17/1/65American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysystemic lupus erythematosus, lupus nephritis, pediatrics, children, PEDSnet, learning health system, multi-institutional systems, health educationOriginal ArticleGlomerular and Tubulointerstitial DiseasesOriginal ArticleGlomerular and Tubulointerstitial Diseasesresearch-article20222022-01-01January 202210.2215/CJN.078106211555-90411555-905X2021-11-03T09:34:38-07:002022-01Clinical Journal of the American Society of NephrologyOriginal Article1716574
- Nocturnal Dipping and Left Ventricular Mass Index in the Chronic Kidney Disease in Children Cohort10.2215/CJN.09810721Fri, 12 Nov 2021 09:18:39 GMT-08:00Nocturnal Dipping and Left Ventricular Mass Index in the Chronic Kidney Disease in Children CohortBakhoum, Christine Y.Katz, RonitSamuels, Joshua A.Al-Rousan, TalaFurth, Susan L.Ix, Joachim H.Garimella, Pranav S.2021-11-12T09:18:39-08:00doi:10.2215/CJN.09810721hwp:resource-id:clinjasn;17/1/75American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyambulatory blood pressure, chronic kidney disease, pediatrics, nondipping, clinical epidemiology, blood pressure, cohort studiesOriginal ArticleHypertensionOriginal ArticleHypertensionresearch-article20222022-01-01January 202210.2215/CJN.098107211555-90411555-905X2021-11-12T09:18:39-08:002022-01Clinical Journal of the American Society of NephrologyOriginal Article1717582
- Post-Transplant Pregnancy and ContraceptionPlaced in a historical context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.10.2215/CJN.14100820Wed, 17 Mar 2021 12:46:02 GMT-07:00Post-Transplant Pregnancy and ContraceptionPlaced in a historical context, this overview focuses on post-transpant pregnancy, fatherhood, and contraception in women and men. The critical importance of early reproductive counseling because of improved sexual function and the early return of ovulation and menses post-transplant is emphasized. We explain the decision making regarding contraception choices. The available data on the safety of immunosuppressive drugs in pregnancy, and for men desiring fatherhood, are detailed. The risk of maternal ingestion of mycophenolate products on the in utero fetus is considered and contrasted with the lack of concern for their use by men fathering children. Pregnancy risks to the allograft, baby, and mother are discussed. An infant’s exposure to specific immunosuppressant medications through breastfeeding is reviewed. The ethics and realities of post-transplant parenthood are explored.Klein, Christina L.Josephson, Michelle A.2021-03-17T12:46:02-07:00doi:10.2215/CJN.14100820hwp:resource-id:clinjasn;17/1/114American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypregnancy, contraception, post-transplant, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-01-01January 202210.2215/CJN.141008201555-90411555-905X2021-03-17T12:46:02-07:002022-01Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges171114120
- Bone and Mineral Disease in Kidney Transplant RecipientsAfter kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.10.2215/CJN.03410321Mon, 14 Jun 2021 11:46:48 GMT-07:00Bone and Mineral Disease in Kidney Transplant RecipientsAfter kidney transplantation, mineral and bone disorders are associated with higher risk of fractures and consequent morbidity and mortality. Disorders of calcium and phosphorus, vitamin D deficiency, and hyperparathyroidism are also common. The epidemiology of bone disease has evolved over the past several decades due to changes in immunosuppressive regimens, mainly glucocorticoid minimization or avoidance. The assessment of bone disease in kidney transplant recipients relies on risk factor recognition and bone mineral density assessment. Several drugs have been trialed for the treatment of post-transplant mineral and bone disorders. This review will focus on the epidemiology, effect, and treatment of metabolic and skeletal derangements in the transplant recipient.Khairallah, PascaleNickolas, Thomas L.2021-06-14T11:46:48-07:00doi:10.2215/CJN.03410321hwp:resource-id:clinjasn;17/1/121American Society of NephrologyCopyright © 2022 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation series, mineral metabolismKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20222022-01-01January 202210.2215/CJN.034103211555-90411555-905X2021-06-14T11:46:48-07:002022-01Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges171121130
- Estimating Nephron Number from Biopsies: Impact on Clinical Studies10.1681/ASN.2021070998Wed, 10 Nov 2021 10:48:42 GMT-08:00Estimating Nephron Number from Biopsies: Impact on Clinical StudiesMorozov, DaryaParvin, NedaConaway, MarkOxley, GavinBaldelomar, Edwin J.Cwiek, AleksandradeRonde, KimBeeman, Scott C.Charlton, Jennifer R.Bennett, Kevin M.2021-11-10T10:48:42-08:00doi:10.1681/ASN.2021070998hwp:resource-id:jnephrol;33/1/39American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologynephron number, cationized ferritin-enhanced magnetic resonance imaging (CFE-MRI), biopsy, single nephron GFR (snGFR), virtual biopsy, glomerular densityRapid CommunicationsRapid Communicationsresearch-article20222022-01-01January 202210.1681/ASN.20210709981046-66731533-34502021-11-10T10:48:42-08:002022-01Journal of the American Society of NephrologyRapid Communications3313948
- Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial10.1681/ASN.2021070942Wed, 03 Nov 2021 09:34:18 GMT-07:00Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD TrialAgarwal, RajivJoseph, AmerAnker, Stefan D.Filippatos, GerasimosRossing, PeterRuilope, Luis M.Pitt, BertramKolkhof, PeterScott, CharlieLawatscheck, RobertWilson, Daniel J.Bakris, George L.,2021-11-03T09:34:18-07:00doi:10.1681/ASN.2021070942hwp:resource-id:jnephrol;33/1/225American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, randomized controlled trials, diabetic nephropathy, hyperkalemia, mineralocorticoid receptor antagonistClinical ResearchClinical Researchresearch-article20222022-01-01January 202210.1681/ASN.20210709421046-66731533-34502021-11-03T09:34:18-07:002022-01Journal of the American Society of NephrologyClinical Research331225237
- Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia10.1681/ASN.2021060825Wed, 03 Nov 2021 09:34:18 GMT-07:00Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of HyperphosphatemiaGoodman, William G.Ward, Donald T.Martin, Kevin J.Drayer, DebraMoore, CarolXu, JiahongLai, JamesChon, YunNemeth, Edward. F.2021-11-03T09:34:18-07:00doi:10.1681/ASN.2021060825hwp:resource-id:jnephrol;33/1/201American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycalcimimetic, etelcalcetide, cinacalcet, calcium receptor, hyperparathyroidism, hyperphosphatemia, parathyroid hormone, calcium, receptors, calcium-sensingClinical ResearchClinical Researchresearch-article20222022-01-01January 202210.1681/ASN.20210608251046-66731533-34502021-11-03T09:34:18-07:002022-01Journal of the American Society of NephrologyClinical Research331201212
- Systematic Review and Meta-Analyses of the Effects of Phosphate-Lowering Agents in Nondialysis CKD10.1681/ASN.2021040554Wed, 13 Oct 2021 08:38:50 GMT-07:00Systematic Review and Meta-Analyses of the Effects of Phosphate-Lowering Agents in Nondialysis CKDLioufas, Nicole M.Pascoe, Elaine M.Hawley, Carmel M.Elder, Grahame J.Badve, Sunil V.Block, Geoffrey A.Johnson, David W.Toussaint, Nigel D.2021-10-13T08:38:50-07:00doi:10.1681/ASN.2021040554hwp:resource-id:jnephrol;33/1/59American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate binders, phosphate, mineral metabolism, cardiovascular diseaseMeta-AnalysisMeta-Analysisresearch-article20222022-01-01January 202210.1681/ASN.20210405541046-66731533-34502021-10-13T08:38:50-07:002022-01Journal of the American Society of NephrologyMeta-Analysis3315976
- Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients10.1681/ASN.2021050715Mon, 01 Nov 2021 08:27:53 GMT-07:00Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant RecipientsLee, Yu HoSato, YukiSaito, MitsuruFukuma, ShingoSaito, MasayaYamamoto, ShigenoriKomatsuda, AtsushiFujiyama, NobuhiroSatoh, ShigeruLee, Sang-HoBoor, PeterHabuchi, TomonoriFloege, JürgenYanagita, Motoko2021-11-01T08:27:53-07:00doi:10.1681/ASN.2021050715hwp:resource-id:jnephrol;33/1/186American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, renal biopsy, transplant outcomes, renal pathology, biopsy, lymphoid tissueClinical ResearchClinical Researchresearch-article20222022-01-01January 202210.1681/ASN.20210507151046-66731533-34502021-11-01T08:27:53-07:002022-01Journal of the American Society of NephrologyClinical Research331144186i867868200i867869
- This Month's Highlights10.1681/ASN.2021111479Thu, 30 Dec 2021 10:00:29 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2021-12-30T10:00:29-08:00doi:10.1681/ASN.2021111479hwp:resource-id:jnephrol;33/1/iAmerican Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20222022-01-01January 202210.1681/ASN.20211114791046-66731533-34502021-12-30T10:00:29-08:002022-01Journal of the American Society of NephrologyThis Month’s Highlights33111111i238108881864i2521201072006
- Nudging Behavioral Economics into Nephrology Care Delivery Research10.1681/ASN.2021111437Thu, 30 Dec 2021 10:00:29 GMT-08:00Nudging Behavioral Economics into Nephrology Care Delivery ResearchWilk, Adam S.Tuot, Delphine S.2021-12-30T10:00:29-08:00doi:10.1681/ASN.2021111437hwp:resource-id:jnephrol;33/1/9American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, behavioral economics, pragmatic randomized controlled trials, social determinants of healthUp Front MattersEditorialsUp Front MattersEditorialseditorial20222022-01-01January 202210.1681/ASN.20211114371046-66731533-34502021-12-30T10:00:29-08:002022-01Journal of the American Society of NephrologyUp Front Matters3311917511185
- GWAS in Mice Maps Susceptibility to HIV-Associated Nephropathy to the Ssbp2 Locus10.1681/ASN.2021040543Fri, 10 Dec 2021 07:22:40 GMT-08:00GWAS in Mice Maps Susceptibility to HIV-Associated Nephropathy to the Ssbp2 LocusSteers, Nicholas J.Gupta, YaskD’Agati, Vivette D.Lim, Tze Y.DeMaria, NataliaMo, AnnaLiang, JudyStevens, Kelsey O.Ahram, Dina F.Lam, Wan YeeGagea, MihaiNagarajan, LalithaSanna-Cherchi, SimoneGharavi, Ali G.2021-12-10T07:22:40-08:00doi:10.1681/ASN.2021040543hwp:resource-id:jnephrol;33/1/108American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyHIV nephropathy, collapsing glomerulopathy, murine GWAS, Ssbp2, focal segmental glomerulosclerosisBasic ResearchBasic Researchresearch-article20222022-01-01January 202210.1681/ASN.20210405431046-66731533-34502021-12-10T07:22:40-08:002022-01Journal of the American Society of NephrologyBasic Research3311108i120i
- Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans10.1681/ASN.2021050653Wed, 27 Oct 2021 10:52:53 GMT-07:00Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black AmericansRuhl, A. ParkerJeffries, NealYang, YuNaik, Rakhi P.Patki, AmitPecker, Lydia H.Mott, Bryan T.Zakai, Neil A.Winkler, Cheryl A.Kopp, Jeffrey B.Lange, Leslie A.Irvin, Marguerite R.Gutierrez, Orlando M.Cushman, MaryAckerman, Hans C.2021-10-27T10:52:53-07:00doi:10.1681/ASN.2021050653hwp:resource-id:jnephrol;33/1/213American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyhuman genetics, nitric oxide, hemodynamics and vascular regulation, alpha globin, alpha thalassemia, kidney disease, African Americans, prevalence, gene dosageClinical ResearchClinical Researchresearch-article20222022-01-01January 202210.1681/ASN.20210506531046-66731533-34502021-10-27T10:52:53-07:002022-01Journal of the American Society of NephrologyClinical Research331213224
- Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States10.1681/ASN.2021050617Wed, 20 Oct 2021 07:19:19 GMT-07:00Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United StatesHorimoto, Andrea R.V.R.Xue, DianeCai, JianwenLash, James P.Daviglus, Martha L.Franceschini, NoraThornton, Timothy A.2021-10-20T07:19:19-07:00doi:10.1681/ASN.2021050617hwp:resource-id:jnephrol;33/1/77American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyadmixture mapping, eGFR, chronic kidney disease, kidney functionBasic ResearchBasic Researchresearch-article20222022-01-01January 202210.1681/ASN.20210506171046-66731533-34502021-10-20T07:19:19-07:002022-01Journal of the American Society of NephrologyBasic Research3311771873
- Real-World Effectiveness and Immunogenicity of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Patients on Hemodialysis10.1681/ASN.2021060778Wed, 17 Nov 2021 10:26:37 GMT-08:00Real-World Effectiveness and Immunogenicity of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Patients on HemodialysisSibbel, ScottMcKeon, KatherineLuo, JiacongWendt, KarlWalker, Adam G.Kelley, TaraLazar, RachaelZywno, Meredith L.Connaire, Jeffrey J.Tentori, FrancescaYoung, AmyBrunelli, Steven M.2021-11-17T10:26:37-08:00doi:10.1681/ASN.2021060778hwp:resource-id:jnephrol;33/1/49American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, end-stage renal disease, ESRD, dialysis, coronavirus disease 2019, COVID-19, SARS-CoV-2, vaccine, BNT162 vaccine, RNA, messengerRapid CommunicationsRapid Communicationsresearch-article20222022-01-01January 202210.1681/ASN.20210607781046-66731533-34502021-11-17T10:26:37-08:002022-01Journal of the American Society of NephrologyRapid Communications3314957
- mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney Transplantation10.1681/ASN.2020121753Mon, 01 Nov 2021 08:27:53 GMT-07:00mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney TransplantationKaminski, HannahMarseres, GabrielYared, NathalieNokin, Marie-JuliePitard, VincentZouine, AtikaGarrigue, IsabelleLoizon, SéverineCapone, MyriamGauthereau, XavierMamani-Matsuda, MariaCoueron, RoxaneDurán, Raúl V.Pinson, BenoîtPellegrin, IsabelleThiébaut, RodolpheCouzi, LionelMerville, PierreDéchanet-Merville, Julie2021-11-01T08:27:53-07:00doi:10.1681/ASN.2020121753hwp:resource-id:jnephrol;33/1/121American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyCMV, mTOR inhibitors, CMV-specific immunity, kidney transplantationBasic ResearchBasic Researchresearch-article20222022-01-01January 202210.1681/ASN.20201217531046-66731533-34502021-11-01T08:27:53-07:002022-01Journal of the American Society of NephrologyBasic Research331112161378
- Effect of Nudge-Based Intervention on Adherence to Physician Visit Recommendations and Early Health Outcomes among Individuals Identified with Chronic Kidney Disease in Screens10.1681/ASN.2021050664Mon, 13 Dec 2021 03:46:39 GMT-08:00Effect of Nudge-Based Intervention on Adherence to Physician Visit Recommendations and Early Health Outcomes among Individuals Identified with Chronic Kidney Disease in ScreensFukuma, ShingoSasaki, ShusakuTaguri, MasatakaGoto, ReiMisumi, ToshihiroSaigusa, YusukeTsugawa, Yusuke2021-12-13T15:46:39-08:00doi:10.1681/ASN.2021050664hwp:resource-id:jnephrol;33/1/175American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, behavioral economic intervention, randomized clinical trial, behavioral economics, outcome assessment, health careClinical ResearchClinical Researchresearch-article20222022-01-01January 202210.1681/ASN.20210506641046-66731533-34502021-12-13T15:46:39-08:002022-01Journal of the American Society of NephrologyClinical Research3311175918511
- We Must all Join the Effort to Dismantle Environmental Racism10.1681/ASN.2021081118Wed, 17 Nov 2021 10:26:37 GMT-08:00We Must all Join the Effort to Dismantle Environmental RacismAl-Aly, Ziyad2021-11-17T10:26:37-08:00doi:10.1681/ASN.2021081118hwp:resource-id:jnephrol;33/1/12American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyracism, air pollution, inequity, environment, environmental justice, environmental racism, pollution, climate change, kidney, racial and ethnic disparitiesUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20222022-01-01January 202210.1681/ASN.20210811181046-66731533-34502021-11-17T10:26:37-08:002022-01Journal of the American Society of NephrologyUp Front Matters3311214
- Three-Dimensional Visualization of the Podocyte Actin Network Using Integrated Membrane Extraction, Electron Microscopy, and Machine Learning10.1681/ASN.2021020182Wed, 10 Nov 2021 10:48:42 GMT-08:00Three-Dimensional Visualization of the Podocyte Actin Network Using Integrated Membrane Extraction, Electron Microscopy, and Machine LearningQu, ChengqingRoth, RobynPuapatanakul, PongpratchLoitman, CharlesHammad, DinaGenin, Guy M.Miner, Jeffrey H.Suleiman, Hani Y.2021-11-10T10:48:42-08:00doi:10.1681/ASN.2021020182hwp:resource-id:jnephrol;33/1/155American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, actin, intermediate filaments, cytoskeletonBasic ResearchBasic Researchresearch-article20222022-01-01January 202210.1681/ASN.20210201821046-66731533-34502021-11-10T10:48:42-08:002022-01Journal of the American Society of NephrologyBasic Research331155173
- Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis10.1681/ASN.2021040575Fri, 22 Oct 2021 10:35:33 GMT-07:00Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during NephritisIchii, OsamuHosotani, MarinaMasum, Md. AbdulHorino, TaroOtani, YukiNamba, TakashiNakamura, TeppeiHosny Ali, Elewa YaserKon, Yasuhiro2021-10-22T10:35:33-07:00doi:10.1681/ASN.2021040575hwp:resource-id:jnephrol;33/1/88American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologychemokine, immunology and pathology, kidney anatomy, chronic inflammation, fibroblast, histopathology, nephritis, pathology, pathophysiology of renal disease and progression, pyelonephritisBasic ResearchBasic Researchresearch-article20222022-01-01January 202210.1681/ASN.20210405751046-66731533-34502021-10-22T10:35:33-07:002022-01Journal of the American Society of NephrologyBasic Research3311188i4107i6
- Disarming the Old Foe. Restoring T-Cell Immune Function with mTor-Inhibitors to Tackle Cytomegalovirus Infection10.1681/ASN.2021111471Thu, 30 Dec 2021 10:00:29 GMT-08:00Disarming the Old Foe. Restoring T-Cell Immune Function with mTor-Inhibitors to Tackle Cytomegalovirus InfectionBestard, OriolCrespo, Elena2021-12-30T10:00:29-08:00doi:10.1681/ASN.2021111471hwp:resource-id:jnephrol;33/1/6American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologycytomegalovirus, kidney transplantation, immunology and pathologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20222022-01-01January 202210.1681/ASN.20211114711046-66731533-34502021-12-30T10:00:29-08:002022-01Journal of the American Society of NephrologyUp Front Matters331161218137
- A Novel Pathological Mechanism of Tertiary Lymphoid Structure Formation in the Renal Pelvis10.1681/ASN.2021111465Mon, 13 Dec 2021 01:40:58 GMT-08:00A Novel Pathological Mechanism of Tertiary Lymphoid Structure Formation in the Renal PelvisYamamoto, ShinyaYanagita, Motoko2021-12-13T13:40:58-08:00doi:10.1681/ASN.2021111465hwp:resource-id:jnephrol;33/1/4American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologytertiary lymphoid structure, tertiary lymphoid tissue, pelvisUp Front MattersEditorialsUp Front MattersEditorialseditorial20222022-01-01January 202210.1681/ASN.20211114651046-66731533-34502021-12-13T13:40:58-08:002022-01Journal of the American Society of NephrologyUp Front Matters331114i886i107
- Genome-wide Admixture Mapping of eGFR and CKD Identify European and African Ancestry-of-Origin Loci in US Hispanics/Latinos10.1681/ASN.2021101346Tue, 14 Dec 2021 05:48:41 GMT-08:00Genome-wide Admixture Mapping of eGFR and CKD Identify European and African Ancestry-of-Origin Loci in US Hispanics/LatinosNestor, Jordan G.Winkler, Cheryl A.2021-12-14T05:48:41-08:00doi:10.1681/ASN.2021101346hwp:resource-id:jnephrol;33/1/1American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologyadmixture, chronic kidney disease, admixture mapping, eGFR, Hispanic, LatinoUp Front MattersEditorialsUp Front MattersEditorialseditorial20222022-01-01January 202210.1681/ASN.20211013461046-66731533-34502021-12-14T05:48:41-08:002022-01Journal of the American Society of NephrologyUp Front Matters3311177387
- Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular Disease10.1681/ASN.2020060858Wed, 01 Dec 2021 09:28:12 GMT-08:00Super-Resolution Imaging of the Filtration Barrier Suggests a Role for Podocin R229Q in Genetic Predisposition to Glomerular DiseaseButt, LinusUnnersjö-Jess, DavidHöhne, MartinHahnfeldt, RobertReilly, DervlaRinschen, Markus M.Plagmann, IngoDiefenhardt, PaulBrähler, SebastianBrinkkötter, Paul T.Brismar, HjalmarBlom, HansSchermer, BernhardBenzing, Thomas2021-12-01T09:28:12-08:00doi:10.1681/ASN.2020060858hwp:resource-id:jnephrol;33/1/138American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, glomerular disease, human genetics, transgenic mouse, albuminuria, focal segmental glomerulosclerosisBasic ResearchBasic Researchresearch-article20222022-01-01January 202210.1681/ASN.20200608581046-66731533-34502021-12-01T09:28:12-08:002022-01Journal of the American Society of NephrologyBasic Research331138154
- Correction: Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells10.1681/ASN.2021111444Thu, 30 Dec 2021 10:00:29 GMT-08:00Correction: Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem CellsAmerican Society of Nephrology2021-12-30T10:00:29-08:00doi:10.1681/ASN.2021111444hwp:resource-id:jnephrol;33/1/253American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20222022-01-01January 202210.1681/ASN.20211114441046-66731533-34502021-12-30T10:00:29-08:002022-01Journal of the American Society of NephrologyErrata3330122253304304253321321
- Regrow or Repair: An Update on Potential Regenerative Therapies for the KidneyFifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.10.1681/ASN.2021081073Wed, 17 Nov 2021 10:26:37 GMT-08:00Regrow or Repair: An Update on Potential Regenerative Therapies for the KidneyFifteen years ago, this journal published a review outlining future options for regenerating the kidney. At that time, stem cell populations were being identified in multiple tissues, the concept of stem cell recruitment to a site of injury was of great interest, and the possibility of postnatal renal stem cells was growing in momentum. Since that time, we have seen the advent of human induced pluripotent stem cells, substantial advances in our capacity to both sequence and edit the genome, global and spatial transcriptional analysis down to the single-cell level, and a pandemic that has challenged our delivery of health care to all. This article will look back over this period of time to see how our view of kidney development, disease, repair, and regeneration has changed and envision a future for kidney regeneration and repair over the next 15 years.Little, Melissa H.Humphreys, Benjamin D.2021-11-17T10:26:37-08:00doi:10.1681/ASN.2021081073hwp:resource-id:jnephrol;33/1/15American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, stem cell, regenerative therapies, single-cell expression profiling, pluripotent stem cell, directed differentiation, tissue repair, gene editingReviewReviewreview-article20222022-01-01January 202210.1681/ASN.20210810731046-66731533-34502021-11-17T10:26:37-08:002022-01Journal of the American Society of NephrologyReview3311532
- Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology10.1681/ASN.2021060794Wed, 03 Nov 2021 09:34:18 GMT-07:00Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune EtiologyWatts, Andrew J.B.Keller, Keith H.Lerner, GabrielRosales, IvyCollins, A. BernardSekulic, MiroslavWaikar, Sushrut S.Chandraker, AnilRiella, Leonardo V.Alexander, Mariam P.Troost, Jonathan P.Chen, JunboFermin, DamianYee, Jennifer L.Sampson, Matthew G.Beck, Laurence H.Henderson, Joel M.Greka, AnnaRennke, Helmut G.Weins, Astrid2021-11-03T09:34:18-07:00doi:10.1681/ASN.2021060794hwp:resource-id:jnephrol;33/1/238American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, proteinuria, nephrin, glomerular disease, glomerular filtration barrier, autoantibodies, idiopathic nephrotic syndrome, immunology, pathologyClinical ResearchClinical Researchresearch-article20222022-01-01January 202210.1681/ASN.20210607941046-66731533-34502021-11-03T09:34:18-07:002022-01Journal of the American Society of NephrologyClinical Research331133238i653654252i654654
- COVID-19 Vaccine Type and Humoral Immune Response in Patients Receiving Dialysis10.1681/ASN.2021070936Wed, 13 Oct 2021 08:38:50 GMT-07:00COVID-19 Vaccine Type and Humoral Immune Response in Patients Receiving DialysisGarcia, PabloAnand, ShuchiHan, JialinMontez-Rath, Maria E.Sun, SumiShang, TiffanyParsonnet, JulieChertow, Glenn M.Schiller, BrigitteAbra, Graham2021-10-13T08:38:50-07:00doi:10.1681/ASN.2021070936hwp:resource-id:jnephrol;33/1/33American Society of NephrologyCopyright © 2022 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, vaccine, SARS-CoV-2, ESKD, immunity, humoral, immunization, COVID-19Research LetterResearch Letterletter20222022-01-01January 202210.1681/ASN.20210709361046-66731533-34502021-10-13T08:38:50-07:002022-01Journal of the American Society of NephrologyResearch Letter3313337
- Quantitative Super-Resolution Microscopy Reveals Promoting Mitochondrial Interconnectivity Protects against AKI10.34067/KID.0001602021Wed, 13 Oct 2021 11:48:09 GMT-07:00Quantitative Super-Resolution Microscopy Reveals Promoting Mitochondrial Interconnectivity Protects against AKITaguchi, KenseiElias, Bertha C.Krystofiak, EvanQian, SuboSant, SnehalYang, HaichunFogo, Agnes B.Brooks, Craig R.2021-10-13T11:48:09-07:00doi:10.34067/KID.0001602021hwp:resource-id:kidney360;2/12/1892American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute renal failure, basic science, cell adhesion, cell biology and structure, electron microscopy, endoplasmic reticulum, ischemia-reperfusion, mitochondria, pathology, renal morphology, renal proximal tubule cellOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-12-3010.34067/KID.00016020212641-76502021-10-13T11:48:09-07:002021-12-30Kidney360Original Investigation21218921907
- The Sisyphean Task of Getting the Arteriovenous Fistula to Mature10.34067/KID.0007452021Thu, 30 Dec 2021 05:30:29 GMT-08:00The Sisyphean Task of Getting the Arteriovenous Fistula to MatureBartolomeo, KoreyVachharajani, Tushar J.Shingarev, Roman2021-12-30T05:30:29-08:00doi:10.34067/KID.0007452021hwp:resource-id:kidney360;2/12/1873American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, AVF failure, AVF maturation, central vein, ESKD, ESRD, hemodialysis, TDC, TVC, vascular accessEditorialEditorialeditorial20212021-12-3010.34067/KID.00074520212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Editorial21218731875
- Pathogenic LAMA5 Variants and Kidney Disease10.34067/KID.0007312021Thu, 30 Dec 2021 05:30:29 GMT-08:00Pathogenic LAMA5 Variants and Kidney DiseaseSavige, JudyHarraka, Philip2021-12-30T05:30:29-08:00doi:10.34067/KID.0007312021hwp:resource-id:kidney360;2/12/1876American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360genetics, Alport syndrome, basement membrane, collagen IV, FSGS, genetic kidney disease, kidney cysts, laminin, modifying variants, pathogenic variants, Pierson syndromeEditorialEditorialeditorial20212021-12-3010.34067/KID.00073120212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Editorial21218761879
- Challenges, Facilitators, and Recommendations for Implementation of Home Dialysis in the Veterans Health Administration: Patient, Caregiver, and Clinician Perceptions10.34067/KID.0000642021Wed, 22 Sep 2021 05:30:15 GMT-07:00Challenges, Facilitators, and Recommendations for Implementation of Home Dialysis in the Veterans Health Administration: Patient, Caregiver, and Clinician PerceptionsJones, Lindsey A.Gordon, Elisa J.Hogan, Timothy P.Fiandaca, Cindi A.Smith, Bridget M.Stroupe, Kevin T.Fischer, Michael J.2021-09-22T05:30:15-07:00doi:10.34067/KID.0000642021hwp:resource-id:kidney360;2/12/1928American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, caregivers, home hemodialysis, kidney diseases, veteransOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-12-3010.34067/KID.00006420212641-76502021-09-22T05:30:15-07:002021-12-30Kidney360Original Investigation21219281944
- Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation10.34067/KID.0005062021Tue, 28 Sep 2021 06:18:54 GMT-07:00Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney TransplantationAkalin, EnverWeir, Matthew R.Bunnapradist, SuphamaiBrennan, Daniel C.Delos Santos, RowenaLangone, AnthonyDjamali, ArjangXu, HuaJin, XiaDholakia, ShamWoodward, Robert N.Bromberg, Jonathan S.2021-09-28T06:18:54-07:00doi:10.34067/KID.0005062021hwp:resource-id:kidney360;2/12/1998American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, allograft rejection, antibody-mediated rejection, donor-derived cell-free DNA, gene expression profiling, kidney transplantation, T cell-mediated rejectionOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-12-3010.34067/KID.00050620212641-76502021-09-28T06:18:54-07:002021-12-30Kidney360Original Investigation21219982009
- Eosinophilia and Skin Rash in a Patient with Uncontrolled Hypertension and AKI10.34067/KID.0004422021Thu, 30 Dec 2021 05:30:29 GMT-08:00Eosinophilia and Skin Rash in a Patient with Uncontrolled Hypertension and AKIAklilu, Abinet M.2021-12-30T05:30:29-08:00doi:10.34067/KID.0004422021hwp:resource-id:kidney360;2/12/2038American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, atheroemboli, cholesterol crystals, eosinophilia, exanthema, hypertension, livedo reticularisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-12-3010.34067/KID.00044220212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Clinical Images in Nephrology and Dialysis21220382039
- Scarce Health Care Resources and Equity during COVID-19: Lessons from the History of Kidney Failure Treatment10.34067/KID.0005292021Sat, 23 Oct 2021 06:07:33 GMT-07:00Scarce Health Care Resources and Equity during COVID-19: Lessons from the History of Kidney Failure TreatmentButler, Catherine R.Wightman, Aaron G.2021-10-23T06:07:33-07:00doi:10.34067/KID.0005292021hwp:resource-id:kidney360;2/12/2024American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, coronavirus disease 2019, COVID-19, delivery of health care, dialysis, ethics, health care resources, policy, renal insufficiency, triagePerspectivePerspectiveresearch-article20212021-12-3010.34067/KID.00052920212641-76502021-10-23T06:07:33-07:002021-12-30Kidney360Perspective21220242026
- Suitability for Kidney Transplantation in AL Amyloidosis: A Survey Study of Transplant and Amyloidosis Physicians10.34067/KID.0004232021Thu, 14 Oct 2021 12:46:20 GMT-07:00Suitability for Kidney Transplantation in AL Amyloidosis: A Survey Study of Transplant and Amyloidosis PhysiciansLam, RobertLim, Mary AnnDember, Laura M.2021-10-14T12:46:20-07:00doi:10.34067/KID.0004232021hwp:resource-id:kidney360;2/12/1987American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, AL amyloidosis, amyloidosis, immunoglobulin light-chain amyloidosis, kidney transplantation, paraprotein-associated kidney disease, physicians, plasma cell disorder, stem cell transplantation, surveys and questionnairesOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-12-3010.34067/KID.00042320212641-76502021-10-14T12:46:20-07:002021-12-30Kidney360Original Investigation21219871997
- The In-Center Hemodialysis Unit, Yet Another Obstacle to Home Dialysis10.34067/KID.0007372021Thu, 30 Dec 2021 05:30:29 GMT-08:00The In-Center Hemodialysis Unit, Yet Another Obstacle to Home DialysisLynch, Matthew R.Shah, Ankur D.2021-12-30T05:30:29-08:00doi:10.34067/KID.0007372021hwp:resource-id:kidney360;2/12/1871American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, home hemodialysis, renal dialysisEditorialEditorialeditorial20212021-12-3010.34067/KID.00073720212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Editorial21218711872
- Impact of Previous Tunneled Vascular Catheters and their Location on Upper Limb Arteriovenous Fistula Function10.34067/KID.0003362021Thu, 07 Oct 2021 01:29:17 GMT-07:00Impact of Previous Tunneled Vascular Catheters and their Location on Upper Limb Arteriovenous Fistula FunctionDiep, JasonMakris, AngelaDe Guzman, ImeldaWong, JefferyAravindan, AnanthakrishnapuramNandakoban, HareeshanNarayanan, Govind2021-10-07T13:29:17-07:00doi:10.34067/KID.0003362021hwp:resource-id:kidney360;2/12/1953American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, catheter, end-stage kidney disease, fistula, function, hemodialysis, patency, tunneled, vascatheter, vascular accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-12-3010.34067/KID.00033620212641-76502021-10-07T13:29:17-07:002021-12-30Kidney360Original Investigation21219531959
- Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis10.34067/KID.0004372021Wed, 22 Sep 2021 05:30:15 GMT-07:00Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient HemodialysisBardossy, Ana CeciliaKorhonen, LaurenSchatzman, SabrinaGable, PaigeHerzig, CarolynBrown, Nicole E.Beshearse, ElizabethVarela, KateSabour, SarahLyons, Amanda K.Overton, RahsaanHudson, MatthewHernandez-Romieu, Alfonso C.Alvarez, JorgeRoman, KaylinWeng, MarkSoda, ElizabethPatel, Priti R.Grate, CrystalDalrymple, Lorien S.Wingard, Rebecca L.Thornburg, Natalie J.Halpin, Alison S. LauferFolster, Jennifer M.Tobin-D’Angelo, MelissaLea, JaniceApata, IbironkeMcDonald, L. CliffordBrown, Allison C.Kutty, Preeta K.Novosad, ShannonWilson, W. WyattTobolowsky, FarrellGilbert, Sarah E.Huang, JenniferGualandi, NicoleAnsari, UzmaPerry-Dow, K. AllisonMcAllister, Gillian A.Whitworth, CarrieSanders, CarrieTamin, AzaibiHarcourt, Jennifer L.Freeman, BrandiLester, SandraMills, LisaStumpf, MeganFurin, WilliamSpicer, LoriAdamczyk, MichelleChan, MonicaBhatnagar, AmeliaReese, NatashiaBalbuena, RocioAnderson, KarenLonsway, DavidBreaker, ErinRasheed, James K.Houston, HollisCrayton, KarlosTran, LisaCampbell, DavinaPaulick, Ashley LynGade, LalithaGalloway, ReneeHartloge, ClaireJenkins, BrentMedrzycki, MagdalenaSahibzada, KashifShewmaker, PatriciaWynn, NhienVelusamy, SrinivasanWong, PhiliZheng, HaoQiangTejada-Strop, AlexandraJain, Shilpi2021-09-22T05:30:15-07:00doi:10.34067/KID.0004372021hwp:resource-id:kidney360;2/12/1917American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, chronic kidney failure, COVID-19, dialysis, end-stage renal disease, ESRD, infectiousness, infectivity, outpatients, SARS-CoV-2Original InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-12-3010.34067/KID.00043720212641-76502021-09-22T05:30:15-07:002021-12-30Kidney360Original Investigation21219171927
- An Unusual Cause of AKI in a Kidney Transplant Patient with Merkel Cell Cancer10.34067/KID.0004472021Thu, 30 Dec 2021 05:30:29 GMT-08:00An Unusual Cause of AKI in a Kidney Transplant Patient with Merkel Cell CancerWu, Henry H.L.Jeyalan, VishnuPonnusamy, Arvind2021-12-30T05:30:29-08:00doi:10.34067/KID.0004472021hwp:resource-id:kidney360;2/12/2040American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, immunosuppression, Merkel cell carcinoma, transplantationClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-12-3010.34067/KID.00044720212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Clinical Images in Nephrology and Dialysis21220402041
- Course Corrections for Clinical AI10.34067/KID.0004152021Mon, 27 Sep 2021 01:35:00 GMT-07:00Course Corrections for Clinical AIDeGrave, Alex J.Janizek, Joseph D.Lee, Su-In2021-09-27T13:35:00-07:00doi:10.34067/KID.0004152021hwp:resource-id:kidney360;2/12/2019American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, AI, artificial intelligence, CAD, clinical decision support, electronic medical record, evidence-based, FDA, job satisfaction, machine learning, MLPerspectivePerspectiveresearch-article20212021-12-3010.34067/KID.00041520212641-76502021-09-27T13:35:00-07:002021-12-30Kidney360Perspective21220192023
- Autosomal Dominant Polycystic Kidney Disease Prevalence among a Racially Diverse United States Population, 2002 through 201810.34067/KID.0004522021Wed, 22 Sep 2021 05:30:15 GMT-07:00Autosomal Dominant Polycystic Kidney Disease Prevalence among a Racially Diverse United States Population, 2002 through 2018Aung, Thet T.Bhandari, Simran K.Chen, QiaolingMalik, Fatima TWilley, Cynthia J.Reynolds, KristiJacobsen, Steven J.Sim, John J.2021-09-22T05:30:15-07:00doi:10.34067/KID.0004522021hwp:resource-id:kidney360;2/12/2010American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, autosomal dominant polycystic kidney, autosomal dominant polycystic kidney disease, electronic health records, epidemiology, genetic kidney disease, prevalence, racial/ethnic diversity, United StatesBrief CommunicationCystic Kidney DiseaseBrief CommunicationCystic Kidney Diseaseresearch-article20212021-12-3010.34067/KID.00045220212641-76502021-09-22T05:30:15-07:002021-12-30Kidney360Brief Communication21220102015
- Global Perspective on Kidney Transplantation: Brazil10.34067/KID.0003612021Thu, 07 Oct 2021 01:29:17 GMT-07:00Global Perspective on Kidney Transplantation: BrazilCristelli, Marina PontelloFerreira, Gustavo FernandesMedina-Pestana, José2021-10-07T13:29:17-07:00doi:10.34067/KID.0003612021hwp:resource-id:kidney360;2/12/2016American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, Brazil, graft survival, kidney transplantationGlobal PerspectiveGlobal Perspectiveresearch-article20212021-12-3010.34067/KID.00036120212641-76502021-10-07T13:29:17-07:002021-12-30Kidney360Global Perspective21220162018
- Optimizing the Electronic Health Record for Clinical Research: Has the Time Come?10.34067/KID.0007052021Thu, 30 Dec 2021 05:30:29 GMT-08:00Optimizing the Electronic Health Record for Clinical Research: Has the Time Come?Rheault, Michelle N.2021-12-30T05:30:29-08:00doi:10.34067/KID.0007052021hwp:resource-id:kidney360;2/12/1880American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, computable phenotype, electronic health recordEditorialEditorialeditorial20212021-12-3010.34067/KID.00070520212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Editorial21218801881
- Polycystic Kidney Disease in the Real World10.34067/KID.0007062021Thu, 30 Dec 2021 05:30:29 GMT-08:00Polycystic Kidney Disease in the Real WorldChapman, Arlene B.McGill, Rita2021-12-30T05:30:29-08:00doi:10.34067/KID.0007062021hwp:resource-id:kidney360;2/12/1882American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, autosomal dominant polycystic kidney disease, economic and social conditions, ethnic groups, United StatesEditorialEditorialeditorial20212021-12-3010.34067/KID.00070620212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Editorial21218821883
- Rationale and Trial Design of MesEnchymal Stem Cell Trial in Preventing Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula (MEST AVF Trial)10.34067/KID.0005182021Mon, 27 Sep 2021 01:35:00 GMT-07:00Rationale and Trial Design of MesEnchymal Stem Cell Trial in Preventing Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula (MEST AVF Trial)Piryani, Ameet K.Kilari, SreenivasuluTakahashi, EdwinDeMartino, Randall R.Mandrekar, JayDietz, Allan B.Misra, Sanjay2021-09-27T13:35:00-07:00doi:10.34067/KID.0005182021hwp:resource-id:kidney360;2/12/1945American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, mesenchymal stem cells, pathologic constriction, vascular diseases, vascular stenosisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-12-3010.34067/KID.00051820212641-76502021-09-27T13:35:00-07:002021-12-30Kidney360Original Investigation21219451952
- The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing Facilities10.34067/KID.0004762021Thu, 14 Oct 2021 12:46:20 GMT-07:00The Association between Prevalence of Peritoneal Dialysis versus Hemodialysis and Patients’ Distance to Dialysis-Providing FacilitiesPattharanitima, PattharawinEl Shamy, OsamaChauhan, KinsukSaha, AparnaWen, Huei HsunSharma, ShuchitaUribarri, JaimeChan, Lili2021-10-14T12:46:20-07:00doi:10.34067/KID.0004762021hwp:resource-id:kidney360;2/12/1908American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, distance, home dialysis, modality, patient choice, peritoneal dialysis, prevalenceOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-12-3010.34067/KID.00047620212641-76502021-10-14T12:46:20-07:002021-12-30Kidney360Original Investigation21219081916
- Acute Onset of Nausea, Vomiting and Left Flank Pain in a Hemodialysis Patient10.34067/KID.0004882021Thu, 30 Dec 2021 05:30:29 GMT-08:00Acute Onset of Nausea, Vomiting and Left Flank Pain in a Hemodialysis PatientGill, JasmeetDiaz, JesseSzerlip, Harold M.2021-12-30T05:30:29-08:00doi:10.34067/KID.0004882021hwp:resource-id:kidney360;2/12/2042American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, ESRD, flank pain, hematoma, hemodialysis, renal hemorrhage, spontaneousClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-12-3010.34067/KID.00048820212641-76502021-12-30T05:30:29-08:002021-12-30Kidney360Clinical Images in Nephrology and Dialysis21220422043
- SGLT2 Inhibitors: Physiology and PharmacologySGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 g (1 mol) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream, where theyremain in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50%–60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.10.34067/KID.0002772021Fri, 17 Sep 2021 09:47:50 GMT-07:00SGLT2 Inhibitors: Physiology and PharmacologySGLTs are sodium glucose transporters found on the luminal membrane of the proximal tubule, where they reabsorb some 180 g (1 mol) of glucose from the glomerular filtrate each day. The natural glucoside phlorizin completely blocks glucose reabsorption. Oral SGLT2 inhibitors are rapidly absorbed into the blood stream, where theyremain in the circulation for hours. On glomerular filtration, they bind specifically to SGLT2 in the luminal membrane of the early proximal tubule to reduce glucose reabsorption by 50%–60%. Because of glucose excretion, these drugs lower plasma glucose and glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. The drugs also protect against heart and renal failure. The aim of this review is to summarize what is known about the physiology of renal SGLTs and the pharmacology of SGLT drugs.Wright, Ernest M.2021-09-17T09:47:50-07:00doi:10.34067/KID.0002772021hwp:resource-id:kidney360;2/12/2027American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360renal physiology, basic science, diabetes, glucose, heart failure, inhibitors, SGLT, SGLT2, sodium glucose transportersBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-12-3010.34067/KID.00027720212641-76502021-09-17T09:47:50-07:002021-12-30Kidney360Basic Science for Clinicians21220272037
- Clear Evidence of LAMA5 Gene Biallelic Truncating Variants Causing Infantile Nephrotic Syndrome10.34067/KID.0004952021Fri, 15 Oct 2021 12:51:19 GMT-07:00Clear Evidence of LAMA5 Gene Biallelic Truncating Variants Causing Infantile Nephrotic SyndromeTaniguchi, YukimasaNagano, ChinaSekiguchi, KiyotoshiTashiro, AtsushiSugawara, NorikoSakaguchi, HaruhideUmeda, ChisatoAoto, YuyaIshiko, ShinyaRossanti, RiniSakakibara, NanaHorinouchi, TomokoYamamura, TomohikoKondo, AtsushiNagai, SadayukiNagase, HiroakiIijima, KazumotoMiner, Jeffrey H.Nozu, Kandai2021-10-15T12:51:19-07:00doi:10.34067/KID.0004952021hwp:resource-id:kidney360;2/12/1968American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, LAMA5, nephrotic syndrome, pathology, SRNSOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-12-3010.34067/KID.00049520212641-76502021-10-15T12:51:19-07:002021-12-30Kidney360Original Investigation21219681978
- Characteristics Associated with Variation in Corticosteroid Exposure in Children with Steroid-Sensitive Nephrotic Syndrome: Results from a Canadian Longitudinal Study10.34067/KID.0002692021Thu, 23 Sep 2021 06:29:13 GMT-07:00Characteristics Associated with Variation in Corticosteroid Exposure in Children with Steroid-Sensitive Nephrotic Syndrome: Results from a Canadian Longitudinal StudyRodriguez-Lopez, SaraChanchlani, RahulDart, Allison B.Morgan, Catherine J.Lapeyraque, Anne-LaureTee, James B.Brobbey, AnitaPerinpanayagam, Maneka A.Samuel, SusanNettel-Aguirre, Alberto2021-09-23T06:29:13-07:00doi:10.34067/KID.0002692021hwp:resource-id:kidney360;2/12/1960American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, adrenal cortex hormones, children, glucocorticoids, longitudinal study, nephrotic syndrome, practice variation, steroidsOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-12-3010.34067/KID.00026920212641-76502021-09-23T06:29:13-07:002021-12-30Kidney360Original Investigation21219601967
- Complement Activation Fragments Are Increased in Critically Ill Pediatric Patients with Severe AKI10.34067/KID.0004542021Thu, 07 Oct 2021 11:02:39 GMT-07:00Complement Activation Fragments Are Increased in Critically Ill Pediatric Patients with Severe AKIStenson, Erin K.You, ZhiyingReeder, RonNorris, JesseScott, Halden F.Dixon, Bradley P.Thurman, Joshua M.Frazer-Abel, AshleyMourani, PeterKendrick, Jessica2021-10-07T11:02:39-07:00doi:10.34067/KID.0004542021hwp:resource-id:kidney360;2/12/1884American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, complement, complement activation, critical illness, pediatric nephrologyOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-12-3010.34067/KID.00045420212641-76502021-10-07T11:02:39-07:002021-12-30Kidney360Original Investigation21218841891
- Validating a Computable Phenotype for Nephrotic Syndrome in Children and Adults Using PCORnet Data10.34067/KID.0002892021Mon, 27 Sep 2021 01:35:00 GMT-07:00Validating a Computable Phenotype for Nephrotic Syndrome in Children and Adults Using PCORnet DataOliverio, Andrea L.Marchel, DorotaTroost, Jonathan P.Ayoub, IsabelleAlmaani, SalemGreco, JessicaTran, Cheryl L.Denburg, Michelle R.Matheny, MichaelDorn, ChadMassengill, Susan F.Desmond, HaileyGipson, Debbie S.Mariani, Laura H.2021-09-27T13:35:00-07:00doi:10.34067/KID.0002892021hwp:resource-id:kidney360;2/12/1979American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, computable phenotype, nephrotic syndrome, validationOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-12-3010.34067/KID.00028920212641-76502021-09-27T13:35:00-07:002021-12-30Kidney360Original Investigation21219791986
- Should We Let Dialysis Patients Eat Their Fruits and Veggies?10.2215/CJN.13521021Wed, 01 Dec 2021 02:31:10 GMT-08:00Should We Let Dialysis Patients Eat Their Fruits and Veggies?Kovesdy, Csaba P.2021-12-01T14:31:10-08:00doi:10.2215/CJN.13521021hwp:resource-id:clinjasn;16/12/1781American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, potassium, dietary intake, potassium restriction, mortality riskEditorialsEditorialseditorial20212021-12-01December 202110.2215/CJN.135210211555-90411555-905X2021-12-01T14:31:10-08:002021-12Clinical Journal of the American Society of NephrologyEditorials1612121781185117831861
- Telehealth and Kidney Disease Care10.2215/CJN.13651021Tue, 07 Dec 2021 11:35:23 GMT-08:00Telehealth and Kidney Disease CareLew, Susie Q.Sikka, Neal2021-12-07T11:35:23-08:00doi:10.2215/CJN.13651021hwp:resource-id:clinjasn;16/12/1784American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytelehealth, telemedicine, chronic kidney disease, nephrology, internet, COVID-19, end stage kidney disease, virtual visitsEditorialsEditorialseditorial20212021-12-01December 202110.2215/CJN.136510211555-90411555-905X2021-12-07T11:35:23-08:002021-12Clinical Journal of the American Society of NephrologyEditorials16121212178418131773178618231774
- Time to Abandon Kidney Biopsy to Diagnose Membranous Nephropathy?10.2215/CJN.11180821Mon, 15 Nov 2021 05:39:42 GMT-08:00Time to Abandon Kidney Biopsy to Diagnose Membranous Nephropathy?Ronco, PierrePlaisier, Emmanuelle2021-11-15T17:39:42-08:00doi:10.2215/CJN.11180821hwp:resource-id:clinjasn;16/12/1787American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulosclerosis, nephrology, membranous nephropathyEditorialsEditorialseditorial20212021-12-01December 202110.2215/CJN.111808211555-90411555-905X2021-11-15T17:39:42-08:002021-12Clinical Journal of the American Society of NephrologyEditorials1612121787183317891839
- When and How Is It Possible to Stop Therapy in Patients with Lupus NephritisGlucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE and lupus nephritis. The refined use of these drugs over the years has allowed us to obtain stable disease remission and improvement of long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review, we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal, around one-quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission for even 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.10.2215/CJN.04830421Wed, 23 Jun 2021 10:54:11 GMT-07:00When and How Is It Possible to Stop Therapy in Patients with Lupus NephritisGlucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE and lupus nephritis. The refined use of these drugs over the years has allowed us to obtain stable disease remission and improvement of long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review, we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal, around one-quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission for even 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.Moroni, GabriellaFrontini, GiuliaPonticelli, Claudio2021-06-23T10:54:11-07:00doi:10.2215/CJN.04830421hwp:resource-id:clinjasn;16/12/1909American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, systemic lupus erythematosus, immunosuppression, immunology and pathologyReviewsReviewsreview-article20212021-12-01December 202110.2215/CJN.048304211555-90411555-905X2021-06-23T10:54:11-07:002021-12Clinical Journal of the American Society of NephrologyReviews161219091917
- Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United States10.2215/CJN.06740521Wed, 20 Oct 2021 02:00:09 GMT-07:00Racial Disparities in Pediatric Kidney Transplantation under the New Kidney Allocation System in the United StatesKrissberg, Jill R.Kaufmann, Matthew B.Gupta, AnshalBendavid, EranStedman, MargaretCheng, Xingxing S.Tan, Jane C.Grimm, Paul C.Chaudhuri, Abanti2021-10-20T14:00:09-07:00doi:10.2215/CJN.06740521hwp:resource-id:clinjasn;16/12/1862American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatric kidney transplantation, disparity, ethnicity, pediatrics, kidney transplantationOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-12-01December 202110.2215/CJN.067405211555-90411555-905X2021-10-20T14:00:09-07:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles161218621871
- Kidney Replacement Therapy for Patients Requiring Cardiopulmonary Bypass Support during Cardiac Surgery10.2215/CJN.07150521Wed, 27 Oct 2021 08:27:54 GMT-07:00Kidney Replacement Therapy for Patients Requiring Cardiopulmonary Bypass Support during Cardiac SurgeryStevens, Jacob S.Radhakrishnan, Jai2021-10-27T08:27:54-07:00doi:10.2215/CJN.07150521hwp:resource-id:clinjasn;16/12/1898American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacidosis, cardiovascular disease, clinical nephrology, dialysis, electrolytes, cardiopulmonary bypass, kidney replacement therapyKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20212021-12-01December 202110.2215/CJN.071505211555-90411555-905X2021-10-27T08:27:54-07:002021-12Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat161218981900
- Correction: Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood10.2215/CJN.13391021Tue, 07 Dec 2021 11:35:23 GMT-08:00Correction: Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in ChildhoodAmerican Society of Nephrology2021-12-07T11:35:23-08:00doi:10.2215/CJN.13391021hwp:resource-id:clinjasn;16/12/1877American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, pediatric nephrology, glomerulopathy, Antineutrophil cytoplasmic antibodyErratumErratumcorrection20212021-12-01December 202110.2215/CJN.133910211555-90411555-905X2021-12-07T11:35:23-08:002021-12Clinical Journal of the American Society of NephrologyErratum16161271877104318771051
- APOL1 Kidney Risk Variants and Acute Kidney Injury in Those with COVID-1910.2215/CJN.13571021Tue, 07 Dec 2021 11:35:23 GMT-08:00APOL1 Kidney Risk Variants and Acute Kidney Injury in Those with COVID-19Gadegbeku, Crystal A.Sedor, John R.2021-12-07T11:35:23-08:00doi:10.2215/CJN.13571021hwp:resource-id:clinjasn;16/12/1779American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, APOL1, acute kidney injury, social determinants, Black Americans, disparityEditorialsEditorialseditorial20212021-12-01December 202110.2215/CJN.135710211555-90411555-905X2021-12-07T11:35:23-08:002021-12Clinical Journal of the American Society of NephrologyEditorials1612121779179017801796
- Humoral Response to BNT162b2 mRNA SARS-CoV-2 Vaccine in Patients with Nondialysis Chronic Kidney Disease10.2215/CJN.09110721Wed, 03 Nov 2021 09:34:38 GMT-07:00Humoral Response to BNT162b2 mRNA SARS-CoV-2 Vaccine in Patients with Nondialysis Chronic Kidney DiseaseKervella, DelphineBraud, PierreGarandeau, ClairePhelizot, CelineAmbrosi, XavierBlancho, GillesHourmant, MaryvonneFigueres, LucileBlancho, GillesBranchereau, JulienCantarovich, DiegoChapelet, AgnèsDantal, JacquesDeltombe, ClémentFigueres, LucileGaisne, RaphaelGarandeau, ClaireGiral, MagaliGourraud-Vercel, CarolineHourmant, MaryvonneKaram, GeorgesKerleau, ClarisseKervella, DelphineMasset, ChristopheMeurette, AurélieVille, SimonKandell, ChristineMoreau, AnneRenaudin, KarineDelbos, FlorentWalencik, AlexandreDevis, Anne2021-11-03T09:34:38-07:00doi:10.2215/CJN.09110721hwp:resource-id:clinjasn;16/12/1872American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, SARS-CoV-2, chronic kidney disease, vaccineResearch LettersResearch Lettersletter20212021-12-01December 202110.2215/CJN.091107211555-90411555-905X2021-11-03T09:34:38-07:002021-12Clinical Journal of the American Society of NephrologyResearch Letters161218721874
- Association of Polypharmacy with Kidney Disease Progression in Adults with CKD10.2215/CJN.03940321Mon, 15 Nov 2021 04:21:19 GMT-08:00Association of Polypharmacy with Kidney Disease Progression in Adults with CKDKimura, HiroshiTanaka, KenichiSaito, HirotakaIwasaki, TsuyoshiOda, AkiraWatanabe, ShuheiKanno, MakotoShimabukuro, MichioAsahi, KoichiWatanabe, TsuyoshiKazama, Junichiro James2021-11-15T16:21:19-08:00doi:10.2215/CJN.03940321hwp:resource-id:clinjasn;16/12/1797American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypolypharmacy, CKD, mortality, cardiovascular disease, prognosis, chronic renal insufficiencyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-12-01December 202110.2215/CJN.039403211555-90411555-905X2021-11-15T16:21:19-08:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles161217971804
- Food Insecurity and Kidney Disease10.2215/CJN.07860621Wed, 13 Oct 2021 08:24:05 GMT-07:00Food Insecurity and Kidney DiseaseMokiao, ReyaHingorani, Sangeeta2021-10-13T08:24:05-07:00doi:10.2215/CJN.07860621hwp:resource-id:clinjasn;16/12/1903American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, disparity, food insecurityPerspectivesPerspectivesresearch-article20212021-12-01December 202110.2215/CJN.078606211555-90411555-905X2021-10-13T08:24:05-07:002021-12Clinical Journal of the American Society of NephrologyPerspectives161219031905
- The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function10.2215/CJN.07340521Wed, 01 Dec 2021 11:42:19 GMT-08:00The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney FunctionWaijer, Simke W.Gansevoort, Ron T.Bakris, George L.Correa-Rotter, RicardoHou, Fan-FanKohan, Donald E.Kitzman, Dalane W.Makino, HirofumiMcMurray, John J.V.Perkovic, VladoTobe, SheldonParving, Hans-Henrikde Zeeuw, DickHeerspink, Hiddo J.L.2021-12-01T11:42:19-08:00doi:10.2215/CJN.07340521hwp:resource-id:clinjasn;16/12/1824American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyatrasentan, endothelin receptor antagonist, albuminuria, kidney outcome, hospitalization for heart failure, heart failure, urinary tract physiological phenomenaOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20212021-12-01December 202110.2215/CJN.073405211555-90411555-905X2021-12-01T11:42:19-08:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles1612121824177518321778
- Classification of Uremic Toxins and Their Role in Kidney FailureAdvances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.10.2215/CJN.02660221Wed, 07 Jul 2021 11:09:02 GMT-07:00Classification of Uremic Toxins and Their Role in Kidney FailureAdvances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.Rosner, Mitchell H.Reis, ThiagoHusain-Syed, FaeqVanholder, RaymondHutchison, ColinStenvinkel, PeterBlankestijn, Peter J.Cozzolino, MarioJuillard, LaurentKashani, KianoushKaushik, ManishKawanishi, HidekiMassy, ZiadSirich, Tammy LisaZuo, LiRonco, Claudio2021-07-07T11:09:02-07:00doi:10.2215/CJN.02660221hwp:resource-id:clinjasn;16/12/1918American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuremia, dialysis, middle molecule, definition, classificationReviewsReviewsreview-article20212021-12-01December 202110.2215/CJN.026602211555-90411555-905X2021-07-07T11:09:02-07:002021-12Clinical Journal of the American Society of NephrologyReviews161219181928
- Patient Views on Telehealth for Kidney Disease Care10.2215/CJN.13531021Tue, 07 Dec 2021 11:35:23 GMT-08:00Patient Views on Telehealth for Kidney Disease CareGlennon, Julie2021-12-07T11:35:23-08:00doi:10.2215/CJN.13531021hwp:resource-id:clinjasn;16/12/1773American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, dialysis, ESRD, telemedicinePatient VoicePatient Voiceresearch-article20212021-12-01December 202110.2215/CJN.135310211555-90411555-905X2021-12-07T11:35:23-08:002021-12Clinical Journal of the American Society of NephrologyPatient Voice16121212177318131784177418231786
- Humoral Response to One and Two Doses of ChAdOx1-S Vaccine in Patients on Hemodialysis10.2215/CJN.10170721Mon, 20 Sep 2021 10:40:31 GMT-07:00Humoral Response to One and Two Doses of ChAdOx1-S Vaccine in Patients on HemodialysisYadav, Ashok KumarGondil, Vijay SinghSingla, ManishGoyal, AjayKaushal, RakaChauhan, MunishJha, Vivekanand2021-09-20T10:40:31-07:00doi:10.2215/CJN.10170721hwp:resource-id:clinjasn;16/12/1875American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, COVID-19, AntibodyResearch LettersResearch Lettersletter20212021-12-01December 202110.2215/CJN.101707211555-90411555-905X2021-09-20T10:40:31-07:002021-12Clinical Journal of the American Society of NephrologyResearch Letters161218751876
- APOL1 Risk Variants and Acute Kidney Injury in Black Americans with COVID-1910.2215/CJN.01070121Tue, 07 Dec 2021 11:35:23 GMT-08:00APOL1 Risk Variants and Acute Kidney Injury in Black Americans with COVID-19Larsen, Christopher P.Wickman, Terrance J.Braga, Juarez R.Matute-Trochez, Luis A.Hasty, Anna E.Buckner, Lyndsey R.Arthur, John M.Haun, Randy S.Velez, Juan Carlos Q.2021-12-07T11:35:23-08:00doi:10.2215/CJN.01070121hwp:resource-id:clinjasn;16/12/1790American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, genetic renal disease, COVID-19, apolipoprotein L1, acute kidney injuryOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-12-01December 202110.2215/CJN.010701211555-90411555-905X2021-12-07T11:35:23-08:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles1612121790177917961780
- Atrasentan: The Difficult Task of Integrating Endothelin A Receptor Antagonists into Current Treatment Paradigm for Diabetic Kidney Disease10.2215/CJN.13601021Wed, 01 Dec 2021 01:40:40 GMT-08:00Atrasentan: The Difficult Task of Integrating Endothelin A Receptor Antagonists into Current Treatment Paradigm for Diabetic Kidney DiseaseOrtiz, AlbertoFernandez-Fernandez, Beatriz2021-12-01T13:40:40-08:00doi:10.2215/CJN.13601021hwp:resource-id:clinjasn;16/12/1775American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, atrasentan, albuminuria, endothelin A receptor antagonistsEditorialsEditorialseditorial20212021-12-01December 202110.2215/CJN.136010211555-90411555-905X2021-12-01T13:40:40-08:002021-12Clinical Journal of the American Society of NephrologyEditorials1612121775182417781832
- What Is the Best Maintenance Therapy for ANCA Vasculitis?10.2215/CJN.09210721Tue, 09 Nov 2021 07:30:46 GMT-08:00What Is the Best Maintenance Therapy for ANCA Vasculitis?Woerner, KattiNachman, Patrick H.2021-11-09T07:30:46-08:00doi:10.2215/CJN.09210721hwp:resource-id:clinjasn;16/12/1906American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, maintenancePerspectivesPerspectivesresearch-article20212021-12-01December 202110.2215/CJN.092107211555-90411555-905X2021-11-09T07:30:46-08:002021-12Clinical Journal of the American Society of NephrologyPerspectives161219061908
- Collectin11 and Complement Activation in IgA Nephropathy10.2215/CJN.04300321Wed, 06 Oct 2021 11:13:55 GMT-07:00Collectin11 and Complement Activation in IgA NephropathyWei, MinGuo, Wei-yiXu, Bo-yangShi, Su-fangLiu, Li-junZhou, Xu-jieLv, Ji-chengZhu, LiZhang, Hong2021-10-06T11:13:55-07:00doi:10.2215/CJN.04300321hwp:resource-id:clinjasn;16/12/1840American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, complement, mesangial cells, complement activation, collectinsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-12-01December 202110.2215/CJN.043003211555-90411555-905X2021-10-06T11:13:55-07:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles161218401850
- Video-Based Telemedicine for Kidney Disease Care10.2215/CJN.06660521Tue, 07 Dec 2021 11:35:23 GMT-08:00Video-Based Telemedicine for Kidney Disease CareYoung, AnnOrchanian-Cheff, AniChan, Christopher T.Wald, RonOng, Stephanie W.2021-12-07T11:35:23-08:00doi:10.2215/CJN.06660521hwp:resource-id:clinjasn;16/12/1813American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvirtual care, chronic kidney disease, review, telemedicine, health services delivery model, digital health, communications mediaOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-12-01December 202110.2215/CJN.066605211555-90411555-905X2021-12-07T11:35:23-08:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles16121212181317731784182317741786
- A Body Size–Adjusted Maximum Ultrafiltration Rate Warning Level Is Not Equitable for Larger Patients10.2215/CJN.04850421Thu, 11 Nov 2021 06:46:19 GMT-08:00A Body Size–Adjusted Maximum Ultrafiltration Rate Warning Level Is Not Equitable for Larger PatientsDaugirdas, John T.2021-11-11T06:46:19-08:00doi:10.2215/CJN.04850421hwp:resource-id:clinjasn;16/12/1901American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, ultrafiltration, hypotension, body sizePerspectivesPerspectivesresearch-article20212021-12-01December 202110.2215/CJN.048504211555-90411555-905X2021-11-11T06:46:19-08:002021-12Clinical Journal of the American Society of NephrologyPerspectives161219011902
- Noninvasive Diagnosis of PLA2R-Associated Membranous Nephropathy10.2215/CJN.05480421Mon, 15 Nov 2021 05:12:51 GMT-08:00Noninvasive Diagnosis of PLA2R-Associated Membranous NephropathyBobart, Shane A.Han, HeedeokTehranian, ShahrzadDe Vriese, An S.Roman, Juan Carlos LeonSethi, SanjeevZand, LadanAndrades Gomez, CristinaGiesen, Callen D.Soler, Maria JoseBomback, Andrew S.Fervenza, Fernando C.2021-11-15T17:12:51-08:00doi:10.2215/CJN.05480421hwp:resource-id:clinjasn;16/12/1833American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, kidney biopsy, receptors, phospholipase A2, glomerulonephritis, membranousOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-12-01December 202110.2215/CJN.054804211555-90411555-905X2021-11-15T17:12:51-08:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles1612121833178718391789
- Change in Physical Activity and Function in Patients with Baseline Advanced Nondialysis CKD10.2215/CJN.07050521Mon, 25 Oct 2021 07:23:51 GMT-07:00Change in Physical Activity and Function in Patients with Baseline Advanced Nondialysis CKDRampersad, ChristieDarcel, JosephHarasemiw, OksanaBrar, Ranveer S.Komenda, PaulRigatto, ClaudioPrasad, BhanuBohm, ClaraTangri, Navdeep2021-10-25T07:23:51-07:00doi:10.2215/CJN.07050521hwp:resource-id:clinjasn;16/12/1805American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, physical activity, physical function, exercise, dialysisOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-12-01December 202110.2215/CJN.070505211555-90411555-905X2021-10-25T07:23:51-07:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles161218051812
- Dietary Potassium Intake and All-Cause Mortality in Adults Treated with Hemodialysis10.2215/CJN.08360621Wed, 01 Dec 2021 02:01:59 GMT-08:00Dietary Potassium Intake and All-Cause Mortality in Adults Treated with HemodialysisBernier-Jean, AmelieWong, GermaineSaglimbene, ValeriaRuospo, MarinellaPalmer, Suetonia C.Natale, PatriziaGarcia-Larsen, VanessaJohnson, David W.Tonelli, MarcelloHegbrant, JörgenCraig, Jonathan C.Teixeira-Pinto, ArmandoStrippoli, Giovanni F.M.2021-12-01T14:01:59-08:00doi:10.2215/CJN.08360621hwp:resource-id:clinjasn;16/12/1851American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, nutrition, mortality, potassium, dietary, cohort studies, dietOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-12-01December 202110.2215/CJN.083606211555-90411555-905X2021-12-01T14:01:59-08:002021-12Clinical Journal of the American Society of NephrologyOriginal Articles1612121851178118611783
- Post-Transplant Cardiovascular DiseaseCardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.10.2215/CJN.00520121Thu, 23 Sep 2021 06:53:28 GMT-07:00Post-Transplant Cardiovascular DiseaseCardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.Birdwell, Kelly A.Park, Meyeon2021-09-23T06:53:28-07:00doi:10.2215/CJN.00520121hwp:resource-id:clinjasn;16/12/1878American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation series, cardiovascular disease, kidney transplantation, diabetes, immunosuppression, obesity, heart failure, coronary artery disease, hypertensionKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-12-01December 202110.2215/CJN.005201211555-90411555-905X2021-09-23T06:53:28-07:002021-12Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161218781889
- Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney TransplantationDespite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.10.2215/CJN.15070920Tue, 23 Mar 2021 07:48:28 GMT-07:00Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney TransplantationDespite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.Ibrahim, Hassan N.Murad, Dina N.Knoll, Greg A.2021-03-23T07:48:28-07:00doi:10.2215/CJN.15070920hwp:resource-id:clinjasn;16/12/1890American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, hypertension, outcomesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-12-01December 202110.2215/CJN.150709201555-90411555-905X2021-03-23T07:48:28-07:002021-12Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161218901897
- Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics without Renal Dysfunction10.1681/ASN.2021010061Wed, 22 Sep 2021 10:24:04 GMT-07:00Heterozygous Mutation of Vegfr3 Reduces Renal Lymphatics without Renal DysfunctionLiu, HaoHiremath, ChitkalePatterson, QuintenVora, SaumyaShang, ZhiguoJamieson, Andrew R.Fiolka, RetoDean, Kevin M.Dellinger, Michael T.Marciano, Denise K.2021-09-22T10:24:04-07:00doi:10.1681/ASN.2021010061hwp:resource-id:jnephrol;32/12/3099American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologylymphatics, kidney, kidney development, lymphangiogenesis, light-sheet microscopy, Vegfr3Basic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210100611046-66731533-34502021-09-22T10:24:04-07:002021-12Journal of the American Society of NephrologyBasic Research321230993113
- It Is Time for Patient-Reported Outcome Measures to Be Included in the Approval Process for Solid Organ Transplant Medications10.1681/ASN.2021081136Tue, 30 Nov 2021 06:14:42 GMT-08:00It Is Time for Patient-Reported Outcome Measures to Be Included in the Approval Process for Solid Organ Transplant MedicationsFormica, Richard N.Turgeon, Nicole2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021081136hwp:resource-id:jnephrol;32/12/2984American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, immunosuppression, patient self-assessment, transplant outcomesUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-12-01December 202110.1681/ASN.20210811361046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyUp Front Matters3212122984325229863264
- Back to the Future: The Role of Metabolic Studies in Therapeutic Advances10.1681/ASN.2021101325Tue, 30 Nov 2021 06:14:42 GMT-08:00Back to the Future: The Role of Metabolic Studies in Therapeutic AdvancesMilliner, Dawn S.Lieske, John C.2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021101325hwp:resource-id:jnephrol;32/12/2980American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium oxalate, primary hyperoxaluria, metabolite, siRNA, nephrolithiasis, kidney failureUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-12-01December 202110.1681/ASN.20211013251046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyUp Front Matters3212122980317529823186
- This Month's Highlights10.1681/ASN.2021101352Tue, 30 Nov 2021 06:14:42 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021101352hwp:resource-id:jnephrol;32/12/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20212021-12-01December 202110.1681/ASN.20211013521046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyThis Month’s Highlights3212ii
- Making the Connection10.1681/ASN.2021101354Wed, 17 Nov 2021 08:13:16 GMT-08:00Making the ConnectionOxburgh, Leif2021-11-17T08:13:16-08:00doi:10.1681/ASN.2021101354hwp:resource-id:jnephrol;32/12/2978American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyconnecting tubule, distal tubule, collecting ductUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-12-01December 202110.1681/ASN.20211013541046-66731533-34502021-11-17T08:13:16-08:002021-12Journal of the American Society of NephrologyUp Front Matters3212122978303529803049
- B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant Recipients10.1681/ASN.2021070966Tue, 19 Oct 2021 05:27:18 GMT-07:00B and T Cell Responses after a Third Dose of SARS-CoV-2 Vaccine in Kidney Transplant RecipientsSchrezenmeier, EvaRincon-Arevalo, HectorStefanski, Ana-LuisaPotekhin, AlexanderStaub-Hohenbleicher, HenrietteChoi, MiraBachmann, FriederikeProβ, VanessaHammett, CharlotteSchrezenmeier, HubertLudwig, CarolinJahrsdörfer, BerndLino, Andreia C.Eckardt, Kai-UweKotsch, KatjaDörner, ThomasBudde, KlemensSattler, ArneHalleck, Fabian2021-10-19T05:27:18-07:00doi:10.1681/ASN.2021070966hwp:resource-id:jnephrol;32/12/3027American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, vaccine, B cells, T cells, T-lymphocytes, SARS-CoV-2, kidney transplantationRapid CommunicationsRapid Communicationsresearch-article20212021-12-01December 202110.1681/ASN.20210709661046-66731533-34502021-10-19T05:27:18-07:002021-12Journal of the American Society of NephrologyRapid Communications321212443027297786987030332978869871
- Activation of the Hypoxia-Inducible Factor Pathway Inhibits Epithelial Sodium Channel–Mediated Sodium Transport in Collecting Duct Principal Cells10.1681/ASN.2021010046Wed, 06 Oct 2021 09:49:36 GMT-07:00Activation of the Hypoxia-Inducible Factor Pathway Inhibits Epithelial Sodium Channel–Mediated Sodium Transport in Collecting Duct Principal CellsDizin, EvaOlivier, ValérieRoth, IsabelleSassi, AliArnoux, GrégoireRamakrishnan, SureshMorel, SandrineKwak, Brenda R.Loffing, JohannesHummler, EdithWenger, Roland H.Frew, Ian J.Feraille, Eric2021-10-06T09:49:36-07:00doi:10.1681/ASN.2021010046hwp:resource-id:jnephrol;32/12/3130American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210100461046-66731533-34502021-10-06T09:49:36-07:002021-12Journal of the American Society of NephrologyBasic Research321231303145
- Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing10.1681/ASN.2021050690Fri, 29 Oct 2021 09:20:56 GMT-07:00Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome SequencingZhang, ZhengmaoBai, HanwenBlumenfeld, JonRamnauth, Andrew B.Barash, IrinaPrince, MartinTan, Adrian Y.Michaeel, AlberLiu, GenyanChicos, InesRennert, LiorGiannakopoulos, StavrosLarbi, KarenHughes, StuartSalvatore, Steven P.Robinson, Brian D.Kapur, SandipRennert, Hanna2021-10-29T09:20:56-07:00doi:10.1681/ASN.2021050690hwp:resource-id:jnephrol;32/12/3114American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, ADPKD, cystic kidney, end-stage renal disease, polycystic kidney disease, polycystic kidney, autosomal dominant, whole genome sequencing, epithelial cells, cystsBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210506901046-66731533-34502021-10-29T09:20:56-07:002021-12Journal of the American Society of NephrologyBasic Research321231143129
- Generation of Distal Renal Segments Involves a Unique Population of Aqp2+ Progenitor Cells10.1681/ASN.2021030399Tue, 19 Oct 2021 05:27:18 GMT-07:00Generation of Distal Renal Segments Involves a Unique Population of Aqp2+ Progenitor CellsGao, ChaoChen, LiheChen, EnuoTsilosani, AkakiXia, YangZhang, Wenzheng2021-10-19T05:27:18-07:00doi:10.1681/ASN.2021030399hwp:resource-id:jnephrol;32/12/3035American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydistal convoluted tubule, connecting tubule, collecting duct, self-renewal, multipotency, lineage tracing, notch activation, progenitor cells, clonogenicityBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210303991046-66731533-34502021-10-19T05:27:18-07:002021-12Journal of the American Society of NephrologyBasic Research3212123035297830492980
- Conversion from Calcineurin Inhibitor– to Belatacept-Based Maintenance Immunosuppression in Renal Transplant Recipients: A Randomized Phase 3b Trial10.1681/ASN.2021050628Wed, 27 Oct 2021 10:52:52 GMT-07:00Conversion from Calcineurin Inhibitor– to Belatacept-Based Maintenance Immunosuppression in Renal Transplant Recipients: A Randomized Phase 3b TrialBudde, KlemensPrashar, RohiniHaller, HermannRial, Maria C.Kamar, NassimAgarwal, Avinashde Fijter, Johan W.Rostaing, LionelBerger, Stefan P.Djamali, ArjangLeca, NicolaeAllamassey, LisaGao, ShengPolinsky, MartinVincenti, Flavio2021-10-27T10:52:52-07:00doi:10.1681/ASN.2021050628hwp:resource-id:jnephrol;32/12/3252American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, randomized controlled trials, acute rejection, renal function, immunosuppression, abatacept, calcineurin inhibitors, kidney transplantation, transplant recipientsClinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210506281046-66731533-34502021-10-27T10:52:52-07:002021-12Journal of the American Society of NephrologyClinical Research3212123252298432642986
- COVID-19 Vaccination in Kidney Transplant Recipients: An Ounce Pre-Transplant is Worth a Pound Post-Transplant10.1681/ASN.2021101347Tue, 30 Nov 2021 06:14:42 GMT-08:00COVID-19 Vaccination in Kidney Transplant Recipients: An Ounce Pre-Transplant is Worth a Pound Post-TransplantChandran, SindhuStock, Peter G.2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021101347hwp:resource-id:jnephrol;32/12/2977American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19 vaccination, COVID-19 vaccination booster, immunosuppression, COVID-19Up Front MattersEditorialsUp Front MattersEditorialseditorial20212021-12-01December 202110.1681/ASN.20211013471046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyUp Front Matters3212122977302729783033
- Removing Race from Kidney Disease Diagnosis10.1681/ASN.2021091284Tue, 09 Nov 2021 06:00:08 GMT-08:00Removing Race from Kidney Disease DiagnosisQuaggin, Susan E.Palevsky, Paul M.2021-11-09T06:00:08-08:00doi:10.1681/ASN.2021091284hwp:resource-id:jnephrol;32/12/2987American Society of NephrologyCopyright © 2021 by American Society of Nephrology and National Kidney Foundation, Inc. All rights reserved.Journal of the American Society of Nephrologykidney disease, disparities, estimated GFR, race, urological diagnostic techniquesUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20212021-12-01December 202110.1681/ASN.20210912841046-66731533-34502021-11-09T06:00:08-08:002021-12Journal of the American Society of NephrologyUp Front Matters3212122987299429893015
- Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study10.1681/ASN.2021070908Wed, 29 Sep 2021 09:52:14 GMT-07:00Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational StudyVan Praet, JensReynders, MarijkeDe Bacquer, DirkViaene, LiesbethSchoutteten, Melanie K.Caluwé, RogierDoubel, PeterHeylen, LineDe Bel, Annelies V.Van Vlem, BrunoSteensels, DeborahDe Vriese, An S.2021-09-29T09:52:14-07:00doi:10.1681/ASN.2021070908hwp:resource-id:jnephrol;32/12/3208American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical trial, dialysis, SARS-CoV-2, vaccination, COVID-19, cellular immunityClinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210709081046-66731533-34502021-09-29T09:52:14-07:002021-12Journal of the American Society of NephrologyClinical Research321232083220
- Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA Nephropathy10.1681/ASN.2021060815Wed, 20 Oct 2021 07:19:19 GMT-07:00Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA NephropathyXie, DiZhao, HaoXu, XinZhou, ZhanmeiSu, CailingJia, NanLiu, YouhuaHou, Fan Fan2021-10-20T07:19:19-07:00doi:10.1681/ASN.2021060815hwp:resource-id:jnephrol;32/12/3187American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, prediction, response, immunosuppression, macrophagesClinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210608151046-66731533-34502021-10-20T07:19:19-07:002021-12Journal of the American Society of NephrologyClinical Research3212123187298231962984
- Guanidinylated Apolipoprotein C3 (ApoC3) Associates with Kidney and Vascular Injury10.1681/ASN.2021040503Wed, 29 Sep 2021 09:52:14 GMT-07:00Guanidinylated Apolipoprotein C3 (ApoC3) Associates with Kidney and Vascular InjurySchunk, Stefan J.Hermann, JulianeSarakpi, TamimTriem, SarahLellig, MichaelaHahm, EunsilZewinger, StephenSchmit, DavidBecker, EllenMöllmann, JuliaLehrke, MichaelKramann, RafaelBoor, PeterLipp, PeterLaufs, UlrichMärz, WinfriedReiser, JochenJankowski, JoachimFliser, DaniloSpeer, ThimoteusJankowski, Vera2021-09-29T09:52:14-07:00doi:10.1681/ASN.2021040503hwp:resource-id:jnephrol;32/12/3146American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, lipoproteins, posttranslational modifications, inflammation, cardiovascular diseaseBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210405031046-66731533-34502021-09-29T09:52:14-07:002021-12Journal of the American Society of NephrologyBasic Research321231463160
- Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection10.1681/ASN.2021040573Fri, 01 Oct 2021 02:00:11 GMT-07:00Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 InfectionCravedi, PaoloAhearn, PatrickWang, LinYalamarti, TanujaHartzell, SusanAzzi, YorgMenon, Madhav C.Jain, AdityaBillah, MarzuqFernandez-Vina, MarceloGebel, Howard M.Woodle, E. SteveHaddad, Natalie S.Morrison-Porter, AndreaLee, F. Eun-HyungSanz, IgnacioAkalin, EnverGirnita, AlinMaltzman, Jonathan S.2021-10-01T14:00:11-07:00doi:10.1681/ASN.2021040573hwp:resource-id:jnephrol;32/12/3221American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, immunology, kidney transplantation, antibodies, SARS-Co-V-2, COVID-19Clinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210405731046-66731533-34502021-10-01T14:00:11-07:002021-12Journal of the American Society of NephrologyClinical Research321232213230
- IgA Nephropathy Needs a Diagnostic Marker of Immunologic Activity to Select the Right Patients for Immunotherapies10.1681/ASN.2021091239Wed, 17 Nov 2021 09:34:17 GMT-08:00IgA Nephropathy Needs a Diagnostic Marker of Immunologic Activity to Select the Right Patients for ImmunotherapiesHilhorst, MarcAnders, Hans-Joachim2021-11-17T09:34:17-08:00doi:10.1681/ASN.2021091239hwp:resource-id:jnephrol;32/12/2982American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, primary glomerulonephritis, glucocorticoids, biomarker, disease activityUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-12-01December 202110.1681/ASN.20210912391046-66731533-34502021-11-17T09:34:17-08:002021-12Journal of the American Society of NephrologyUp Front Matters3212122982318729843196
- CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant Recipients10.1681/ASN.2021050689Tue, 30 Nov 2021 06:14:42 GMT-08:00CRISPR/Cas9-Engineered HLA-Deleted Glomerular Endothelial Cells as a Tool to Predict Pathogenic Non-HLA Antibodies in Kidney Transplant RecipientsLamarthée, BaptisteBurger, CaroleLeclaire, CharlotteLebraud, EmilieZablocki, AnielaMorin, LiseLebreton, XavierCharreau, BéatriceSnanoudj, RenaudCharbonnier, SoëliBlein, TifanieHardy, MélanieZuber, JulienSatchell, SimonGallazzini, MorganTerzi, FabiolaLegendre, ChristopheTaupin, Jean LucRabant, MarionTinel, ClaireAnglicheau, Dany2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021050689hwp:resource-id:jnephrol;32/12/3231American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyantibody-mediated rejection, non-HLA antibodies, kidney rejection, endothelial inflammation, kidney transplantation, endothelial cells, CRISPR-Cas systems, antibodiesClinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210506891046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyClinical Research321232313251
- Global Health Education in Nephrology: The Time has Come10.1681/ASN.2021060731Wed, 13 Oct 2021 08:38:50 GMT-07:00Global Health Education in Nephrology: The Time has ComeIngenhoff, RebeccaBrewster, UrsulaRastegar, AsgharKalyesubula, RobertKnauf, Felix2021-10-13T08:38:50-07:00doi:10.1681/ASN.2021060731hwp:resource-id:jnephrol;32/12/2990American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglobal health education, nephrology, bilateral exchange, educational statusUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20212021-12-01December 202110.1681/ASN.20210607311046-66731533-34502021-10-13T08:38:50-07:002021-12Journal of the American Society of NephrologyUp Front Matters321229902993
- A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease10.1681/ASN.2021070988Thu, 23 Sep 2021 09:30:08 GMT-07:00A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney DiseaseDelgado, CynthiaBaweja, MuktaCrews, Deidra C.Eneanya, Nwamaka D.Gadegbeku, Crystal A.Inker, Lesley A.Mendu, Mallika L.Miller, W. GregMoxey-Mims, Marva M.Roberts, Glenda V.St. Peter, Wendy L.Warfield, CurtisPowe, Neil R.2021-09-23T09:30:08-07:00doi:10.1681/ASN.2021070988hwp:resource-id:jnephrol;32/12/2994American Society of NephrologyCopyright © 2021 by the American Society of Nephrology and National Kidney Foundation, Inc. All rights reserved.Journal of the American Society of NephrologyeGFR, health disparities, creatinine, ethnicity, chronic kidney disease, clinical nephrology, glomerular filtration rate, drug excretion, epidemiology and outcomesUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20212021-12-01December 202110.1681/ASN.20210709881046-66731533-34502021-09-23T09:30:08-07:002021-12Journal of the American Society of NephrologyUp Front Matters3212122994298730152989
- Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical Trial10.1681/ASN.2021050598Wed, 22 Sep 2021 10:24:04 GMT-07:00Effect of Low-Dose Methotrexate on eGFR and Kidney Adverse Events: A Randomized Clinical TrialSparks, Jeffrey A.Vanni, Kathleen M. M.Sparks, Matthew A.Xu, ChangSantacroce, Leah M.Glynn, Robert J.Ridker, Paul M.Solomon, Daniel H.2021-09-22T10:24:04-07:00doi:10.1681/ASN.2021050598hwp:resource-id:jnephrol;32/12/3197American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic inflammation, randomized controlled trials, immunology, methotrexateClinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210505981046-66731533-34502021-09-22T10:24:04-07:002021-12Journal of the American Society of NephrologyClinical Research321231973207
- CHOP-ASO Ameliorates Glomerular and Tubular Damage on Top of ACE Inhibition in Diabetic Kidney Disease10.1681/ASN.2021040431Fri, 03 Sep 2021 09:49:58 GMT-07:00CHOP-ASO Ameliorates Glomerular and Tubular Damage on Top of ACE Inhibition in Diabetic Kidney DiseaseShahzad, KhurrumFatima, SameenAl-Dabet, Moh’d MohanadGadi, IhsanKhawaja, HamzahAmbreen, SairaElwakiel, AhmedKlöting, NoraBlüher, MatthiasNawroth, Peter P.Mertens, Peter R.Michel, SvenJaschinski, FrankKlar, RichardIsermann, Berend2021-09-03T09:49:58-07:00doi:10.1681/ASN.2021040431hwp:resource-id:jnephrol;32/12/3066American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, chronic nephropathy, diabetic nephropathyBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210404311046-66731533-34502021-09-03T09:49:58-07:002021-12Journal of the American Society of NephrologyBasic Research321230663079
- Physiologic Regulation of Systemic Klotho Levels by Renal CaSR Signaling in Response to CaSR Ligands and pHo10.1681/ASN.2021020276Wed, 22 Sep 2021 10:24:03 GMT-07:00Physiologic Regulation of Systemic Klotho Levels by Renal CaSR Signaling in Response to CaSR Ligands and pHoYoon, JoonhoLiu, ZhenanLee, EunyoungLiu, LipingFerre, SilviaPastor, JohanneZhang, JianningMoe, Orson W.Chang, Audrey N.Miller, R. Tyler2021-09-22T10:24:03-07:00doi:10.1681/ASN.2021020276hwp:resource-id:jnephrol;32/12/3051American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyADAM10, calcium sensing receptor, distal convoluted tubule, kidney, KlothoBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210202761046-66731533-34502021-09-22T10:24:03-07:002021-12Journal of the American Society of NephrologyBasic Research321230513065
- Polygenic Risk Scores for Kidney Function and Their Associations with Circulating Proteome, and Incident Kidney Diseases10.1681/ASN.2020111599Tue, 21 Sep 2021 10:35:12 GMT-07:00Polygenic Risk Scores for Kidney Function and Their Associations with Circulating Proteome, and Incident Kidney DiseasesYu, ZhiJin, JinTin, AdrienneKöttgen, AnnaYu, BingChen, JingshaSurapaneni, AdityaZhou, LindaBallantyne, Christie M.Hoogeveen, Ron C.Arking, Dan E.Chatterjee, NilanjanGrams, Morgan E.Coresh, Josef2021-09-21T10:35:12-07:00doi:10.1681/ASN.2020111599hwp:resource-id:jnephrol;32/12/3161American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygenetics and development, epidemiology and outcomes, glomerular filtration rate, chronic kidney disease, end stage kidney disease, kidney diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20212021-12-01December 202110.1681/ASN.20201115991046-66731533-34502021-09-21T10:35:12-07:002021-12Journal of the American Society of NephrologyClinical Epidemiology321231613173
- IL-17 Receptor C Signaling Controls CD4+ TH17 Immune Responses and Tissue Injury in Immune-Mediated Kidney Diseases10.1681/ASN.2021030426Tue, 30 Nov 2021 06:14:42 GMT-08:00IL-17 Receptor C Signaling Controls CD4+ TH17 Immune Responses and Tissue Injury in Immune-Mediated Kidney DiseasesSchmidt, TilmanLuebbe, JonasKilian, ChristophRiedel, Jan-HendrikHiekmann, SonjaAsada, NariakiGinsberg, PaulineRobben, LennartSong, NingKaffke, AnnaPeters, AnettBorchers, AlinaFlavell, Richard A.Gagliani, NicolaPelzcar, PenelopeHuber, SamuelHuber, Tobias B.Turner, Jan-EricPaust, Hans-JoachimKrebs, Christian F.Panzer, Ulf2021-11-30T06:14:42-08:00doi:10.1681/ASN.2021030426hwp:resource-id:jnephrol;32/12/3081American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycytokines, glomerulonephritis, immunology, lymphocytesBasic ResearchBasic Researchresearch-article20212021-12-01December 202110.1681/ASN.20210304261046-66731533-34502021-11-30T06:14:42-08:002021-12Journal of the American Society of NephrologyBasic Research321230813098
- Endogenous Oxalate Production in Primary Hyperoxaluria Type 1 Patients10.1681/ASN.2021060729Fri, 22 Oct 2021 10:35:33 GMT-07:00Endogenous Oxalate Production in Primary Hyperoxaluria Type 1 PatientsGarrelfs, Sander F.van Harskamp, DewiPeters-Sengers, Hesselvan den Akker, Chris H.P.Wanders, Ronald J.A.Wijburg, Frits A.van Goudoever, Johannes B.Groothoff, Jaap W.Schierbeek, HenkOosterveld, Michiel J.S.2021-10-22T10:35:33-07:00doi:10.1681/ASN.2021060729hwp:resource-id:jnephrol;32/12/3175American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperoxaluria, genetic kidney disease, stable isotope, oxalate, kinetics, mass spectrometry, primary hyperoxaluria type 1Clinical ResearchClinical Researchresearch-article20212021-12-01December 202110.1681/ASN.20210607291046-66731533-34502021-10-22T10:35:33-07:002021-12Journal of the American Society of NephrologyClinical Research3212123175298031862982
- Patient Activation Measure in Dialysis-Dependent Patients in the United States10.1681/ASN.2021030315Wed, 01 Sep 2021 02:00:10 GMT-07:00Patient Activation Measure in Dialysis-Dependent Patients in the United StatesCukor, DanielZelnick, Leila R.Charytan, David M.Shallcross, Amanda J.Mehrotra, Rajnish2021-09-01T14:00:10-07:00doi:10.1681/ASN.2021030315hwp:resource-id:jnephrol;32/12/3017American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypatient self-assessmentResearch LettersResearch Lettersletter20212021-12-01December 202110.1681/ASN.20210303151046-66731533-34502021-09-01T14:00:10-07:002021-12Journal of the American Society of NephrologyResearch Letters321230173019
- Use of a Smartphone Camera at the Bedside to Assess Adequacy of Kidney Biopsies10.1681/ASN.2021070898Mon, 13 Sep 2021 11:27:11 GMT-07:00Use of a Smartphone Camera at the Bedside to Assess Adequacy of Kidney BiopsiesSingh, GurmukteshwarMassak, MarkCzaplicki, MichaelYoung, EvanSharma, ShreeChang, AlexBhanushali, AshokAnand, Prince2021-09-13T11:27:11-07:00doi:10.1681/ASN.2021070898hwp:resource-id:jnephrol;32/12/3024American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, renal biopsy, pathology, smartphone, renal pathologyResearch LettersResearch Lettersletter20212021-12-01December 202110.1681/ASN.20210708981046-66731533-34502021-09-13T11:27:11-07:002021-12Journal of the American Society of NephrologyResearch Letters321230243026
- Second Wave Antibodies in Autoimmune Renal Diseases: The Case of Lupus Nephritis10.1681/ASN.2021050659Fri, 01 Oct 2021 10:37:16 GMT-07:00Second Wave Antibodies in Autoimmune Renal Diseases: The Case of Lupus NephritisAngeletti, AndreaBruschi, MaurizioMoroni, GabriellaSinico, Renato AlbertoFranceschini, FrancoFredi, MicaelaVaglio, AugustoCavagna, LorenzoPetretto, AndreaPratesi, FedericoMigliorini, PaolaLocatelli, FrancescoPazzola, GiuliaPesce, GiampaolaBagnasco, MarcelloManfredi, AngeloRamirez, Giuseppe A.Esposito, PasqualeMurdaca, GiuseppeNegrini, SimoneCipriani, LedaTrezzi, BarbaraEmmi, GiacomoCavazzana, IlariaBinda, Valentinad’Alessandro, MatteoFenaroli, ParidePisani, IsabellaGaribotto, GiacomoMontecucco, CarlomaurizioSantoro, DomenicoScolari, FrancescoVolpi, StefanoMosca, MartaTincani, AngelaCandiano, GiovanniPrunotto, MarcoVerrina, EnricoRavelli, AngeloGhiggeri, Gian Marco2021-10-01T10:37:16-07:00doi:10.1681/ASN.2021050659hwp:resource-id:jnephrol;32/12/3020American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysystemic lupus erythematosus, lupus nephritis, glomerulonephritis, rheumatology, clinical trialResearch LettersResearch Lettersletter20212021-12-01December 202110.1681/ASN.20210506591046-66731533-34502021-10-01T10:37:16-07:002021-12Journal of the American Society of NephrologyResearch Letters321230203023
- Reconsidering Donor Race in Predicting Allograft and Patient Survival Among Kidney Transplant Recipients10.34067/KID.0002932021Thu, 19 Aug 2021 11:39:27 GMT-07:00Reconsidering Donor Race in Predicting Allograft and Patient Survival Among Kidney Transplant RecipientsChong, KellyLitvinovich, IgorChen, Shan ShanZhu, YiliangArgyropoulos, ChristosNg, Yue-Harn2021-08-19T11:39:27-07:00doi:10.34067/KID.0002932021hwp:resource-id:kidney360;2/11/1831American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, allograft survival, allografts, donor race, kidney discard, kidney donor risk index, kidney transplantation, patient survivalBrief CommunicationTransplantationBrief CommunicationTransplantationresearch-article20212021-11-2510.34067/KID.00029320212641-76502021-08-19T11:39:27-07:002021-11-25Kidney360Brief Communication21118311835
- An Unusual Cause of AKI in a Kidney Transplant Recipient10.34067/KID.0004332021Wed, 24 Nov 2021 02:00:34 GMT-08:00An Unusual Cause of AKI in a Kidney Transplant RecipientMalhotra, DivyanshuDahl, Neera K.2021-11-24T14:00:34-08:00doi:10.34067/KID.0004332021hwp:resource-id:kidney360;2/11/1869American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, acute kidney injury, hydronephrosis, kidney transplantation, perinephric hematoma, stentClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-11-2510.34067/KID.00043320212641-76502021-11-24T14:00:34-08:002021-11-25Kidney360Clinical Images in Nephrology and Dialysis21118691870
- A Computable Phenotype for Autosomal Dominant Polycystic Kidney Disease10.34067/KID.0000852021Thu, 16 Sep 2021 09:50:05 GMT-07:00A Computable Phenotype for Autosomal Dominant Polycystic Kidney DiseaseKalot, Mohamad A.El Alayli, AbdallahAl Khatib, MohammadHusainat, NedaaMcGreal, KerriJalal, Diana I.Yu, Alan S.L.Mustafa, Reem A.2021-09-16T09:50:05-07:00doi:10.34067/KID.0000852021hwp:resource-id:kidney360;2/11/1728American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, computable phenotype, diagnosis, ICD code, polycystic kidney, test accuracyOriginal InvestigationCystic Kidney DiseaseOriginal InvestigationCystic Kidney Diseaseresearch-article20212021-11-2510.34067/KID.00008520212641-76502021-09-16T09:50:05-07:002021-11-25Kidney360Original Investigation21117281733
- Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized Trial10.34067/KID.0001922021Thu, 16 Sep 2021 09:50:05 GMT-07:00Timing of Antihypertensive Medications on Key Outcomes in Hemodialysis: A Cluster Randomized TrialChang, Tara I.Tatoian, Emily TamarMontez-Rath, Maria E.Chertow, Glenn M.2021-09-16T09:50:05-07:00doi:10.34067/KID.0001922021hwp:resource-id:kidney360;2/11/1752American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, blood pressure, clinical trial, dialysis, end stage kidney disease, hemodialysisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-11-2510.34067/KID.00019220212641-76502021-09-16T09:50:05-07:002021-11-25Kidney360Original Investigation21117521760
- Hematuria and Flank Pain in a Patient with Sickle Cell Trait Who Is Taking NSAIDs10.34067/KID.0003642021Wed, 24 Nov 2021 02:00:34 GMT-08:00Hematuria and Flank Pain in a Patient with Sickle Cell Trait Who Is Taking NSAIDsHoman, Travis D.Buck, Jonathan B.Miyata, Kana N.2021-11-24T14:00:34-08:00doi:10.34067/KID.0003642021hwp:resource-id:kidney360;2/11/1865American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, anti-inflammatory agents, non-steroidal, hematuria, NSAIDs, papillary necrosis, sickle cell traitClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-11-2510.34067/KID.00036420212641-76502021-11-24T14:00:34-08:002021-11-25Kidney360Clinical Images in Nephrology and Dialysis21118651866
- The Role of Myeloid Cells in Acute Kidney Injury and Kidney RepairAKI remains highly prevalent, yet no optimal therapy is available to prevent it or promote recovery after initial insult. Experimental studies have demonstrated that both innate and adaptive immune responses play a central role during AKI. In response to injury, myeloid cells are first recruited and activated on the basis of specific signals from the damaged microenvironment. The subsequent recruitment and activation state of the immune cells depends on the stage of injury and recovery, reflecting a dynamic and diverse spectrum of immunophenotypes. In this review, we highlight our current understanding of the mechanisms by which myeloid cells contribute to injury, repair, and fibrosis after AKI.10.34067/KID.0000672021Wed, 22 Sep 2021 05:30:15 GMT-07:00The Role of Myeloid Cells in Acute Kidney Injury and Kidney RepairAKI remains highly prevalent, yet no optimal therapy is available to prevent it or promote recovery after initial insult. Experimental studies have demonstrated that both innate and adaptive immune responses play a central role during AKI. In response to injury, myeloid cells are first recruited and activated on the basis of specific signals from the damaged microenvironment. The subsequent recruitment and activation state of the immune cells depends on the stage of injury and recovery, reflecting a dynamic and diverse spectrum of immunophenotypes. In this review, we highlight our current understanding of the mechanisms by which myeloid cells contribute to injury, repair, and fibrosis after AKI.Xu, Leyuan2021-09-22T05:30:15-07:00doi:10.34067/KID.0000672021hwp:resource-id:kidney360;2/11/1852American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, basic science, CKD, dendritic cell, fibrosis, kidney repair, macrophage, myeloid cell, neutrophilReview ArticleReview Articlereview-article20212021-11-2510.34067/KID.00006720212641-76502021-09-22T05:30:15-07:002021-11-25Kidney360Review Article21118521864
- Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: COMMENTARY10.34067/KID.0002492021Mon, 19 Apr 2021 09:28:55 GMT-07:00Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: COMMENTARYKlomjit, NattawatZand, Ladan2021-04-19T09:28:55-07:00doi:10.34067/KID.0002492021hwp:resource-id:kidney360;2/11/1702American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, cyclophosphamide, glomerulonephritis, membranous, membranous nephropathy, MN, Ponticelli regimen, rituximabModerator CommentaryModerator Commentaryresearch-article20212021-11-2510.34067/KID.00024920212641-76502021-04-19T09:28:55-07:002021-11-25Kidney360Moderator Commentary21117021705
- Number of Donor Renal Arteries and Early Outcomes after Deceased Donor Kidney Transplantation10.34067/KID.0005152021Wed, 08 Sep 2021 01:35:20 GMT-07:00Number of Donor Renal Arteries and Early Outcomes after Deceased Donor Kidney TransplantationHusain, S. AliKing, Kristen L.Robbins-Juarez, SheliefAdler, Joel T.McCune, Kasi R.Mohan, Sumit2021-09-08T13:35:20-07:00doi:10.34067/KID.0005152021hwp:resource-id:kidney360;2/11/1819American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, deceased donor kidney transplant, delayed graft function, donor anatomy, kidney transplantation, renal artery, tissue donors, transplant outcomesOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-11-2510.34067/KID.00051520212641-76502021-09-08T13:35:20-07:002021-11-25Kidney360Original Investigation21118191826
- Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: PRO10.34067/KID.0001842021Mon, 19 Apr 2021 09:28:55 GMT-07:00Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: PROOliva-Damaso, NestorBomback, Andrew S.2021-04-19T09:28:55-07:00doi:10.34067/KID.0001842021hwp:resource-id:kidney360;2/11/1696American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, cyclophosphamide, immunosuppressive agents, membranous glomerulonephritis, rituximabDebates in NephrologyDebates in Nephrologyresearch-article20212021-11-2510.34067/KID.00018420212641-76502021-04-19T09:28:55-07:002021-11-25Kidney360Debates in Nephrology21116961698
- Deletion of Mocos Induces Xanthinuria with Obstructive Nephropathy and Major Metabolic Disorders in Mice10.34067/KID.0001732021Fri, 17 Sep 2021 11:21:16 GMT-07:00Deletion of Mocos Induces Xanthinuria with Obstructive Nephropathy and Major Metabolic Disorders in MiceSedda, DelphineMackowiak, ClairePailloux, JulieCulerier, ElodieDudas, AnaRontani, PaulineErard, NicolasLefevre, AntoineMavel, SylvieEmond, PatrickFoucher, FredericLe Bert, MarcQuesniaux, Valerie F.J.Mihatsch, Michael J.Ryffel, BernhardErard-Garcia, Madeleine2021-09-17T11:21:16-07:00doi:10.34067/KID.0001732021hwp:resource-id:kidney360;2/11/1793American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephrolithiasis, cyrstallopathy, inflammation, kidney diseases, kidney stones, MOCOS, obstructive nephropathy, oxidative stress, purine-pyrimidine metabolism, inborn errors, purines, renal failure, transgenic mouse, uremia, urethral diseases, urogenital abnormalities, xanthinuriaOriginal InvestigationNephrolithiasisOriginal InvestigationNephrolithiasisresearch-article20212021-11-2510.34067/KID.00017320212641-76502021-09-17T11:21:16-07:002021-11-25Kidney360Original Investigation21117931806
- Acute Onset of Dark Urine in a Patient with LVAD Pump Dysfunction10.34067/KID.0003482021Wed, 24 Nov 2021 02:00:34 GMT-08:00Acute Onset of Dark Urine in a Patient with LVAD Pump DysfunctionAlstott, JamesJhagroo, Roy2021-11-24T14:00:34-08:00doi:10.34067/KID.0003482021hwp:resource-id:kidney360;2/11/1867American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, databases, genetic, hemoglobinuria, hemolysis, kidney diseases, LVAD, urinalysis, urination disordersClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-11-2510.34067/KID.00034820212641-76502021-11-24T14:00:34-08:002021-11-25Kidney360Clinical Images in Nephrology and Dialysis21118671868
- Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: CON10.34067/KID.0001432021Mon, 19 Apr 2021 09:28:55 GMT-07:00Rituximab Is Preferable to Cyclophosphamide for Treatment of Membranous Nephropathy: CONvan de Logt, Anne-ElsWetzels, Jack F.2021-04-19T09:28:55-07:00doi:10.34067/KID.0001432021hwp:resource-id:kidney360;2/11/1699American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, cyclophosphamide, membranous, membranous glomerulonephritis, nephrotic syndrome, rituximabDebates in NephrologyGlomerular and Tubulointerstitial DiseasesDebates in NephrologyGlomerular and Tubulointerstitial Diseasesresearch-article20212021-11-2510.34067/KID.00014320212641-76502021-04-19T09:28:55-07:002021-11-25Kidney360Debates in Nephrology21116991701
- Arteriovenous Fistula Nonmaturation: What’s the Immune System Got to Do with It?10.34067/KID.0003112021Tue, 14 Sep 2021 11:42:21 GMT-07:00Arteriovenous Fistula Nonmaturation: What’s the Immune System Got to Do with It?Farrington, Crystal A.Cutter, GaryAllon, Michael2021-09-14T11:42:21-07:00doi:10.34067/KID.0003112021hwp:resource-id:kidney360;2/11/1743American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous access, arteriovenous fistula, AVF, AVF failure, dialysis access, immune system, immunology, nonmaturation, panel reactive antibodies, vascular accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-11-2510.34067/KID.00031120212641-76502021-09-14T11:42:21-07:002021-11-25Kidney360Original Investigation21117431751
- Global Perspective on Kidney Transplantation: Spain10.34067/KID.0002502021Thu, 02 Sep 2021 11:34:30 GMT-07:00Global Perspective on Kidney Transplantation: SpainCrespo, MartaMazuecos, AuxiliadoraDomínguez-Gil, Beatriz2021-09-02T11:34:30-07:00doi:10.34067/KID.0002502021hwp:resource-id:kidney360;2/11/1840American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, perspective, Spain, transplantationGlobal PerspectivesGlobal Perspectivesresearch-article20212021-11-2510.34067/KID.00025020212641-76502021-09-02T11:34:30-07:002021-11-25Kidney360Global Perspectives21118401843
- Untangling the Association between Anemia Treatment and Stroke Risk in CKD10.34067/KID.0006232021Wed, 24 Nov 2021 02:00:34 GMT-08:00Untangling the Association between Anemia Treatment and Stroke Risk in CKDWish, Jay B.2021-11-24T14:00:34-08:00doi:10.34067/KID.0006232021hwp:resource-id:kidney360;2/11/1693American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, anemia, chronic kidney disease, erythropoietin, hemodialysis, hypoxia-inducible factor, iron, strokeEditorialEditorialeditorial20212021-11-2510.34067/KID.00062320212641-76502021-11-24T14:00:34-08:002021-11-25Kidney360Editorial21116931695
- Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study10.34067/KID.0003562021Thu, 09 Sep 2021 03:47:12 GMT-07:00Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort StudyLambert, Douglas C.Abramowitz, Matthew K.2021-09-09T15:47:12-07:00doi:10.34067/KID.0003562021hwp:resource-id:kidney360;2/11/1706American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, anion gap, metabolic acidosis, obesity, overweightOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20212021-11-2510.34067/KID.00035620212641-76502021-09-09T15:47:12-07:002021-11-25Kidney360Original Investigation21117061715
- Relaxin Attenuates Organ Fibrosis via an Angiotensin Type 2 Receptor Mechanism in Aged Hypertensive Female Rats10.34067/KID.0002722021Fri, 10 Sep 2021 07:52:36 GMT-07:00Relaxin Attenuates Organ Fibrosis via an Angiotensin Type 2 Receptor Mechanism in Aged Hypertensive Female RatsBarsha, GiannieWalton, Sarah L.Kwok, EdmundMirabito Colafella, Katrina M.Pinar, Anita A.Hilliard Krause, Lucinda M.Gaspari, Tracey A.Widdop, Robert E.Samuel, Chrishan S.Denton, Kate M.2021-09-10T07:52:36-07:00doi:10.34067/KID.0002722021hwp:resource-id:kidney360;2/11/1781American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360hypertension, aging, angiotensin type 2 receptor, basic science, cardiovascular system, females, fibrosis, hypertension, rats, relaxinOriginal InvestigationHypertensionOriginal InvestigationHypertensionresearch-article20212021-11-2510.34067/KID.00027220212641-76502021-09-10T07:52:36-07:002021-11-25Kidney360Original Investigation21117811792
- Impact of AKI in Patients with Out-of-Hospital Cardiac Arrest Managed with VA ECMO10.34067/KID.0006592020Wed, 08 Sep 2021 01:35:20 GMT-07:00Impact of AKI in Patients with Out-of-Hospital Cardiac Arrest Managed with VA ECMORavipati, PrasanthMurray, SeanYannopoulos, DemetrisDrawz, Paul E.Bartos, Jason A.2021-09-08T13:35:20-07:00doi:10.34067/KID.0006592020hwp:resource-id:kidney360;2/11/1827American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, electrolytes, extracorporeal membrane oxygenation, hypothermia, out-of-hospital cardiac arrest, veno-arterial extracorporeal membrane oxygenationBrief CommunicationAcute Kidney Injury and ICU NephrologyBrief CommunicationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-11-2510.34067/KID.00065920202641-76502021-09-08T13:35:20-07:002021-11-25Kidney360Brief Communication21118271830
- Identification of Diabetic Nephropathy in Patients Undergoing Kidney Biopsy through Blood and Urinary Profiles of d-Serine10.34067/KID.0004282021Thu, 09 Sep 2021 07:23:06 GMT-07:00Identification of Diabetic Nephropathy in Patients Undergoing Kidney Biopsy through Blood and Urinary Profiles of d-SerineIwata, YukimasaOkushima, HirokiHesaka, AtsushiKawamura, MasatakaImamura, RyoichiTakahara, ShiroHorio, MasaruTanaka, YoukoIkeda, TatsuhikoNakane, MaikoMita, MasashiHayashi, TerumasaIsaka, YoshitakaKimura, Tomonori2021-09-09T07:23:06-07:00doi:10.34067/KID.0004282021hwp:resource-id:kidney360;2/11/1734American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, biomarker, chiral amino acids, d-serine, diabetes, diabetic kidney disease, diabetic nephropathy, diagnosis, glomerulonephritis, kidney biopsyOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20212021-11-2510.34067/KID.00042820212641-76502021-09-09T07:23:06-07:002021-11-25Kidney360Original Investigation21117341742
- Declined Offers for Deceased Donor Kidneys Are Not an Independent Reflection of Organ Quality10.34067/KID.0004052021Tue, 24 Aug 2021 12:25:50 GMT-07:00Declined Offers for Deceased Donor Kidneys Are Not an Independent Reflection of Organ QualityKing, Kristen L.Chaudhry, Sulemon G.Ratner, Lloyd E.Cohen, David J.Husain, S. AliMohan, Sumit2021-08-24T12:25:50-07:00doi:10.34067/KID.0004052021hwp:resource-id:kidney360;2/11/1807American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, declined offers, kidney transplantation, organ allocation, tissue donorsOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-11-2510.34067/KID.00040520212641-76502021-08-24T12:25:50-07:002021-11-25Kidney360Original Investigation21118071818
- Stroke in Hemodialysis Patients Randomized to Different Intravenous Iron Strategies: A Prespecified Analysis from the PIVOTAL Trial10.34067/KID.0004272021Thu, 16 Sep 2021 11:27:18 GMT-07:00Stroke in Hemodialysis Patients Randomized to Different Intravenous Iron Strategies: A Prespecified Analysis from the PIVOTAL TrialMark, Patrick B.Jhund, Pardeep S.Walters, Matthew R.Petrie, Mark C.Power, AlbertWhite, ClaireRobertson, MicheleConnolly, EugeneAnker, Stefan D.Bhandari, SunilFarrington, KennethKalra, Philip A.Tomson, Charles R.V.Wheeler, David C.Winearls, Christopher G.McMurray, John J.V.Macdougall, Iain C.Ford, Ian,Winnett, GeorgiaAkbani, HabibWessels, JulieAyub, WaqarConnor, AndrewBrown, AlisonMoriarty, JimChowdury, ParamitGriffiths, MeganDasgupta, IndranilDoulton, TimothyBarratt, JonathanVilar, EnricMitra, SandipRamakrishna, BabuNicholas, JohannRoss, CalumKhwaja, ArifHall, MattKirk, AdamSmith, StuartJesky, MarkDay, ClaraAlchi, BassamStratton, JonClarke, HelenWalsh, StephenBrown, RebeccaMcCafferty, KieranSolomon, LaurieRamadoss, SureshRamakrishna, BabuBasanyake, KolithaLawman, SarahBalasubramaniam, GowrieBanerjee, DebasishSwift, PaulineWellberry-Smith, MattGoldsmith, ChristopherLedson, ThomasMikhail, AshrafBenzimra, RuthBell, SamiraSevern, AlisonNeary, JohnDoyle, ArthurThomson, PeterShivashankar, GirishBolton, StephanieQuinn, MichaelMaxwell, PeterHarty, John2021-09-16T11:27:18-07:00doi:10.34067/KID.0004272021hwp:resource-id:kidney360;2/11/1761American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, administration, anemia, cardiovascular disease, heart failure, hemodialysis, iron, randomized controlled trials, renal dialysis, stroke, survivalOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-11-2510.34067/KID.00042720212641-76502021-09-16T11:27:18-07:002021-11-25Kidney360Original Investigation21117611769
- Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients10.34067/KID.0002642021Thu, 09 Sep 2021 03:47:12 GMT-07:00Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI PatientsDaniels, Jaclyn R.Ma, Jennie Z.Cao, ZhijunBeger, Richard D.Sun, JinchunSchnackenberg, LauraPence, LisaChoudhury, DevasmitaPalevsky, Paul M.Portilla, DidierYu, Li-Rong2021-09-09T15:47:12-07:00doi:10.34067/KID.0002642021hwp:resource-id:kidney360;2/11/1716American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, basic science, biomarker, dialysis, kidney recovery, Olink assay, proteomics, serum proteins, SOMAscan assay, survival and growthOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-11-2510.34067/KID.00026420212641-76502021-09-09T15:47:12-07:002021-11-25Kidney360Original Investigation21117161727
- What to Do with Race: Social Factors and Evaluating Clinical Risk in Kidney Transplantation10.34067/KID.0006282021Tue, 05 Oct 2021 12:51:16 GMT-07:00What to Do with Race: Social Factors and Evaluating Clinical Risk in Kidney TransplantationMcKinney, Warren T.Hart, Allyson2021-10-05T12:51:16-07:00doi:10.34067/KID.0006282021hwp:resource-id:kidney360;2/11/1691American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, kidney donor risk index, kidney transplantation, race, social factorsEditorialEditorialeditorial20212021-11-2510.34067/KID.00062820212641-76502021-10-05T12:51:16-07:002021-11-25Kidney360Editorial21116911692
- Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 Cases10.34067/KID.0005372021Thu, 16 Sep 2021 09:50:05 GMT-07:00Glomerular Disease in Temporal Association with SARS-CoV-2 Vaccination: A Series of 29 CasesCaza, Tiffany N.Cassol, Clarissa A.Messias, NidiaHannoudi, AndrewHaun, Randy S.Walker, Patrick D.May, Rebecca M.Seipp, Regan M.Betchick, Elizabeth J.Amin, HassanZiadie, Mandolin S.Haderlie, MichaelEduwu-okwuwa, JoyVancea, IrinaSeek, MelvinElashi, Essam B.Shenoy, GaneshKhalillullah, SayeedFlaxenburg, Jesse A.Brandt, JohnDiamond, Matthew J.Frome, AdamKim, Eugene H.Schlessinger, GregoryUlozas, ErlandasWeatherspoon, Janice L.Hoerschgen, Ethan ThomasFabian, Steven L.Bae, Sung YongIqbal, BilalChouhan, Kanwalijit K.Karam, ZeinaHenry, James T.Larsen, Christopher P.2021-09-16T09:50:05-07:00doi:10.34067/KID.0005372021hwp:resource-id:kidney360;2/11/1770American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, ANCA, APOL1, collapsing glomerulopathy, COVID-19, crescentic glomerulonephritis, IgA nephropathy, lupus nephritis, membranous nephropathy, minimal change disease, SARS-CoV-2 vaccineOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-11-2510.34067/KID.00053720212641-76502021-09-16T09:50:05-07:002021-11-25Kidney360Original Investigation21117701780
- Myeloid Heterogeneity in Kidney Disease as Revealed through Single-Cell RNA SequencingKidney disease represents a global health burden of increasing prevalence and is an independent risk factor for cardiovascular disease. Myeloid cells are a major cellular compartment of the immune system; they are found in the healthy kidney and in increased numbers in the damaged and/or diseased kidney, where they act as key players in the progression of injury, inflammation, and fibrosis. They possess enormous plasticity and heterogeneity, adopting different phenotypic and functional characteristics in response to stimuli in the local milieu. Although this inherent complexity remains to be fully understood in the kidney, advances in single-cell genomics promise to change this. Specifically, single-cell RNA sequencing (scRNA-seq) has had a transformative effect on kidney research, enabling the profiling and analysis of the transcriptomes of single cells at unprecedented resolution and throughput, and subsequent generation of cell atlases. Moving forward, combining scRNA- and single-nuclear RNA-seq with greater-resolution spatial transcriptomics will allow spatial mapping of kidney disease of varying etiology to further reveal the patterning of immune cells and nonimmune renal cells. This review summarizes the roles of myeloid cells in kidney health and disease, the experimental workflow in currently available scRNA-seq technologies, and published findings using scRNA-seq in the context of myeloid cells and the kidney.10.34067/KID.0003682021Thu, 02 Sep 2021 11:34:30 GMT-07:00Myeloid Heterogeneity in Kidney Disease as Revealed through Single-Cell RNA SequencingKidney disease represents a global health burden of increasing prevalence and is an independent risk factor for cardiovascular disease. Myeloid cells are a major cellular compartment of the immune system; they are found in the healthy kidney and in increased numbers in the damaged and/or diseased kidney, where they act as key players in the progression of injury, inflammation, and fibrosis. They possess enormous plasticity and heterogeneity, adopting different phenotypic and functional characteristics in response to stimuli in the local milieu. Although this inherent complexity remains to be fully understood in the kidney, advances in single-cell genomics promise to change this. Specifically, single-cell RNA sequencing (scRNA-seq) has had a transformative effect on kidney research, enabling the profiling and analysis of the transcriptomes of single cells at unprecedented resolution and throughput, and subsequent generation of cell atlases. Moving forward, combining scRNA- and single-nuclear RNA-seq with greater-resolution spatial transcriptomics will allow spatial mapping of kidney disease of varying etiology to further reveal the patterning of immune cells and nonimmune renal cells. This review summarizes the roles of myeloid cells in kidney health and disease, the experimental workflow in currently available scRNA-seq technologies, and published findings using scRNA-seq in the context of myeloid cells and the kidney.Bell, Rachel M.B.Denby, Laura2021-09-02T11:34:30-07:00doi:10.34067/KID.0003682021hwp:resource-id:kidney360;2/11/1844American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, basic science, dendritic cells, kidney disease, macrophage, monocytes, myeloid cells, scRNA-sequencing, sequence analysis, RNABasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-11-2510.34067/KID.00036820212641-76502021-09-02T11:34:30-07:002021-11-25Kidney360Basic Science for Clinicians21118441851
- Global Perspective on Kidney Transplantation: United States10.34067/KID.0002472021Thu, 19 Aug 2021 11:39:27 GMT-07:00Global Perspective on Kidney Transplantation: United StatesWang, Jeffrey H.Hart, Allyson2021-08-19T11:39:27-07:00doi:10.34067/KID.0002472021hwp:resource-id:kidney360;2/11/1836American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, kidney transplant, United States, waitlistGlobal PerspectivesGlobal Perspectivesresearch-article20212021-11-2510.34067/KID.00024720212641-76502021-08-19T11:39:27-07:002021-11-25Kidney360Global Perspectives21118361839
- Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes10.2215/CJN.03290321Fri, 08 Oct 2021 12:18:10 GMT-07:00Timing of Kidney Clamping and Deceased Donor Kidney Transplant OutcomesVille, SimonLorent, MarineKerleau, ClarisseAsberg, AndersLegendre, ChristopheMorelon, EmmanuelBuron, FannyGarrigue, ValérieLe Quintrec, MoglieGirerd, SophieLadrière, MarcAlbano, LaetitiaSicard, AntoineGlotz, DenisLefaucheur, CarmenBranchereau, JulienJacobi, DavidGiral, MagaliReisæter, Anna V.Line, Pål-DagÅsberg, AndersBlancho, GillesBranchereau, JulienCantarovich, DiegoChapelet, AgnèsDantal, JacquesDeltombe, ClémentFigueres, LucileGarandeau, ClaireGiral, MagaliGourraud-Vercel, CarolineHourmant, MaryvonneKaram, GeorgesKerleau, ClarisseMeurette, AurélieVille, SimonKandell, ChristineMoreau, AnneRenaudin, KarineDelbos, FlorentWalencik, AlexandreDevis, AnneMasset, ChristopheKervella, DelphineAmrouche, LucileAnglicheau, DanyAubert, OlivierBererhi, LyndaLegendre, ChristopheLoupy, AlexandreMartinez, FrankSberro-Soussan, RébeccaScemla, AnneZuber, JulienMéjean, ArnaudTimsit, Marc OlivierEschwege, PascalFrimat, LucGirerd, SophieHubert, JacquesLadriere, MarcLaurain, EmmanuelleLeblanc, LouisLecoanet, PierreLemelle, Jean-LouisBadet, LionelBrunet, MariaBuron, FannyCahen, RémiDaoud, SamehFournie, CoralieGrégoire, ArnaudKoenig, AliceLévi, CharlèneMorelon, EmmanuelPouteil-Noble, ClaireRimmelé, ThomasThaunat, OlivierDelmas, SylvieLe Quintrec, MogliePernin, VincentSerre, Jean-EmmanuelGlotz, DenisLefaucheur, CarmenAlbano, LaetitiaSicard, Etienne2021-10-08T12:18:10-07:00doi:10.2215/CJN.03290321hwp:resource-id:clinjasn;16/11/1704American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycadaver organ transplantation, delayed graft function, ischemia-reperfusion, kidney transplantation, organ transplant, constriction, graft survival, kidneyOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-11-01November 202110.2215/CJN.032903211555-90411555-905X2021-10-08T12:18:10-07:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles161117041714
- Coffee Metabolites and Kidney Disease10.2215/CJN.12420921Thu, 04 Nov 2021 01:57:04 GMT-07:00Coffee Metabolites and Kidney DiseaseCornelis, Marilyn C.Burton-Freeman, Britt2021-11-04T13:57:04-07:00doi:10.2215/CJN.12420921hwp:resource-id:clinjasn;16/11/1615American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycoffee, kidney disease, metabolomics, caffeineEditorialEditorialeditorial20212021-11-01November 202110.2215/CJN.124209211555-90411555-905X2021-11-04T13:57:04-07:002021-11Clinical Journal of the American Society of NephrologyEditorial1611111615162016161629
- ANCA Vasculitis Treatment in the Dialysis Patient10.2215/CJN.11960921Mon, 08 Nov 2021 11:40:20 GMT-08:00ANCA Vasculitis Treatment in the Dialysis PatientHendren, ElizabethRadhakrishnan, Jai2021-11-08T11:40:20-08:00doi:10.2215/CJN.11960921hwp:resource-id:clinjasn;16/11/1617American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyantineutrophil cytoplasmic antibodies, vasculitis, renal dialysisEditorialEditorialeditorial20212021-11-01November 202110.2215/CJN.119609211555-90411555-905X2021-11-08T11:40:20-08:002021-11Clinical Journal of the American Society of NephrologyEditorial1611111617166516191675
- Muscle Abnormalities with Kidney Failure10.2215/CJN.12550921Mon, 08 Nov 2021 11:40:20 GMT-08:00Muscle Abnormalities with Kidney FailureBárány, Peter2021-11-08T11:40:20-08:00doi:10.2215/CJN.12550921hwp:resource-id:clinjasn;16/11/1613American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, skeletal muscle, mitochondria, energy metabolism, exercise, muscle abnormalitiesEditorialEditorialeditorial20212021-11-01November 202110.2215/CJN.125509211555-90411555-905X2021-11-08T11:40:20-08:002021-11Clinical Journal of the American Society of NephrologyEditorial1611111613167616141685
- Could This Be Alport Syndrome?10.2215/CJN.00120121Tue, 13 Apr 2021 08:05:32 GMT-07:00Could This Be Alport Syndrome?Lennon, RachelFornoni, Alessia2021-04-13T08:05:32-07:00doi:10.2215/CJN.00120121hwp:resource-id:clinjasn;16/11/1743American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, genetic kidney disease, podocyte, glomerular filtration barrierKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20212021-11-01November 202110.2215/CJN.001201211555-90411555-905X2021-04-13T08:05:32-07:002021-11Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat161117431745
- Airflow Limitation, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients10.2215/CJN.06600521Mon, 08 Nov 2021 11:40:20 GMT-08:00Airflow Limitation, Fatigue, and Health-Related Quality of Life in Kidney Transplant RecipientsKnobbe, Tim J.Kremer, DaanEisenga, Michele F.van Londen, MarcoGomes-Neto, António W.Douwes, Rianne M.Gan, C. TjiCorpeleijn, EvaAnnema, CobyNavis, GerjanBerger, Stefan P.Bakker, Stephan J.L.Jong, Jacoba Annema-deBakker, StephanBerger, StefanBlokzijl, JohannesBodewes, Frankde Boer, MariekeDamman, Kevinde Borst, MartinDiepstra, ArjanDijkstra, GerardDouwes, RianneEisenga, MicheleErasmus, MichielGan, ChiNeto, Antonio GomesGrootjans, HeleenHak, EelkoHeiner-Fokkema, RebeccaHepkema, BoukeKlont, FrankKnobbe, TimKremer, DaanLeuvenink, HenriLexmond, Willemde Meijer, VincentNiesters, Bertvan Pelt, JoostPol, RobertPorte, RobertRanchor, AdelitaSanders, Jan-StephanSchutten, JoëlleSiebelink, MarionSlart, RiemerSwarte, CasTimens, WimTouw, Daanvan den Heuvel, Mariusvan Leer-Buter, Corettavan Londen, MarcoVerschuuren, ErikVos, MichelWeersma, Rinse2021-11-08T11:40:20-08:00doi:10.2215/CJN.06600521hwp:resource-id:clinjasn;16/11/1686American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycomorbidities, cardiovascular disease, diabetes mellitus, quality of life, kidney transplantation, fatigue, respiratory physiological phenomenaOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-11-01November 202110.2215/CJN.066005211555-90411555-905X2021-11-08T11:40:20-08:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles1611111686161116941612
- Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis10.2215/CJN.03190321Mon, 08 Nov 2021 11:40:20 GMT-08:00Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term DialysisKauffmann, MaëlisBobot, MickaëlRobert, ThomasBurtey, StéphaneCouvrat-Desvergnes, GrégoireLavainne, FrédéricPuéchal, XavierTerrier, BenjaminQuéméneur, ThomasFaguer, StanislasKarras, AlexandreBrunet, PhilippeCouchoud, CécileJourde-Chiche, Noémie2021-11-08T11:40:20-08:00doi:10.2215/CJN.03190321hwp:resource-id:clinjasn;16/11/1665American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, end stage kidney disease, chronic dialysis, cardiovascular, immunosuppression, disease activity, relapse, infectionsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-11-01November 202110.2215/CJN.031903211555-90411555-905X2021-11-08T11:40:20-08:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles1611111665161716751619
- Family Members’ Understanding of the End-of-Life Wishes of People Undergoing Maintenance Dialysis10.2215/CJN.04860421Fri, 10 Sep 2021 02:00:11 GMT-07:00Family Members’ Understanding of the End-of-Life Wishes of People Undergoing Maintenance DialysisSaeed, FahadButler, Catherine R.Clark, CarlynO’Loughlin, KristenEngelberg, Ruth A.Hebert, Paul L.Lavallee, Danielle C.Vig, Elizabeth K.Tamura, Manjula KurellaCurtis, J. RandallO’Hare, Ann M.2021-09-10T14:00:11-07:00doi:10.2215/CJN.04860421hwp:resource-id:clinjasn;16/11/1630American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal dialysis, family, knowledge, maintenance, death, terminal careOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20212021-11-01November 202110.2215/CJN.048604211555-90411555-905X2021-09-10T14:00:11-07:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles161116301638
- Kidney Disease among People Who Are IncarceratedCKD affects 15% of US adults and is associated with higher morbidity and mortality. CKD disproportionately affects certain populations, including racial and ethnic minorities and individuals from disadvantaged socioeconomic backgrounds. These groups are also disproportionately affected by incarceration and barriers to accessing health services. Incarceration represents an opportunity to link marginalized individuals to CKD care. Despite a legal obligation to provide a community standard of care including the screening and treatment of individuals with CKD, there is little evidence to suggest systematic efforts are in place to address this prevalent, costly, and ultimately fatal condition. This review highlights unrealized opportunities to connect individuals with CKD to care within the criminal justice system and as they transition to the community, and it underscores the need for more evidence-based strategies to address the health effect of CKD on over-represented communities in the criminal justice system.10.2215/CJN.01910221Wed, 16 Jun 2021 10:53:39 GMT-07:00Kidney Disease among People Who Are IncarceratedCKD affects 15% of US adults and is associated with higher morbidity and mortality. CKD disproportionately affects certain populations, including racial and ethnic minorities and individuals from disadvantaged socioeconomic backgrounds. These groups are also disproportionately affected by incarceration and barriers to accessing health services. Incarceration represents an opportunity to link marginalized individuals to CKD care. Despite a legal obligation to provide a community standard of care including the screening and treatment of individuals with CKD, there is little evidence to suggest systematic efforts are in place to address this prevalent, costly, and ultimately fatal condition. This review highlights unrealized opportunities to connect individuals with CKD to care within the criminal justice system and as they transition to the community, and it underscores the need for more evidence-based strategies to address the health effect of CKD on over-represented communities in the criminal justice system.Murphy, MatthewDing, AnnBerk, JustinRich, JosiahBayliss, George2021-06-16T10:53:39-07:00doi:10.2215/CJN.01910221hwp:resource-id:clinjasn;16/11/1766American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, disparity, equity, prisonersReviewReviewreview-article20212021-11-01November 202110.2215/CJN.019102211555-90411555-905X2021-06-16T10:53:39-07:002021-11Clinical Journal of the American Society of NephrologyReview161117661772
- Understanding Fatigue with Kidney Disease10.2215/CJN.12430921Mon, 08 Nov 2021 11:40:20 GMT-08:00Understanding Fatigue with Kidney DiseaseForfang, Derek2021-11-08T11:40:20-08:00doi:10.2215/CJN.12430921hwp:resource-id:clinjasn;16/11/1611American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFatiguePatient VoicePatient Voiceresearch-article20212021-11-01November 202110.2215/CJN.124309211555-90411555-905X2021-11-08T11:40:20-08:002021-11Clinical Journal of the American Society of NephrologyPatient Voice1611111611168616121694
- Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation10.2215/CJN.02390221Mon, 08 Nov 2021 11:40:20 GMT-08:00Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney TransplantationSouweine, Jean-SébastienGouzi, FaresBadia, ÉricPomies, PascalGarrigue, ValérieMorena, MarionHayot, MauriceMercier, JacquesAyoub, BroniaQuintrec, Moglie LeRaynaud, FabriceCristol, Jean-Paul2021-11-08T11:40:20-08:00doi:10.2215/CJN.02390221hwp:resource-id:clinjasn;16/11/1676American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycell signaling, chronic hemodialysis, chronic kidney disease, mitochondria, transplantation, phenotype, signal transductionOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-11-01November 202110.2215/CJN.023902211555-90411555-905X2021-11-08T11:40:20-08:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles1611111676161316851614
- Poly-IgA Complexes and Disease Severity in IgA Nephropathy10.2215/CJN.01300121Mon, 04 Oct 2021 11:25:32 GMT-07:00Poly-IgA Complexes and Disease Severity in IgA NephropathyZhang, XueLv, JichengLiu, PanXie, XinfangWang, ManliuLiu, DanZhang, HongJin, Jing2021-10-04T11:25:32-07:00doi:10.2215/CJN.01300121hwp:resource-id:clinjasn;16/11/1652American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, glomerulonephritis, immune complexes, Fc receptorsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-11-01November 202110.2215/CJN.013001211555-90411555-905X2021-10-04T11:25:32-07:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles161116521664
- Metabolites Associated with Coffee Consumption and Incident Chronic Kidney Disease10.2215/CJN.05520421Thu, 04 Nov 2021 01:41:55 GMT-07:00Metabolites Associated with Coffee Consumption and Incident Chronic Kidney DiseaseHe, William J.Chen, JingshaRazavi, Alexander C.Hu, Emily A.Grams, Morgan E.Yu, BingParikh, Chirag R.Boerwinkle, EricBazzano, LydiaQi, LuKelly, Tanika N.Coresh, JosefRebholz, Casey M.2021-11-04T13:41:55-07:00doi:10.2215/CJN.05520421hwp:resource-id:clinjasn;16/11/1620American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymetabolomics, chronic kidney disease, coffee, nutrition, physiological phenomenaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-11-01November 202110.2215/CJN.055204211555-90411555-905X2021-11-04T13:41:55-07:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles1611111620161516291616
- The Future Nephrology Workforce: There Will Be One10.2215/CJN.05040421Mon, 19 Jul 2021 10:54:28 GMT-07:00The Future Nephrology Workforce: There Will Be OneParker, Mark G.Sozio, Stephen M.2021-07-19T10:54:28-07:00doi:10.2215/CJN.05040421hwp:resource-id:clinjasn;16/11/1752American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyworkforce, nephrology training, nephrologyPerspectivePerspectiveresearch-article20212021-11-01November 202110.2215/CJN.050404211555-90411555-905X2021-07-19T10:54:28-07:002021-11Clinical Journal of the American Society of NephrologyPerspective161117521754
- Training Nephrology Fellows in Home Dialysis in the United States10.2215/CJN.03110321Wed, 21 Jul 2021 07:02:00 GMT-07:00Training Nephrology Fellows in Home Dialysis in the United StatesGupta, NupurMiller, Brent W.2021-07-21T07:02:00-07:00doi:10.2215/CJN.03110321hwp:resource-id:clinjasn;16/11/1749American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, dialysis, Home DialysisPerspectivePerspectiveresearch-article20212021-11-01November 202110.2215/CJN.031103211555-90411555-905X2021-07-21T07:02:00-07:002021-11Clinical Journal of the American Society of NephrologyPerspective161117491751
- COVID-19–Associated Mortality among Kidney Transplant Recipients and Candidates in the United States10.2215/CJN.02690221Wed, 29 Sep 2021 01:48:33 GMT-07:00COVID-19–Associated Mortality among Kidney Transplant Recipients and Candidates in the United StatesMohan, SumitKing, Kristen L.Husain, S. AliSchold, Jesse D.2021-09-29T13:48:33-07:00doi:10.2215/CJN.02690221hwp:resource-id:clinjasn;16/11/1695American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, mortality, COVID-19, United StatesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-11-01November 202110.2215/CJN.026902211555-90411555-905X2021-09-29T13:48:33-07:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles161116951703
- Humoral Response to mRNA versus an Adenovirus Vector-Based SARS-CoV-2 Vaccine in Dialysis Patients10.2215/CJN.06450521Mon, 26 Jul 2021 10:16:49 GMT-07:00Humoral Response to mRNA versus an Adenovirus Vector-Based SARS-CoV-2 Vaccine in Dialysis PatientsMulhern, Jeffrey G.Fadia, AmitPatel, RuchirFicociello, Linda H.Willetts, JoannaDahne-Steuber, Ines A.Pollan, Melanie C.Mullon, ClaudyDeLisi, JosephineJohnson, CurtisMysayphonh, ChanceKossmann, Robert J.Anger, Michael S.Hymes, Jeffrey L.2021-07-26T10:16:49-07:00doi:10.2215/CJN.06450521hwp:resource-id:clinjasn;16/11/1720American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, COVID-19, vaccination, antibody, SARS-CoV-2Research LetterResearch Letterletter20212021-11-01November 202110.2215/CJN.064505211555-90411555-905X2021-07-26T10:16:49-07:002021-11Clinical Journal of the American Society of NephrologyResearch Letter161117201722
- Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19–associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19–associated kidney disease.10.2215/CJN.04560421Mon, 14 Jun 2021 12:53:52 GMT-07:00Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19–associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19–associated kidney disease.Hassler, LuiseReyes, FabiolaSparks, Matthew A.Welling, PaulBatlle, Daniel2021-06-14T12:53:52-07:00doi:10.2215/CJN.04560421hwp:resource-id:clinjasn;16/11/1755American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, proximal tubule, podocyte, interstitial nephritis, pyelonephritisFeatureFeatureresearch-article20212021-11-01November 202110.2215/CJN.045604211555-90411555-905X2021-06-14T12:53:52-07:002021-11Clinical Journal of the American Society of NephrologyFeature161117551765
- COVID-19 Vaccination Imperatives in People on Maintenance Dialysis10.2215/CJN.07260521Mon, 19 Jul 2021 10:54:28 GMT-07:00COVID-19 Vaccination Imperatives in People on Maintenance DialysisBlake, Peter G.Hladunewich, Michelle A.Oliver, Matthew J.2021-07-19T10:54:28-07:00doi:10.2215/CJN.07260521hwp:resource-id:clinjasn;16/11/1746American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, chronic dialysis, vaccinationPerspectivePerspectiveresearch-article20212021-11-01November 202110.2215/CJN.072605211555-90411555-905X2021-07-19T10:54:28-07:002021-11Clinical Journal of the American Society of NephrologyPerspective161117461748
- Kidney Effects of Empagliflozin in People with Type 1 Diabetes10.2215/CJN.07700621Fri, 17 Sep 2021 10:39:07 GMT-07:00Kidney Effects of Empagliflozin in People with Type 1 DiabetesCherney, David Z.I.Bjornstad, PetterPerkins, Bruce A.Rosenstock, JulioNeubacher, DietmarMarquard, JanSoleymanlou, Nima2021-09-17T10:39:07-07:00doi:10.2215/CJN.07700621hwp:resource-id:clinjasn;16/11/1715American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney protection, kidney function decline, glomerular filtration rate, diabetic kidney disease, diabetes, clinical trial, sodium-glucose co-transporter-2 inhibitor, diabetes mellitus, type 1, empagliflozin, glucosidesResearch LetterResearch Letterletter20212021-11-01November 202110.2215/CJN.077006211555-90411555-905X2021-09-17T10:39:07-07:002021-11Clinical Journal of the American Society of NephrologyResearch Letter161117151719
- C3 Glomerulopathy and Related Disorders in Children10.2215/CJN.00320121Wed, 22 Sep 2021 10:24:42 GMT-07:00C3 Glomerulopathy and Related Disorders in ChildrenWong, Edwin K.S.Marchbank, Kevin J.Lomax-Browne, HannahPappworth, Isabel Y.Denton, HarrietCooke, KatieWard, SophieMcLoughlin, Amy-ClaireRichardson, GrantWilson, ValerieHarris, Claire L.Morgan, B. PaulHakobyan, SvetlanaMcAlinden, PaulGale, Daniel P.Maxwell, HeatherChristian, MartinMalcomson, RogerGoodship, Timothy H.J.Marks, Stephen D.Pickering, Matthew C.Kavanagh, DavidCook, H. TerenceJohnson, Sally A.Brimble, SuCook, H. TerenceGale, Daniel P.Gibbs, JulieGilbert, RodneyHarper, LorraineHarris, Claire L.Jessup, KimJohnson, Sally A.Jones, HelenKavanagh, DavidLevine, AdamLomax-Browne, HannahLongfellow, AndrewMalcomson, RogerMarchbank, Kevin J.Marks, Stephen D.Maxwell, HeatherMcAlinden, PaulMilford, DavidPickering, Matthew C.Richardson, SandraRichardson, StephenSebire, NeilTaylor, MarkWessels, JulieWhittall, SarahWong, Edwin K.S.Christian, MartinFinlay, EricGilbert, RodneyHegde, ShivaramJohnson, Sally A.Jones, CarolineMarks, Stephen D.Maxwell, HeatherMilford, DavidSaleem, MoinSinha, ManishWebb, Nick2021-09-22T10:24:42-07:00doi:10.2215/CJN.00320121hwp:resource-id:clinjasn;16/11/1639American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycomplement, membranoproliferative glomerulonephritis (MPGN), children, C3 glomerulopathyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-11-01November 202110.2215/CJN.003201211555-90411555-905X2021-09-22T10:24:42-07:002021-11Clinical Journal of the American Society of NephrologyOriginal Articles161116391651
- Recurrent Glomerular Disease after Kidney TransplantationRecurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.10.2215/CJN.00280121Fri, 22 Oct 2021 06:42:10 GMT-07:00Recurrent Glomerular Disease after Kidney TransplantationRecurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.Uffing, AudreyHullekes, FrankRiella, Leonardo V.Hogan, Jonathan J.2021-10-22T06:42:10-07:00doi:10.2215/CJN.00280121hwp:resource-id:clinjasn;16/11/1730American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulonephritis, kidney transplantation, glomerular disease, allograft failure, recurrent glomerular disease, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-11-01November 202110.2215/CJN.002801211555-90411555-905X2021-10-22T06:42:10-07:002021-11Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161117301742
- Chronic Allograft InjuryWith the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.10.2215/CJN.15590920Mon, 05 Apr 2021 07:48:23 GMT-07:00Chronic Allograft InjuryWith the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.Langewisch, EricMannon, Roslyn B.2021-04-05T07:48:23-07:00doi:10.2215/CJN.15590920hwp:resource-id:clinjasn;16/11/1723American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, renal fibrosis, renal injury, chronic allograft failure, allografts, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-11-01November 202110.2215/CJN.155909201555-90411555-905X2021-04-05T07:48:23-07:002021-11Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161117231729
- Early Response in Albuminuria and Long-Term Kidney Protection during Treatment with an Endothelin Receptor Antagonist: A Prespecified Analysis from the SONAR Trial10.1681/ASN.2021030391Wed, 22 Sep 2021 10:24:03 GMT-07:00Early Response in Albuminuria and Long-Term Kidney Protection during Treatment with an Endothelin Receptor Antagonist: A Prespecified Analysis from the SONAR TrialHeerspink, Hiddo J. L.Xie, DiBakris, GeorgeCorrea-Rotter, RicardoHou, Fan-FanKitzman, Dalane W.Kohan, DonaldMakino, HirofumiMcMurray, John J. V.Perkovic, VladoRossing, PeterParving, Hans-Henrikde Zeeuw, Dick,2021-09-22T10:24:03-07:00doi:10.1681/ASN.2021030391hwp:resource-id:jnephrol;32/11/2900American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical trial, albuminuria, Endothelin Receptor Antagonist, type 2 diabetes, SONARClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210303911046-66731533-34502021-09-22T10:24:03-07:002021-11Journal of the American Society of NephrologyClinical Research3211112900268929112691
- PodoSighter: A Cloud-Based Tool for Label-Free Podocyte Detection in Kidney Whole-Slide Images10.1681/ASN.2021050630Fri, 03 Sep 2021 09:49:58 GMT-07:00PodoSighter: A Cloud-Based Tool for Label-Free Podocyte Detection in Kidney Whole-Slide ImagesGovind, DarshanaBecker, Jan U.Miecznikowski, JeffreyRosenberg, Avi Z.Dang, JulienTharaux, Pierre LouisYacoub, RabiThaiss, FriedrichHoyer, Peter F.Manthey, DavidLutnick, BrendonWorral, Amber M.Mohammad, ImtiazWalavalkar, VighneshTomaszewski, John E.Jen, Kuang-YuSarder, Pinaki2021-09-03T09:49:58-07:00doi:10.1681/ASN.2021050630hwp:resource-id:jnephrol;32/11/2795American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte detection, deep learning, pix2pix GAN, Deeplab, cloud, cloud computing, urinary tract, viscera, podocytes, CNNBasic ResearchBasic Researchresearch-article20212021-11-01November 202110.1681/ASN.20210506301046-66731533-34502021-09-03T09:49:58-07:002021-11Journal of the American Society of NephrologyBasic Research321127952813
- Donor-Specific Antibody Is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified as No Rejection10.1681/ASN.2021040433Mon, 12 Jul 2021 10:21:53 GMT-07:00Donor-Specific Antibody Is Associated with Increased Expression of Rejection Transcripts in Renal Transplant Biopsies Classified as No RejectionMadill-Thomsen, Katelynn S.Böhmig, Georg A.Bromberg, JonathanEinecke, GunillaEskandary, FarsadGupta, GauravHidalgo, Luis G.Myslak, MarekViklicky, OndrejPerkowska-Ptasinska, AgnieszkaHalloran, Philip F.,Mannon, RoslynSerón, DanielSellarés, JoanaAkalin, Enverde Freitas, DeclanPicton, MichaelBromberg, JonathanWeir, MattBudde, KlemensHeinbokel, TimmEinecke, GunillaYang, HaroldNarins, SethSamaniego-Picota, MilagrosLefaucheur, CarmenLoupy, AlexandreMyslak, MarekPerkowska-Ptasinska, AgnieszkaBingaman, AdamBrennan, DanielMalone, AndrewKasiske, BertramHalloran, Philip FMatas, ArthurDjamali, ArjangBöhmig, GeorgEskandary, FarsadGupta, Gaurav2021-07-12T10:21:53-07:00doi:10.1681/ASN.2021040433hwp:resource-id:jnephrol;32/11/2743American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, transplantation, gene expression, renal transplantation, rejectionBasic ResearchBasic Researchresearch-article20212021-11-01November 202110.1681/ASN.20210404331046-66731533-34502021-07-12T10:21:53-07:002021-11Journal of the American Society of NephrologyBasic Research321127432758
- Podocyte Aging: Why and How Getting Old MattersThe effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population’s increasing longevity. Age-associated changes to podocytes, which are terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses the molecular and cellular mechanisms underlying podocyte aging, how these mechanisms might be augmented by disease in the aged kidney, and approaches to mitigate progressive damage to podocytes. Furthermore, we address how biologic pathways such as those associated with cellular growth confound aging in humans and rodents.10.1681/ASN.2021050614Fri, 29 Oct 2021 12:45:34 GMT-07:00Podocyte Aging: Why and How Getting Old MattersThe effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population’s increasing longevity. Age-associated changes to podocytes, which are terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses the molecular and cellular mechanisms underlying podocyte aging, how these mechanisms might be augmented by disease in the aged kidney, and approaches to mitigate progressive damage to podocytes. Furthermore, we address how biologic pathways such as those associated with cellular growth confound aging in humans and rodents.Shankland, Stuart J.Wang, YuliangShaw, Andrey S.Vaughan, Joshua C.Pippin, Jeffrey W.Wessely, Oliver2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021050614hwp:resource-id:jnephrol;32/11/2697American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, aging, glomerulosclerosis, senescence, RNA sequencing, glomerulusUp Front MattersReviewsUp Front MattersReviewsreview-article20212021-11-01November 202110.1681/ASN.20210506141046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyUp Front Matters321126972713
- Incidence of Arteritis and Peritubular Capillaritis in ANCA-associated Vasculitis10.1681/ASN.2021081057Fri, 15 Oct 2021 06:20:56 GMT-07:00Incidence of Arteritis and Peritubular Capillaritis in ANCA-associated VasculitisHakroush, SamyTampe, Björn2021-10-15T06:20:56-07:00doi:10.1681/ASN.2021081057hwp:resource-id:jnephrol;32/11/2974American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyANCA-associated vasculitis, arteritis, peritubular capillaritis, incidenceLetters to the EditorLetters to the Editorletter20212021-11-01November 202110.1681/ASN.20210810571046-66731533-34502021-10-15T06:20:56-07:002021-11Journal of the American Society of NephrologyLetters to the Editor321192974236229752374
- Tribute to Barbara T. Murphy10.1681/ASN.2021091171Fri, 29 Oct 2021 12:45:34 GMT-07:00Tribute to Barbara T. MurphyQuaggin, Susan E.Gill, John S.2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021091171hwp:resource-id:jnephrol;32/11/2685American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyobituaryObituaryObituaryresearch-article20212021-11-01November 202110.1681/ASN.20210911711046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyObituary321126852686
- Understanding Risks and Our Responsibility to Living Donors10.1681/ASN.2021081129Fri, 29 Oct 2021 12:45:34 GMT-07:00Understanding Risks and Our Responsibility to Living DonorsGill, John S.Schold, JesseKaplan, Bruce2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021081129hwp:resource-id:jnephrol;32/11/2691American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydonor, kidney transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-11-01November 202110.1681/ASN.20210811291046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyUp Front Matters3211112691293326932947
- Predictive Enrichment in Kidney RCTs: Is Albuminuria the Answer?10.1681/ASN.2021091235Fri, 29 Oct 2021 12:45:34 GMT-07:00Predictive Enrichment in Kidney RCTs: Is Albuminuria the Answer?Odutayo, AyodeleCherney, David Z.I.2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021091235hwp:resource-id:jnephrol;32/11/2689American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, clinical trial, clinical epidemiologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-11-01November 202110.1681/ASN.20210912351046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyUp Front Matters3211112689290026912911
- Beyond Transcription Factors: Remodeling Chromatin in the Metanephric Mesenchyme10.1681/ASN.2021081038Fri, 29 Oct 2021 12:45:34 GMT-07:00Beyond Transcription Factors: Remodeling Chromatin in the Metanephric MesenchymeEl-Dahr, Samir S.2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021081038hwp:resource-id:jnephrol;32/11/2687American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, transcription factors, chromatin remodeling, metanephric mesenchyme, mouseUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-11-01November 202110.1681/ASN.20210810381046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyUp Front Matters32111111268728152834268928332850
- This Month's Highlights10.1681/ASN.2021091197Fri, 29 Oct 2021 12:45:34 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021091197hwp:resource-id:jnephrol;32/11/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20212021-11-01November 202110.1681/ASN.20210911971046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyThis Month’s Highlights3211ii
- The Clinical Application of Urine Soluble CD163 in ANCA-Associated Vasculitis10.1681/ASN.2021030382Mon, 13 Sep 2021 11:27:11 GMT-07:00The Clinical Application of Urine Soluble CD163 in ANCA-Associated VasculitisMoran, Sarah M.Scott, JenniferClarkson, Michael R.Conlon, NiallDunne, JeanGriffin, Matthew D.Griffin, Tomas P.Groarke, ElizabethHolian, JohnJudge, ConorWyse, JasonMcLoughlin, KirstyO’Hara, Paul V.Kretzler, MatthiasLittle, Mark A.,Sedor, J.Dell, K.Schachere, M.Negrey, J.Lemley, K.Lim, E.Srivastava, T.Garrett, A.Sethna, C.Laurent, K.Appel, G.Toledo, M.Greenbaum, L.Wang, C.Kang, C.Adler, S.LaPage, J.Athavale, A.Itteera, M.Atkinson, M.Boynton, S.Fervenza, F.Lieske, J.Hogan, M.Chernitskiy, V.Kaskel, F.Ross, M.Flynn, P.Kopp, J.Blake, J.Trachtman, H.Zhdanova, O.Modersitzki, F.Vento, S.Lafayette, R.Mehta, K.Gadegbeku, C.Quinn-Boyle, S.Hladunewich, M.Reich, H.Ling, P.Romano, M.Fornoni, A.Bidot, C.Kretzler, M.Gipson, D.Williams, A.LaVigne, J.Derebail, V.Gibson, K.Froment, A.Grubbs, S.Holzman, L.Meyers, K.Kallem, K.Lalli, J.Sambandam, K.Wang, Z.Rogers, M.Jefferson, A.Hingorani, S.Tuttle, K.Bray, M.Kelton, M.Cooper, A.Lin, J.J.Baker, StefanieKretzler, M.Barisoni, L.Desmond, H.Gadegbeku, C.Gillespie, B.Gipson, D.Holzman, L.Kurtz, V.Mariani, L.Sampson, M.Larkina, M.Zee, J.Li, S.Lienczewski, C.Liu, J.Mainieri, T.Wladkowski, M.Williams, A.Avila-Casado, CarmenBagnasco, SerenaGaut, JosephHewitt, StephenHodgin, JeffLemley, KevinMariani, LauraPalmer, MatthewRosenberg, AviRoyal, VirginieThomas, DavidZee, JarcyBarisoni, LauraNast, Cynthia2021-09-13T11:27:11-07:00doi:10.1681/ASN.2021030382hwp:resource-id:jnephrol;32/11/2920American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, CD163, biomarker, crescentic glomerulonephritis, macrophage, urineClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210303821046-66731533-34502021-09-13T11:27:11-07:002021-11Journal of the American Society of NephrologyClinical Research321129202932
- Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney Donors10.1681/ASN.2021040548Thu, 21 Oct 2021 07:54:09 GMT-07:00Intermediate Renal Outcomes, Kidney Failure, and Mortality in Obese Kidney DonorsIbrahim, Hassan N.Murad, Dina N.Hebert, Sean A.Adrogue, Horacio E.Nguyen, HanaNguyen, Duc T.Matas, Arthur J.Graviss, Edward A.2021-10-21T07:54:09-07:00doi:10.1681/ASN.2021040548hwp:resource-id:jnephrol;32/11/2933American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, kidney donation, living donation, glomerular filtration rate, hypertension, outcomesClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210405481046-66731533-34502021-10-21T07:54:09-07:002021-11Journal of the American Society of NephrologyClinical Research3211112933269129472693
- Authors’ Reply10.1681/ASN.2021070993Tue, 05 Oct 2021 05:51:20 GMT-07:00Authors’ ReplyHarris, Raymond C.Zhang, Ming-Zhi2021-10-05T05:51:20-07:00doi:10.1681/ASN.2021070993hwp:resource-id:jnephrol;32/11/2972-aAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosisLetters to the EditorLetters to the Editorletter20212021-11-01November 202110.1681/ASN.20210709931046-66731533-34502021-10-05T05:51:20-07:002021-11Journal of the American Society of NephrologyLetters to the Editor3211115297229711037297229721052
- Authors’ Reply10.1681/ASN.2021081039Fri, 29 Oct 2021 12:45:34 GMT-07:00Authors’ ReplyBunnapradist, SuphamaiTabriziani, Hossein2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021081039hwp:resource-id:jnephrol;32/11/2973American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute rejection, acute allograft rejection, chronic allograft rejection, kidney, kidney biopsy, transplantationLetters to the EditorLetters to the Editorresearch-article20212021-11-01November 202110.1681/ASN.20210810391046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyLetters to the Editor32111110297329722439297429732441
- Need for a Validation Study before Using the Two-Step Algorithm for dd-cfDNA to Screen for Acute Rejection10.1681/ASN.2021070938Fri, 29 Oct 2021 12:45:34 GMT-07:00Need for a Validation Study before Using the Two-Step Algorithm for dd-cfDNA to Screen for Acute RejectionGupta, AditiKaplan, Bruce2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021070938hwp:resource-id:jnephrol;32/11/2972American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrejection, donor derived cell free DNA, biomarker, kidney transplant, cell-free nucleic acids, algorithmsLetters to the EditorLetters to the Editorletter20212021-11-01November 202110.1681/ASN.20210709381046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyLetters to the Editor32111171029722973222124392973297422322441
- Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD10.1681/ASN.2020091310Fri, 29 Oct 2021 12:45:34 GMT-07:00Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKDWalker, Joshua A.Richards, SeanWhelan, Stephen A.Yoo, Sung BokRussell, Teresa L.Arinze, NkirukaLotfollahzadeh, SaranNapoleon, Marc A.Belghasem, MostafaLee, NormanDember, Laura M.Ravid, KatyaChitalia, Vipul C.2021-10-29T12:45:34-07:00doi:10.1681/ASN.2020091310hwp:resource-id:jnephrol;32/11/2834American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, cell signaling, thrombosis, uremic toxins, indoxyl sulfate, kynurenine, IDO1, uremic toxicity, arteriovenous fistulaBasic ResearchBasic Researchresearch-article20212021-11-01November 202110.1681/ASN.20200913101046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyBasic Research3211112834268728502689
- Heterogenous Role of IRF4 in Kidney Fibrosis10.1681/ASN.2021060835Tue, 05 Oct 2021 06:18:34 GMT-07:00Heterogenous Role of IRF4 in Kidney FibrosisLiu, ZhenyuZhang, Jingbo2021-10-05T06:18:34-07:00doi:10.1681/ASN.2021060835hwp:resource-id:jnephrol;32/11/2971American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, renal fibrosis, interferon regulatory factor 4, macrophages, arteriosclerosis, urinary tractLetters to the EditorLetters to the Editorletter20212021-11-01November 202110.1681/ASN.20210608351046-66731533-34502021-10-05T06:18:34-07:002021-11Journal of the American Society of NephrologyLetters to the Editor3211115297129721037297229721052
- Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous Glomerulonephritis10.1681/ASN.2020121699Fri, 29 Oct 2021 12:45:34 GMT-07:00Glomerular Endothelial Cell-Derived microRNA-192 Regulates Nephronectin Expression in Idiopathic Membranous GlomerulonephritisMüller-Deile, JaninaSopel, NinaOhs, AlexandraRose, VictoriaGröner, MarwinWrede, ChristophHegermann, JanDaniel, ChristophAmann, KerstinZahner, GuntherSchiffer, Mario2021-10-29T12:45:34-07:00doi:10.1681/ASN.2020121699hwp:resource-id:jnephrol;32/11/2777American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, membranous nephropathy, glomerular filtration barrier, podocyte, glomerular basement membrane, microRNAs, glomerular endothelial cells, nephronectinBasic ResearchBasic Researchresearch-article20212021-11-01November 202110.1681/ASN.20201216991046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyBasic Research321127772794
- Analysis of Performance Trends from 2010–2019 on the American Board of Internal Medicine Nephrology Certifying Exam10.1681/ASN.2021020160Wed, 27 Oct 2021 01:33:36 GMT-07:00Analysis of Performance Trends from 2010–2019 on the American Board of Internal Medicine Nephrology Certifying ExamBerns, Jeffrey S.Weng, WeifengJaar, Bernard G.Lipner, Rebecca S.Brossman, Bradley G.McDonald, Furman S.2021-10-27T13:33:36-07:00doi:10.1681/ASN.2021020160hwp:resource-id:jnephrol;32/11/2714American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephrology fellowship, certifying exam, ABIM, international medical graduate, US medical graduateUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20212021-11-01November 202110.1681/ASN.20210201601046-66731533-34502021-10-27T13:33:36-07:002021-11Journal of the American Society of NephrologyUp Front Matters3211112714269427232696
- Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease10.1681/ASN.2021030336Wed, 18 Aug 2021 09:07:10 GMT-07:00Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney DiseaseMair, Robert D.Lee, SeolhyunPlummer, Natalie S.Sirich, Tammy L.Meyer, Timothy W.2021-08-18T09:07:10-07:00doi:10.1681/ASN.2021030336hwp:resource-id:jnephrol;32/11/2877American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal failureClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210303361046-66731533-34502021-08-18T09:07:10-07:002021-11Journal of the American Society of NephrologyClinical Research321128772884
- Chromatin Remodelers Interact with Eya1 and Six2 to Target Enhancers to Control Nephron Progenitor Cell Maintenance10.1681/ASN.2021040525Fri, 29 Oct 2021 12:45:34 GMT-07:00Chromatin Remodelers Interact with Eya1 and Six2 to Target Enhancers to Control Nephron Progenitor Cell MaintenanceLi, JunXu, JinshuJiang, HuihuiZhang, TingRamakrishnan, AarthiShen, LiXu, Pin-Xian2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021040525hwp:resource-id:jnephrol;32/11/2815American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyEya1/Six2-regulatory network, interaction of chromatin remodeling SWI/SNF proteins with Eya1/Six2, nephron progenitor cell maintenance, Pbx1 distal enhancers, Mycn proximal enhancer, Eya1 enhancersBasic ResearchBasic Researchresearch-article20212021-11-01November 202110.1681/ASN.20210405251046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyBasic Research3211112815268728332689
- The Art and Science of Medicine … and Standardized Test Scores10.1681/ASN.2021091245Wed, 27 Oct 2021 01:33:37 GMT-07:00The Art and Science of Medicine … and Standardized Test ScoresQuaggin, Susan E.Safar-Boueri, Luisa2021-10-27T13:33:37-07:00doi:10.1681/ASN.2021091245hwp:resource-id:jnephrol;32/11/2694American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephrology fellowship, ABIM, certifying exam, international medical graduate, US medical graduateUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20212021-11-01November 202110.1681/ASN.20210912451046-66731533-34502021-10-27T13:33:37-07:002021-11Journal of the American Society of NephrologyUp Front Matters3211112694271426962723
- Ferroptosis Promotes Cyst Growth in Autosomal Dominant Polycystic Kidney Disease Mouse Models10.1681/ASN.2021040460Fri, 29 Oct 2021 12:45:34 GMT-07:00Ferroptosis Promotes Cyst Growth in Autosomal Dominant Polycystic Kidney Disease Mouse ModelsZhang, XiaoqinLi, Linda XiaoyanDing, HaoTorres, Vicente E.Yu, ChenLi, Xiaogang2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021040460hwp:resource-id:jnephrol;32/11/2759American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyferroptosis, iron metabolism, lipid peroxidation, 4HNE, cell proliferationBasic ResearchBasic Researchresearch-article20212021-11-01November 202110.1681/ASN.20210404601046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyBasic Research321127592776
- mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy10.1681/ASN.2021030333Mon, 04 Oct 2021 12:36:06 GMT-07:00mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and CardiomyopathySchlingmann, Karl P.Jouret, FrançoisShen, KuangNigam, AnukratiArjona, Francisco J.Dafinger, ClaudiaHouillier, PascalJones, Deborah P.Kleinerüschkamp, FelixOh, JunGodefroid, NathalieEltan, MehmetGüran, TülayBurtey, StéphaneParotte, Marie-ChristineKönig, JensBraun, AlinaBos, CaroIbars Serra, MariaRehmann, HolgerZwartkruis, Fried J.T.Renkema, Kirsten Y.Klingel, KarinSchulze-Bahr, EricSchermer, BernhardBergmann, CarstenAltmüller, JanineThiele, HolgerBeck, Bodo B.Dahan, KarinSabatini, DavidLiebau, Max C.Vargas-Poussou, RosaKnoers, Nine V.A.M.Konrad, Martinde Baaij, Jeroen H.F.2021-10-04T12:36:06-07:00doi:10.1681/ASN.2021030333hwp:resource-id:jnephrol;32/11/2885American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhypomagnesemia, Bartter syndrome, genetic renal disease, magnesium, kidney stones, TRPM6, nephrocalcinosis, hypokalemia, mTOR, rag complex, salt wastingClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210303331046-66731533-34502021-10-04T12:36:06-07:002021-11Journal of the American Society of NephrologyClinical Research321155288510461048289910481049
- Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic Hemodialysis10.1681/ASN.2021020193Mon, 13 Sep 2021 11:27:11 GMT-07:00Preserved Cerebral Oxygenation with Worsening Global Myocardial Strain during Pediatric Chronic HemodialysisIdrovo, AlexandraPignatelli, RicardoLoar, RobertNieuwsma, AselaGeer, JessicaSolomon, CatharinaSwartz, SarahGhanayem, NancyAkcan-Arikan, AyseSrivaths, Poyyapakkam2021-09-13T11:27:11-07:00doi:10.1681/ASN.2021020193hwp:resource-id:jnephrol;32/11/2912American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycerebral oxygenation, central venous oxygen saturation, global longitudinal strainClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210201931046-66731533-34502021-09-13T11:27:11-07:002021-11Journal of the American Society of NephrologyClinical Research321129122919
- Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease10.1681/ASN.2021010044Wed, 04 Aug 2021 12:11:01 GMT-07:00Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive DiseaseQuinn, Ghazal Z.Abedini, AminLiu, HongboMa, ZiyuanCucchiara, AndrewHavasi, AndreaHill, JonPalmer, Matthew B.Susztak, Katalin2021-08-04T12:11:01-07:00doi:10.1681/ASN.2021010044hwp:resource-id:jnephrol;32/11/2863American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, histopathology, fibrosis, glomerulosclerosisClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210100441046-66731533-34502021-08-04T12:11:01-07:002021-11Journal of the American Society of NephrologyClinical Research321128632876
- Immunogenicity of SARS-CoV-2 Vaccine in Dialysis10.1681/ASN.2021040432Wed, 04 Aug 2021 12:11:00 GMT-07:00Immunogenicity of SARS-CoV-2 Vaccine in DialysisLacson, EduardoArgyropoulos, Christos P.Manley, Harold J.Aweh, GideonChin, Andrew I.Salman, Loay H.Hsu, Caroline M.Johnson, Doug S.Weiner, Daniel E.2021-08-04T12:11:00-07:00doi:10.1681/ASN.2021040432hwp:resource-id:jnephrol;32/11/2735American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, end-stage kidney disease, chronic kidney disease, vaccine, SARS-CoV-2, COVID-19, immune deficiency, clinical immunology, end-stage kidney diseaseRapid CommunicationsRapid Communicationsresearch-article20212021-11-01November 202110.1681/ASN.20210404321046-66731533-34502021-08-04T12:11:00-07:002021-11Journal of the American Society of NephrologyRapid Communications321127352742
- Kidney Outcomes in Long COVID10.1681/ASN.2021060734Wed, 01 Sep 2021 06:00:08 GMT-07:00Kidney Outcomes in Long COVIDBowe, BenjaminXie, YanXu, EvanAl-Aly, Ziyad2021-09-01T06:00:08-07:00doi:10.1681/ASN.2021060734hwp:resource-id:jnephrol;32/11/2851American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, ESKD, acute kidney injury, post-acute sequelae of SARS-CoV-2 infection, PASC, post-acute COVID, long COVID, eGFR decline, kidney function, COVID-19Clinical EpidemiologyClinical Epidemiologyresearch-article20212021-11-01November 202110.1681/ASN.20210607341046-66731533-34502021-09-01T06:00:08-07:002021-11Journal of the American Society of NephrologyClinical Epidemiology321128512862
- Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 Pandemic10.1681/ASN.2021040579Fri, 17 Sep 2021 10:39:33 GMT-07:00Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 PandemicWetmore, James B.Johansen, Kirsten L.Liu, JiannongPeng, YiGilbertson, David T.Weinhandl, Eric D.2021-09-17T10:39:33-07:00doi:10.1681/ASN.2021040579hwp:resource-id:jnephrol;32/11/2948American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, dialysis, ESKD, transplantation, USRDSClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210405791046-66731533-34502021-09-17T10:39:33-07:002021-11Journal of the American Society of NephrologyClinical Research32112229484554552957455457
- Longitudinal Outcomes of COVID-19–Associated Collapsing Glomerulopathy and Other Podocytopathies10.1681/ASN.2021070931Wed, 20 Oct 2021 07:19:19 GMT-07:00Longitudinal Outcomes of COVID-19–Associated Collapsing Glomerulopathy and Other PodocytopathiesKudose, SatoruSantoriello, DominickBomback, Andrew S.Sekulic, MiroslavBatal, IbrahimStokes, M. BarryGhavami, Iman A.Kim, Jung S.Marasa, MaddalenaXu, KatherinePeleg, YonatanBarasch, JonathanCanetta, PietroRasouly, Hila MiloGharavi, Ali G.Markowitz, Glen S.D’Agati, Vivette D.2021-10-20T07:19:19-07:00doi:10.1681/ASN.2021070931hwp:resource-id:jnephrol;32/11/2958American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycollapsing FSGS, virology, pathology, COVID-19, kidney biopsy, podocytopathy, SARS, FSGSClinical ResearchClinical Researchresearch-article20212021-11-01November 202110.1681/ASN.20210709311046-66731533-34502021-10-20T07:19:19-07:002021-11Journal of the American Society of NephrologyClinical Research321129582969
- Large Between-Patient Variability in eGFR Decline before Clinical Trial Enrollment and Impact on Atrasentan’s Efficacy: A Post Hoc Analysis from the SONAR Trial10.1681/ASN.2021040498Fri, 20 Aug 2021 10:25:58 GMT-07:00Large Between-Patient Variability in eGFR Decline before Clinical Trial Enrollment and Impact on Atrasentan’s Efficacy: A Post Hoc Analysis from the SONAR TrialWaijer, Simke W.de Vries, Sieta T.Busch, RobertXie, DiGansevoort, Ron T.Hou, Fan FanGórriz, Jose L.Laverman, Gozewijn D.De Nicola, LucaPascual, JulioProvenzano, MichelePergola, Pablo E.Tang, Sydney C.W.Wanner, ChristophZaoui, PhilippeParving, Hans-Henrikde Zeeuw, DickHeerspink, Hiddo J.L.2021-08-20T10:25:58-07:00doi:10.1681/ASN.2021040498hwp:resource-id:jnephrol;32/11/2731American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyeGFR decline, type 2 diabetes, endothelin receptor antagonist, chronic kidney disease, randomized controlled trialsResearch LettersResearch Lettersletter20212021-11-01November 202110.1681/ASN.20210404981046-66731533-34502021-08-20T10:25:58-07:002021-11Journal of the American Society of NephrologyResearch Letters321127312734
- Testing of Worn Face Masks for Timely Diagnosis of SARS-CoV-2 in Hemodialysis Patients10.1681/ASN.2021060812Mon, 19 Jul 2021 11:44:34 GMT-07:00Testing of Worn Face Masks for Timely Diagnosis of SARS-CoV-2 in Hemodialysis PatientsWang, XiaolingGrobe, NadjaHaq, ZahinThwin, OhnmarFuentes, Lemuel RiveraMaddux, DuganKotanko, Peter2021-07-19T11:44:34-07:00doi:10.1681/ASN.2021060812hwp:resource-id:jnephrol;32/11/2728American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymask, dialysis, SARS-CoV-2, COVID-19Research LettersResearch Lettersletter20212021-11-01November 202110.1681/ASN.20210608121046-66731533-34502021-07-19T11:44:34-07:002021-11Journal of the American Society of NephrologyResearch Letters321127282730
- Impaired Humoral but Substantial Cellular Immune Response to Variants of Concern B1.1.7 and B.1.351 in Hemodialysis Patients after Vaccination with BNT162b210.1681/ASN.2021050672Fri, 29 Oct 2021 12:45:34 GMT-07:00Impaired Humoral but Substantial Cellular Immune Response to Variants of Concern B1.1.7 and B.1.351 in Hemodialysis Patients after Vaccination with BNT162b2Thieme, Constantin J.Blazquez-Navarro, ArturoSafi, LemaKaliszczyk, SviatlanaPaniskaki, KrystalleniaNeumann, Isabel E.Schmidt, KitaStockhausen, MaraHörstrup, JanCinkilic, OcanFlitsch-Kiefner, LinusMeister, Toni L.Marheinecke, CorinnaPfaender, StephanieSteinmann, EikeSeibert, Felix S.Stervbo, UlrikWesthoff, Timm H.Roch, ToralfBabel, Nina2021-10-29T12:45:34-07:00doi:10.1681/ASN.2021050672hwp:resource-id:jnephrol;32/11/2725American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, clinical immunology, kidney disease, SARS-CoV-2, vaccination, infectious diseases, mRNA vaccine, immunity, cellular, COVID-19Research LettersResearch Lettersletter20212021-11-01November 202110.1681/ASN.20210506721046-66731533-34502021-10-29T12:45:34-07:002021-11Journal of the American Society of NephrologyResearch Letters321127252727
- Unexpected Kidney Imaging in a Patient with UTI10.34067/KID.0003022021Thu, 28 Oct 2021 08:50:34 GMT-07:00Unexpected Kidney Imaging in a Patient with UTIGill, JasmeetSchuller, Joris M.Szerlip, Harold M.2021-10-28T08:50:34-07:00doi:10.34067/KID.0003022021hwp:resource-id:kidney360;2/10/1688American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, cystic kidney disease, unilateralClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-10-2810.34067/KID.00030220212641-76502021-10-28T08:50:34-07:002021-10-28Kidney360Clinical Images in Nephrology and Dialysis21016881689
- Still Learning from Our Patients: Hypokalemia in Patients with Lupus Nephritis10.34067/KID.0005302021Thu, 28 Oct 2021 08:50:34 GMT-07:00Still Learning from Our Patients: Hypokalemia in Patients with Lupus NephritisRodan, Aylin R.2021-10-28T08:50:34-07:00doi:10.34067/KID.0005302021hwp:resource-id:kidney360;2/10/1546American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, hypokalemia, lupus nephritis, renal tubular acidosis, systemic lupus erythematosusEditorialsEditorialseditorial20212021-10-2810.34067/KID.00053020212641-76502021-10-28T08:50:34-07:002021-10-28Kidney360Editorials21015461548
- POCUS for Nephrologists: Basic Principles and a General ApproachPoint-of-care ultrasonography (POCUS) has evolved as a valuable adjunct to physical examination in the recent past and various medical specialties have embraced it. However, POCUS training and scope of practice remain relatively undefined in nephrology. The utility of diagnostic POCUS beyond kidney and vascular access is under-recognized. Assessment of fluid status is a frequent dilemma faced by nephrologists in day-to-day practice where multiorgan POCUS can enhance the sensitivity of conventional physical examination. POCUS also reduces fragmentation of care, facilitates timely diagnosis, and expedites management. Although the need for further imaging studies is obviated in selected patients, POCUS is not meant to serve as an alternative to consultative imaging. In addition, the utility of POCUS depends on the skills and experience of the operator, which in turn depend on the quality of training. In this review, we discuss the rationale behind nephrologists performing POCUS, discuss patient examples to illustrate the basic principles of focused ultrasonography, and share our experience-based opinion about developing a POCUS training program at the institutional level.10.34067/KID.0002482021Thu, 05 Aug 2021 09:25:28 GMT-07:00POCUS for Nephrologists: Basic Principles and a General ApproachPoint-of-care ultrasonography (POCUS) has evolved as a valuable adjunct to physical examination in the recent past and various medical specialties have embraced it. However, POCUS training and scope of practice remain relatively undefined in nephrology. The utility of diagnostic POCUS beyond kidney and vascular access is under-recognized. Assessment of fluid status is a frequent dilemma faced by nephrologists in day-to-day practice where multiorgan POCUS can enhance the sensitivity of conventional physical examination. POCUS also reduces fragmentation of care, facilitates timely diagnosis, and expedites management. Although the need for further imaging studies is obviated in selected patients, POCUS is not meant to serve as an alternative to consultative imaging. In addition, the utility of POCUS depends on the skills and experience of the operator, which in turn depend on the quality of training. In this review, we discuss the rationale behind nephrologists performing POCUS, discuss patient examples to illustrate the basic principles of focused ultrasonography, and share our experience-based opinion about developing a POCUS training program at the institutional level.Koratala, AbhilashReisinger, Nathaniel2021-08-05T09:25:28-07:00doi:10.34067/KID.0002482021hwp:resource-id:kidney360;2/10/1660American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, educational personnel, nephrologists, nephrology, physical examination, POCUS, point of care ultrasound, sonography, trainingReview ArticleReview Articlereview-article20212021-10-2810.34067/KID.00024820212641-76502021-08-05T09:25:28-07:002021-10-28Kidney360Review Article21016601668
- A Randomized Intervention to Assess the Effectiveness of an Educational Video on Organ Donation Intent10.34067/KID.0001392021Wed, 28 Jul 2021 09:58:52 GMT-07:00A Randomized Intervention to Assess the Effectiveness of an Educational Video on Organ Donation IntentMolmenti, Ernesto P.Finuf, Kayla D.Patel, Vidhi H.Molmenti, Christine L.Thornton, DarylPekmezaris, Renee2021-07-28T09:58:52-07:00doi:10.34067/KID.0001392021hwp:resource-id:kidney360;2/10/1625American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, basic science, educational status, health disparities, organ donation, organ registry, organ transplantation, survey research, tissue and organ procurementOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-10-2810.34067/KID.00013920212641-76502021-07-28T09:58:52-07:002021-10-28Kidney360Original Investigation21016251632
- d-Serine Mediates Cellular Proliferation for Kidney Remodeling10.34067/KID.0000832021Mon, 16 Aug 2021 01:27:39 GMT-07:00d-Serine Mediates Cellular Proliferation for Kidney RemodelingHesaka, AtsushiTsukamoto, YusukeNada, ShigeyukiKawamura, MasatakaIchimaru, NaotsuguSakai, ShinsukeNakane, MaikoMita, MasashiOkuzaki, DaisukeOkada, MasatoIsaka, YoshitakaKimura, Tomonori2021-08-16T13:27:39-07:00doi:10.34067/KID.0000832021hwp:resource-id:kidney360;2/10/1611American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360renal-physiology, basic science, biomarker, cell cycle, chronic kidney disease, d-serine, glomerular filtration rate, kidney remodeling, kidney transplantation, mTOR, physiological activity, urinary excretionOriginal InvestigationRenal PhysiologyOriginal InvestigationRenal Physiologyresearch-article20212021-10-2810.34067/KID.00008320212641-76502021-08-16T13:27:39-07:002021-10-28Kidney360Original Investigation21016111624
- Moving Hearts and Minds: Video Intervention To Improve Organ Donor Registration Intent10.34067/KID.0002732021Thu, 28 Oct 2021 08:50:34 GMT-07:00Moving Hearts and Minds: Video Intervention To Improve Organ Donor Registration IntentOng, SongWille, Keith2021-10-28T08:50:34-07:00doi:10.34067/KID.0002732021hwp:resource-id:kidney360;2/10/1551American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, communications media, education, intention, minorities, organ donorsEditorialsEditorialseditorial20212021-10-2810.34067/KID.00027320212641-76502021-10-28T08:50:34-07:002021-10-28Kidney360Editorials21015511552
- A Blueprint for an Integrated Point-of-Care Ultrasound Curriculum for Nephrology TraineesPoint-of-care ultrasonography (POCUS) is a limited ultrasound study performed by the clinician at the bedside as a component or an adjunct to physical examination. POCUS has multiple applications in nephrology practice, including evaluation of obstructive uropathy, objective assessment of volume status, arteriovenous access assessment, and procedural guidance. However, unlike specialties such as emergency medicine, POCUS training is not yet integrated into most nephrology fellowship curricula, and the sonographic applications taught vary widely among fellowship programs. In this article, we have used our institutional experience to provide a roadmap or blueprint for nephrology programs looking to create a POCUS program. We provide an overview of the curriculum, including the basic organization, applications taught, online resources, milestone development, and quality assessment. We also discuss the nuances of POCUS workflow and perspectives on billing for these limited studies. In addition, we share the evaluation forms and sample documentation we use in our program. Future support, in the form of endorsed nephrology society guidelines, is needed before POCUS training is universally incorporated across nephrology fellowship programs.10.34067/KID.0005082021Fri, 13 Aug 2021 12:53:58 GMT-07:00A Blueprint for an Integrated Point-of-Care Ultrasound Curriculum for Nephrology TraineesPoint-of-care ultrasonography (POCUS) is a limited ultrasound study performed by the clinician at the bedside as a component or an adjunct to physical examination. POCUS has multiple applications in nephrology practice, including evaluation of obstructive uropathy, objective assessment of volume status, arteriovenous access assessment, and procedural guidance. However, unlike specialties such as emergency medicine, POCUS training is not yet integrated into most nephrology fellowship curricula, and the sonographic applications taught vary widely among fellowship programs. In this article, we have used our institutional experience to provide a roadmap or blueprint for nephrology programs looking to create a POCUS program. We provide an overview of the curriculum, including the basic organization, applications taught, online resources, milestone development, and quality assessment. We also discuss the nuances of POCUS workflow and perspectives on billing for these limited studies. In addition, we share the evaluation forms and sample documentation we use in our program. Future support, in the form of endorsed nephrology society guidelines, is needed before POCUS training is universally incorporated across nephrology fellowship programs.Koratala, AbhilashOlaoye, Olanrewaju A.Bhasin-Chhabra, BhavnaKazory, Amir2021-08-13T12:53:58-07:00doi:10.34067/KID.0005082021hwp:resource-id:kidney360;2/10/1669American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, billing, curriculum, nephrology, POCUS, point-of-care ultrasound, quality assessmentReview ArticleReview Articlereview-article20212021-10-2810.34067/KID.00050820212641-76502021-08-13T12:53:58-07:002021-10-28Kidney360Review Article21016691676
- Global Perspective on Kidney Transplantation: France10.34067/KID.0002402021Fri, 06 Aug 2021 11:35:17 GMT-07:00Global Perspective on Kidney Transplantation: FranceDivard, GillianGoutaudier, Valentin2021-08-06T11:35:17-07:00doi:10.34067/KID.0002402021hwp:resource-id:kidney360;2/10/1637American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, epidemiology, France, global, kidney transplantationGlobal PerspectivesGlobal Perspectivesresearch-article20212021-10-2810.34067/KID.00024020212641-76502021-08-06T11:35:17-07:002021-10-28Kidney360Global Perspectives21016371640
- Perceptions of Multidisciplinary Renal Team Members toward Home Dialysis Therapies10.34067/KID.0006222020Mon, 09 Aug 2021 01:20:57 GMT-07:00Perceptions of Multidisciplinary Renal Team Members toward Home Dialysis TherapiesPoinen, KrishnaVan Der Hoek, MaryCopland, Michael A.Tennankore, KarthikCanney, Mark2021-08-09T13:20:57-07:00doi:10.34067/KID.0006222020hwp:resource-id:kidney360;2/10/1592American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, education, home dialysis therapies, perception, peritoneal dialysisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-10-2810.34067/KID.00062220202641-76502021-08-09T13:20:57-07:002021-10-28Kidney360Original Investigation21015921599
- Global Perspective on Kidney Transplantation: Australia10.34067/KID.0003692021Thu, 05 Aug 2021 09:25:28 GMT-07:00Global Perspective on Kidney Transplantation: AustraliaWyld, Melanie L.R.Wyburn, Kate R.Chadban, Steve J.2021-08-05T09:25:28-07:00doi:10.34067/KID.0003692021hwp:resource-id:kidney360;2/10/1641American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, Australia, health servicesGlobal PerspectivesGlobal Perspectivesresearch-article20212021-10-2810.34067/KID.00036920212641-76502021-08-05T09:25:28-07:002021-10-28Kidney360Global Perspectives21016411644
- Multi-Target Drugs for Kidney DiseasesKidney diseases such as AKI, CKD, and GN can lead to dialysis and the need for kidney transplantation. The pathologies for kidney diseases are extremely complex, progress at different rates, and involve several cell types and cell signaling pathways. Complex kidney diseases require therapeutics that can act on multiple targets. In the past 10 years, in silico design of drugs has allowed for multi-target drugs to progress quickly from concept to reality. Several multi-target drugs have been made successfully to target AA pathways and transcription factors for the treatment of inflammatory, fibrotic, and metabolic diseases. Multi-target drugs have also demonstrated great potential to treat diabetic nephropathy and fibrotic kidney disease. These drugs act by decreasing renal TGF-β signaling, inflammation, mitochondrial dysfunction, and oxidative stress. There are several other recently developed multi-target drugs that have yet to be tested for their ability to combat kidney diseases. Overall, there is excellent potential for multi-target drugs that act on several cell types and signaling pathways to treat kidney diseases.10.34067/KID.0003582021Mon, 02 Aug 2021 01:50:51 GMT-07:00Multi-Target Drugs for Kidney DiseasesKidney diseases such as AKI, CKD, and GN can lead to dialysis and the need for kidney transplantation. The pathologies for kidney diseases are extremely complex, progress at different rates, and involve several cell types and cell signaling pathways. Complex kidney diseases require therapeutics that can act on multiple targets. In the past 10 years, in silico design of drugs has allowed for multi-target drugs to progress quickly from concept to reality. Several multi-target drugs have been made successfully to target AA pathways and transcription factors for the treatment of inflammatory, fibrotic, and metabolic diseases. Multi-target drugs have also demonstrated great potential to treat diabetic nephropathy and fibrotic kidney disease. These drugs act by decreasing renal TGF-β signaling, inflammation, mitochondrial dysfunction, and oxidative stress. There are several other recently developed multi-target drugs that have yet to be tested for their ability to combat kidney diseases. Overall, there is excellent potential for multi-target drugs that act on several cell types and signaling pathways to treat kidney diseases.Imig, John D.Merk, DanielProschak, Eugen2021-08-02T13:50:51-07:00doi:10.34067/KID.0003582021hwp:resource-id:kidney360;2/10/1645American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephro-pharmacology, basic science, chronic kidney disease, diabetes, drug delivery systems, eicosanoids, fatty acids, hypertension, kidney diseases, multi-ligand drugs, pharmaceutical preparations, transcription factorsBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-10-2810.34067/KID.00035820212641-76502021-08-02T13:50:51-07:002021-10-28Kidney360Basic Science for Clinicians21016451653
- Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)10.34067/KID.0002002021Fri, 27 Aug 2021 11:33:29 GMT-07:00Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)Block, Geoffrey A.Bleyer, Anthony J.Silva, Arnold L.Weiner, Daniel E.Lynn, Robert I.Yang, YangRosenbaum, David P.Chertow, Glenn M.Abdeen, OmaranAbdullah, RaiedAgha, IrfanAqeel, AhmedArfeen, ShahabulAssefi, AliAwad, AhmedBailey, AshaBaker, BruceBaranski, JoelBell, JeffreyBellovich, KeithBerenji, RaminBernardo, MarializaBetts, JudithBoiskin, MarkBrezina, BartonCharytan, ChaimConnaire, JeffreyCook, MDommu, AaronDua, SohanDukes, CarlEcheverri, DiegoElliott, MatthewEl-Shahawy, MohamedErinle, AyodeleFadda, GeorgeFadem, StephenFernandez, JuanForero, CarlosGeller, AriGouge, Carlos Gonzalez StevenGutierrez-Alsina, RodolfoHernandez, GermanHernandez, OscarHernandez, PedroHon, GeorgeIjaz, AdeelJacob, RaduJamal, AamirJohn, RekhaKalirao, ParamjitKamath, SureshKambhampati, GaneshKapoian, TorosKashif, MohammadKathresal, AmarnathKhalil, TaherKhawar, OsmanKleinman, KennethKooienga, LauraKovalchuk, OleksandrKronfli, SaeedLee, MarkLinfert, DouglasMaasarani, EssamMahankali, BhavaniManllo-Karim, RobertoMatalon, AlbertMehta, BhaskerMeyer, JillMiller, RichardMinasian, RaffiMizani, MohammadMordujovich, JorgeMoustafa, MoustafaNadella, RamaNarvarte, JavierNavarro, JesusNazeer, ImranNewman, GeorgeNeyra, NildaNiu, PaulNtoso, KwabenaO'Shaughnessy, AndrewPankhaniya, RohitPatak, RamachandraPolack, DonovanPosada, JorgeRaissi, SinaRajan, JamesRich, LisaRivers, DeniseRoppolo, MichaelRoss, DennisRubin, OlegSchlessinger, FabiolaSemerjian, AvedikShakeel, MuhammadSholer, ChrisSubramanian, VaragurSuchinda, PusadeeSun, Chao-HungSuri, AtulTietjen, DavidTruong, PhuongWooldridge, ThomasZabaneh, Raja2021-08-27T11:33:29-07:00doi:10.34067/KID.0002002021hwp:resource-id:kidney360;2/10/1600American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360mineral metabolism, dialysis, FGF23, hyperphosphatemia, NHE3, phosphate uptake, phosphate, tenapanorOriginal InvestigationMineral MetabolismOriginal InvestigationMineral Metabolismresearch-article20212021-10-2810.34067/KID.00020020212641-76502021-08-27T11:33:29-07:002021-10-28Kidney360Original Investigation21016001610
- Acute Kidney Injury in a Patient on High-dose Glucocorticoid Therapy10.34067/KID.0003072021Thu, 28 Oct 2021 08:50:34 GMT-07:00Acute Kidney Injury in a Patient on High-dose Glucocorticoid TherapyDiFranza, Lanny T.Santoriello, Dominick2021-10-28T08:50:34-07:00doi:10.34067/KID.0003072021hwp:resource-id:kidney360;2/10/1686American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, aki, aspergillosis, aspergillus, disseminated, glucocorticoids, invasiveClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-10-2810.34067/KID.00030720212641-76502021-10-28T08:50:34-07:002021-10-28Kidney360Clinical Images in Nephrology and Dialysis21016861687
- Hemoglobinuria in the Early Poststem-Cell–Transplant Period: Risk Factors and Association with Outcomes10.34067/KID.0002262021Wed, 25 Aug 2021 09:57:54 GMT-07:00Hemoglobinuria in the Early Poststem-Cell–Transplant Period: Risk Factors and Association with OutcomesKompotiatis, PanagiotisManohar, SandhyaAlkhateeb, Hassan B.Hogan, William J.Nath, Karl A.Leung, Nelson2021-08-25T09:57:54-07:00doi:10.34067/KID.0002262021hwp:resource-id:kidney360;2/10/1569American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, bone marrow transplant, fludarabine, hematopoietic stem cell transplantation, hemoglobinuria, lymphoma, peripheral blood stem cell, risk factors, stem cell transplantation, transplantOriginal InvestigationClinical NephrologyOriginal InvestigationClinical Nephrologyresearch-article20212021-10-2810.34067/KID.00022620212641-76502021-08-25T09:57:54-07:002021-10-28Kidney360Original Investigation21015691575
- Global Dialysis Perspective: Iceland10.34067/KID.0002332021Fri, 06 Aug 2021 11:35:17 GMT-07:00Global Dialysis Perspective: IcelandEmilsdottir, Arna R.Palsson, Ragnar2021-08-06T11:35:17-07:00doi:10.34067/KID.0002332021hwp:resource-id:kidney360;2/10/1632American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, delivery of health care, dialysis, Iceland, kidney failure, kidney transplantation, renal dialysisGlobal PerspectivesGlobal Perspectivesresearch-article20212021-10-2810.34067/KID.00023320212641-76502021-08-06T11:35:17-07:002021-10-28Kidney360Global Perspectives21016321637
- The Impact of Outpatient Laboratory Alerting Mechanisms in Patients with AKI10.34067/KID.0003312021Wed, 14 Jul 2021 12:17:39 GMT-07:00The Impact of Outpatient Laboratory Alerting Mechanisms in Patients with AKITolan, Nicole V.Ahmed, SalmanTerebo, TolumofeVirk, Zain M.Petrides, Athena K.Ransohoff, Jaime R.Demetriou, Christiana A.Kelly, Yvelynne P.Melanson, Stacy E.F.Mendu, Mallika L.2021-07-14T12:17:39-07:00doi:10.34067/KID.0003312021hwp:resource-id:kidney360;2/10/1560American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, creatinine, documentation, laboratory alerts, nephrotoxins, outcomes, outpatientsOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-10-2810.34067/KID.00033120212641-76502021-07-14T12:17:39-07:002021-10-28Kidney360Original Investigation21015601568
- Kidney Injury in a Patient with Hypocomplementemia and Diffuse Lymphadenopathy10.34067/KID.0003892021Thu, 28 Oct 2021 08:50:34 GMT-07:00Kidney Injury in a Patient with Hypocomplementemia and Diffuse LymphadenopathyRehan, Anam2021-10-28T08:50:34-07:00doi:10.34067/KID.0003892021hwp:resource-id:kidney360;2/10/1684American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, corticosteroids, hematologic diseases, hypocomplementemia, IgG4, immune system diseases, infrarenal aorta, kidney, lymphadenopathy, rituximab, storiform, tubulointerstitial nephritisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-10-2810.34067/KID.00038920212641-76502021-10-28T08:50:34-07:002021-10-28Kidney360Clinical Images in Nephrology and Dialysis21016841685
- Idiopathic Hypokalemia in Lupus Nephritis: A Newly Recognized Entity10.34067/KID.0004352021Fri, 06 Aug 2021 01:32:05 GMT-07:00Idiopathic Hypokalemia in Lupus Nephritis: A Newly Recognized EntityAdomako, Emmanuel A.Bilal, SairaLiu, Yu-lunMalik, AyeshaVan Buren, Peter N.Shastri, ShaniSambandam, Kamalanathan K.2021-08-06T13:32:05-07:00doi:10.34067/KID.0004352021hwp:resource-id:kidney360;2/10/1553American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, autoantibody, hypokalemia, lupus nephritis, renal tubular acidosisOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20212021-10-2810.34067/KID.00043520212641-76502021-08-06T13:32:05-07:002021-10-28Kidney360Original Investigation21015531559
- Monocytes and Macrophages in Kidney Transplantation and Insights from Single Cell RNA-Seq StudiesSingle-cell RNA sequencing (scRNA-seq) is a powerful technology that allows for the identification of minority cell types in complex tissues, such as immune cells in the kidney. Previously, gene expression from infrequent cell types was missed using bulk RNA-sequencing methods due to an averaging effect. Additionally, scRNA-seq facilitates assignment of cell origin in a sample, a shortcoming of previous bulk sequencing technologies. Thus, scRNA-seq is ideal to study the immune cell landscape and the alloimmune response in the human kidney transplant. However, there are few studies published to date. Macrophages are known to play an important role in health and disease in the kidney. Furthermore, it is known that macrophages play key roles in rejection of the kidney transplant. The definition, ontogeny, and function of these cells is complex and nomenclature has evolved as new technologies have become available. In this review, an overview is provided of monocyte and macrophage nomenclature, ontogeny, and function, with a specific focus on kidney transplantation, and including novel scRNA-seq findings. scRNA-seq offers an unbiased transcriptional approach to defining macrophages and provides insights into macrophage ontogeny and function not possible with contemporary methods.10.34067/KID.0003842021Tue, 17 Aug 2021 01:18:43 GMT-07:00Monocytes and Macrophages in Kidney Transplantation and Insights from Single Cell RNA-Seq StudiesSingle-cell RNA sequencing (scRNA-seq) is a powerful technology that allows for the identification of minority cell types in complex tissues, such as immune cells in the kidney. Previously, gene expression from infrequent cell types was missed using bulk RNA-sequencing methods due to an averaging effect. Additionally, scRNA-seq facilitates assignment of cell origin in a sample, a shortcoming of previous bulk sequencing technologies. Thus, scRNA-seq is ideal to study the immune cell landscape and the alloimmune response in the human kidney transplant. However, there are few studies published to date. Macrophages are known to play an important role in health and disease in the kidney. Furthermore, it is known that macrophages play key roles in rejection of the kidney transplant. The definition, ontogeny, and function of these cells is complex and nomenclature has evolved as new technologies have become available. In this review, an overview is provided of monocyte and macrophage nomenclature, ontogeny, and function, with a specific focus on kidney transplantation, and including novel scRNA-seq findings. scRNA-seq offers an unbiased transcriptional approach to defining macrophages and provides insights into macrophage ontogeny and function not possible with contemporary methods.Malone, Andrew F.2021-08-17T13:18:43-07:00doi:10.34067/KID.0003842021hwp:resource-id:kidney360;2/10/1654American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, allografts, basic science, biopsy, kidney transplant, macrophage, monocytes, scRNA-seq, transcriptome, transplantationBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-10-2810.34067/KID.00038420212641-76502021-08-17T13:18:43-07:002021-10-28Kidney360Basic Science for Clinicians21016541659
- Identifying Acute Kidney Injury in the Outpatient Setting: The First Step10.34067/KID.0005742021Thu, 28 Oct 2021 08:50:34 GMT-07:00Identifying Acute Kidney Injury in the Outpatient Setting: The First StepGoldstein, Stuart L.2021-10-28T08:50:34-07:00doi:10.34067/KID.0005742021hwp:resource-id:kidney360;2/10/1549American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, outpatientsEditorialsEditorialseditorial20212021-10-2810.34067/KID.00057420212641-76502021-10-28T08:50:34-07:002021-10-28Kidney360Editorials21015491550
- Pkd1 Mutation Has No Apparent Effects on Peroxisome Structure or Lipid Metabolism10.34067/KID.0000962021Fri, 16 Jul 2021 01:27:01 GMT-07:00Pkd1 Mutation Has No Apparent Effects on Peroxisome Structure or Lipid MetabolismTerabayashi, TakeshiMenezes, Luis F.Zhou, FangCai, HongyiWalter, Peter J.Garraffo, Hugo M.Germino, Gregory G.2021-07-16T13:27:01-07:00doi:10.34067/KID.0000962021hwp:resource-id:kidney360;2/10/1576American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, basic science, cystic kidney disease, fatty acids, genetic diseases, metabolism, peroxisomesOriginal InvestigationCystic Kidney DiseaseOriginal InvestigationCystic Kidney Diseaseresearch-article20212021-10-2810.34067/KID.00009620212641-76502021-07-16T13:27:01-07:002021-10-28Kidney360Original Investigation21015761591
- Value-Based Care in Nephrology: The Kidney Care Choices Model and Other ReformsThe Advancing American Kidney Health (AAKH) initiative has reinvigorated the focus on improving the care of patients with advanced CKD. Multiple interventions have been planned, focusing on education campaigns for both clinicians and patients, delaying the progression of kidney disease and improving utilization of home dialysis modalities and kidney transplantation. Value-based care models for patients with advanced kidney disease are being rolled out, with the ESKD treatment choices model starting in January 2021, and the Kidney Care Choices model planned to start in January 2022. There is increasing emphasis on the role of the nephrologist as the “captain of the ship,” leading efforts in care coordination as physician leaders. The transplant reforms have focused on changes to organ procurement organizations aiming to increase availability of organs, and transplants performed, both deceased and living donor, and removing financial disincentives from live organ donation. The American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) are partnering with the Department of Health and Human Services to develop educational material for clinicians and patients. In this review, we discuss these reforms, potential challenges that have arisen, and potential solutions, with emphasis on the Kidney Care Choices model.10.34067/KID.0004552021Mon, 16 Aug 2021 10:48:11 GMT-07:00Value-Based Care in Nephrology: The Kidney Care Choices Model and Other ReformsThe Advancing American Kidney Health (AAKH) initiative has reinvigorated the focus on improving the care of patients with advanced CKD. Multiple interventions have been planned, focusing on education campaigns for both clinicians and patients, delaying the progression of kidney disease and improving utilization of home dialysis modalities and kidney transplantation. Value-based care models for patients with advanced kidney disease are being rolled out, with the ESKD treatment choices model starting in January 2021, and the Kidney Care Choices model planned to start in January 2022. There is increasing emphasis on the role of the nephrologist as the “captain of the ship,” leading efforts in care coordination as physician leaders. The transplant reforms have focused on changes to organ procurement organizations aiming to increase availability of organs, and transplants performed, both deceased and living donor, and removing financial disincentives from live organ donation. The American Society of Nephrology (ASN) and the National Kidney Foundation (NKF) are partnering with the Department of Health and Human Services to develop educational material for clinicians and patients. In this review, we discuss these reforms, potential challenges that have arisen, and potential solutions, with emphasis on the Kidney Care Choices model.Jain, GauravWeiner, Daniel E.2021-08-16T10:48:11-07:00doi:10.34067/KID.0004552021hwp:resource-id:kidney360;2/10/1677American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, chronic kidney disease, dialysis, ETC, KCC, kidney care choices, patient activation measure, value-based careReview ArticleReview Articlereview-article20212021-10-2810.34067/KID.00045520212641-76502021-08-16T10:48:11-07:002021-10-28Kidney360Review Article21016771683
- Soluble Klotho and Incident Hypertension10.2215/CJN.05020421Thu, 23 Sep 2021 06:53:28 GMT-07:00Soluble Klotho and Incident HypertensionDrew, David A.Katz, RonitKritchevsky, StephenIx, Joachim H.Shlipak, Michael G.Newman, Anne B.Hoofnagle, Andrew N.Fried, Linda F.Sarnak, MarkGutiérrez, Orlando M.Semba, Richard D.Neyra, Javier A.2021-09-23T06:53:28-07:00doi:10.2215/CJN.05020421hwp:resource-id:clinjasn;16/10/1502American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyklotho, hypertension, blood pressure, systolic blood pressureOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20212021-10-01October 202110.2215/CJN.050204211555-90411555-905X2021-09-23T06:53:28-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles161015021511
- Race and Evaluation for a Kidney Transplant10.2215/CJN.11010821Thu, 07 Oct 2021 12:05:16 GMT-07:00Race and Evaluation for a Kidney TransplantAdams, Artemeshia2021-10-07T12:05:16-07:00doi:10.2215/CJN.11010821hwp:resource-id:clinjasn;16/10/1457American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrace and transplant, kidney transplantation, race, disparityPatient VoicePatient Voiceresearch-article20212021-10-01October 202110.2215/CJN.110108211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyPatient Voice16101010145715521464145815591466
- Organizational Characteristics Associated with High Performance in Medicare’s Comprehensive End-Stage Renal Disease Care Initiative10.2215/CJN.04020321Thu, 07 Oct 2021 12:05:16 GMT-07:00Organizational Characteristics Associated with High Performance in Medicare’s Comprehensive End-Stage Renal Disease Care InitiativeDrewry, Kelsey M.Trivedi, Amal N.Wilk, Adam S.2021-10-07T12:05:16-07:00doi:10.2215/CJN.04020321hwp:resource-id:clinjasn;16/10/1522American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, clinical nephrology, dialysis, disparity, end stage kidney disease, end-stage renal disease, ESRD, hemodialysis, nephrology, comprehensive health careOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-10-01October 202110.2215/CJN.040203211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles1610101522146715301469
- Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease10.2215/CJN.01930221Mon, 30 Aug 2021 10:34:54 GMT-07:00Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney DiseaseEdwards, Nicola C.Price, Anna M.Mehta, SamirHiemstra, Thomas F.Kaur, AmreenGreasley, Peter J.Webb, David J.Dhaun, NeerajMacIntyre, Iain M.Farrah, TariqMelville, VanessaHerrey, Anna S.Slinn, GemmaWale, RebekahIves, NatalieWheeler, David C.Wilkinson, IanSteeds, Richard P.Ferro, Charles J.Townend, Jonathan N.2021-08-30T10:34:54-07:00doi:10.2215/CJN.01930221hwp:resource-id:clinjasn;16/10/1491American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, aldosterone, randomized controlled trials, chlorthalidone, spironolactone, cardiovascular systemOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-10-01October 202110.2215/CJN.019302211555-90411555-905X2021-08-30T10:34:54-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles161014911501
- Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft StatusImmune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.10.2215/CJN.14010820Tue, 27 Apr 2021 08:22:12 GMT-07:00Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft StatusImmune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.Lubetzky, Michelle L.Salinas, ThaliaSchwartz, Joseph E.Suthanthiran, Manikkam2021-04-27T08:22:12-07:00doi:10.2215/CJN.14010820hwp:resource-id:clinjasn;16/10/1565American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyurinary cell mRNA, kidney transplantation, acute allograft rejection, gene expression, kidney biopsy, mRNA, allografts, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-10-01October 202110.2215/CJN.140108201555-90411555-905X2021-04-27T08:22:12-07:002021-10Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges161015651577
- Transforming the Care of Patients with Diabetic Kidney DiseaseDiabetes and its associated complications pose an immediate threat to humankind. Diabetic kidney disease is one of the most devastating complications, increasing the risk of death more than ten-fold over the general population. Until very recently, the only drugs proven and recommended to slow the progression of diabetic kidney disease were angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, which act by inhibiting the renin-angiotensin system. Despite their efficacy as kidney and cardiovascular protective therapies and as antihypertensive agents, renin-angiotensin system inhibitors have been grossly underutilized. Moreover, even when renin-angiotensin system inhibitors are used, patients still have a high residual risk of diabetic kidney disease progression. Finally, the kidney-protective effect of renin-angiotensin system inhibitors has been categorically demonstrated only in patients with macroalbuminuria included in the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trials, not in other individuals. The lack of new therapies to treat diabetic kidney disease over the past 2 decades has therefore represented a tremendous challenge for patients and health care providers alike. In recent years, a number of powerful new therapies have emerged that promise to transform care of patients with diabetes and kidney disease. The challenge to the community is to ensure rapid implementation of these treatments. This white paper highlights advances in treatment, opportunities for patients, challenges, and possible solutions to advance kidney health, and introduces the launch of the Diabetic Kidney Disease Collaborative at the American Society of Nephrology, to aid in accomplishing these goals.10.2215/CJN.18641120Tue, 08 Jun 2021 06:52:50 GMT-07:00Transforming the Care of Patients with Diabetic Kidney DiseaseDiabetes and its associated complications pose an immediate threat to humankind. Diabetic kidney disease is one of the most devastating complications, increasing the risk of death more than ten-fold over the general population. Until very recently, the only drugs proven and recommended to slow the progression of diabetic kidney disease were angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers, which act by inhibiting the renin-angiotensin system. Despite their efficacy as kidney and cardiovascular protective therapies and as antihypertensive agents, renin-angiotensin system inhibitors have been grossly underutilized. Moreover, even when renin-angiotensin system inhibitors are used, patients still have a high residual risk of diabetic kidney disease progression. Finally, the kidney-protective effect of renin-angiotensin system inhibitors has been categorically demonstrated only in patients with macroalbuminuria included in the Irbesartan Diabetic Nephropathy Trial (IDNT) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trials, not in other individuals. The lack of new therapies to treat diabetic kidney disease over the past 2 decades has therefore represented a tremendous challenge for patients and health care providers alike. In recent years, a number of powerful new therapies have emerged that promise to transform care of patients with diabetes and kidney disease. The challenge to the community is to ensure rapid implementation of these treatments. This white paper highlights advances in treatment, opportunities for patients, challenges, and possible solutions to advance kidney health, and introduces the launch of the Diabetic Kidney Disease Collaborative at the American Society of Nephrology, to aid in accomplishing these goals.Brosius, Frank C.Cherney, DavidGee, Patrick O.Harris, Raymond C.Kliger, Alan S.Tuttle, Katherine R.Quaggin, Susan E.2021-06-08T06:52:50-07:00doi:10.2215/CJN.18641120hwp:resource-id:clinjasn;16/10/1590American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, kidney disease, SGLT2 inhibitor, disparity, equityReviewsReviewsreview-article20212021-10-01October 202110.2215/CJN.186411201555-90411555-905X2021-06-08T06:52:50-07:002021-10Clinical Journal of the American Society of NephrologyReviews161015901600
- Being an ADVOCATE for People with ANCA Vasculitis10.2215/CJN.03670321Thu, 03 Jun 2021 10:41:09 GMT-07:00Being an ADVOCATE for People with ANCA VasculitisAnders, Hans-JoachimNakazawa, Daigo2021-06-03T10:41:09-07:00doi:10.2215/CJN.03670321hwp:resource-id:clinjasn;16/10/1581American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvasculitis, glomerulonephritis, ANCA, complementPerspectivesPerspectivesresearch-article20212021-10-01October 202110.2215/CJN.036703211555-90411555-905X2021-06-03T10:41:09-07:002021-10Clinical Journal of the American Society of NephrologyPerspectives161015811583
- Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients10.2215/CJN.05530421Thu, 07 Oct 2021 12:05:16 GMT-07:00Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant RecipientsPark, SookhyeonGuo, KexinHeilman, Raymond L.Poggio, Emilio D.Taber, David J.Marsh, Christopher L.Kurian, Sunil M.Kleiboeker, SteveWeems, JustonHolman, JohnZhao, LihuiSinha, RohitaBrietigam, SusanRebello, ChristabelAbecassis, Michael M.Friedewald, John J.2021-10-07T12:05:16-07:00doi:10.2215/CJN.05530421hwp:resource-id:clinjasn;16/10/1539American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, gene expression, rejection, diagnostic tests, routine, graft rejection, cellfree nucleic acidOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-10-01October 202110.2215/CJN.055304211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles1610101539146215511463
- The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation10.2215/CJN.05920421Wed, 18 Aug 2021 09:06:52 GMT-07:00The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial FibrillationHarel, ZivMcArthur, EricJeyakumar, NivethikaSood, Manish M.Garg, Amit X.Silver, Samuel A.Dorian, PaulBlum, DanielBeaubien-Souligny, WilliamYan, Andrew T.Badve, Sunil V.Smyth, BrendanJun, MinJandoc, RacquelKitchlu, AbhijatWald, Ron2021-08-18T09:06:52-07:00doi:10.2215/CJN.05920421hwp:resource-id:clinjasn;16/10/1470American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, atrial fibrillation, anticoagulantsOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-10-01October 202110.2215/CJN.059204211555-90411555-905X2021-08-18T09:06:52-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles161014701479
- Race-Based eGFR Assessment for Kidney Transplantation10.2215/CJN.11020821Thu, 07 Oct 2021 12:05:16 GMT-07:00Race-Based eGFR Assessment for Kidney TransplantationHoenig, Melanie P.Pavlakis, Martha2021-10-07T12:05:16-07:00doi:10.2215/CJN.11020821hwp:resource-id:clinjasn;16/10/1464American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, transplantation, GFREditorialsEditorialseditorial20212021-10-01October 202110.2215/CJN.110208211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyEditorials16101010146415521457146615591458
- Value-Based Kidney Care10.2215/CJN.11250821Thu, 07 Oct 2021 12:05:16 GMT-07:00Value-Based Kidney CareTummalapalli, Sri LekhaMohan, Sumit2021-10-07T12:05:16-07:00doi:10.2215/CJN.11250821hwp:resource-id:clinjasn;16/10/1467American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvalue-based care, ESCOs, alternative payment models, kidney care choices, health policy, ESRD Seamless Care Organizations, comprehensive ESRD care modelEditorialsEditorialseditorial20212021-10-01October 202110.2215/CJN.112508211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyEditorials1610101467152214691530
- Two Can Be Better Than One10.2215/CJN.10630821Thu, 07 Oct 2021 12:05:16 GMT-07:00Two Can Be Better Than OneKhilnani, CallaHeeger, Peter S.2021-10-07T12:05:16-07:00doi:10.2215/CJN.10630821hwp:resource-id:clinjasn;16/10/1462American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantationEditorialsEditorialseditorial20212021-10-01October 202110.2215/CJN.106308211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyEditorials1610101462153914631551
- Prevention of Acute Kidney Injury after Cardiac Surgery10.2215/CJN.11000821Thu, 07 Oct 2021 12:05:16 GMT-07:00Prevention of Acute Kidney Injury after Cardiac SurgeryBasu, Rajit K.Gist, Katja M.2021-10-07T12:05:16-07:00doi:10.2215/CJN.11000821hwp:resource-id:clinjasn;16/10/1459American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, cardiovascular disease, pediatric intensive care medicineEditorialsEditorialseditorial20212021-10-01October 202110.2215/CJN.110008211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyEditorials1610101459148014611490
- Arterial Stiffness Is Independently Associated with Acute Kidney Injury in SPRINT10.2215/CJN.06420521Fri, 27 Aug 2021 09:06:27 GMT-07:00Arterial Stiffness Is Independently Associated with Acute Kidney Injury in SPRINTPengshung, Michelle H.Bispham, Nina Z.You, ZhiyingOh, EsterSupiano, Mark A.Chonchol, Michel B.Nowak, Kristen L.Jovanovich, Anna J.2021-08-27T09:06:27-07:00doi:10.2215/CJN.06420521hwp:resource-id:clinjasn;16/10/1560American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, pulse wave velocity, risk factors, vascular stiffnessResearch LettersResearch Lettersletter20212021-10-01October 202110.2215/CJN.064205211555-90411555-905X2021-08-27T09:06:27-07:002021-10Clinical Journal of the American Society of NephrologyResearch Letters161015601561
- Advancing American Kidney Health and the Role of Sodium-Glucose Cotransporter-2 Inhibitors10.2215/CJN.05450421Wed, 16 Jun 2021 10:53:39 GMT-07:00Advancing American Kidney Health and the Role of Sodium-Glucose Cotransporter-2 InhibitorsLi, JiahuaTummalapalli, Sri LekhaMendu, Mallika L.2021-06-16T10:53:39-07:00doi:10.2215/CJN.05450421hwp:resource-id:clinjasn;16/10/1584American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, United States, sodium-glucose transporter 2 inhibitors, diabetes mellitus, type 2, sodium-glucose transporter 2, proteinuria, SGLT2iPerspectivesPerspectivesresearch-article20212021-10-01October 202110.2215/CJN.054504211555-90411555-905X2021-06-16T10:53:39-07:002021-10Clinical Journal of the American Society of NephrologyPerspectives161015841586
- Recovery after Critical Illness and Acute Kidney InjuryAKI is a common complication in hospitalized and critically ill patients. Its incidence has steadily increased over the past decade. Whether transient or prolonged, AKI is an independent risk factor associated with poor short- and long-term outcomes, even if patients do not require KRT. Most patients with early AKI improve with conservative management; however, some will require dialysis for a few days, a few weeks, or even months. Approximately 10%–30% of AKI survivors may still need dialysis after hospital discharge. These patients have a higher associated risk of death, rehospitalization, recurrent AKI, and CKD, and a lower quality of life. Survivors of critical illness may also suffer from cognitive dysfunction, muscle weakness, prolonged ventilator dependence, malnutrition, infections, chronic pain, and poor wound healing. Collaboration and communication among nephrologists, primary care physicians, rehabilitation providers, physical therapists, nutritionists, nurses, pharmacists, and other members of the health care team are essential to create a holistic and patient-centric care plan for overall recovery. Integration of the patient and family members in health care decisions, and ongoing education throughout the process, are vital to improve patient well-being. From the nephrologist standpoint, assessing and promoting recovery of kidney function, and providing appropriate short- and long-term follow-up, are crucial to prevent rehospitalizations and to reduce complications. Return to baseline functional status is the ultimate goal for most patients, and dialysis independence is an important part of that goal. In this review, we seek to highlight the varying aspects and stages of recovery from AKI complicating critical illness, and propose viable strategies to promote recovery of kidney function and dialysis independence. We also emphasize the need for ongoing research and multidisciplinary collaboration to improve outcomes in this vulnerable population.10.2215/CJN.19601220Mon, 30 Aug 2021 08:28:42 GMT-07:00Recovery after Critical Illness and Acute Kidney InjuryAKI is a common complication in hospitalized and critically ill patients. Its incidence has steadily increased over the past decade. Whether transient or prolonged, AKI is an independent risk factor associated with poor short- and long-term outcomes, even if patients do not require KRT. Most patients with early AKI improve with conservative management; however, some will require dialysis for a few days, a few weeks, or even months. Approximately 10%–30% of AKI survivors may still need dialysis after hospital discharge. These patients have a higher associated risk of death, rehospitalization, recurrent AKI, and CKD, and a lower quality of life. Survivors of critical illness may also suffer from cognitive dysfunction, muscle weakness, prolonged ventilator dependence, malnutrition, infections, chronic pain, and poor wound healing. Collaboration and communication among nephrologists, primary care physicians, rehabilitation providers, physical therapists, nutritionists, nurses, pharmacists, and other members of the health care team are essential to create a holistic and patient-centric care plan for overall recovery. Integration of the patient and family members in health care decisions, and ongoing education throughout the process, are vital to improve patient well-being. From the nephrologist standpoint, assessing and promoting recovery of kidney function, and providing appropriate short- and long-term follow-up, are crucial to prevent rehospitalizations and to reduce complications. Return to baseline functional status is the ultimate goal for most patients, and dialysis independence is an important part of that goal. In this review, we seek to highlight the varying aspects and stages of recovery from AKI complicating critical illness, and propose viable strategies to promote recovery of kidney function and dialysis independence. We also emphasize the need for ongoing research and multidisciplinary collaboration to improve outcomes in this vulnerable population.Vijayan, AnithaAbdel-Rahman, Emaad M.Liu, Kathleen D.Goldstein, Stuart L.Agarwal, AnupamOkusa, Mark D.Cerda, Jorge2021-08-30T08:28:42-07:00doi:10.2215/CJN.19601220hwp:resource-id:clinjasn;16/10/1601American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical illness, acute kidney injuryReviewsReviewsreview-article20212021-10-01October 202110.2215/CJN.196012201555-90411555-905X2021-08-30T08:28:42-07:002021-10Clinical Journal of the American Society of NephrologyReviews161016011609
- Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis10.2215/CJN.01430121Wed, 07 Jul 2021 11:09:02 GMT-07:00Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal DialysisGanesan, Lakshmi L.O’Brien, Frank J.Sirich, Tammy L.Plummer, Natalie S.Sheth, RitaFajardo, CecileBrakeman, PaulSutherland, Scott M.Meyer, Timothy W.2021-07-07T11:09:02-07:00doi:10.2215/CJN.01430121hwp:resource-id:clinjasn;16/10/1531American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatrics, peritoneal dialysis, plasma, solutions, uremiaOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-10-01October 202110.2215/CJN.014301211555-90411555-905X2021-07-07T11:09:02-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles161015311538
- Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery10.2215/CJN.05800421Thu, 07 Oct 2021 12:05:16 GMT-07:00Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac SurgeryVan den Eynde, JefCloet, NicolasVan Lerberghe, RobinSá, Michel Pompeu B.O.Vlasselaers, DirkToelen, JaanVerbakel, Jan Y.Budts, WernerGewillig, MarcKutty, ShelbyPottel, HansMekahli, Djalila2021-10-07T12:05:16-07:00doi:10.2215/CJN.05800421hwp:resource-id:clinjasn;16/10/1480American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, acute renal failure, children, network meta-analysis, cardiac surgical procedures, specialties, surgical, heart, congenital heart diseaseOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-10-01October 202110.2215/CJN.058004211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles1610101480145914901461
- Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis10.2215/CJN.03850321Wed, 01 Sep 2021 08:24:50 GMT-07:00Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term HemodialysisBielesz, BernhardLorenz, MatthiasMonteforte, RossellaPrikoszovich, ThomasGabriel, MichaelaWolzt, MichaelGleiss, AndreasHörl, Walter H.Sunder-Plassmann, Gere2021-09-01T08:24:50-07:00doi:10.2215/CJN.03850321hwp:resource-id:clinjasn;16/10/1512American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, hemodialysis, end stage kidney disease, clinical trial, dialysis, iron, ferritinsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-10-01October 202110.2215/CJN.038503211555-90411555-905X2021-09-01T08:24:50-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles161015121521
- Transplant Clinician Opinions on Use of Race in the Estimation of Glomerular Filtration Rate10.2215/CJN.05490421Thu, 07 Oct 2021 12:05:16 GMT-07:00Transplant Clinician Opinions on Use of Race in the Estimation of Glomerular Filtration RateDoshi, Mona D.Singh, NeerajHippen, Benjamin E.Woodside, Kenneth J.Mohan, PrinceByford, Hannah L.Cooper, MatthewDadhania, Darshana M.Ainapurapu, SruthiLentine, Krista L.2021-10-07T12:05:16-07:00doi:10.2215/CJN.05490421hwp:resource-id:clinjasn;16/10/1552American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyequity, glomerular filtration rate, ethnicity, transplantation, ambulatory care facilitiesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-10-01October 202110.2215/CJN.054904211555-90411555-905X2021-10-07T12:05:16-07:002021-10Clinical Journal of the American Society of NephrologyOriginal Articles16101010155214571464155914581466
- Barriers and Solutions to Kidney Transplantation for the Undocumented Latinx Community with Kidney Failure10.2215/CJN.03900321Thu, 23 Sep 2021 06:53:28 GMT-07:00Barriers and Solutions to Kidney Transplantation for the Undocumented Latinx Community with Kidney FailureRizzolo, KatherineCervantes, Lilia2021-09-23T06:53:28-07:00doi:10.2215/CJN.03900321hwp:resource-id:clinjasn;16/10/1587American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, equity, chronic kidney disease, transplantationPerspectivesPerspectivesresearch-article20212021-10-01October 202110.2215/CJN.039003211555-90411555-905X2021-09-23T06:53:28-07:002021-10Clinical Journal of the American Society of NephrologyPerspectives161015871589
- Black Race Coefficient in GFR Estimation and Prevalence of CKD-Related Complications10.2215/CJN.04430321Mon, 14 Jun 2021 11:46:48 GMT-07:00Black Race Coefficient in GFR Estimation and Prevalence of CKD-Related ComplicationsWalther, Carl P.Winkelmayer, Wolfgang C.Navaneethan, Sankar D.2021-06-14T11:46:48-07:00doi:10.2215/CJN.04430321hwp:resource-id:clinjasn;16/10/1562American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrace, eGFR, chronic kidney disease, prevalence, glomerular filtration rate, African Americans, creatinine, disparityResearch LettersResearch Lettersletter20212021-10-01October 202110.2215/CJN.044303211555-90411555-905X2021-06-14T11:46:48-07:002021-10Clinical Journal of the American Society of NephrologyResearch Letters161015621564
- GLP-1 Receptor Agonists in Diabetic Kidney Disease10.2215/CJN.18771220Tue, 13 Apr 2021 08:05:32 GMT-07:00GLP-1 Receptor Agonists in Diabetic Kidney DiseaseMichos, Erin D.Tuttle, Katherine R.2021-04-13T08:05:32-07:00doi:10.2215/CJN.18771220hwp:resource-id:clinjasn;16/10/1578American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, chronic diabetic complications, chronic kidney disease, glucagon-like peptide-1 receptorKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20212021-10-01October 202110.2215/CJN.187712201555-90411555-905X2021-04-13T08:05:32-07:002021-10Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat161015781580
- Considerations in the Study of Body Mass Index Variability10.1681/ASN.2021060844Fri, 01 Oct 2021 10:51:44 GMT-07:00Considerations in the Study of Body Mass Index VariabilityGregg, L. ParkerNavaneethan, Sankar D.2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021060844hwp:resource-id:jnephrol;32/10/2395American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyBMI, CKD, mortalityUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-10-01October 202110.1681/ASN.20210608441046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyUp Front Matters3210102395259523972612
- Urine APOL1 Isoforms Reflect Plasma-Derived Liver-Synthesized Proteins10.1681/ASN.2021030411Wed, 23 Jun 2021 11:32:46 GMT-07:00Urine APOL1 Isoforms Reflect Plasma-Derived Liver-Synthesized ProteinsAlthage, MagnusHeinrich, Timothy M.Miliotis, TassoBogstedt, AnnaMa, LijunGautreaux, Michael D.Hicks, Pamela J.Palmer, Nicholette D.MacPhee, IainHartleib-Geschwindner, JudithGreasley, Peter J.Freedman, Barry I.2021-06-23T11:32:46-07:00doi:10.1681/ASN.2021030411hwp:resource-id:jnephrol;32/10/2442American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, end-stage renal disease, focal segmental glomerulosclerosis, human genetics, hypertension, kidney, kidney transplantation, kidney disease, ethnic minority, APOL1Research LettersResearch Lettersresearch-article20212021-10-01October 202110.1681/ASN.20210304111046-66731533-34502021-06-23T11:32:46-07:002021-10Journal of the American Society of NephrologyResearch Letters321024422444
- This Month's Highlights10.1681/ASN.2021081049Fri, 01 Oct 2021 10:51:44 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021081049hwp:resource-id:jnephrol;32/10/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsresearch-article20212021-10-01October 202110.1681/ASN.20210810491046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyThis Month's Highlights32101010101010i25012517242526132419i25162528243426212421
- Toward Antiracist Reimbursement Policy in End-Stage Kidney Disease: From Equality to Equity10.1681/ASN.2021020189Mon, 12 Jul 2021 10:21:52 GMT-07:00Toward Antiracist Reimbursement Policy in End-Stage Kidney Disease: From Equality to EquityTaylor, KathrynCrews, Deidra C.2021-07-12T10:21:52-07:00doi:10.1681/ASN.2021020189hwp:resource-id:jnephrol;32/10/2422American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, epidemiology and outcomes, racial and ethnic disparitiesUp Front MattersAddressing Racial and Ethnic Disparities in Kidney DiseaseUp Front MattersAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20212021-10-01October 202110.1681/ASN.20210201891046-66731533-34502021-07-12T10:21:52-07:002021-10Journal of the American Society of NephrologyUp Front Matters321024222424
- Long-Term Outcomes of Children Undergoing Dialysis-treated AKI: Some Opinions and Prospects10.1681/ASN.2021060862Thu, 16 Sep 2021 01:36:25 GMT-07:00Long-Term Outcomes of Children Undergoing Dialysis-treated AKI: Some Opinions and ProspectsWei, Shiyuan2021-09-16T13:36:25-07:00doi:10.1681/ASN.2021060862hwp:resource-id:jnephrol;32/10/2679American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychildren, acute renal failure, dialysis, acute kidney injuryLetters to the EditorLetters to the Editorletter20212021-10-01October 202110.1681/ASN.20210608621046-66731533-34502021-09-16T13:36:25-07:002021-10Journal of the American Society of NephrologyLetters to the Editor32101010826792680268120052679268026822019
- Integrative Cistromic and Transcriptomic Analyses Identify CREB Target Genes in Cystic Renal Epithelial Cells10.1681/ASN.2021010101Wed, 23 Jun 2021 02:05:28 GMT-07:00Integrative Cistromic and Transcriptomic Analyses Identify CREB Target Genes in Cystic Renal Epithelial CellsLiu, ZhihengLiu, YunjingDang, LinGeng, MeijuanSun, YongzhanLu, YiFang, ZhongzeXiong, HuiChen, Yupeng2021-06-23T14:05:28-07:00doi:10.1681/ASN.2021010101hwp:resource-id:jnephrol;32/10/2529American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, CREB, transcription factors, cAMP, kidney diseases, CUT&RUNBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20210101011046-66731533-34502021-06-23T14:05:28-07:002021-10Journal of the American Society of NephrologyBasic Research321025292541
- Racial Inequalities in Drinking Water Lead Exposure: A Wake-Up Call to Protect Patients with End Stage Kidney Disease10.1681/ASN.2021060793Mon, 20 Sep 2021 11:11:45 GMT-07:00Racial Inequalities in Drinking Water Lead Exposure: A Wake-Up Call to Protect Patients with End Stage Kidney DiseaseNigra, Anne E.Navas-Acien, Ana2021-09-20T11:11:45-07:00doi:10.1681/ASN.2021060793hwp:resource-id:jnephrol;32/10/2419American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, end stage kidney disease, racial and ethnic disparitiesUp Front MattersAddressing Racial and Ethnic Disparities in Kidney DiseaseUp Front MattersAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20212021-10-01October 202110.1681/ASN.20210607931046-66731533-34502021-09-20T11:11:45-07:002021-10Journal of the American Society of NephrologyUp Front Matters3210101024192425i24212434i
- Introducing a Special Series: Addressing Racial and Ethnic Disparities in Kidney Disease10.1681/ASN.2021081033Fri, 01 Oct 2021 10:51:44 GMT-07:00Introducing a Special Series: Addressing Racial and Ethnic Disparities in Kidney DiseaseBriggs, Josephine P.Wesson, Donald2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021081033hwp:resource-id:jnephrol;32/10/2417American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyracial inequities, racism, kidney disease, racial and ethnic disparitiesUp Front MattersAddressing Racial and Ethnic Disparities in Kidney DiseaseUp Front MattersAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20212021-10-01October 202110.1681/ASN.20210810331046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyUp Front Matters321024172418
- Erythropoietin Reduces Auto- and Alloantibodies by Inhibiting T Follicular Helper Cell Differentiation10.1681/ASN.2021010098Wed, 14 Jul 2021 09:30:45 GMT-07:00Erythropoietin Reduces Auto- and Alloantibodies by Inhibiting T Follicular Helper Cell DifferentiationGuglielmo, ChiaraBin, SofiaCantarelli, ChiaraHartzell, SusanAngeletti, AndreaDonadei, ChiaraCumpelik, ArunAnderson, LisaCody, EvanSage, Peter T.La Manna, GaetanoFiaccadori, EnricoHeeger, Peter S.Cravedi, Paolo2021-07-14T09:30:45-07:00doi:10.1681/ASN.2021010098hwp:resource-id:jnephrol;32/10/2542American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, rejection, immunologyBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20210100981046-66731533-34502021-07-14T09:30:45-07:002021-10Journal of the American Society of NephrologyBasic Research321025422560
- O- and N-Glycosylation of Serum Immunoglobulin A is Associated with IgA Nephropathy and Glomerular Function10.1681/ASN.2020081208Mon, 14 Jun 2021 11:36:36 GMT-07:00O- and N-Glycosylation of Serum Immunoglobulin A is Associated with IgA Nephropathy and Glomerular FunctionDotz, ViktoriaVisconti, AlessiaLomax-Browne, Hannah J.Clerc, FlorentHipgrave Ederveen, Agnes L.Medjeral-Thomas, Nicholas R.Cook, H. TerencePickering, Matthew C.Wuhrer, ManfredFalchi, Mario2021-06-14T11:36:36-07:00doi:10.1681/ASN.2020081208hwp:resource-id:jnephrol;32/10/2455American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, glycosylation, immunoglobulin, mass spectrometry, posttranslational modificationBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20200812081046-66731533-34502021-06-14T11:36:36-07:002021-10Journal of the American Society of NephrologyBasic Research321024552465
- Mendelian Randomization Analysis as a Tool to Gain Insights into Causes of Diseases: A PrimerMany Mendelian randomization (MR) studies have been published recently, with inferences on the causal relationships between risk factors and diseases that have potential implications for clinical research. In nephrology, MR methods have been applied to investigate potential causal relationships of traditional risk factors, lifestyle factors, and biomarkers from omics technologies with kidney function or CKD. This primer summarizes the basic concepts of MR studies, highlighting methods used in recent applications, and emphasizes key elements in conducting and reporting of MR studies that are important for interpreting the results.10.1681/ASN.2020121760Wed, 16 Jun 2021 10:31:17 GMT-07:00Mendelian Randomization Analysis as a Tool to Gain Insights into Causes of Diseases: A PrimerMany Mendelian randomization (MR) studies have been published recently, with inferences on the causal relationships between risk factors and diseases that have potential implications for clinical research. In nephrology, MR methods have been applied to investigate potential causal relationships of traditional risk factors, lifestyle factors, and biomarkers from omics technologies with kidney function or CKD. This primer summarizes the basic concepts of MR studies, highlighting methods used in recent applications, and emphasizes key elements in conducting and reporting of MR studies that are important for interpreting the results.Tin, AdrienneKöttgen, Anna2021-06-16T10:31:17-07:00doi:10.1681/ASN.2020121760hwp:resource-id:jnephrol;32/10/2400American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyEpidemiology and outcomesUp Front MattersReviewsUp Front MattersReviewsresearch-article20212021-10-01October 202110.1681/ASN.20201217601046-66731533-34502021-06-16T10:31:17-07:002021-10Journal of the American Society of NephrologyUp Front Matters321024002407
- A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor10.1681/ASN.2021020267Fri, 18 Jun 2021 11:02:43 GMT-07:00A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for TumorRicaurte Archila, LuisaDenic, AleksandarMullan, Aidan F.Narasimhan, RamyaBogojevic, MarijaThompson, R. HoustonLeibovich, Bradley C.Sangaralingham, S. JesonSmith, Maxwell L.Alexander, Mariam P.Rule, Andrew D.2021-06-18T11:02:43-07:00doi:10.1681/ASN.2021020267hwp:resource-id:jnephrol;32/10/2623American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, interstitial fibrosis, tubular atrophy, radical nephrectomyClinical ResearchClinical Researchresearch-article20212021-10-01October 202110.1681/ASN.20210202671046-66731533-34502021-06-18T11:02:43-07:002021-10Journal of the American Society of NephrologyClinical Research321026232633
- Macula Densa NOS1β Modulates Renal Hemodynamics and Blood Pressure during Pregnancy: Role in Gestational Hypertensionjwei@usf.edu10.1681/ASN.2020070969Mon, 14 Jun 2021 11:36:35 GMT-07:00Macula Densa NOS1β Modulates Renal Hemodynamics and Blood Pressure during Pregnancy: Role in Gestational HypertensionWei, JinZhang, JieJiang, ShanXu, LanQu, LarryPang, BoJiang, KunWang, LeiIntapad, SuttiraBuggs, JacenthaCheng, FengMohapatra, ShyamJuncos, Luis A.Osborn, Jeffrey L.Granger, Joey P.Liu, Ruisheng2021-06-14T11:36:35-07:00doi:10.1681/ASN.2020070969hwp:resource-id:jnephrol;32/10/2485American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytubologlomerular feedback, macula densa, nitric oxide, renal hemodynamics, blood pressure, preeclampsiaBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20200709691046-66731533-34502021-06-14T11:36:35-07:002021-10Journal of the American Society of NephrologyBasic Research321024852500
- Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Miceckurts@web.de10.1681/ASN.2021010110Fri, 18 Jun 2021 11:02:42 GMT-07:00Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in MiceBöhner, Alexander M.C.Jacob, Alice M.Heuser, ChristophStumpf, Natascha E.Effland, AlexanderAbdullah, ZeinabMeyer-Schwesiger, Catherinevon Vietinghoff, SibylleKurts, Christian2021-06-18T11:02:42-07:00doi:10.1681/ASN.2021010110hwp:resource-id:jnephrol;32/10/2445American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal denervation, chronic glomerulonephritis, pyelonephritis, sterile inflammation, septic kidney injury, neutrophilsRapid CommunicationsRapid Communicationsresearch-article20212021-10-01October 202110.1681/ASN.20210101101046-66731533-34502021-06-18T11:02:42-07:002021-10Journal of the American Society of NephrologyRapid Communications3210102445239324532395
- The Prognostic Significance of Body Mass Index and Metabolic Parameter Variabilities in Predialysis CKD: A Nationwide Observational Cohort Study10.1681/ASN.2020121694Thu, 12 Aug 2021 09:53:45 GMT-07:00The Prognostic Significance of Body Mass Index and Metabolic Parameter Variabilities in Predialysis CKD: A Nationwide Observational Cohort StudyPark, SehoonCho, SeminLee, SoojinKim, YaerimPark, SanghyunKim, Yong ChulHan, Seung SeokLee, HajeongLee, Jung PyoJoo, Kwon WookLim, Chun SooKim, Yon SuHan, KyungdoKim, Dong Ki2021-08-12T09:53:45-07:00doi:10.1681/ASN.2020121694hwp:resource-id:jnephrol;32/10/2595American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologybody mass index, epidemiology, chronic kidney diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20212021-10-01October 202110.1681/ASN.20201216941046-66731533-34502021-08-12T09:53:45-07:002021-10Journal of the American Society of NephrologyClinical Epidemiology3210102595239526122397
- Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Micehutchenm@ohsu.edu10.1681/ASN.2020030263Mon, 02 Aug 2021 09:41:21 GMT-07:00Cilastatin Ameliorates Rhabdomyolysis-induced AKI in MiceMatsushita, KatsuyukiMori, KiyoshiSaritas, TurgayEiwaz, Mahaba B.Funahashi, YoshioNickerson, Megan N.Hebert, Jessica F.Munhall, Adam C.McCormick, James A.Yanagita, MotokoHutchens, Michael P.2021-08-02T09:41:21-07:00doi:10.1681/ASN.2020030263hwp:resource-id:jnephrol;32/10/2579American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrhabdomyolysis, endocytosis, acute renal failure, chronic kidney disease, renal protectionBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20200302631046-66731533-34502021-08-02T09:41:21-07:002021-10Journal of the American Society of NephrologyBasic Research321025792594
- Using both the Fraction and Quantity of Donor-Derived Cell-Free DNA to Detect Kidney Allograft Rejection10.1681/ASN.2021050645Wed, 23 Jun 2021 11:32:46 GMT-07:00Using both the Fraction and Quantity of Donor-Derived Cell-Free DNA to Detect Kidney Allograft RejectionBunnapradist, SuphamaiHomkrailas, PiyavadeeAhmed, EbadFehringer, GordonBillings, Paul R.Tabriziani, Hossein2021-06-23T11:32:46-07:00doi:10.1681/ASN.2021050645hwp:resource-id:jnephrol;32/10/2439American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney, acute allograft rejection, chronic allograft rejection, kidney biopsy, cell-free nucleic acids, allografts, acute rejection, transplantationResearch LettersResearch Lettersresearch-article20212021-10-01October 202110.1681/ASN.20210506451046-66731533-34502021-06-23T11:32:46-07:002021-10Journal of the American Society of NephrologyResearch Letters32101111243929732972244129742973
- Renal Nerve Ablation in Nephritis and Beyondroland.veelken@uk-erlangen.de10.1681/ASN.2021060748Fri, 01 Oct 2021 10:51:44 GMT-07:00Renal Nerve Ablation in Nephritis and BeyondRodionova, KristinaDitting, TilmannVeelken, Roland2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021060748hwp:resource-id:jnephrol;32/10/2393American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal innervation, kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-10-01October 202110.1681/ASN.20210607481046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyUp Front Matters3210102393244523952453
- Associations of Community Water Lead Concentrations with Hemoglobin Concentrations and Erythropoietin-Stimulating Agent Use among Patients with Advanced CKD10.1681/ASN.2020091281Thu, 15 Jul 2021 01:18:28 GMT-07:00Associations of Community Water Lead Concentrations with Hemoglobin Concentrations and Erythropoietin-Stimulating Agent Use among Patients with Advanced CKDDanziger, JohnMukamal, Kenneth J.Weinhandl, Eric2021-07-15T13:18:28-07:00doi:10.1681/ASN.2020091281hwp:resource-id:jnephrol;32/10/2425American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologylead toxicity, anemia, environmental risk factors, disparities, racial and ethnic disparitiesUp Front MattersAddressing Racial and Ethnic Disparities in Kidney DiseaseUp Front MattersAddressing Racial and Ethnic Disparities in Kidney Diseaseresearch-article20212021-10-01October 202110.1681/ASN.20200912811046-66731533-34502021-07-15T13:18:28-07:002021-10Journal of the American Society of NephrologyUp Front Matters3210101024252419i24342421i
- MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA Synthesiszhaobinghai01@vip.163.comzhaobinghai01@vip.163.com10.1681/ASN.2021010133Fri, 03 Sep 2021 09:49:58 GMT-07:00MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA SynthesisLi, HongzhiChen, ZhichaoChen, WeitianLi, JingyiLiu, YunshuangMa, HongchuangShi, MingmingSun, XuelianYao, XiusongLi, ZhijunPawluczyk, Izabella Z.AZhang, ShuchenBarratt, JonathanLv, JichengWang, KaiZhao, Binghai2021-09-03T09:49:58-07:00doi:10.1681/ASN.2021010133hwp:resource-id:jnephrol;32/10/2561American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, IgA, immunologyBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20210101331046-66731533-34502021-09-03T09:49:58-07:002021-10Journal of the American Society of NephrologyBasic Research321025612578
- Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children10.1681/ASN.2021010094Mon, 20 Sep 2021 10:39:42 GMT-07:00Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in ChildrenGreenberg, Jason H.Abraham, Alison G.Xu, YunwenSchelling, Jeffrey R.Feldman, Harold I.Sabbisetti, Venkata S.Ix, Joachim H.Jogalekar, Manasi P.Coca, StevenWaikar, Sushrut S.Shlipak, Michael G.Warady, Bradley A.Vasan, Ramachandran S.Kimmel, Paul L.Bonventre, Joseph V.Denburg, MichelleParikh, Chirag R.Furth, Susan,,Ramachandran, Vasan S.Schelling, JeffreyDenburg, MichelleFurth, SusanWarady, BradleyBonventre, JosephWaikar, SushrutSabbisetti, VenkataCoresh, JosefGrams, MorganRebholz, CaseyAbraham, AlisonParikh, ChiragCoca, StevenRhee, EugeneKimmel, Paul L.Kusek, John W.Rovin, BradShlipak, Michael G.Sarnak, MarkGutiérrez, Orlando M.Ix, JoachimDubin, RuthHostetter, TomDeo, RajatFeldman, Harold I.Xie, DaweiShou, HaochangBallard, ShawnWhitehead, KristaCollins, HeatherGreenberg, Jason H.Ganz, Peter2021-09-20T10:39:42-07:00doi:10.1681/ASN.2021010094hwp:resource-id:jnephrol;32/10/2664American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, children, end-stage kidney disease, pediatric nephrologyClinical ResearchClinical Researchresearch-article20212021-10-01October 202110.1681/ASN.20210100941046-66731533-34502021-09-20T10:39:42-07:002021-10Journal of the American Society of NephrologyClinical Research321026642677
- Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial10.1681/ASN.2021040561Mon, 20 Sep 2021 10:39:41 GMT-07:00Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized TrialRavani, PietroColucci, ManuelaBruschi, MaurizioVivarelli, MarinaCioni, MichelaDiDonato, ArmandoCravedi, PaoloLugani, FrancescaAntonini, FrancescaPrunotto, MarcoEmma, FrancescoAngeletti, AndreaGhiggeri, Gian Marco2021-09-20T10:39:41-07:00doi:10.1681/ASN.2021040561hwp:resource-id:jnephrol;32/10/2652American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysteroid dependent nephrotic syndrome, calcineurin inhibitor-dependent nephrotic syndrome, human anti-CD20 monoclonal antibodies, ofatumumab, rituximab, memory B cells, prediction of response, antirituximab antibodies, idiopathic nephrotic syndrome, glomerular diseaseClinical ResearchClinical Researchresearch-article20212021-10-01October 202110.1681/ASN.20210405611046-66731533-34502021-09-20T10:39:41-07:002021-10Journal of the American Society of NephrologyClinical Research321088265216251626266316251626
- Kim-1 Targeted Extracellular Vesicles: A New Therapeutic Platform for RNAi to Treat AKI10.1681/ASN.2020111561Mon, 14 Jun 2021 11:36:35 GMT-07:00Kim-1 Targeted Extracellular Vesicles: A New Therapeutic Platform for RNAi to Treat AKITang, Tao-TaoWang, BinLi, Zuo-LinWen, YiFeng, Song-TaoWu, MinLiu, DanCao, Jing-YuanYin, QingYin, DiFu, Yu-QiGao, Yue-MingDing, Zhao-YingQian, Jing-YiWu, Qiu-LiLv, Lin-LiLiu, Bi-Cheng2021-06-14T11:36:35-07:00doi:10.1681/ASN.2020111561hwp:resource-id:jnephrol;32/10/2467American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, kidney injury molecule-1, extracellular vesicles, RNAi, P65, Snai1Basic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20201115611046-66731533-34502021-06-14T11:36:35-07:002021-10Journal of the American Society of NephrologyBasic Research321024672483
- Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of GlucoseUltrafiltration is essential in peritoneal dialysis (PD) for maintenance of euvolemia, making ultrafiltration insufficiency—preferably called ultrafiltration failure—an important complication. The mechanisms of ultrafiltration and ultrafiltration failure are more complex than generally assumed, especially after long-term treatment. Initially, ultrafiltration failure is mainly explained by a large number of perfused peritoneal microvessels, leading to a rapid decline of the crystalloid osmotic gradient, thereby decreasing aquaporin-mediated free water transport. The contribution of peritoneal interstitial tissue to ultrafiltration failure is limited during the first few years of PD, but becomes more important in long-term PD due to the development of interstitial fibrosis, which mainly consists of myofibroblasts. A dual hypothesis has been developed to explain why the continuous exposure of peritoneal tissues to the extremely high dialysate glucose concentrations causes progressive ultrafiltration decline. First, glucose absorption causes an increase of the intracellular NADH/NAD+ ratio, also called pseudohypoxia. Intracellular hypoxia stimulates myofibroblasts to produce profibrotic and angiogenetic factors, and the glucose transporter GLUT-1. Second, the increased GLUT-1 expression by myofibroblasts increases glucose uptake in these cells, leading to a reduction of the osmotic gradient for ultrafiltration. Reduction of peritoneal glucose exposure to prevent this vicious circle is essential for high-quality, long-term PD.r.t.krediet@amsterdamumc.nl10.1681/ASN.2021010080Wed, 28 Jul 2021 09:47:04 GMT-07:00Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of GlucoseUltrafiltration is essential in peritoneal dialysis (PD) for maintenance of euvolemia, making ultrafiltration insufficiency—preferably called ultrafiltration failure—an important complication. The mechanisms of ultrafiltration and ultrafiltration failure are more complex than generally assumed, especially after long-term treatment. Initially, ultrafiltration failure is mainly explained by a large number of perfused peritoneal microvessels, leading to a rapid decline of the crystalloid osmotic gradient, thereby decreasing aquaporin-mediated free water transport. The contribution of peritoneal interstitial tissue to ultrafiltration failure is limited during the first few years of PD, but becomes more important in long-term PD due to the development of interstitial fibrosis, which mainly consists of myofibroblasts. A dual hypothesis has been developed to explain why the continuous exposure of peritoneal tissues to the extremely high dialysate glucose concentrations causes progressive ultrafiltration decline. First, glucose absorption causes an increase of the intracellular NADH/NAD+ ratio, also called pseudohypoxia. Intracellular hypoxia stimulates myofibroblasts to produce profibrotic and angiogenetic factors, and the glucose transporter GLUT-1. Second, the increased GLUT-1 expression by myofibroblasts increases glucose uptake in these cells, leading to a reduction of the osmotic gradient for ultrafiltration. Reduction of peritoneal glucose exposure to prevent this vicious circle is essential for high-quality, long-term PD.Krediet, Raymond T.2021-07-28T09:47:04-07:00doi:10.1681/ASN.2021010080hwp:resource-id:jnephrol;32/10/2408American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, free water transport, small pore fluid transport, pseudohypoxia, ultrafiltration insufficiency, hypoxia, glucose transporters, myofibroblasts, osmolalityUp Front MattersReviewsUp Front MattersReviewsresearch-article20212021-10-01October 202110.1681/ASN.20210100801046-66731533-34502021-07-28T09:47:04-07:002021-10Journal of the American Society of NephrologyUp Front Matters321024082415
- Authors’ Reply10.1681/ASN.2021060879Thu, 16 Sep 2021 01:36:25 GMT-07:00Authors’ ReplyRobinson, Cal H.Jeyakumar, NivethikaWald, RonZappitelli, MichaelChanchlani, Rahul2021-09-16T13:36:25-07:00doi:10.1681/ASN.2021060879hwp:resource-id:jnephrol;32/10/2681American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, pediatric nephrology, children, chronic kidney diseaseLetters to the EditorLetters to the Editorletter20212021-10-01October 202110.1681/ASN.20210608791046-66731533-34502021-09-16T13:36:25-07:002021-10Journal of the American Society of NephrologyLetters to the Editor32101010826812679268020052682267926802019
- High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome10.1681/ASN.2021010059Fri, 04 Jun 2021 11:03:04 GMT-07:00High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 OutcomeCaceres, Paulo S.Savickas, GinaMurray, Shannon L.Umanath, KausikUduman, JuniorYee, JerryLiao, Tang-DongBolin, StevenLevin, Albert M.Khan, Moomal N.Sarkar, SarahFitzgerald, JamieMaskey, DipakOrmsby, Adrian H.Sharma, YuvrajOrtiz, Pablo A.2021-06-04T11:03:04-07:00doi:10.1681/ASN.2021010059hwp:resource-id:jnephrol;32/10/2517American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, virology, renal injury, mortality risk, COVID-19Basic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20210100591046-66731533-34502021-06-04T11:03:04-07:002021-10Journal of the American Society of NephrologyBasic Research3210102517i2528i
- Antibody Response to COVID-19 Vaccination in Patients Receiving Dialysis10.1681/ASN.2021050611Fri, 11 Jun 2021 06:31:07 GMT-07:00Antibody Response to COVID-19 Vaccination in Patients Receiving DialysisAnand, ShuchiMontez-Rath, Maria E.Han, JialinGarcia, PabloCadden, LinaCelHunsader, PattiKerschmann, RussellBeyer, PaulDittrich, MaryBlock, Geoffrey A.Boyd, Scott D.Parsonnet, JulieChertow, Glenn M.2021-06-11T06:31:07-07:00doi:10.1681/ASN.2021050611hwp:resource-id:jnephrol;32/10/2435American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, chronic dialysis, clinical nephrology, immunosuppression, COVID-19, antibody formation, renal dialysis, vaccinationResearch LettersResearch Lettersresearch-article20212021-10-01October 202110.1681/ASN.20210506111046-66731533-34502021-06-11T06:31:07-07:002021-10Journal of the American Society of NephrologyResearch Letters321024352438
- Pediatric Acute Kidney Injury Survivors Need Risk Stratification and Individualized Follow-Up10.1681/ASN.2021060753Thu, 16 Sep 2021 01:36:25 GMT-07:00Pediatric Acute Kidney Injury Survivors Need Risk Stratification and Individualized Follow-UpZhao, YuliangPu, YajunZhang, LingFu, Ping2021-09-16T13:36:25-07:00doi:10.1681/ASN.2021060753hwp:resource-id:jnephrol;32/10/2680American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypediatric, acute kidney injury, follow-up, outcomes, survivors, risk assessmentLetters to the EditorLetters to the Editorresearch-article20212021-10-01October 202110.1681/ASN.20210607531046-66731533-34502021-09-16T13:36:25-07:002021-10Journal of the American Society of NephrologyLetters to the Editor32101010826802679268120052680267926822019
- Patient Health Outcomes following Dialysis Facility Closures in the United States10.1681/ASN.2021020244Fri, 01 Oct 2021 10:51:44 GMT-07:00Patient Health Outcomes following Dialysis Facility Closures in the United StatesNiu, JingboSaeed, Maryam K.Winkelmayer, Wolfgang C.Erickson, Kevin F.2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021020244hwp:resource-id:jnephrol;32/10/2613American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, end stage kidney disease, epidemiology and outcomes, hemodialysis, United States Renal Data SystemClinical EpidemiologyClinical Epidemiologyresearch-article20212021-10-01October 202110.1681/ASN.20210202441046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyClinical Epidemiology3210102613i2621i
- Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney Fibrosis10.1681/ASN.2020081143Mon, 21 Jun 2021 09:55:14 GMT-07:00Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney FibrosisLu, Yueh-AnLiao, Chia-TeRaybould, RachelTalabani, BnarGrigorieva, IrinaSzomolay, BarbaraBowen, TimothyAndrews, RobertTaylor, Philip R.Fraser, Donald2021-06-21T09:55:14-07:00doi:10.1681/ASN.2020081143hwp:resource-id:jnephrol;32/10/2501American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycell biology and structure, chronic kidney disease, epithelial, kidney tubule, mRNA, proximal tubule, renal epithelial cell, renal fibrosis, renal tubular epithelial cells, scRNA-seqBasic ResearchBasic Researchresearch-article20212021-10-01October 202110.1681/ASN.20200811431046-66731533-34502021-06-21T09:55:14-07:002021-10Journal of the American Society of NephrologyBasic Research3210102501i2516i
- Correction: Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy10.1681/ASN.2021071000Fri, 01 Oct 2021 10:51:44 GMT-07:00Correction: Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic NephropathyAmerican Society of Nephrology2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021071000hwp:resource-id:jnephrol;32/10/2683American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathyErrataErratacorrection20212021-10-01October 202110.1681/ASN.20210710001046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyErrata321062683135526831370
- Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes10.1681/ASN.2020101457Wed, 14 Jul 2021 09:30:46 GMT-07:00Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 (HSD17B14) with Reduced Progression to End Stage Kidney Disease in Type 1 DiabetesMychaleckyj, Josyf C.Valo, ErkkaIchimura, TakaharuAhluwalia, Tarunveer S.Dina, ChristianMiller, Rachel G.Shabalin, Ivan G.Gyorgy, BeataCao, JingJingOnengut-Gumuscu, SunaSatake, EiichiroSmiles, Adam M.Haukka, Jani K.Tregouet, David-AlexandreCostacou, TinaO’Neil, KristinaPaterson, Andrew D.Forsblom, CarolKeenan, Hillary A.Pezzolesi, Marcus G.Pragnell, MarlonGalecki, AndrzejRich, Stephen S.Sandholm, NiinaKlein, RonaldKlein, Barbara E.Susztak, KatalinOrchard, Trevor J.Korstanje, RonKing, George L.Hadjadj, SamyRossing, PeterBonventre, Joseph V.Groop, Per-HenrikWarram, James H.Krolewski, Andrzej S.2021-07-14T09:30:46-07:00doi:10.1681/ASN.2020101457hwp:resource-id:jnephrol;32/10/2634American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytype 1 diabetes, hydroxysteroid 17-beta dehydrogenase 14, end stage kidney disease, gene-based tests, rare variants, diabetic nephropathy, diabetic kidney diseaseClinical ResearchClinical Researchresearch-article20212021-10-01October 202110.1681/ASN.20201014571046-66731533-34502021-07-14T09:30:46-07:002021-10Journal of the American Society of NephrologyClinical Research3210102634239726512399
- Coding Variants in Susceptibility to Diabetic Kidney Disease10.1681/ASN.2021081088Fri, 01 Oct 2021 10:51:44 GMT-07:00Coding Variants in Susceptibility to Diabetic Kidney DiseaseLiu, LiliKiryluk, Krzysztof2021-10-01T10:51:44-07:00doi:10.1681/ASN.2021081088hwp:resource-id:jnephrol;32/10/2397American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic kidney disease, coding variant, gene-based burden tests, type 1 diabetes, diabetic nephropathyUp Front MattersEditorialsUp Front MattersEditorialsresearch-article20212021-10-01October 202110.1681/ASN.20210810881046-66731533-34502021-10-01T10:51:44-07:002021-10Journal of the American Society of NephrologyUp Front Matters3210102397263423992651
- Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A ReviewDue to age and impaired kidney function, older adults with kidney disease are at increased risk of medication-related problems and related hospitalizations. One proa ctive approach to minimize this risk is deprescribing. Deprescribing refers to the systematic process of reducing or stopping a medication. Aside from preventing harm, deprescribing can potentially optimize patients’ quality of life by aligning medications with their goals of care. For some patients, deprescribing could involve less aggressive management of their diabetes and/or hypertension. In other instances, deprescribing targets may include potentially inappropriate medications that carry greater risk of harm than benefit in older adults, medications that have questionable efficacy, including medications that have varying efficacy by degree of kidney function, and that increase medication regimen complexity. We include a guide for clinicians to utilize in deprescribing, the List, Evaluate, Shared Decision-Making, Support (LESS) framework. The LESS framework provides key considerations at each step of the deprescribing process that can be tailored for the medications and context of individu al patients. Patient characteristics or clinical events that warrant consideration of deprescribing include limited life expectancy, cognitive impairment, and health status changes, such as dialysis initiation or recent hospitalization. We acknowledge patient-, clinician-, and system-level challenges to the depre scribing process. These include patient hesitancy and challenges to discussing goals of care, clinician time constraints and a lack of evidence-based guidelines, and system-level challenges of interoperable electronic health records and limited incentives for deprescribing. However, novel evidence-based tools designed to facilitate deprescribing and future evidence on effectiveness of deprescribing could help mitigate these barriers. This review provides foundational knowledge on deprescribing as an emerging component of clinical practice and research within nephrology.10.34067/KID.0001942021Fri, 09 Jul 2021 09:29:49 GMT-07:00Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A ReviewDue to age and impaired kidney function, older adults with kidney disease are at increased risk of medication-related problems and related hospitalizations. One proa ctive approach to minimize this risk is deprescribing. Deprescribing refers to the systematic process of reducing or stopping a medication. Aside from preventing harm, deprescribing can potentially optimize patients’ quality of life by aligning medications with their goals of care. For some patients, deprescribing could involve less aggressive management of their diabetes and/or hypertension. In other instances, deprescribing targets may include potentially inappropriate medications that carry greater risk of harm than benefit in older adults, medications that have questionable efficacy, including medications that have varying efficacy by degree of kidney function, and that increase medication regimen complexity. We include a guide for clinicians to utilize in deprescribing, the List, Evaluate, Shared Decision-Making, Support (LESS) framework. The LESS framework provides key considerations at each step of the deprescribing process that can be tailored for the medications and context of individu al patients. Patient characteristics or clinical events that warrant consideration of deprescribing include limited life expectancy, cognitive impairment, and health status changes, such as dialysis initiation or recent hospitalization. We acknowledge patient-, clinician-, and system-level challenges to the depre scribing process. These include patient hesitancy and challenges to discussing goals of care, clinician time constraints and a lack of evidence-based guidelines, and system-level challenges of interoperable electronic health records and limited incentives for deprescribing. However, novel evidence-based tools designed to facilitate deprescribing and future evidence on effectiveness of deprescribing could help mitigate these barriers. This review provides foundational knowledge on deprescribing as an emerging component of clinical practice and research within nephrology.Mohottige, DinushikaManley, Harold J.Hall, Rasheeda K.2021-07-09T09:29:49-07:00doi:10.34067/KID.0001942021hwp:resource-id:kidney360;2/9/1510American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360geriatric and palliative nephrology, aged, deprescriptions, dialysis, kidney diseasesReview ArticleReview Articlereview-article20212021-09-3010.34067/KID.00019420212641-76502021-07-09T09:29:49-07:002021-09-30Kidney360Review Article2915101522
- Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: PRO10.34067/KID.0000022021Fri, 09 Apr 2021 09:22:47 GMT-07:00Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: PRODevabhaktuni, Subodh R.Mounsey, J. Paul2021-04-09T09:22:47-07:00doi:10.34067/KID.0000022021hwp:resource-id:kidney360;2/9/1405American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, apixaban, coumadin, ESKD, ESRD, OACDebates in NephrologyDebates in Nephrologyresearch-article20212021-09-3010.34067/KID.00000220212641-76502021-04-09T09:22:47-07:002021-09-30Kidney360Debates in Nephrology2914051408
- Renal Sensing of Bacterial Metabolites in the Gut-kidney AxisSeminal works have now revealed the gut microbiota is connected with several diseases, including renal disorders. The balance between optimal and dysregulated host-microbiota interactions has completely changed our understanding of immunity and inflammation. Kidney injury is associated with accumulation of uremic toxins in the intestine, augmented intestinal permeability, and systemic inflammation. Intestinal bacteria can signal through innate receptors and induce immune cell activation in the lamina propria and release of inflammatory mediators into the bloodstream . But the gut microbiota can also modulate immune functions through soluble products as short-chain fatty acids (SCFAs). The three most common SCFAs are propionate, butyrate, and acetate, which can signal through specific G-protein coupled receptors (GPCRs), such as GPR43, GPR41, and GPR109a, expressed on the surface of epithelial, myeloid, endothelial, and immune cells, among others. The triggered signaling can change cell metabolism, immune cell activation, and cell death. In this study, we reviewed the gut-kidney axis, how kidney cells can sense SCFAs, and its implication in kidney diseases.10.34067/KID.0000292021Fri, 02 Jul 2021 11:27:00 GMT-07:00Renal Sensing of Bacterial Metabolites in the Gut-kidney AxisSeminal works have now revealed the gut microbiota is connected with several diseases, including renal disorders. The balance between optimal and dysregulated host-microbiota interactions has completely changed our understanding of immunity and inflammation. Kidney injury is associated with accumulation of uremic toxins in the intestine, augmented intestinal permeability, and systemic inflammation. Intestinal bacteria can signal through innate receptors and induce immune cell activation in the lamina propria and release of inflammatory mediators into the bloodstream . But the gut microbiota can also modulate immune functions through soluble products as short-chain fatty acids (SCFAs). The three most common SCFAs are propionate, butyrate, and acetate, which can signal through specific G-protein coupled receptors (GPCRs), such as GPR43, GPR41, and GPR109a, expressed on the surface of epithelial, myeloid, endothelial, and immune cells, among others. The triggered signaling can change cell metabolism, immune cell activation, and cell death. In this study, we reviewed the gut-kidney axis, how kidney cells can sense SCFAs, and its implication in kidney diseases.Foresto-Neto, OrestesGhirotto, BrunoCâmara, Niels Olsen Saraiva2021-07-02T11:27:00-07:00doi:10.34067/KID.0000292021hwp:resource-id:kidney360;2/9/1501American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360renal physiology, AKI, basic science, CKD, gastrointestinal microbiome, GCPR, inflammation, short chain fatty acidsBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-09-3010.34067/KID.00002920212641-76502021-07-02T11:27:00-07:002021-09-30Kidney360Basic Science for Clinicians2915011509
- Collagen Remodeling Biomarkers in Lupus Nephritis10.34067/KID.0004732021Thu, 30 Sep 2021 05:30:25 GMT-07:00Collagen Remodeling Biomarkers in Lupus NephritisCaster, Dawn J.Merchant, Michael L.2021-09-30T05:30:25-07:00doi:10.34067/KID.0004732021hwp:resource-id:kidney360;2/9/1395American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, biomarkers, chronic kidney disease, collagen remodeling, extracellular matrix, interstitial fibrosis, lupus nephritisEditorialEditorialeditorial20212021-09-3010.34067/KID.00047320212641-76502021-09-30T05:30:25-07:002021-09-30Kidney360Editorial2913951398
- Peroxisomal L-bifunctional Protein Deficiency Causes Male-specific Kidney Hypertrophy and Proximal Tubular Injury in Mice10.34067/KID.0003772021Wed, 30 Jun 2021 01:27:41 GMT-07:00Peroxisomal L-bifunctional Protein Deficiency Causes Male-specific Kidney Hypertrophy and Proximal Tubular Injury in MiceRanea-Robles, PabloPortman, KenseyBender, AaronLee, KyungHe, John CijiangMulholland, David J.Argmann, CarmenHouten, Sander M.2021-06-30T13:27:41-07:00doi:10.34067/KID.0003772021hwp:resource-id:kidney360;2/9/1441American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, androgens, basic science, hypertrophy, kidney, mice, multifunctional protein 1, peroxisomal bifunctional protein, peroxisomes, proximal tubule, sex differencesOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-09-3010.34067/KID.00037720212641-76502021-06-30T13:27:41-07:002021-09-30Kidney360Original Investigation2914411454
- Frailty, Age, and Postdialysis Recovery Time in a Population New to Hemodialysis10.34067/KID.0001052021Tue, 13 Jul 2021 07:36:55 GMT-07:00Frailty, Age, and Postdialysis Recovery Time in a Population New to HemodialysisFitzpatrick, JessicaSozio, Stephen M.Jaar, Bernard G.Estrella, Michelle M.Segev, Dorry L.Shafi, TariqMonroy-Trujillo, Jose M.Parekh, Rulan S.McAdams-DeMarco, Mara A.2021-07-13T07:36:55-07:00doi:10.34067/KID.0001052021hwp:resource-id:kidney360;2/9/1455American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, age, dialysis recovery time, end-stage kidney disease, frailty, hemodialysisOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-09-3010.34067/KID.00010520212641-76502021-07-13T07:36:55-07:002021-09-30Kidney360Original Investigation2914551462
- Tribute to Barbara Murphy10.34067/KID.0005002021Fri, 06 Aug 2021 05:55:47 GMT-07:00Tribute to Barbara MurphyCoca, Steven G.2021-08-06T05:55:47-07:00doi:10.34067/KID.0005002021hwp:resource-id:kidney360;2/9/1499American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, tributePerspectivePerspectiveresearch-article20212021-09-3010.34067/KID.00050020212641-76502021-08-06T05:55:47-07:002021-09-30Kidney360Perspective2914991500
- Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney Disease10.34067/KID.0002622021Thu, 08 Jul 2021 10:20:23 GMT-07:00Peripheral Insulin Resistance Is Associated with Copeptin in Patients with Chronic Kidney DiseaseArroyo, Juan PabloAkwo, Elvis A.Terker, Andrew S.Alsouqi, AseelBhave, GautamHarris, Raymond C.Hung, Adriana M.Ikizler, T. Alp2021-07-08T10:20:23-07:00doi:10.34067/KID.0002622021hwp:resource-id:kidney360;2/9/1434American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, chronic renal insufficiency, copeptin, hepatic insulin resistance, HOMA-IR, insulin resistance, insulin sensitivity, ISI, routine diagnostic tests, vasopressinOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-09-3010.34067/KID.00026220212641-76502021-07-08T10:20:23-07:002021-09-30Kidney360Original Investigation2914341440
- From Dropsy to Chart Biopsy: Opportunities and Pitfalls of Electronic Health Records10.34067/KID.0004392021Thu, 30 Sep 2021 05:30:25 GMT-07:00From Dropsy to Chart Biopsy: Opportunities and Pitfalls of Electronic Health RecordsCervantes, C. ElenaSperati, C. John2021-09-30T05:30:25-07:00doi:10.34067/KID.0004392021hwp:resource-id:kidney360;2/9/1399American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, algorithms, CKD, electronic health records, hospital recordsEditorialEditorialeditorial20212021-09-3010.34067/KID.00043920212641-76502021-09-30T05:30:25-07:002021-09-30Kidney360Editorial2913991401
- The Evaluation of Kidney Function in Living Kidney Donor CandidatesLiving kidney donors incur a small increased risk of ESKD, of which predonation GFR is an important determinant. As a result, kidney function assessment is central to the donor candidate evaluation and selection process. This article reviews the different methods of GFR assessment, including eGFR, creatinine clearance, and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. eGFR obtained using the 2009 CKD Epidemiology Collaboration equation that, although the best of estimating estimations, tends to underestimate levels and has limited accuracy, especially near-normal GFR values. In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of the evaluation. Measured GFR is considered the gold standard, although there is some variation in performance characteristics, depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion. GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria. The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cutoff of <60 ml/min per 1.73m2 for exclusion and ≥90 ml/min per 1.73m2 for acceptance, and determination of candidacy with intermediate GFR on the basis of long-term ESKD risk. However, several concerns exist for this strategy, including inappropriate acceptance of younger candidates due to underestimation of risk, and exclusion of older candidates whose kidney function is in fact appropriate for age. The role of cystatin C and other newer biomarkers, and data on the effect of predonation GFR on not just ESKD risk, but also advanced CKD risk and cardiovascular outcomes are needed.10.34067/KID.0003052021Thu, 01 Jul 2021 09:38:52 GMT-07:00The Evaluation of Kidney Function in Living Kidney Donor CandidatesLiving kidney donors incur a small increased risk of ESKD, of which predonation GFR is an important determinant. As a result, kidney function assessment is central to the donor candidate evaluation and selection process. This article reviews the different methods of GFR assessment, including eGFR, creatinine clearance, and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. eGFR obtained using the 2009 CKD Epidemiology Collaboration equation that, although the best of estimating estimations, tends to underestimate levels and has limited accuracy, especially near-normal GFR values. In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of the evaluation. Measured GFR is considered the gold standard, although there is some variation in performance characteristics, depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion. GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria. The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cutoff of <60 ml/min per 1.73m2 for exclusion and ≥90 ml/min per 1.73m2 for acceptance, and determination of candidacy with intermediate GFR on the basis of long-term ESKD risk. However, several concerns exist for this strategy, including inappropriate acceptance of younger candidates due to underestimation of risk, and exclusion of older candidates whose kidney function is in fact appropriate for age. The role of cystatin C and other newer biomarkers, and data on the effect of predonation GFR on not just ESKD risk, but also advanced CKD risk and cardiovascular outcomes are needed.Garg, NeetikaPoggio, Emilio D.Mandelbrot, Didier2021-07-01T09:38:52-07:00doi:10.34067/KID.0003052021hwp:resource-id:kidney360;2/9/1523American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, CKD-EPI, creatinine clearance, GFR, kidney function, living kidney donor, measure GFRReview ArticleReview Articlereview-article20212021-09-3010.34067/KID.00030520212641-76502021-07-01T09:38:52-07:002021-09-30Kidney360Review Article2915231530
- Comparison of Patients with Hospital-Recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: A Nationwide Study in Denmark10.34067/KID.0000362021Thu, 03 Jun 2021 11:46:41 GMT-07:00Comparison of Patients with Hospital-Recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: A Nationwide Study in DenmarkVestergaard, Søren ViborgBirn, HenrikHansen, Anette TarpNørgaard, MetteNitsch, DorotheaChristiansen, Christian Fynbo2021-06-03T11:46:41-07:00doi:10.34067/KID.0000362021hwp:resource-id:kidney360;2/9/1482American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, albuminuria, algorithms, epidemiology, hospital records, hypoalbuminemia, nephrotic syndrome, proteinuriaOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-09-3010.34067/KID.00003620212641-76502021-06-03T11:46:41-07:002021-09-30Kidney360Original Investigation2914821490
- Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: COMMENTARY10.34067/KID.0001372021Fri, 09 Apr 2021 09:22:47 GMT-07:00Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: COMMENTARYMavrakanas, Thomas A.2021-04-09T09:22:47-07:00doi:10.34067/KID.0001372021hwp:resource-id:kidney360;2/9/1412American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, anticoagulation, apixaban, atrial fibrillation, bleeding, hemodialysis, rivaroxaban, stroke, warfarinModerator CommentaryModerator Commentaryarticle-commentary20212021-09-3010.34067/KID.00013720212641-76502021-04-09T09:22:47-07:002021-09-30Kidney360Moderator Commentary2914121414
- Unilateral Pleural Effusion in a Hemodialysis Patient10.34067/KID.0001592021Thu, 30 Sep 2021 05:30:25 GMT-07:00Unilateral Pleural Effusion in a Hemodialysis PatientSpithoven, Edwin M.Abrahams, Alferso C.2021-09-30T05:30:25-07:00doi:10.34067/KID.0001592021hwp:resource-id:kidney360;2/9/1542American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, pleural effusion, renal dialysis, thrombus, vascular accessClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-09-3010.34067/KID.00015920212641-76502021-09-30T05:30:25-07:002021-09-30Kidney360Clinical Images in Nephrology and Dialysis2915421543
- Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia10.34067/KID.0000992021Wed, 30 Jun 2021 11:45:12 GMT-07:00Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype PreeclampsiaAlrahmani, LayanGonzalez Suarez, Maria L.Cousin, Margot A.Moyer, Ann M.Willrich, Maria Alice V.White, Wendy M.Wick, Myra J.Tostrud, Linda J.Narang, KavitaGarovic, Vesna D.2021-06-30T11:45:12-07:00doi:10.34067/KID.0000992021hwp:resource-id:kidney360;2/9/1463American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360genetics, allele variant, basic science, complement alternative pathway, eclampsia, HELLP syndrome, molecular genetics, next generation sequencing, preeclampsia, pregnancy, thrombotic microangiopathyOriginal InvestigationGeneticsOriginal InvestigationGeneticsresearch-article20212021-09-3010.34067/KID.00009920212641-76502021-06-30T11:45:12-07:002021-09-30Kidney360Original Investigation2914631472
- Collagen Type III and VI Remodeling Biomarkers Are Associated with Kidney Fibrosis in Lupus Nephritis10.34067/KID.0001132021Fri, 18 Jun 2021 11:50:07 GMT-07:00Collagen Type III and VI Remodeling Biomarkers Are Associated with Kidney Fibrosis in Lupus NephritisGenovese, FedericaAkhgar, AhmadLim, Sung SamFarris, Alton B.Battle, MonicaCobb, JasonSinibaldi, DominicKarsdal, Morten A.White, Wendy I.2021-06-18T11:50:07-07:00doi:10.34067/KID.0001132021hwp:resource-id:kidney360;2/9/1473American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, basic science, biomarkers, collagen, collagen type III, endotrophin, extracellular matrix, fibrosis, lupus nephritisOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-09-3010.34067/KID.00011320212641-76502021-06-18T11:50:07-07:002021-09-30Kidney360Original Investigation2914731481
- Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per Day10.34067/KID.0004402021Thu, 08 Jul 2021 10:20:23 GMT-07:00Osmotic Demyelination Syndrome following Correction of Hyponatremia by ≤10 mEq/L per DayTandukar, SrijanSterns, Richard H.Rondon-Berrios, Helbert2021-07-08T10:20:23-07:00doi:10.34067/KID.0004402021hwp:resource-id:kidney360;2/9/1415American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, central pontine myelinolysis, demyelinating diseases, hyponatremia, osmosis, osmotic demyelination syndrome, rate of correctionOriginal InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20212021-09-3010.34067/KID.00044020212641-76502021-07-08T10:20:23-07:002021-09-30Kidney360Original Investigation2914151423
- Post-Discharge Mortality and Rehospitalization among Participants in a Comprehensive Acute Kidney Injury Rehabilitation Program10.34067/KID.0003672021Tue, 13 Jul 2021 11:42:24 GMT-07:00Post-Discharge Mortality and Rehospitalization among Participants in a Comprehensive Acute Kidney Injury Rehabilitation ProgramSingh, GurmukteshwarHu, YiruiJacobs, StevenBrown, JasonGeorge, JasonBermudez, MariaHo, KevinGreen, Jamie A.Kirchner, H. LesterChang, Alex R.2021-07-13T11:42:24-07:00doi:10.34067/KID.0003672021hwp:resource-id:kidney360;2/9/1424American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, acute renal failure, aftercare, economic impact, epidemiology and outcomes, hospitalization, mortality, mortality risk, renal failure, survivalOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-09-3010.34067/KID.00036720212641-76502021-07-13T11:42:24-07:002021-09-30Kidney360Original Investigation2914241433
- Novel Uses of Ultrasound to Assess Kidney Mechanical PropertiesUltrasound is a key imaging tool for evaluating the kidney. Over the last two decades, methods to measure the mechanical properties of soft tissues have been developed and used in clinical practice, although use in the kidney has not been as widespread as for other applications. The mechanical properties of the kidney are determined by the structure and composition of the renal parenchyma and perfusion characteristics. Because pathologic processes change these factors, the mechanical properties change and can be used for diagnostic purposes and for monitoring treatment or disease progression. Ultrasound-based elastography methods for evaluating the mechanical properties of the kidney use focused ultrasound beams to perturb the kidney and then high frame-rate ultrasound methods are used to measure the resulting motion. The motion is analyzed to estimate the mechanical properties. This review will describe the principles of these methods and discuss several seminal studies related to characterizing the kidney. Additionally, an overview of the clinical use of elastography methods in native and kidney allografts will be provided. Perspectives on future developments and uses of elastography technology along with other complementary ultrasound imaging modalities will be provided.10.34067/KID.0002942021Thu, 01 Jul 2021 09:38:52 GMT-07:00Novel Uses of Ultrasound to Assess Kidney Mechanical PropertiesUltrasound is a key imaging tool for evaluating the kidney. Over the last two decades, methods to measure the mechanical properties of soft tissues have been developed and used in clinical practice, although use in the kidney has not been as widespread as for other applications. The mechanical properties of the kidney are determined by the structure and composition of the renal parenchyma and perfusion characteristics. Because pathologic processes change these factors, the mechanical properties change and can be used for diagnostic purposes and for monitoring treatment or disease progression. Ultrasound-based elastography methods for evaluating the mechanical properties of the kidney use focused ultrasound beams to perturb the kidney and then high frame-rate ultrasound methods are used to measure the resulting motion. The motion is analyzed to estimate the mechanical properties. This review will describe the principles of these methods and discuss several seminal studies related to characterizing the kidney. Additionally, an overview of the clinical use of elastography methods in native and kidney allografts will be provided. Perspectives on future developments and uses of elastography technology along with other complementary ultrasound imaging modalities will be provided.Urban, Matthew W.Rule, Andrew D.Atwell, Thomas D.Chen, Shigao2021-07-01T09:38:52-07:00doi:10.34067/KID.0002942021hwp:resource-id:kidney360;2/9/1531American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, basic science, elasticity, shear wave, ultrasound, viscoelasticityReview ArticlesReview Articlesreview-article20212021-09-3010.34067/KID.00029420212641-76502021-07-01T09:38:52-07:002021-09-30Kidney360Review Articles2915311539
- Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: CON10.34067/KID.0006602020Fri, 09 Apr 2021 09:22:47 GMT-07:00Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: CONLidgard, BenjaminBansal, Nisha2021-04-09T09:22:47-07:00doi:10.34067/KID.0006602020hwp:resource-id:kidney360;2/9/1409American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, anticoagulants, atrial fibrillation, blood coagulation, ESKD, hemodialysisDebates in NephrologyDebates in Nephrologyresearch-article20212021-09-3010.34067/KID.00066020202641-76502021-04-09T09:22:47-07:002021-09-30Kidney360Debates in Nephrology2914091411
- An Unexpected Kidney Biopsy Finding in a Patient with Newly Diagnosed SLE10.34067/KID.0003192021Thu, 30 Sep 2021 05:30:25 GMT-07:00An Unexpected Kidney Biopsy Finding in a Patient with Newly Diagnosed SLECrane, Clarkson R.Shayan, KatayoonIngulli, Elizabeth2021-09-30T05:30:25-07:00doi:10.34067/KID.0003192021hwp:resource-id:kidney360;2/9/1544American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, biophysical phenomena, children, IgG4 related disease, immunoglobulin G, immunologic tests, lupus erythematosus, systemic, lupus nephritis, membranous glomerulonephritisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-09-3010.34067/KID.00031920212641-76502021-09-30T05:30:25-07:002021-09-30Kidney360Clinical Images in Nephrology and Dialysis2915441545
- An Unusual Cause of Peritoneal Dialysis Catheter Dysfunction10.34067/KID.0001762021Thu, 30 Sep 2021 05:30:25 GMT-07:00An Unusual Cause of Peritoneal Dialysis Catheter DysfunctionSundararajan, AnushaDahl, Neera K.Latich, Igor2021-09-30T05:30:25-07:00doi:10.34067/KID.0001762021hwp:resource-id:kidney360;2/9/1540American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, catheter dysfunction, catheterization, neurogenic bladder, peritoneal dialysis, urinary retentionClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-09-3010.34067/KID.00017620212641-76502021-09-30T05:30:25-07:002021-09-30Kidney360Clinical Images in Nephrology and Dialysis2915401541
- SARS-CoV-2 Vaccination: The Time Is Now10.34067/KID.0005352021Thu, 30 Sep 2021 05:30:25 GMT-07:00SARS-CoV-2 Vaccination: The Time Is NowWiegel, Joshua J.2021-09-30T05:30:25-07:00doi:10.34067/KID.0005352021hwp:resource-id:kidney360;2/9/1402American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, booster, COVID-19, COVID-19 vaccines, SARS-CoV-2, transplantation, vaccinationEditorialEditorialeditorial20212021-09-3010.34067/KID.00053520212641-76502021-09-30T05:30:25-07:002021-09-30Kidney360Editorial2914021404
- Impaired Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients and in Kidney Transplant Recipients10.34067/KID.0003512021Tue, 13 Jul 2021 06:19:55 GMT-07:00Impaired Immune Response to SARS-CoV-2 Vaccination in Dialysis Patients and in Kidney Transplant RecipientsKolb, ThiloFischer, SvenjaMüller, LisaLübke, NadineHillebrandt, JonasAndrée, MarcelSchmitz, MichaelSchmidt, ClaudiaKüçükköylü, SeherKoster, LynnKittel, MargaretheWeiland, LeaDreyling, Karl W.Hetzel, GerdAdams, OrtwinSchaal, HeinerIvens, KatrinRump, Lars C.Timm, JörgStegbauer, Johannes2021-07-13T06:19:55-07:00doi:10.34067/KID.0003512021hwp:resource-id:kidney360;2/9/1491American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, clinical immunology, COVID-19, humoral immune response, immunity, kidney failure, kidney transplantation, renal insufficiency, SARS-CoV-2 specific antibody, vaccination, virologyOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-09-3010.34067/KID.00035120212641-76502021-07-13T06:19:55-07:002021-09-30Kidney360Original Investigation2914911498
- Assessment of Acid-Base Status10.2215/CJN.02760221Fri, 04 Jun 2021 11:54:31 GMT-07:00Assessment of Acid-Base StatusKraut, Jeffrey A.Raphael, Kalani L.2021-06-04T11:54:31-07:00doi:10.2215/CJN.02760221hwp:resource-id:clinjasn;16/9/1429American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyserum bicarbonatePerspectivesPerspectivesresearch-article20212021-09-01September 202110.2215/CJN.027602211555-90411555-905X2021-06-04T11:54:31-07:002021-09Clinical Journal of the American Society of NephrologyPerspectives16914291431
- Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell Transplantation10.2215/CJN.19801220Wed, 16 Jun 2021 10:53:39 GMT-07:00Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell TransplantationAbramson, Matthew H.Gutgarts, VictoriaZheng, JuntingMaloy, Molly A.Ruiz, Josel D.Scordo, MichaelJaimes, Edgar A.Sathick, Insara Jaffer2021-06-16T10:53:39-07:00doi:10.2215/CJN.19801220hwp:resource-id:clinjasn;16/9/1318American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyonconephrology, bone marrow transplant, stem cell transplant, acute kidney injury, chronic kidney disease, graft vs host disease, gvhd, hemodialysis, drug nephrotoxicity, thrombotic microangiopathyOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-09-01September 202110.2215/CJN.198012201555-90411555-905X2021-06-16T10:53:39-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16913181327
- Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance10.2215/CJN.13100820Wed, 07 Jul 2021 11:09:02 GMT-07:00Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression AvoidanceKaufman, Dixon B.Woodle, E. SteveShields, Adele RikeLeone, JohnMatas, ArthurWiseman, AlexanderWest-Thielke, PatriciaSa, TingKing, Eileen C.Alloway, Rita R.,,Brailey, PaulDorst, TonyaGirnita, AlinNaciff-Stahl, AmandaThomas, JessicaTremblay, SimonSchneider, KristiStucke, AlyssaFernandez, Deborah A.Farnsworth, MaryCicerchi, JanisCline, AnnBruno, KellyLipscombe, JessiRohan, Jennifer2021-07-07T11:09:02-07:00doi:10.2215/CJN.13100820hwp:resource-id:clinjasn;16/9/1387American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, immunosuppression, transplant outcomesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-09-01September 202110.2215/CJN.131008201555-90411555-905X2021-07-07T11:09:02-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16913871397
- Evaluation of PROMIS Preference Scoring System (PROPr) in Patients Undergoing Hemodialysis or Kidney Transplant10.2215/CJN.01880221Fri, 16 Jul 2021 10:13:47 GMT-07:00Evaluation of PROMIS Preference Scoring System (PROPr) in Patients Undergoing Hemodialysis or Kidney TransplantZhang, JingDewitt, BarryTang, EvanBreitner, DanielSaqib, MohammedLi, DanSiddiqui, RabailEdwards, NathanielPeipert, John DevinHays, Ron D.Hanmer, JanelMucsi, Istvan2021-07-16T10:13:47-07:00doi:10.2215/CJN.01880221hwp:resource-id:clinjasn;16/9/1328American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPROMIS, PROPr, dialysis, kidney transplantation, patient-reported outcomes, health utility, SF-6D, EQ-5D-5L, kidney failureOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-09-01September 202110.2215/CJN.018802211555-90411555-905X2021-07-16T10:13:47-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16991328130113361302
- Reappraisal of Hemodiafiltration for Managing Uremic Complications10.2215/CJN.07760621Wed, 08 Sep 2021 05:37:36 GMT-07:00Reappraisal of Hemodiafiltration for Managing Uremic ComplicationsGrooteman, MurielNubé, Menso2021-09-08T05:37:36-07:00doi:10.2215/CJN.07760621hwp:resource-id:clinjasn;16/9/1303American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodiafiltration, neuropathy, hemodialysis, survivalEditorialsEditorialseditorial20212021-09-01September 202110.2215/CJN.077606211555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyEditorials16991303136513051375
- Fatigue in CKDFatigue is a commonly reported and debilitating symptom among patients with CKD, yet little is known about its epidemiology, pathogenesis, and treatment. Various measurement tools have been used in published studies to identify and quantify fatigue. These include several single-item measures embedded in longer questionnaires for assessing depression, quality of life, or symptom burden in patients with kidney disease. Approximately 70% of patients with CKD report fatigue, with up to 25% reporting severe symptoms. Patient-reported fatigue is associated with death, dialysis initiation, and hospitalization among individuals with CKD. The pathophysiology is multifactorial and likely includes decreased oxygen delivery and increased reliance on anaerobic metabolism, thus generating lactic acidosis in response to exertion; the effects of chronic metabolic acidosis and hyperphosphatemia on skeletal muscle myocytes; protein-energy wasting and sarcopenia; and depression. Physical activity has been shown to improve fatigue in some small but promising trials, and so should be recommended, given the additional benefits of exercise. Targeting higher hemoglobin levels with erythropoiesis-stimulating agents may improve fatigue, but potential adverse cardiovascular effects preclude their use to solely treat fatigue without the presence of another indication. Current guidelines recommend cautious individualization of hemoglobin targets for those at low cardiovascular risk who still experience fatigue or functional limitation despite a hemoglobin level of 10 g/dl. Sodium bicarbonate supplementation for the treatment of metabolic acidosis may also improve functional status. Selective serotonin reuptake inhibitors have not been consistently shown to improve fatigue in patients with kidney disease, but an ongoing trial will evaluate the effect of alternative antidepressant drug and behavioral activation therapy on fatigue in patients with CKD. Overall, more research is needed to further clarify underlying mechanisms of fatigue and identify effective, targeted treatments for patients with CKD.10.2215/CJN.19891220Thu, 15 Apr 2021 06:45:48 GMT-07:00Fatigue in CKDFatigue is a commonly reported and debilitating symptom among patients with CKD, yet little is known about its epidemiology, pathogenesis, and treatment. Various measurement tools have been used in published studies to identify and quantify fatigue. These include several single-item measures embedded in longer questionnaires for assessing depression, quality of life, or symptom burden in patients with kidney disease. Approximately 70% of patients with CKD report fatigue, with up to 25% reporting severe symptoms. Patient-reported fatigue is associated with death, dialysis initiation, and hospitalization among individuals with CKD. The pathophysiology is multifactorial and likely includes decreased oxygen delivery and increased reliance on anaerobic metabolism, thus generating lactic acidosis in response to exertion; the effects of chronic metabolic acidosis and hyperphosphatemia on skeletal muscle myocytes; protein-energy wasting and sarcopenia; and depression. Physical activity has been shown to improve fatigue in some small but promising trials, and so should be recommended, given the additional benefits of exercise. Targeting higher hemoglobin levels with erythropoiesis-stimulating agents may improve fatigue, but potential adverse cardiovascular effects preclude their use to solely treat fatigue without the presence of another indication. Current guidelines recommend cautious individualization of hemoglobin targets for those at low cardiovascular risk who still experience fatigue or functional limitation despite a hemoglobin level of 10 g/dl. Sodium bicarbonate supplementation for the treatment of metabolic acidosis may also improve functional status. Selective serotonin reuptake inhibitors have not been consistently shown to improve fatigue in patients with kidney disease, but an ongoing trial will evaluate the effect of alternative antidepressant drug and behavioral activation therapy on fatigue in patients with CKD. Overall, more research is needed to further clarify underlying mechanisms of fatigue and identify effective, targeted treatments for patients with CKD.Gregg, L. ParkerBossola, MaurizioOstrosky-Frid, MauricioHedayati, S. Susan2021-04-15T06:45:48-07:00doi:10.2215/CJN.19891220hwp:resource-id:clinjasn;16/9/1445American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfatigue, chronic kidney disease, sarcopenia, protein-energy wasting, depression, functional impairment, anemiaReviewReviewreview-article20212021-09-01September 202110.2215/CJN.198912201555-90411555-905X2021-04-15T06:45:48-07:002021-09Clinical Journal of the American Society of NephrologyReview16914451455
- Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical Presentation10.2215/CJN.17511120Wed, 08 Sep 2021 05:37:36 GMT-07:00Infection in Patients with Suspected Thrombotic Microangiopathy Based on Clinical PresentationThoreau, Benjaminvon Tokarski, FlorentBauvois, AdelineBayer, GuillaumeBarbet, ChristelleCloarec, SylvieMérieau, ElodieLachot, SébastienGarot, DenisBernard, LouisGyan, EmmanuelPerrotin, FranckPouplard, ClaireMaillot, FrançoisGatault, PhilippeSautenet, BénédicteRusch, EmmanuelFrémeaux-Bacchi, VéroniqueVigneau, CécileFakhouri, FadiHalimi, Jean-Michel2021-09-08T05:37:36-07:00doi:10.2215/CJN.17511120hwp:resource-id:clinjasn;16/9/1355American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, cytomegalovirus, acute kidney injury, clinical epidemiology, epidemiology and outcomes, hemolytic uremic syndrome, thrombotic microangiopathies, infectionsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-09-01September 202110.2215/CJN.175111201555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16913551364
- Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor–Associated Adverse Events10.2215/CJN.00920121Fri, 09 Jul 2021 06:46:32 GMT-07:00Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor–Associated Adverse EventsAdam, Benjamin A.Murakami, NaokaReid, GraemeDu, KatieJasim, RuqayaBoils, Christie L.Bu, LihongHill, Peter D.Murray, Allan G.Renaudin, KarineRoufosse, CandiceWeins, AstridWen, KevinRiella, Leonardo V.Mengel, Michael2021-07-09T06:46:32-07:00doi:10.2215/CJN.00920121hwp:resource-id:clinjasn;16/9/1376American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, drug nephrotoxicity, acute rejection, gene expression, histopathology, cancer, immune checkpoint inhibitors, gene expression profiling, allograftsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-09-01September 202110.2215/CJN.009201211555-90411555-905X2021-07-09T06:46:32-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16991376131513861317
- Changing Demographics of NIDDK-Funded Physician-Scientists Doing Kidney Research10.2215/CJN.02440221Wed, 14 Jul 2021 09:12:42 GMT-07:00Changing Demographics of NIDDK-Funded Physician-Scientists Doing Kidney ResearchAbood, Delaney C.King, Spencer A.Eaton, Douglas C.Wall, Susan M.2021-07-14T09:12:42-07:00doi:10.2215/CJN.02440221hwp:resource-id:clinjasn;16/9/1337American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyphysician scientist, renal research, National Institute of Diabetes and Digestive and Kidney Diseases, demographyOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-09-01September 202110.2215/CJN.024402211555-90411555-905X2021-07-14T09:12:42-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16991337131213441314
- Evolving Demographics of Nephrology Research Workforce in the United States10.2215/CJN.09950721Wed, 08 Sep 2021 05:37:36 GMT-07:00Evolving Demographics of Nephrology Research Workforce in the United StatesQuaggin, Susan E.Humphreys, Benjamin D.2021-09-08T05:37:36-07:00doi:10.2215/CJN.09950721hwp:resource-id:clinjasn;16/9/1312American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, workforce, diversityEditorialsEditorialseditorial20212021-09-01September 202110.2215/CJN.099507211555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyEditorials16991312133713141344
- Understanding and Overcoming the Challenges Related to Cardiovascular Trials Involving Patients with Kidney DiseaseCardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%–60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population.10.2215/CJN.17561120Fri, 23 Apr 2021 09:43:33 GMT-07:00Understanding and Overcoming the Challenges Related to Cardiovascular Trials Involving Patients with Kidney DiseaseCardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%–60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population.Ishida, Julie H.Chauhan, CynthiaGillespie, BarbaraGruchalla, KenMcCullough, Peter A.Quella, SusanRomero, AlainRossignol, PatrickWheeler, David C.Malley, Meaghan A.West, MelissaHerzog, Charles A.2021-04-23T09:43:33-07:00doi:10.2215/CJN.17561120hwp:resource-id:clinjasn;16/9/1435American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular, kidney disease, cardiorenal, cardiovascular trialsFeatureFeatureresearch-article20212021-09-01September 202110.2215/CJN.175611201555-90411555-905X2021-04-23T09:43:33-07:002021-09Clinical Journal of the American Society of NephrologyFeature16914351444
- Net Endogenous Acid Excretion and Kidney Allograft Outcomes10.2215/CJN.00780121Wed, 16 Jun 2021 10:53:39 GMT-07:00Net Endogenous Acid Excretion and Kidney Allograft OutcomesYeung, Stanley M.H.Gomes-Neto, Antonio W.Osté, Maryse C.J.van den Berg, ElseKootstra-Ros, Jenny E.Sanders, Jan Stephan F.Berger, Stefan P.Carrero, Juan JesusDe Borst, Martin H.Navis, Gerjan J.Bakker, Stephan J.L.2021-06-16T10:53:39-07:00doi:10.2215/CJN.00780121hwp:resource-id:clinjasn;16/9/1398American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, kidney transplantation, outcomes, transplant outcomes, chronic allograft failure, chronic metabolic acidosis, clinical epidemiology, dietary acid load, net endogenous acid productionOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-09-01September 202110.2215/CJN.007801211555-90411555-905X2021-06-16T10:53:39-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16991398130614061308
- Gene Expression Profiling in Kidney Transplant Recipients on Immune Checkpoint Inhibitors10.2215/CJN.09860721Wed, 08 Sep 2021 05:37:36 GMT-07:00Gene Expression Profiling in Kidney Transplant Recipients on Immune Checkpoint InhibitorsJethwani, PriyankaShirali, Anushree C.2021-09-08T05:37:36-07:00doi:10.2215/CJN.09860721hwp:resource-id:clinjasn;16/9/1315American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute allograft rejection, acute interstitial nephritis, kidney transplantation, immune checkpoint inhibitors, gene expression profilingEditorialsEditorialseditorial20212021-09-01September 202110.2215/CJN.098607211555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyEditorials16991315137613171386
- Ertugliflozin and Slope of Chronic eGFR10.2215/CJN.01130121Fri, 18 Jun 2021 10:59:27 GMT-07:00Ertugliflozin and Slope of Chronic eGFRCherney, David Z.I.Cosentino, FrancescoDagogo-Jack, SamuelMcGuire, Darren K.Pratley, RichardFrederich, RobertMaldonado, MarioLiu, Chih-ChinLiu, JiePong, AnnpeyCannon, Christopher P.,Pozzi, Jose MariaMaffei, LauraNardone, LucreciaSessa, HoracioBrasca, Daniela GarciaAizenberg, DiegoBaccaro, Claudia EmilceGelersztein, Elizabeth SilvanaRosario, Fabian Calella PedroLeon de la Fuente, Ricardode Lapertosa, Silvia GorbanMaldonado, NatachaCruciani, AdrianBartolacci, InesHasbani, EduardoFrechtel, GustavoPapini, Nelson RodriguezPereyra, AlejandroMontana, OscarZaidman, CesarMansilla, MariaAyres, BronteSimpson, RichardGlastras, SarahWilliam, MagedDavis, TimothyColquhoun, DavidProietto, JosephRoberts, AdamRoberts, AnthonyStuckey, BronwynWittert, GarySoldatos, GeorgiaVora, ParindKusljugic, ZumretaAvdagic, AzraDurak-Nalbantic, AzraIbrahimpasic, KanitaHorozic, BosankoSpuzic, MuhamedSoldat-Stankovic, ValentinaStevanovic, DraganKoco, DamirJatic, ZaimTerzic, IbrahimPotkonjak, Ljiljana MarkovicPrnjavorac, BesimRadanovic, AleksandarSalihbasic, MuhamedDimitrov, DimitarStoikov, AnastasDamyanova, VelichkaVasileva, DarinaKirilov, KirilLefterov, IvailoLyubenova, LyudmilaRaev, DimitarTsanova, VeskaMitkov, MitkoShumkova, RositsaKichukov, KostadinSimeonova-Nikolova, TatyanaEkoe, Jean-MariePandey, Shekhar A.Dumas, RichardWoo, VincentSaunders, KevinConway, JamesBreger, LaurieConstance, ChristianO'Mahony, MichaelPerron, PatriceGarceau, ClaudeCsanadi, MichaelBourgeois, RonaldSalter, TimothyFrechette, AndreDiaz, ArielRansom, ThomasSanchez-Vallejo, GregorioSilva, Sandra Isabel BarreraMendoza, Jose AcciniOrtiz, Luis GarciaLozno, Hernan Yupanquide Salazar, Dora MolinaArroyo, Julian CoronelOrozco Linares, Luis AlejandroLenis Rendon, Claudia PatriciaDarko, PocanicTusek, SreckoWeiss, Sonja SlosicSilvija, Canecki-VarzicVelimir, AltabasSidbela, ZukanovicCikac, TatjanaVucak, JasnaCenan, LjiljanaBoljkovac, ZrinkaMargetic, SreckoKranjcevic, KsenijaCop, RenataAdamkova, VeraPavlina, KyselovaWasserburger, BedrichHrdina, TomasSmolenakova, KaterinaKetevan, ChagunavaPagava, ZurabMamatsashvili, MerabBurnadze, KobaChumburidze, VakhtangLominadze, ZazaNikoleishvili, LaliKobulia, BondoKoberidze, NanaEmukhvari, NodarKipiani, ZviadMetreveli, DavidGlonti, SalomeGiorgadze, EleneShaburishvili, TamazChapidze, GulnaraGulua, JulietaGogorishvili, IrakliBerukashvili, EkaterinePetriashvili, ShalvaKurashvili, GiviElisaf, MosesBousboulas, StavrosTentolouris, NikolaosTsioufis, KonstantinosLymperi, SotiriaLuk, AndreaYiu, Kelvin Kai HangTsang, Chiu ChiYeung, Vincent Tok FaiLee, Alex Pui-WaiTan, Kathryn Choon BengWan Ma, Ronald ChingWudi, Krisztina BeatrixBujtor, ZoltanFeher, ZsuzsannaKoranyi, LaszloParagh, GyorgyVasas, SzilardPauker, ZsoltKesmarki, NoraTakacs, JanosNagy, LaszloSalamon, CsabaPapp, ZsuzsannaHajdu, CsabaAbramov, GalinaHussein, OsamahVishlitzky, VictorDicker, DrorDarawsha, MahmudItzhak, BaruchGavish, DovWainstein, JulioLewis, BasilKlainman, EliezerKatz, AmosElias, MazenNess-Abramof, RosaneHayek, TonyOrsi, EmanuelaLembo, GiuseppePiatti, PiermarcoConsoli, AgostinoBerti, SergioPugliese, GiuseppeDerosa, GiuseppePaolisso, GiuseppeLimone, Paolo PieroJang, Hak ChulLee, Moon-KyuKim, Nam HoonCha, Bong-SooPark, Kyong SooYoon, Kun HoAhn, Chul WooLee, Kwan WooBaik, Sei HyunPirags, ValdisPastare, SigitaKavaliauskiene, JurateAugusteniene, AudroneNavickas, AntanasUrbanavicius, VaidotasKavaliauskiene, RomaSirutaviciene, AusraLlamas Esperon, Guillermo AntonioMesa, Juan VillagordoaGarcia Hernandez, Pedro AlbertoCeballos, Rosa LunaSalinas, Carlos AguilarGalvez, Guillermo GonzalezMelendez-Mier, GuillermoOrozco, Raul AguilarCrijns, HarryHoogenberg, KlaasVoors-Pette, ChristineLunt, HelenScott, RussellBaker, JohnWilliams, MichaelKerr, Jane ElizabethDenopol, MarianPanelo, AraceliTirador, LouieAquitania, GraceRogelio, GregorioAmorado-Santos, FlorenceHabaluyas, RamoncitoRosa, Allyn SyPalomares, EllenEbo, GeraldineRomero, Chela MarieGladczak, JoannaHawryluk, JaroslawFranek, EdwardLukaszewicz, MonikaMadej-Dmochowska, AleksandraJeznach-Steinhagen, AnnaSokolowski, GrzegorzRuxer, JanKarczmarczyk, AgnieszkaKrzyzagorska, EwaWozniak, IwonaOlech-Cudzik, AnnaDwojak, MarekAnand, IzabelaStrojek, KrzysztofCzernecka, EwaAntkowiak-Piatyszek, KarolinaRozanska, AleksandraGadzinski, WaldemarMader, PiotrKuligowska-jakubowska, MonikaArciszewska, MalgorzataStankiewicz, AndrzejCypryk, KatarzynaWittek, AndrzejSawer-Szewczyk, JoannaPieniazek, AdamNegrisanu, GabrielaPletea, NoemiZaharie, DanielaPintilei, EllaCif, AdrianaDuma, LiviaSzilagyi, IosifHalmagyi, IldikoMorosanu, MagdalenaMunteanu, MirceaAlbota, AdrianPopescu, AlexandrinaEnculescu, Dan AntonHancu, NicolaeNafornita, ValericaCroitoru, LacramioaraSebestyen, Lucia LuanaPavlysh, ElenaNikolaev, KonstantinVishnevsky, AlexandrReshetko, OlgaKvitkova, LiudmilaBarbarash, OlgaRodionova, TatianaShaydyuk, OxanaErshova, OlgaChizhov, PetrBerns, SvetlanaRechkova, ElenaYakushin, SergeyZanozina, OlgaLukyanov, YuriVorobeva, ElenaZateyshchikov, DmitryVerbovaya, NellyBolshakova, OlgaKhrustalev, OlegStrongin, LeonidBondar, IrinaZalevskaya, AlsuFilippova, EkaterinaChumakova, GalinaRepin, AlexeyPanov, AlexeyZivkovic, Teodora BeljicPetakov, MilanSumarac-Dumanovic, MirjanaBrankovic, Georgina PudarKendereski, AleksandraStojic, StevoMacut, DjuroBabikova, JanaTeplanova, MiriamTomasova, LiviaMartinka, EmilLachova, BeataIvancova, GabrielaRociakova, JanaSchroner, ZbynekDonicova, VieraIlavska, AdrianaRaslova, KatarinaAfrica, SouthDistiller, LawrenceSiebert, HeidiBadat, AyshaBlignaut, SuzanneSarvan, MahomedGovender, ThirumaniGani, MashraNortje, HendrikMookadam, MohamedNaiker, Puvanesveride Jong, DouweVan Zyl, LouisSeeber, MaryUrbach-Bolus, DorotheaBayat, JunaidBoyd, Warrendu Toit, MargarethaPunt, ZeldaArnold, SusanVan Dyk, ChristoRobertson, Leslie IvanKotze, Hester JohannaAnders, LutsMartin, LundvallCarl-Johan, LindholmBengt-Olov, TengmarkDan, CuriacPeter, BossonPekka, KoskinenHajimirsadeghi, AliHuang, Chen-LingJiang, Ju-YingHsia, Te- LinUeng, Kwo-ChangYang, Wei-ShiungLu, Yung-ChuanYang, Chwen-YiSheu, Wayne Huey-HerngChiang, Chern-EnYeh, Hung-ISuwanwalaikorn, SompongseKosachunhanun, NatapongSritippayawan, SuchaiTejavanija, SirakarnSilaruks, SongkwanAraz, MustafaSari, RamazanBerker, Dilek SensozArslan, Muyesser SaykiGodlevska, OlgaChopey, IvanTeliatnikova, ZinaidaKuskalo, PetroAbrahamovych, OrestMankovskyi, BorysFushtey, IvanMyshanych, GalynaTykhonova, SusannaTseluyko, ViraKoval, OlenaParkhomenko, OleksandrProkhorov, OleksandrVayda, MyroslavaMartymianova, LarysaZharinova, ViktoriiaPrystupa, LyudmylaPererva, LarysaKovalov, OleksandrSokolova, LyubovBotsyurko, VolodymyrMaslyanko, VitaliyVlasenko, MarynaKhomazyuk, TetyanaKulyk, AnnaSynenko, VolodymyrKarpenko, OleksandrMostovoy, YuriyGyrina, OlgaDolzhenko, MarynaDonets, OleksandraSorokina, InnaMalynovsky, YaroslavLysunets, OlenaPetrovskyy, RomanPanina, SvitlanaAvornyo, AnthonyEyre, SusannahRyan, JohnCardwell, GlennRobinson, AnthonyClark, RebeccaIssa, BasilWeeraratne, DevindaMcCrimmon, RoryJones, ThomasPhilip, SamBeboso, RonnieDavies, MelanieKyriakidou, ChristinaSaxena, ManishThomas, HawysGowda, MadhuArif, ImroziaOyesile, BabatundeCecil, JohnBrunskill, Jonathan Mark EdwinAkinboboye, OlakunleAkright, LauraArora, ChanderBall, EricBenjamin, SabrinaBudoff, MatthewCathcart, HaroldDaboul, NizarDenker, PaulGarner, AndrewJabbour, SergeJaffrani, NaseemJeanfreau, RobertKnutson, ThomasLillestol, MichaelMcNeil, DonaldNakhle, SamerRandall, WilliamMallepalli, JyothiSchmidt, JaySerje, JorgeShoemaker, JamesStorey, DanielWarner, AlbertaPimentel, SeverinoQuintero, LuisGalvez, JuanBernard, DavidCruz, HumbertoO'Donnell, PhilipThawani, HemantSorial, EhabSchwartzbard, ArthurAgaiby, JohnGarcia, BernardCone, ClancyDoshi, AnkurIranmanesh, AliLingvay, IldikoSmith, KimberlyMcLean, BarryNeutel, JoelOdugbesan, AdeniyiSligh, TeresaLesh, KurtRohr, KathrynAjani, DilawarDaniel, JeromeCornett, GeorgeDykstra, GaryMahal, SharanAdams, MichaelRamstad, DavidArif, AhmedMartin, EarlSastre, RamonSrivastava, SunnyFeld, LawrenceBush, KelvinShah, VinayKonigsberg, SarahAllaw, MohammedKelly, RichardMacGillivray, BrianMcGuire, MichaelWeinstein, DebraBudhraja, MadhusudanTahirkheli, NaeemBinker, JosefaBernstein, MarcAndrawis, NabilAbdullah, ShuaibChristensen, TomKhan, MisalEl Shahawy, MahfouzTripathy, DevjitRanadive, NandkishoreGrena, PaulVillafuerte, BettyCook, CharlesBautista, JoseMarar, IsamKaunzinger, ChristianBittar, NevilleFrias, JuanDavit, RajeshBays, HaroldCohen, RobertGarvey, WilliamSmith, StephenRuiz, Jose-LuisHartman, AaronDiener, JamesChochinov, RonaldHunter, JohnAronoff, StephenReed, LarryEvans, JohnAckermann, JeremyHaaksma, JamesTorres-Consuegra, AurelioKhan, JalilYousuf, KabirBermudez, LidiaLumicao, BenjaminOlmeda, Jorge TorresKessler, EvanWinnie, MichaelLending, RobertRazzaque, NaveedMcCartney, MichaelMunoz, FranciscoBuynak, RobertAbles, Lilia RodriguezMakam, SashiLozano, JosefinaPaez, HenryGore, AshwiniAl-Karadsheh, AmerMasri, BassemGorrela, SushmaAl-Amin, Jessie LouiseAlani, FirasHaffizulla, JasonHsieh, RonHernandez, Luis CastilloTurner, MerleFrench, WilliamJetty, PreethamSheikh-Ali, MaeLeggett, RichardPerlman, RichardGoldstein, GaryOsea, Edgardo A.Bartkowiak, Anthony JamesGimness, Michael PaulHiggins, Alexander JohnKhan, Sohail MohyuddinRahimi, Ali RShah, Anil VallabhdasLillo, Joseph LeonardHartman, Israel AlejandroWhitney, Edwin J.Johnston, Janice G.Juarez, Mario R.Perley, Michael J.Kahn, Brian HowardAmine, Maged A.Pace, Michael AnthonyPeters, Shirin SabinaHidalgo, Horacio AugustoKrichmar, PerrySinha, Rabi Ranjan2021-06-18T10:59:27-07:00doi:10.2215/CJN.01130121hwp:resource-id:clinjasn;16/9/1345American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal protection, renal function decline, glomerular filtration rate, diabetic nephropathy, type 2 diabetes mellitus, clinical trial, sodium-glucose cotransporter 2 inhibitorOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20212021-09-01September 202110.2215/CJN.011301211555-90411555-905X2021-06-18T10:59:27-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16991345130913541311
- The RALES Legacy and Finerenone Use on CKD Patients10.2215/CJN.02150221Fri, 06 Aug 2021 09:21:35 GMT-07:00The RALES Legacy and Finerenone Use on CKD PatientsMoura-Neto, José A.Ronco, Claudio2021-08-06T09:21:35-07:00doi:10.2215/CJN.02150221hwp:resource-id:clinjasn;16/9/1432American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic kidney failure, aldosterone, randomized controlled trialsPerspectivesPerspectivesresearch-article20212021-09-01September 202110.2215/CJN.021502211555-90411555-905X2021-08-06T09:21:35-07:002021-09Clinical Journal of the American Society of NephrologyPerspectives16914321434
- Effect of Hemodiafiltration on the Progression of Neuropathy with Kidney Failure10.2215/CJN.17151120Wed, 07 Jul 2021 11:09:02 GMT-07:00Effect of Hemodiafiltration on the Progression of Neuropathy with Kidney FailureKang, AmyArnold, RiaGallagher, MartinSnelling, PaulGreen, JulianneFernando, MangaleeKiernan, Matthew C.Hand, SamanthaGrimley, KimBurman, JennyHeath, AnneRogers, KrisBhattacharya, AmritenduSmyth, BrendanBradbury, ThomasHawley, CarmelPerkovic, VladoKrishnan, Arun V.Jardine, Meg J.2021-07-07T11:09:02-07:00doi:10.2215/CJN.17151120hwp:resource-id:clinjasn;16/9/1365American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, randomized controlled trials, hemodiafiltration, neuropathy, chronic dialysis, chronic hemodialysis, clinical trial, dialysis, end-stage renal disease, uremic neuropathyOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-09-01September 202110.2215/CJN.171511201555-90411555-905X2021-07-07T11:09:02-07:002021-09Clinical Journal of the American Society of NephrologyOriginal Articles16991365130313751305
- Renal Denervation for the Treatment of Hypertension10.2215/CJN.03070221Thu, 03 Jun 2021 10:41:09 GMT-07:00Renal Denervation for the Treatment of HypertensionSarathy, HariniCohen, Jordana B.2021-06-03T10:41:09-07:00doi:10.2215/CJN.03070221hwp:resource-id:clinjasn;16/9/1426American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, blood pressure, renal denervation, sympathetic activity, medication intolerance, blood pressure management, medication nonadherence, treatment-resistant hypertensionPerspectivesPerspectivesresearch-article20212021-09-01September 202110.2215/CJN.030702211555-90411555-905X2021-06-03T10:41:09-07:002021-09Clinical Journal of the American Society of NephrologyPerspectives16914261428
- An Apple a Day Keeps Dialysis Away10.2215/CJN.09610721Wed, 08 Sep 2021 05:37:36 GMT-07:00An Apple a Day Keeps Dialysis AwayStenson, Erin K.Kendrick, Jessica2021-09-08T05:37:36-07:00doi:10.2215/CJN.09610721hwp:resource-id:clinjasn;16/9/1306American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, dietary acid load, chronic metabolic acidosisEditorialsEditorialseditorial20212021-09-01September 202110.2215/CJN.096107211555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyEditorials16991306139813081406
- Are All SGLT2 Inhibitors Created Equal?10.2215/CJN.09720721Wed, 08 Sep 2021 05:37:36 GMT-07:00Are All SGLT2 Inhibitors Created Equal?Gregg, L. ParkerNavaneethan, Sankar D.2021-09-08T05:37:36-07:00doi:10.2215/CJN.09720721hwp:resource-id:clinjasn;16/9/1309American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyeGFR, kidney disease, SGLT2 inhibitors, sodium-glucose cotransporter-2EditorialsEditorialseditorial20212021-09-01September 202110.2215/CJN.097207211555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyEditorials16991309134513111354
- Patiromer to Enable Spironolactone in Patients with Resistant Hypertension and CKD (AMBER)10.2215/CJN.02890221Wed, 23 Jun 2021 10:54:11 GMT-07:00Patiromer to Enable Spironolactone in Patients with Resistant Hypertension and CKD (AMBER)Agarwal, RajivRossignol, PatrickMayo, Martha R.Conrad, AnsgarArthur, SusanWilliams, BryanWhite, William B.2021-06-23T10:54:11-07:00doi:10.2215/CJN.02890221hwp:resource-id:clinjasn;16/9/1407American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, patiromer, resistant hypertension, spironolactone, diabetes, polymers, chronic renal insufficiency, hypertensionResearch LettersResearch Lettersresearch-article20212021-09-01September 202110.2215/CJN.028902211555-90411555-905X2021-06-23T10:54:11-07:002021-09Clinical Journal of the American Society of NephrologyResearch Letters16914071409
- COVID-19 among Adults Receiving Home versus In-Center Dialysis10.2215/CJN.04170321Fri, 04 Jun 2021 11:54:31 GMT-07:00COVID-19 among Adults Receiving Home versus In-Center DialysisPerl, JeffreyThomas, DonealTang, YiwenYeung, AngieIp, JaneOliver, Matthew J.Blake, Peter G.2021-06-04T11:54:31-07:00doi:10.2215/CJN.04170321hwp:resource-id:clinjasn;16/9/1410American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, hemodialysis, peritoneal dialysis, mortality risk, research design, cohort studiesResearch LettersResearch Lettersresearch-article20212021-09-01September 202110.2215/CJN.041703211555-90411555-905X2021-06-04T11:54:31-07:002021-09Clinical Journal of the American Society of NephrologyResearch Letters16914101412
- Patient Management When Returning to Dialysis after a Failed Kidney Transplant10.2215/CJN.19731220Thu, 15 Apr 2021 06:45:49 GMT-07:00Patient Management When Returning to Dialysis after a Failed Kidney TransplantMoist, Louise M.Gill, John S.2021-04-15T06:45:49-07:00doi:10.2215/CJN.19731220hwp:resource-id:clinjasn;16/9/1423American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, dialysis, failed transplantKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20212021-09-01September 202110.2215/CJN.197312201555-90411555-905X2021-04-15T06:45:49-07:002021-09Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire16914231425
- Developing Patient-Reported Outcome Measures that Can Improve Kidney Care10.2215/CJN.09800721Wed, 08 Sep 2021 05:37:36 GMT-07:00Developing Patient-Reported Outcome Measures that Can Improve Kidney CareHartwell, Lori2021-09-08T05:37:36-07:00doi:10.2215/CJN.09800721hwp:resource-id:clinjasn;16/9/1301American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-reported outcome measures, kidney carePatient VoicePatient Voiceresearch-article20212021-09-01September 202110.2215/CJN.098007211555-90411555-905X2021-09-08T05:37:36-07:002021-09Clinical Journal of the American Society of NephrologyPatient Voice16991301132813021336
- Beyond the Biopsy: Monitoring Immune Status in Kidney RecipientsImproved long-term kidney allograft survival is largely related to better outcomes at 12 months, in association with declining acute rejection rates and more efficacious immunosuppression. Finding the right balance between under- and overimmunosuppression or rejection versus immunosuppression toxicity remains one of transplant’s holy grails. In the absence of precise measures of immunosuppression burden, transplant clinicians rely on nonspecific, noninvasive tests and kidney allograft biopsy generally performed for cause. This review appraises recent advances of conventional monitoring strategies and critically examines the plethora of emerging tests utilizing tissue, urine, and blood samples to improve upon the diagnostic precision of allograft surveillance.10.2215/CJN.14840920Fri, 06 Aug 2021 09:21:35 GMT-07:00Beyond the Biopsy: Monitoring Immune Status in Kidney RecipientsImproved long-term kidney allograft survival is largely related to better outcomes at 12 months, in association with declining acute rejection rates and more efficacious immunosuppression. Finding the right balance between under- and overimmunosuppression or rejection versus immunosuppression toxicity remains one of transplant’s holy grails. In the absence of precise measures of immunosuppression burden, transplant clinicians rely on nonspecific, noninvasive tests and kidney allograft biopsy generally performed for cause. This review appraises recent advances of conventional monitoring strategies and critically examines the plethora of emerging tests utilizing tissue, urine, and blood samples to improve upon the diagnostic precision of allograft surveillance.Bloom, Roy D.Augustine, Joshua J.2021-08-06T09:21:35-07:00doi:10.2215/CJN.14840920hwp:resource-id:clinjasn;16/9/1413American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, transplant outcomes, molecular genetics, immunosuppression, biopsy, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-09-01September 202110.2215/CJN.148409201555-90411555-905X2021-08-06T09:21:35-07:002021-09Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges16914131422
- Authors’ Reply10.1681/ASN.2021060866Wed, 18 Aug 2021 05:20:49 GMT-07:00Authors’ ReplyDe Vriese, An S.2021-08-18T05:20:49-07:00doi:10.1681/ASN.2021060866hwp:resource-id:jnephrol;32/9/2390American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, hemodialysis, randomized controlled trials, renal transplantation, cardiovascular eventsLetters to the EditorLetters to the Editorletter20212021-09-01September 202110.1681/ASN.20210608661046-66731533-34502021-08-18T05:20:49-07:002021-09Journal of the American Society of NephrologyLetters to the Editor32996239023891474239123901483
- Self-Reported Medication Use and Urinary Drug Metabolites in the German Chronic Kidney Disease (GCKD) Study10.1681/ASN.2021010063Thu, 17 Jun 2021 07:41:25 GMT-07:00Self-Reported Medication Use and Urinary Drug Metabolites in the German Chronic Kidney Disease (GCKD) StudyKotsis, FruzsinaSchultheiss, Ulla T.Wuttke, MatthiasSchlosser, PascalMielke, JohannaBecker, Michael S.Oefner, Peter J.Karoly, Edward D.Mohney, Robert P.Eckardt, Kai-UweSekula, PeggyKöttgen, Anna,,Eckardt, Kai-UweMeiselbach, HeikeSchneider, Markus P.Schiffer, MarioProkosch, Hans-UlrichBärthlein, BarbaraBeck, AndreasReis, AndréEkici, Arif B.Becker, SusanneBecker-Grosspitsch, DinahAlberth-Schmidt, UlrikeHausknecht, BirgitWeigel, AnkeWalz, GerdKöttgen, AnnaSchultheiß, Ulla T.Kotsis, FruzsinaMeder, SimoneMitsch, ErnaReinhard, UrsulaFloege, JürgenSaritas, TurgaySchaeffner, ElkeBaid-Agrawal, SeemaTheisen, KerstinHaller, HermannMenne, JanZeier, MartinSommerer, ClaudiaTheilinger, JohannaWolf, GunterBusch, MartinPaul, RainerSitter, ThomasWanner, ChristophKrane, VeraBörner-Klein, AntjeBauer, BrittaKronenberg, FlorianRaschenberger, JuliaKollerits, BarbaraForer, LukasSchönherr, SebastianWeissensteiner, HansiOefner, PeterGronwald, WolframSchmid, MatthiasNadal, Jennifer2021-06-17T07:41:25-07:00doi:10.1681/ASN.2021010063hwp:resource-id:jnephrol;32/9/2315American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, urine metabolites, pharmacometabolomics, medication useClinical EpidemiologyClinical Epidemiologyresearch-article20212021-09-01September 202110.1681/ASN.20210100631046-66731533-34502021-06-17T07:41:25-07:002021-09Journal of the American Society of NephrologyClinical Epidemiology32923152329
- Novel Phenotypes for Acute Kidney Transplant Rejection Using Semi-Supervised Clustering10.1681/ASN.2021040572Mon, 16 Aug 2021 06:09:49 GMT-07:00Novel Phenotypes for Acute Kidney Transplant Rejection Using Semi-Supervised ClusteringMatas, Arthur J.Mannon, Roslyn B.Rush, DavidHelgeson, Erika2021-08-16T06:09:49-07:00doi:10.1681/ASN.2021040572hwp:resource-id:jnephrol;32/9/2387American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, kidney transplantation, pathologyLetters to the EditorLetters to the Editorletter20212021-09-01September 202110.1681/ASN.20210405721046-66731533-34502021-08-16T06:09:49-07:002021-09Journal of the American Society of NephrologyLetters to the Editor32995238723881084238823891096
- The Bloody Mystery of Glomerular Tuft Development10.1681/ASN.2021070900Tue, 31 Aug 2021 11:00:30 GMT-07:00The Bloody Mystery of Glomerular Tuft DevelopmentMarciano, Denise K.2021-08-31T11:00:30-07:00doi:10.1681/ASN.2021070900hwp:resource-id:jnephrol;32/9/2104American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular endothelial cells, kidney development, cell signaling, vascular development, Slit, RoboUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-09-01September 202110.1681/ASN.20210709001046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyUp Front Matters32992104225521062272
- Sex-Dependent Effects of Nephron Ift88 Disruption on BP, Renal Function, and Cystogenesis10.1681/ASN.2020111571Thu, 27 May 2021 10:50:43 GMT-07:00Sex-Dependent Effects of Nephron Ift88 Disruption on BP, Renal Function, and CystogenesisHu, ChunyanLakshmipathi, JayalakshmiBinning, ElizabethHyndman, Kelly A.Stuart, DeborahKohan, Donald E.2021-05-27T10:50:43-07:00doi:10.1681/ASN.2020111571hwp:resource-id:jnephrol;32/9/2210American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephron, blood pressure, cystic kidney, sex, ift88, nitric oxideBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20201115711046-66731533-34502021-05-27T10:50:43-07:002021-09Journal of the American Society of NephrologyBasic Research32922102222
- Authors’ Reply10.1681/ASN.2021060796Mon, 16 Aug 2021 06:09:49 GMT-07:00Authors’ ReplyVaulet, ThibautThaunat, OlivierNaesens, Maarten2021-08-16T06:09:49-07:00doi:10.1681/ASN.2021060796hwp:resource-id:jnephrol;32/9/2388American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, histopathology, survival, rejection, acute allograft rejection, chronic allograft rejectionLetters to the EditorLetters to the Editorletter20212021-09-01September 202110.1681/ASN.20210607961046-66731533-34502021-08-16T06:09:49-07:002021-09Journal of the American Society of NephrologyLetters to the Editor32995238823871084238923881096
- Proteins Associated with Risk of Kidney Function Decline in the General Population10.1681/ASN.2020111607Tue, 31 Aug 2021 11:00:30 GMT-07:00Proteins Associated with Risk of Kidney Function Decline in the General PopulationGrams, Morgan E.Surapaneni, AdityaChen, JingshaZhou, LindaYu, ZhiDutta, DiptavoWelling, Paul A.Chatterjee, NilanjanZhang, JingningArking, Dan E.Chen, Teresa K.Rebholz, Casey M.Yu, BingSchlosser, PascalRhee, Eugene P.Ballantyne, Christie M.Boerwinkle, EricLutsey, Pamela L.Mosley, ThomasFeldman, Harold I.Dubin, Ruth F.Ganz, PeterLee, HongzheZheng, ZiheCoresh, Josef2021-08-31T11:00:30-07:00doi:10.1681/ASN.2020111607hwp:resource-id:jnephrol;32/9/2291American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyESKD, proteomicsClinical EpidemiologyClinical Epidemiologyresearch-article20212021-09-01September 202110.1681/ASN.20201116071046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyClinical Epidemiology32922912302
- Recent Approaches to Targeting Canonical NFκB Signaling in the Early Inflammatory Response to Renal IRIIschemia reperfusion injury (IRI) is the most common cause of in-hospital AKI and is associated with increased morbidity and mortality. IRI is associated with an early phase of inflammation primarily regulated by the canonical NFκB signaling pathway. Despite recent advances in our understanding of the pathogenesis of IRI, few therapeutic strategies have emerged. The purpose of this manuscript is to review interventions targeting NFκB after IRI.10.1681/ASN.2021010069Wed, 09 Jun 2021 10:56:04 GMT-07:00Recent Approaches to Targeting Canonical NFκB Signaling in the Early Inflammatory Response to Renal IRIIschemia reperfusion injury (IRI) is the most common cause of in-hospital AKI and is associated with increased morbidity and mortality. IRI is associated with an early phase of inflammation primarily regulated by the canonical NFκB signaling pathway. Despite recent advances in our understanding of the pathogenesis of IRI, few therapeutic strategies have emerged. The purpose of this manuscript is to review interventions targeting NFκB after IRI.Reid, ShelbyScholey, James W.2021-06-09T10:56:04-07:00doi:10.1681/ASN.2021010069hwp:resource-id:jnephrol;32/9/2117American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, NF kappaB, inflammationReviewsReviewsreview-article20212021-09-01September 202110.1681/ASN.20210100691046-66731533-34502021-06-09T10:56:04-07:002021-09Journal of the American Society of NephrologyReviews32921172124
- This Month's Highlights10.1681/ASN.2021070896Tue, 31 Aug 2021 11:00:30 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2021-08-31T11:00:30-07:00doi:10.1681/ASN.2021070896hwp:resource-id:jnephrol;32/9/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20212021-09-01September 202110.1681/ASN.20210708961046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyThis Month's Highlights329ii
- Addressing Transplant Candidacy When Evaluating Safety of Direct Oral Anticoagulant Agents in Patients on Hemodialysis10.1681/ASN.2021060814Wed, 18 Aug 2021 05:20:49 GMT-07:00Addressing Transplant Candidacy When Evaluating Safety of Direct Oral Anticoagulant Agents in Patients on HemodialysisHeher, EliotElias, Nahel2021-08-18T05:20:49-07:00doi:10.1681/ASN.2021060814hwp:resource-id:jnephrol;32/9/2389American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, anticoagulation, drug metabolism, renal dialysisLetters to the EditorLetters to the Editorletter20212021-09-01September 202110.1681/ASN.20210608141046-66731533-34502021-08-18T05:20:49-07:002021-09Journal of the American Society of NephrologyLetters to the Editor32996238923901474239023911483
- Comparative Health Care Spending for Dialysis: An Example of Public Cost Containment?10.1681/ASN.2021050694Mon, 16 Aug 2021 11:11:35 GMT-07:00Comparative Health Care Spending for Dialysis: An Example of Public Cost Containment?Tummalapalli, Sri LekhaAnderson, Gerard F.2021-08-16T11:11:35-07:00doi:10.1681/ASN.2021050694hwp:resource-id:jnephrol;32/9/2103American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhealth policyUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-09-01September 202110.1681/ASN.20210506941046-66731533-34502021-08-16T11:11:35-07:002021-09Journal of the American Society of NephrologyUp Front Matters32992103213721042139
- Prevalence Estimates of Predicted Pathogenic COL4A3–COL4A5 Variants in a Population Sequencing Database and Their Implications for Alport Syndrome10.1681/ASN.2020071065Fri, 18 Jun 2021 11:02:43 GMT-07:00Prevalence Estimates of Predicted Pathogenic COL4A3–COL4A5 Variants in a Population Sequencing Database and Their Implications for Alport SyndromeGibson, JoelFieldhouse, RachelChan, Melanie M.Y.Sadeghi-Alavijeh, OmidBurnett, LeslieIzzi, ValerioPersikov, Anton V.Gale, Daniel P.Storey, HelenSavige, Judy,2021-06-18T11:02:43-07:00doi:10.1681/ASN.2020071065hwp:resource-id:jnephrol;32/9/2273American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyAlport syndrome, thin basement membrane nephropathy, hematuria, COL4A5, COL4A3, COL4A4, collagen IV, genetic renal disease, glomerular basement membrane, Gly substitutionsBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20200710651046-66731533-34502021-06-18T11:02:43-07:002021-09Journal of the American Society of NephrologyBasic Research32922732290
- Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome10.1681/ASN.2020071074Mon, 21 Jun 2021 09:55:14 GMT-07:00Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and OutcomeBoudhabhay, IdrisDelestre, FlorenceCoutance, GuillaumeGnemmi, VivianeQuemeneur, ThomasVandenbussche, CyrilleLazareth, HeleneCanaud, GuillaumeTricot, LeilaGosset, ClémentHummel, AurélieTerrier, BenjaminRabant, Marionvan Daalen, Emma E.Wester Trejo, Maria A.C.Bajema, Ingeborg M.Karras, AlexandreDuong Van Huyen, Jean-Paul2021-06-21T09:55:14-07:00doi:10.1681/ASN.2020071074hwp:resource-id:jnephrol;32/9/2362American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, ANCA renal risk score, risk factors, small kidney arteries arteritis, histopathological classificationClinical ResearchClinical Researchresearch-article20212021-09-01September 202110.1681/ASN.20200710741046-66731533-34502021-06-21T09:55:14-07:002021-09Journal of the American Society of NephrologyClinical Research32911226236229744574581226237429754584591227
- High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients10.1681/ASN.2020121793Mon, 19 Jul 2021 11:44:34 GMT-07:00High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis PatientsPfau, AnjaErmer, TheresaCoca, Steven G.Tio, Maria ClarissaGenser, BerndReichel, MartinFinkelstein, Fredric O.März, WinfriedWanner, ChristophWaikar, Sushrut S.Eckardt, Kai-UweAronson, Peter S.Drechsler, ChristianeKnauf, Felix2021-07-19T11:44:34-07:00doi:10.1681/ASN.2020121793hwp:resource-id:jnephrol;32/9/2375American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyuremic toxins, oxalate, sudden cardiac death, cardiovascular disease, chronic hemodialysis, chronic kidney failureClinical ResearchClinical Researchresearch-article20212021-09-01September 202110.1681/ASN.20201217931046-66731533-34502021-07-19T11:44:34-07:002021-09Journal of the American Society of NephrologyClinical Research32977237514271428238514271428
- Barriers to Reducing Hemodialysis Time and Frequency in Patients with Residual Kidney Function10.1681/ASN.2021030361Tue, 31 Aug 2021 11:00:30 GMT-07:00Barriers to Reducing Hemodialysis Time and Frequency in Patients with Residual Kidney FunctionMeyer, Timothy W.Blanco, Ignacio J.Grimm, John C.Leypoldt, John K.Sirich, Tammy L.2021-08-31T11:00:30-07:00doi:10.1681/ASN.2021030361hwp:resource-id:jnephrol;32/9/2112American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis adequacyPerspectivesPerspectivesresearch-article20212021-09-01September 202110.1681/ASN.20210303611046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyPerspectives32921122116
- Molecular Mechanisms of Renal Magnesium ReabsorptionMagnesium is an essential cofactor in many cellular processes, and aberrations in magnesium homeostasis can have life-threatening consequences. The kidney plays a central role in maintaining serum magnesium within a narrow range (0.70–1.10 mmol/L). Along the proximal tubule and thick ascending limb, magnesium reabsorption occurs via paracellular pathways. Members of the claudin family form the magnesium pores in these segments, and also regulate magnesium reabsorption by adjusting the transepithelial voltage that drives it. Along the distal convoluted tubule transcellular reabsorption via heteromeric TRPM6/7 channels predominates, although paracellular reabsorption may also occur. In this segment, the NaCl cotransporter plays a critical role in determining transcellular magnesium reabsorption. Although the general machinery involved in renal magnesium reabsorption has been identified by studying genetic forms of magnesium imbalance, the mechanisms regulating it are poorly understood. This review discusses pathways of renal magnesium reabsorption by different segments of the nephron, emphasizing newer findings that provide insight into regulatory process, and outlining critical unanswered questions.10.1681/ASN.2021010042Thu, 27 May 2021 10:50:43 GMT-07:00Molecular Mechanisms of Renal Magnesium ReabsorptionMagnesium is an essential cofactor in many cellular processes, and aberrations in magnesium homeostasis can have life-threatening consequences. The kidney plays a central role in maintaining serum magnesium within a narrow range (0.70–1.10 mmol/L). Along the proximal tubule and thick ascending limb, magnesium reabsorption occurs via paracellular pathways. Members of the claudin family form the magnesium pores in these segments, and also regulate magnesium reabsorption by adjusting the transepithelial voltage that drives it. Along the distal convoluted tubule transcellular reabsorption via heteromeric TRPM6/7 channels predominates, although paracellular reabsorption may also occur. In this segment, the NaCl cotransporter plays a critical role in determining transcellular magnesium reabsorption. Although the general machinery involved in renal magnesium reabsorption has been identified by studying genetic forms of magnesium imbalance, the mechanisms regulating it are poorly understood. This review discusses pathways of renal magnesium reabsorption by different segments of the nephron, emphasizing newer findings that provide insight into regulatory process, and outlining critical unanswered questions.Ellison, David H.Maeoka, YujiroMcCormick, James A.2021-05-27T10:50:43-07:00doi:10.1681/ASN.2021010042hwp:resource-id:jnephrol;32/9/2125American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycell and transport physiology, magnesium, claudin, ion transport, Gitelman syndromeReviewsReviewsreview-article20212021-09-01September 202110.1681/ASN.20210100421046-66731533-34502021-05-27T10:50:43-07:002021-09Journal of the American Society of NephrologyReviews32921252136
- Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney10.1681/ASN.2020071035Tue, 06 Jul 2021 10:49:17 GMT-07:00Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the KidneyWu, QiPoulsen, Søren B.Murali, Sathish K.Grimm, Paul R.Su, Xiao-TongDelpire, EricWelling, Paul A.Ellison, David H.Fenton, Robert A.2021-07-06T10:49:17-07:00doi:10.1681/ASN.2020071035hwp:resource-id:jnephrol;32/9/2195American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyurinary extracellular vesicle, kidney, proteomics, label-free, exosome, biomarker, transgenic mouseBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20200710351046-66731533-34502021-07-06T10:49:17-07:002021-09Journal of the American Society of NephrologyBasic Research32921952209
- Big Data and Glomerular Disease: Uncovering Common Outcomes of Rare Disease10.1681/ASN.2021070954Tue, 31 Aug 2021 11:00:30 GMT-07:00Big Data and Glomerular Disease: Uncovering Common Outcomes of Rare DiseaseGlenn, Dorey A.Hogan, Susan L.2021-08-31T11:00:30-07:00doi:10.1681/ASN.2021070954hwp:resource-id:jnephrol;32/9/2106American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, nephrotic syndrome, epidemiology and outcomes, cardiovascular disease, mortality, end stage kidney disease, ICD-9-CM codesUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-09-01September 202110.1681/ASN.20210709541046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyUp Front Matters32992106230321082314
- Inhibiting Focal Adhesion Kinase Ameliorates Cyst Development in Polycystin-1–Deficient Polycystic Kidney Disease in Animal Model10.1681/ASN.2020111560Tue, 31 Aug 2021 11:00:30 GMT-07:00Inhibiting Focal Adhesion Kinase Ameliorates Cyst Development in Polycystin-1–Deficient Polycystic Kidney Disease in Animal ModelHe, JinzhaoZhang, ShunQiu, ZhiweiLi, XiaoweiHuang, HuihuiJin, WilliamXu, YueShao, GuangyingWang, LiangMeng, JiaWang, ShuyuanGeng, XiaoqiangJia, YingliLi, MinYang, BaoxueJenny Lu, Hua A.Zhou, Hong2021-08-31T11:00:30-07:00doi:10.1681/ASN.2020111560hwp:resource-id:jnephrol;32/9/2159American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycyst growth, FAK, proliferation, ADPKD, cAMPBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20201115601046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyBasic Research32921592174
- Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development10.1681/ASN.2020111640Mon, 02 Aug 2021 01:46:16 GMT-07:00Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron DevelopmentLi, JinyuGeraldo, Luiz HenriqueDubrac, AlexandreZarkada, GeorgiaEichmann, Anne2021-08-02T13:46:16-07:00doi:10.1681/ASN.2020111640hwp:resource-id:jnephrol;32/9/2255American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular endothelial cells, Slit2, nephrogenesisBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20201116401046-66731533-34502021-08-02T13:46:16-07:002021-09Journal of the American Society of NephrologyBasic Research32992255210422722106
- Tripartite Separation of Glomerular Cell Types and Proteomes from Reporter-Free Mice10.1681/ASN.2020091346Tue, 01 Jun 2021 10:24:06 GMT-07:00Tripartite Separation of Glomerular Cell Types and Proteomes from Reporter-Free MiceHatje, Favian A.Wedekind, UtaSachs, WiebkeLoreth, DesireeReichelt, JuliaDemir, FatihKosub, ChristopherHeintz, LukasTomas, Nicola M.Huber, Tobias B.Skuza, SinahSachs, MarliesZielinski, StephanieRinschen, Markus M.Meyer-Schwesinger, Catherine2021-06-01T10:24:06-07:00doi:10.1681/ASN.2020091346hwp:resource-id:jnephrol;32/9/2175American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular endothelial cells, mesangial cells, podocyte, membranous nephropathy, glomerular filtration barrier, glomerulonephritis, cell biology and structure, THSD7A, slit diaphragm, timMEPBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20200913461046-66731533-34502021-06-01T10:24:06-07:002021-09Journal of the American Society of NephrologyBasic Research32921752193
- Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of ESKD in Diabetes10.1681/ASN.2021010105Thu, 17 Jun 2021 07:41:24 GMT-07:00Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of ESKD in DiabetesSatake, EiichiroSaulnier, Pierre-JeanKobayashi, HirokiGupta, Manoj K.Looker, Helen C.Wilson, Jonathan M.Md Dom, Zaipul I.Ihara, KatsuhitoO’Neil, KristinaKrolewski, BozenaPipino, CaterinaPavkov, Meda E.Nair, VijiBitzer, MarkusNiewczas, Monika A.Kretzler, MatthiasMauer, MichaelDoria, AlessandroNajafian, BehzadKulkarni, Rohit N.Duffin, Kevin L.Pezzolesi, Marcus G.Kahn, C. RonaldNelson, Robert G.Krolewski, Andrzej S.2021-06-17T07:41:24-07:00doi:10.1681/ASN.2021010105hwp:resource-id:jnephrol;32/9/2331American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, diabetic nephropathy, end stage kidney disease, progression of renal failureClinical ResearchClinical Researchresearch-article20212021-09-01September 202110.1681/ASN.20210101051046-66731533-34502021-06-17T07:41:24-07:002021-09Journal of the American Society of NephrologyClinical Research32992331210823512111
- Predictors of Kidney Disease Progression in Diabetes and Precision Medicine: Something Old, Something New, and Something Borrowed10.1681/ASN.2021070945Tue, 31 Aug 2021 11:00:30 GMT-07:00Predictors of Kidney Disease Progression in Diabetes and Precision Medicine: Something Old, Something New, and Something BorrowedVasquez-Rios, GeorgeCoca, Steven G.2021-08-31T11:00:30-07:00doi:10.1681/ASN.2021070945hwp:resource-id:jnephrol;32/9/2108American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyDKDUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-09-01September 202110.1681/ASN.20210709451046-66731533-34502021-08-31T11:00:30-07:002021-09Journal of the American Society of NephrologyUp Front Matters32992108233121112351
- Signatures and Specificity of Tissue-Resident Lymphocytes Identified in Human Renal Peritumor and Tumor Tissue10.1681/ASN.2020101528Tue, 01 Jun 2021 12:21:07 GMT-07:00Signatures and Specificity of Tissue-Resident Lymphocytes Identified in Human Renal Peritumor and Tumor TissueDornieden, TheresaSattler, ArnePascual-Reguant, AnnaRuhm, Annkathrin HelenaThiel, Lion GabrielBergmann, Yasmin SamiraThole, Linda Marie LauraKöhler, RalfKühl, Anja AndreaHauser, Anja ErikaBoral, SengülFriedersdorff, FrankKotsch, Katja2021-06-01T12:21:07-07:00doi:10.1681/ASN.2020101528hwp:resource-id:jnephrol;32/9/2223American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, renal carcinoma, tissue-resident T cells, memory, antigen specificBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20201015281046-66731533-34502021-06-01T12:21:07-07:002021-09Journal of the American Society of NephrologyBasic Research32922232241
- Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study10.1681/ASN.2020111583Fri, 18 Jun 2021 11:02:42 GMT-07:00Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome StudyGo, Alan S.Tan, Thida C.Chertow, Glenn M.Ordonez, Juan D.Fan, DongjieLaw, DavidYankulin, LeonidWojcicki, Janet M.Zheng, SijieChen, Kenneth K.Khoshniat-Rad, FarzienYang, JingrongParikh, Rishi V.2021-06-18T11:02:42-07:00doi:10.1681/ASN.2020111583hwp:resource-id:jnephrol;32/9/2303American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, end-stage kidney disease, cardiovascular events, mortality risk, heart failure, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20212021-09-01September 202110.1681/ASN.20201115831046-66731533-34502021-06-18T11:02:42-07:002021-09Journal of the American Society of NephrologyClinical Epidemiology32992303210623142108
- Antibody and T Cell Response to SARS-CoV-2 Messenger RNA BNT162b2 Vaccine in Kidney Transplant Recipients and Hemodialysis Patients10.1681/ASN.2021040480Thu, 10 Jun 2021 11:55:37 GMT-07:00Antibody and T Cell Response to SARS-CoV-2 Messenger RNA BNT162b2 Vaccine in Kidney Transplant Recipients and Hemodialysis PatientsBertrand, DominiqueHamzaoui, MouadLemée, VeroniqueLamulle, JulieHanoy, MélanieLaurent, CharlotteLebourg, LudivineEtienne, IsabelleLemoine, MathildeLe Roy, FrankNezam, DorianPlantier, Jean-ChristopheBoyer, OlivierGuerrot, DominiqueCandon, Sophie2021-06-10T11:55:37-07:00doi:10.1681/ASN.2021040480hwp:resource-id:jnephrol;32/9/2147American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, hemodialysis, clinical immunology, COVID-19Rapid CommunicationsRapid Communicationsresearch-article20212021-09-01September 202110.1681/ASN.20210404801046-66731533-34502021-06-10T11:55:37-07:002021-09Journal of the American Society of NephrologyRapid Communications32921472152
- Humoral Response after SARS-CoV-2 mRNA Vaccination in a Cohort of Hemodialysis Patients and Kidney Transplant Recipients10.1681/ASN.2021040490Wed, 16 Jun 2021 10:31:16 GMT-07:00Humoral Response after SARS-CoV-2 mRNA Vaccination in a Cohort of Hemodialysis Patients and Kidney Transplant RecipientsDanthu, ClémentHantz, SébastienDahlem, ArthurDuval, MarionBa, BacaryGuibbert, ManonEl Ouafi, ZhourPonsard, SéverineBerrahal, InsafAchard, Jean-MichelBocquentin, FrédériqueAllot, VincentRerolle, Jean-PhilippeAlain, SophieTouré, Fatouma2021-06-16T10:31:16-07:00doi:10.1681/ASN.2021040490hwp:resource-id:jnephrol;32/9/2153American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyvaccine, humoral response, kinetic, hemodialyzed, kidney transplant recipients, COVID-19Rapid CommunicationsRapid Communicationsresearch-article20212021-09-01September 202110.1681/ASN.20210404901046-66731533-34502021-06-16T10:31:16-07:002021-09Journal of the American Society of NephrologyRapid Communications32921532158
- Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease10.1681/ASN.2021020167Fri, 16 Jul 2021 10:14:04 GMT-07:00Effects of Dapagliflozin in Stage 4 Chronic Kidney DiseaseChertow, Glenn M.Vart, PriyaJongs, NielsToto, Robert D.Gorriz, Jose LuisHou, Fan FanMcMurray, John J.V.Correa-Rotter, RicardoRossing, PeterSjöström, C. DavidStefánsson, Bergur V.Langkilde, Anna MariaWheeler, David C.Heerspink, Hiddo J.L.,2021-07-16T10:14:04-07:00doi:10.1681/ASN.2021020167hwp:resource-id:jnephrol;32/9/2352American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydapagliflozin, SGLT2 inhibitor, chronic kidney disease, stage 4 CKDClinical ResearchClinical Researchresearch-article20212021-09-01September 202110.1681/ASN.20210201671046-66731533-34502021-07-16T10:14:04-07:002021-09Journal of the American Society of NephrologyClinical Research32923522361
- Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions10.1681/ASN.2020111546Thu, 10 Jun 2021 10:55:33 GMT-07:00Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal InteractionsOmer, DoritPleniceanu, OrenGnatek, YehuditNamestnikov, MichaelCohen-Zontag, OsnatGoldberg, SanjaFriedman, Yehudit EdenFriedman, NehemyaMandelboim, MichalVitner, Einat B.Achdout, HagitAvraham, RoyZahavy, EranIsraely, TomerMayan, HaimDekel, Benjamin2021-06-10T10:55:33-07:00doi:10.1681/ASN.2020111546hwp:resource-id:jnephrol;32/9/2242American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal tubular epithelial cells, COVID-19, kidney spheroids, acute kidney injury, interferon pathway, SARS-CoV-2, cytopathic damage, kidney stem cells, renal progenitors, human tubular kidney cellsBasic ResearchBasic Researchresearch-article20212021-09-01September 202110.1681/ASN.20201115461046-66731533-34502021-06-10T10:55:33-07:002021-09Journal of the American Society of NephrologyBasic Research32922422254
- Dialysis and Total Health Care Costs in the United States and Worldwide: The Financial Impact of a Single-Payer Dominant System in the US10.1681/ASN.2021010082Fri, 06 Aug 2021 09:22:04 GMT-07:00Dialysis and Total Health Care Costs in the United States and Worldwide: The Financial Impact of a Single-Payer Dominant System in the USPockros, Benjamin M.Finch, Daniel J.Weiner, Daniel E.2021-08-06T09:22:04-07:00doi:10.1681/ASN.2021010082hwp:resource-id:jnephrol;32/9/2137American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, single payer, dialysis, health economics, health care costsResearch LettersResearch Lettersresearch-article20212021-09-01September 202110.1681/ASN.20210100821046-66731533-34502021-08-06T09:22:04-07:002021-09Journal of the American Society of NephrologyResearch Letters32992137210321392104
- Hemodialysis Patients Make Long-Lived Antibodies against SARS-CoV-2 that May Be Associated with Reduced Reinfection10.1681/ASN.2021020188Mon, 02 Aug 2021 01:46:17 GMT-07:00Hemodialysis Patients Make Long-Lived Antibodies against SARS-CoV-2 that May Be Associated with Reduced ReinfectionBanham, Gemma D.Godlee, AlexandraFaustini, Sian E.Cunningham, Adam F.Richter, AlexHarper, Lorraine,2021-08-02T13:46:17-07:00doi:10.1681/ASN.2021020188hwp:resource-id:jnephrol;32/9/2140American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, SARS-CoV-2, COVID-19, antibodyResearch LettersResearch Lettersresearch-article20212021-09-01September 202110.1681/ASN.20210201881046-66731533-34502021-08-02T13:46:17-07:002021-09Journal of the American Society of NephrologyResearch Letters32921402142
- Racial Adjustment Adversely Affects Glomerular Filtration Estimates in Black Americans Living with HIV10.1681/ASN.2021030311Thu, 17 Jun 2021 07:41:25 GMT-07:00Racial Adjustment Adversely Affects Glomerular Filtration Estimates in Black Americans Living with HIVAtta, Mohamed G.Zook, KatieBrown, Todd T.Vaidya, DhananjayTao, XuetingMaier, PaulaSchwartz, George J.Lucas, Gregory M.2021-06-17T07:41:25-07:00doi:10.1681/ASN.2021030311hwp:resource-id:jnephrol;32/9/2143American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyeGFR, CKD-EPI, Black Americans, raceResearch LettersResearch Lettersresearch-article20212021-09-01September 202110.1681/ASN.20210303111046-66731533-34502021-06-17T07:41:25-07:002021-09Journal of the American Society of NephrologyResearch Letters32921432147
- Bleeding Complications of Percutaneous Kidney Biopsy: Does Gender Matter?10.34067/KID.0002432021Wed, 16 Jun 2021 09:35:00 GMT-07:00Bleeding Complications of Percutaneous Kidney Biopsy: Does Gender Matter?Anpalahan, AksharaaMalacova, EvaHegerty, KatharineMalett, AndrewRanganathan, DwarakanathanHealy, Helen G.Gois, Pedro Henrique Franca2021-06-16T09:35:00-07:00doi:10.34067/KID.0002432021hwp:resource-id:kidney360;2/8/1308American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, biopsy, bleeding complications, nephrectomy, percutaneous kidney biopsy, predictorsBrief CommunicationClinical NephrologyBrief CommunicationClinical Nephrologyresearch-article20212021-08-2610.34067/KID.00024320212641-76502021-06-16T09:35:00-07:002021-08-26Kidney360Brief Communication2813081312
- Intimal Hyperplasia and Arteriovenous Fistula Failure: Looking Beyond Size DifferencesThe development of venous intimal hyperplasia (IH) has been historically associated with failure of arteriovenous fistulas (AVFs) used for hemodialysis. This long-standing assumption, made on the basis of histologic observations, has been recently challenged by clinical studies indicating that the size of the intima by itself is not enough to explain stenosis or AVF maturation failure. Irrespective of this lack of association, IH is present in most native veins and fistulas, is prominent in many patients, and suggests a role in the vein that may not be reflected by its dimensions. Therefore, the contribution of IH to AVF dysfunction remains controversial. Using only clinical data and avoiding extrapolations from animal models, we critically discuss the biologic significance of IH in vein remodeling, vascular access function, and the response of the venous wall to repeated trauma in patients receiving hemodialysis. We address questions and pose new ones such as the following: What are the factors that contribute to IH in preaccess veins and AVFs? Do cellular phenotypes and composition of the intima influence AVF function? Are there protective roles of the venous intima? This review explores these possibilities, with hopes of rekindling a critical discussion about venous IH that goes beyond thickness and AVF outcomes.10.34067/KID.0002022021Thu, 03 Jun 2021 11:46:41 GMT-07:00Intimal Hyperplasia and Arteriovenous Fistula Failure: Looking Beyond Size DifferencesThe development of venous intimal hyperplasia (IH) has been historically associated with failure of arteriovenous fistulas (AVFs) used for hemodialysis. This long-standing assumption, made on the basis of histologic observations, has been recently challenged by clinical studies indicating that the size of the intima by itself is not enough to explain stenosis or AVF maturation failure. Irrespective of this lack of association, IH is present in most native veins and fistulas, is prominent in many patients, and suggests a role in the vein that may not be reflected by its dimensions. Therefore, the contribution of IH to AVF dysfunction remains controversial. Using only clinical data and avoiding extrapolations from animal models, we critically discuss the biologic significance of IH in vein remodeling, vascular access function, and the response of the venous wall to repeated trauma in patients receiving hemodialysis. We address questions and pose new ones such as the following: What are the factors that contribute to IH in preaccess veins and AVFs? Do cellular phenotypes and composition of the intima influence AVF function? Are there protective roles of the venous intima? This review explores these possibilities, with hopes of rekindling a critical discussion about venous IH that goes beyond thickness and AVF outcomes.Vazquez-Padron, Roberto I.Duque, Juan C.Tabbara, MarwanSalman, Loay H.Martinez, Laisel2021-06-03T11:46:41-07:00doi:10.34067/KID.0002022021hwp:resource-id:kidney360;2/8/1360American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360hemodynamics and vascular regulation, arteriovenous fistula, hyperplasia, intimal hyperplasia, outcomes, pre-access vein, stenosis, vascular accessReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00020220212641-76502021-06-03T11:46:41-07:002021-08-26Kidney360Review Article2813601372
- Association of Blood Pressure Genetic Risk Score with Cardiovascular Disease and CKD Progression: Findings from the CRIC Study10.34067/KID.0007632020Fri, 09 Apr 2021 06:02:57 GMT-07:00Association of Blood Pressure Genetic Risk Score with Cardiovascular Disease and CKD Progression: Findings from the CRIC StudyNierenberg, Jovia L.Anderson, Amanda H.He, JiangParsa, AfshinSrivastava, AnandCohen, Jordana B.Saraf, Santosh L.Rahman, MahboobRosas, Sylvia E.Kelly, Tanika N.,2021-04-09T06:02:57-07:00doi:10.34067/KID.0007632020hwp:resource-id:kidney360;2/8/1251American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360genetics, blood pressure, cardiovascular disease, chronic kidney disease, CRIC Study, disease progression, genetic risk scoreOriginal InvestigationGeneticsOriginal InvestigationGeneticsresearch-article20212021-08-2610.34067/KID.00076320202641-76502021-04-09T06:02:57-07:002021-08-26Kidney360Original Investigation2812511260
- New Frontiers in Vascular Access Practice: From Standardized to Patient-tailored Care and Shared Decision MakingVascular access planning is critical in the management of patients with advanced kidney disease who elect for hemodialysis for RRT. Policies put in place more than two decades ago attempted to standardize vascular access care around the model of optimal, namely arteriovenous fistula, and least preferred, namely central venous catheter, type of access. This homogenized approach to vascular access care emerged ineffective in the increasingly heterogeneous and complex dialysis population. The most recent vascular access guidelines acknowledge the limitations of standardized care and encourage tailoring vascular access care on the basis of patient and disease characteristics. In this article, we discuss available literature in support of patient-tailored access care on the basis of differences in vascular access outcomes by biologic and social factors—age, sex, and race. Further, we draw attention to the overlooked dimension of patient-reported preferences and shared decision making in the practice of vascular access planning. We discuss milestones to overcome as requisite steps to implement effective shared decision making in vascular access care. Finally, we take into consideration local practice cofactors as major players in vascular access fate. We conclude that a personalized approach to hemodialysis vascular access will require dynamic care specifically relevant to the individual on the basis of biologic factors, fluctuating clinical needs, values, and preferences.10.34067/KID.0002882021Tue, 15 Jun 2021 01:17:18 GMT-07:00New Frontiers in Vascular Access Practice: From Standardized to Patient-tailored Care and Shared Decision MakingVascular access planning is critical in the management of patients with advanced kidney disease who elect for hemodialysis for RRT. Policies put in place more than two decades ago attempted to standardize vascular access care around the model of optimal, namely arteriovenous fistula, and least preferred, namely central venous catheter, type of access. This homogenized approach to vascular access care emerged ineffective in the increasingly heterogeneous and complex dialysis population. The most recent vascular access guidelines acknowledge the limitations of standardized care and encourage tailoring vascular access care on the basis of patient and disease characteristics. In this article, we discuss available literature in support of patient-tailored access care on the basis of differences in vascular access outcomes by biologic and social factors—age, sex, and race. Further, we draw attention to the overlooked dimension of patient-reported preferences and shared decision making in the practice of vascular access planning. We discuss milestones to overcome as requisite steps to implement effective shared decision making in vascular access care. Finally, we take into consideration local practice cofactors as major players in vascular access fate. We conclude that a personalized approach to hemodialysis vascular access will require dynamic care specifically relevant to the individual on the basis of biologic factors, fluctuating clinical needs, values, and preferences.Murea, MarianaWoo, Karen2021-06-15T13:17:18-07:00doi:10.34067/KID.0002882021hwp:resource-id:kidney360;2/8/1380American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, age, hemodialysis, patient-centered care, patient-reported, race, reference standards, sex, vascular accessReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00028820212641-76502021-06-15T13:17:18-07:002021-08-26Kidney360Review Article2813801389
- Prevalence of Frailty in Patients Referred to the Kidney Transplant Waitlist10.34067/KID.0001892021Fri, 28 May 2021 06:11:29 GMT-07:00Prevalence of Frailty in Patients Referred to the Kidney Transplant WaitlistWorthen, GeorgeVinson, AmandaCardinal, HéloiseDoucette, SteveGogan, NessaGunaratnam, LakshmanKeough-Ryan, TammyKiberd, Bryce A.Prasad, BhanuRockwood, KennethSills, LauraSuri, Rita S.Tangri, NavdeepWalsh, MichaelWest, KennethYohanna, SeychelleTennankore, Karthik2021-05-28T06:11:29-07:00doi:10.34067/KID.0001892021hwp:resource-id:kidney360;2/8/1287American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, ESRD, frailty, geriatric nephrology, kidney, kidney transplantation, prevalence, waiting listsOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-08-2610.34067/KID.00018920212641-76502021-05-28T06:11:29-07:002021-08-26Kidney360Original Investigation2812871295
- The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular MechanismsIgA nephropathy (IgAn), defined by the pre dominant de position of IgA in the glomerular mesangium, is the most common form of GN throughout the world. However, its incidence, sex distribution, clinical presentation, and progression and pathogenic initiating factors are largely variable and do not fit such a simple definition. To assess the heterogeneity of this disease, we recently conducted a clinical survey on the presentation and clinical management of patients with IgAn in Europe and Japan. This clinical survey highlights similarities and differences in patients from different cont inents. The survey revealed obvious differences between nations in the frequency of gastrointestinal complications, including inflammatory bowel diseases (IBD) and celiac disease, which were more frequent in European patients. Such findings are compatible with susceptibility loci related to intestinal immunity and IBD in recent genome wide association studies (GWAS) on IgAn. However, most of the molecules in these mucosal-related loci fulfill the immunologic function not only of gut-associated lymphoid tissue (GALT), but also nasopharyngeal/bronchial-associated lymphoid tissues (NALT/BALT). Indeed, a similar frequency of macrohematuria coinciding with upper respiratory infection, a hallmark manifestation of this disease, was found in the survey, emphasizing the pathogenic roles of these molecules in the NALT/BALT of patients with IgAn. Recent experimental and clinical studies including GWAS on multiple common infections and IBD indicate immune crosstalk between GALT and NALT/BALT, and some related mediators, such as TNF superfamily ligands (APRIL/BAFF). This review explains the epidemiologic heterogeneity of this disease with the clinical survey, and discusses race and sex-dependent molecular mechanisms.10.34067/KID.0002972021Fri, 28 May 2021 07:45:33 GMT-07:00The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular MechanismsIgA nephropathy (IgAn), defined by the pre dominant de position of IgA in the glomerular mesangium, is the most common form of GN throughout the world. However, its incidence, sex distribution, clinical presentation, and progression and pathogenic initiating factors are largely variable and do not fit such a simple definition. To assess the heterogeneity of this disease, we recently conducted a clinical survey on the presentation and clinical management of patients with IgAn in Europe and Japan. This clinical survey highlights similarities and differences in patients from different cont inents. The survey revealed obvious differences between nations in the frequency of gastrointestinal complications, including inflammatory bowel diseases (IBD) and celiac disease, which were more frequent in European patients. Such findings are compatible with susceptibility loci related to intestinal immunity and IBD in recent genome wide association studies (GWAS) on IgAn. However, most of the molecules in these mucosal-related loci fulfill the immunologic function not only of gut-associated lymphoid tissue (GALT), but also nasopharyngeal/bronchial-associated lymphoid tissues (NALT/BALT). Indeed, a similar frequency of macrohematuria coinciding with upper respiratory infection, a hallmark manifestation of this disease, was found in the survey, emphasizing the pathogenic roles of these molecules in the NALT/BALT of patients with IgAn. Recent experimental and clinical studies including GWAS on multiple common infections and IBD indicate immune crosstalk between GALT and NALT/BALT, and some related mediators, such as TNF superfamily ligands (APRIL/BAFF). This review explains the epidemiologic heterogeneity of this disease with the clinical survey, and discusses race and sex-dependent molecular mechanisms.Suzuki, YusukeMonteiro, Renato C.Coppo, RosannaSuzuki, Hitoshi2021-05-28T07:45:33-07:00doi:10.34067/KID.0002972021hwp:resource-id:kidney360;2/8/1339American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, APRIL, BAFF, sex, gut, HORMAD2, IgA nephropathy, mucosa, pIgR, race, tonsilReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00029720212641-76502021-05-28T07:45:33-07:002021-08-26Kidney360Review Article2813391348
- Novel Clinical Therapies and Technologies in Dialysis Vascular AccessThe hemodialysis population continues to grow. Although procedures for dialysis have existed for >60 years, significant challenges with vascular access to support hemodialysis persist. Failure of arteriovenous fistulas (AVFs) to mature, loss of AVF and graft patency, thrombosis, and infection hinder long-term access, and add extra health care costs and patient morbidity. There have been numerous innovations over the last decade aimed at addressing the issues. In this study, we review the literature and summarize the recent evolution of drug delivery, graft development, minimally invasive AVF creation, and stem-cell therapy for hemodialysis access.10.34067/KID.0002962021Thu, 10 Jun 2021 01:48:29 GMT-07:00Novel Clinical Therapies and Technologies in Dialysis Vascular AccessThe hemodialysis population continues to grow. Although procedures for dialysis have existed for >60 years, significant challenges with vascular access to support hemodialysis persist. Failure of arteriovenous fistulas (AVFs) to mature, loss of AVF and graft patency, thrombosis, and infection hinder long-term access, and add extra health care costs and patient morbidity. There have been numerous innovations over the last decade aimed at addressing the issues. In this study, we review the literature and summarize the recent evolution of drug delivery, graft development, minimally invasive AVF creation, and stem-cell therapy for hemodialysis access.Takahashi, Edwin A.Kilari, SreenivasuluMisra, Sanjay2021-06-10T13:48:29-07:00doi:10.34067/KID.0002962021hwp:resource-id:kidney360;2/8/1373American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, arteriovenous fistula, dialysis, drug delivery, stenosisReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00029620212641-76502021-06-10T13:48:29-07:002021-08-26Kidney360Review Article2813731379
- New Vancomycin Dosing Guidelines for Hemodialysis Patients: Rationale, Caveats, and Limitations10.34067/KID.0000192021Fri, 21 May 2021 01:33:40 GMT-07:00New Vancomycin Dosing Guidelines for Hemodialysis Patients: Rationale, Caveats, and LimitationsLewis, Susan J.Nolin, Thomas D.2021-05-21T13:33:40-07:00doi:10.34067/KID.0000192021hwp:resource-id:kidney360;2/8/1313American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephro-pharmacology, hemodialysis, patients, vancomycinPerspectivePerspectiveresearch-article20212021-08-2610.34067/KID.00001920212641-76502021-05-21T13:33:40-07:002021-08-26Kidney360Perspective2813131315
- Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney DiseaseThrough the discovery of direct-acting antiviral therapies over the last decade, hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease, is a risk factor for progression of CKD, is associated with higher morbidity and mortality in patients receiving dialysis, and leads to worse allograft and patient outcomes in recipients of kidney transplants. Clinical trial and real-world data of direct-acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease, including patients with CKD, ESKD, and those who have received a kidney transplant.10.34067/KID.0001812021Fri, 21 May 2021 11:34:27 GMT-07:00Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney DiseaseThrough the discovery of direct-acting antiviral therapies over the last decade, hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease, is a risk factor for progression of CKD, is associated with higher morbidity and mortality in patients receiving dialysis, and leads to worse allograft and patient outcomes in recipients of kidney transplants. Clinical trial and real-world data of direct-acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease, including patients with CKD, ESKD, and those who have received a kidney transplant.Strohbehn, Ian A.Seethapathy, RituvanthikaaLee, MeghanSise, Meghan E.2021-05-21T11:34:27-07:00doi:10.34067/KID.0001812021hwp:resource-id:kidney360;2/8/1316American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, hepacivirus, hepatitis C virus, kidney diseasesReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00018120212641-76502021-05-21T11:34:27-07:002021-08-26Kidney360Review Article2813161325
- Unusual Kidney Findings in a Patient with Abdominal Pain and Kidney Dysfunction10.34067/KID.0001352021Thu, 26 Aug 2021 05:30:24 GMT-07:00Unusual Kidney Findings in a Patient with Abdominal Pain and Kidney DysfunctionFerreira, FilipaRelvas, MiguelVale, Luís2021-08-26T05:30:24-07:00doi:10.34067/KID.0001352021hwp:resource-id:kidney360;2/8/1392American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephrolithiasis, staghorn calculi, urinary tract infectionsClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-08-2610.34067/KID.00013520212641-76502021-08-26T05:30:24-07:002021-08-26Kidney360Clinical Images in Nephrology and Dialysis2813921393
- Use of Ultrasound to Assess Hemodynamics in Acutely Ill PatientsEarly diagnosis of AKI and preventive measures can likely decrease the severity of the injury and improve patient outcomes. Current hemodynamic monitoring variables, including BP, heart and respiratory rates, temperature, and oxygenation status, have been used to identify patients at high risk for AKI. Despite the widespread use of such variables, their ability to accurately and timely detect patients who are high risk has been questioned. Therefore, there is a critical need to develop and validate tools that can measure new and more kidney-specific hemodynamic and laboratory variables, potentially assisting with AKI risk stratification, implementing appropriate and timely preventive measures, and hopefully improved outcomes. The new ultrasonography techniques provide novel insights into kidney hemodynamics and potential management and/or therapeutic targets. Contrast-enhanced ultrasonography; Doppler flow patterns of hepatic veins, portal vein, and intrakidney veins; and ultrasound elastography are among approaches that may provide such information, particularly related to vascular changes in AKI, venous volume excess or congestion, and fluid tolerance. This review summarizes the current state of these techniques and their relevance to kidney hemodynamic management.10.34067/KID.0002322021Wed, 02 Jun 2021 12:53:39 GMT-07:00Use of Ultrasound to Assess Hemodynamics in Acutely Ill PatientsEarly diagnosis of AKI and preventive measures can likely decrease the severity of the injury and improve patient outcomes. Current hemodynamic monitoring variables, including BP, heart and respiratory rates, temperature, and oxygenation status, have been used to identify patients at high risk for AKI. Despite the widespread use of such variables, their ability to accurately and timely detect patients who are high risk has been questioned. Therefore, there is a critical need to develop and validate tools that can measure new and more kidney-specific hemodynamic and laboratory variables, potentially assisting with AKI risk stratification, implementing appropriate and timely preventive measures, and hopefully improved outcomes. The new ultrasonography techniques provide novel insights into kidney hemodynamics and potential management and/or therapeutic targets. Contrast-enhanced ultrasonography; Doppler flow patterns of hepatic veins, portal vein, and intrakidney veins; and ultrasound elastography are among approaches that may provide such information, particularly related to vascular changes in AKI, venous volume excess or congestion, and fluid tolerance. This review summarizes the current state of these techniques and their relevance to kidney hemodynamic management.Safadi, SamiMurthi, SarahKashani, Kianoush B.2021-06-02T12:53:39-07:00doi:10.34067/KID.0002322021hwp:resource-id:kidney360;2/8/1349American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI, hemodynamics, intravenous fluids, IVF, kidney congestion, POCU, ultrasound, volume overload, volume toleranceReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00023220212641-76502021-06-02T12:53:39-07:002021-08-26Kidney360Review Article2813491359
- Transforming Growth Factor Beta Receptor 3 (TGFBR3)–Associated Membranous Nephropathy10.34067/KID.0001492021Fri, 11 Jun 2021 11:47:29 GMT-07:00Transforming Growth Factor Beta Receptor 3 (TGFBR3)–Associated Membranous NephropathyCaza, Tiffany N.Hassen, Samar I.Kenan, Daniel J.Storey, AaronArthur, John M.Herzog, ChristianEdmondson, Rick D.Bourne, T. DavidBeck, Laurence H.Larsen, Christopher P.2021-06-11T11:47:29-07:00doi:10.34067/KID.0001492021hwp:resource-id:kidney360;2/8/1275American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, betaglycan, mass spectrometry, membranous lupus nephritis, membranous nephropathy, proteoglycans, systemic lupus erythematosus, transforming growth factor beta receptorsOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-08-2610.34067/KID.00014920212641-76502021-06-11T11:47:29-07:002021-08-26Kidney360Original Investigation2812751286
- Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease10.34067/KID.0007552020Fri, 21 May 2021 08:25:58 GMT-07:00Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney DiseaseMartin, William P.Conroy, ChloeNaicker, Serika D.Cormican, SarahGriffin, Tomás P.Islam, Md NahidulMcCole, Eibhlin M.McConnell, IvanLamont, JohnFitzGerald, PeterFerguson, John P.Richardson, CiaránLogue, Susan E.Griffin, Matthew D.2021-05-21T08:25:58-07:00doi:10.34067/KID.0007552020hwp:resource-id:kidney360;2/8/1225American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, biomarkers, C3a-desArg, end stage renal disease, machine learning, mortality, multiplex assays, neutrophil gelatinase-associated lipocalin, renal function decline, soluble tumor necrosis factor receptorOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-08-2610.34067/KID.00075520202641-76502021-05-21T08:25:58-07:002021-08-26Kidney360Original Investigation2812251239
- Comprehensive Assessment of Fluid Status by Point-of-Care UltrasonographyThe management of complex fluid and electrolyte disorders is central to the practice of nephrologists. The sensitivity of physical examination alone to determine fluid status is limited, precluding accurate clinical decision making. Point-of-care ultrasonography (POCUS) is emerging as a valuable, noninvasive, bedside diagnostic tool for objective evaluation of physiologic and hemodynamic parameters related to fluid status, tolerance, and responsiveness. Rapid bedside sonographic evaluation can obtain qualitative data on cardiac function and quantitative data on pulmonary congestion. Advanced POCUS, including goal-directed Doppler echocardiography, provides additional quantitative information, including flow velocities and pressures across the cardiac structures. Recently, abnormal Doppler flow patterns in abdominal organs secondary to increased right atrial pressure have been linked to congestive organ damage, adding another component to the hemodynamic assessment. Integrating POCUS findings with clinical and laboratory data can further elucidate a patient’s hemodynamic status. This drives decisions regarding crystalloid administration or, conversely, diuresis or ultrafiltration and allows tailored therapy for individual patients. In this article, we provide an overview of the focused assessment of cardiovascular function and pulmonary and venous congestion using POCUS and review relevant literature.10.34067/KID.0006482020Fri, 28 May 2021 06:11:29 GMT-07:00Comprehensive Assessment of Fluid Status by Point-of-Care UltrasonographyThe management of complex fluid and electrolyte disorders is central to the practice of nephrologists. The sensitivity of physical examination alone to determine fluid status is limited, precluding accurate clinical decision making. Point-of-care ultrasonography (POCUS) is emerging as a valuable, noninvasive, bedside diagnostic tool for objective evaluation of physiologic and hemodynamic parameters related to fluid status, tolerance, and responsiveness. Rapid bedside sonographic evaluation can obtain qualitative data on cardiac function and quantitative data on pulmonary congestion. Advanced POCUS, including goal-directed Doppler echocardiography, provides additional quantitative information, including flow velocities and pressures across the cardiac structures. Recently, abnormal Doppler flow patterns in abdominal organs secondary to increased right atrial pressure have been linked to congestive organ damage, adding another component to the hemodynamic assessment. Integrating POCUS findings with clinical and laboratory data can further elucidate a patient’s hemodynamic status. This drives decisions regarding crystalloid administration or, conversely, diuresis or ultrafiltration and allows tailored therapy for individual patients. In this article, we provide an overview of the focused assessment of cardiovascular function and pulmonary and venous congestion using POCUS and review relevant literature.Argaiz, Eduardo R.Koratala, AbhilashReisinger, Nathaniel2021-05-28T06:11:29-07:00doi:10.34067/KID.0006482020hwp:resource-id:kidney360;2/8/1326American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360hemodynamics and vascular regulation, congestion, doppler, fluid status, heart failure, hemodynamics, hypervolemia, POCUS, point of care ultrasound, VExUS, volume statusReview ArticleReview Articlereview-article20212021-08-2610.34067/KID.00064820202641-76502021-05-28T06:11:29-07:002021-08-26Kidney360Review Article2813261338
- Nodular Lesions on the Hands of an ESKD Patient on Hemodialysis10.34067/KID.0001772021Thu, 26 Aug 2021 05:30:24 GMT-07:00Nodular Lesions on the Hands of an ESKD Patient on HemodialysisFung, Winston Wing ShingChow, Kai MingSzeto, Cheuk Chun2021-08-26T05:30:24-07:00doi:10.34067/KID.0001772021hwp:resource-id:kidney360;2/8/1390American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, ESKD, hemodialysis, hand, hypercalcemia, hyperparathyroidism, hyperphosphatemia, renal dialysis, vascular calcificationClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-08-2610.34067/KID.00017720212641-76502021-08-26T05:30:24-07:002021-08-26Kidney360Clinical Images in Nephrology and Dialysis2813901391
- Genetic Risk Scores and Blood Pressure — The Heart is What Matters10.34067/KID.0003272021Thu, 26 Aug 2021 05:30:24 GMT-07:00Genetic Risk Scores and Blood Pressure — The Heart is What MattersBoumitri, MirnaRai, Nayanjot K.Drawz, Paul E.2021-08-26T05:30:24-07:00doi:10.34067/KID.0003272021hwp:resource-id:kidney360;2/8/1209American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360genetics, blood pressure, blood pressure determination, heart, risk factorsEditorialEditorialeditorial20212021-08-2610.34067/KID.00032720212641-76502021-08-26T05:30:24-07:002021-08-26Kidney360Editorial2812091211
- A Non-purine Xanthine Oxidoreductase Inhibitor Reduces Albuminuria in Patients with DKD: A Randomized Controlled Trial10.34067/KID.0001672021Wed, 30 Jun 2021 11:45:12 GMT-07:00A Non-purine Xanthine Oxidoreductase Inhibitor Reduces Albuminuria in Patients with DKD: A Randomized Controlled TrialBakris, George L.Mikami, HidetakaHirata, MasayukiNakajima, AkihiroCressman, Michael D.2021-06-30T11:45:12-07:00doi:10.34067/KID.0001672021hwp:resource-id:kidney360;2/8/1240American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, albuminuria, diabetic kidney disease, drug hypersensitivity, enzyme inhibitors, serum uric acid, urine albumin-creatinine ratio, xanthine oxidoreductase inhibitorOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20212021-08-2610.34067/KID.00016720212641-76502021-06-30T11:45:12-07:002021-08-26Kidney360Original Investigation2812401250
- Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study10.34067/KID.0000862021Thu, 03 Jun 2021 06:17:21 GMT-07:00Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter StudyMalik, Rubab F.Jia, YaqiMansour, Sherry G.Reese, Peter P.Hall, Isaac E.Alasfar, SamiDoshi, Mona D.Akalin, EnverBromberg, Jonathan S.Harhay, Meera N.Mohan, SumitMuthukumar, ThangamaniSchröppel, BerndSingh, PoojaWeng, Francis L.Thiessen Philbrook, Heather R.Parikh, Chirag R.2021-06-03T06:17:21-07:00doi:10.34067/KID.0000862021hwp:resource-id:kidney360;2/8/1296American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, complication: medical/metabolic, diabetes: new-onset/post-transplant, graft survival, United Network for Organ Sharing (UNOS)Original InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-08-2610.34067/KID.00008620212641-76502021-06-03T06:17:21-07:002021-08-26Kidney360Original Investigation2812961307
- New Onset Diabetes Mellitus after Transplant: The Challenge Continues10.34067/KID.0004042021Thu, 26 Aug 2021 05:30:24 GMT-07:00New Onset Diabetes Mellitus after Transplant: The Challenge ContinuesAziz, Fahad2021-08-26T05:30:24-07:00doi:10.34067/KID.0004042021hwp:resource-id:kidney360;2/8/1212American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, diabetes mellitus, transplantsEditorialEditorialeditorial20212021-08-2610.34067/KID.00040420212641-76502021-08-26T05:30:24-07:002021-08-26Kidney360Editorial2812121214
- Association of AKI-D with Urinary Findings and Baseline eGFR in Hospitalized COVID-19 Patients10.34067/KID.0001612021Thu, 20 May 2021 11:51:54 GMT-07:00Association of AKI-D with Urinary Findings and Baseline eGFR in Hospitalized COVID-19 PatientsPatel, Dipal M.Phadke, ManaliDai, FengSimonov, MichaelDahl, Neera K.Kodali, Ravi2021-05-20T11:51:54-07:00doi:10.34067/KID.0001612021hwp:resource-id:kidney360;2/8/1215American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney failure, acute kidney injury, COVID-19, dialysis, hematuria, proteinuria, risk factorsOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-08-2610.34067/KID.00016120212641-76502021-05-20T11:51:54-07:002021-08-26Kidney360Original Investigation2812151224
- The Gut and Blood Microbiome in IgA Nephropathy and Healthy Controls10.34067/KID.0000132021Wed, 09 Jun 2021 01:36:50 GMT-07:00The Gut and Blood Microbiome in IgA Nephropathy and Healthy ControlsShah, Neal B.Nigwekar, Sagar U.Kalim, SahirLelouvier, BenjaminServant, FlorenceDalal, MonikaKrinsky, ScottFasano, AlessioTolkoff-Rubin, NinaAllegretti, Andrew S.2021-06-09T13:36:50-07:00doi:10.34067/KID.0000132021hwp:resource-id:kidney360;2/8/1261American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, 16S, bacterial DNA, blood microbiome, gastrointestinal microbiome, gut microbiome, IgA glomerulonephritis, IgA nephropathy, L-form bacteria, microbiotaOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-08-2610.34067/KID.00001320212641-76502021-06-09T13:36:50-07:002021-08-26Kidney360Original Investigation2812611274
- Introduction to Kidney Transplantation: Long-Term Management Challenges10.2215/CJN.13440820Wed, 10 Mar 2021 09:39:07 GMT-08:00Introduction to Kidney Transplantation: Long-Term Management ChallengesSawinski, DeirdrePoggio, Emilio D.2021-03-10T09:39:07-08:00doi:10.2215/CJN.13440820hwp:resource-id:clinjasn;16/8/1262American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Kidney Transplantation SeriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesother20212021-08-01August 202110.2215/CJN.134408201555-90411555-905X2021-03-10T09:39:07-08:002021-08Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges16812621263
- Metabolite Biomarkers of CKD Progression in Children10.2215/CJN.00220121Fri, 06 Aug 2021 11:00:21 GMT-07:00Metabolite Biomarkers of CKD Progression in ChildrenDenburg, Michelle R.Xu, YunwenAbraham, Alison G.Coresh, JosefChen, JingshaGrams, Morgan E.Feldman, Harold I.Kimmel, Paul L.Rebholz, Casey M.Rhee, Eugene P.Vasan, Ramachandran S.Warady, Bradley A.Furth, Susan L.,Ramachandran, Vasan S.Massaro, JosephClish, ClarySchelling, JeffreyDenburg, MichelleFurth, SusanWarady, BradleyBonventre, JosephWaikar, SushrutMcMahon, GearoidSabbisetti, VenkataCoresh, JosefGrams, MorganRebholz, CaseyAbraham, AlisonTin, AdrieneParikh, ChiragKlein, JonCoca, StevenFerket, Bart SNadkarni, Girish N.Rhee, EugeneKimmel, Paul L.Gossett, DanielRovin, BradShlipak, Michael G.Sarnak, MLevey, Andrew S.Inker, Lesley A.Foster, MeredithGutiérrez, Orlando M.Ix, JoachimDubin, RuthSeegmiller, JesseHostetter, TomDeo, RajatFeldman, Harold I.Anderson, AmandaMifflin, TheodoreXie, DaweiShou, HaochangBallard, ShawnWhitehead, KristaCollins, HeatherGreenberg, JasonGanz, Peter2021-08-06T11:00:21-07:00doi:10.2215/CJN.00220121hwp:resource-id:clinjasn;16/8/1178American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, chronic kidney disease, metabolism, pediatric nephrology, progression of chronic renal failure, biomarkersOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-08-01August 202110.2215/CJN.002201211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16881178115211891154
- The Promise of Metabolomics in Decelerating CKD Progression in Children10.2215/CJN.07400521Fri, 06 Aug 2021 11:00:21 GMT-07:00The Promise of Metabolomics in Decelerating CKD Progression in ChildrenSchultheiss, Ulla T.Sekula, Peggy2021-08-06T11:00:21-07:00doi:10.2215/CJN.07400521hwp:resource-id:clinjasn;16/8/1152American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMetabolomics, chronic kidney diseaseEditorialsEditorialseditorial20212021-08-01August 202110.2215/CJN.074005211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyEditorials16881152117811541189
- Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor TherapySodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na+-glucose–coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes to include slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration. Inhibition of sodium-glucose cotransporter-2 in the proximal tubule alters kidney ATP turnover so that filtered ketoacids are preferentially excreted as Na+ or K+ salts, leading to indirect loss of bicarbonate from the body and systemic acidosis under conditions of increased ketogenesis. Risk factors include reductions in insulin dose, increased insulin demand, metabolic stress, low carbohydrate intake, women, and latent autoimmune diabetes of adulthood. The lack of hyperglycemia and nonspecific symptoms of ketoacidosis can lead to delays in diagnosis. Treatment strategies and various precautions are discussed that can decrease the likelihood of this complication.10.2215/CJN.17621120Tue, 09 Feb 2021 06:53:45 GMT-08:00Euglycemic Ketoacidosis as a Complication of SGLT2 Inhibitor TherapySodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na+-glucose–coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes to include slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration. Inhibition of sodium-glucose cotransporter-2 in the proximal tubule alters kidney ATP turnover so that filtered ketoacids are preferentially excreted as Na+ or K+ salts, leading to indirect loss of bicarbonate from the body and systemic acidosis under conditions of increased ketogenesis. Risk factors include reductions in insulin dose, increased insulin demand, metabolic stress, low carbohydrate intake, women, and latent autoimmune diabetes of adulthood. The lack of hyperglycemia and nonspecific symptoms of ketoacidosis can lead to delays in diagnosis. Treatment strategies and various precautions are discussed that can decrease the likelihood of this complication.Palmer, Biff F.Clegg, Deborah J.2021-02-09T06:53:45-08:00doi:10.2215/CJN.17621120hwp:resource-id:clinjasn;16/8/1284American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyeuglycemic ketoacidosis, sodium glucose co-transporter inhibitorReviewsReviewsreview-article20212021-08-01August 202110.2215/CJN.176211201555-90411555-905X2021-02-09T06:53:45-08:002021-08Clinical Journal of the American Society of NephrologyReviews16812841291
- Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis Patientsb.caplin@ucl.ac.uk10.2215/CJN.03180321Tue, 01 Jun 2021 10:26:55 GMT-07:00Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis PatientsCaplin, BenAshby, DamienMcCafferty, KieranHull, RichardAsgari, ElhamFord, Martin L.Cole, NicholasAntonelou, MarilinaBlakey, Sarah A.Srinivasa, VinayBraide-Azikwe, Dandisonba C.B.Roper, TayebaClark, GraceCronin, HelenHayes, Nathan J.Manson, BethiaSarnowski, AlexanderCorbett, RichardBramham, KateLioudaki, EiriniKumar, NicolaFrankel, AndrewMakanjuola, DavidSharpe, Claire C.Banerjee, DebasishSalama, Alan D.,,Elham, AsgariDamien, AshbyDebasish, BanerjeeSarah, BlakeyKate, BramhamRosalind, BrewsterDandisonba, Briade-AzikweHugh, CairnsBen, CaplinParamit, ChowdhuryGrace, ClarkNicholas, ColeRichard, CorbettAndrea, Cove-SmithHelen, CroninMaria, DavariAbigail, DiasKevin, EvansSuzanne, ForbesMartin, FordAndrew, FrankelSahana, GnansampanthanCatriona, GoodladNathan, HayesHeidy, HendraRichard, HullNicola, KumarEirini, LioudakiMarina, LoucaidouDavid, MakanjuolaBethia, MansonKieran, McCaffertyDaniel, McGuinnessAegida, NeradovaMysore, PhanishKatherine, PriceRavi, RajakariarAlex, RankinTayeba, RoperNoam, RothAlan, SalamaAlexander, SarnowskiCassim, SchottClaire, SharpeVinay, SrinivasaDamir, TandaricSujanita, ThyagarajanGisele, VajgelGregor, Young2021-06-01T10:26:55-07:00doi:10.2215/CJN.03180321hwp:resource-id:clinjasn;16/8/1237American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, COVID-19, infection controlOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-08-01August 202110.2215/CJN.031803211555-90411555-905X2021-06-01T10:26:55-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16888123711411146124611421148
- Pharmacokinetics of Remdesivir and GS-441524 during PIRRT and Seraph 100 Therapy10.2215/CJN.17601120Fri, 23 Jul 2021 02:15:11 GMT-07:00Pharmacokinetics of Remdesivir and GS-441524 during PIRRT and Seraph 100 TherapySchmidt, Julius J.Bode-Böger, Stefanie M.Martens-Lobenhoffer, JensHoeper, Marius M.Kielstein, Jan T.2021-07-23T14:15:11-07:00doi:10.2215/CJN.17601120hwp:resource-id:clinjasn;16/8/1256American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, remdesivir, PIRRTResearch LettersResearch Lettersresearch-article20212021-08-01August 202110.2215/CJN.176011201555-90411555-905X2021-07-23T14:15:11-07:002021-08Clinical Journal of the American Society of NephrologyResearch Letters16812561257
- Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-1910.2215/CJN.04080321Mon, 24 May 2021 02:37:49 GMT-07:00Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-19Chan, LiliFuca, NicholasZeldis, EttiCampbell, Kirk N.Shaikh, Aisha2021-05-24T14:37:49-07:00doi:10.2215/CJN.04080321hwp:resource-id:clinjasn;16/8/1258American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, hemodialysis, antibody formation, COVID-19 vaccines, maintenance, RNA, messengerResearch LettersResearch Lettersresearch-article20212021-08-01August 202110.2215/CJN.040803211555-90411555-905X2021-05-24T14:37:49-07:002021-08Clinical Journal of the American Society of NephrologyResearch Letters16812581260
- Evidence-Based Practices to Reduce COVID-19 Transmission in Dialysis Facilities10.2215/CJN.07220521Wed, 04 Aug 2021 06:10:08 GMT-07:00Evidence-Based Practices to Reduce COVID-19 Transmission in Dialysis FacilitiesKliger, Alan S.Garrick, Renee2021-08-04T06:10:08-07:00doi:10.2215/CJN.07220521hwp:resource-id:clinjasn;16/8/1146American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, hemodialysis, evidence-based practiceEditorialsEditorialseditorial20212021-08-01August 202110.2215/CJN.072205211555-90411555-905X2021-08-04T06:10:08-07:002021-08Clinical Journal of the American Society of NephrologyEditorials16888114612371141114812461142
- Predictive Approaches for Acute Dialysis Requirement and Death in COVID-1910.2215/CJN.17311120Mon, 24 May 2021 02:37:49 GMT-07:00Predictive Approaches for Acute Dialysis Requirement and Death in COVID-19Vaid, AkhilChan, LiliChaudhary, KumardeepJaladanki, Suraj K.Paranjpe, IshanRussak, AdamKia, ArashTimsina, PremLevin, Matthew A.He, John CijiangBöttinger, Erwin P.Charney, Alexander W.Fayad, Zahi A.Coca, Steven G.Glicksberg, Benjamin S.Nadkarni, Girish N.,Charney, AlexJust, Allan C.Glicksberg, BenjaminNadkarni, GirishHuckins, LauraO’Reilly, PaulMiotto, RiccardoFayad, ZahiRussak, Adam J.Rahman, AdeebVaid, AkhilLe Dobbyn, AmandaLeader, AndrewMoscati, ArdenKapoor, ArjunChang, ChristieBellaire, ChristopherCarrion, DanielChaudhry, FayzanRichter, FelixSoultanidis, GeorgiosParanjpe, IshanNabeel, IsmailDe Freitas, JessicaXu, JiayiRush, JohnathanJohnson, KippVemuri, KrishnaChaudhary, KumardeepLepow, LaurenCotter, LiamLiharska, LoraPereanez, MarcoBicak, MesudeDeFelice, NicholasNaik, NidhiBeckmann, NoamNadukuru, RajivO’Hagan, RossZhao, ShanSomani, SulaimanVan Vleck, Tielman T.Mutetwa, TinayeWanyan, TingyiFauveau, ValentinYang, YangLavin, YonitLanksy, AlonaAtreja, AshishDel Valle, DianeMeyer, DaraGolden, EddyeFasihuddin, FarahHsun Wen, HueiRogers, JasonLilly Gutierrez, JenniferWalker, LauraSingh, ManbirDanieletto, MatteoNieves, Melissa A.Zweig, MicolPyzik, RenataFayad, RimaGlowe, PatriciaCalorossi, SharleneKaur, SparshdeepAscolillo, StevenRoa, YovannaLala-Trindade, AnuradhaCoca, Steven G.Percha, BethanySigel, KeithPolak, PazHirten, RobertSwartz, TaliaDo, RonLoos, Ruth J. F.Charney, DennisNestler, EricMurphy, BarbaraReich, DavidBöttinger, ErwinChatani, KumarMartin, GlennNestler, EricKovatch, PatriciaFinkelstein, JosephMurphy, BarbaraBuxbaum, JosephCho, JudyKasarskis, AndrewHorowitz, CarolCordon-Cardo, CarlosSohn, MonicaMartin, GlennGarcia-Sastre, AdolfoBagiella, EmiliaKrammer, FlorianAberg, JudithNarula, JagatWright, RobertLium, ErikWright, RosalindGelijns, AnnetineFuster, ValentinMerad, Miriam2021-05-24T14:37:49-07:00doi:10.2215/CJN.17311120hwp:resource-id:clinjasn;16/8/1158American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, dialysis, machine learning, prediction, AKIOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-08-01August 202110.2215/CJN.173111201555-90411555-905X2021-05-24T14:37:49-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16811581168
- A Case of Focal Segmental Glomerulosclerosis10.2215/CJN.19591220Tue, 09 Mar 2021 06:42:55 GMT-08:00A Case of Focal Segmental GlomerulosclerosisHogan, Jonathan J.2021-03-09T06:42:55-08:00doi:10.2215/CJN.19591220hwp:resource-id:clinjasn;16/8/1272American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular diseaseKidney Case Conference: Nephrology Quiz & QuestionnaireKidney Case Conference: Nephrology Quiz & Questionnaireresearch-article20212021-08-01August 202110.2215/CJN.195912201555-90411555-905X2021-03-09T06:42:55-08:002021-08Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz & Questionnaire16812721274
- Keeping Dialysis Patients Safe10.2215/CJN.08090621Wed, 04 Aug 2021 06:10:08 GMT-07:00Keeping Dialysis Patients SafeWager, Roberta L.2021-08-04T06:10:08-07:00doi:10.2215/CJN.08090621hwp:resource-id:clinjasn;16/8/1141American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, dialysisPatient VoicePatient Voiceresearch-article20212021-08-01August 202110.2215/CJN.080906211555-90411555-905X2021-08-04T06:10:08-07:002021-08Clinical Journal of the American Society of NephrologyPatient Voice16888114112371146114212461148
- Long-Term Immunosuppression ManagementThe long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5–8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor–based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.10.2215/CJN.15040920Wed, 14 Apr 2021 06:10:56 GMT-07:00Long-Term Immunosuppression ManagementThe long-term management of maintenance immunosuppression in kidney transplant recipients remains complex. The vast majority of patients are treated with the calcineurin inhibitor tacrolimus as the primary agent in combination with mycophenolate, with or without corticosteroids. A tacrolimus trough target 5–8 ng/ml seems to be optimal for rejection prophylaxis, but long-term tacrolimus-related side effects and nephrotoxicity support the ongoing evaluation of noncalcineurin inhibitor–based regimens. Current alternatives include belatacept or mammalian target of rapamycin inhibitors. For the former, superior kidney function at 7 years post-transplant compared with cyclosporin generated initial enthusiasm, but utilization has been hampered by high initial rejection rates. Mammalian target of rapamycin inhibitors have yielded mixed results as well, with improved kidney function tempered by higher risk of rejection, proteinuria, and adverse effects leading to higher discontinuation rates. Mammalian target of rapamycin inhibitors may play a role in the secondary prevention of squamous cell skin cancer as conversion from a calcineurin inhibitor to an mammalian target of rapamycin inhibitor resulted in a reduction of new lesion development. Early withdrawal of corticosteroids remains an attractive strategy but also is associated with a higher risk of rejection despite no difference in 5-year patient or graft survival. A major barrier to long-term graft survival is chronic alloimmunity, and regardless of agent used, managing the toxicities of immunosuppression against the risk of chronic antibody-mediated rejection remains a fragile balance.Wojciechowski, DavidWiseman, Alexander2021-04-14T06:10:56-07:00doi:10.2215/CJN.15040920hwp:resource-id:clinjasn;16/8/1264American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunosuppression, immune tolerance, kidney transplantation seriesKidney Transplantation Long-Term Management ChallengesKidney Transplantation Long-Term Management Challengesresearch-article20212021-08-01August 202110.2215/CJN.150409201555-90411555-905X2021-04-14T06:10:56-07:002021-08Clinical Journal of the American Society of NephrologyKidney Transplantation Long-Term Management Challenges16812641271
- Virtual Interviews for Nephrology Fellowship Candidates10.2215/CJN.19971220Tue, 15 Jun 2021 11:37:17 GMT-07:00Virtual Interviews for Nephrology Fellowship CandidatesFarouk, Samira S.Campbell, Kirk N.2021-06-15T11:37:17-07:00doi:10.2215/CJN.19971220hwp:resource-id:clinjasn;16/8/1275American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymedical education, virtual, interviews, fellowship, application, nephrologyPerspectivesPerspectivesresearch-article20212021-08-01August 202110.2215/CJN.199712201555-90411555-905X2021-06-15T11:37:17-07:002021-08Clinical Journal of the American Society of NephrologyPerspectives16812751277
- Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor Initiation10.2215/CJN.02480221Tue, 20 Apr 2021 11:01:49 GMT-07:00Clinical Implications of an Acute Dip in eGFR after SGLT2 Inhibitor InitiationHeerspink, Hiddo J. L.Cherney, David Z.I.2021-04-20T11:01:49-07:00doi:10.2215/CJN.02480221hwp:resource-id:clinjasn;16/8/1278American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologySGLT2 inhibitor, glomerularhyperfiltration glomerular filtration rate, clinical nephrology, sodium-glucose cotransporter2PerspectivesPerspectivesresearch-article20212021-08-01August 202110.2215/CJN.024802211555-90411555-905X2021-04-20T11:01:49-07:002021-08Clinical Journal of the American Society of NephrologyPerspectives16812781280
- Prioritizing Peritoneal Catheter Placement during the COVID-19 Pandemic10.2215/CJN.19141220Fri, 12 Mar 2021 06:08:00 GMT-08:00Prioritizing Peritoneal Catheter Placement during the COVID-19 PandemicOliver, Matthew J.Crabtree, John H.2021-03-12T06:08:00-08:00doi:10.2215/CJN.19141220hwp:resource-id:clinjasn;16/8/1281American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, COVID-19PerspectivesPerspectivesresearch-article20212021-08-01August 202110.2215/CJN.191412201555-90411555-905X2021-03-12T06:08:00-08:002021-08Clinical Journal of the American Society of NephrologyPerspectives16812811283
- HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy10.2215/CJN.18021120Thu, 03 Jun 2021 10:41:09 GMT-07:00HLA Alleles and Prognosis of PLA2R-Related Membranous NephropathyLe, Wei-BoShi, Jing-SongFan, YangGong, Si-Wen2021-06-03T10:41:09-07:00doi:10.2215/CJN.18021120hwp:resource-id:clinjasn;16/8/1221American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, PLA2R, HLA, glomerular disease, genetics, haplotypes, prognosisOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-08-01August 202110.2215/CJN.180211201555-90411555-905X2021-06-03T10:41:09-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16812211227
- Cardiovascular Safety of Roxadustat in CKD Anemia10.2215/CJN.08280621Fri, 06 Aug 2021 11:00:21 GMT-07:00Cardiovascular Safety of Roxadustat in CKD AnemiaWinkelmayer, Wolfgang C.Walther, Carl P.2021-08-06T11:00:21-07:00doi:10.2215/CJN.08280621hwp:resource-id:clinjasn;16/8/1155American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular, anemiaEditorialsEditorialseditorial20212021-08-01August 202110.2215/CJN.082806211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyEditorials16881155119011571200
- Latency, Anti-Bacterial Resistance Pattern, and Bacterial Infection–Related Glomerulonephritis10.2215/CJN.18631120Mon, 07 Jun 2021 11:50:50 GMT-07:00Latency, Anti-Bacterial Resistance Pattern, and Bacterial Infection–Related GlomerulonephritisJohn, Elenjickal EliasThomas, AthulEapen, Jeethu JosephYusuf, SabinaRoy, SanjeetValson, Anna T.David, Vinoi GeorgeVarughese, SantoshAlexander, Suceena2021-06-07T11:50:50-07:00doi:10.2215/CJN.18631120hwp:resource-id:clinjasn;16/8/1210American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, immunology and pathology, kidney biopsy, nephritis, primary glomerulonephritis, bacterial infectionsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-08-01August 202110.2215/CJN.186311201555-90411555-905X2021-06-07T11:50:50-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16881210114912201151
- Temporal Trends of Acute Kidney Injury and Associated Risk Exposures in Extremely Preterm Infantshuangped@mail.ncku.edu.tw10.2215/CJN.19301220Wed, 04 Aug 2021 07:07:05 GMT-07:00Temporal Trends of Acute Kidney Injury and Associated Risk Exposures in Extremely Preterm InfantsChen, Chih-ChiaLin, Yung-ChiehWang, Shan-TairHuang, Chao-Ching,,Li-Wen, ChenYung-Chieh, LinWen-Hao, YuChih-Chia, ChenYen-Ju, ChenChia-Lin, KohYi-Shan, TsaiRay-Bing, ChenKuo-Jung, LeeChih-Chung, HsuChi‐Hsiang, ChuChiou-Feng, LinCheng-Chin, Kuo2021-08-04T07:07:05-07:00doi:10.2215/CJN.19301220hwp:resource-id:clinjasn;16/8/1169American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, care practice, extremely preterm infantsOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-08-01August 202110.2215/CJN.193012201555-90411555-905X2021-08-04T07:07:05-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16811691177
- The Continuum of Acid StressAcid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This “acid stress” continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.10.2215/CJN.17541120Fri, 19 Mar 2021 07:37:54 GMT-07:00The Continuum of Acid StressAcid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This “acid stress” continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.Wesson, Donald E.2021-03-19T07:37:54-07:00doi:10.2215/CJN.17541120hwp:resource-id:clinjasn;16/8/1292American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, nutrition, oxidative stress, progression of chronic renal failureReviewsReviewsreview-article20212021-08-01August 202110.2215/CJN.175411201555-90411555-905X2021-03-19T07:37:54-07:002021-08Clinical Journal of the American Society of NephrologyReviews16812921299
- The Effects of Oral Energy-Dense Supplements on Nutritional Status in Nondiabetic Maintenance Hemodialysis Patients10.2215/CJN.16821020Mon, 21 Jun 2021 09:54:33 GMT-07:00The Effects of Oral Energy-Dense Supplements on Nutritional Status in Nondiabetic Maintenance Hemodialysis PatientsYang, YayaQin, XianhuiChen, JunzhiWang, QiKong, YaozhongWan, QijunTao, HuiqinLiu, AiqunLi, YoubaoLin, ZizhenHuang, YanHe, YanhuanLei, ZihanLiang, Min2021-06-21T09:54:33-07:00doi:10.2215/CJN.16821020hwp:resource-id:clinjasn;16/8/1228American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, dialysis, nutritional status, maintenance hemodialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-08-01August 202110.2215/CJN.168210201555-90411555-905X2021-06-21T09:54:33-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16881228114312361145
- Effect of Vitamin D Supplementation on Kidney Function in Adults with Prediabetes10.2215/CJN.00420121Fri, 06 Aug 2021 11:00:21 GMT-07:00Effect of Vitamin D Supplementation on Kidney Function in Adults with PrediabetesKim, Sun H.Brodsky, Irwin G.Chatterjee, RaneeKashyap, Sangeeta R.Knowler, William C.Liao, EmiliaNelson, JasonPratley, RichardRasouli, NedaVickery, Ellen M.Sarnak, MarkPittas, Anastassios G.,,Pittas, Anastassios G.Brodsky, IrwinCeglia, LisaChadha, ChhaviChatterjee, RaneeDawson-Hughes, BessDesouza, CyrusDolor, RowenaForeyt, JohnGhazi, AdlineHsia, Daniel S.Johnson, Karen C.Kashyap, Sangeeta R.Kim, SunLeBlanc, Erin S.Lewis, Michael R.Liao, EmiliaMalozowski, SaulNeff, Lisa M.O'Neil, PatrickPark, JeanPeters, AnnePhillips, Lawrence S.Pratley, RichardRaskin, PhilipRasouli, NedaRobbins, DavidRosen, CliffordAroda, Vanita R.Sheehan, PatriciaStaten, Myrlene A.Knowler, William C.2021-08-06T11:00:21-07:00doi:10.2215/CJN.00420121hwp:resource-id:clinjasn;16/8/1201American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvitamin D, glomerular filtration rate, albuminuria, diabetes mellitus, microalbuminuria, proteinuriaOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20212021-08-01August 202110.2215/CJN.004201211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16812011209
- Correction: Major Bleeding and Risk of Death after Percutaneous Native Kidney Biopsies: A French Nationwide Cohort Study10.2215/CJN.08200621Fri, 06 Aug 2021 11:00:21 GMT-07:00Correction: Major Bleeding and Risk of Death after Percutaneous Native Kidney Biopsies: A French Nationwide Cohort StudyAmerican Society of Nephrology2021-08-06T11:00:21-07:00doi:10.2215/CJN.08200621hwp:resource-id:clinjasn;16/8/1261American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, bleeding, epidemiology and outcomes, nationwide data, score, diabetic nephropathies, thrombocytopenia chromosome breakage, frailty, hemorrhage, hematomaErratumErratumcorrection20212021-08-01August 202110.2215/CJN.082006211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyErratum16158111261158712611594
- Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non–Dialysis-Dependent CKD10.2215/CJN.16191020Fri, 06 Aug 2021 11:00:21 GMT-07:00Efficacy and Cardiovascular Safety of Roxadustat for Treatment of Anemia in Patients with Non–Dialysis-Dependent CKDProvenzano, RobertSzczech, LyndaLeong, RobertSaikali, Khalil G.Zhong, MingLee, Tyson T.Little, Dustin J.Houser, Mark T.Frison, LarsHoughton, JohnNeff, Thomas B.2021-08-06T11:00:21-07:00doi:10.2215/CJN.16191020hwp:resource-id:clinjasn;16/8/1190American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyroxadustat, anemia, chronic kidney disease, efficacy, MACE, safetyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-08-01August 202110.2215/CJN.161910201555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16881190115512001157
- Better Nutrition Care for Patients on Hemodialysis10.2215/CJN.06800521Wed, 04 Aug 2021 08:03:44 GMT-07:00Better Nutrition Care for Patients on HemodialysisIkizler, T. Alp2021-08-04T08:03:44-07:00doi:10.2215/CJN.06800521hwp:resource-id:clinjasn;16/8/1143American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisease control and pest management, ecology and epidemiology, genetics and resistance, mycology, disease resistance.EditorialsEditorialseditorial20212021-08-01August 202110.2215/CJN.068005211555-90411555-905X2021-08-04T08:03:44-07:002021-08Clinical Journal of the American Society of NephrologyEditorials16881143122811451236
- New Insights into Epidemiology and Outcome of Bacterial Infection–Related Glomerulonephritis10.2215/CJN.07910621Fri, 06 Aug 2021 11:00:21 GMT-07:00New Insights into Epidemiology and Outcome of Bacterial Infection–Related GlomerulonephritisMedjeral-Thomas, Nicholas R.Pusey, Charles D.2021-08-06T11:00:21-07:00doi:10.2215/CJN.07910621hwp:resource-id:clinjasn;16/8/1149American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyepidemiology and outcomes, glomerulonephritisEditorialsEditorialseditorial20212021-08-01August 202110.2215/CJN.079106211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyEditorials16881149121011511220
- Recurrence of IgA Nephropathy after Kidney Transplantation in Adults10.2215/CJN.00910121Fri, 06 Aug 2021 11:00:21 GMT-07:00Recurrence of IgA Nephropathy after Kidney Transplantation in AdultsUffing, AudreyPérez-Saéz, Maria JoséJouve, ThomasBugnazet, MathildeMalvezzi, PaoloMuhsin, Saif A.Lafargue, Marie-CamilleReindl-Schwaighofer, RomanMorlock, AlinaOberbauer, RainerBuxeda, AnnaBurballa, CarlaPascual, Juliovon Moos, SerainaSeeger, HaraldLa Manna, GaetanoComai, GiorgiaBini, ClaudiaRusso, Luis SanchezFarouk, SamiraNissaisorakarn, PitchaphonPatel, HetAgrawal, NikhilMastroianni-Kirsztajn, GiannaMansur, JulianaTedesco-Silva, HélioVentura, Carlucci GualbertoAgena, FabianaDavid-Neto, EliasAkalin, EnverAlani, OmarMazzali, MarildaManfro, Roberto CerattiBauer, Andrea CarlaWang, Aileen X.Cheng, Xingxing S.Schold, Jesse D.Berger, Stefan P.Cravedi, PaoloRiella, Leonardo V.2021-08-06T11:00:21-07:00doi:10.2215/CJN.00910121hwp:resource-id:clinjasn;16/8/1247American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, IgA nephropathy, IgA deposition, glomerular disease, recurrence, graft survivalOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-08-01August 202110.2215/CJN.009101211555-90411555-905X2021-08-06T11:00:21-07:002021-08Clinical Journal of the American Society of NephrologyOriginal Articles16812471255
- Transplant Biopsy Assessment in 21st Century10.1681/ASN.2021060804Mon, 19 Jul 2021 01:48:31 GMT-07:00Transplant Biopsy Assessment in 21st CenturyMalone, Andrew F.2021-07-19T13:48:31-07:00doi:10.1681/ASN.2021060804hwp:resource-id:jnephrol;32/8/1827American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygene expression, transplantationEditorialsEditorialseditorial20212021-08-01August 202110.1681/ASN.20210608041046-66731533-34502021-07-19T13:48:31-07:002021-08Journal of the American Society of NephrologyEditorials32881827193318281945
- Biobanks Linked to Electronic Health Records Accelerate Genomic Discovery10.1681/ASN.2021060836Fri, 09 Jul 2021 06:39:02 GMT-07:00Biobanks Linked to Electronic Health Records Accelerate Genomic DiscoveryCrawford, Dana C.Sedor, John R.2021-07-09T06:39:02-07:00doi:10.1681/ASN.2021060836hwp:resource-id:jnephrol;32/8/1828American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyGWAS, PheWAS, complementEditorialsEditorialseditorial20212021-08-01August 202110.1681/ASN.20210608361046-66731533-34502021-07-09T06:39:02-07:002021-08Journal of the American Society of NephrologyEditorials32881828203118292047
- Data-Driven Kidney Transplant Phenotyping as a Histology-Independent Framework for Biomarker Discovery10.1681/ASN.2020121685Wed, 02 Jun 2021 11:42:25 GMT-07:00Data-Driven Kidney Transplant Phenotyping as a Histology-Independent Framework for Biomarker DiscoveryBuscher, KonradHeitplatz, Barbaravan Marck, VeerleSong, JianLoismann, SophieRixen, RebeccaHüchtmann, BirteKurian, SunilEhinger, ErikWolf, DennisLey, KlausPavenstädt, HermannReuter, Stefan2021-06-02T11:42:25-07:00doi:10.1681/ASN.2020121685hwp:resource-id:jnephrol;32/8/1933American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, transcriptional profiling, transplant pathology, acute allograft rejection, kidney transplantationBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20201216851046-66731533-34502021-06-02T11:42:25-07:002021-08Journal of the American Society of NephrologyBasic Research32881933182719451828
- Prevention of Post-Transplantation Diabetes: Small Steps, Big Opportunities10.1681/ASN.2021060777Fri, 30 Jul 2021 11:00:32 GMT-07:00Prevention of Post-Transplantation Diabetes: Small Steps, Big OpportunitiesSharif, Adnan2021-07-30T11:00:32-07:00doi:10.1681/ASN.2021060777hwp:resource-id:jnephrol;32/8/1833American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes mellitus, kidney transplantation, outcomes, transplantation, transplant outcomes, randomized controlled trialsEditorialsEditorialseditorial20212021-08-01August 202110.1681/ASN.20210607771046-66731533-34502021-07-30T11:00:32-07:002021-08Journal of the American Society of NephrologyEditorials32881833208318342098
- Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial10.1681/ASN.2021010127Fri, 30 Jul 2021 11:00:32 GMT-07:00Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized TrialSchwaiger, ElisabethKrenn, SimonKurnikowski, AmelieBergfeld, LeonPérez-Sáez, María JoséFrey, AlexanderTopitz, DavidBergmann, MichaelHödlmoser, SebastianBachmann, FriederikeHalleck, FabianKron, SusanneHafner-Giessauf, HildegardEller, KathrinRosenkranz, Alexander R.Crespo, MartaFaura, AnnaTura, AndreaSong, Peter X. K.Port, Friedrich K.Pascual, JulioBudde, KlemensRistl, RobinWerzowa, JohannesHecking, Manfred2021-07-30T11:00:32-07:00doi:10.1681/ASN.2021010127hwp:resource-id:jnephrol;32/8/2083American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, diabetes mellitus, clinical trial, diabetes, organ transplant, randomized controlled trials, renal transplantation, hyperglycemia, cardiovascularClinical ResearchClinical Researchresearch-article20212021-08-01August 202110.1681/ASN.20210101271046-66731533-34502021-07-30T11:00:32-07:002021-08Journal of the American Society of NephrologyClinical Research32882083183320981834
- Increasing mTORC1 Pathway Activity or Methionine Supplementation during Pregnancy Reverses the Negative Effect of Maternal Malnutrition on the Developing Kidney10.1681/ASN.2020091321Thu, 06 May 2021 05:18:48 GMT-07:00Increasing mTORC1 Pathway Activity or Methionine Supplementation during Pregnancy Reverses the Negative Effect of Maternal Malnutrition on the Developing KidneyMakayes, YanivResnick, EladHinden, LiadAizenshtein, ElinaShlomi, TomerKopan, RaphaelNechama, MorrisVolovelsky, Oded2021-05-06T05:18:48-07:00doi:10.1681/ASN.2020091321hwp:resource-id:jnephrol;32/8/1898American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, malnutrition, intrauterine environment, methionine, mTOR pathway, nephron progenitor cells, stem cellBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20200913211046-66731533-34502021-05-06T05:18:48-07:002021-08Journal of the American Society of NephrologyBasic Research32818981912
- Long-Term Kidney Outcomes Following Dialysis-Treated Childhood Acute Kidney Injury: A Population-Based Cohort Study10.1681/ASN.2020111665Wed, 26 May 2021 12:00:54 GMT-07:00Long-Term Kidney Outcomes Following Dialysis-Treated Childhood Acute Kidney Injury: A Population-Based Cohort StudyRobinson, Cal H.Jeyakumar, NivethikaLuo, BinWald, RonGarg, Amit X.Nash, Danielle M.McArthur, EricGreenberg, Jason H.Askenazi, DavidMammen, CherryThabane, LehanaGoldstein, StuartParekh, Rulan S.Zappitelli, MichaelChanchlani, Rahul2021-05-26T12:00:54-07:00doi:10.1681/ASN.2020111665hwp:resource-id:jnephrol;32/8/2005American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, children, chronic kidney disease, clinical epidemiology, end stage kidney disease, hypertension, mortality, pediatric nephrology, acute renal failure, dialysisClinical EpidemiologyClinical Epidemiologyresearch-article20212021-08-01August 202110.1681/ASN.20201116651046-66731533-34502021-05-26T12:00:54-07:002021-08Journal of the American Society of NephrologyClinical Epidemiology32810101020052679268026812019267926802682
- Racial and Neighborhood-Level Disparities in COVID-19 Incidence among Patients on Hemodialysis in New York City10.1681/ASN.2020111606Thu, 03 Jun 2021 10:55:07 GMT-07:00Racial and Neighborhood-Level Disparities in COVID-19 Incidence among Patients on Hemodialysis in New York CityTummalapalli, Sri LekhaSilberzweig, JeffreyCukor, DanielLin, Jonathan T.Barbar, TarekLiu, YaoKim, KwanParker, Thomas S.Levine, Daniel M.Ibrahim, Said A.2021-06-03T10:55:07-07:00doi:10.1681/ASN.2020111606hwp:resource-id:jnephrol;32/8/2048American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, hemodialysis, disparities, social determinants of healthClinical ResearchClinical Researchresearch-article20212021-08-01August 202110.1681/ASN.20201116061046-66731533-34502021-06-03T10:55:07-07:002021-08Journal of the American Society of NephrologyClinical Research32882048i2056i
- Procurement Biopsies in Kidney Transplantation: More Information May Not Lead to Better Decisions10.1681/ASN.2021030403Thu, 27 May 2021 10:50:43 GMT-07:00Procurement Biopsies in Kidney Transplantation: More Information May Not Lead to Better DecisionsLentine, Krista L.Kasiske, BertramAxelrod, David A.2021-05-27T10:50:43-07:00doi:10.1681/ASN.2021030403hwp:resource-id:jnephrol;32/8/1835American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycadaver organ transplantation, kidney biopsy, transplantationPerspectivesPerspectivesresearch-article20212021-08-01August 202110.1681/ASN.20210304031046-66731533-34502021-05-27T10:50:43-07:002021-08Journal of the American Society of NephrologyPerspectives32818351837
- Antibody Status, Disease History, and Incidence of SARS-CoV-2 Infection Among Patients on Chronic Dialysis10.1681/ASN.2021030387Fri, 02 Jul 2021 08:30:07 GMT-07:00Antibody Status, Disease History, and Incidence of SARS-CoV-2 Infection Among Patients on Chronic DialysisCohen, Dena E.Sibbel, ScottMarlowe, GilbertBludorn, KelseyMiller, DawnKelley, TaraConnaire, JeffreyYoung, AmyTentori, FrancescaBrunelli, Steven M.2021-07-02T08:30:07-07:00doi:10.1681/ASN.2021030387hwp:resource-id:jnephrol;32/8/1880American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, hemodialysis, immunityRapid CommunicationsRapid Communicationsresearch-article20212021-08-01August 202110.1681/ASN.20210303871046-66731533-34502021-07-02T08:30:07-07:002021-08Journal of the American Society of NephrologyRapid Communications32818801886
- A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans10.1681/ASN.2020121762Fri, 28 May 2021 10:31:36 GMT-07:00A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in HumansDai, LeiLi, JingzhiXie, LiangqunWang, WeinanLu, YangXie, MingkunHuang, JingruiShen, KuifangYang, HuiPei, ChenlinZhao, YanhuaZhang, Weishe2021-05-28T10:31:36-07:00doi:10.1681/ASN.2020121762hwp:resource-id:jnephrol;32/8/1871American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologybilateral renal agenesis, new pathogenic gene, nephronectinRapid CommunicationsRapid Communicationsresearch-article20212021-08-01August 202110.1681/ASN.20201217621046-66731533-34502021-05-28T10:31:36-07:002021-08Journal of the American Society of NephrologyRapid Communications32818711879
- Presence of SARS-CoV-2 Antibodies in Spent Peritoneal Dialysate10.1681/ASN.2021020161Tue, 06 Jul 2021 11:35:56 GMT-07:00Presence of SARS-CoV-2 Antibodies in Spent Peritoneal DialysateWang, XiaolingGrobe, NadjaPatel, AmrishSharma, ShuchitaUribarri, JaimeKotanko, Peter2021-07-06T11:35:56-07:00doi:10.1681/ASN.2021020161hwp:resource-id:jnephrol;32/8/1865American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, antibody, SARS-CoV-2, COVID-19Research LettersResearch Lettersresearch-article20212021-08-01August 202110.1681/ASN.20210201611046-66731533-34502021-07-06T11:35:56-07:002021-08Journal of the American Society of NephrologyResearch Letters32818651867
- Race-Free Equations for eGFR: Comparing Effects on CKD Classification10.1681/ASN.2021020224Thu, 29 Jul 2021 01:47:08 GMT-07:00Race-Free Equations for eGFR: Comparing Effects on CKD ClassificationDiao, James A.Powe, Neil R.Manrai, Arjun K.2021-07-29T13:47:08-07:00doi:10.1681/ASN.2021020224hwp:resource-id:jnephrol;32/8/1868American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rate, ethnicity, epidemiology and outcomes, chronic kidney diseaseResearch LettersResearch Lettersresearch-article20212021-08-01August 202110.1681/ASN.20210202241046-66731533-34502021-07-29T13:47:08-07:002021-08Journal of the American Society of NephrologyResearch Letters32818681870
- Considerations in Comparing Proximal Tubule Cell Culture Models10.1681/ASN.2021040510Mon, 12 Jul 2021 04:19:15 GMT-07:00Considerations in Comparing Proximal Tubule Cell Culture ModelsWeisz, Ora A.2021-07-12T16:19:15-07:00doi:10.1681/ASN.2021040510hwp:resource-id:jnephrol;32/8/2099American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal proximal tubule cellLetters to the EditorLetters to the Editorletter20212021-08-01August 202110.1681/ASN.20210405101046-66731533-34502021-07-12T16:19:15-07:002021-08Journal of the American Society of NephrologyLetters to the Editor3281209986210097
- Correction: Long-Term Exposure to Ambient PM2.5 and Increased Risk of Chronic Kidney Disease Prevalence in China10.1681/ASN.2021050692Thu, 17 Jun 2021 07:41:24 GMT-07:00Correction: Long-Term Exposure to Ambient PM2.5 and Increased Risk of Chronic Kidney Disease Prevalence in ChinaAmerican Society of Nephrology2021-06-17T07:41:24-07:00doi:10.1681/ASN.2021050692hwp:resource-id:jnephrol;32/8/2101American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20212021-08-01August 202110.1681/ASN.20210506921046-66731533-34502021-06-17T07:41:24-07:002021-08Journal of the American Society of NephrologyErrata32328221014482101458
- Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer10.1681/ASN.2020091340Thu, 08 Jul 2021 08:10:52 GMT-07:00Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic TracerStremke, Elizabeth R.Wiese, Gretchen N.Moe, Sharon M.Wastney, Meryl E.Moorthi, Ranjani N.Hill Gallant, Kathleen M.2021-07-08T08:10:52-07:00doi:10.1681/ASN.2020091340hwp:resource-id:jnephrol;32/8/2057American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphorus, chronic kidney disease, intestinal absorption, nutrition, CKD-MBDClinical ResearchClinical Researchresearch-article20212021-08-01August 202110.1681/ASN.20200913401046-66731533-34502021-07-08T08:10:52-07:002021-08Journal of the American Society of NephrologyClinical Research32882057183020691832
- Novel Insights into Mechanisms of Intestinal Phosphate Absorption in Patients with Chronic Kidney Disease10.1681/ASN.2021050610Fri, 30 Jul 2021 11:00:32 GMT-07:00Novel Insights into Mechanisms of Intestinal Phosphate Absorption in Patients with Chronic Kidney DiseaseKritmetapak, KittraweeKumar, Rajiv2021-07-30T11:00:32-07:00doi:10.1681/ASN.2021050610hwp:resource-id:jnephrol;32/8/1830American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate uptake, vitamin D, parathyroid hormone, 1,25-dihydroxyvitamin D, FGF-23, intestinal phosphate absorption, transcellular intestinal phosphate absorption, paracellular intestinal phosphate absorption, chronic kidney failureEditorialsEditorialseditorial20212021-08-01August 202110.1681/ASN.20210506101046-66731533-34502021-07-30T11:00:32-07:002021-08Journal of the American Society of NephrologyEditorials32881830205718322069
- Missing Self–Induced Microvascular Rejection of Kidney Allografts: A Population-Based Study10.1681/ASN.2020111558Thu, 22 Jul 2021 06:31:45 GMT-07:00Missing Self–Induced Microvascular Rejection of Kidney Allografts: A Population-Based StudyCallemeyn, JasperSenev, AleksandarCoemans, MaartenLerut, EvelyneSprangers, BenKuypers, DirkKoenig, AliceThaunat, OlivierEmonds, Marie-PauleNaesens, Maarten2021-07-22T06:31:45-07:00doi:10.1681/ASN.2020111558hwp:resource-id:jnephrol;32/8/2070American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynatural killer cells, kidney transplantation, missing self, microvascular inflammation, antibody-mediated rejectionClinical ResearchClinical Researchresearch-article20212021-08-01August 202110.1681/ASN.20201115581046-66731533-34502021-07-22T06:31:45-07:002021-08Journal of the American Society of NephrologyClinical Research32820702082
- Phase Separation of MAGI2-Mediated Complex Underlies Formation of Slit Diaphragm Complex in Glomerular Filtration Barrier10.1681/ASN.2020111590Fri, 30 Jul 2021 11:00:32 GMT-07:00Phase Separation of MAGI2-Mediated Complex Underlies Formation of Slit Diaphragm Complex in Glomerular Filtration BarrierZhang, HaijiaoLin, LinLiu, JianpingPan, LifengLin, ZhijieZhang, MingjieZhang, JiongCao, YingZhu, JinweiZhang, Rongguang2021-07-30T11:00:32-07:00doi:10.1681/ASN.2020111590hwp:resource-id:jnephrol;32/8/1946American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycell adhesion, nephrotic syndrome, nephrin, cytoskeleton, phase separation, MAGI2, slit diaphragmBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20201115901046-66731533-34502021-07-30T11:00:32-07:002021-08Journal of the American Society of NephrologyBasic Research32819461960
- TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2020071094Mon, 21 Jun 2021 09:55:14 GMT-07:00TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney DiseaseCordido, AdrianNuñez-Gonzalez, LauraMartinez-Moreno, Julio M.Lamas-Gonzalez, OlayaRodriguez-Osorio, LauraPerez-Gomez, Maria VanessaMartin-Sanchez, DiegoOuteda, PatriciaChiaravalli, MarcoWatnick, TerryBoletta, AlessandraDiaz, CandidoCarracedo, AngelSanz, Ana B.Ortiz, AlbertoGarcia-Gonzalez, Miguel A.2021-06-21T09:55:14-07:00doi:10.1681/ASN.2020071094hwp:resource-id:jnephrol;32/8/1913American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyTWEAK, autosomal dominant polycystic kidney disease, Pkd1, Fn14, inflammationBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20200710941046-66731533-34502021-06-21T09:55:14-07:002021-08Journal of the American Society of NephrologyBasic Research32819131932
- Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia10.1681/ASN.2020101531Thu, 08 Jul 2021 08:10:52 GMT-07:00Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without AnemiaGuedes, MuriloMuenz, Daniel G.Zee, JarcyBieber, BrianStengel, BenedicteMassy, Ziad A.Mansencal, NicolasWong, Michelle M.Y.Charytan, David M.Reichel, HelmutWaechter, SandraPisoni, Ronald L.Robinson, Bruce M.Pecoits-Filho, Roberto2021-07-08T08:10:52-07:00doi:10.1681/ASN.2020101531hwp:resource-id:jnephrol;32/8/2020American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, anemia, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20212021-08-01August 202110.1681/ASN.20201015311046-66731533-34502021-07-08T08:10:52-07:002021-08Journal of the American Society of NephrologyClinical Epidemiology3288332020i6546552030i655656
- Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Diseasedborza@mmc.edu10.1681/ASN.2020101431Fri, 23 Apr 2021 09:46:52 GMT-07:00Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM DiseaseShen, Cong-rongJia, Xiao-yuLuo, WentianOlaru, FlorinaCui, ZhaoZhao, Ming-huiBorza, Dorin-Bogdan2021-04-23T09:46:52-07:00doi:10.1681/ASN.2020101431hwp:resource-id:jnephrol;32/8/1887American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, extracellular matrix, glomerulonephritis, Goodpasture’s syndrome, laminin, autoantibodies, pulmonary hemorrhage, glomerular basement membraneBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20201014311046-66731533-34502021-04-23T09:46:52-07:002021-08Journal of the American Society of NephrologyBasic Research32881887i1897i
- REST and Stress Resistance in the Aging Kidney10.1681/ASN.2021020231Wed, 02 Jun 2021 11:22:10 GMT-07:00REST and Stress Resistance in the Aging KidneyMagassa, SatoAron, LiviuHoguin, ClémentIsnard, PierreTerzi, FabiolaLegendre, ChristopheYankner, Bruce A.Canaud, Guillaume2021-06-02T11:22:10-07:00doi:10.1681/ASN.2021020231hwp:resource-id:jnephrol;32/8/1974American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, aging, REST, cytoskeleton, apoptosisBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20210202311046-66731533-34502021-06-02T11:22:10-07:002021-08Journal of the American Society of NephrologyBasic Research32819741986
- Circulating Soluble Fms-like Tyrosine Kinase in Renal Diseases Other than PreeclampsiaSoluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a naturally occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature of distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in various diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (e.g., endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with CKD and after kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this study, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.giodimarco@gmail.com10.1681/ASN.2020111579Mon, 21 Jun 2021 09:55:14 GMT-07:00Circulating Soluble Fms-like Tyrosine Kinase in Renal Diseases Other than PreeclampsiaSoluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a naturally occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature of distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in various diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (e.g., endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with CKD and after kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this study, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.Wewers, Theresa M.Schulz, AnnikaNolte, IngoPavenstädt, HermannBrand, MarcusDi Marco, Giovana S.2021-06-21T09:55:14-07:00doi:10.1681/ASN.2020111579hwp:resource-id:jnephrol;32/8/1853American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, soluble Fms-like tyrosine kinase, kidney disease, risk factors, vascular endothelial growth factor, acute renal failure, chronic kidney disease, renal transplantationReviewsReviewsreview-article20212021-08-01August 202110.1681/ASN.20201115791046-66731533-34502021-06-21T09:55:14-07:002021-08Journal of the American Society of NephrologyReviews32818531863
- Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse Model10.1681/ASN.2020060777Thu, 27 May 2021 10:50:43 GMT-07:00Uncovering Modifier Genes of X-Linked Alport Syndrome Using a Novel Multiparent Mouse ModelTakemon, YukaWright, ValerieDavenport, BernardGatti, Daniel M.Sheehan, Susan M.Letson, KelseySavage, Holly S.Lennon, RachelKorstanje, Ron2021-05-27T10:50:43-07:00doi:10.1681/ASN.2020060777hwp:resource-id:jnephrol;32/8/1961American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, Alport-s syndrome, gene expression, genetics and developmentBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20200607771046-66731533-34502021-05-27T10:50:43-07:002021-08Journal of the American Society of NephrologyBasic Research32819611973
- This Month's Highlights10.1681/ASN.2021060755Fri, 30 Jul 2021 11:00:32 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2021-07-30T11:00:32-07:00doi:10.1681/ASN.2021060755hwp:resource-id:jnephrol;32/8/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsarticle-commentary20212021-08-01August 202110.1681/ASN.20210607551046-66731533-34502021-07-30T11:00:32-07:002021-08Journal of the American Society of NephrologyThis Month’s Highlights328888i188720202048i189720302056
- Medical Records-Based Genetic Studies of the Complement Systemkk473@columbia.edu10.1681/ASN.2020091371Mon, 03 May 2021 06:08:23 GMT-07:00Medical Records-Based Genetic Studies of the Complement SystemKhan, AtlasShang, NingPetukhova, LynnZhang, JunShen, YufengHebbring, Scott J.Moncrieffe, HalimaKottyan, Leah C.Namjou-Khales, BahramKnevel, RachelRaychaudhuri, SoumyaKarlson, Elizabeth W.Harley, John B.Stanaway, Ian B.Crosslin, DavidDenny, Joshua C.Elkind, Mitchell S.V.Gharavi, Ali G.Hripcsak, GeorgeWeng, ChunhuaKiryluk, Krzysztof2021-05-03T06:08:23-07:00doi:10.1681/ASN.2020091371hwp:resource-id:jnephrol;32/8/2031American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyelectronic health records, genome wide association study, phenome wide association study, complement system, autoimmunityClinical ResearchClinical Researchresearch-article20212021-08-01August 202110.1681/ASN.20200913711046-66731533-34502021-05-03T06:08:23-07:002021-08Journal of the American Society of NephrologyClinical Research32882031182820471829
- Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy10.1681/ASN.2020091373Wed, 16 Jun 2021 10:31:16 GMT-07:00Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic NephropathyKim, Seo RinPuranik, Amrutesh S.Jiang, KaiChen, XiaojunZhu, Xiang-YangTaylor, IanKhodadadi-Jamayran, AlirezaLerman, AmirHickson, LaTonya J.Childs, Bennett G.Textor, Stephen C.Tchkonia, TamaraNiewold, Timothy B.Kirkland, James L.Lerman, Lilach O.2021-06-16T10:31:16-07:00doi:10.1681/ASN.2020091373hwp:resource-id:jnephrol;32/8/1987American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysenescence, renal artery stenosis, transcriptome, dasatinib, quercetinBasic ResearchBasic Researchresearch-article20212021-08-01August 202110.1681/ASN.20200913731046-66731533-34502021-06-16T10:31:16-07:002021-08Journal of the American Society of NephrologyBasic Research32819872004
- Current Methodological Challenges of Single-Cell and Single-Nucleus RNA-Sequencing in Glomerular DiseasesSingle-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) allow transcriptomic profiling of thousands of cells from a renal biopsy specimen at a single-cell resolution. Both methods are promising tools to unravel the underlying pathophysiology of glomerular diseases. This review provides an overview of the technical challenges that should be addressed when designing single-cell transcriptomics experiments that focus on glomerulopathies. The isolation of glomerular cells from core needle biopsy specimens for single-cell transcriptomics remains difficult and depends upon five major factors. First, core needle biopsies generate little tissue material, and several samples are required to identify glomerular cells. Second, both fresh and frozen tissue samples may yield glomerular cells, although every experimental pipeline has different (dis)advantages. Third, enrichment for glomerular cells in human tissue before single-cell analysis is challenging because no effective standardized pipelines are available. Fourth, the current warm cell-dissociation protocols may damage glomerular cells and induce transcriptional artifacts, which can be minimized by using cold dissociation techniques at the cost of less efficient cell dissociation. Finally, snRNA-seq methods may be superior to scRNA-seq in isolating glomerular cells; however, the efficacy of snRNA-seq on core needle biopsy specimens remains to be proven. The field of single-cell omics is rapidly evolving, and the integration of these techniques in multiomics assays will undoubtedly create new insights in the complex pathophysiology of glomerular diseases.ben.sprangers@uzleuven.be10.1681/ASN.2021020157Thu, 17 Jun 2021 07:41:25 GMT-07:00Current Methodological Challenges of Single-Cell and Single-Nucleus RNA-Sequencing in Glomerular DiseasesSingle-cell RNA sequencing (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) allow transcriptomic profiling of thousands of cells from a renal biopsy specimen at a single-cell resolution. Both methods are promising tools to unravel the underlying pathophysiology of glomerular diseases. This review provides an overview of the technical challenges that should be addressed when designing single-cell transcriptomics experiments that focus on glomerulopathies. The isolation of glomerular cells from core needle biopsy specimens for single-cell transcriptomics remains difficult and depends upon five major factors. First, core needle biopsies generate little tissue material, and several samples are required to identify glomerular cells. Second, both fresh and frozen tissue samples may yield glomerular cells, although every experimental pipeline has different (dis)advantages. Third, enrichment for glomerular cells in human tissue before single-cell analysis is challenging because no effective standardized pipelines are available. Fourth, the current warm cell-dissociation protocols may damage glomerular cells and induce transcriptional artifacts, which can be minimized by using cold dissociation techniques at the cost of less efficient cell dissociation. Finally, snRNA-seq methods may be superior to scRNA-seq in isolating glomerular cells; however, the efficacy of snRNA-seq on core needle biopsy specimens remains to be proven. The field of single-cell omics is rapidly evolving, and the integration of these techniques in multiomics assays will undoubtedly create new insights in the complex pathophysiology of glomerular diseases.Deleersnijder, DriesCallemeyn, JasperArijs, IngridNaesens, MaartenVan Craenenbroeck, Amaryllis H.Lambrechts, DietherSprangers, Ben2021-06-17T07:41:25-07:00doi:10.1681/ASN.2021020157hwp:resource-id:jnephrol;32/8/1838American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, transcriptional profiling, molecular biology, renal cell biologyReviewsReviewsreview-article20212021-08-01August 202110.1681/ASN.20210201571046-66731533-34502021-06-17T07:41:25-07:002021-08Journal of the American Society of NephrologyReviews32818381852
- Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 PandemicAKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and—therefore—safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.10.34067/KID.0000652021Fri, 14 May 2021 11:46:11 GMT-07:00Protocol for Local On-Site Dialysate Production for Continuous Renal Replacement Therapy during the COVID-19 PandemicAKI frequently occurs in patients with COVID-19, and kidney injury severe enough to require RRT is a common complication among patients who are critically ill. During the surge of the pandemic, there was a high demand for dialysate for continuous RRT, and this increase in demand, coupled with vulnerabilities in the supply chain, necessitated alternative approaches, including internal production of dialysate. Using a standard hemodialysis machine and off-the-shelf supplies, as per Food and Drug Administration guidelines, we developed a method for on-site dialysate production that is adaptable and can be used to fill multiple bags at once. The use of a central reverse osmosis unit, dedicated hemodialysis machine, sterile bags with separate ports for fill and use, and frequent testing will ensure stability, sterility, and—therefore—safety of the produced dialysate. The dialysate made in house was tested and it showed both stability and sterility for at least 30 hours. This detailed description of our process for generating dialysate can serve as a guide for other programs experiencing similar vulnerabilities in the demand versus supply of dialysate.Moses, Andrew A.Stevens, Jacob S.Fine, DerekCarrera, RobertLi, AlinaParikh, Chirag R.Mohan, Sumit2021-05-14T11:46:11-07:00doi:10.34067/KID.0000652021hwp:resource-id:kidney360;2/7/1152American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, continuous kidney replacement, continuous renal replacement therapy, COVID-19, dialysate, dialysate production, disaster planningInnovative Technology and MethodologyAcute Kidney Injury and ICU NephrologyInnovative Technology and MethodologyAcute Kidney Injury and ICU Nephrologyresearch-article20212021-07-2910.34067/KID.00006520212641-76502021-05-14T11:46:11-07:002021-07-29Kidney360Innovative Technology and Methodology2711521155
- Living Organ Donor Hesitancy about COVID-19 Vaccines: A New Kind of “Source Control Issue”10.34067/KID.0003402021Thu, 29 Jul 2021 05:30:28 GMT-07:00Living Organ Donor Hesitancy about COVID-19 Vaccines: A New Kind of “Source Control Issue”Jorgenson, Margaret R.2021-07-29T05:30:28-07:00doi:10.34067/KID.0003402021hwp:resource-id:kidney360;2/7/1076American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, COVID-19, COVID-19 vaccines, living donors, SARS-CoV-2, vaccinesEditorialTransplantationEditorialTransplantationeditorial20212021-07-2910.34067/KID.00034020212641-76502021-07-29T05:30:28-07:002021-07-29Kidney360Editorial2710761077
- Expression of ACE2 in the Intact and Acutely Injured Kidney10.34067/KID.0001562021Tue, 18 May 2021 01:29:37 GMT-07:00Expression of ACE2 in the Intact and Acutely Injured KidneyNath, Karl A.Singh, Raman DeepGrande, Joseph P.Garovic, Vesna D.Croatt, Anthony J.Ackerman, Allan W.Barry, Michael A.Agarwal, Anupam2021-05-18T13:29:37-07:00doi:10.34067/KID.0001562021hwp:resource-id:kidney360;2/7/1095American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, angiotensin-converting enzyme 2, basic science, heme oxygenase, ischemia reperfusion, lipopolysaccharide, peptidyl-dipeptidase A, urinary tract obstructionOriginal investigationAcute Kidney Injury and ICU NephrologyOriginal investigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-07-2910.34067/KID.00015620212641-76502021-05-18T13:29:37-07:002021-07-29Kidney360Original investigation2710951106
- Risks and Benefits of Kidney Transplantation during the COVID-19 Pandemic: Transplant or Not Transplant?COVID-19 has significantly affected the transplant community, by leading to decreased transplant activity and increased waiting list time. As expected, COVID-19 causes substantial mortality in both ESKD and kidney transplant populations. This is due to underlying CKD and a high prevalence of comorbid conditions, such as diabetes mellitus, hypertension, and cardiovascular disease in this group. Transplant programs have faced the difficult decision of weighing the risks and benefits of transplantation during the pandemic. On one hand, there is a risk of COVID-19 exposure leading to infection while patients are on maximum immunosuppression. Alternatively, there are risks of delaying transplantation, which will increase waitlist times and may lead to waitlist-associated morbidity and mortality. Cautious and thoughtful selection of both the recipient’s and donor’s post-transplant management has been required during the pandemic, to mitigate the risk of morbidity and mortality associated with COVID-19. In this review article, we aimed to discuss previous publications related to clinical outcomes of COVID-19 disease in kidney transplant recipients, patients with ESKD on dialysis, or on the transplant waiting list, and the precautions transplant centers should take in decision making for recipient and donor selection and immunosuppressive management during the pandemic. Nevertheless, transplantation in this milieu does seem to be the correct decision, with careful patient and donor selection and safeguard protocols for infection prevention. Each center should conduct risk assessment on the basis of the patient’s age and medical comorbidities, waitlist time, degree of sensitization, cold ischemia time, status of vaccination, and severity of pandemic in their region.10.34067/KID.0002532021Thu, 13 May 2021 05:57:09 GMT-07:00Risks and Benefits of Kidney Transplantation during the COVID-19 Pandemic: Transplant or Not Transplant?COVID-19 has significantly affected the transplant community, by leading to decreased transplant activity and increased waiting list time. As expected, COVID-19 causes substantial mortality in both ESKD and kidney transplant populations. This is due to underlying CKD and a high prevalence of comorbid conditions, such as diabetes mellitus, hypertension, and cardiovascular disease in this group. Transplant programs have faced the difficult decision of weighing the risks and benefits of transplantation during the pandemic. On one hand, there is a risk of COVID-19 exposure leading to infection while patients are on maximum immunosuppression. Alternatively, there are risks of delaying transplantation, which will increase waitlist times and may lead to waitlist-associated morbidity and mortality. Cautious and thoughtful selection of both the recipient’s and donor’s post-transplant management has been required during the pandemic, to mitigate the risk of morbidity and mortality associated with COVID-19. In this review article, we aimed to discuss previous publications related to clinical outcomes of COVID-19 disease in kidney transplant recipients, patients with ESKD on dialysis, or on the transplant waiting list, and the precautions transplant centers should take in decision making for recipient and donor selection and immunosuppressive management during the pandemic. Nevertheless, transplantation in this milieu does seem to be the correct decision, with careful patient and donor selection and safeguard protocols for infection prevention. Each center should conduct risk assessment on the basis of the patient’s age and medical comorbidities, waitlist time, degree of sensitization, cold ischemia time, status of vaccination, and severity of pandemic in their region.Ajaimy, MariaLiriano-Ward, LuzGraham, Jay A.Akalin, Enver2021-05-13T05:57:09-07:00doi:10.34067/KID.0002532021hwp:resource-id:kidney360;2/7/1179American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, chronic kidney failure, COVID-19, kidney transplantation, pandemics, risk assessment, SARS-CoV-2, transplantsReview ArticleReview Articleresearch-article20212021-07-2910.34067/KID.00025320212641-76502021-05-13T05:57:09-07:002021-07-29Kidney360Review Article2711791187
- Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 Illness10.34067/KID.0002592021Mon, 17 May 2021 01:38:21 GMT-07:00Increased Mortality Associated with Hypermagnesemia in Severe COVID-19 IllnessStevens, Jacob S.Moses, Andrew A.Nickolas, Thomas L.Husain, Syed AliMohan, Sumit2021-05-17T13:38:21-07:00doi:10.34067/KID.0002592021hwp:resource-id:kidney360;2/7/1087American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, coronavirus, COVID-19, hypermagnesemia, magnesium, rhabdomyolysis, SARS-CoV-2Original InvestigationAcid/Base and Electrolyte DisordersOriginal InvestigationAcid/Base and Electrolyte Disordersresearch-article20212021-07-2910.34067/KID.00025920212641-76502021-05-17T13:38:21-07:002021-07-29Kidney360Original Investigation2710871094
- Living Organ Donor Perspectives and Sources of Hesitancy about COVID-19 Vaccines10.34067/KID.0002112021Thu, 22 Apr 2021 01:34:55 GMT-07:00Living Organ Donor Perspectives and Sources of Hesitancy about COVID-19 VaccinesHarhay, Meera N.Klassen, Ann C.Zaidi, HasanMittelman, MichaelBertha, RebeccaMannon, Roslyn B.Lentine, Krista L.2021-04-22T13:34:55-07:00doi:10.34067/KID.0002112021hwp:resource-id:kidney360;2/7/1132American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, COVID-19, dysuria, kidney transplant, liver transplant, living donor, organ donation, vaccineOriginal investigationTransplantationOriginal investigationTransplantationresearch-article20212021-07-2910.34067/KID.00021120212641-76502021-04-22T13:34:55-07:002021-07-29Kidney360Original investigation2711321140
- Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-1910.34067/KID.0006852020Thu, 06 May 2021 01:38:52 GMT-07:00Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19Khatri, MineshCharytan, David M.Parnia, SamPetrilli, Christopher M.Michael, JeffreyLiu, DavidTatapudi, VasishtaJones, SimonBenstein, JudithHorwitz, Leora I.2021-05-06T13:38:52-07:00doi:10.34067/KID.0006852020hwp:resource-id:kidney360;2/7/1107American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, CKD, COVID-19, dialysis, end stage renal disease, mortality, SARS-CoV-2Original InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-07-2910.34067/KID.00068520202641-76502021-05-06T13:38:52-07:002021-07-29Kidney360Original Investigation2711071114
- Corticosteroids Should Be Used to Treat Slowly Progressive IgA Nephropathy: COMMENTARY10.34067/KID.0006832020Fri, 05 Feb 2021 01:36:13 GMT-08:00Corticosteroids Should Be Used to Treat Slowly Progressive IgA Nephropathy: COMMENTARYCampbell, Kirk N.2021-02-05T13:36:13-08:00doi:10.34067/KID.0006832020hwp:resource-id:kidney360;2/7/1084American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, adrenal cortex hormones, debates in nephrology, IgA, IGA glomerulonephritis, steroidsModerator CommentaryModerator Commentaryresearch-article20212021-07-2910.34067/KID.00068320202641-76502021-02-05T13:36:13-08:002021-07-29Kidney360Moderator Commentary2710841086
- Corticosteroids Should Be Used To Treat Slowly Progressive IgA Nephropathy: PRO10.34067/KID.0007192020Fri, 05 Feb 2021 03:31:07 GMT-08:00Corticosteroids Should Be Used To Treat Slowly Progressive IgA Nephropathy: PROCunningham, Amanda M.Reich, Heather N.2021-02-05T15:31:07-08:00doi:10.34067/KID.0007192020hwp:resource-id:kidney360;2/7/1078American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, adrenal cortex hormones, corticosteroids, glomerulonephritis, IGA glomerulonephritis, IgA nephropathy, therapy, treatmentDebates in NephrologyDebates in Nephrologyresearch-article20212021-07-2910.34067/KID.00071920202641-76502021-02-05T15:31:07-08:002021-07-29Kidney360Debates in Nephrology2710781080
- Corticosteroids Should Be Used to Treat Slowly Progressive IgA Nephropathy: CON10.34067/KID.0007672020Fri, 05 Feb 2021 02:06:35 GMT-08:00Corticosteroids Should Be Used to Treat Slowly Progressive IgA Nephropathy: CONBarratt, Jonathan2021-02-05T14:06:35-08:00doi:10.34067/KID.0007672020hwp:resource-id:kidney360;2/7/1081American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, adrenal cortex hormones, IgA glomerulonephritis, IgA nephropathy, steroidsDebates in NephrologyDebates in Nephrologyresearch-article20212021-07-2910.34067/KID.00076720202641-76502021-02-05T14:06:35-08:002021-07-29Kidney360Debates in Nephrology2710811083
- Confounding in Observational Studies Evaluating the Safety and Effectiveness of Medical Treatments10.34067/KID.0007022020Fri, 14 May 2021 09:25:02 GMT-07:00Confounding in Observational Studies Evaluating the Safety and Effectiveness of Medical TreatmentsAssimon, Magdalene M.2021-05-14T09:25:02-07:00doi:10.34067/KID.0007022020hwp:resource-id:kidney360;2/7/1156American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, confouding, observational researchClinical Research MethodsClinical Research Methodsresearch-article20212021-07-2910.34067/KID.00070220202641-76502021-05-14T09:25:02-07:002021-07-29Kidney360Clinical Research Methods2711561159
- Global Perspective on Kidney Transplantation: Thailand10.34067/KID.0002102021Fri, 14 May 2021 09:25:02 GMT-07:00Global Perspective on Kidney Transplantation: ThailandLarpparisuth, NuttasithCheungpasitporn, WisitLumpaopong, Adisorn2021-05-14T09:25:02-07:00doi:10.34067/KID.0002102021hwp:resource-id:kidney360;2/7/1163American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, Asia, graft survival, kidney transplantation, reimbursement, renal transplantation, ThailandGlobal PerspectivesGlobal Perspectivesresearch-article20212021-07-2910.34067/KID.00021020212641-76502021-05-14T09:25:02-07:002021-07-29Kidney360Global Perspectives2711631165
- Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For?10.34067/KID.0000732021Thu, 22 Apr 2021 01:34:55 GMT-07:00Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Transplantation: What Are We Waiting For?Patel, NiraleeHindi, JudyFarouk, Samira S.2021-04-22T13:34:55-07:00doi:10.34067/KID.0000732021hwp:resource-id:kidney360;2/7/1174American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, diabetes, kidney transplant, proteinuria, SGLT2 inhibitorsPerspectivePerspectiveresearch-article20212021-07-2910.34067/KID.00007320212641-76502021-04-22T13:34:55-07:002021-07-29Kidney360Perspective2711741178
- Global Perspective on Kidney Transplantation: Turkey10.34067/KID.0002542021Wed, 12 May 2021 11:39:45 GMT-07:00Global Perspective on Kidney Transplantation: TurkeyAndacoglu, OyaAki, Fazil Tuncay2021-05-12T11:39:45-07:00doi:10.34067/KID.0002542021hwp:resource-id:kidney360;2/7/1160American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, deceased donor, living donor, renal transplant, TurkeyGlobal PerspectivesGlobal Perspectivesresearch-article20212021-07-2910.34067/KID.00025420212641-76502021-05-12T11:39:45-07:002021-07-29Kidney360Global Perspectives2711601162
- A Perspective on the Metabolic Potential for Microbial Contributions to Urolithiasis10.34067/KID.0000492021Thu, 22 Apr 2021 08:00:35 GMT-07:00A Perspective on the Metabolic Potential for Microbial Contributions to UrolithiasisAgudelo, JoseMiller, Aaron W.2021-04-22T08:00:35-07:00doi:10.34067/KID.0000492021hwp:resource-id:kidney360;2/7/1170American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephrolithiasis, basic science, kidney stones, metabolome, microbiome, microbiota, urolithiasisPerspectivePerspectiveresearch-article20212021-07-2910.34067/KID.00004920212641-76502021-04-22T08:00:35-07:002021-07-29Kidney360Perspective2711701173
- Strategies for Continuous Renal Replacement Therapy De-escalation10.34067/KID.0000912021Thu, 15 Apr 2021 11:38:16 GMT-07:00Strategies for Continuous Renal Replacement Therapy De-escalationGautam, Samir C.Srialluri, NityasreeJaar, Bernard G.2021-04-15T11:38:16-07:00doi:10.34067/KID.0000912021hwp:resource-id:kidney360;2/7/1166American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, biomarkers, CRRT, diuretics, weaning trialPerspectivePerspectiveresearch-article20212021-07-2910.34067/KID.00009120212641-76502021-04-15T11:38:16-07:002021-07-29Kidney360Perspective2711661169
- Improving Clearance for Renal Replacement TherapyThe adequacy of hemodialysis is now assessed by measuring the removal of a single solute, urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and, therefore, cannot be increased much further. However, other solutes, which are less effectively cleared than urea, may contribute more to the residual uremic illness suffered by patients on hemodialysis. Here, we review a variety of methods that could be used to increase the clearance of such nonurea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients’ health.10.34067/KID.0002922021Wed, 12 May 2021 11:39:45 GMT-07:00Improving Clearance for Renal Replacement TherapyThe adequacy of hemodialysis is now assessed by measuring the removal of a single solute, urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and, therefore, cannot be increased much further. However, other solutes, which are less effectively cleared than urea, may contribute more to the residual uremic illness suffered by patients on hemodialysis. Here, we review a variety of methods that could be used to increase the clearance of such nonurea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients’ health.Lee, SeolhyunSirich, Tammy L.Meyer, Timothy W.2021-05-12T11:39:45-07:00doi:10.34067/KID.0002922021hwp:resource-id:kidney360;2/7/1188American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, blood urea nitrogen, hemodialysis adequacy, hemodynamics, renal dialysisReview ArticleReview Articleresearch-article20212021-07-2910.34067/KID.00029220212641-76502021-05-12T11:39:45-07:002021-07-29Kidney360Review Article2711881195
- G protein- and β-arrestin Signaling Profiles of Endothelin Derivatives at the Type A Endothelin Receptor10.34067/KID.0005462020Mon, 17 May 2021 01:38:21 GMT-07:00G protein- and β-arrestin Signaling Profiles of Endothelin Derivatives at the Type A Endothelin ReceptorXiong, XinyuNazo, NourRevoori, RitikaRajagopal, SudarshanSparks, Matthew A.2021-05-17T13:38:21-07:00doi:10.34067/KID.0005462020hwp:resource-id:kidney360;2/7/1124American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephro-pharmacology, beta arrestin, endothelin, GPCR, hypertension, signalingOriginal investigationNephroPharmacologyOriginal investigationNephroPharmacologyresearch-article20212021-07-2910.34067/KID.00054620202641-76502021-05-17T13:38:21-07:002021-07-29Kidney360Original investigation2711241131
- An Unusual Cause of Kidney Allograft Dysfunction10.34067/KID.0001062021Thu, 29 Jul 2021 05:30:28 GMT-07:00An Unusual Cause of Kidney Allograft DysfunctionRosenstiel, Paul E.Markowitz, Glen S.Amante, Brigani2021-07-29T05:30:28-07:00doi:10.34067/KID.0001062021hwp:resource-id:kidney360;2/7/1207American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, allografts, CMV, crystals, foscarnet, glomerular, homologous transplantation, kidney diseases, kidney glomerulus, kidney transplantationClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-07-2910.34067/KID.00010620212641-76502021-07-29T05:30:28-07:002021-07-29Kidney360Clinical Images in Nephrology and Dialysis2712071208
- Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease10.34067/KID.0007342020Tue, 18 May 2021 01:29:37 GMT-07:00Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney DiseaseAkihisa, TaroManabe, ShunKataoka, HiroshiMakabe, ShihoYoshida, RieUshio, YusukeWatanabe, KentaroSato, MasayoTsuchiya, KenMochizuki, ToshioNitta, Kosaku2021-05-18T13:29:37-07:00doi:10.34067/KID.0007342020hwp:resource-id:kidney360;2/7/1148American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, dose-dependent, estimated glomerular filtration rate, prognostic factor, renal prognosis, tolvaptan, total kidney volumeBrief CommunicationCystic Kidney DiseaseBrief CommunicationCystic Kidney Diseaseresearch-article20212021-07-2910.34067/KID.00073420202641-76502021-05-18T13:29:37-07:002021-07-29Kidney360Brief Communication2711481151
- Single Cell Technologies: Beyond MicrofluidicsSingle-cell RNA-sequencing (scRNA-seq) has been widely adopted in recent years due to standardized protocols and automation, reliability, and standardized bioinformatic pipelines. The most widely adopted platform is the 10× Genomics solution. Although powerful, this system is limited by its high cost, moderate throughput, and the inability to customize due to fixed kit components. This study will cover new approaches that do not rely on microfluidics and thus have low entry costs, are highly customizable, and are within the reach of any laboratory possessing molecular biology expertise.10.34067/KID.0001822021Fri, 14 May 2021 09:25:02 GMT-07:00Single Cell Technologies: Beyond MicrofluidicsSingle-cell RNA-sequencing (scRNA-seq) has been widely adopted in recent years due to standardized protocols and automation, reliability, and standardized bioinformatic pipelines. The most widely adopted platform is the 10× Genomics solution. Although powerful, this system is limited by its high cost, moderate throughput, and the inability to customize due to fixed kit components. This study will cover new approaches that do not rely on microfluidics and thus have low entry costs, are highly customizable, and are within the reach of any laboratory possessing molecular biology expertise.Li, HaikuoHumphreys, Benjamin D.2021-05-14T09:25:02-07:00doi:10.34067/KID.0001822021hwp:resource-id:kidney360;2/7/1196American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360genetics, basic science, genomics, single-cell analysis, small cytoplasmic RNAReview ArticleReview Articleresearch-article20212021-07-2910.34067/KID.00018220212641-76502021-05-14T09:25:02-07:002021-07-29Kidney360Review Article2711961204
- Stakeholder-Guided Development of Dialysis Vascular Access Education Materials10.34067/KID.0002382021Mon, 03 May 2021 07:24:05 GMT-07:00Stakeholder-Guided Development of Dialysis Vascular Access Education MaterialsDorough, AdelineNarendra, Julia H.Wilkie, CarolineHegde, AkhilSwain, KawanChang, Emily H.Oliver, TerenceFlythe, Jennifer E.2021-05-03T07:24:05-07:00doi:10.34067/KID.0002382021hwp:resource-id:kidney360;2/7/1115American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, animation, arteriovenous, catheter, education, fistula, graft, hemodialysis, mixed methods, stakeholder, vascular access, videoOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-07-2910.34067/KID.00023820212641-76502021-05-03T07:24:05-07:002021-07-29Kidney360Original Investigation2711151123
- An Atypical Kidney-Related Presentation of Multiple Myeloma10.34067/KID.0000762021Thu, 29 Jul 2021 05:30:28 GMT-07:00An Atypical Kidney-Related Presentation of Multiple MyelomaMuniz, Monique Pereira Rêgoda Silva Neto, João BatistaSilva, Gyl Eanes2021-07-29T05:30:28-07:00doi:10.34067/KID.0000762021hwp:resource-id:kidney360;2/7/1205American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, immunoglobulin light chains, kidney tubules, multiple myelomaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-07-2910.34067/KID.00007620212641-76502021-07-29T05:30:28-07:002021-07-29Kidney360Clinical Images in Nephrology and Dialysis2712051206
- Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort Study10.34067/KID.0000692021Tue, 18 May 2021 01:29:37 GMT-07:00Long-Term Impact of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients: A 5-Year Follow-Up Observational Cohort StudySalehi, TaniaMontarello, Nicholas J.Juneja, NishantStokes, Michael B.Scherer, Daniel J.Williams, Kerry F.King, DavidMacaulay, EwanRussell, Christine H.Olakkengil, Santosh A.Carroll, Robert P.Faull, Randall J.Teo, Karen S.L.McDonald, Stephen P.Worthley, Matthew I.Coates, Patrick T.Rao, Nitesh N.2021-05-18T13:29:37-07:00doi:10.34067/KID.0000692021hwp:resource-id:kidney360;2/7/1141American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, arteriovenous fistula, cardiac magnetic resonance imaging, heart ventricles, kidney transplantation, left ventricular mass, ligationOriginal investigationTransplantationOriginal investigationTransplantationresearch-article20212021-07-2910.34067/KID.00006920212641-76502021-05-18T13:29:37-07:002021-07-29Kidney360Original investigation2711411147
- Kidney Disease Burden and Kidney Transplantation: A True Story10.2215/CJN.06620521Mon, 12 Jul 2021 07:54:45 GMT-07:00Kidney Disease Burden and Kidney Transplantation: A True StoryRodriguez, David2021-07-12T07:54:45-07:00doi:10.2215/CJN.06620521hwp:resource-id:clinjasn;16/7/989American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient, burden, transplant, dialysis, depression, aspirations, paired-exchange, independentPatient VoicePatient Voiceresearch-article20212021-07-01July 202110.2215/CJN.066205211555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyPatient Voice167798910839901093
- Over Four Decades of Life with Dialysis: A Tale of Self-Empowerment10.2215/CJN.03210321Mon, 12 Jul 2021 07:54:45 GMT-07:00Over Four Decades of Life with Dialysis: A Tale of Self-EmpowermentStrauss, Franklin G.Weintraub, Judy2021-07-12T07:54:45-07:00doi:10.2215/CJN.03210321hwp:resource-id:clinjasn;16/7/993American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, chronic dialysis, chronic renal disease, end stage kidney diseasePatient VoicePatient Voiceresearch-article20212021-07-01July 202110.2215/CJN.032103211555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyPatient Voice167993995
- Mixed Methods Research To Advance Nephrology10.34067/KID.0005972020Wed, 17 Mar 2021 01:22:31 GMT-07:00Mixed Methods Research To Advance NephrologyWong, Susan P. Y.2021-03-17T13:22:31-07:00doi:10.34067/KID.0005972020hwp:resource-id:kidney360;2/6/1011American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, qualitative research, quantitative researchClinical Research MethodsClinical Research Methodsresearch-article20212021-06-2410.34067/KID.00059720202641-76502021-03-17T13:22:31-07:002021-06-24Kidney360Clinical Research Methods2610111014
- eGFR Decline after SGLT2 Inhibitor Initiation: The Tortoise and the Hare Reimagined10.34067/KID.0001172021Fri, 26 Mar 2021 07:32:10 GMT-07:00eGFR Decline after SGLT2 Inhibitor Initiation: The Tortoise and the Hare ReimaginedMeraz-Muñoz, Alejandro Y.Weinstein, JordanWald, Ron2021-03-26T07:32:10-07:00doi:10.34067/KID.0001172021hwp:resource-id:kidney360;2/6/1042American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, AKI, eGFR, glomerular filtration rate, SGLT2i, tubuloglomerular feedbackPerspectivesPerspectivesresearch-article20212021-06-2410.34067/KID.00011720212641-76502021-03-26T07:32:10-07:002021-06-24Kidney360Perspectives2610421047
- Global Dialysis Perspective: Mauritius10.34067/KID.0000982021Fri, 26 Mar 2021 12:18:40 GMT-07:00Global Dialysis Perspective: MauritiusIp Min Wan, DavyFagoonee, Kevin2021-03-26T12:18:40-07:00doi:10.34067/KID.0000982021hwp:resource-id:kidney360;2/6/1021American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, free dialysis, funding, government, hemodialysis, Mauritius, peritoneal dialysis, transplantation, workforceGlobal PerspectivesGlobal Perspectivesresearch-article20212021-06-2410.34067/KID.00009820212641-76502021-03-26T12:18:40-07:002021-06-24Kidney360Global Perspectives2610211026
- Global Dialysis Perspective: Kuwait10.34067/KID.0000392021Wed, 07 Apr 2021 01:28:30 GMT-07:00Global Dialysis Perspective: KuwaitAlSahow, AliAlYousef, Anas2021-04-07T13:28:30-07:00doi:10.34067/KID.0000392021hwp:resource-id:kidney360;2/6/1015American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, calcium bath, dialysis adequacy, dialysis cost, dialysis modality, dialysis mortality, hemodialysis, hepatitis, Kuwait, vascular accessGlobal PerspectivesGlobal PerspectivesGlobal PerspectivesGlobal Perspectivesresearch-article20212021-06-2410.34067/KID.00003920212641-76502021-04-07T13:28:30-07:002021-06-24Kidney360Global Perspectives2610151020
- Payment, Coverage, and Health Economics of SGLT2 Inhibitors10.34067/KID.0000742021Thu, 18 Mar 2021 09:25:01 GMT-07:00Payment, Coverage, and Health Economics of SGLT2 InhibitorsPham, Ngoc-Yen T.Argyropoulos, Christos P.Koppula, Sireesha2021-03-18T09:25:01-07:00doi:10.34067/KID.0000742021hwp:resource-id:kidney360;2/6/1031American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, coverage, diabetic kidney disease, health economics, sodium glucose cotransporter two inhibitorsPerspectivesPerspectivesresearch-article20212021-06-2410.34067/KID.00007420212641-76502021-03-18T09:25:01-07:002021-06-24Kidney360Perspectives2610311035
- The Challenges of Acute Interstitial Nephritis: Time to Standardize10.34067/KID.0001742021Thu, 01 Apr 2021 01:28:36 GMT-07:00The Challenges of Acute Interstitial Nephritis: Time to StandardizeMoledina, Dennis G.Perazella, Mark A.2021-04-01T13:28:36-07:00doi:10.34067/KID.0001742021hwp:resource-id:kidney360;2/6/1051American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, acute interstitial nephritis, acute kidney injury, chronic kidney disease, corticosteroids, eosinophiluria inflammatory cells, kidney biopsy, leukocyte casts, leukocyturia prognosis, treatment, urine microscopyPerspectivePerspectiveresearch-article20212021-06-2410.34067/KID.00017420212641-76502021-04-01T13:28:36-07:002021-06-24Kidney360Perspective2610511055
- Examining the Role of Novel CKD Therapies for the ADPKD Patient10.34067/KID.0007422020Wed, 24 Mar 2021 09:49:59 GMT-07:00Examining the Role of Novel CKD Therapies for the ADPKD PatientPatel, Dipal M.Dahl, Neera K.2021-03-24T09:49:59-07:00doi:10.34067/KID.0007422020hwp:resource-id:kidney360;2/6/1036American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, HIF-PHi, SGLT2iPerspectivesPerspectivesresearch-article20212021-06-2410.34067/KID.00074220202641-76502021-03-24T09:49:59-07:002021-06-24Kidney360Perspectives2610361041
- Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients10.34067/KID.0002172021Wed, 14 Apr 2021 11:50:46 GMT-07:00Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 PatientsGeorge, SantoshPal, Anasuya ChattopadhyayGagnon, JacquelineTimalsina, SushmaSingh, PallaviVydyam, PratapMunshi, MuhammadChiu, Joy E.Renard, IsalineHarden, Christina A.Ott, Isabel M.Watkins, Anne E.Vogels, Chantal B.F.Lu, PeiwenTokuyama, MariaVenkataraman, ArvindCasanovas-Massana, ArnauWyllie, Anne L.Rao, VeenaCampbell, MelissaFarhadian, Shelli F.Grubaugh, Nathan D.Dela Cruz, Charles S.Ko, Albert I.Berna Perez, Amalia Z.Akaho, Elikplim H.Moledina, Dennis G.Testani, JeffreyJohn, Audrey R.Ledizet, MichelMamoun, Choukri Ben,2021-04-14T11:50:46-07:00doi:10.34067/KID.0002172021hwp:resource-id:kidney360;2/6/924American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, body fluids, coronavirus, COVID-19, enzyme-linked immunosorbent assay, SARS-CoV-2, spike glycoprotein, spike protein, viral envelope proteinsOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-06-2410.34067/KID.00021720212641-76502021-04-14T11:50:46-07:002021-06-24Kidney360Original Investigation26924936
- Ly6chi Infiltrating Macrophages Promote Cyst Progression in Injured Conditional Ift88 Mice10.34067/KID.0000882021Wed, 28 Apr 2021 12:29:36 GMT-07:00Ly6chi Infiltrating Macrophages Promote Cyst Progression in Injured Conditional Ift88 MiceAloria, Ernald Jules G.Song, Cheng J.Li, ZhangCroyle, Mandy J.Mrug, MichalZimmerman, Kurt A.Yoder, Bradley K.2021-04-28T12:29:36-07:00doi:10.34067/KID.0000882021hwp:resource-id:kidney360;2/6/989American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, basic science, cilia, ciliopathy, infiltrating macrophages, polycystic kidney disease, renal cystsBrief CommunicationCystic Kidney DiseaseBrief CommunicationCystic Kidney Diseaseresearch-article20212021-06-2410.34067/KID.00008820212641-76502021-04-28T12:29:36-07:002021-06-24Kidney360Brief Communication26989995
- Late Relapses of Membranous Nephropathy: A Case Series10.34067/KID.0007712020Wed, 28 Apr 2021 07:54:54 GMT-07:00Late Relapses of Membranous Nephropathy: A Case SeriesPeleg, YonatanBomback, Andrew S.Canetta, Pietro A.Radhakrishnan, JaiAppel, Gerald B.Ahn, Wooin2021-04-28T07:54:54-07:00doi:10.34067/KID.0007712020hwp:resource-id:kidney360;2/6/974American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, late relapse, membranous nephropathy, natural history, nephrotic syndrome, proteinuria, relapseOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-06-2410.34067/KID.00077120202641-76502021-04-28T07:54:54-07:002021-06-24Kidney360Original Investigation26974982
- Glucocorticoid Therapy in ANCA Vasculitis: Using the Glucocorticoid Toxicity Index as an Outcome Measure10.34067/KID.0000502021Tue, 20 Apr 2021 12:33:13 GMT-07:00Glucocorticoid Therapy in ANCA Vasculitis: Using the Glucocorticoid Toxicity Index as an Outcome MeasureFloyd, LaurenMorris, AdamJoshi, MilandDhaygude, Ajay2021-04-20T12:33:13-07:00doi:10.34067/KID.0000502021hwp:resource-id:kidney360;2/6/1002American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, ANCA, ANCA-associated vasculitis, glucocorticoid, glucocorticoid toxicity, Glucocorticoid Toxicity Index, health care outcome assessment, prednisolone, steroid, vasculitisInnovative Technology and MethodologyGlomerular and Tubulointerstitial DiseasesInnovative Technology and MethodologyGlomerular and Tubulointerstitial Diseasesresearch-article20212021-06-2410.34067/KID.00005020212641-76502021-04-20T12:33:13-07:002021-06-24Kidney360Innovative Technology and Methodology2610021010
- Evaluation of Suspected Outflow Stenosis in an Aneurysmal AVF10.34067/KID.0000562021Tue, 13 Jul 2021 06:20:42 GMT-07:00Evaluation of Suspected Outflow Stenosis in an Aneurysmal AVFSharma, Mukesh K.Niyyar, Vandana D.2021-07-13T06:20:42-07:00doi:10.34067/KID.0000562021hwp:resource-id:kidney360;2/6/1072American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, cardiovascular abnormalities, dialysis access, hemodialysis, pathologic constriction, physical examClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-06-2410.34067/KID.00005620212641-76502021-07-13T06:20:42-07:002021-06-24Kidney360Clinical Images in Nephrology and Dialysis2610721073
- Evolution of Vascular Access Use among Incident Patients during the First Year on Hemodialysis: A National Cohort Study10.34067/KID.0006842020Thu, 22 Apr 2021 09:59:21 GMT-07:00Evolution of Vascular Access Use among Incident Patients during the First Year on Hemodialysis: A National Cohort StudyHussein, Wael F.Ahmed, GasimBrowne, Leonard D.Plant, William D.Stack, Austin G.2021-04-22T09:59:21-07:00doi:10.34067/KID.0006842020hwp:resource-id:kidney360;2/6/955American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, central venous catheter, hemodialysis, Irish healthcare system, vascular accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-06-2410.34067/KID.00068420202641-76502021-04-22T09:59:21-07:002021-06-24Kidney360Original Investigation26955965
- Implementation of Surprise Question Assessments using the Electronic Health Record in Older Adults with Advanced CKD10.34067/KID.0007062020Thu, 01 Apr 2021 09:33:58 GMT-07:00Implementation of Surprise Question Assessments using the Electronic Health Record in Older Adults with Advanced CKDErnecoff, Natalie C.Abdel-Kader, KhaledCai, ManqiYabes, JonathanShah, NiravSchell, Jane O.Jhamb, Manisha2021-04-01T09:33:58-07:00doi:10.34067/KID.0007062020hwp:resource-id:kidney360;2/6/966American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360geriatric and palliative nephrology, advance care planning, chronic kidney disease, electronic health records, health services research, palliative careOriginal InvestigationGeriatric and Palliative NephrologyOriginal InvestigationGeriatric and Palliative Nephrologyresearch-article20212021-06-2410.34067/KID.00070620202641-76502021-04-01T09:33:58-07:002021-06-24Kidney360Original Investigation26966973
- Patient-Reported Experiences with Dialysis Care and Provider Visit Frequencykevin.erickson@bcm.edu10.2215/CJN.16621020Mon, 12 Jul 2021 07:54:45 GMT-07:00Patient-Reported Experiences with Dialysis Care and Provider Visit FrequencyBrady, Brian M.Zhao, BoDang, Bich N.Winkelmayer, Wolfgang C.Chertow, Glenn M.Erickson, Kevin F.2021-07-12T07:54:45-07:00doi:10.2215/CJN.16621020hwp:resource-id:clinjasn;16/7/1052American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, dialysis, epidemiology and outcomesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-07-01July 202110.2215/CJN.166210201555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles16710521060
- Dialysis-Associated Neurovascular Injury (DANI) in Acute Brain Injury10.2215/CJN.15000920Thu, 11 Feb 2021 11:46:09 GMT-08:00Dialysis-Associated Neurovascular Injury (DANI) in Acute Brain InjuryGhoshal, ShivaniParikh, Amay2021-02-11T11:46:09-08:00doi:10.2215/CJN.15000920hwp:resource-id:clinjasn;16/7/1110American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycerebral edema, cerebral blood flow, cerebral ischemia, acute brain injury, kidney disease, critical care, renal replacement therapyKidney Case Conferences: How I TreatKidney Case Conferences: How I Treatresearch-article20212021-07-01July 202110.2215/CJN.150009201555-90411555-905X2021-02-11T11:46:09-08:002021-07Clinical Journal of the American Society of NephrologyKidney Case Conferences: How I Treat16711101112
- The Patient Voice in Health Care Decision Making10.2215/CJN.18191120Tue, 09 Mar 2021 06:42:55 GMT-08:00The Patient Voice in Health Care Decision MakingSadusky, TamiHurst, Clint2021-03-09T06:42:55-08:00doi:10.2215/CJN.18191120hwp:resource-id:clinjasn;16/7/991American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, kidney disease, decision making, chronic kidney diseasePatient VoicePatient Voiceresearch-article20212021-07-01July 202110.2215/CJN.181911201555-90411555-905X2021-03-09T06:42:55-08:002021-07Clinical Journal of the American Society of NephrologyPatient Voice167991992
- Racial Health Inequities and Clinical Algorithms10.2215/CJN.01780221Fri, 05 Mar 2021 02:00:07 GMT-08:00Racial Health Inequities and Clinical AlgorithmsNeal, Richard E.Morse, Michelle2021-03-05T14:00:07-08:00doi:10.2215/CJN.01780221hwp:resource-id:clinjasn;16/7/1120American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhealth equity, clinical algorithms, race correction, eGFR racism, race, algorithms, equityPerspectivesPerspectivesresearch-article20212021-07-01July 202110.2215/CJN.017802211555-90411555-905X2021-03-05T14:00:07-08:002021-07Clinical Journal of the American Society of NephrologyPerspectives16711201121
- Slowing Progression in CKD10.2215/CJN.20211220Wed, 10 Mar 2021 08:09:01 GMT-08:00Slowing Progression in CKDLarmour, KathrynLevin, Adeera2021-03-10T08:09:01-08:00doi:10.2215/CJN.20211220hwp:resource-id:clinjasn;16/7/1117American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, progression, delay, evidence, SGLT2i, MRA chronic kidney diseasePerspectivesPerspectivesresearch-article20212021-07-01July 202110.2215/CJN.202112201555-90411555-905X2021-03-10T08:09:01-08:002021-07Clinical Journal of the American Society of NephrologyPerspectives16711171119
- Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood10.2215/CJN.19181220Wed, 26 May 2021 10:45:44 GMT-07:00Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in ChildhoodCalatroni, MartaConsonni, FilippoAllinovi, MarcoBettiol, AlessandraJawa, NatashaFiasella, SusannaCuri, DritanAbu Rumeileh, SarahTomei, LeonardoFortunato, LauraGelain, ElenaGianfreda, DavideOliva, ElenaJeannin, GuidoSalviani, ChiaraEmmi, GiacomoBodria, MonicaSinico, Renato A.Moroni, GabriellaRamirez, Giuseppe A.Bozzolo, EnricaTombetti, EnricoMonti, SaraBracaglia, ClaudiaMarucci, GiuliaPastore, SerenaEsposito, PasqualeCatanoso, Maria G.Crapella, BarbaraMontini, GiovanniRoperto, RosaMaterassi, MarcoRossi, Giovanni M.Badalamenti, SalvatoreYeung, Rae S.M.Romagnani, PaolaGhiggeri, Gian M.Noone, DamienVaglio, Augusto2021-05-26T10:45:44-07:00doi:10.2215/CJN.19181220hwp:resource-id:clinjasn;16/7/1043American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, pediatric nephrology, glomerulopathy, antineutrophil cytoplasmic antibodyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-07-01July 202110.2215/CJN.191812201555-90411555-905X2021-05-26T10:45:44-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles16167121043187710511877
- Genetic Basis of Type IV Collagen Disorders of the KidneyThe glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the α3(IV), α4(IV), and α5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.10.2215/CJN.19171220Tue, 13 Apr 2021 08:05:32 GMT-07:00Genetic Basis of Type IV Collagen Disorders of the KidneyThe glomerular basement membrane is a vital component of the filtration barrier of the kidney and is primarily composed of a highly structured matrix of type IV collagen. Specific isoforms of type IV collagen, the α3(IV), α4(IV), and α5(IV) isoforms, assemble into trimers that are required for normal glomerular basement membrane function. Disruption or alteration in these isoforms leads to breakdown of the glomerular basement membrane structure and function and can lead to progressive CKD known as Alport syndrome. However, there is wide variability in phenotype among patients with mutations affecting type IV collagen that depends on a complex interplay of sex, genotype, and X-chromosome inactivation. This article reviews the genetic basis of collagen disorders of the kidney as well as potential treatments for these conditions, including direct alteration of the DNA, RNA therapies, and manipulation of collagen proteins.Quinlan, CatherineRheault, Michelle N.2021-04-13T08:05:32-07:00doi:10.2215/CJN.19171220hwp:resource-id:clinjasn;16/7/1101American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, type IV collagen, gene therapy, collagen diseases, kidney genomics seriesGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-07-01July 202110.2215/CJN.191712201555-90411555-905X2021-04-13T08:05:32-07:002021-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease16711011109
- Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 110.2215/CJN.14730920Thu, 13 May 2021 06:13:18 GMT-07:00Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1Frishberg, YaacovDeschênes, GeorgesGroothoff, Jaap W.Hulton, Sally-AnneMagen, DaniellaHarambat, Jérômevan’t Hoff, William G.Lorch, UlrikeMilliner, Dawn S.Lieske, John C.Haslett, PatrickGarg, Pushkal P.Vaishnaw, Akshay K.Talamudupula, SandeepLu, JiandongHabtemariam, Bahru A.Erbe, David V.McGregor, Tracy L.Cochat, Pierre,,Bandara, AselaBowen, JonathanChong, Wei LiCoates, SimonDe Barr, PatrickDe Beer, JanineGayed, JuleenHill, TimothyKotak, AlexOno, JunkoTaubel, JorgThayalan, MeeraWong, RobynneCoch, ChristophCoenen, MartinFeldkotter, MarkusHeiland, Nils HenningHohenadel, MaximilianHoppe, BerndKyrieleis, HenrietteSchalk, GesaCooper, LucyGupta, AsheetaMilford, DavidMuorah, MordiBacchetta, JustineBernoux, DelphineBertholet-Thomas, AureliaCheyssac, ElodiePortefaix, AurelieRanchin, BrunoSellier-Leclerc, Anne-LaureLlanas, BrigitteBaudouin, VeroniqueCouderc, AnneHogan, JulienKaguelidou, FlorentiaKwon, TheresaMaisin, AnneSas, DavidBecker-Cohen, RachelBen-Shalom, EfratRinat, ChoniBehr, Shimrit TzviBockenhauer, DetlefMansour, BsharaPollack, ShirleyGarrelfs, SanderOosterveld, MichielMoochhala, ShabbirWalsh, StephenKamesh, LavanyaLipkin, Graham2021-05-13T06:13:18-07:00doi:10.2215/CJN.14730920hwp:resource-id:clinjasn;16/7/1025American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyprimary hyperoxaluria type 1, RNAi, lumasiran, urinary oxalate, kidney stones, nephrocalcinosis, oxalosis, plasma oxalate, RNAi therapeuticsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-07-01July 202110.2215/CJN.147309201555-90411555-905X2021-05-13T06:13:18-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles16710251036
- Shining More Light on RAS Inhibition during the COVID-19 Pandemic10.2215/CJN.06000521Mon, 12 Jul 2021 07:54:45 GMT-07:00Shining More Light on RAS Inhibition during the COVID-19 PandemicRianto, FitraSparks, Matthew A.2021-07-12T07:54:45-07:00doi:10.2215/CJN.06000521hwp:resource-id:clinjasn;16/7/1002American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, ACE inhibitors, angiotensin, kidney transplantation, dialysis, mortality, virologyEditorialEditorialeditorial20212021-07-01July 202110.2215/CJN.060005211555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyEditorial16777100210611005100410721014
- Renin-Angiotensin System Blockers and the Risk of COVID-19–Related Mortality in Patients with Kidney Failure10.2215/CJN.18961220Fri, 04 Jun 2021 11:54:31 GMT-07:00Renin-Angiotensin System Blockers and the Risk of COVID-19–Related Mortality in Patients with Kidney FailureSoler, Maria JoseNoordzij, MarliesAbramowicz, Danielde Arriba, GabrielBasile, Carlovan Buren, MarjolijnCovic, AdrianCrespo, MartaDuivenvoorden, RaphaëlMassy, Ziad A.Ortiz, AlbertoSanchez, J. EmilioPetridou, EmilyStevens, KateWhite, ColinVart, PriyaGansevoort, Ron T.,,van der Net, Jeroen B.Essig, Mariedu Buf-Vereijken, Peggy W.G.van Ginneken, BettyMaas, NandaVogt, Liffertvan Jaarsveld, Brigit C.Jager, Kitty J.Bemelman, Frederike J.Klingenberg-Salahova, FarahHeenan-Vos, FrederiekVervloet, Marc G.Nurmohamed, AzamVerhofstede, SabineMaoujoud, OmarMalfait, ThomasFialova, JanaMelilli, EdoardoFavà, AlexandreCruzado, Josep M.Perez, Nuria MonteroLips, JoyKrepel, HarmenAdilovic, HarunHengst, MaaikeRydzewski, AndrzejGellert, RyszardOliveira, JoãoAlferes, Daniela G.Zakharova, Elena V.Ambuehl, Patrice MaxWinzeler, RebeccaLepeytre, FannyRabaté, ClémentineRostoker, GuyMarques, SofiaAzasevac, TijanaKaticic, DajanaDam, Marc tenKrüger, ThiloBrzosko, Szymonvan Zanen, A.L.Logtenberg, Susan J.J.Fricke, LutzSlebe, Jeroen J.P.Kemlin, Delphinevan de Wetering, JacquelineReinders, Marlies E.J.Eiselt, JaromirKielberger, LukasEl-Wakil, Hala S.ElHafeez, Samar AbdCanal, CristinaFacundo, CarmeRamos, Ana M.Debska-Slizien, AlicjaVeldhuizen, Nicoline M.H.Panagoutsos, StylianosMatceac, IrinaNistor, IonutCordos, MonicaGroeneveld, J.H.MJousma, JolandaDiekmann, FritzPereira, Tiago AssisSantos, Augusto Cesar S.Arias-Cabrales, CarlosLlinàs-Mallol, LauraBuxeda, AnnaTàrrega, Carla BurballaRedondo-Pachon, DoloresArenas Jimenez, Maria DoloresHofstra, Julia M.Franco, AntonioArroyo, DavidRodríguez-Ferrero, Maria LuisaManzanos, Sagrario BaldaSosa Barrios, R. HaridianLemahieu, WimBartelet, KarlijnDirim, Ahmet BurakDemir, ErolSever, Mehmet SukruTurkmen, AydinHollander, Daan A.M.J.Büttner, Stefande Vries, Aiko P.J.Meziyerh, Soufianvan der Helm, DannyMallat, MarkoBouwsma, HannekeSridharan, SivakumarPetruliene, KristinaMaloney, Sharon-RoseVerberk, Irisvan der Sande, Frank M.Christiaans, Maarten H.L.Hemmelder, MarcDi Luca, MarinaTuğlular, Serhan Z.Beerenhout, CharlesLuik, Peter T.Kerschbaum, JuliaTiefenthaler, MartinWatschinger, BrunoAdema, Aaltje Y.Stepanov, Vadim A.Zulkarnaev, Alexey B.Turkmen, KultiginFliedner, AnselmÅsberg, AndersMjoen, GeirMiyasato, Hitoshide Fijter, Carola W.H.Pini, Stefanode Biase, ConsueloHilbrands, LuukKerckhoffs, Angelevan de Logt, Anne ElsMaas, RutgerLebedeva, OlgaLopez, VeronicaReichert, Louis J.M.Verhave, JacobienTitov, DenisParshina, Ekaterina V.Zanoli, LucaMarcantoni, Carmelitavan Gils-Verrij, Liesbeth E.A.Harty, John C.Meurs, MarleenMyslak, MarekBattaglia, YuriLentini, Paoloden Deurwaarder, EdwinStendahl, MariaRahimzadeh, HormatSchouten, MarcelRychlik, IvanCabezas-Reina, Carlos J.Roca, Ana MariaNauta, FerdauGoffin, EricKanaan, NadaLabriola, LauraDevresse, ArnaudDiaz-Mareque, AnabelCoca, ArmandoMeijers, Björn K.I.Naesens, MaartenKuypers, DirkDesschans, BrunoTonnerlier, AnneliesWissing, Karl M.Dedinska, IvanaPessolano, GiuseppinaGandolfini, IlariaMaggiore, UmbertoMalik, ShafiPapachristou, EvangelosFranssen, Casper F.M.Berger, Stefan P.Meijer, EstherSanders, Jan Stephan F.Ponikvar, Jadranka ButurovićPernat, Andreja MarnKovac, DamjanArnol, MihaEkart, RobertAbrahams, Alferso C.Molenaar, Femke M.van Zuilen, Arjan D.Meijvis, Sabine C.A.Dolmans, HelmaEsposito, PasqualeKrzesinski, Jean-MarieBarahira, Jean DamacèneGallieni, MaurizioMartin-Moreno, Paloma LeticiaGuglielmetti, GabrieleGuzzo, GabriellaLuik, Antinus J.van Kuijk, Willi H.M.Stikkelbroeck, Lonneke W.H.Hermans, Marc M.H.Rimsevicius, LaurynasRighetti, MarcoIslam, MahmudBraak, Nicole Heitink-ter2021-06-04T11:54:31-07:00doi:10.2215/CJN.18961220hwp:resource-id:clinjasn;16/7/1061American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, renin angiotensin system, dialysis, kidney transplantation, kidney failureOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-07-01July 202110.2215/CJN.189612201555-90411555-905X2021-06-04T11:54:31-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles16771061100210721004
- Balancing the Needs of Acute and Maintenance Dialysis Patients during the COVID-19 PandemicThe COVID-19 pandemic continues to strain health care systems and drive shortages in medical supplies and equipment around the world. Resource allocation in times of scarcity requires transparent, ethical frameworks to optimize decision making and reduce health care worker and patient distress. The complexity of allocating dialysis resources for both patients receiving acute and maintenance dialysis has not previously been addressed. Using a rapid, collaborative, and iterative process, BC Renal, a provincial network in Canada, engaged patients, doctors, ethicists, administrators, and nurses to develop a framework for addressing system capacity, communication challenges, and allocation decisions. The guiding ethical principles that underpin this framework are (1) maximizing benefits, (2) treating people fairly, (3) prioritizing the worst-off individuals, and (4) procedural justice. Algorithms to support resource allocation and triage of patients were tested using simulations, and the final framework was reviewed and endorsed by members of the provincial nephrology community. The unique aspects of this allocation framework are the consideration of two diverse patient groups who require dialysis (acute and maintenance), and the application of two allocation criteria (urgency and prognosis) to each group in a sequential matrix. We acknowledge the context of the Canadian health care system, and a universal payer in which this framework was developed. The intention is to promote fair decision making and to maintain an equitable reallocation of limited resources for a complex problem during a pandemic.10.2215/CJN.07460520Mon, 08 Feb 2021 09:47:52 GMT-08:00Balancing the Needs of Acute and Maintenance Dialysis Patients during the COVID-19 PandemicThe COVID-19 pandemic continues to strain health care systems and drive shortages in medical supplies and equipment around the world. Resource allocation in times of scarcity requires transparent, ethical frameworks to optimize decision making and reduce health care worker and patient distress. The complexity of allocating dialysis resources for both patients receiving acute and maintenance dialysis has not previously been addressed. Using a rapid, collaborative, and iterative process, BC Renal, a provincial network in Canada, engaged patients, doctors, ethicists, administrators, and nurses to develop a framework for addressing system capacity, communication challenges, and allocation decisions. The guiding ethical principles that underpin this framework are (1) maximizing benefits, (2) treating people fairly, (3) prioritizing the worst-off individuals, and (4) procedural justice. Algorithms to support resource allocation and triage of patients were tested using simulations, and the final framework was reviewed and endorsed by members of the provincial nephrology community. The unique aspects of this allocation framework are the consideration of two diverse patient groups who require dialysis (acute and maintenance), and the application of two allocation criteria (urgency and prognosis) to each group in a sequential matrix. We acknowledge the context of the Canadian health care system, and a universal payer in which this framework was developed. The intention is to promote fair decision making and to maintain an equitable reallocation of limited resources for a complex problem during a pandemic.Carson, Rachel C.Forzley, BrianThomas, SarahPreto, NinaHargrove, GayleneVirani, AliceAntonsen, JohnBrown, MelanieCopland, MichaelMichaud, MarieSingh, AnuragLevin, Adeera2021-02-08T09:47:52-08:00doi:10.2215/CJN.07460520hwp:resource-id:clinjasn;16/7/1122American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, chronic disease, renal replacement therapy, acute care, ethics, acute kidney injury, triageInvited FeaturesInvited Featuresother20212021-07-01July 202110.2215/CJN.074605201555-90411555-905X2021-02-08T09:47:52-08:002021-07Clinical Journal of the American Society of NephrologyInvited Features16711221130
- Early Humoral Responses of Hemodialysis Patients after COVID-19 Vaccination with BNT162b210.2215/CJN.03700321Mon, 24 May 2021 02:37:49 GMT-07:00Early Humoral Responses of Hemodialysis Patients after COVID-19 Vaccination with BNT162b2Speer, ClaudiusGöth, DanielBenning, LouiseBuylaert, MirabelSchaier, MatthiasGrenz, JuliaNusshag, ChristianKälble, FlorianKreysing, MartinReichel, PaulaTöllner, MaximilianHidmark, AsaPonath, GeraldSchnitzler, PaulZeier, MartinSüsal, CanerMorath, ChristianKlein, Katrin2021-05-24T14:37:49-07:00doi:10.2215/CJN.03700321hwp:resource-id:clinjasn;16/7/1073American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvaccination, COVID-19, SARS-CoV-2, dialysis, humoral response, hemodialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-07-01July 202110.2215/CJN.037003211555-90411555-905X2021-05-24T14:37:49-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles167710739961082998
- Prevalence of SARS-CoV-2-IgG Antibodies in Children with CKD or Immunosuppression10.2215/CJN.00330121Mon, 07 Jun 2021 02:18:37 GMT-07:00Prevalence of SARS-CoV-2-IgG Antibodies in Children with CKD or ImmunosuppressionMorello, WilliamMastrangelo, AntonioGuzzo, IsabellaCusinato, LisaAnnicchiarico Petruzzelli, LuigiBenevenuta, ChiaraMartelli, LauraDall’Amico, RobertoVianello, Federica AlessandraPuccio, GiuseppeMassella, LauraBenetti, ElisaPecoraro, CarminePeruzzi, LiciaMontini, Giovanni,,Peruzzi, LiciaPetruzzelli, Luigi AnnicchiaricoBecherucci, FrancescaBenetti, ElisaBenevenuta, ChiaraBrugnara, MilenaCasadio, LucaChimenz, RobertoConti, GiovanniCorrado, CiroD’Agostino, VivianaDall’Amico, RobertoGianoglio, BrunoGiordano, MarioGualeni, ChiaraGuarino, StefanoGuzzo, IsabellaLa Manna, AngelaLa Scola, ClaudioMartelli, LauraMassella, LauraMastrangelo, AntonioMaterassi, MarcoMontini, GiovanniMorello, WilliamPani, AntonelloPapalia, TeresaPasini, AndreaPecoraro, CarminePelliccia, PiernicolaPennesi, MarcoPugliese, FabrizioRatsch, Ilse MariaRomagnani, PaolaRoperto, Rosa MariaTamburello, ChiaraVergine, GianlucaVergori, AntonioVianello, Federica AlessandraVidal, Enrico2021-06-07T14:18:37-07:00doi:10.2215/CJN.00330121hwp:resource-id:clinjasn;16/7/1097American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, SARS-CoV-2 IgG, CKD, immunosuppression, children, chronic kidney disease, idiopathic nephrotic syndromeResearch LetterResearch Letterresearch-article20212021-07-01July 202110.2215/CJN.003301211555-90411555-905X2021-06-07T14:18:37-07:002021-07Clinical Journal of the American Society of NephrologyResearch Letter16710971099
- mRNA COVID-19 Vaccine for People with Kidney Failure: Hope but Prudence Warranted10.2215/CJN.04500421Thu, 27 May 2021 09:25:51 GMT-07:00mRNA COVID-19 Vaccine for People with Kidney Failure: Hope but Prudence WarrantedMiskulin, Dana C.Combe, Christian2021-05-27T09:25:51-07:00doi:10.2215/CJN.04500421hwp:resource-id:clinjasn;16/7/996American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, dialysis, seroresponse, vaccinesEditorialEditorialeditorial20212021-07-01July 202110.2215/CJN.045004211555-90411555-905X2021-05-27T09:25:51-07:002021-07Clinical Journal of the American Society of NephrologyEditorial167779961037107399810421082
- Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis10.2215/CJN.03500321Tue, 06 Apr 2021 07:54:43 GMT-07:00Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance HemodialysisGrupper, AyeletSharon, NechamaFinn, TalyaCohen, RegevIsrael, MeitalAgbaria, AmirRechavi, YoavSchwartz, Idit F.Schwartz, DoronLellouch, YonatanShashar, Moshe2021-04-06T07:54:43-07:00doi:10.2215/CJN.03500321hwp:resource-id:clinjasn;16/7/1037American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, vaccine, hemodialysis, BNT162 vaccine, renal dialysisOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-07-01July 202110.2215/CJN.035003211555-90411555-905X2021-04-06T07:54:43-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles167710379961042998
- Nephrology—Taking the Lead10.2215/CJN.20061220Mon, 01 Mar 2021 06:01:34 GMT-08:00Nephrology—Taking the LeadAgarwal, Anupam2021-03-01T06:01:34-08:00doi:10.2215/CJN.20061220hwp:resource-id:clinjasn;16/7/1113American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyworkforce, diversity, innovation, COVID-19, nephrologyPerspectivesPerspectivesresearch-article20212021-07-01July 202110.2215/CJN.200612201555-90411555-905X2021-03-01T06:01:34-08:002021-07Clinical Journal of the American Society of NephrologyPerspectives16711131116
- Correction: Inherited Tubulopathies of the Kidney: Insights from Genetics10.2215/CJN.05570421Thu, 27 May 2021 09:25:51 GMT-07:00Correction: Inherited Tubulopathies of the Kidney: Insights from GeneticsAmerican Society of Nephrology2021-05-27T09:25:51-07:00doi:10.2215/CJN.05570421hwp:resource-id:clinjasn;16/7/1100American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney tubule, renal tubular acidosis, tubulopathies, nephrogenic diabetes insipidus, magnesium wasting disordersErratumErratumeditorial20212021-07-01July 202110.2215/CJN.055704211555-90411555-905X2021-05-27T09:25:51-07:002021-07Clinical Journal of the American Society of NephrologyErratum167411006201100630
- Kidney Disease Symptoms before and after Kidney Transplantationmara@jhu.edu10.2215/CJN.19031220Fri, 18 Jun 2021 10:59:27 GMT-07:00Kidney Disease Symptoms before and after Kidney TransplantationTaylor, KathrynChu, Nadia M.Chen, XiaomengShi, ZhanRosello, EileenKunwar, SnehaButz, PaulNorman, Silas P.Crews, Deidra C.Greenberg, Keiko I.Mathur, AartiSegev, Dorry L.Shafi, TariqMcAdams-DeMarco, Mara A.2021-06-18T10:59:27-07:00doi:10.2215/CJN.19031220hwp:resource-id:clinjasn;16/7/1083American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantationOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-07-01July 202110.2215/CJN.190312201555-90411555-905X2021-06-18T10:59:27-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles167710839891093990
- Nephrologist Follow-Up versus Usual Care after an Acute Kidney Injury Hospitalization (FUSION): A Randomized Controlled Trial10.2215/CJN.17331120Fri, 21 May 2021 04:58:47 GMT-07:00Nephrologist Follow-Up versus Usual Care after an Acute Kidney Injury Hospitalization (FUSION): A Randomized Controlled TrialSilver, Samuel A.Adhikari, Neill K.Bell, Chaim M.Chan, Christopher T.Harel, ZivKitchlu, AbhijatMeraz-Muñoz, AlejandroNorman, Patrick A.Perez, AdicZahirieh, AlirezaWald, Ron2021-05-21T04:58:47-07:00doi:10.2215/CJN.17331120hwp:resource-id:clinjasn;16/7/1005American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, acute renal failure, chronic kidney disease, progression of chronic renal failure, randomized controlled trials, nephrologists, hospitalizationOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-07-01July 202110.2215/CJN.173311201555-90411555-905X2021-05-21T04:58:47-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles1677710059991002101410011004
- Planning Patient Care after Acute Kidney Injury: Not as Easy as It May Seem10.2215/CJN.06380521Mon, 12 Jul 2021 07:54:45 GMT-07:00Planning Patient Care after Acute Kidney Injury: Not as Easy as It May SeemSelby, Nicholas M.Noble, Rebecca A.2021-07-12T07:54:45-07:00doi:10.2215/CJN.06380521hwp:resource-id:clinjasn;16/7/999American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, hospitalization, follow-up, patient careEditorialEditorialeditorial20212021-07-01July 202110.2215/CJN.063805211555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyEditorial1677999100510011014
- Sodium-Glucose Cotransporter-2 Inhibitors and the Risk of Abnormal Serum Potassium Level10.2215/CJN.02130221Mon, 12 Jul 2021 07:54:45 GMT-07:00Sodium-Glucose Cotransporter-2 Inhibitors and the Risk of Abnormal Serum Potassium LevelHwang, Y. JosephLyu, BeiniChang, Alex R.Inker, Lesley A.Grams, Morgan E.Shin, Jung-Im2021-07-12T07:54:45-07:00doi:10.2215/CJN.02130221hwp:resource-id:clinjasn;16/7/1094American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysodium-glucose cotransporter-2 inhibitor, hyperkalemia, hypokalemia, potassium, type 2 diabetes mellitus, SGLT2iResearch LetterResearch Letterresearch-article20212021-07-01July 202110.2215/CJN.021302211555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyResearch Letter16710941096
- Management of Heart Failure Patient with CKDCKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m2. Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m2). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.10.2215/CJN.14180920Mon, 25 Jan 2021 07:53:45 GMT-08:00Management of Heart Failure Patient with CKDCKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m2. Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m2). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.Banerjee, DebasishRosano, GiuseppeHerzog, Charles A.2021-01-25T07:53:45-08:00doi:10.2215/CJN.14180920hwp:resource-id:clinjasn;16/7/1131American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, heart failure, dialysisReviewsReviewsreview-article20212021-07-01July 202110.2215/CJN.141809201555-90411555-905X2021-01-25T07:53:45-08:002021-07Clinical Journal of the American Society of NephrologyReviews16711311139
- Prediction of Incident Atrial Fibrillation in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Study10.2215/CJN.01060121Mon, 12 Jul 2021 07:54:45 GMT-07:00Prediction of Incident Atrial Fibrillation in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort StudyZelnick, Leila R.Shlipak, Michael G.Soliman, Elsayed Z.Anderson, AmandaChristenson, RobertLash, JamesDeo, RajatRao, PandurangaAfshinnia, FarsadChen, JingHe, JiangSeliger, StephenTownsend, RaymondCohen, Debbie L.Go, AlanBansal, Nisha2021-07-12T07:54:45-07:00doi:10.2215/CJN.01060121hwp:resource-id:clinjasn;16/7/1015American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, clinical epidemiology, atrial fibrillationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-07-01July 202110.2215/CJN.010601211555-90411555-905X2021-07-12T07:54:45-07:002021-07Clinical Journal of the American Society of NephrologyOriginal Articles16710151024
- This Month’s Highlights10.1681/ASN.2021040536Mon, 12 Jul 2021 06:29:52 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2021-07-12T06:29:52-07:00doi:10.1681/ASN.2021040536hwp:resource-id:jnephrol;32/6/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsarticle-commentary20212021-06-01June 202110.1681/ASN.20210405361046-66731533-34502021-07-12T06:29:52-07:002021-06Journal of the American Society of NephrologyThis Month’s Highlights32666666i13711389144415271270i13881408145315351273
- The Sniffing Kidney: Roles for Renal Olfactory Receptors in Health and DiseaseOlfactory receptors (ORs) represent the largest gene family in the human genome. Despite their name, functions exist for these receptors outside of the nose. Among the tissues known to take advantage of OR signaling is the kidney. From mouse to man, the list of renal ORs continues to expand, and they have now been linked to a variety of processes involved in the maintenance of renal homeostasis, including the modulation of blood pressure, response to acidemia, and the development of diabetes. In this review, we highlight the recent progress made on the growing appreciation for renal ORs in physiology and pathophysiology.10.34067/KID.0000712021Mon, 19 Apr 2021 02:13:27 GMT-07:00The Sniffing Kidney: Roles for Renal Olfactory Receptors in Health and DiseaseOlfactory receptors (ORs) represent the largest gene family in the human genome. Despite their name, functions exist for these receptors outside of the nose. Among the tissues known to take advantage of OR signaling is the kidney. From mouse to man, the list of renal ORs continues to expand, and they have now been linked to a variety of processes involved in the maintenance of renal homeostasis, including the modulation of blood pressure, response to acidemia, and the development of diabetes. In this review, we highlight the recent progress made on the growing appreciation for renal ORs in physiology and pathophysiology.Shepard, Blythe D.2021-04-19T14:13:27-07:00doi:10.34067/KID.0000712021hwp:resource-id:kidney360;2/6/1056American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360renal physiology, acidemia, basic science, blood pressure, diabetes, GPCR, odorant receptors, olfactory receptorBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-06-2410.34067/KID.00007120212641-76502021-04-19T14:13:27-07:002021-06-24Kidney360Basic Science for Clinicians2610561062
- Global Dialysis Perspective: Brunei Darussalam10.34067/KID.0002342021Mon, 19 Apr 2021 02:13:27 GMT-07:00Global Dialysis Perspective: Brunei DarussalamLim, Chiao YuenTan, Jackson2021-04-19T14:13:27-07:00doi:10.34067/KID.0002342021hwp:resource-id:kidney360;2/6/1027American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, Brunei, dialysis, end stage kidney disease, epidemiology, funding, policy, registryGlobal PerspectivesGlobal Perspectivesresearch-article20212021-06-2410.34067/KID.00023420212641-76502021-04-19T14:13:27-07:002021-06-24Kidney360Global Perspectives2610271030
- Adding Life to Their Years: The Current State of Pediatric Palliative Care in CKDDespite continued advances in medical treatment, pediatric CKD remains an unremitting, burdensome condition characterized by decreased quality of life and earlier death. These burdens underscore the need for integration of pediatric palliative care (PPC) into nephrology practice. PPC is an evolving field that strives to (1) relieve physical, psychologic, social, practical, and existential suffering; (2) improve quality of life; (3) facilitate decision making; and (4) assist with care coordination in children with life-threatening or life-shortening conditions. Integration of palliative care into routine care has already begun for adults with kidney disease and children with other chronic diseases; however, similar integration has not occurred in pediatric nephrology. This review serves to provide a comprehensive definition of PPC, highlight the unmet need in pediatric nephrology and current integration efforts, discuss the state of palliative care in adult nephrology and analogous chronic pediatric disease states, and introduce future opportunities for study.10.34067/KID.0000282021Wed, 07 Apr 2021 01:28:30 GMT-07:00Adding Life to Their Years: The Current State of Pediatric Palliative Care in CKDDespite continued advances in medical treatment, pediatric CKD remains an unremitting, burdensome condition characterized by decreased quality of life and earlier death. These burdens underscore the need for integration of pediatric palliative care (PPC) into nephrology practice. PPC is an evolving field that strives to (1) relieve physical, psychologic, social, practical, and existential suffering; (2) improve quality of life; (3) facilitate decision making; and (4) assist with care coordination in children with life-threatening or life-shortening conditions. Integration of palliative care into routine care has already begun for adults with kidney disease and children with other chronic diseases; however, similar integration has not occurred in pediatric nephrology. This review serves to provide a comprehensive definition of PPC, highlight the unmet need in pediatric nephrology and current integration efforts, discuss the state of palliative care in adult nephrology and analogous chronic pediatric disease states, and introduce future opportunities for study.House, Taylor R.Wightman, Aaron2021-04-07T13:28:30-07:00doi:10.34067/KID.0000282021hwp:resource-id:kidney360;2/6/1063American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360geriatric and palliative nephrology, chronic kidney disease, dialysis, end stage kidney disease, kidney supportive care, pediatric nephrology, pediatric palliative careReview ArticleReview Articlereview-article20212021-06-2410.34067/KID.00002820212641-76502021-04-07T13:28:30-07:002021-06-24Kidney360Review Article2610631071
- SARS-CoV-2 Infection Risk Factors among Maintenance Hemodialysis Patients and Health Care Personnel In Outpatient Hemodialysis Centers10.34067/KID.0001282021Wed, 21 Apr 2021 06:02:44 GMT-07:00SARS-CoV-2 Infection Risk Factors among Maintenance Hemodialysis Patients and Health Care Personnel In Outpatient Hemodialysis CentersGandra, SumanthLi, TingtingReske, Kimberly A.Dang, Na LeFarnsworth, Christopher W.Hock, Karl G.Miller, CandaceOlsen, Margaret A.Kwon, Jennie H.Warren, David K.Fraser, Victoria J.2021-04-21T06:02:44-07:00doi:10.34067/KID.0001282021hwp:resource-id:kidney360;2/6/996American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, delivery of health care, ESRD, health personnel, hemodialysis, outpatients, risk factors, SARS-CoV-2Brief CommunicationDialysisBrief CommunicationDialysisresearch-article20212021-06-2410.34067/KID.00012820212641-76502021-04-21T06:02:44-07:002021-06-24Kidney360Brief Communication269961001
- Autosomal Dominant Polycystic Kidney Disease Does Not Significantly Alter Major COVID-19 Outcomes among Veterans10.34067/KID.0007282020Wed, 28 Apr 2021 12:29:36 GMT-07:00Autosomal Dominant Polycystic Kidney Disease Does Not Significantly Alter Major COVID-19 Outcomes among VeteransCui, XiangqinGallini, Julia W.Jasien, Christine L.Mrug, Michal2021-04-28T12:29:36-07:00doi:10.34067/KID.0007282020hwp:resource-id:kidney360;2/6/983American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, chronic kidney disease, coronavirus disease 2019, COVID-19, hospital admission, ICU admission, kidney failure, mortality, polycystic kidney disease, SARS-CoV-2, ventilator, veteransBrief CommunicationCystic Kidney DiseaseBrief CommunicationCystic Kidney Diseaseresearch-article20212021-06-2410.34067/KID.00072820202641-76502021-04-28T12:29:36-07:002021-06-24Kidney360Brief Communication26983988
- Vaccine and the Need To Be Heard: Considerations for COVID-19 Immunization in ESKD10.34067/KID.0001932021Thu, 08 Apr 2021 01:50:57 GMT-07:00Vaccine and the Need To Be Heard: Considerations for COVID-19 Immunization in ESKDSrivatana, VeshWilkie, CarolinePerl, JefferyWatnick, Suzanne2021-04-08T13:50:57-07:00doi:10.34067/KID.0001932021hwp:resource-id:kidney360;2/6/1048American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, COVID-19, vaccinePerspectivePerspectiveresearch-article20212021-06-2410.34067/KID.00019320212641-76502021-04-08T13:50:57-07:002021-06-24Kidney360Perspective2610481050
- Development and Validation of a Transfusion Risk Score for Patients Receiving Maintenance Hemodialysis10.34067/KID.0004512020Fri, 09 Apr 2021 08:03:38 GMT-07:00Development and Validation of a Transfusion Risk Score for Patients Receiving Maintenance HemodialysisGilbertson, David T.Yan, HengXu, HairongSinsakul, MarvinPeng, YiWetmore, James B.Liu, JiannongLi, Suying2021-04-09T08:03:38-07:00doi:10.34067/KID.0004512020hwp:resource-id:kidney360;2/6/948American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, blood transfusion, hemodialysis, maintenance, risk factorsOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-06-2410.34067/KID.00045120202641-76502021-04-09T08:03:38-07:002021-06-24Kidney360Original Investigation26948954
- Performance and Hemocompatibility of a Novel Polysulfone Dialyzer: A Randomized Controlled Trial10.34067/KID.0000302021Wed, 07 Apr 2021 01:28:30 GMT-07:00Performance and Hemocompatibility of a Novel Polysulfone Dialyzer: A Randomized Controlled TrialEhlerding, GötzErlenkötter, AnsgarGauly, AdelheidGriesshaber, BettinaKennedy, JamesRauber, LenaRies, WolfgangSchmidt-Gürtler, HansStauss-Grabo, ManuelaWagner, StephanZawada, Adam M.Zschätzsch, SebastianKempkes-Koch, Manuela2021-04-07T13:28:30-07:00doi:10.34067/KID.0000302021hwp:resource-id:kidney360;2/6/937American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, β2-microglobulin removal rate, complement activation, dialyzer, hemocompatibility, leukocytes, polymersOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-06-2410.34067/KID.00003020212641-76502021-04-07T13:28:30-07:002021-06-24Kidney360Original Investigation26937947
- This Month’s Highlights10.1681/ASN.2021050662Fri, 02 Jul 2021 12:51:34 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2021-07-02T12:51:34-07:00doi:10.1681/ASN.2021050662hwp:resource-id:jnephrol;32/7/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsarticle-commentary20212021-07-01July 202110.1681/ASN.20210506621046-66731533-34502021-07-02T12:51:34-07:002021-07Journal of the American Society of NephrologyThis Month’s Highlights327777107777i16491713154122531733154417791747i16651732154322621746154517901763
- Identification of an Altered Matrix Signature in Kidney Aging and Disease10.1681/ASN.2020101442Fri, 28 May 2021 11:41:26 GMT-07:00Identification of an Altered Matrix Signature in Kidney Aging and DiseaseRandles, Michael J.Lausecker, FranziskaKong, QingyangSuleiman, HaniReid, GraemeKolatsi-Joannou, MariaDavenport, BernardTian, PinyuanFalcone, SaraPotter, PaulVan Agtmael, TomNorman, Jill T.Long, David A.Humphries, Martin J.Miner, Jeffrey H.Lennon, Rachel2021-05-28T11:41:26-07:00doi:10.1681/ASN.2020101442hwp:resource-id:jnephrol;32/7/1713American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyextracellular matrix, basement membrane, mass spectrometry, proteomics, tubulointerstitium, fibrosis, matrix signature, nephronectin, type VI collagen, type IV collagenBasic ResearchBasic Researchresearch-article20212021-07-01June 202110.1681/ASN.20201014421046-66731533-34502021-05-28T11:41:26-07:002021-07Journal of the American Society of NephrologyBasic Research3277717131541i17321543i
- High Incidence of Circuit Clotting in Critically Ill COVID-19 Patients Treated with Renal Replacement Therapy10.1681/ASN.2021040528Fri, 28 May 2021 10:31:36 GMT-07:00High Incidence of Circuit Clotting in Critically Ill COVID-19 Patients Treated with Renal Replacement TherapyGrenon, EloïseCanet, Emmanuel2021-05-28T10:31:36-07:00doi:10.1681/ASN.2021040528hwp:resource-id:jnephrol;32/7/1823American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, renal replacement therapy, circuit clotting, intensive care unit, acute kidney injuryLetters to the EditorLetters to the Editorletter20212021-07-01July 202110.1681/ASN.20210405281046-66731533-34502021-05-28T10:31:36-07:002021-07Journal of the American Society of NephrologyLetters to the Editor327118231611824176
- Epidemiology and Outcomes of COVID-19 in Home Dialysis Patients Compared with In-Center Dialysis Patients10.1681/ASN.2020111653Wed, 09 Jun 2021 01:22:33 GMT-07:00Epidemiology and Outcomes of COVID-19 in Home Dialysis Patients Compared with In-Center Dialysis PatientsHsu, Caroline M.Weiner, Daniel E.Aweh, GideonSalenger, PageJohnson, Doug S.Lacson, Eduardo2021-06-09T13:22:33-07:00doi:10.1681/ASN.2020111653hwp:resource-id:jnephrol;32/7/1569American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, chronic kidney disease, epidemiology and outcomes, ESKD, peritoneal dialysis, risk factors, SARS-CoV-2, COVID-19Research lettersResearch lettersletter20212021-07-01July 202110.1681/ASN.20201116531046-66731533-34502021-06-09T13:22:33-07:002021-07Journal of the American Society of NephrologyResearch letters32715691573
- Patients with High Priority for Kidney Transplant Who Are Not Given Expedited Placement on the Transplant Waiting List Represent Lost Opportunities10.1681/ASN.2020081146Thu, 17 Jun 2021 02:32:26 GMT-07:00Patients with High Priority for Kidney Transplant Who Are Not Given Expedited Placement on the Transplant Waiting List Represent Lost OpportunitiesSchold, Jesse D.Huml, Anne M.Poggio, Emilio D.Sedor, John R.Husain, Syed A.King, Kristin L.Mohan, Sumit2021-06-17T14:32:26-07:00doi:10.1681/ASN.2020081146hwp:resource-id:jnephrol;32/7/1733American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, epidemiology and outcomes, kidney transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20212021-07-01July 202110.1681/ASN.20200811461046-66731533-34502021-06-17T14:32:26-07:002021-07Journal of the American Society of NephrologyClinical Epidemiology327777173315441541i174615451543i
- Diagnosis, Education, and Care of Patients with APOL1-Associated Nephropathy: A Delphi Consensus and Systematic Review10.1681/ASN.2020101399Wed, 14 Apr 2021 08:05:58 GMT-07:00Diagnosis, Education, and Care of Patients with APOL1-Associated Nephropathy: A Delphi Consensus and Systematic ReviewFreedman, Barry I.Burke, WylieDivers, JasminEberhard, LucyGadegbeku, Crystal A.Gbadegesin, RasheedHall, Michael E.Jones-Smith, TiffanyKnight, RichardKopp, Jeffrey B.Kovesdy, Csaba P.Norris, Keith C.Olabisi, Opeyemi A.Roberts, Glenda V.Sedor, John R.Blacksher, Erika2021-04-14T08:05:58-07:00doi:10.1681/ASN.2020101399hwp:resource-id:jnephrol;32/7/1765American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, focal segmental glomerulosclerosis, genetic renal disease, HIV nephropathy, hypertension, lupus nephritis, pediatrics, polymorphisms, APOL1Clinical ResearchClinical Researchresearch-article20212021-07-01July 202110.1681/ASN.20201013991046-66731533-34502021-04-14T08:05:58-07:002021-07Journal of the American Society of NephrologyClinical Research32717651778
- Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart Failure10.1681/ASN.2020071029Mon, 12 Apr 2021 08:29:15 GMT-07:00Empagliflozin Inhibits Proximal Tubule NHE3 Activity, Preserves GFR, and Restores Euvolemia in Nondiabetic Rats with Induced Heart FailureBorges-Júnior, Flávio A.Silva dos Santos, DanúbiaBenetti, AcarisPolidoro, Juliano Z.Wisnivesky, Aline C.T.Crajoinas, Renato O.Antônio, Ednei L.Jensen, LeonardoCaramelli, BrunoMalnic, GerhardTucci, Paulo J.Girardi, Adriana C.C.2021-04-12T08:29:15-07:00doi:10.1681/ASN.2020071029hwp:resource-id:jnephrol;32/7/1616American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysodium-glucose cotransporter type 2, Na+/H+ exchanger isoform 3, gliflozins, renal function, cardiorenal protectionBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20200710291046-66731533-34502021-04-12T08:29:15-07:002021-07Journal of the American Society of NephrologyBasic Research32716161629
- New Kidney and Pancreas Allocation Policy: Moving to a Circle as the First Unit of Allocation10.1681/ASN.2020121679Thu, 17 Jun 2021 01:44:29 GMT-07:00New Kidney and Pancreas Allocation Policy: Moving to a Circle as the First Unit of AllocationIsrani, AjayWey, AndrewThompson, BrynMiller, JonCasingal, VincentPavlakis, MarthaNiederhaus, SilkeForbes, RachelWilk, AmberMcKinney, WarrenKandaswamy, RajaStock, PeterSnyder, Jon2021-06-17T13:44:29-07:00doi:10.1681/ASN.2020121679hwp:resource-id:jnephrol;32/7/1546American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, organ transplant, kidney transplantationPerspectivesPerspectivesresearch-article20212021-07-01July 202110.1681/ASN.20201216791046-66731533-34502021-06-17T13:44:29-07:002021-07Journal of the American Society of NephrologyPerspectives32715461550
- SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey10.1681/ASN.2021010104Thu, 29 Apr 2021 04:53:52 GMT-07:00SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide SurveyGarcia, PabloMontez-Rath, Maria E.Moore, HeatherFlotte, JohnieFults, ChrisBlock, Martha S.Han, JialinDittrich, MaryParsonnet, JulieChertow, Glenn M.Block, Geoffrey A.Anand, Shuchi2021-04-29T04:53:52-07:00doi:10.1681/ASN.2021010104hwp:resource-id:jnephrol;32/7/1575American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, vaccine, SARS-CoV-2, ESKD, COVID-19Rapid CommunicationRapid Communicationresearch-article20212021-07-01July 202110.1681/ASN.20210101041046-66731533-34502021-04-29T04:53:52-07:002021-07Journal of the American Society of NephrologyRapid Communication32715751581
- Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy10.1681/ASN.2020101395Wed, 05 May 2021 11:31:21 GMT-07:00Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous NephropathyAl-Rabadi, Laith FarahCaza, TiffanyTrivin-Avillach, ClaireRodan, Aylin R.Andeen, NicoleHayashi, NorifumiWilliams, BrandiRevelo, Monica P.Clayton, FredAbraham, JoLin, EdwinLiou, WillisaZou, Chang-JiangRamkumar, NirupamaCummins, TimWilkey, Daniel W.Kawalit, IssaHerzog, ChristianStorey, AaronEdmondson, RickSjoberg, RonaldYang, TianxinChien, JeremyMerchant, MichaelArthur, JohnKlein, JonLarsen, ChrisBeck, Laurence H.2021-05-05T11:31:21-07:00doi:10.1681/ASN.2020101395hwp:resource-id:jnephrol;32/7/1666American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, podocyte, nephrotic syndromeBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20201013951046-66731533-34502021-05-05T11:31:21-07:002021-07Journal of the American Society of NephrologyBasic Research32716661681
- Utility of Phosphate Binder Equivalent Dose Concept10.1681/ASN.2021040440Wed, 30 Jun 2021 07:50:25 GMT-07:00Utility of Phosphate Binder Equivalent Dose ConceptKulkarni, Manjunath2021-06-30T19:50:25-07:00doi:10.1681/ASN.2021040440hwp:resource-id:jnephrol;32/7/1824American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytenapanor, phosphate binders, hyperphosphatemia, sevelamerLetters to the editorLetters to the editorletter20212021-07-01July 202110.1681/ASN.20210404401046-66731533-34502021-06-30T19:50:25-07:002021-07Journal of the American Society of NephrologyLetters to the editor32776182418241465182418251473
- The Effect of Tolvaptan on BP in Polycystic Kidney Disease: A Post Hoc Analysis of the TEMPO 3:4 Trial10.1681/ASN.2020101512Thu, 22 Apr 2021 09:57:01 GMT-07:00The Effect of Tolvaptan on BP in Polycystic Kidney Disease: A Post Hoc Analysis of the TEMPO 3:4 TrialHeida, Judith E.Gansevoort, Ron T.Torres, Vicente E.Devuyst, OlivierPerrone, Ronald D.Lee, JenniferLi, HuiOuyang, JohnChapman, Arlene B.2021-04-22T09:57:01-07:00doi:10.1681/ASN.2020101512hwp:resource-id:jnephrol;32/7/1801American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, vasopressin, blood pressure, V2 receptor antagonistClinical ResearchClinical Researchresearch-article20212021-07-01July 202110.1681/ASN.20201015121046-66731533-34502021-04-22T09:57:01-07:002021-07Journal of the American Society of NephrologyClinical Research32718011812
- Role of Platelets in Chronic Kidney DiseasePlatelet-dependent mechanisms for excessive clotting and bleeding in CKD remain undefined. Moreover, platelets’ contribution to inflammation, and specifically to CKD, are equally elusive. To date, descriptions of changes in the functional properties of circulating platelets during CKD have provided confusing interpretations. Experimental approaches that can advance our understanding of platelet dysfunction in CKD are needed, and studies that provide mechanistic insights into the dynamic relationships between thrombosis, bleeding, and inflammation associated with CKD will be essential to improve clinical management and outcomes for this vulnerable population. This article summarizes existing literature characterizing platelets in CKD and identifies areas that need further investigation.10.1681/ASN.2020121806Thu, 17 Jun 2021 01:44:29 GMT-07:00Role of Platelets in Chronic Kidney DiseasePlatelet-dependent mechanisms for excessive clotting and bleeding in CKD remain undefined. Moreover, platelets’ contribution to inflammation, and specifically to CKD, are equally elusive. To date, descriptions of changes in the functional properties of circulating platelets during CKD have provided confusing interpretations. Experimental approaches that can advance our understanding of platelet dysfunction in CKD are needed, and studies that provide mechanistic insights into the dynamic relationships between thrombosis, bleeding, and inflammation associated with CKD will be essential to improve clinical management and outcomes for this vulnerable population. This article summarizes existing literature characterizing platelets in CKD and identifies areas that need further investigation.Jain, NishankCorken, Adam L.Kumar, AmudhaDavis, Clayton L.Ware, JerryArthur, John M.2021-06-17T13:44:29-07:00doi:10.1681/ASN.2020121806hwp:resource-id:jnephrol;32/7/1551American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyplatelets, chronic inflammation, chronic kidney disease, thrombosis, bleedingReviewsReviewsreview-article20212021-07-01July 202110.1681/ASN.20201218061046-66731533-34502021-06-17T13:44:29-07:002021-07Journal of the American Society of NephrologyReviews32715511558
- A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS10.1681/ASN.2020081234Fri, 16 Apr 2021 06:48:33 GMT-07:00A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGSLane, Brandon M.Murray, SusanBenson, KatherineBierzynska, AgnieszkaChryst-Stangl, MeganWang, LimingWu, GuanghongCavalleri, GianpieroDoyle, BrendanFennelly, NeilDorman, AnthonyConlon, ShaneVega-Warner, VirginiaFermin, DamianVijayan, PoornimaQureshi, Mohammad AzfarShril, ShirleeBarua, MoumitaHildebrandt, FriedhelmPollak, MartinHowell, DavidSampson, Matthew G.Saleem, MoinConlon, Peter J.Spurney, RobertGbadegesin, Rasheed2021-04-16T06:48:33-07:00doi:10.1681/ASN.2020081234hwp:resource-id:jnephrol;32/7/1682American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, glomerular disease, genetic renal disease, nephrotic syndrome, tacrolimus, chronic kidney disease, calcineurin inhibitors, calcineurin, podocyteBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20200812341046-66731533-34502021-04-16T06:48:33-07:002021-07Journal of the American Society of NephrologyBasic Research32716821695
- Effects of a Knowledge-Translation Intervention on Early Dialysis Initiation: A Cluster Randomized Trial10.1681/ASN.2020091254Thu, 15 Apr 2021 06:16:02 GMT-07:00Effects of a Knowledge-Translation Intervention on Early Dialysis Initiation: A Cluster Randomized TrialTangri, NavdeepGarg, Amit X.Ferguson, Thomas W.Dixon, StephanieRigatto, ClaudioAllu, SelinaChau, ElaineKomenda, PaulNaimark, DavidNesrallah, Gihad E.Soroka, Steven D.Beaulieu, MonicaAlam, AhsanKim, S. JosephSood, Manish M.Manns, Braden2021-04-15T06:16:02-07:00doi:10.1681/ASN.2020091254hwp:resource-id:jnephrol;32/7/1791American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrandomized controlled trials, clinical trial, chronic dialysis, glomerular filtration rate, hospitalization, kidney failureClinical ResearchClinical Researchresearch-article20212021-07-01July 202110.1681/ASN.20200912541046-66731533-34502021-04-15T06:16:02-07:002021-07Journal of the American Society of NephrologyClinical Research32717911800
- Cardiac and Noncardiac Determinants of Exercise Capacity in CKD10.1681/ASN.2020091319Fri, 18 Jun 2021 11:02:43 GMT-07:00Cardiac and Noncardiac Determinants of Exercise Capacity in CKDChinnappa, ShanmugakumarLewis, NigelBaldo, OmerShih, Ming-ChiehTu, Yu-KangMooney, Andrew2021-06-18T11:02:43-07:00doi:10.1681/ASN.2020091319hwp:resource-id:jnephrol;32/7/1813American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, exercise capacity, determinants, heart failureClinical ResearchClinical Researchresearch-article20212021-07-01July 202110.1681/ASN.20200913191046-66731533-34502021-06-18T11:02:43-07:002021-07Journal of the American Society of NephrologyClinical Research32718131822
- Authors’ Reply10.1681/ASN.2021050606Wed, 30 Jun 2021 07:50:25 GMT-07:00Authors’ ReplyPergola, Pablo E.Rosenbaum, David P.Yang, YangChertow, Glenn M.2021-06-30T19:50:25-07:00doi:10.1681/ASN.2021050606hwp:resource-id:jnephrol;32/7/1824-aAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytenapanor, hyperphosphatemia, phosphate binders, dialysis, phosphate uptakeLetters to the editorLetters to the editorletter20212021-07-01July 202110.1681/ASN.20210506061046-66731533-34502021-06-30T19:50:25-07:002021-07Journal of the American Society of NephrologyLetters to the editor32776182418241465182518241473
- Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Studypamela.matias@helmholtz-muenchen.depamela.matias@helmholtz-muenchen.de10.1681/ASN.2020071070Wed, 16 Jun 2021 10:31:16 GMT-07:00Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization StudyMatías-García, Pamela R.Wilson, RoryGuo, QiZaghlool, Shaza B.Eales, James M.Xu, XiaoguangCharchar, Fadi J.Dormer, JohnMaalmi, HaifaSchlosser, PascalElhadad, Mohamed A.Nano, JanaSharma, SapnaPeters, AnnetteFornoni, AlessiaMook-Kanamori, Dennis O.Winkelmann, JulianeDanesh, JohnDi Angelantonio, EmanueleOuwehand, Willem H.Watkins, Nicholas A.Roberts, David J.Petrera, AgneseGraumann, JohannesKoenig, WolfgangHveem, KristianJonasson, ChristianKöttgen, AnnaButterworth, AdamPrunotto, MarcoHauck, Stefanie M.Herder, ChristianSuhre, KarstenGieger, ChristianTomaszewski, MaciejTeumer, AlexanderWaldenberger, Melanie,2021-06-16T10:31:16-07:00doi:10.1681/ASN.2020071070hwp:resource-id:jnephrol;32/7/1747American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyMendelian randomization, chronic kidney disease, glomerular filtration rate, epidemiology and outcomes, plasma proteomics, biomarker discovery, testican-2, gene expression, genetic epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20212021-07-01July 202110.1681/ASN.20200710701046-66731533-34502021-06-16T10:31:16-07:002021-07Journal of the American Society of NephrologyClinical Epidemiology32771747i1763i
- Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury10.1681/ASN.2020121723Mon, 19 Apr 2021 08:55:47 GMT-07:00Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion InjuryHasegawa, ShoInoue, TsuyoshiNakamura, YasunaFukaya, DaichiUni, RieWu, Chia-HsienFujii, RiePeerapanyasut, WachirasekTaguchi, AkashiKohro, TakahideYamada, ShintaroKatagiri, MikakoKo, ToshiyukiNomura, SeitaroNakanishi Ozeki, AtsukoSusaki, Etsuo A.Ueda, Hiroki R.Akimitsu, NobuyoshiWada, YouichiroKomuro, IsseiNangaku, MasaomiInagi, Reiko2021-04-19T08:55:47-07:00doi:10.1681/ASN.2020121723hwp:resource-id:jnephrol;32/7/1599American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, macrophages, cell biology and structure, cell signaling, cell transfer, clinical immunology, cytokines, immunology, ischemia-reperfusion, kidneyBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20201217231046-66731533-34502021-04-19T08:55:47-07:002021-07Journal of the American Society of NephrologyBasic Research32715991615
- Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD10.1681/ASN.2020091311Wed, 21 Apr 2021 06:27:51 GMT-07:00Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKDNangaku, MasaomiKondo, KazuokiKokado, YoshimasaUeta, KiichiroKaneko, GenkiTandai, TsubasaKawaguchi, YutakaKomatsu, Yasuhiro2021-04-21T06:27:51-07:00doi:10.1681/ASN.2020091311hwp:resource-id:jnephrol;32/7/1779American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, erythropoiesis, HIF prolyl hydroxylase inhibitor, Japan, nondialysis-dependent CKD, vadadustatClinical ResearchClinical Researchresearch-article20212021-07-01July 202110.1681/ASN.20200913111046-66731533-34502021-04-21T06:27:51-07:002021-07Journal of the American Society of NephrologyClinical Research32771779i1790i
- Primacy in Kidney Allocation: Does It Alleviate the Barriers to Transplantation?10.1681/ASN.2021040474Thu, 17 Jun 2021 02:05:27 GMT-07:00Primacy in Kidney Allocation: Does It Alleviate the Barriers to Transplantation?Gill, John S.Butler, Catherine R.Powe, Neil R.2021-06-17T14:05:27-07:00doi:10.1681/ASN.2021040474hwp:resource-id:jnephrol;32/7/1544American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologytransplantationEditorialsEditorialseditorial20212021-07-01July 202110.1681/ASN.20210404741046-66731533-34502021-06-17T14:05:27-07:002021-07Journal of the American Society of NephrologyEditorials3277715441733i15451746i
- Autonomous Calcium Signaling in Human and Zebrafish Podocytes Controls Kidney Filtration Barrier Morphogenesis10.1681/ASN.2020101525Wed, 28 Apr 2021 06:02:25 GMT-07:00Autonomous Calcium Signaling in Human and Zebrafish Podocytes Controls Kidney Filtration Barrier MorphogenesisDjenoune, LydiaTomar, RituDorison, AudeGhobrial, IreneSchenk, HeikoHegermann, JanBeverly-Staggs, LynneHidalgo-Gonzalez, AlejandroLittle, Melissa H.Drummond, Iain A.2021-04-28T06:02:25-07:00doi:10.1681/ASN.2020101525hwp:resource-id:jnephrol;32/7/1697American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, calcium signaling, zebrafish, kidney organoid, organoid glomeruli, glomerulusBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20201015251046-66731533-34502021-04-28T06:02:25-07:002021-07Journal of the American Society of NephrologyBasic Research32716971712
- 3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development10.1681/ASN.2020081204Mon, 19 Apr 2021 08:55:48 GMT-07:003D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney DevelopmentLipp, Sarah N.Jacobson, Kathryn R.Hains, David S.Schwarderer, Andrew L.Calve, Sarah2021-04-19T08:55:48-07:00doi:10.1681/ASN.2020081204hwp:resource-id:jnephrol;32/7/1649American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyinterstitial matrix, basement membrane, mass spectrometry, 3D imaging, kidney development, extracellular matrix, kidney anatomyBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20200812041046-66731533-34502021-04-19T08:55:48-07:002021-07Journal of the American Society of NephrologyBasic Research3277716491541i16651543i
- Platelet Function in CKD: A Systematic Review and Meta-Analysis10.1681/ASN.2020101440Mon, 03 May 2021 06:08:23 GMT-07:00Platelet Function in CKD: A Systematic Review and Meta-AnalysisBaaten, Constance C.F.M.J.Sternkopf, MariekeHenning, TobiasMarx, NikolausJankowski, JoachimNoels, Heidi2021-05-03T06:08:23-07:00doi:10.1681/ASN.2020101440hwp:resource-id:jnephrol;32/7/1583American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, platelets, thrombosis, bleeding, uremic toxinsMeta-analysisMeta-analysisresearch-article20212021-07-01July 202110.1681/ASN.20201014401046-66731533-34502021-05-03T06:08:23-07:002021-07Journal of the American Society of NephrologyMeta-analysis32715831598
- Too Little or Too Much? Extracellular Matrix Remodeling in Kidney Health and Disease10.1681/ASN.2021050654Wed, 16 Jun 2021 10:31:16 GMT-07:00Too Little or Too Much? Extracellular Matrix Remodeling in Kidney Health and DiseaseClotet-Freixas, SergiKonvalinka, Ana2021-06-16T10:31:16-07:00doi:10.1681/ASN.2021050654hwp:resource-id:jnephrol;32/7/1541American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyextracellular matrix, proteomics, protease, glomerular basement membrane, tubular basement membrane, multi-channel time-lapse confocal imaging, formalin-fixed paraffin embedded, mass spectrometry, activity-based protein profiling, isotope labelingEditorialsEditorialseditorial20212021-07-01July 202110.1681/ASN.20210506541046-66731533-34502021-06-16T10:31:16-07:002021-07Journal of the American Society of NephrologyEditorials32777771541171317331649i1543173217461665i
- Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and FibrosisThe effectiveness of cisplatin, a mainstay in the treatment of many solid organ cancers, is hindered by dose-limiting nephrotoxicity. Cisplatin causes AKI in 30% of patients. Patients who do not develop AKI by clinical standards during treatment are still at risk for long-term decline in kidney function and the development of CKD. The connection between AKI and CKD has become increasingly studied, with renal fibrosis a hallmark of CKD development. To prevent both the short- and long-term effects of cisplatin, researchers must use models that reflect both types of pathology. Although a lot is known about cisplatin-induced AKI, very little is known about the mechanisms by which repeated low levels of cisplatin lead to fibrosis development. In this review, strategies used in various rodent models to prevent kidney injury, its progression to fibrosis, or both, are examined to gain mechanistic insights and identify potential therapeutic targets for cisplatin-induced kidney pathologies. Reviewing the results from these models highlights the diverse and highly complex role of cell death, cell senescence, endoplasmic reticulum stress, autophagy, and immune cell activation in acute and chronic kidney injuries. The use of several models of kidney injury is needed for development of agents that will prevent all aspects of cisplatin-induced kidney injury.10.1681/ASN.2020101455Fri, 28 May 2021 10:31:36 GMT-07:00Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and FibrosisThe effectiveness of cisplatin, a mainstay in the treatment of many solid organ cancers, is hindered by dose-limiting nephrotoxicity. Cisplatin causes AKI in 30% of patients. Patients who do not develop AKI by clinical standards during treatment are still at risk for long-term decline in kidney function and the development of CKD. The connection between AKI and CKD has become increasingly studied, with renal fibrosis a hallmark of CKD development. To prevent both the short- and long-term effects of cisplatin, researchers must use models that reflect both types of pathology. Although a lot is known about cisplatin-induced AKI, very little is known about the mechanisms by which repeated low levels of cisplatin lead to fibrosis development. In this review, strategies used in various rodent models to prevent kidney injury, its progression to fibrosis, or both, are examined to gain mechanistic insights and identify potential therapeutic targets for cisplatin-induced kidney pathologies. Reviewing the results from these models highlights the diverse and highly complex role of cell death, cell senescence, endoplasmic reticulum stress, autophagy, and immune cell activation in acute and chronic kidney injuries. The use of several models of kidney injury is needed for development of agents that will prevent all aspects of cisplatin-induced kidney injury.Sears, Sophia M.Siskind, Leah J.2021-05-28T10:31:36-07:00doi:10.1681/ASN.2020101455hwp:resource-id:jnephrol;32/7/1559American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, acute kidney injury, chronic kidney disease, fibrosisReviewsReviewsreview-article20212021-07-01July 202110.1681/ASN.20201014551046-66731533-34502021-05-28T10:31:36-07:002021-07Journal of the American Society of NephrologyReviews32715591567
- Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse Model10.1681/ASN.2020101458Fri, 23 Apr 2021 09:46:51 GMT-07:00Anti Human CX3CR1 VHH Molecule Attenuates Venous Neointimal Hyperplasia of Arteriovenous Fistula in Mouse ModelMisra, SanjayKilari, SreenivasuluYang, BinxiaSharma, AmitWu, Chih-ChengVazquez-Padron, Roberto I.Broadwater, John2021-04-23T09:46:51-07:00doi:10.1681/ASN.2020101458hwp:resource-id:jnephrol;32/7/1630American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, chemokine receptor, vascular accessBasic ResearchBasic Researchresearch-article20212021-07-01July 202110.1681/ASN.20201014581046-66731533-34502021-04-23T09:46:51-07:002021-07Journal of the American Society of NephrologyBasic Research32716301648
- The Impact of Medication Cost on Dialysis Patients10.34067/KID.0002162021Tue, 20 Apr 2021 07:28:38 GMT-07:00The Impact of Medication Cost on Dialysis PatientsGedney, Nieltje2021-04-20T07:28:38-07:00doi:10.34067/KID.0002162021hwp:resource-id:kidney360;2/6/922American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, CKD, dialysis, drug costs, ESKD, medication, patient, pharmacist, renal dialysisPatient PerspectivePatient Perspectiveresearch-article20212021-06-2410.34067/KID.00021620212641-76502021-04-20T07:28:38-07:002021-06-24Kidney360Patient Perspective26922923
- The Financial Burden of CKD: The Medication Edition10.34067/KID.0002192021Tue, 20 Apr 2021 07:28:38 GMT-07:00The Financial Burden of CKD: The Medication EditionGee, Patrick O.2021-04-20T07:28:38-07:00doi:10.34067/KID.0002192021hwp:resource-id:kidney360;2/6/920American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, cost, financial burden, medications, patient, prescription, basic sciencePatient perspectivePatient perspectiveresearch-article20212021-06-2410.34067/KID.00021920212641-76502021-04-20T07:28:38-07:002021-06-24Kidney360Patient perspective26920921
- Ulceration and Necrosis of Fingers and Toes in an ESKD Patient10.34067/KID.0000342021Thu, 24 Jun 2021 07:56:22 GMT-07:00Ulceration and Necrosis of Fingers and Toes in an ESKD PatientPiggott, Raymond SimonMellotte, GeorgeSexton, Donal J.2021-06-24T19:56:22-07:00doi:10.34067/KID.0000342021hwp:resource-id:kidney360;2/6/1074American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, calcific uremic arteriolopathy, CKD, dialysis, ESKD, fingers, mineral metabolism, necrosis, toes, ulcerationClinical images in nephrology and dialysisClinical images in nephrology and dialysisresearch-article20212021-06-2410.34067/KID.00003420212641-76502021-06-24T19:56:22-07:002021-06-24Kidney360Clinical images in nephrology and dialysis2610741075
- Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKD10.2215/CJN.18501120Wed, 28 Apr 2021 06:05:35 GMT-07:00Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKDWan, Eric Yuk FaiYu, Esther Yee TakChan, LindaMok, Anna Hoi YingWang, YuanChan, Esther Wai YinWong, Ian Chi KeiLam, Cindy Lo Kuen2021-04-28T06:05:35-07:00doi:10.2215/CJN.18501120hwp:resource-id:clinjasn;16/6/898American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, chronic kidney disease, anti-inflammatory agents, non-steroidal, NSAID, etoricoxib ibuprofenOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-06-01June 202110.2215/CJN.185011201555-90411555-905X2021-04-28T06:05:35-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles166898907
- Severe Acute Kidney Injury and Mortality in Extremely Low Gestational Age Neonates10.2215/CJN.18841220Fri, 11 Jun 2021 12:06:56 GMT-07:00Severe Acute Kidney Injury and Mortality in Extremely Low Gestational Age NeonatesHingorani, SangeetaSchmicker, Robert H.Brophy, Patrick D.Heagerty, Patrick J.Juul, Sandra E.Goldstein, Stuart L.Askenazi, David,2021-06-11T12:06:56-07:00doi:10.2215/CJN.18841220hwp:resource-id:clinjasn;16/6/862American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, pediatric nephrology, mortality, neonatal, gestational ageOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-06-01June 202110.2215/CJN.188412201555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666862839869839
- Vaccines and Disease Relapses in Children with Nephrotic Syndrome10.2215/CJN.01890221Fri, 11 Jun 2021 12:06:56 GMT-07:00Vaccines and Disease Relapses in Children with Nephrotic SyndromeAngeletti, AndreaBruschi, MaurizioBianchin, SilviaBonato, IreneMontobbio, CarolinaVerrina, EnricoLugani, FrancescaCravedi, PaoloGhiggeri, Gian Marco2021-06-11T12:06:56-07:00doi:10.2215/CJN.01890221hwp:resource-id:clinjasn;16/6/937American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyidiopathic nephrotic syndrome, vaccines, rituximab, COVID-19, pediatric nephrology, steroid dependent nephrotic syndrome, children, nephrotic syndromeResearch LettersResearch Lettersresearch-article20212021-06-01June 202110.2215/CJN.018902211555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyResearch Letters166937938
- Dialysis Facility Profit Status and Early Steps in Kidney Transplantation in the Southeastern United States10.2215/CJN.17691120Wed, 26 May 2021 02:21:46 GMT-07:00Dialysis Facility Profit Status and Early Steps in Kidney Transplantation in the Southeastern United StatesMcPherson, Laura J.Walker, Elizabeth R.Lee, Yi-Ting HanaGander, Jennifer C.Wang, ZhenshengReeves-Daniel, Amber M.Browne, TeriEllis, Matthew J.Rossi, Ana P.Pastan, Stephen O.Patzer, Rachel E.,,Adams, AngelaAdler, Joel ThomasAllison, CynthiaArnold, EmilyBaliga, PrabhakarBelmonte, KathleenBerlin, AlexanderBooth, EleanorBroughton, PaulBrowne, TeriCanavan, KelleyCaponi, SueCarter, RosalynCipriani, KatherynChikhliker, BlakelyClynes, DianaCoe, MarshiaCollins, BradleyCruz, AlexandreaDetwiler, RandyDuBay, DerekDubbs, JilDunn, DuaneEllis, MatthewEvans, DebraFarrell, JessicaFlemming, ShaunaFrance, NicoleFuller, EddieGander, Jennifer C.Gibney, EricGivens, JoVonnGodwin, NatalieGrace, TerryGraves, HannahGreen, GaryGulotta, JosephHayden, RobertHarding, JessicaHarrill, JenniferHeald, ChuckHill, MichelleHippen, BenHuml, AnneHumphry, RustyHymes, BenImundo, SandyArriola, Kimberly JacobJames, HeatherJohnson, DougJones, HeatherKahle, ErinKearns, LaurenKlemen, MarkKluge, LindaKnowles, LeahKozlowski, TomaszKrisher, JennaKutner, NancyLloyd, ScottLyman, LynnMalik, SanaMcCanna, LisaMcCorquodale, GriseldaMcKinney, CaraMcMath, SandyMcPherson, LauraMichaels, RitaMilfort, MargaretMohan, SumitMoore, LindaMorinelli, ThomasMoshiri, RebekahMuench, DoriMulloy, LauraMutell, RichNewsome, JessicaNiedfeldt, DanielleOliver, KathyPastan, StephenPatzer, RachelPaul, SudeshnaPerryman, JenniePilch, NicolePilgrim, JeaninePlantinga, LauraPorter, AliciaPriester, KarlaReeves-Daniel, AmberRetzloff, SamanthaRossi, AnaRudd, MartieSauls, LeighannScoggins, ToryScott, JohnSharp, JoeSimpkins, Carrie LynnStanton, DanielStone, CynthiaStone, MaureenStratta, BobTaber, DavidTaylor, RobertTeunis, LarissaThrasher, BrendaUrbanski, MeganVail, KimWaite, SueWang, ZhenshengWhite, KelleeWhite, KellyWhite, John JasonWhite, TyreeWiggins, ChristinaWilk, AdamWilliams, MyraWise, ElijahWoodard, AmyWright, ShannonZayas, CarlosZimmerman, Eddie2021-05-26T14:21:46-07:00doi:10.2215/CJN.17691120hwp:resource-id:clinjasn;16/6/926American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUnited States Renal Data System, transplantation, kidney transplantation, epidemiology and outcomes, end stage kidney disease, dialysisOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-06-01June 202110.2215/CJN.176911201555-90411555-905X2021-05-26T14:21:46-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666926846936847
- Post-Transplant CMV Glomerulitis10.2215/CJN.19061220Wed, 10 Feb 2021 08:08:30 GMT-08:00Post-Transplant CMV GlomerulitisAziz, FahadDjamali, Arjang2021-02-10T08:08:30-08:00doi:10.2215/CJN.19061220hwp:resource-id:clinjasn;16/6/957American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycytomegalovirus, nephritis, glomerulitis, presentation, treatmentKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireother20212021-06-01June 202110.2215/CJN.190612201555-90411555-905X2021-02-10T08:08:30-08:002021-06Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire166957959
- Inherited Kidney Complement DiseasesIn the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients’ outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopathies (complement factor H, complement component 3, complement factor H–related proteins) or only aHUS (complement factor B, complement factor I, and membrane cofactor protein). Key questions and challenges are highlighted, along with potential avenues for future directions.10.2215/CJN.11830720Wed, 03 Feb 2021 11:29:56 GMT-08:00Inherited Kidney Complement DiseasesIn the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients’ outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopathies (complement factor H, complement component 3, complement factor H–related proteins) or only aHUS (complement factor B, complement factor I, and membrane cofactor protein). Key questions and challenges are highlighted, along with potential avenues for future directions.Lemaire, MathieuNoone, DamienLapeyraque, Anne-LaureLicht, ChristophFrémeaux-Bacchi, Véronique2021-02-03T11:29:56-08:00doi:10.2215/CJN.11830720hwp:resource-id:clinjasn;16/6/942American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycomplement, glomerulopathy, hemolytic uremic syndrome, genetic renal disease, immune complexes, human genetics, membranoproliferative glomerulonephritis (MPGN)Genomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-06-01June 202110.2215/CJN.118307201555-90411555-905X2021-02-03T11:29:56-08:002021-06Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease166942956
- Depressive Symptoms and Rapid Kidney Function Decline10.2215/CJN.04050321Sat, 29 May 2021 11:28:20 GMT-07:00Depressive Symptoms and Rapid Kidney Function DeclineWu, Mary H.2021-05-29T11:28:20-07:00doi:10.2215/CJN.04050321hwp:resource-id:clinjasn;16/6/839American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepression, kidney function declinePatient VoicePatient Voiceeditorial20212021-06-01June 202110.2215/CJN.040503211555-90411555-905X2021-05-29T11:28:20-07:002021-06Clinical Journal of the American Society of NephrologyPatient Voice16666839889862839897869
- eGFR Testing around the World: Justice, Access, and Accuracy10.2215/CJN.16001020Thu, 07 Jan 2021 09:39:06 GMT-08:00eGFR Testing around the World: Justice, Access, and AccuracyJha, VivekanandModi, Gopesh K.2021-01-07T09:39:06-08:00doi:10.2215/CJN.16001020hwp:resource-id:clinjasn;16/6/963American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, equityPerspectivesPerspectivesresearch-article20212021-06-01June 202110.2215/CJN.160010201555-90411555-905X2021-01-07T09:39:06-08:002021-06Clinical Journal of the American Society of NephrologyPerspectives166963965
- The Influence of Medical School Debt on Career Choices in Nephrology10.2215/CJN.14260920Mon, 07 Dec 2020 08:29:59 GMT-08:00The Influence of Medical School Debt on Career Choices in NephrologyGinsberg, Charles2020-12-07T08:29:59-08:00doi:10.2215/CJN.14260920hwp:resource-id:clinjasn;16/6/960American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, student debt, salary, economic effect, medical schoolPerspectivesPerspectivesresearch-article20212021-06-01June 202110.2215/CJN.142609201555-90411555-905X2020-12-07T08:29:59-08:002021-06Clinical Journal of the American Society of NephrologyPerspectives166960962
- BLISS in the Treatment of Lupus Nephritis10.2215/CJN.17991120Wed, 03 Feb 2021 11:29:56 GMT-08:00BLISS in the Treatment of Lupus NephritisThurman, Joshua M.2021-02-03T11:29:56-08:00doi:10.2215/CJN.17991120hwp:resource-id:clinjasn;16/6/969American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, B cell, biologicPerspectivesPerspectivesresearch-article20212021-06-01June 202110.2215/CJN.179911201555-90411555-905X2021-02-03T11:29:56-08:002021-06Clinical Journal of the American Society of NephrologyPerspectives166969971
- Contextualizing the FHN Nocturnal Trial a Decade Later: How Nocturnal Home Hemodialysis Is Performed Matters to Outcomes10.2215/CJN.09160620Thu, 12 Nov 2020 10:50:00 GMT-08:00Contextualizing the FHN Nocturnal Trial a Decade Later: How Nocturnal Home Hemodialysis Is Performed Matters to OutcomesPauly, Robert P.Miller, Brent W.2020-11-12T10:50:00-08:00doi:10.2215/CJN.09160620hwp:resource-id:clinjasn;16/6/966American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydaily hemodialysis, Epidemiology and outcomes, chronic dialysisPerspectivesPerspectivesresearch-article20212021-06-01June 202110.2215/CJN.091606201555-90411555-905X2020-11-12T10:50:00-08:002021-06Clinical Journal of the American Society of NephrologyPerspectives166966968
- Smoking Cessation and Coronary Artery Calcification in CKD10.2215/CJN.15751020Tue, 20 Apr 2021 11:01:50 GMT-07:00Smoking Cessation and Coronary Artery Calcification in CKDLee, Mi JungPark, Jung TakChang, Tae IkJoo, Young SuYoo, Tae-HyunPark, Sue KyungChung, WookyungKim, Yong-SooKim, Soo WanOh, Kook-HwanKang, Shin-WookChoi, Kyu HunAhn, CurieHan, Seung Hyeok2021-04-20T11:01:50-07:00doi:10.2215/CJN.15751020hwp:resource-id:clinjasn;16/6/870American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, coronary calcification, coronary artery disease, smoking cessation, smokingOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-06-01June 202110.2215/CJN.157510201555-90411555-905X2021-04-20T11:01:50-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles166870879
- Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney Failure10.2215/CJN.04460421Fri, 11 Jun 2021 12:06:56 GMT-07:00Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney FailureSoomro, Qandeel H.Charytan, David M.2021-06-11T12:06:56-07:00doi:10.2215/CJN.04460421hwp:resource-id:clinjasn;16/6/843American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, hemodialysis, mineralocorticoid receptor antagonists, kidney failure, heart failureEditorialsEditorialseditorial20212021-06-01June 202110.2215/CJN.044604211555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyEditorials1666843916845925
- Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney Function10.2215/CJN.18441120Sat, 29 May 2021 11:11:56 GMT-07:00Association of Depressive Symptoms with Rapid Kidney Function Decline in Adults with Normal Kidney FunctionZhang, ZhuxianHe, PanpanLiu, MengyiZhou, ChunLiu, ChengzhangLi, HuanZhang, YuanyuanLi, QinqinYe, ZiliangWu, QimengWang, GuobaoLiang, MinQin, Xianhui2021-05-29T11:11:56-07:00doi:10.2215/CJN.18441120hwp:resource-id:clinjasn;16/6/889American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepressive symptom, depression, kidney function decline, chronic kidney disease, CHARLSOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-06-01June 202110.2215/CJN.184411201555-90411555-905X2021-05-29T11:11:56-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666889839897839
- Why Is the GFR So High?: Implications for the Treatment of Kidney FailureThe high GFR in vertebrates obligates large energy expenditure. Homer Smith’s teleologic argument that this high GFR was needed to excrete water as vertebrates evolved in dilute seas is outdated. The GFR is proportional to the metabolic rate among vertebrate species and higher in warm-blooded mammals and birds than in cold-blooded fish, amphibians, and reptiles. The kidney clearance of some solutes is raised above the GFR by tubular secretion, and we presume secretion evolved to eliminate particularly toxic compounds. In this regard, high GFRs may provide a fluid stream into which toxic solutes can be readily secreted. Alternatively, the high GFR may be required to clear solutes that are too large or too varied to be secreted, especially bioactive small proteins and peptides. These considerations have potentially important implications for the understanding and treatment of kidney failure.10.2215/CJN.14300920Thu, 10 Dec 2020 07:26:23 GMT-08:00Why Is the GFR So High?: Implications for the Treatment of Kidney FailureThe high GFR in vertebrates obligates large energy expenditure. Homer Smith’s teleologic argument that this high GFR was needed to excrete water as vertebrates evolved in dilute seas is outdated. The GFR is proportional to the metabolic rate among vertebrate species and higher in warm-blooded mammals and birds than in cold-blooded fish, amphibians, and reptiles. The kidney clearance of some solutes is raised above the GFR by tubular secretion, and we presume secretion evolved to eliminate particularly toxic compounds. In this regard, high GFRs may provide a fluid stream into which toxic solutes can be readily secreted. Alternatively, the high GFR may be required to clear solutes that are too large or too varied to be secreted, especially bioactive small proteins and peptides. These considerations have potentially important implications for the understanding and treatment of kidney failure.Meyer, Timothy W.Hostetter, Thomas H.2020-12-10T07:26:23-08:00doi:10.2215/CJN.14300920hwp:resource-id:clinjasn;16/6/980American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular filtration rate, hemodialysis, uremiaReviewsReviewsreview-article20212021-06-01June 202110.2215/CJN.143009201555-90411555-905X2020-12-10T07:26:23-08:002021-06Clinical Journal of the American Society of NephrologyReviews166980987
- Sincere Integration of Patients’ Perspectives into Kidney Care: Affirming and Adopting Patient Activation10.2215/CJN.05050421Fri, 11 Jun 2021 12:06:56 GMT-07:00Sincere Integration of Patients’ Perspectives into Kidney Care: Affirming and Adopting Patient ActivationNair, DevikaCavanaugh, Kerri L.2021-06-11T12:06:56-07:00doi:10.2215/CJN.05050421hwp:resource-id:clinjasn;16/6/840American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, patient perspectiveEditorialsEditorialseditorial20212021-06-01June 202110.2215/CJN.050504211555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyEditorials1666840880842888
- Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-Analysis10.2215/CJN.15841020Fri, 11 Jun 2021 12:06:56 GMT-07:00Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-AnalysisChen, Kuan-TingKang, Yi-NoLin, Yen-ChungTsai, I-LinChang, Wei-ChiaoFang, Te-ChaoWu, Mai-SzuKao, Chih-Chin2021-06-11T12:06:56-07:00doi:10.2215/CJN.15841020hwp:resource-id:clinjasn;16/6/916American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic dialysis, chronic renal failure, electrolytes, end-stage renal disease, heart disease, peritoneal dialysis, renin angiotensin system, hemodialysis, mineralocorticoid receptor antagonistsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-06-01June 202110.2215/CJN.158410201555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666916843925845
- Reliability and Validity of the Patient Activation Measure in Kidney Disease: Results of Rasch Analysis10.2215/CJN.19611220Fri, 11 Jun 2021 12:06:56 GMT-07:00Reliability and Validity of the Patient Activation Measure in Kidney Disease: Results of Rasch AnalysisLightfoot, Courtney J.Wilkinson, Thomas J.Memory, Katherine E.Palmer, JaredSmith, Alice C.2021-06-11T12:06:56-07:00doi:10.2215/CJN.19611220hwp:resource-id:clinjasn;16/6/880American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypsychometric properties, validation, Rasch measurement model, patient activation, PAM, kidney diseaseOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-06-01June 202110.2215/CJN.196112201555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666880840888842
- Overweight and Obesity and Progression of ADPKD10.2215/CJN.16871020Fri, 11 Jun 2021 12:06:56 GMT-07:00Overweight and Obesity and Progression of ADPKDNowak, Kristen L.Steele, CortneyGitomer, BereniceWang, WenchyiOuyang, JohnChonchol, Michel B.2021-06-11T12:06:56-07:00doi:10.2215/CJN.16871020hwp:resource-id:clinjasn;16/6/908American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, epidemiology and outcomes, obesity, polycystic kidney disease, overweight, disease progressionOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20212021-06-01June 202110.2215/CJN.168710201555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666908850915852
- Dialyzing Acute Kidney Injury Patients after Hospital Discharge10.2215/CJN.04590421Fri, 11 Jun 2021 12:06:56 GMT-07:00Dialyzing Acute Kidney Injury Patients after Hospital DischargeMcCoy, IanHsu, Chi-yuan2021-06-11T12:06:56-07:00doi:10.2215/CJN.04590421hwp:resource-id:clinjasn;16/6/848American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, patient discharge, dialysis, chronic dialysisEditorialsEditorialseditorial20212021-06-01June 202110.2215/CJN.045904211555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyEditorials1666848853849861
- Acute Kidney Injury Requiring Dialysis and Incident Dialysis Patient Outcomes in US Outpatient Dialysis Facilities10.2215/CJN.18311120Thu, 27 May 2021 09:25:51 GMT-07:00Acute Kidney Injury Requiring Dialysis and Incident Dialysis Patient Outcomes in US Outpatient Dialysis FacilitiesDahlerus, ClaudiaSegal, Jonathan H.He, KevinWu, WenboChen, ShuShearon, Tempie H.Sun, YatingPearson, AaronLi, XiangMessana, Joseph M.2021-05-27T09:25:51-07:00doi:10.2215/CJN.18311120hwp:resource-id:clinjasn;16/6/853American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, dialysis, ESRD, mortality risk, outcomesOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-06-01June 202110.2215/CJN.183111201555-90411555-905X2021-05-27T09:25:51-07:002021-06Clinical Journal of the American Society of NephrologyOriginal Articles1666853848861849
- To Add Weight to Overweight10.2215/CJN.04150321Fri, 11 Jun 2021 12:06:56 GMT-07:00To Add Weight to Overweightvan Gastel, Maatje D.A.Meijer, Esther2021-06-11T12:06:56-07:00doi:10.2215/CJN.04150321hwp:resource-id:clinjasn;16/6/850American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybody mass index, ADPKD, overweight, autosomal dominant polycystic kidney diseaseEditorialsEditorialseditorial20212021-06-01June 202110.2215/CJN.041503211555-90411555-905X2021-06-11T12:06:56-07:002021-06Clinical Journal of the American Society of NephrologyEditorials1666850908852915
- Limited Significance of Antifactor H Antibodies in Patients with Membranous Nephropathy10.2215/CJN.16631020Thu, 15 Apr 2021 06:45:49 GMT-07:00Limited Significance of Antifactor H Antibodies in Patients with Membranous NephropathySethi, AmitMiao, JingWillrich, Maria Alice V.Frinack, Jody L.Cattran, Daniel C.Fervenza, Fernando C.,,Fervenza, Fernando C.Appel, Gerald B.Barbour, Sean J.Rovin, Brad H.Lafayette, Richard A.Aslam, NabeelJefferson, Jonathan A.Gipson, Patrick E.Rizk, Dana V.Sedor, John R.Simon, James F.McCarthy, Ellen T.Brenchley, PaulSethi, SanjeevAvila-Casado, CarmenBeanlands, HeatherLieske, John C.Philibert, DavidLi, TingtingThomas, Lesley F.Green, Dolly F.Juncos, Luis A.Beara-Lasic, LadaBlumenthal, Samuel S.Sussman, Amy N.Erickson, Stephen B.Hladunewich, MichelleCanetta, Pietro A.Hebert, Lee A.Leung, NelsonRadhakrishnan, JayReich, Heather N.Parikh, Samir V.Gipson, Debbie S.Cattran, Daniel C.2021-04-15T06:45:49-07:00doi:10.2215/CJN.16631020hwp:resource-id:clinjasn;16/6/939American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, PLA2R complement, factor H, antibodiesResearch LettersResearch Lettersletter20212021-06-01June 202110.2215/CJN.166310201555-90411555-905X2021-04-15T06:45:49-07:002021-06Clinical Journal of the American Society of NephrologyResearch Letters166939941
- NephroTalk Multimodal Conservative Care Curriculum for Nephrology FellowsConservative care, a comprehensive treatment path for advanced kidney disease most suitable for individuals unlikely to benefit from dialysis, is underutilized in the United States. One reason is an absence of robust education about this approach and how to discuss it with potential candidates. To address this need, we developed a multimodal conservative care curriculum for nephrology fellows. This curriculum consists of four online modules that address essential concepts and communication skills related to conservative care. It is followed by an in-person, interactive, “flipped classroom” session facilitated by designated nephrology educators at participating Accreditation Council for Graduate Medical Education nephrology training programs. Curriculum effect was assessed using surveys completed by participating fellows immediately before and following the curriculum and for participating nephrology educators following flipped classroom teaching; 148 nephrology trainees from 19 programs participated, with 108 completing both pre- and postcurriculum surveys. Mean self-reported preparedness (measured on a five-point Likert scale) increased significantly for all ten concepts taught in the curriculum. The mean correct score on eight knowledge questions increased from 69% to 82% following the curriculum (P<0.001). Fellows rated the curriculum highly and reported that they plan to practice skills learned. For the 19 nephrology program educators, the mean perceived preparedness to teach all curriculum domains increased after, compared with before, facilitating the flipped classroom, reaching significance for seven of the ten concepts measured. Data suggest that fellows' participation in a multimodal curriculum increased knowledge and preparation for fundamental conservative care concepts and communication skills. Fellows rated the curriculum highly. Educator participation appears to have increased preparedness for teaching the curriculum concepts, making it likely that future education in conservative care will become more widespread. Herein, we describe the curriculum content, which we have made publicly available in order to encourage broader implementation, and its effect on participating fellows and the nephrology educators who facilitated it.10.2215/CJN.11770720Fri, 12 Feb 2021 06:48:38 GMT-08:00NephroTalk Multimodal Conservative Care Curriculum for Nephrology FellowsConservative care, a comprehensive treatment path for advanced kidney disease most suitable for individuals unlikely to benefit from dialysis, is underutilized in the United States. One reason is an absence of robust education about this approach and how to discuss it with potential candidates. To address this need, we developed a multimodal conservative care curriculum for nephrology fellows. This curriculum consists of four online modules that address essential concepts and communication skills related to conservative care. It is followed by an in-person, interactive, “flipped classroom” session facilitated by designated nephrology educators at participating Accreditation Council for Graduate Medical Education nephrology training programs. Curriculum effect was assessed using surveys completed by participating fellows immediately before and following the curriculum and for participating nephrology educators following flipped classroom teaching; 148 nephrology trainees from 19 programs participated, with 108 completing both pre- and postcurriculum surveys. Mean self-reported preparedness (measured on a five-point Likert scale) increased significantly for all ten concepts taught in the curriculum. The mean correct score on eight knowledge questions increased from 69% to 82% following the curriculum (P<0.001). Fellows rated the curriculum highly and reported that they plan to practice skills learned. For the 19 nephrology program educators, the mean perceived preparedness to teach all curriculum domains increased after, compared with before, facilitating the flipped classroom, reaching significance for seven of the ten concepts measured. Data suggest that fellows' participation in a multimodal curriculum increased knowledge and preparation for fundamental conservative care concepts and communication skills. Fellows rated the curriculum highly. Educator participation appears to have increased preparedness for teaching the curriculum concepts, making it likely that future education in conservative care will become more widespread. Herein, we describe the curriculum content, which we have made publicly available in order to encourage broader implementation, and its effect on participating fellows and the nephrology educators who facilitated it.Cohen, Robert A.Bursic, AlexandraChan, EmilyNorman, Marie K.Arnold, Robert M.Schell, Jane O.2021-02-12T06:48:38-08:00doi:10.2215/CJN.11770720hwp:resource-id:clinjasn;16/6/972American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyconservative care, communication skills, goals of care, online curriculum, flipped classroom, nephrologyFeaturesFeaturesresearch-article20212021-06-01June 202110.2215/CJN.117707201555-90411555-905X2021-02-12T06:48:38-08:002021-06Clinical Journal of the American Society of NephrologyFeatures166972979
- Dialysis and Transplant Access: Kidney Capitalism at a Crossroads?10.2215/CJN.04680421Wed, 26 May 2021 02:53:21 GMT-07:00Dialysis and Transplant Access: Kidney Capitalism at a Crossroads?Raghavan, DivyaHall, Isaac E.2021-05-26T14:53:21-07:00doi:10.2215/CJN.04680421hwp:resource-id:clinjasn;16/6/846American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, kidney transplantation, transplant outcomesEditorialsEditorialseditorial20212021-06-01June 202110.2215/CJN.046804211555-90411555-905X2021-05-26T14:53:21-07:002021-06Clinical Journal of the American Society of NephrologyEditorials1666846926847936
- Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task ForceFor almost two decades, equations that use serum creatinine, age, sex, and race to eGFR have included “race” as Black or non-Black. Given considerable evidence of disparities in health and healthcare delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase one, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made.10.1681/ASN.2021010039Fri, 09 Apr 2021 01:00:12 GMT-07:00Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task ForceFor almost two decades, equations that use serum creatinine, age, sex, and race to eGFR have included “race” as Black or non-Black. Given considerable evidence of disparities in health and healthcare delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase one, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made.Delgado, CynthiaBaweja, MuktaBurrows, Nilka RíosCrews, Deidra C.Eneanya, Nwamaka D.Gadegbeku, Crystal A.Inker, Lesley A.Mendu, Mallika L.Miller, W. GregMoxey-Mims, Marva M.Roberts, Glenda V.St. Peter, Wendy L.Warfield, CurtisPowe, Neil R.2021-04-09T01:00:12-07:00doi:10.1681/ASN.2021010039hwp:resource-id:jnephrol;32/6/1305American Society of NephrologyCopyright © 2021 by the American Society of Nephrology and the National Kidney Foundation, Inc. All rights reserved.Journal of the American Society of Nephrologyestimated glomerular filtration rate, kidney function, health equity, health disparities, raceSpecial ArticleSpecial Articleresearch-article20212021-06-01June 202110.1681/ASN.20210100391046-66731533-34502021-04-09T01:00:12-07:002021-06Journal of the American Society of NephrologySpecial Article32661305126913171270
- Advance Care Planning in Older Adults with CKD: Patient, Care Partner, and Clinician Perspectives10.1681/ASN.2020091298Wed, 07 Apr 2021 10:27:29 GMT-07:00Advance Care Planning in Older Adults with CKD: Patient, Care Partner, and Clinician PerspectivesLadin, KerenNeckermann, IsabelD’Arcangelo, NoahKoch-Weser, SusanWong, John B.Gordon, Elisa J.Rossi, AnaRifkin, DenaIsakova, TamaraWeiner, Daniel E.2021-04-07T10:27:29-07:00doi:10.1681/ASN.2020091298hwp:resource-id:jnephrol;32/6/1527American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, patient centered, advance care planning, advance directives, qualitative, disparities, chronic kidney failure, ethnic minority, quality of lifeClinical ResearchClinical Researchresearch-article20212021-06-01June 202110.1681/ASN.20200912981046-66731533-34502021-04-07T10:27:29-07:002021-06Journal of the American Society of NephrologyClinical Research3266615271273i15351274i
- Race and the Estimation of GFR: Getting it Right10.1681/ASN.2021020206Fri, 09 Apr 2021 01:00:12 GMT-07:00Race and the Estimation of GFR: Getting it RightFeldman, Harold I.Briggs, Josephine P.2021-04-09T01:00:12-07:00doi:10.1681/ASN.2021020206hwp:resource-id:jnephrol;32/6/1269American Society of NephrologyCopyright © 2021 by the American Society of Nephrology and the National Kidney Foundation, Inc. All rights reserved.Journal of the American Society of NephrologyGFR, race-based medicine, racial disparities, task forceEditorialsEditorialseditorial20212021-06-01June 202110.1681/ASN.20210202061046-66731533-34502021-04-09T01:00:12-07:002021-06Journal of the American Society of NephrologyEditorials32661269130512701317
- Medicaid Expansion and Incidence of Kidney Failure among Nonelderly Adults10.1681/ASN.2020101511Thu, 01 Apr 2021 09:56:38 GMT-07:00Medicaid Expansion and Incidence of Kidney Failure among Nonelderly AdultsThorsness, RebeccaSwaminathan, ShailenderLee, YoojinSommers, Benjamin D.Mehrotra, RajnishNguyen, Kevin H.Kim, DaehoRivera-Hernandez, MaricruzTrivedi, Amal N.2021-04-01T09:56:38-07:00doi:10.1681/ASN.2020101511hwp:resource-id:jnephrol;32/6/1425American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, kidney failure, health insurance, Medicaid, uninsured, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20212021-06-01June 202110.1681/ASN.20201015111046-66731533-34502021-04-01T09:56:38-07:002021-06Journal of the American Society of NephrologyClinical Epidemiology32614251435
- Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness10.1681/ASN.2020111587Fri, 02 Apr 2021 09:16:23 GMT-07:00Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural DeafnessSchlingmann, Karl P.Renigunta, AparnaHoorn, Ewout J.Forst, Anna-LenaRenigunta, VijayAtanasov, VelkoMahendran, SinthuraBarakat, Tahsin StefanGillion, ValentineGodefroid, NathalieBrooks, Alice S.Lugtenberg, DorienLake, JenniferDebaix, HuguetteRudin, ChristophKnebelmann, BertrandTellier, StephanieRousset-Rouvière, CarolineViering, Daande Baaij, Jeroen H. F.Weber, StefaniePalygin, OlegStaruschenko, AlexanderKleta, RobertHouillier, PascalBockenhauer, DetlefDevuyst, OlivierVargas-Poussou, RosaWarth, RichardZdebik, Anselm A.Konrad, Martin2021-04-02T09:16:23-07:00doi:10.1681/ASN.2020111587hwp:resource-id:jnephrol;32/6/1498American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypotassium channels, proximal tubule, distal tubule, tubulopathy, KCNJ16, KCNJ10, KCNJ15, deafness, acid-base homeostasis, hypokalemiaClinical ResearchClinical Researchresearch-article20212021-06-01June 202110.1681/ASN.20201115871046-66731533-34502021-04-02T09:16:23-07:002021-06Journal of the American Society of NephrologyClinical Research32614981512
- Initial Effects of COVID-19 on Patients with ESKD10.1681/ASN.2021010009Thu, 08 Apr 2021 07:35:09 GMT-07:00Initial Effects of COVID-19 on Patients with ESKDWeinhandl, Eric D.Wetmore, James B.Peng, YiLiu, JiannongGilbertson, David T.Johansen, Kirsten L.2021-04-08T07:35:09-07:00doi:10.1681/ASN.2021010009hwp:resource-id:jnephrol;32/6/1444American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, dialysis, hospitalization, mortality, transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20212021-06-01June 202110.1681/ASN.20210100091046-66731533-34502021-04-08T07:35:09-07:002021-06Journal of the American Society of NephrologyClinical Epidemiology32661444i1453i
- Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus10.1681/ASN.2020010031Tue, 16 Mar 2021 07:22:13 GMT-07:00Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes InsipidusPetrillo, FedericaIervolino, AnnaAngrisano, TizianaJelen, SabinaCostanzo, VincenzoD’Acierno, MariavittoriaCheng, LeiWu, QiGuerriero, IlariaMazzarella, Maria CristinaDe Falco, AlfonsoD’Angelo, FulvioCeccarelli, MicheleCaraglia, MicheleCapasso, GiovambattistaFenton, Robert A.Trepiccione, Francesco2021-03-16T07:22:13-07:00doi:10.1681/ASN.2020010031hwp:resource-id:jnephrol;32/6/1339American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyAQP2, Dicer, miRNA, ENaC, DNA methylation, epigeneticsBasic ResearchBasic Researchresearch-article20212021-06-01June 202110.1681/ASN.20200100311046-66731533-34502021-03-16T07:22:13-07:002021-06Journal of the American Society of NephrologyBasic Research32613391354
- Could NAD+ Precursor Supplements Induce a Legacy of Protection against Diabetic Nephropathy?10.1681/ASN.2021020275Wed, 14 Apr 2021 08:35:30 GMT-07:00Could NAD+ Precursor Supplements Induce a Legacy of Protection against Diabetic Nephropathy?Hyndman, Kelly A.Griffin, Matthew D.2021-04-14T08:35:30-07:00doi:10.1681/ASN.2021020275hwp:resource-id:jnephrol;32/6/1270American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyepigenetics, diabetic nephropathy, sirtuin, NAD metabolismEditorialsEditorialseditorial20212021-06-01June 202110.1681/ASN.20210202751046-66731533-34502021-04-14T08:35:30-07:002021-06Journal of the American Society of NephrologyEditorials3266612701355i12731370i
- Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy10.1681/ASN.2020081188Thu, 01 Apr 2021 09:56:37 GMT-07:00Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic NephropathyYasuda, ItaruHasegawa, KazuhiroSakamaki, YusukeMuraoka, HirokazuKawaguchi, TakahisaKusahana, EiOno, TakashiKanda, TakeshiTokuyama, HirobumiWakino, ShuItoh, Hiroshi2021-04-01T09:56:37-07:00doi:10.1681/ASN.2020081188hwp:resource-id:jnephrol;32/6/1355American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathyBasic ResearchBasic Researchresearch-article20212021-06-01June 202110.1681/ASN.20200811881046-66731533-34502021-04-01T09:56:37-07:002021-06Journal of the American Society of NephrologyBasic Research326610135512702683137012732683
- How to Get Started with Single Cell RNA Sequencing Data AnalysisOver the last 5 years, single cell methods have enabled the monitoring of gene and protein expression, genetic, and epigenetic changes in thousands of individual cells in a single experiment. With the improved measurement and the decreasing cost of the reactions and sequencing, the size of these datasets is increasing rapidly. The critical bottleneck remains the analysis of the wealth of information generated by single cell experiments. In this review, we give a simplified overview of the analysis pipelines, as they are typically used in the field today. We aim to enable researchers starting out in single cell analysis to gain an overview of challenges and the most commonly used analytical tools. In addition, we hope to empower others to gain an understanding of how typical readouts from single cell datasets are presented in the published literature.10.1681/ASN.2020121742Mon, 15 Mar 2021 11:23:41 GMT-07:00How to Get Started with Single Cell RNA Sequencing Data AnalysisOver the last 5 years, single cell methods have enabled the monitoring of gene and protein expression, genetic, and epigenetic changes in thousands of individual cells in a single experiment. With the improved measurement and the decreasing cost of the reactions and sequencing, the size of these datasets is increasing rapidly. The critical bottleneck remains the analysis of the wealth of information generated by single cell experiments. In this review, we give a simplified overview of the analysis pipelines, as they are typically used in the field today. We aim to enable researchers starting out in single cell analysis to gain an overview of challenges and the most commonly used analytical tools. In addition, we hope to empower others to gain an understanding of how typical readouts from single cell datasets are presented in the published literature.Balzer, Michael S.Ma, ZiyuanZhou, JianfuAbedini, AminSusztak, Katalin2021-03-15T11:23:41-07:00doi:10.1681/ASN.2020121742hwp:resource-id:jnephrol;32/6/1279American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysingle cell RNA-sequencing, transcriptomics, kidney, analysisReviewsReviewsreview-article20212021-06-01June 202110.1681/ASN.20201217421046-66731533-34502021-03-15T11:23:41-07:002021-06Journal of the American Society of NephrologyReviews32612791292
- An Introduction to Qualitative Inquiry10.1681/ASN.2021040473Wed, 26 May 2021 02:56:33 GMT-07:00An Introduction to Qualitative InquiryButler, Catherine R.O’Hare, Ann M.Kestenbaum, Bryan R.Sayre, George G.Wong, Susan P.Y.2021-05-26T14:56:33-07:00doi:10.1681/ASN.2021040473hwp:resource-id:jnephrol;32/6/1275American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyqualitative methodsPerspectivesPerspectivesresearch-article20212021-06-01June 202110.1681/ASN.20210404731046-66731533-34502021-05-26T14:56:33-07:002021-06Journal of the American Society of NephrologyPerspectives32612751278
- Black Race Coefficient in GFR Estimation and Diabetes Medications in CKD: National Estimates10.1681/ASN.2020121724Thu, 08 Apr 2021 08:00:09 GMT-07:00Black Race Coefficient in GFR Estimation and Diabetes Medications in CKD: National EstimatesWalther, Carl P.Winkelmayer, Wolfgang C.Navaneethan, Sankar D.2021-04-08T08:00:09-07:00doi:10.1681/ASN.2020121724hwp:resource-id:jnephrol;32/6/1319American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrace, eGFR, diabetes, CKD, NHANES, SGLT2i, GLP1-RA, metforminResearch LettersResearch Lettersletter20212021-06-01June 202110.1681/ASN.20201217241046-66731533-34502021-04-08T08:00:09-07:002021-06Journal of the American Society of NephrologyResearch Letters32613191321
- Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature Podocytes10.1681/ASN.2020081177Fri, 26 Mar 2021 06:14:51 GMT-07:00Super-Enhancer-Associated Transcription Factors Maintain Transcriptional Regulation in Mature PodocytesYang, JingpingZhang, DifeiMotojima, MasaruKume, TsutomuHou, QingPan, YuDuan, AipingZhang, MingchaoJiang, SongHou, JinhuaShi, JingsongQin, ZhaohuiLiu, Zhihong2021-03-26T06:14:51-07:00doi:10.1681/ASN.2020081177hwp:resource-id:jnephrol;32/6/1323American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysuper enhancer, glomeruli, FOXC, transcriptional regulation, podocytopathyBasic ResearchBasic Researchresearch-article20212021-06-01June 202110.1681/ASN.20200811771046-66731533-34502021-03-26T06:14:51-07:002021-06Journal of the American Society of NephrologyBasic Research32613231337
- Advance Care Planning in Kidney Disease: A Tale of Two Conversations10.1681/ASN.2021040476Wed, 26 May 2021 02:56:33 GMT-07:00Advance Care Planning in Kidney Disease: A Tale of Two ConversationsSchell, Jane O.2021-05-26T14:56:33-07:00doi:10.1681/ASN.2021040476hwp:resource-id:jnephrol;32/6/1273American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyadvance care planning, patient-centered care, patient prioritiesEditorialsEditorialsresearch-article20212021-06-01June 202110.1681/ASN.20210404761046-66731533-34502021-05-26T14:56:33-07:002021-06Journal of the American Society of NephrologyEditorials32661273152712741535
- Low Health Literacy is Associated with the Onset of CKD during the Life Course10.1681/ASN.2020081155Thu, 25 Mar 2021 09:05:32 GMT-07:00Low Health Literacy is Associated with the Onset of CKD during the Life CourseGurgel do Amaral, Matheus S.Reijneveld, Sijmen A.Geboers, BasNavis, Gerjan J.Winter, Andrea F de2021-03-25T09:05:32-07:00doi:10.1681/ASN.2020081155hwp:resource-id:jnephrol;32/6/1436American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhealth literacy, chronic kidney disease, prevention, cohort, BMIClinical EpidemiologyClinical Epidemiologyresearch-article20212021-06-01June 202110.1681/ASN.20200811551046-66731533-34502021-03-25T09:05:32-07:002021-06Journal of the American Society of NephrologyClinical Epidemiology32614361443
- On the Increased Event Rate of Urinary Tract Infection and Pneumonia in CKD Patients Treated with Roxadustat for Anemia10.1681/ASN.2021020204Tue, 13 Apr 2021 08:18:31 GMT-07:00On the Increased Event Rate of Urinary Tract Infection and Pneumonia in CKD Patients Treated with Roxadustat for AnemiaEleftheriadis, TheodorosPissas, GeorgiosLiakopoulos, VassiliosStefanidis, Ioannis2021-04-13T08:18:31-07:00doi:10.1681/ASN.2021020204hwp:resource-id:jnephrol;32/6/1537American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyroxadustat anemia, infection, T cell, immune responseLetters to the EditorLetters to the Editorletter20212021-06-01June 202110.1681/ASN.20210202041046-66731533-34502021-04-13T08:18:31-07:002021-06Journal of the American Society of NephrologyLetters to the Editor326631537153773715371538755
- Tubuloglomerular Feedback Synchronization in Nephrovascular NetworksTo perform their functions, the kidneys maintain stable blood perfusion in the face of fluctuations in systemic BP. This is done through autoregulation of blood flow by the generic myogenic response and the kidney-specific tubuloglomerular feedback (TGF) mechanism. The central theme of this paper is that, to achieve autoregulation, nephrons do not work as single units to manage their individual blood flows, but rather communicate electrically over long distances to other nephrons via the vascular tree. Accordingly, we define the nephrovascular unit (NVU) to be a structure consisting of the nephron, glomerulus, afferent arteriole, and efferent arteriole. We discuss features that require and enable distributed autoregulation mediated by TGF across the kidney. These features include the highly variable topology of the renal vasculature which creates variability in circulation and the potential for mismatch between tubular oxygen demand and delivery; the self-sustained oscillations in each NVU arising from the autoregulatory mechanisms; and the presence of extensive gap junctions formed by connexins and their properties that enable long-distance transmission of TGF signals. The existence of TGF synchronization across the renal microvascular network enables an understanding of how NVUs optimize oxygenation-perfusion matching while preventing transmission of high systemic pressure to the glomeruli, which could lead to progressive glomerular and vascular injury.10.1681/ASN.2020040423Thu, 08 Apr 2021 08:00:10 GMT-07:00Tubuloglomerular Feedback Synchronization in Nephrovascular NetworksTo perform their functions, the kidneys maintain stable blood perfusion in the face of fluctuations in systemic BP. This is done through autoregulation of blood flow by the generic myogenic response and the kidney-specific tubuloglomerular feedback (TGF) mechanism. The central theme of this paper is that, to achieve autoregulation, nephrons do not work as single units to manage their individual blood flows, but rather communicate electrically over long distances to other nephrons via the vascular tree. Accordingly, we define the nephrovascular unit (NVU) to be a structure consisting of the nephron, glomerulus, afferent arteriole, and efferent arteriole. We discuss features that require and enable distributed autoregulation mediated by TGF across the kidney. These features include the highly variable topology of the renal vasculature which creates variability in circulation and the potential for mismatch between tubular oxygen demand and delivery; the self-sustained oscillations in each NVU arising from the autoregulatory mechanisms; and the presence of extensive gap junctions formed by connexins and their properties that enable long-distance transmission of TGF signals. The existence of TGF synchronization across the renal microvascular network enables an understanding of how NVUs optimize oxygenation-perfusion matching while preventing transmission of high systemic pressure to the glomeruli, which could lead to progressive glomerular and vascular injury.Zehra, TayyabaCupples, William A.Braam, Branko2021-04-08T08:00:10-07:00doi:10.1681/ASN.2020040423hwp:resource-id:jnephrol;32/6/1293American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal autoregulation, tubuloglomerular feedback, chronic kidney disease, synchronization, oxygenation-perfusion, nephronReviewsReviewsreview-article20212021-06-01June 202110.1681/ASN.20200404231046-66731533-34502021-04-08T08:00:10-07:002021-06Journal of the American Society of NephrologyReviews32612931304
- Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization Study10.1681/ASN.2020071086Tue, 30 Mar 2021 07:30:31 GMT-07:00Causal Effects of Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism on Kidney Function: A Mendelian Randomization StudyPark, SehoonLee, SoojinKim, YaerimLee, YeonheeKang, Min WooKim, KwangsooKim, Yong ChulHan, Seung SeokLee, HajeongLee, Jung PyoJoo, Kwon WookLim, Chun SooKim, Yon SuKim, Dong Ki2021-03-30T07:30:31-07:00doi:10.1681/ASN.2020071086hwp:resource-id:jnephrol;32/6/1484American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologywellbeing, psychological, depression, chronic kidney disease, Mendelian randomizationClinical ResearchClinical Researchresearch-article20212021-06-01June 202110.1681/ASN.20200710861046-66731533-34502021-03-30T07:30:31-07:002021-06Journal of the American Society of NephrologyClinical Research32614841496
- Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled Trial10.1681/ASN.2020111566Mon, 22 Mar 2021 08:16:39 GMT-07:00Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: A Multicenter Randomized Controlled TrialDe Vriese, An S.Caluwé, RogierVan Der Meersch, HansDe Boeck, KoenDe Bacquer, Dirk2021-03-22T08:16:39-07:00doi:10.1681/ASN.2020111566hwp:resource-id:jnephrol;32/6/1474American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, hemodialysis, randomized controlled trialsClinical ResearchClinical Researchresearch-article20212021-06-01June 202110.1681/ASN.20201115661046-66731533-34502021-03-22T08:16:39-07:002021-06Journal of the American Society of NephrologyClinical Research32699147423892390148323902391
- Addendum: Passage of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act—a Chance to Celebrate and Reflect10.1681/ASN.2021030427Fri, 28 May 2021 11:00:33 GMT-07:00Addendum: Passage of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act—a Chance to Celebrate and ReflectAmerican Society of Nephrology2021-05-28T11:00:33-07:00doi:10.1681/ASN.2021030427hwp:resource-id:jnephrol;32/6/1540American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyAddendumAddendumaddendum20212021-06-01June 202110.1681/ASN.20210304271046-66731533-34502021-05-28T11:00:33-07:002021-06Journal of the American Society of NephrologyAddendum326415407741540776
- How Many Disparate Measurements of Kidney Function Unfairly Allow Selected Candidates to Accumulate Time on the Deceased Donor Kidney Transplant Waiting List?10.1681/ASN.2021030415Fri, 21 May 2021 01:58:52 GMT-07:00How Many Disparate Measurements of Kidney Function Unfairly Allow Selected Candidates to Accumulate Time on the Deceased Donor Kidney Transplant Waiting List?Steiner, Robert W.2021-05-21T13:58:52-07:00doi:10.1681/ASN.2021030415hwp:resource-id:jnephrol;32/6/1539American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyeGFR, kidney transplant, waitlist, ethicsLetters to the EditorLetters to the Editorletter20212021-06-01June 202110.1681/ASN.20210304151046-66731533-34502021-05-21T13:58:52-07:002021-06Journal of the American Society of NephrologyLetters to the Editor326315395231540525
- The Basolateral Polarity Module Promotes Slit Diaphragm Formation in Drosophila Nephrocytes, a Model of Vertebrate Podocytes10.1681/ASN.2020071050Thu, 01 Apr 2021 09:56:37 GMT-07:00The Basolateral Polarity Module Promotes Slit Diaphragm Formation in Drosophila Nephrocytes, a Model of Vertebrate PodocytesMysh, MichaelPoulton, John S.2021-04-01T09:56:37-07:00doi:10.1681/ASN.2020071050hwp:resource-id:jnephrol;32/6/1409American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycytoskeleton, endocytosis, glomerular disease, glomerular filtration barrier, podocyteBasic ResearchBasic Researchresearch-article20212021-06-01June 202110.1681/ASN.20200710501046-66731533-34502021-04-01T09:56:37-07:002021-06Journal of the American Society of NephrologyBasic Research32614091424
- Authors’ Reply10.1681/ASN.2021030334Tue, 13 Apr 2021 08:05:47 GMT-07:00Authors’ ReplyFishbane, StevenEl-Shahawy, Mohamed A.Van, Bui PhamLittle, Dustin J.2021-04-13T08:05:47-07:00doi:10.1681/ASN.2021030334hwp:resource-id:jnephrol;32/6/1537-aAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic kidney disease, erythropoietinLetters to the EditorLetters to the Editorletter20212021-06-01June 202110.1681/ASN.20210303341046-66731533-34502021-04-13T08:05:47-07:002021-06Journal of the American Society of NephrologyLetters to the Editor326631537153773715381537755
- Exploring the Complexity of Death-Censored Kidney Allograft Failure10.1681/ASN.2020081215Wed, 21 Apr 2021 06:27:50 GMT-07:00Exploring the Complexity of Death-Censored Kidney Allograft FailureMayrdorfer, ManuelLiefeldt, LutzWu, KaiyinRudolph, BirgitZhang, QiangFriedersdorff, FrankLachmann, NilsSchmidt, DaniloOsmanodja, BilginNaik, Marcel G.Duettmann, WiebkeHalleck, FabianMerkel, MarinaSchrezenmeier, EvaWaiser, JohannesDuerr, MichaelBudde, Klemens2021-04-21T06:27:50-07:00doi:10.1681/ASN.2020081215hwp:resource-id:jnephrol;32/6/1513American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, chronic allograft failure, clinical nephrology, transplant outcomes, transplant pathologyClinical ResearchClinical Researchresearch-article20212021-06-01June 202110.1681/ASN.20200812151046-66731533-34502021-04-21T06:27:50-07:002021-06Journal of the American Society of NephrologyClinical Research32615131526
- ADAM10-Mediated Ectodomain Shedding Is an Essential Driver of Podocyte Damage10.1681/ASN.2020081213Tue, 30 Mar 2021 07:30:32 GMT-07:00ADAM10-Mediated Ectodomain Shedding Is an Essential Driver of Podocyte DamageSachs, MarliesWetzel, SebastianReichelt, JuliaSachs, WiebkeSchebsdat, LisaZielinski, StephanieSeipold, LisaHeintz, LukasMüller, Stephan A.Kretz, OliverLindenmeyer, MajaWiech, ThorstenHuber, Tobias B.Lüllmann-Rauch, RenateLichtenthaler, Stefan F.Saftig, PaulMeyer-Schwesinger, Catherine2021-03-30T07:30:32-07:00doi:10.1681/ASN.2020081213hwp:resource-id:jnephrol;32/6/1389American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, podocyte, glomerular disease, membranous nephropathyBasic ResearchBasic Researchresearch-article20212021-06-01June 202110.1681/ASN.20200812131046-66731533-34502021-03-30T07:30:32-07:002021-06Journal of the American Society of NephrologyBasic Research32661389i1408i
- A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY)10.1681/ASN.2020101398Thu, 25 Mar 2021 09:05:33 GMT-07:00A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY)Pergola, Pablo E.Rosenbaum, David P.Yang, YangChertow, Glenn M.2021-03-25T09:05:33-07:00doi:10.1681/ASN.2020101398hwp:resource-id:jnephrol;32/6/1465American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytenapanor, hyperphosphatemia, NHE3 dialysis, phosphorus, phosphate binders, phosphate uptake, FGF23Clinical ResearchClinical Researchresearch-article20212021-06-01June 202110.1681/ASN.20201013981046-66731533-34502021-03-25T09:05:33-07:002021-06Journal of the American Society of NephrologyClinical Research32677146518241824147318241825
- Hypercholesterolemia in Progressive Renal Failure Is Associated with Changes in Hepatic Heparan Sulfate - PCSK9 Interaction10.1681/ASN.2020091376Tue, 23 Mar 2021 07:44:29 GMT-07:00Hypercholesterolemia in Progressive Renal Failure Is Associated with Changes in Hepatic Heparan Sulfate - PCSK9 InteractionShrestha, PragyiAdepu, SarithaVivès, Romain R.Masri, Rana ElKlooster, AstridKaptein, FleurDam, WendyBakker, Stephan J. L.van Goor, Harryvan de Sluis, Bartvan den Born, Jacob2021-03-23T07:44:29-07:00doi:10.1681/ASN.2020091376hwp:resource-id:jnephrol;32/6/1371American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, dyslipidemia, PCSK9, heparan sulfate, syndecan-1Basic ResearchBasic Researchresearch-article20212021-06-01June 202110.1681/ASN.20200913761046-66731533-34502021-03-23T07:44:29-07:002021-06Journal of the American Society of NephrologyBasic Research32661371i1388i
- National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race10.1681/ASN.2020121780Thu, 06 May 2021 05:18:48 GMT-07:00National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without RaceDuggal, VishalThomas, I-chunMontez-Rath, Maria E.Chertow, Glenn M.Kurella Tamura, Manjula2021-05-06T05:18:48-07:00doi:10.1681/ASN.2020121780hwp:resource-id:jnephrol;32/6/1454American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, glomerular filtration rateClinical EpidemiologyClinical Epidemiologyresearch-article20212021-06-01June 202110.1681/ASN.20201217801046-66731533-34502021-05-06T05:18:48-07:002021-06Journal of the American Society of NephrologyClinical Epidemiology32614541463
- Renal Recovery and Mortality Risk among Patients with Hepatorenal Syndrome Receiving Chronic Maintenance Dialysis10.34067/KID.0005182020Wed, 03 Mar 2021 07:43:39 GMT-08:00Renal Recovery and Mortality Risk among Patients with Hepatorenal Syndrome Receiving Chronic Maintenance DialysisMcAllister, SophieLai, Jennifer C.Copeland, Timothy P.Johansen, Kirsten L.McCulloch, Charles E.Kwong, Yuenting D.Seth, DivyaGrimes, BarbaraKu, Elaine2021-03-03T07:43:39-08:00doi:10.34067/KID.0005182020hwp:resource-id:kidney360;2/5/819American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, acute tubular necrosis, end stage kidney disease, hemodialysis, hepatorenal syndrome, renal failure, renal replacement therapy, United States Renal Data SystemOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-05-2710.34067/KID.00051820202641-76502021-03-03T07:43:39-08:002021-05-27Kidney360Original Investigation25819827
- Utility of Kinetic GFR for Predicting Severe Persistent AKI in Critically Ill Children and Young Adults10.34067/KID.0006892020Wed, 17 Mar 2021 01:22:31 GMT-07:00Utility of Kinetic GFR for Predicting Severe Persistent AKI in Critically Ill Children and Young AdultsMenon, ShinaBasu, Rajit K.Barhight, Matthew F.Goldstein, Stuart L.Gist, Katja M.2021-03-17T13:22:31-07:00doi:10.34067/KID.0006892020hwp:resource-id:kidney360;2/5/869American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, child, critical illness, glomerular filtration rate, KeGFR, kinetic, pediatric, young adultBrief CommunicationAcute Kidney Injury and ICU NephrologyBrief CommunicationAcute Kidney Injury and ICU Nephrologybrief-report20212021-05-2710.34067/KID.00068920202641-76502021-03-17T13:22:31-07:002021-05-27Kidney360Brief Communication25869872
- Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? CON10.34067/KID.0004102020Thu, 14 Jan 2021 06:25:51 GMT-08:00Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? CONGlassock, Richard J.2021-01-14T06:25:51-08:00doi:10.34067/KID.0004102020hwp:resource-id:kidney360;2/5/779American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, ANCA vasculitis, diffuse alveolar hemorrhage, plasmapheresis, PLEXDebates in NephrologyDebates in Nephrologyresearch-article20212021-05-2710.34067/KID.00041020202641-76502021-01-14T06:25:51-08:002021-05-27Kidney360Debates in Nephrology25779781
- Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? PRO10.34067/KID.0006762020Thu, 14 Jan 2021 06:25:51 GMT-08:00Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? PRODerebail, Vimal K.2021-01-14T06:25:51-08:00doi:10.34067/KID.0006762020hwp:resource-id:kidney360;2/5/776American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, ANCA, plasma exchange, PLEX, vasculitisDebates in NephrologyDebates in Nephrologyresearch-article20212021-05-2710.34067/KID.00067620202641-76502021-01-14T06:25:51-08:002021-05-27Kidney360Debates in Nephrology25776778
- Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? COMMENTARY10.34067/KID.0000072021Thu, 14 Jan 2021 06:25:51 GMT-08:00Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? COMMENTARYFalk, Ronald J.2021-01-14T06:25:51-08:00doi:10.34067/KID.0000072021hwp:resource-id:kidney360;2/5/782American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, ANCA-associated vasculitis, PLEX, pulmonary hemorrhageModerator CommentaryModerator Commentaryresearch-article20212021-05-2710.34067/KID.00000720212641-76502021-01-14T06:25:51-08:002021-05-27Kidney360Moderator Commentary25782783
- Introduction to Supervised Machine Learning10.34067/KID.0000182021Wed, 03 Mar 2021 09:28:26 GMT-08:00Introduction to Supervised Machine LearningBiswas, AdityaSaran, IshanWilson, F. Perry2021-03-03T09:28:26-08:00doi:10.34067/KID.0000182021hwp:resource-id:kidney360;2/5/878American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, algorithms, artificial intelligence, classification, machine learning, methods, prediction, supervisedClinical Research MethodsClinical Research Methodsresearch-article20212021-05-2710.34067/KID.00001820212641-76502021-03-03T09:28:26-08:002021-05-27Kidney360Clinical Research Methods25878880
- The Potential Role of the Gut Microbiota in Kidney Transplantation10.34067/KID.0006912020Fri, 05 Mar 2021 07:38:15 GMT-08:00The Potential Role of the Gut Microbiota in Kidney TransplantationHuang, JenniferSalinas, ThaliaWestblade, Lars F.Lee, John R.2021-03-05T07:38:15-08:00doi:10.34067/KID.0006912020hwp:resource-id:kidney360;2/5/890American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, dysbiosis, gastrointestinal microbiome, microbiota, mycophenolate mofetil, tacrolimus, transplantation, urinary tract infectionPerspectivesPerspectivesresearch-article20212021-05-2710.34067/KID.00069120202641-76502021-03-05T07:38:15-08:002021-05-27Kidney360Perspectives25890893
- Kidney–Gut Crosstalk in AKI10.34067/KID.0007722020Mon, 22 Feb 2021 11:24:26 GMT-08:00Kidney–Gut Crosstalk in AKIJo, Sang Kyung2021-02-22T11:24:26-08:00doi:10.34067/KID.0007722020hwp:resource-id:kidney360;2/5/886American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI, bacterial translocation, basic science, dysbiosis, gastrointestinal microbiome, immune modulation, intestinal barrier, microbiotaPerspectivesPerspectivesresearch-article20212021-05-2710.34067/KID.00077220202641-76502021-02-22T11:24:26-08:002021-05-27Kidney360Perspectives25886889
- A Hyaluronan Synthesis Inhibitor Delays the Progression of Diabetic Kidney Disease in A Mouse Experimental Model10.34067/KID.0004642020Tue, 02 Mar 2021 10:28:08 GMT-08:00A Hyaluronan Synthesis Inhibitor Delays the Progression of Diabetic Kidney Disease in A Mouse Experimental ModelSelman, GuillermoMartinez, LaiselLightle, AndreaAguilar, AlejandraWoltmann, DanielXiao, YuxuanVazquez-Padron, Roberto I.Salman, Loay H.2021-03-02T10:28:08-08:00doi:10.34067/KID.0004642020hwp:resource-id:kidney360;2/5/809American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, 4-methylumbelliferone, animal disease models, basic science, biochemical phenomena, diabetic kidney disease, diabetic nephropathies, disease progression, hyaluronan, hyaluronic acid, miceOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20212021-05-2710.34067/KID.00046420202641-76502021-03-02T10:28:08-08:002021-05-27Kidney360Original Investigation25809818
- Free Deoxycholic Acid Exacerbates Vascular Calcification in CKD through ER Stress-Mediated ATF4 Activation10.34067/KID.0007502020Fri, 26 Mar 2021 07:32:10 GMT-07:00Free Deoxycholic Acid Exacerbates Vascular Calcification in CKD through ER Stress-Mediated ATF4 ActivationMiyazaki-Anzai, ShinobuMasuda, MasashiShiozaki, YujiKeenan, Audrey L.Chonchol, MichelKremoser, ClausMiyazaki, Makoto2021-03-26T07:32:10-07:00doi:10.34067/KID.0007502020hwp:resource-id:kidney360;2/5/857American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360mineral metabolism, ATF4, basic science, deoxycholic acid, ER stress, Farnesoid X receptor, vascular calcificationOriginal InvestigationMineral MetabolismOriginal InvestigationMineral Metabolismresearch-article20212021-05-2710.34067/KID.00075020202641-76502021-03-26T07:32:10-07:002021-05-27Kidney360Original Investigation25857868
- Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral Obstruction10.34067/KID.0007182020Thu, 18 Mar 2021 06:22:47 GMT-07:00Twist1 in T Lymphocytes Augments Kidney Fibrosis after Ureteral ObstructionRen, JiafaLu, XiaohanGriffiths, RobertPrivratsky, Jamie R.Crowley, Steven D.2021-03-18T06:22:47-07:00doi:10.34067/KID.0007182020hwp:resource-id:kidney360;2/5/784American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, basic science, kidney fibrosis, T lymphocytes, Twist1Original InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-05-2710.34067/KID.00071820202641-76502021-03-18T06:22:47-07:002021-05-27Kidney360Original Investigation25784794
- Whole-Exome Sequencing Application for Genetic Diagnosis of Kidney Diseases: A Study from Southwest of Iran10.34067/KID.0006902020Wed, 10 Mar 2021 01:23:10 GMT-08:00Whole-Exome Sequencing Application for Genetic Diagnosis of Kidney Diseases: A Study from Southwest of IranZamani, MinaSeifi, TaherehSedighzadeh, SaharNegahdari, SamiraZeighami, JawaherSedaghat, AlirezaYadegari, TaherehSaberi, AlihosseinHamid, MohammadShariati, GholamrezaGalehdari, Hamid2021-03-10T13:23:10-08:00doi:10.34067/KID.0006902020hwp:resource-id:kidney360;2/5/873American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360Genetics, Basic Science, genetic diagnosis, Iran, Kidney Diseases, Pathogenic variants, Whole-Exome SequencingBrief CommunicationGeneticsBrief CommunicationGeneticsresearch-article20212021-05-2710.34067/KID.00069020202641-76502021-03-10T13:23:10-08:002021-05-27Kidney360Brief Communication25873877
- The Transcription Factor Sox6 Controls Renin Expression during Renal Artery Stenosis10.34067/KID.0002792020Fri, 26 Mar 2021 01:24:02 GMT-07:00The Transcription Factor Sox6 Controls Renin Expression during Renal Artery StenosisSaleem, MohammadSaavedra-Sánchez, LuzBarturen-Larrea, PierinaGomez, Jose A.2021-03-26T13:24:02-07:00doi:10.34067/KID.0002792020hwp:resource-id:kidney360;2/5/842American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360hypertension, basic science, kidney, mice, renal artery obstruction, renal artery stenosis, renin, renovascular hypertension, Sox6, SOXD transcription factorsOriginal InvestigationHypertensionOriginal InvestigationHypertensionresearch-article20212021-05-2710.34067/KID.00027920202641-76502021-03-26T13:24:02-07:002021-05-27Kidney360Original Investigation25842856
- Are the Protective Effects of SGLT2 Inhibitors a “Class-Effect” or Are There Differences between Agents?10.34067/KID.0000622021Fri, 05 Feb 2021 09:45:50 GMT-08:00Are the Protective Effects of SGLT2 Inhibitors a “Class-Effect” or Are There Differences between Agents?Schmidt, Darren W.Argyropoulos, ChristosSingh, Namita2021-02-05T09:45:50-08:00doi:10.34067/KID.0000622021hwp:resource-id:kidney360;2/5/881American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, class effects, clinical trials, heart failure, SGLT2 inhibitors, sodium glucose cotransporter two inhibitorsPerspectivesPerspectivesresearch-article20212021-05-2710.34067/KID.00006220212641-76502021-02-05T09:45:50-08:002021-05-27Kidney360Perspectives25881885
- Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy10.34067/KID.0006972020Wed, 10 Mar 2021 11:30:25 GMT-08:00Total Nephron Number and Single-Nephron Parameters in Patients with IgA NephropathyMarumoto, HirokazuTsuboi, NobuoD’Agati, Vivette D.Sasaki, TakayaOkabayashi, YusukeHaruhara, KotaroKanzaki, GoKoike, KentaroShimizu, AkiraKawamura, TetsuyaRule, Andrew D.Bertram, John F.Yokoo, Takashi2021-03-10T11:30:25-08:00doi:10.34067/KID.0006972020hwp:resource-id:kidney360;2/5/828American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, chronic kidney disease, IgA nephropathy, kidney biopsy, proteinuria, renal pathologyOriginal InvestigationGlomerular and Tubulointerstitial DiseasesOriginal InvestigationGlomerular and Tubulointerstitial Diseasesresearch-article20212021-05-2710.34067/KID.00069720202641-76502021-03-10T11:30:25-08:002021-05-27Kidney360Original Investigation25828841
- Worsening Kidney Function, Proteinuria, and Hematuria in a Patient with CLL10.34067/KID.0003452020Thu, 27 May 2021 01:00:23 GMT-07:00Worsening Kidney Function, Proteinuria, and Hematuria in a Patient with CLLChopra, PavanAndeen, Nicole K.Spurgeon, Stephen E.2021-05-27T13:00:23-07:00doi:10.34067/KID.0003452020hwp:resource-id:kidney360;2/5/916American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, chronic lymphocytic leukemia, hematuria, proteinuriaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-05-2710.34067/KID.00034520202641-76502021-05-27T13:00:23-07:002021-05-27Kidney360Clinical Images in Nephrology and Dialysis25916917
- Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial Participants10.34067/KID.0005962020Thu, 11 Mar 2021 09:36:45 GMT-08:00Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial ParticipantsHallows, Kenneth R.Althouse, Andrew D.Li, HuiSaitta, BiagioAbebe, Kaleab Z.Bae, Kyongtae T.Miskulin, Dana C.Perrone, Ronald D.Seliger, Stephen L.Watnick, Terry J.2021-03-11T09:36:45-08:00doi:10.34067/KID.0005962020hwp:resource-id:kidney360;2/5/795American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, biomarkers, GFR, metabolism, metforminOriginal InvestigationCystic Kidney DiseaseOriginal InvestigationCystic Kidney Diseaseresearch-article20212021-05-2710.34067/KID.00059620202641-76502021-03-11T09:36:45-08:002021-05-27Kidney360Original Investigation25795808
- Renal Hemodynamics, Function, and Oxygenation in Critically Ill Patients and after Major SurgeryThis review outlines the available data from the work of our group on renal hemodynamics, function, and oxygenation in patients who are critically ill with acute renal dysfunction, such as those with postoperative AKI, those in early clinical septic shock, in patients undergoing cardiac surgery with cardiopulmonary bypass, or in patients undergoing liver transplantation. We also provide information on renal hemodynamics, function, and oxygenation in patients with chronic renal impairment due to congestive heart failure. This review will argue that, for all of these groups of patients, the common denominator is that renal oxygenation is impaired due to a lower renal oxygen delivery or a pronounced increase in renal oxygen consumption.10.34067/KID.0007012020Wed, 03 Mar 2021 09:28:26 GMT-08:00Renal Hemodynamics, Function, and Oxygenation in Critically Ill Patients and after Major SurgeryThis review outlines the available data from the work of our group on renal hemodynamics, function, and oxygenation in patients who are critically ill with acute renal dysfunction, such as those with postoperative AKI, those in early clinical septic shock, in patients undergoing cardiac surgery with cardiopulmonary bypass, or in patients undergoing liver transplantation. We also provide information on renal hemodynamics, function, and oxygenation in patients with chronic renal impairment due to congestive heart failure. This review will argue that, for all of these groups of patients, the common denominator is that renal oxygenation is impaired due to a lower renal oxygen delivery or a pronounced increase in renal oxygen consumption.Ricksten, Sven-ErikBragadottir, GudrunLannemyr, LukasRedfors, BengtSkytte, Jenny2021-03-03T09:28:26-08:00doi:10.34067/KID.0007012020hwp:resource-id:kidney360;2/5/894American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, critical illness, glomerular filtration rate, hemodynamics, renal blood flow, renal oxygen consumption, renal oxygenation, respiratory physiologic phenomena, tubular injuryReview ArticleReview Articlereview-article20212021-05-2710.34067/KID.00070120202641-76502021-03-03T09:28:26-08:002021-05-27Kidney360Review Article25894904
- Role of Virus-Specific T Cell Therapy for Cytomegalovirus and BK Infections in Kidney Transplant RecipientsCytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well described. However, despite improvement in screening and prophylaxis strategies, CMV and BKV continue to negatively affect both short- and long-term graft survival. Adequate cell-mediated immunity is essential for the control and prevention of opportunistic viral infections, such as CMV and BKV. Therefore, immune reconstitution, in particular T cell recovery, is a key factor in antiviral control after kidney transplantation. Cell-based immunotherapy offers an attractive alternative approach to traditional interventions. Adoptive T cell transfer, via infusions of allogeneic virus-specific T lymphocytes is capable of restoring virus-specific T cell immunity, and are safe and effective in the treatment of viral infections after hematopoietic stem cell transplantation. In this article, we review the emerging role of virus-specific T cell therapy in the management of CMV and BKV after kidney transplantation. On the basis of the available data, virus-specific T cell therapy may be a promising addition to the antiviral treatment armamentarium after kidney transplantation. Future studies are needed to more clearly define the efficacy and risks of virus-specific T cell therapy in the kidney transplant population.10.34067/KID.0001572021Fri, 26 Mar 2021 12:18:40 GMT-07:00Role of Virus-Specific T Cell Therapy for Cytomegalovirus and BK Infections in Kidney Transplant RecipientsCytomegalovirus (CMV) and BK virus (BKV) are common viral infections after kidney transplant. Their negative effects on patient and graft outcomes have been well described. However, despite improvement in screening and prophylaxis strategies, CMV and BKV continue to negatively affect both short- and long-term graft survival. Adequate cell-mediated immunity is essential for the control and prevention of opportunistic viral infections, such as CMV and BKV. Therefore, immune reconstitution, in particular T cell recovery, is a key factor in antiviral control after kidney transplantation. Cell-based immunotherapy offers an attractive alternative approach to traditional interventions. Adoptive T cell transfer, via infusions of allogeneic virus-specific T lymphocytes is capable of restoring virus-specific T cell immunity, and are safe and effective in the treatment of viral infections after hematopoietic stem cell transplantation. In this article, we review the emerging role of virus-specific T cell therapy in the management of CMV and BKV after kidney transplantation. On the basis of the available data, virus-specific T cell therapy may be a promising addition to the antiviral treatment armamentarium after kidney transplantation. Future studies are needed to more clearly define the efficacy and risks of virus-specific T cell therapy in the kidney transplant population.Parajuli, SandeshJorgenson, MargaretMeyers, Ross O.Djamali, ArjangGalipeau, Jacques2021-03-26T12:18:40-07:00doi:10.34067/KID.0001572021hwp:resource-id:kidney360;2/5/905American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, BK infection, cell- and tissue-based therapy, CMV, cytomegalovirus infections, kidney transplantation, viral-specific T cell therapyReview ArticleReview Articlereview-article20212021-05-2710.34067/KID.00015720212641-76502021-03-26T12:18:40-07:002021-05-27Kidney360Review Article25905915
- AKI in a Patient with Fever, Rash, and Joint Pain10.34067/KID.0000402021Thu, 27 May 2021 01:00:23 GMT-07:00AKI in a Patient with Fever, Rash, and Joint PainAron, Abraham W.Brewster, Ursula C.2021-05-27T13:00:23-07:00doi:10.34067/KID.0000402021hwp:resource-id:kidney360;2/5/918American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, cryoglobulinemia, cryoglobulinemia vasculitis, renal biopsy, rheumatology, vasculitisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-05-2710.34067/KID.00004020212641-76502021-05-27T13:00:23-07:002021-05-27Kidney360Clinical Images in Nephrology and Dialysis25918919
- Provider Perception of Frailty Is Associated with Dialysis Decision Making in Patients with Advanced CKD10.2215/CJN.12480720Fri, 26 Mar 2021 06:05:27 GMT-07:00Provider Perception of Frailty Is Associated with Dialysis Decision Making in Patients with Advanced CKDBrar, Ranveer S.Whitlock, Reid H.Komenda, Paul V.J.Rigatto, ClaudioPrasad, BhanuBohm, ClaraTangri, Navdeep2021-03-26T06:05:27-07:00doi:10.2215/CJN.12480720hwp:resource-id:clinjasn;16/4/552American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfrailty, dialysis, chronic kidney disease, decision makingOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-04-07Month XX, 202110.2215/CJN.124807201555-90411555-905X2021-03-26T06:05:27-07:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles164552559
- Identification of Patients with CKD in Medical Databases10.2215/CJN.15691020Thu, 11 Mar 2021 08:20:27 GMT-08:00Identification of Patients with CKD in Medical DatabasesVestergaard, Søren ViborgChristiansen, Christian FynboThomsen, Reimar WernichBirn, HenrikHeide-Jørgensen, Uffe2021-03-11T08:20:27-08:00doi:10.2215/CJN.15691020hwp:resource-id:clinjasn;16/4/543American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, incidence, prevalence, prognosis, glomerular filtration rate, registries, mortality, epidemiology, hospital records, algorithmsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-04-07April 07, 202110.2215/CJN.156910201555-90411555-905X2021-03-11T08:20:27-08:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles164543551
- Racial Differences in AKI Incidence Following Percutaneous Coronary Intervention10.1681/ASN.2020040502Fri, 18 Dec 2020 11:57:36 GMT-08:00Racial Differences in AKI Incidence Following Percutaneous Coronary InterventionLunyera, JosephClare, Robert M.Chiswell, KarenScialla, Julia J.Pun, Patrick H.Thomas, Kevin L.Starks, Monique A.Diamantidis, Clarissa J.2020-12-18T11:57:36-08:00doi:10.1681/ASN.2020040502hwp:resource-id:jnephrol;32/3/654American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, African Americans, racial disparities, percutaneous coronary interventionClinical EpidemiologyClinical Epidemiologyresearch-article20212021-03-01March 202110.1681/ASN.20200405021046-66731533-34502020-12-18T11:57:36-08:002021-03Journal of the American Society of NephrologyClinical Epidemiology323654662
- Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time10.1681/ASN.2020081144Tue, 23 Feb 2021 11:36:42 GMT-08:00Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist TimeKu, ElaineMcCulloch, Charles E.Adey, Deborah B.Li, LiboJohansen, Kirsten L.2021-02-23T11:36:42-08:00doi:10.1681/ASN.2020081144hwp:resource-id:jnephrol;32/3/677American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, transplantation, dialysis, progression of chronic renal failure, glomerular filtration rateClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200811441046-66731533-34502021-02-23T11:36:42-08:002021-03Journal of the American Society of NephrologyClinical Research3233677523685525
- Promoting Equity in Eligibility for Registration on the Kidney Transplantation Waiting List: Looking beyond eGFRcr10.1681/ASN.2020121802Tue, 23 Feb 2021 11:21:27 GMT-08:00Promoting Equity in Eligibility for Registration on the Kidney Transplantation Waiting List: Looking beyond eGFRcrLevey, Andrew S.Inker, Lesley A.Goyal, Nitender2021-02-23T11:21:27-08:00doi:10.1681/ASN.2020121802hwp:resource-id:jnephrol;32/3/523American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rate, kidney transplantation, creatinine, race disparity, waiting listEditorialsEditorialseditorial20212021-03-01March 202110.1681/ASN.20201218021046-66731533-34502021-02-23T11:21:27-08:002021-03Journal of the American Society of NephrologyEditorials3233652367715395256851540
- Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank10.1681/ASN.2020050659Mon, 14 Dec 2020 09:25:12 GMT-08:00Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK BiobankZhao, Jie V.Schooling, C. Mary2020-12-14T09:25:12-08:00doi:10.1681/ASN.2020050659hwp:resource-id:jnephrol;32/3/686American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, risk factors, gender difference, sex hormone binding globulinClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200506591046-66731533-34502020-12-14T09:25:12-08:002021-03Journal of the American Society of NephrologyClinical Research323686694
- Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome10.1681/ASN.2020040490Tue, 16 Feb 2021 08:29:16 GMT-08:00Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat SyndromeMann, NinaMzoughi, SlimSchneider, RonenKühl, Susanne J.Schanze, DennyKlämbt, VerenaLovric, SvjetlanaMao, YouyingShi, ShashaTan, WeizhenKühl, MichaelOnuchic-Whitford, Ana C.Treimer, ErnestineKitzler, Thomas M.Kause, FranziskaSchumann, SvenNakayama, MakikoBuerger, FlorianShril, Shirleevan der Ven, Amelie T.Majmundar, Amar J.Holton, Kristina MarieKolb, AmyBraun, Daniela A.Rao, JiaJobst-Schwan, TilmanMildenberger, EvaLennert, ThomasKuechler, AlmaWieczorek, DagmarGross, OliverErmisch-Omran, BeateWerberger, AnjaSkalej, MartinJanecke, Andreas R.Soliman, Neveen A.Mane, Shrikant M.Lifton, Richard P.Kadlec, JanGuccione, ErnestoSchmeisser, Michael J.Zenker, MartinHildebrandt, Friedhelm2021-02-16T08:29:16-08:00doi:10.1681/ASN.2020040490hwp:resource-id:jnephrol;32/3/580American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, genetics and development, nephrotic syndromeBasic ResearchBasic Researchresearch-article20212021-03-01March 202110.1681/ASN.20200404901046-66731533-34502021-02-16T08:29:16-08:002021-03Journal of the American Society of NephrologyBasic Research323580596
- Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)10.2215/CJN.16281020Mon, 29 Mar 2021 10:58:19 GMT-07:00Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)Rivero, JesúsMerino-López, MaribelOlmedo, RossanaGarrido-Roldan, RubénMoguel, BernardoRojas, GustavoChavez-Morales, AlfonsoAlvarez-Maldonado, PabloDuarte-Molina, PabloCastaño-Guerra, RodolfoRuiz-Lopez, Ivon KarinaSoria-Castro, ElizabethLuna, CesarBonilla-Méndez, AlejandroBaranda, FranciscoZabal, CarlosMadero, MagdalenaValdez-Ortiz, RafaelSoto-Abraham, Ma. VirgiliaVazquez-Rangel, Armando2021-03-29T10:58:19-07:00doi:10.2215/CJN.16281020hwp:resource-id:clinjasn;16/5/685American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypostmortem, kidney biopsy, acute kidney injury, SARS-CoV-2, COVID-19Original ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-05-08May 08, 202110.2215/CJN.162810201555-90411555-905X2021-03-29T10:58:19-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles165685693
- Trust the Patient: An Unusual Case of Metabolic Alkalosis10.2215/CJN.18031120Tue, 16 Mar 2021 07:19:36 GMT-07:00Trust the Patient: An Unusual Case of Metabolic AlkalosisHoenig, Melanie PaigeLecker, Stewart H.2021-03-16T07:19:36-07:00doi:10.2215/CJN.18031120hwp:resource-id:clinjasn;16/5/800American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymetabolic alkalosis, diarrhea, hypokalemia, stool electrolytes, electrolytesKidney Case Conference: Nephrology Quiz & QuestionnaireKidney Case Conference: Nephrology Quiz & Questionnaireother20212021-05-08May 08, 202110.2215/CJN.180311201555-90411555-905X2021-03-16T07:19:36-07:002021-05-08Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz & Questionnaire165800802
- Mass Disasters and Burnout in Nephrology PersonnelMass disasters result in extensive health problems and make health care delivery problematic, as has been the case during the COVID-19 pandemic. Although COVID-19 was initially considered a pulmonary problem, it soon became clear that various other organs were involved. Thus, many care providers, including kidney health personnel, were overwhelmed or developed burnout. This review aims to describe the spectrum of burnout in mass disasters and suggests solutions specifically for nephrology personnel by extending previous experience to the COVID-19 pandemic. Burnout (a psychologic response to work-related stress) is already a frequent part of routine nephrology practice and, not surprisingly, is even more common during mass disasters due to increased workload and specific conditions, in addition to individual factors. Avoiding burnout is essential to prevent psychologic and somatic health problems in personnel as well as malpractice, understaffing, and inadequate health care delivery, all of which increase the health care burden of disasters. Burnout may be prevented by predisaster organizational measures, which include developing an overarching plan and optimizing health care infrastructure, and ad hoc disaster-specific measures that encompass both organizational and individual measures. Organizational measures include increasing safety, decreasing workload and fear of malpractice, optimizing medical staffing and material supplies, motivating personnel, providing mental health support, and enabling flexibility in working circumstances. Individual measures include training on coping with stress and problematic conditions, minimizing the stigma of emotional distress, and maintaining physical health. If these measures fall short, asking for external help is mandatory to avoid an inefficient disaster health care response. Minimizing burnout by applying these measures will improve health care provision, thus saving as many lives as possible.10.2215/CJN.08400520Thu, 07 Jan 2021 09:39:06 GMT-08:00Mass Disasters and Burnout in Nephrology PersonnelMass disasters result in extensive health problems and make health care delivery problematic, as has been the case during the COVID-19 pandemic. Although COVID-19 was initially considered a pulmonary problem, it soon became clear that various other organs were involved. Thus, many care providers, including kidney health personnel, were overwhelmed or developed burnout. This review aims to describe the spectrum of burnout in mass disasters and suggests solutions specifically for nephrology personnel by extending previous experience to the COVID-19 pandemic. Burnout (a psychologic response to work-related stress) is already a frequent part of routine nephrology practice and, not surprisingly, is even more common during mass disasters due to increased workload and specific conditions, in addition to individual factors. Avoiding burnout is essential to prevent psychologic and somatic health problems in personnel as well as malpractice, understaffing, and inadequate health care delivery, all of which increase the health care burden of disasters. Burnout may be prevented by predisaster organizational measures, which include developing an overarching plan and optimizing health care infrastructure, and ad hoc disaster-specific measures that encompass both organizational and individual measures. Organizational measures include increasing safety, decreasing workload and fear of malpractice, optimizing medical staffing and material supplies, motivating personnel, providing mental health support, and enabling flexibility in working circumstances. Individual measures include training on coping with stress and problematic conditions, minimizing the stigma of emotional distress, and maintaining physical health. If these measures fall short, asking for external help is mandatory to avoid an inefficient disaster health care response. Minimizing burnout by applying these measures will improve health care provision, thus saving as many lives as possible.Sever, Mehmet SukruOrtiz, AlbertoMaggiore, UmbertoBac-García, EnriqueVanholder, Raymond2021-01-07T09:39:06-08:00doi:10.2215/CJN.08400520hwp:resource-id:clinjasn;16/5/829American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyburnout, massive disaster, earthquake, hurricane, COVID-19, pandemic, nephrologyReviewsReviewsreview-article20212021-05-08May 08, 202110.2215/CJN.084005201555-90411555-905X2021-01-07T09:39:06-08:002021-05-08Clinical Journal of the American Society of NephrologyReviews165829837
- Outcomes of COVID-19 in CKD Patients10.2215/CJN.13820820Mon, 08 Feb 2021 09:47:53 GMT-08:00Outcomes of COVID-19 in CKD PatientsPakhchanian, HaigRaiker, RahulMukherjee, AmritaKhan, AhmadSingh, ShailendraChatterjee, Arka2021-02-08T09:47:53-08:00doi:10.2215/CJN.13820820hwp:resource-id:clinjasn;16/5/785American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, chronic kidney disease, end stage kidney disease, Electronic Health RecordsResearch LettersResearch Lettersletter20212021-05-08May 08, 202110.2215/CJN.138208201555-90411555-905X2021-02-08T09:47:53-08:002021-05-08Clinical Journal of the American Society of NephrologyResearch Letters165785786
- Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic StudiesAutosomal dominant polycystic kidney disease is the most common monogenic cause of ESKD. Genetic studies from patients and animal models have informed disease pathobiology and strongly support a “threshold model” in which cyst formation is triggered by reduced functional polycystin dosage below a critical threshold within individual tubular epithelial cells due to (1) germline and somatic PKD1 and/or PKD2 mutations, (2) mutations of genes (e.g., SEC63, SEC61B, GANAB, PRKCSH, DNAJB11, ALG8, and ALG9) in the endoplasmic reticulum protein biosynthetic pathway, or (3) somatic mosaicism. Genetic testing has the potential to provide diagnostic and prognostic information in cystic kidney disease. However, mutation screening of PKD1 is challenging due to its large size and complexity, making it both costly and labor intensive. Moreover, conventional Sanger sequencing–based genetic testing is currently limited in elucidating the causes of atypical polycystic kidney disease, such as within-family disease discordance, atypical kidney imaging patterns, and discordant disease severity between total kidney volume and rate of eGFR decline. In addition, environmental factors, genetic modifiers, and somatic mosaicism also contribute to disease variability, further limiting prognostication by mutation class in individual patients. Recent innovations in next-generation sequencing are poised to transform and extend molecular diagnostics at reasonable costs. By comprehensive screening of multiple cystic disease and modifier genes, targeted gene panel, whole-exome, or whole-genome sequencing is expected to improve both diagnostic and prognostic accuracy to advance personalized medicine in autosomal dominant polycystic kidney disease.10.2215/CJN.02320220Mon, 20 Jul 2020 02:00:20 GMT-07:00Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic StudiesAutosomal dominant polycystic kidney disease is the most common monogenic cause of ESKD. Genetic studies from patients and animal models have informed disease pathobiology and strongly support a “threshold model” in which cyst formation is triggered by reduced functional polycystin dosage below a critical threshold within individual tubular epithelial cells due to (1) germline and somatic PKD1 and/or PKD2 mutations, (2) mutations of genes (e.g., SEC63, SEC61B, GANAB, PRKCSH, DNAJB11, ALG8, and ALG9) in the endoplasmic reticulum protein biosynthetic pathway, or (3) somatic mosaicism. Genetic testing has the potential to provide diagnostic and prognostic information in cystic kidney disease. However, mutation screening of PKD1 is challenging due to its large size and complexity, making it both costly and labor intensive. Moreover, conventional Sanger sequencing–based genetic testing is currently limited in elucidating the causes of atypical polycystic kidney disease, such as within-family disease discordance, atypical kidney imaging patterns, and discordant disease severity between total kidney volume and rate of eGFR decline. In addition, environmental factors, genetic modifiers, and somatic mosaicism also contribute to disease variability, further limiting prognostication by mutation class in individual patients. Recent innovations in next-generation sequencing are poised to transform and extend molecular diagnostics at reasonable costs. By comprehensive screening of multiple cystic disease and modifier genes, targeted gene panel, whole-exome, or whole-genome sequencing is expected to improve both diagnostic and prognostic accuracy to advance personalized medicine in autosomal dominant polycystic kidney disease.Lanktree, Matthew B.Haghighi, Amirrezadi Bari, IghliSong, XuewenPei, York2020-07-20T14:00:20-07:00doi:10.2215/CJN.02320220hwp:resource-id:clinjasn;16/5/790American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypolycystic kidney disease, Kidney Genomics SeriesGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-05-08May 08, 202110.2215/CJN.023202201555-90411555-905X2020-07-20T14:00:20-07:002021-05-08Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease1655790671799673
- A Dialysis Patient’s View on Dialysis Employment Loss10.2215/CJN.03450321Thu, 15 Apr 2021 07:54:43 GMT-07:00A Dialysis Patient’s View on Dialysis Employment LossDitschman, Erich2021-04-15T07:54:43-07:00doi:10.2215/CJN.03450321hwp:resource-id:clinjasn;16/5/669American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, employmentPatient VoicePatient Voiceeditorial20212021-05-08May 08, 202110.2215/CJN.034503211555-90411555-905X2021-04-15T07:54:43-07:002021-05-08Clinical Journal of the American Society of NephrologyPatient Voice1655669746670756
- A Patient Perspective on Genetic Testing for ADPKD10.2215/CJN.14051119Thu, 30 Jul 2020 07:14:46 GMT-07:00A Patient Perspective on Genetic Testing for ADPKDOdland, Dwight2020-07-30T07:14:46-07:00doi:10.2215/CJN.14051119hwp:resource-id:clinjasn;16/5/671American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, genetic renal disease, genetic testing, end stage kidney disease, end-stage renal disease, ESRD, family history, genetics and development, kidney, kidney disease, kidney failure, nephrotoxicityPatient VoicePatient Voiceeditorial20212021-05-08May 08, 202110.2215/CJN.140511191555-90411555-905X2020-07-30T07:14:46-07:002021-05-08Clinical Journal of the American Society of NephrologyPatient Voice1655671790673799
- Social Determinants of Kidney Health10.2215/CJN.12710820Wed, 13 Jan 2021 07:09:12 GMT-08:00Social Determinants of Kidney HealthNorris, Keith C.Beech, Bettina M.2021-01-13T07:09:12-08:00doi:10.2215/CJN.12710820hwp:resource-id:clinjasn;16/5/809American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, social determinants of health, structural inequities, poverty, race, equityPerspectivesPerspectivesresearch-article20212021-05-08May 08, 202110.2215/CJN.127108201555-90411555-905X2021-01-13T07:09:12-08:002021-05-08Clinical Journal of the American Society of NephrologyPerspectives16555555809803806812818815811805808814819817
- The Seen and the Unseen: Race and Social Inequities Affecting Kidney Care10.2215/CJN.12630820Wed, 13 Jan 2021 07:09:12 GMT-08:00The Seen and the Unseen: Race and Social Inequities Affecting Kidney CareBoulware, L. EbonyMohottige, Dinushika2021-01-13T07:09:12-08:00doi:10.2215/CJN.12630820hwp:resource-id:clinjasn;16/5/815American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrace, social context, racism, social inequity, health equity, equityPerspectivesPerspectivesresearch-article20212021-05-08May 08, 202110.2215/CJN.126308201555-90411555-905X2021-01-13T07:09:12-08:002021-05-08Clinical Journal of the American Society of NephrologyPerspectives16555555815803806809812818817805808811814819
- Social Determinants of Health in People with Kidney Disease10.2215/CJN.12600720Wed, 13 Jan 2021 07:09:13 GMT-08:00Social Determinants of Health in People with Kidney DiseaseWeinstein, Alan M.Kimmel, Paul L.2021-01-13T07:09:13-08:00doi:10.2215/CJN.12600720hwp:resource-id:clinjasn;16/5/803American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologystructural racism, residential segregation, dialysis, chronic kidney disease, psychosocial, mortality, morbidity, EquityPerspectivesPerspectivesresearch-article20212021-05-08May 08, 202110.2215/CJN.126007201555-90411555-905X2021-01-13T07:09:13-08:002021-05-08Clinical Journal of the American Society of NephrologyPerspectives16555555803806809815812818805808811817814819
- Reducing the Burden of CKD among Latinx10.2215/CJN.12890820Wed, 13 Jan 2021 07:09:13 GMT-08:00Reducing the Burden of CKD among LatinxPereira, Rocio I.Cervantes, Lilia2021-01-13T07:09:13-08:00doi:10.2215/CJN.12890820hwp:resource-id:clinjasn;16/5/812American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney failure, chronic kidney disease, disparityPerspectivesPerspectivesresearch-article20212021-05-08May 08, 202110.2215/CJN.128908201555-90411555-905X2021-01-13T07:09:13-08:002021-05-08Clinical Journal of the American Society of NephrologyPerspectives16555555812803806809815818814805808811817819
- Personal Experiences of Patients in the Interaction of Culture and Kidney Disease10.2215/CJN.12400720Wed, 13 Jan 2021 07:09:13 GMT-08:00Personal Experiences of Patients in the Interaction of Culture and Kidney DiseaseCukor, DanielEdwards, Dawn P.,2021-01-13T07:09:13-08:00doi:10.2215/CJN.12400720hwp:resource-id:clinjasn;16/5/818American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, patient experience, chronic kidney diseasePerspectivesPerspectivesresearch-article20212021-05-08May 08, 202110.2215/CJN.124007201555-90411555-905X2021-01-13T07:09:13-08:002021-05-08Clinical Journal of the American Society of NephrologyPerspectives16555555818803806809812815819805808811814817
- The Pathogenesis of Race and Ethnic Disparities10.2215/CJN.12640820Wed, 13 Jan 2021 07:09:12 GMT-08:00The Pathogenesis of Race and Ethnic DisparitiesPowe, Neil R.2021-01-13T07:09:12-08:00doi:10.2215/CJN.12640820hwp:resource-id:clinjasn;16/5/806American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, disparity, end-stage renal disease, equity, ethnicity, genetic renal disease, kidney disease, kidney failure, Pathophysiology of Renal Disease and Progression, transplantationPerspectivesPerspectivesresearch-article20212021-05-08May 08, 202110.2215/CJN.126408201555-90411555-905X2021-01-13T07:09:12-08:002021-05-08Clinical Journal of the American Society of NephrologyPerspectives16555555806803809815812818808805811817814819
- Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome10.2215/CJN.16751020Tue, 27 Apr 2021 09:07:41 GMT-07:00Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary SyndromeKalantar-Zadeh, KamyarSchwartz, Gregory G.Nicholls, Stephen J.Buhr, Kevin A.Ginsberg, Henry N.Johansson, Jan O.Kulikowski, EwelinaLebioda, KennethToth, Peter P.Wong, NormanSweeney, MichaelRay, Kausik K.,,Ray, Kausik K.Schwartz, Gregory G.Nicholls, Stephen J.Kalantar-Zadeh, KaymarToth, PeterGinsberg, HenrySweeney, MichaelWong, NormanJohansson, JanLorenzatti, AlbertoVico, MarisaMilanova, MariaMilicevic, GoranPopovic, ZeljkoEbelt, HenningKiss, Róbert GáborLewis, BasilLlamas, Edmundo BayramBanach, MaciejTereschenko, SergeyPavlovic, MilanPella, DanielChiang, Chern-EnLonn, EvaWatkins, PaulWaters, DavidSzarek, MichaelCurrier, JudithLeiter, Lawrence AlanMcMurray, JohnPetrie, MarkJhund, PardeepWalters, MatthewConnolly, EugeneLang, NinianSchiavi, LiliaVico, MarisaMaffei, LauraBordonava, AnselmoPrado, AldoVallejos, JulioFarias, JavierNardone, LucreciaResk, JorgeCaruso, OrlandoLorenzatti, AlbertoMaldonado, NatachaPadilla, LucioHominal, MiguelLuquez, HugoSposetti, GeorginaCaccavo, AlbertoGlenny, JorgeMansilla, VirginiaAlvarez, MariaParody, MariaSarjanovich, RodolfoKlyver, MariaValdez, Maria EugeniaColombo, HugoBaccaro, ClaudiaVisco, VirginiaBono, JulioCuneo, CarlosPácora, Fredy FerréGuzman, PabloPiskorz, DanielVogel, DanielGrigorov, MladenGatzov, PlamenStoyanov, MiroslavApostolova, EmilyaMilanova, MariaPetrov, IvoAngelov, AtanasLazov, PetarGrigorova, ValentinaYanev, TodorVuchkova, EmilenaVassilev, DobrinTisheva, SnezhankaGelev, ValeriCanecki-Varzic, SilviaPopovic, ZeljkoTusek, SreckoŠunić, Ema DrvodelićMilicevic, GoranJandric-Balen, MaricaMarinic, NikolinaMoser, NatasaEbelt, HenningNatour, MohammedSchwimmbeck, PeterAppel, Karl-FriedrichKleinertz, KlausMerkely, BélaPapp, AndrásKiss, RobertKovács, ZsoltVértes, AndrásSárszegi, ZsoltKis, ErnöBenedek, AmáliaTakács, JánosPapp, AnikoMatoltsy, AndrasAndrassy, PeterUngi, ImreShechter, MichaelAtar, ShaulShotan, AvrahamVazan, AliciaAlcalai, RonnyLotan, ChaimLewis, BasilHayek, TonyMoriel, MadyKatz, AmosLiberty, IditHarman-Boehm, IlanaSchiff, EladKracoff, OscarRozenman, YosephMosseri, MorrisSlezak, LadislavSabbah, MuhammadZeltser, DavidAdawi, KhaledOmary, MuhamedNess, Rosane AbramofAdawi, FaiadRuiz, Jose GarzaCarrillo, JorgeNevarez Ruiz, Luis AlejandroHernandez, Pedro GarciaArechavaleta-Granell, Marialos Rios Ibarra, Manuel DeVelasco-Sanchez, RaulMolina, Hugo LaviadaMorales, Lucas SolisGonzalez, Efrain MontanoEsperón, Guillermo LlamasBayram Llamas, Edmundo AlfredoRocha, Cynthia MustielesSuarez-Otero, RodrigoReal, Manuel AguileraCruz, Eliud MontesLopez, Humberto AlvarezVaca, Susano LaraFanghanel-Salmon, GuillermoHerrera, Carlos HernandezSaldaña, Joel RodriguezGarcia, Elier PedrozaVelázquez, Maricela VidrioBriones, Ignacio RodriguezHamer, BasSlagboom, TonZurakowski, AleksanderDebinski, MarcinKobielusz-Gembala, IwonaBartkowiak, RadoslawRajzer, MarekWitkowski, AdamKowalisko, AlicjaPiepiorka, MarekStania, KarolDomzal, MichalKorecki, JanuszKorzeniak, RomualdMazurkiewicz, LukaszMirek-Bryniarska, EwaBanach, MaciejMadziarska, KatarzynaMlodziankowski, AdamRewerska, BarbaraGaciong, ZbigniewMazurkiewicz, MaciejMaksimov, IvanShvarts, YuriKhaisheva, LarisaSamitin, VasilyBoldueva, SvetlanaZykov, MikhailBarbarash, OlgaKostenko, VictorKulibaba, ElenaSmolenskaya, OlgaTarasov, NikolayShogenov, ZaurStrongin, LeonidKuzin, AnatolyMakukhin, ValeriyNikolaev, KonstantinTereschenko, SergeyVezikova, NatalyaMiloradovic, VladimirPavlovic, MilanIlic, Marina DeljaninSimic, DraganPudar-Brankovic, GeorginaJozic, TanjaDodic, SlobodanRistic, ArsenHinic, SasaMitov, VladimirStokuca-Korac, NatasaStokic, EditaCelic, VeraDespotovic, NebojsaDincic, DraganTosic, Biljana PutnikovicSelakovic, AleksandarPella, DanielBanik, MilanFedacko, JanMicko, KarolDuris, TiborKokles, MartinLachova, BeataDzupina, AndrejMazur, JurajBuganova, IngridBehuncik, MilanVadinova, SilviaYeh, Hung-IChiang, Chern-EnLee, Cheng-HenHsieh, I-ChangJiunn-Lee, LinLin, We-HsiangWu, Yen-WenHsia, Chien HsunLo, Ping Han2021-04-27T09:07:41-07:00doi:10.2215/CJN.16751020hwp:resource-id:clinjasn;16/5/705American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyepigenetic pharmacotherapy, apabetalone, alkaline phosphatase, major adverse cardiovascular events, CKD stage 5, chronic kidney disease, diabetes, diabetes mellitus, cardiovascularOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-05-08May 08, 202110.2215/CJN.167510201555-90411555-905X2021-04-27T09:07:41-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1655705682716684
- Uromodulin, Salt, and 24-Hour Blood Pressure in the General Population10.2215/CJN.11230720Thu, 21 Jan 2021 08:10:09 GMT-08:00Uromodulin, Salt, and 24-Hour Blood Pressure in the General PopulationPonte, BelenPruijm, MennoAckermann, DanielOlinger, EricYouhanna, SoniaVogt, BrunoBurnier, MichelPechere-Bertschi, AntoinetteBochud, MurielleDevuyst, Olivier2021-01-21T08:10:09-08:00doi:10.2215/CJN.11230720hwp:resource-id:clinjasn;16/5/787American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuromodulin, salt, urinary sodium excretion, blood pressureResearch LettersResearch Lettersletter20212021-05-08May 08, 202110.2215/CJN.112307201555-90411555-905X2021-01-21T08:10:09-08:002021-05-08Clinical Journal of the American Society of NephrologyResearch Letters165787789
- Twenty-First Century Solutions to Increase Medication Optimization and Safety in Kidney Transplant Patients10.2215/CJN.04160321Fri, 30 Apr 2021 11:43:51 GMT-07:00Twenty-First Century Solutions to Increase Medication Optimization and Safety in Kidney Transplant PatientsSt. Peter, Wendy L.Aungst, Timothy D.2021-04-30T11:43:51-07:00doi:10.2215/CJN.04160321hwp:resource-id:clinjasn;16/5/679American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, medication optimization, medication safety, pharmacistsEditorialsEditorialseditorial20212021-05-08May 08, 202110.2215/CJN.041603211555-90411555-905X2021-04-30T11:43:51-07:002021-05-08Clinical Journal of the American Society of NephrologyEditorials1655679776681784
- Prasugrel and Ticagrelor in Patients with Drug-Eluting Stents and Kidney Failure10.2215/CJN.12120720Fri, 02 Apr 2021 09:27:23 GMT-07:00Prasugrel and Ticagrelor in Patients with Drug-Eluting Stents and Kidney FailureMavrakanas, Thomas A.Kamal, OmerCharytan, David M.2021-04-02T09:27:23-07:00doi:10.2215/CJN.12120720hwp:resource-id:clinjasn;16/5/757American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydrug eluting stents, maintenance dialysis, prasugrel, ticagrelor myocardial infarctionOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-05-08May 08, 202110.2215/CJN.121207201555-90411555-905X2021-04-02T09:27:23-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles165757764
- Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis10.2215/CJN.16931020Wed, 07 Apr 2021 09:00:59 GMT-07:00Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving HemodialysisBushinsky, David A.Raggi, PaoloBover, JordiKetteler, MarkusBellasi, AntonioRodriguez, MarianoSinha, SmeetaGarg, RekhaPerelló, JoanGold, AlexChertow, Glenn M.,,Nash, Kevin W.Kaskas, Marwan O.Martin, Edouard ReneBernardo, Marializa VictorinoMehta, BhaskerHon, GeorgeMeyer, Jill MarieSteer, Dylan LiorBhat, PremilaKapoian, TorosSullivan, JamesKopyt, Nelson P.Zeig, StevenCuellar, Juan MauricioLynn, Robert IsaacRoer, David A.Gandhi, Nirav DineshKleinman, Kenneth ScottArenas Guadiz, Ramon NarcisoYan, JieshiSeek, Melvin M.Durham, William TracyRakowski, Daniel A.Topf, Joel MichelsLehrner, Lawrence MarshallGraham, Stephen LawrenceJamal, Aamir Z.Khawar, Osman SaleemDua, SohanPatak, Ramachandra V.Navarro, Jesus OvidioIrby, Braxter PleasantJoshi, Sudhir ShyamDarwish, Riad YAnger, Michael S.Gandhi, Kamal V.Al-Saghir, FahdJim, BunSingh, HarmeetBelart Rodríguez, María MontserratParra, Emilio GonzálezPlanas Pons, Antonio FranciscoNieto, Silvia ColladoIbeas López, José AntonioEscola, Joaquín ManriqueMarques, Gonzalo GómezDíaz Gómez, Joan ManuelPortillo, Mariano RodríguezBuades Fuster, Juan ManuelTerrades, Natalia RamosFernández, Isabel MartínezPuchades Montesa, María JesúsVila, Pablo MolinaVilaro, Meritxell IbernónLazo, Mercedes SalgueiraArnal, Luis Miguel LouVarela, Jesús CalviñoSarró Sobrín, José FelipeCanals, Francisco MaduellSinha, SmeetaMitra, SandipHutchinson, AlastairEardley, Kevin S.Balasubramaniam, GowrieMikhail, AshrafBansal, Tarun,2021-04-07T09:00:59-07:00doi:10.2215/CJN.16931020hwp:resource-id:clinjasn;16/5/736American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybone mineral density, matrix mineralization, bone modeling and remodeling, SNF472, cardiovascularOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-05-08May 08, 202110.2215/CJN.169310201555-90411555-905X2021-04-07T09:00:59-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles165736745
- Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant Recipients10.2215/CJN.18101120Wed, 10 Mar 2021 08:09:01 GMT-08:00Deceased-Donor Acute Kidney Injury and BK Polyomavirus in Kidney Transplant RecipientsHall, Isaac E.Reese, Peter PhilipMansour, Sherry G.Mohan, SumitJia, YaqiThiessen-Philbrook, Heather R.Brennan, Daniel C.Doshi, Mona D.Muthukumar, ThangamaniAkalin, EnverHarhay, Meera NairSchröppel, BerndSingh, PoojaWeng, Francis L.Bromberg, Jonathan S.Parikh, Chirag R.2021-03-10T08:09:01-08:00doi:10.2215/CJN.18101120hwp:resource-id:clinjasn;16/5/765American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, kidney transplantation, acute kidney injuryOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-05-08May 08, 202110.2215/CJN.181011201555-90411555-905X2021-03-10T08:09:01-08:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles165765775
- Novel Therapeutic Options for Cardiovascular Disease with CKD10.2215/CJN.03270321Tue, 27 Apr 2021 09:17:42 GMT-07:00Novel Therapeutic Options for Cardiovascular Disease with CKDZoccali, CarmineMallamaci, Francesca2021-04-27T09:17:42-07:00doi:10.2215/CJN.03270321hwp:resource-id:clinjasn;16/5/682American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, mortality risk, epigenetic modifiers, apabetalone, heart failureEditorialsEditorialseditorial20212021-05-08May 08, 202110.2215/CJN.032703211555-90411555-905X2021-04-27T09:17:42-07:002021-05-08Clinical Journal of the American Society of NephrologyEditorials1655682705684716
- Pharmacist-Led Mobile Health Intervention and Transplant Medication Safety10.2215/CJN.15911020Fri, 30 Apr 2021 11:25:54 GMT-07:00Pharmacist-Led Mobile Health Intervention and Transplant Medication SafetyGonzales, Haley M.Fleming, James N.Gebregziabher, MulugetaPosadas-Salas, Maria AuroraSu, ZeminMcGillicuddy, John W.Taber, David J.2021-04-30T11:25:54-07:00doi:10.2215/CJN.15911020hwp:resource-id:clinjasn;16/5/776American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, hospitalization, drug interactions, pharmacistsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-05-08May 08, 202110.2215/CJN.159110201555-90411555-905X2021-04-30T11:25:54-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1655776679784681
- Moving beyond Sedentarism in CKD10.2215/CJN.03460321Thu, 22 Apr 2021 11:09:17 GMT-07:00Moving beyond Sedentarism in CKDKim, Tae YounRoshanravan, Baback2021-04-22T11:09:17-07:00doi:10.2215/CJN.03460321hwp:resource-id:clinjasn;16/5/674American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysedentarism, chronic kidney disease, physical activity, sedentary behavior, exercise, accelerometer, walking, mobility, physical function, physical performanceEditorialsEditorialseditorial20212021-05-08May 08, 202110.2215/CJN.034603211555-90411555-905X2021-04-22T11:09:17-07:002021-05-08Clinical Journal of the American Society of NephrologyEditorials1655674717676726
- Targeting Sedentary Behavior in CKD10.2215/CJN.12300720Thu, 22 Apr 2021 10:51:28 GMT-07:00Targeting Sedentary Behavior in CKDLyden, KateBoucher, RobertWei, GuoZhou, NaChristensen, JesseChertow, Glenn M.Greene, TomBeddhu, Srinivasan2021-04-22T10:51:28-07:00doi:10.2215/CJN.12300720hwp:resource-id:clinjasn;16/5/717American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysedentary behavior, chronic kidney disease, behavioral interventionOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-05-08May 08, 202110.2215/CJN.123007201555-90411555-905X2021-04-22T10:51:28-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1655717674726676
- Growing Understanding of the Antigenic Basis for Membranous Nephropathy10.2215/CJN.03530321Tue, 13 Apr 2021 09:02:45 GMT-07:00Growing Understanding of the Antigenic Basis for Membranous NephropathyBrglez, VesnaSeitz-Polski, Barbara2021-04-13T09:02:45-07:00doi:10.2215/CJN.03530321hwp:resource-id:clinjasn;16/5/677American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathyEditorialsEditorialseditorial20212021-05-08May 08, 202110.2215/CJN.035303211555-90411555-905X2021-04-13T09:02:45-07:002021-05-08Clinical Journal of the American Society of NephrologyEditorials1655677727678735
- Cognitive Dysfunction and Gait Abnormalities in CKD10.2215/CJN.16091020Tue, 06 Apr 2021 07:54:42 GMT-07:00Cognitive Dysfunction and Gait Abnormalities in CKDKoren, Melanie J.Blumen, Helena M.Ayers, Emmeline I.Verghese, JoeAbramowitz, Matthew K.2021-04-06T07:54:42-07:00doi:10.2215/CJN.16091020hwp:resource-id:clinjasn;16/5/694American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, chronic kidney disease, cognitive dysfunction, gaitOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-05-08May 08, 202110.2215/CJN.160910201555-90411555-905X2021-04-06T07:54:42-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles165694704
- Estimated Loss of Lifetime Employment Duration for Patients Undergoing Maintenance Dialysis in Taiwan10.2215/CJN.13480820Thu, 15 Apr 2021 07:41:26 GMT-07:00Estimated Loss of Lifetime Employment Duration for Patients Undergoing Maintenance Dialysis in TaiwanChang, Yu-TzuWang, FuhmeiHuang, Wen-YenHsiao, HsuanWang, Jung-DerLin, Chang-Ching2021-04-15T07:41:26-07:00doi:10.2215/CJN.13480820hwp:resource-id:clinjasn;16/5/746American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyloss of lifetime employment duration, productivity loss, employment, cost-effectiveness, end-stage kidney disease, dialysis, maintenanceOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-05-08May 08, 202110.2215/CJN.134808201555-90411555-905X2021-04-15T07:41:26-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1655746669756670
- Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement TherapyAmong its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.10.2215/CJN.09670620Wed, 28 Oct 2020 06:51:19 GMT-07:00Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement TherapyAmong its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.Hryciw, NicoleJoannidis, MichaelHiremath, SwapnilCallum, JeannieClark, Edward G.2020-10-28T06:51:19-07:00doi:10.2215/CJN.09670620hwp:resource-id:clinjasn;16/5/820American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, dialysis, hemodialysis, hypotension, albumin, intravenous albumin, kidney replacement therapy, intradialytic hypotension, ultrafiltration, acute kidney injuryReviewsReviewsreview-article20212021-05-08May 08, 202110.2215/CJN.096706201555-90411555-905X2020-10-28T06:51:19-07:002021-05-08Clinical Journal of the American Society of NephrologyReviews165820828
- Neural Epidermal Growth Factor–Like 1 Protein–Positive Membranous Nephropathy in Chinese Patients10.2215/CJN.11860720Tue, 13 Apr 2021 08:27:15 GMT-07:00Neural Epidermal Growth Factor–Like 1 Protein–Positive Membranous Nephropathy in Chinese PatientsWang, GuoqinSun, LijunDong, HongruiWang, YanyanXu, XiaoyiZhao, ZhiruiCheng, WenrongLiu, XuejiaoZhao, XiaoyiGeng, YanqiuBao, SiqinChen, YipuCheng, Hong2021-04-13T08:27:15-07:00doi:10.2215/CJN.11860720hwp:resource-id:clinjasn;16/5/727American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, neural epidermal growth factor-like 1 protein, phospholipaseA2 receptor, thrombospondintype 1 domain-containing7AOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-05-08May 08, 202110.2215/CJN.118607201555-90411555-905X2021-04-13T08:27:15-07:002021-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1655727677735678
- Anti-CD20 mAb-Induced B Cell Apoptosis Generates T Cell Regulation of Experimental Myeloperoxidase ANCA-Associated Vasculitis10.1681/ASN.2020060834Wed, 31 Mar 2021 11:43:04 GMT-07:00Anti-CD20 mAb-Induced B Cell Apoptosis Generates T Cell Regulation of Experimental Myeloperoxidase ANCA-Associated VasculitisGan, Poh-YiDick, JonathanO’Sullivan, Kim M.Oudin, VirginieCao Le, AnneKoo Yuk Cheong, DanielShim, RaymondAlikhan, MalihaKitching, A. RichardOoi, Joshua D.Holdsworth, Stephen R.2021-03-31T11:43:04-07:00doi:10.1681/ASN.2020060834hwp:resource-id:jnephrol;32/5/1071American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, glomerulonephritis, end stage kidney disease, immunosuppression, apoptosisBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20200608341046-66731533-34502021-03-31T11:43:04-07:002021-05-03Journal of the American Society of NephrologyBasic Research32510711083
- Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United States10.1681/ASN.2020081242Fri, 12 Mar 2021 11:18:20 GMT-08:00Association between Longer Travel Distance for Transplant Care and Access to Kidney Transplantation and Graft Survival in the United StatesWhelan, Adrian M.Johansen, Kirsten L.Brar, SandeepMcCulloch, Charles E.Adey, Deborah B.Roll, Garrett R.Grimes, BarbaraKu, Elaine2021-03-12T11:18:20-08:00doi:10.1681/ASN.2020081242hwp:resource-id:jnephrol;32/5/1151American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, health policy, organ allocation, patient preferencesClinical EpidemiologyClinical Epidemiologyresearch-article20212021-05-03May 202110.1681/ASN.20200812421046-66731533-34502021-03-12T11:18:20-08:002021-05-03Journal of the American Society of NephrologyClinical Epidemiology32551151i1161i
- Kidney Transplant Rejection Clusters and Graft Outcomes: Revisiting Banff in the Era of “Big Data”10.1681/ASN.2021030348Tue, 06 Apr 2021 07:32:39 GMT-07:00Kidney Transplant Rejection Clusters and Graft Outcomes: Revisiting Banff in the Era of “Big Data”Vasquez-Rios, GeorgeMenon, Madhav C.2021-04-06T07:32:39-07:00doi:10.1681/ASN.2021030348hwp:resource-id:jnephrol;32/5/1009American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant pathology, clusteringEditorialsEditorialseditorial20212021-05-03May 202110.1681/ASN.20210303481046-66731533-34502021-04-06T07:32:39-07:002021-05-03Journal of the American Society of NephrologyEditorials32551009108410111096
- Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised Clustering10.1681/ASN.2020101418Tue, 09 Mar 2021 07:02:39 GMT-08:00Data-driven Derivation and Validation of Novel Phenotypes for Acute Kidney Transplant Rejection using Semi-supervised ClusteringVaulet, ThibautDivard, GillianThaunat, OlivierLerut, EvelyneSenev, AleksandarAubert, OlivierVan Loon, ElisabetCallemeyn, JasperEmonds, Marie-PauleVan Craenenbroeck, AmaryllisDe Vusser, KatrienSprangers, BenRabeyrin, MaudDubois, ValérieKuypers, DirkDe Vos, MaartenLoupy, AlexandreDe Moor, BartNaesens, Maarten2021-03-09T07:02:39-08:00doi:10.1681/ASN.2020101418hwp:resource-id:jnephrol;32/5/1084American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, kidney biopsy, transplant pathology, transplant outcomes, kidney transplantationBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20201014181046-66731533-34502021-03-09T07:02:39-08:002021-05-03Journal of the American Society of NephrologyBasic Research32559910841009238723881096101123882389
- COVID-19 and Dialysis Patients: Unsolved Problems in Early 202110.1681/ASN.2020121766Fri, 26 Feb 2021 10:17:36 GMT-08:00COVID-19 and Dialysis Patients: Unsolved Problems in Early 2021Kliger, Alan S.Silberzweig, Jeffrey2021-02-26T10:17:36-08:00doi:10.1681/ASN.2020121766hwp:resource-id:jnephrol;32/5/1018American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, COVID-19PerspectivesPerspectivesresearch-article20212021-05-03May 202110.1681/ASN.20201217661046-66731533-34502021-02-26T10:17:36-08:002021-05-03Journal of the American Society of NephrologyPerspectives32510181020
- SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know?10.1681/ASN.2021010023Wed, 24 Mar 2021 07:54:56 GMT-07:00SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know?Heldman, Madeleine R.Limaye, Ajit P.2021-03-24T07:54:56-07:00doi:10.1681/ASN.2021010023hwp:resource-id:jnephrol;32/5/1021American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, virology, organ transplant, COVID-19PerspectivesPerspectivesresearch-article20212021-05-03May 202110.1681/ASN.20210100231046-66731533-34502021-03-24T07:54:56-07:002021-05-03Journal of the American Society of NephrologyPerspectives32510211024
- COVID-19 and AKI: Where Do We Stand?10.1681/ASN.2020121768Fri, 26 Feb 2021 10:17:36 GMT-08:00COVID-19 and AKI: Where Do We Stand?Palevsky, Paul M.2021-02-26T10:17:36-08:00doi:10.1681/ASN.2020121768hwp:resource-id:jnephrol;32/5/1029American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, COVID-19, kidney replacement therapy, SARS-CoV-2ReviewsReviewsreview-article20212021-05-03May 202110.1681/ASN.20201217681046-66731533-34502021-02-26T10:17:36-08:002021-05-03Journal of the American Society of NephrologyReviews32510291032
- Impact of the COVID-19 Pandemic on Nephrology Fellow Training and Well-Being in the United States: A National Survey10.1681/ASN.2020111636Wed, 03 Mar 2021 08:44:12 GMT-08:00Impact of the COVID-19 Pandemic on Nephrology Fellow Training and Well-Being in the United States: A National SurveyPivert, Kurtis A.Boyle, Suzanne M.Halbach, Susan M.Chan, LiliShah, Hitesh H.Waitzman, Joshua S.Mehdi, AliNorouzi, SaynaSozio, Stephen M.2021-03-03T08:44:12-08:00doi:10.1681/ASN.2020111636hwp:resource-id:jnephrol;32/5/1236American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologynephrology training, COVID-19 pandemic, physician burnout, COVID-19Clinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20201116361046-66731533-34502021-03-03T08:44:12-08:002021-05-03Journal of the American Society of NephrologyClinical Research32512361248
- Kinetics of Anti–SARS-CoV-2 IgG Antibodies in Hemodialysis Patients Six Months after Infection10.1681/ASN.2020111618Fri, 26 Feb 2021 10:17:37 GMT-08:00Kinetics of Anti–SARS-CoV-2 IgG Antibodies in Hemodialysis Patients Six Months after InfectionSakhi, HamzaDahmane, DjamalAttias, PhilippeKofman, ThomasBouvier, MagaliLapidus, NathanaelFourati, SlimEl Karoui, Khalil,,Audard, VincentBentaarit, BoutheinaBoueilh, AnnaGallien, SébastienGrimbert, PhilippeHüe, SophieJoher, NizarJouan, NarindraLamriben, LarbiLelièvre, Jean-DanielLepeule, RaphaëlMahévas, MatthieuMatignon, MarieMelica, GiovannaOniszczuk, JuliePawlotsky, Jean-MichelStehlé, ThomasVindrios, WilliamWemmert, Charlotte2021-02-26T10:17:37-08:00doi:10.1681/ASN.2020111618hwp:resource-id:jnephrol;32/5/1033American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, SARS-CoV-2, serology, SARS-CoV-2 antibody, COVID-19Rapid CommunicationRapid Communicationresearch-article20212021-05-03May 202110.1681/ASN.20201116181046-66731533-34502021-02-26T10:17:37-08:002021-05-03Journal of the American Society of NephrologyRapid Communication32551033i1036i
- IgM Autoantibodies to Complement Factor H in Atypical Hemolytic Uremic Syndrome10.1681/ASN.2020081224Fri, 12 Mar 2021 11:18:20 GMT-08:00IgM Autoantibodies to Complement Factor H in Atypical Hemolytic Uremic SyndromeCugno, MassimoBerra, SilviaDepetri, FedericaTedeschi, SilvanaGriffini, SamanthaGrovetti, ElenaCaccia, SoniaCresseri, DonataMessa, PiergiorgioTesta, SaraGiglio, FabioPeyvandi, FloraArdissino, Gianluigi2021-03-12T11:18:20-08:00doi:10.1681/ASN.2020081224hwp:resource-id:jnephrol;32/5/1227American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyatypical hemolytic uremic syndrome, thrombotic microangiopathy, transplant associated thrombotic microangiopathy, complement, factor H, IgM, autoantibodiesClinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20200812241046-66731533-34502021-03-12T11:18:20-08:002021-05-03Journal of the American Society of NephrologyClinical Research32512271235
- Deletion of Myeloid Interferon Regulatory Factor 4 (Irf4) in Mouse Model Protects against Kidney Fibrosis after Ischemic Injury by Decreased Macrophage Recruitment and Activation10.1681/ASN.2020071010Mon, 22 Feb 2021 07:24:26 GMT-08:00Deletion of Myeloid Interferon Regulatory Factor 4 (Irf4) in Mouse Model Protects against Kidney Fibrosis after Ischemic Injury by Decreased Macrophage Recruitment and ActivationSasaki, KensukeTerker, Andrew S.Pan, YuLi, ZhilianCao, ShirongWang, YinqiuNiu, AoleiWang, SuwanFan, XiaofengZhang, Ming-ZhiHarris, Raymond C.2021-02-22T07:24:26-08:00doi:10.1681/ASN.2020071010hwp:resource-id:jnephrol;32/5/1037American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, acute renal failure, fibrosis, interstitial fibrosis, ischemia-reperfusion, macrophagesBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20200710101046-66731533-34502021-02-22T07:24:26-08:002021-05-03Journal of the American Society of NephrologyBasic Research3251111103729712972105229722972
- Receptor-Mediated Endocytosis and Differentiation in Proximal Tubule Cell Systems10.1681/ASN.2021020253Mon, 12 Apr 2021 08:29:14 GMT-07:00Receptor-Mediated Endocytosis and Differentiation in Proximal Tubule Cell SystemsBerquez, MarineKrohn, PatrickLuciani, AlessandroDevuyst, Olivier2021-04-12T08:29:14-07:00doi:10.1681/ASN.2021020253hwp:resource-id:jnephrol;32/5/1265American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyendocytosis proximal tubule, proliferation, renal tubular epithelial cellsLetters to the EditorLetters to the Editorletter20212021-05-03May 202110.1681/ASN.20210202531046-66731533-34502021-04-12T08:29:14-07:002021-05-03Journal of the American Society of NephrologyLetters to the Editor3251126586126797
- Urinary Vesicles: Are They Ready for Real-World Use?10.1681/ASN.2021030332Mon, 29 Mar 2021 10:41:45 GMT-07:00Urinary Vesicles: Are They Ready for Real-World Use?Hunter, Robert W.Dear, James W.2021-03-29T10:41:45-07:00doi:10.1681/ASN.2021030332hwp:resource-id:jnephrol;32/5/1013American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrologyEditorialsEditorialseditorial20212021-05-03May 202110.1681/ASN.20210303321046-66731533-34502021-03-29T10:41:45-07:002021-05-03Journal of the American Society of NephrologyEditorials32551013121010151226
- Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits10.1681/ASN.2020101541Mon, 08 Mar 2021 12:11:24 GMT-08:00Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin DepositsZand, LadanRajkumar, S. VincentLeung, NelsonSethi, SanjeevEl Ters, MireilleFervenza, Fernando C.2021-03-08T12:11:24-08:00doi:10.1681/ASN.2020101541hwp:resource-id:jnephrol;32/5/1163American Society of NephrologyCopyright © 2021 by the American Society of Nephrology This is an Open Access article: American Society of NephrologyJournal of the American Society of Nephrologyproliferative, glomerulonephritis, monoclonal, daratumumabClinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20201015411046-66731533-34502021-03-08T12:11:24-08:002021-05-03Journal of the American Society of NephrologyClinical Research32511631173
- BP in Young Adults with CKD and Associations with Cardiovascular Events and Decline in Kidney Function10.1681/ASN.2020081156Wed, 10 Mar 2021 05:57:48 GMT-08:00BP in Young Adults with CKD and Associations with Cardiovascular Events and Decline in Kidney FunctionKula, Alexander J.Prince, David K.Flynn, Joseph T.Bansal, Nisha2021-03-10T05:57:48-08:00doi:10.1681/ASN.2020081156hwp:resource-id:jnephrol;32/5/1200American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, chronic kidney disease, cardiovascular disease, outcomesClinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20200811561046-66731533-34502021-03-10T05:57:48-08:002021-05-03Journal of the American Society of NephrologyClinical Research32512001209
- Authors’ Reply10.1681/ASN.2021020207Wed, 28 Apr 2021 06:20:44 GMT-07:00Authors’ ReplyReese, Peter. P.Aubert, OlivierLoupy, Alexandre2021-04-28T06:20:44-07:00doi:10.1681/ASN.2021020207hwp:resource-id:jnephrol;32/5/1264American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyepidemiology and outcomes, kidney transplantation, kidney biopsyLetters to the EditorLetters to the Editorletter20212021-05-03May 202110.1681/ASN.20210202071046-66731533-34502021-04-28T06:20:44-07:002021-05-03Journal of the American Society of NephrologyLetters to the Editor325521264126339712651264409
- Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD10.1681/ASN.2020071077Mon, 08 Mar 2021 12:11:24 GMT-08:00Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKDRamspek, Chava L.Evans, MarieWanner, ChristophDrechsler, ChristianeChesnaye, Nicholas C.Szymczak, MaciejKrajewska, MagdalenaTorino, ClaudiaPorto, GaetanaHayward, SamanthaCaskey, FergusDekker, Friedo W.Jager, Kitty J.van Diepen, Merel,,Cupisti, AdamascoSagliocca, AdeliaFerraro, AlbertoMusiała, AleksandraMele, AlessandraNaticchia, AlessandroCòsaro, AlexWoodman, AlistairRanghino, AndreaStucchi, AndreaJonsson, AndreasSchneider, AndreasPignataro, AngeloSchrander, AnitaTorp, AnkeMcKeever, AnnaSzymczak, AnnaBlom, Anna-LenaDe Blasio, AntonellaPani, AntonelloTsalouichos, ArisUllah, AsadMcLaren, Barbaravan Dam, BastiaanIwig, BeateAntonio, BellasiDi Iorio, Biagio RaffaeleRogland, BjörnPerras, BorisAlessandra, ButtiHarron, CamilleWallquist, CarinSiegert, CarlBarrett, CarlaGaillard, CarloGarofalo, CarloAbaterusso, CataldoBeerenhout, CharlesO’Toole, CharlotteSomma, ChiaraMarx, ChristianSummersgill, ChristinaBlaser, ChristofD’alessandro, ClaudiaEmde, ClaudiaZullo, ClaudiaPozzi, ClaudioGeddes, ColinVerburgh, CornelisBergamo, DanielaCiurlino, DanieleMotta, DariaGlowski, DeborahMcGlynn, DeborahVargas, DenesKrieter, DetlefRusso, DomenicoFuchs, DunjaSands, DympnaHoogeveen, EllenIrmler, EllenDimény, EmökeFavaro, EnricoPlaten, EvaOlczyk, EwelinaHoorn, EwoutVigotti, FedericaAnsali, FerruccioConte, FerruccioCianciotta, FrancescaGiacchino, FrancescaCappellaio, FrancescoPizzarelli, FrancescoSundelin, FredrikUhlin, FredrikGreco, GaetanoRoy, GeenaPorto, GaetanaBigatti, GiadaMarinangeli, GiancarloCabiddu, GianfrancaHirst, GillianFumagalli, GiordanoCaloro, GiorgiaPiccoli, GiorginaCapasso, GiovanbattistaGambaro, GiovanniTognarelli, GiulianaBonforte, GiuseppeConte, GiuseppeToscano, GiuseppeDel Rosso, GoffredoWelander, GunillaAugustyniak-Bartosik, HannaBoots, HansSchmidt-Gürtler, HansKing, HayleyMcNally, HelenSchlee, HendrikBoom, HenkNaujoks, HolgerMasri-Senghor, HoudaMurtagh, HughRayner, HughMiśkowiec-Wiśniewska, IlonaSchlee, InesCapizzi, IreneBascaran Hernandez, IsabelBaragetti, IvanoManitius, JacekTurner, JaneEijgenraam, Jan-WillemKooman, JeroenBeige, JoachimPondel, JoannaWilcox, JoanneBerdeprado, JocelynRöthele, JochenWong, JonathanRotmans, JorisBanda, JoyceMazur, JustynaHahn, KaiJędrzejak, KamilaNowańska, KatarzynaBlouin, KatjaNeumeier, KatrinJones, KirsteenAnding-Rost, KirstenGröntoft, Knut-ChristianOldrizzi, LambertoHaydock, LesleyVogt, LiffertWilkinson, LilyGesualdo, LoretoSchramm, LotharBiancone, LuigiNowak, ŁukaszRaasveld, MaartenDurlik, MagdalenaMagnano, ManuelaVervloet, MarcRicardi, MarcoCarmody, MargaretDi Bari, MariaLaudato, MariaLuisa Sirico, MariaStendahl, MariaSvensson, MariaWeetman, Mariavan Buren, MarjolijnJoinson, MartinFerraresi, MartinaDutton, Maryvan Diepen, MerelMatthews, MichaelProvenzano, MicheleHopf, MonikaMalaguti, MorenoWuttke, NadjaMorgan, NealPalmieri, NicolaFrischmuth, NikolausBleakley, NinaMurrone, PaolaCockwell, PaulLeurs, PaulRoderick, PaulVoskamp, PaulineKashioulis, PavlosIchtiaris, PawlosBlankestijn, PeterKirste, PetraSchulz, PetraMason, PhilKalra, PhilipCirillo, PietroDattolo, PietroAcampora, PinaSajith, RincyNigro, RitaBoero, RobertoScarpioni, RobertoSicoli, RosaMalandra, RosellaAign, SabineCäsar, Sabinevan Esch, SadieChapman, SallyBiribauer, SandraNavjee, SanteeCrosbie, SarahBrown, SharonTickle, SheilaManan, SherinRöser, SilkeSavoldi, SilvanaBertoli, SilvioBorrelli, SilvioBoorsma, SiskaHeidenreich, StefanMelander, StefanMaxia, StefaniaMaffei, StefanoMangano, StefanoPalm, StephanieKonings, StijnMathavakkannan, SureshSchwedler, SusanneDelrieux, SylkeRenker, SylviaSchättel, SylviaDorota, SzyszkowskaCicchetti, TeresaNieszporek, TeresaStephan, TheresaSchmiedeke, ThomasWeinreich, ThomasLeimbach, TilRappa, TizianaAlmquist, ToraStövesand, TorstenBahner, UdoJensen, UlrikaPalazzo, ValentinaDe Simone, WalterSeeger, WolfgangKuan, YingHeleniak, ZbigniewAydin, Zeynep2021-03-08T12:11:24-08:00doi:10.1681/ASN.2020071077hwp:resource-id:jnephrol;32/5/1174American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyprediction, kidney failure, epidemiology and outcomes, chronic kidney disease, progression of chronic renal failure, prognosis, external validationClinical EpidemiologyClinical Epidemiologyresearch-article20212021-05-03May 202110.1681/ASN.20200710771046-66731533-34502021-03-08T12:11:24-08:002021-05-03Journal of the American Society of NephrologyClinical Epidemiology32511741186
- Obituary for Robert Schrier10.1681/ASN.2021020239Mon, 29 Mar 2021 09:51:41 GMT-07:00Obituary for Robert SchrierBerl, Tomas2021-03-29T09:51:41-07:00doi:10.1681/ASN.2021020239hwp:resource-id:jnephrol;32/5/1016American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyobituary, Schrier, JASNObituaryObituaryother20212021-05-03May 202110.1681/ASN.20210202391046-66731533-34502021-03-29T09:51:41-07:002021-05-03Journal of the American Society of NephrologyObituary32510161017
- The Urine Anion Gap: Common MisconceptionsTwo papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH4) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH4. This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (i.e., UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH4 excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH4, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.10.1681/ASN.2020101509Fri, 05 Mar 2021 05:55:20 GMT-08:00The Urine Anion Gap: Common MisconceptionsTwo papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH4) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH4. This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (i.e., UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH4 excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH4, when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.Uribarri, JaimeOh, Man S.2021-03-05T05:55:20-08:00doi:10.1681/ASN.2020101509hwp:resource-id:jnephrol;32/5/1025American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis, chronic metabolic acidosis, electrolytes, mineral metabolism, renal tubular acidosisReviewsReviewsreview-article20212021-05-03May 202110.1681/ASN.20201015091046-66731533-34502021-03-05T05:55:20-08:002021-05-03Journal of the American Society of NephrologyReviews32510251028
- Procurement Biopsy Data Quality Limits Comparability of United States and French Deceased Donor Kidney Biopsies10.1681/ASN.2020121788Wed, 28 Apr 2021 06:37:50 GMT-07:00Procurement Biopsy Data Quality Limits Comparability of United States and French Deceased Donor Kidney BiopsiesHusain, S. AliMohan, Sumit2021-04-28T06:37:50-07:00doi:10.1681/ASN.2020121788hwp:resource-id:jnephrol;32/5/1263American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, cadaver organ transplantationLetters to the EditorLetters to the Editorletter20212021-05-03May 202110.1681/ASN.20201217881046-66731533-34502021-04-28T06:37:50-07:002021-05-03Journal of the American Society of NephrologyLetters to the Editor325521263126439712641265409
- Renal Inflammation Induces Salt Sensitivity in Male db/db Mice through Dysregulation of ENaC10.1681/ASN.2020081112Wed, 17 Mar 2021 08:36:21 GMT-07:00Renal Inflammation Induces Salt Sensitivity in Male db/db Mice through Dysregulation of ENaCVeiras, Luciana C.Shen, Justin Z. Y.Bernstein, Ellen A.Regis, Giovanna C.Cao, DuoYaoOkwan-Duodu, DerickKhan, ZakirGibb, David R.Dominici, Fernando P.Bernstein, Kenneth E.Giani, Jorge F.2021-03-17T08:36:21-07:00doi:10.1681/ASN.2020081112hwp:resource-id:jnephrol;32/5/1131American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysex differences, diabetes, obesity, hypertension, renin angiotensin system, inflammation, interleukin-6, sodium transportersBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20200811121046-66731533-34502021-03-17T08:36:21-07:002021-05-03Journal of the American Society of NephrologyBasic Research32511311149
- Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension10.1681/ASN.2020101486Wed, 24 Feb 2021 06:58:01 GMT-08:00Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and HypertensionHaruhara, KotaroSasaki, Takayade Zoysa, NatashaOkabayashi, YusukeKanzaki, GoYamamoto, IzumiHarper, Ian S.Puelles, Victor G.Shimizu, AkiraCullen-McEwen, Luise A.Tsuboi, NobuoYokoo, TakashiBertram, John F.2021-02-24T06:58:01-08:00doi:10.1681/ASN.2020101486hwp:resource-id:jnephrol;32/5/1187American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte number, Japanese, nephron number, living kidney donor, agingClinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20201014861046-66731533-34502021-02-24T06:58:01-08:002021-05-03Journal of the American Society of NephrologyClinical Research32511871199
- Crumbs2 Is an Essential Slit Diaphragm Protein of the Renal Filtration Barrier10.1681/ASN.2020040501Tue, 09 Mar 2021 07:02:39 GMT-08:00Crumbs2 Is an Essential Slit Diaphragm Protein of the Renal Filtration BarrierMöller-Kerutt, AnnikaRodriguez-Gatica, Juan E.Wacker, KarinBhatia, RohanSiebrasse, Jan-PeterBoon, NandaVan Marck, VeerleBoor, PeterKubitscheck, UlrichWijnholds, JanPavenstädt, HermannWeide, Thomas2021-03-09T07:02:39-08:00doi:10.1681/ASN.2020040501hwp:resource-id:jnephrol;32/5/1053American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, podocyte, proteinuria, Crumbs2, slit diaphragm, ER stress, Crb2, CRB2, glomerular filtration barrierBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20200405011046-66731533-34502021-03-09T07:02:39-08:002021-05-03Journal of the American Society of NephrologyBasic Research32551053i1070i
- The Rhesus Macaque Serves As a Model for Human Lateral Branch Nephrogenesis10.1681/ASN.2020101459Wed, 31 Mar 2021 11:43:03 GMT-07:00The Rhesus Macaque Serves As a Model for Human Lateral Branch NephrogenesisSchuh, Meredith P.Alkhudairy, LyanPotter, AndrewPotter, S. StevenChetal, KashishThakkar, KairaveeSalomonis, NathanKopan, Raphael2021-03-31T11:43:03-07:00doi:10.1681/ASN.2020101459hwp:resource-id:jnephrol;32/5/1097American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyprematurity, chronic kidney disease, nephrogenesis, lateral branch nephrogenesisBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20201014591046-66731533-34502021-03-31T11:43:03-07:002021-05-03Journal of the American Society of NephrologyBasic Research32551097101111121013
- Comparing Approaches to Normalize, Quantify, and Characterize Urinary Extracellular Vesicles10.1681/ASN.2020081142Mon, 29 Mar 2021 10:58:37 GMT-07:00Comparing Approaches to Normalize, Quantify, and Characterize Urinary Extracellular VesiclesBlijdorp, Charles J.Tutakhel, Omar A. Z.Hartjes, Thomas A.van den Bosch, Thierry P. P.van Heugten, Martijn H.Rigalli, Juan PabloWillemsen, RobMusterd-Bhaggoe, Usha M.Barros, Eric R.Carles-Fontana, RogerCarvajal, Cristian A.Arntz, Onno J.van de Loo, Fons A. J.Jenster, GuidoClahsen-van Groningen, Marian C.Cuevas, Cathy A.Severs, DavidFenton, Robert A.van Royen, Martin E.Hoenderop, Joost G. J.Bindels, René J. M.Hoorn, Ewout J.2021-03-29T10:58:37-07:00doi:10.1681/ASN.2020081142hwp:resource-id:jnephrol;32/5/1210American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycreatinine, osmolality, exosomes, urinary extracellular vesicles, biomarker, uromodulin, particles, aquaporin-2, tetraspanin, normalizationClinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20200811421046-66731533-34502021-03-29T10:58:37-07:002021-05-03Journal of the American Society of NephrologyClinical Research325551210i10131226i1015
- Monkeying about with Nephron Formation10.1681/ASN.2021030320Wed, 07 Apr 2021 11:05:56 GMT-07:00Monkeying about with Nephron FormationSmyth, Ian M.2021-04-07T11:05:56-07:00doi:10.1681/ASN.2021030320hwp:resource-id:jnephrol;32/5/1011American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, nephronEditorialsEditorialseditorial20212021-05-03May 202110.1681/ASN.20210303201046-66731533-34502021-04-07T11:05:56-07:002021-05-03Journal of the American Society of NephrologyEditorials325551011i10971013i1112
- Protocadherin 7–Associated Membranous Nephropathy10.1681/ASN.2020081165Thu, 08 Apr 2021 08:07:41 GMT-07:00Protocadherin 7–Associated Membranous NephropathySethi, SanjeevMadden, BenjaminDebiec, HannaMorelle, JohannCharlesworth, M. CristineGross, LouAnnNegron, VivianBuob, DavidChaudhry, SidharthJadoul, MichelFervenza, Fernando C.Ronco, Pierre2021-04-08T08:07:41-07:00doi:10.1681/ASN.2020081165hwp:resource-id:jnephrol;32/5/1249American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, renal biopsy, renal pathology, glomerular disease, immunology and pathology, nephrotic syndromeClinical ResearchClinical Researchresearch-article20212021-05-03May 202110.1681/ASN.20200811651046-66731533-34502021-04-08T08:07:41-07:002021-05-03Journal of the American Society of NephrologyClinical Research32551249i1261i
- This Month's Highlights10.1681/ASN.2021030385Sat, 01 May 2021 06:48:23 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2021-05-01T06:48:23-07:00doi:10.1681/ASN.2021030385hwp:resource-id:jnephrol;32/5/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsarticle-commentary20212021-05-03May 202110.1681/ASN.20210303851046-66731533-34502021-05-01T06:48:23-07:002021-05-03Journal of the American Society of NephrologyThis Month's Highlights325555555i103310531210101111511249i103610701226101311611261
- Protective Role of the M-Sec–Tunneling Nanotube System in Podocytes10.1681/ASN.2020071076Mon, 15 Mar 2021 11:23:42 GMT-07:00Protective Role of the M-Sec–Tunneling Nanotube System in PodocytesBarutta, FedericaKimura, ShunsukeHase, KojiBellini, StefaniaCorbetta, BeatriceCorbelli, AlessandroFiordaliso, FabioBarreca, AntonellaPapotti, Mauro GiulioGhiggeri, Gian MarcoSalvidio, GennaroRoccatello, DarioAudrito, ValentinaDeaglio, SilviaGambino, RobertoBruno, StefaniaCamussi, GiovanniMartini, MiriamHirsch, EmilioDurazzo, MarilenaOhno, HiroshiGruden, Gabriella2021-03-15T11:23:42-07:00doi:10.1681/ASN.2020071076hwp:resource-id:jnephrol;32/5/1114American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, mitochondria, M-Sec, podocytes, tunneling nanotubesBasic ResearchBasic Researchresearch-article20212021-05-03May 202110.1681/ASN.20200710761046-66731533-34502021-03-15T11:23:42-07:002021-05-03Journal of the American Society of NephrologyBasic Research32511141130
- Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including Glucose-Lowering Drugs and Diuretics10.34067/KID.0000412021Mon, 01 Feb 2021 12:07:36 GMT-08:00Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including Glucose-Lowering Drugs and DiureticsLam, DavidShaikh, Aisha2021-02-01T12:07:36-08:00doi:10.34067/KID.0000412021hwp:resource-id:kidney360;2/4/742American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, diabetic kidney disease, diuretics, glucose, pharmaceutical preparations, SGLT2i, sodium-glucose transporter 2 inhibitorsPerspectivesPerspectivesresearch-article20212021-04-2910.34067/KID.00004120212641-76502021-02-01T12:07:36-08:002021-04-29Kidney360Perspectives24742746
- Lower Urinary Tract Symptoms Should Be Queried When Initiating Sodium Glucose Co-Transporter 2 Inhibitors10.34067/KID.0000472021Wed, 03 Feb 2021 09:27:12 GMT-08:00Lower Urinary Tract Symptoms Should Be Queried When Initiating Sodium Glucose Co-Transporter 2 InhibitorsKrepostman, NicolasKramer, Holly2021-02-03T09:27:12-08:00doi:10.34067/KID.0000472021hwp:resource-id:kidney360;2/4/751American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, adverse effects, aging, diabetes, diuresis, lower urinary tract symptoms, nocturia, SGLT2 inhibitors, thirst, urine outputPerspectivesPerspectivesresearch-article20212021-04-2910.34067/KID.00004720212641-76502021-02-03T09:27:12-08:002021-04-29Kidney360Perspectives24751754
- Dialysis Care around the World: A Global Perspectives Series10.34067/KID.0001082021Fri, 26 Feb 2021 12:04:31 GMT-08:00Dialysis Care around the World: A Global Perspectives SeriesLee, TimmyFlythe, Jennifer E.Allon, Michael2021-02-26T12:04:31-08:00doi:10.34067/KID.0001082021hwp:resource-id:kidney360;2/4/604American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, dialysis financing, hemodialysis, peritoneal dialysis, vascular accessEditorialsEditorialseditorial20212021-04-2910.34067/KID.00010820212641-76502021-02-26T12:04:31-08:002021-04-29Kidney360Editorials24604607
- Opportunities To Improve Diabetes Care in the Hemodialysis Unit: A Cohort Study in Ontario, Canada10.34067/KID.0007082020Fri, 19 Feb 2021 10:37:14 GMT-08:00Opportunities To Improve Diabetes Care in the Hemodialysis Unit: A Cohort Study in Ontario, CanadaClemens, Kristin K.Ouédraogo, Alexandra M.Garg, Amit X.Silver, Samuel A.Nash, Danielle M.2021-02-19T10:37:14-08:00doi:10.34067/KID.0007082020hwp:resource-id:kidney360;2/4/653American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, chronic hemodialysis, cohort studies, diabetes mellitus, hemodialysis units, Ontario, quality of careOriginal InvestigationDiabetes and the KidneyOriginal InvestigationDiabetes and the Kidneyresearch-article20212021-04-2910.34067/KID.00070820202641-76502021-02-19T10:37:14-08:002021-04-29Kidney360Original Investigation24653665
- Podocyte Lipotoxicity in CKDCKD represents the ninth most common cause of death in the United States but, despite this large health burden, treatment options for affected patients remain limited. To remedy this, several relevant pathways have been identified that may lead to novel therapeutic options. Among them, altered renal lipid metabolism, first described in 1982, has been recognized as a common pathway in clinical and experimental CKD of both metabolic and nonmetabolic origin. This observation has led many researchers to investigate the cause of this renal parenchyma lipid accumulation and its downstream effect on renal structure and function. Among key cellular components of the kidney parenchyma, podocytes are terminally differentiated cells that cannot be easily replaced when lost. Clinical and experimental evidence supports a role of reduced podocyte number in the progression of CKD. Given the importance of the podocytes in the maintenance of the glomerular filtration barrier and the accumulation of TG and cholesterol-rich lipid droplets in the podocyte and glomerulus in kidney diseases that cause CKD, understanding the upstream cause and downstream consequences of lipid accumulation in podocytes may lead to novel therapeutic opportunities. In this review, we hope to consolidate our understanding of the causes and consequences of dysregulated renal lipid metabolism in CKD development and progression, with a major focus on podocytes.10.34067/KID.0006152020Fri, 26 Feb 2021 09:59:35 GMT-08:00Podocyte Lipotoxicity in CKDCKD represents the ninth most common cause of death in the United States but, despite this large health burden, treatment options for affected patients remain limited. To remedy this, several relevant pathways have been identified that may lead to novel therapeutic options. Among them, altered renal lipid metabolism, first described in 1982, has been recognized as a common pathway in clinical and experimental CKD of both metabolic and nonmetabolic origin. This observation has led many researchers to investigate the cause of this renal parenchyma lipid accumulation and its downstream effect on renal structure and function. Among key cellular components of the kidney parenchyma, podocytes are terminally differentiated cells that cannot be easily replaced when lost. Clinical and experimental evidence supports a role of reduced podocyte number in the progression of CKD. Given the importance of the podocytes in the maintenance of the glomerular filtration barrier and the accumulation of TG and cholesterol-rich lipid droplets in the podocyte and glomerulus in kidney diseases that cause CKD, understanding the upstream cause and downstream consequences of lipid accumulation in podocytes may lead to novel therapeutic opportunities. In this review, we hope to consolidate our understanding of the causes and consequences of dysregulated renal lipid metabolism in CKD development and progression, with a major focus on podocytes.Kim, Jin-JuWilbon, Sydney S.Fornoni, Alessia2021-02-26T09:59:35-08:00doi:10.34067/KID.0006152020hwp:resource-id:kidney360;2/4/755American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, basic science, lipid accumulation, podocyte lipotoxicityBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-04-2910.34067/KID.00061520202641-76502021-02-26T09:59:35-08:002021-04-29Kidney360Basic Science for Clinicians24755762
- Qualitative Research in Nephrology: An Introduction to Methods and Critical Appraisal10.34067/KID.0006302020Mon, 22 Feb 2021 09:50:11 GMT-08:00Qualitative Research in Nephrology: An Introduction to Methods and Critical AppraisalAmir, NoaMcCarthy, Hugh J.Tong, Allison2021-02-22T09:50:11-08:00doi:10.34067/KID.0006302020hwp:resource-id:kidney360;2/4/737American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, chronic renal insufficiency, decision making, patient-centered care, qualitative research, resource allocationClinical Research MethodsClinical Research Methodsother20212021-04-2910.34067/KID.00063020202641-76502021-02-22T09:50:11-08:002021-04-29Kidney360Clinical Research Methods24737741
- COVID-19–associated Nephropathy Includes Tubular Necrosis and Capillary Congestion, with Evidence of SARS-CoV-2 in the Nephron10.34067/KID.0006992020Fri, 12 Feb 2021 09:23:36 GMT-08:00COVID-19–associated Nephropathy Includes Tubular Necrosis and Capillary Congestion, with Evidence of SARS-CoV-2 in the NephronBouquegneau, AntoineErpicum, PaulineGrosch, StéphanieHabran, LionelHougrand, OlivierHuart, JustineKrzesinski, Jean-MarieMisset, BenoîtHayette, Marie-PierreDelvenne, PhilippeBovy, ChristopheKylies, DominikHuber, Tobias B.Puelles, Victor G.Delanaye, PierreJouret, Francois2021-02-12T09:23:36-08:00doi:10.34067/KID.0006992020hwp:resource-id:kidney360;2/4/639American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, histology, immunostaining, in situ hybridization, kidney, SARS-CoV-2Original InvestigationClinical NephrologyOriginal InvestigationClinical Nephrologyresearch-article20212021-04-2910.34067/KID.00069920202641-76502021-02-12T09:23:36-08:002021-04-29Kidney360Original Investigation24639652
- Equity Is Key to Build Back Better after COVID-19: Prioritize Noncommunicable Diseases and Kidney Health10.34067/KID.0006932020Mon, 01 Feb 2021 12:07:36 GMT-08:00Equity Is Key to Build Back Better after COVID-19: Prioritize Noncommunicable Diseases and Kidney HealthLuyckx, Valerie Ann2021-02-01T12:07:36-08:00doi:10.34067/KID.0006932020hwp:resource-id:kidney360;2/4/747American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, build back better, chronic kidney disease, COVID-19, equity, global health, health systems, kidney health, multisectoral action, non-communicable diseases, public health, sustainable development goalsPerspectivesPerspectivesresearch-article20212021-04-2910.34067/KID.00069320202641-76502021-02-01T12:07:36-08:002021-04-29Kidney360Perspectives24747750
- AKI in COVID-19–Associated Multisystem Inflammatory Syndrome in Children (MIS-C)10.34067/KID.0005372020Wed, 03 Feb 2021 09:27:12 GMT-08:00AKI in COVID-19–Associated Multisystem Inflammatory Syndrome in Children (MIS-C)Lipton, MarissaMahajan, RuchiKavanagh, CatherineShen, CarolBatal, IbrahimDogra, SamritiJain, Namrata G.Lin, FangmingUy, Natalie S.2021-02-03T09:27:12-08:00doi:10.34067/KID.0005372020hwp:resource-id:kidney360;2/4/611American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI, child, COVID-19, MIS-C, pediatric multisystem inflammatory disease, pediatric nephrologyOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-04-2910.34067/KID.00053720202641-76502021-02-03T09:27:12-08:002021-04-29Kidney360Original Investigation24611618
- AKI in Hospitalized Patients with COVID-19 and Seasonal Influenza: A Comparative Analysis10.34067/KID.0007322020Fri, 26 Feb 2021 12:04:31 GMT-08:00AKI in Hospitalized Patients with COVID-19 and Seasonal Influenza: A Comparative AnalysisBhasin, BhavnaVeitla, VineetDawson, Aprill Z.Garacci, ZhupingSturgill, DanielOzieh, Mukoso N.Regner, Kevin R.2021-02-26T12:04:31-08:00doi:10.34067/KID.0007322020hwp:resource-id:kidney360;2/4/619American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, COVID-19, influenza, mortality, renal replacement therapyOriginal InvestigationAcute Kidney Injury and ICU NephrologyOriginal InvestigationAcute Kidney Injury and ICU Nephrologyresearch-article20212021-04-2910.34067/KID.00073220202641-76502021-02-26T12:04:31-08:002021-04-29Kidney360Original Investigation24619628
- Electrolyte Changes in Contemporary Hemodialysis: A Secondary Analysis of the Monitoring in Dialysis Study10.34067/KID.0007452020Fri, 19 Feb 2021 06:11:19 GMT-08:00Electrolyte Changes in Contemporary Hemodialysis: A Secondary Analysis of the Monitoring in Dialysis StudyCorrea, SimonScovner, Katherine MikovnaTumlin, James A.Roy-Chaudhury, PrabirKoplan, Bruce A.Costea, Alexandru I.Kher, VijayWilliamson, DonPokhariyal, SaurabhMcClure, Candace K.Mc Causland, Finnian R.Charytan, David M.,,2021-02-19T06:11:19-08:00doi:10.34067/KID.0007452020hwp:resource-id:kidney360;2/4/695American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, albumin, bicarbonate, BUN, calcium, dialysis, electrolyte, magnesium, phosphate, potassium, sodiumOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-04-2910.34067/KID.00074520202641-76502021-02-19T06:11:19-08:002021-04-29Kidney360Original Investigation24695707
- Citric Acid–Containing Dialysate and Survival Rate in the Dialysis Outcomes and Practice Patterns Study10.34067/KID.0006182020Thu, 04 Feb 2021 01:57:27 GMT-08:00Citric Acid–Containing Dialysate and Survival Rate in the Dialysis Outcomes and Practice Patterns StudyUreña-Torres, PabloBieber, BrianGuebre-Egziabher, FitsumOssman, RimJadoul, MichelInaba, MasaakiRobinson, Bruce M.Port, FriedrichJacquelinet, ChristianCombe, Christian2021-02-04T13:57:27-08:00doi:10.34067/KID.0006182020hwp:resource-id:kidney360;2/4/666American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, acetate, acidosis, bicarbonate, chronic kidney disease, citrate, citric acid, dialysis solutions, hemodialysis, renal dialysis, routine diagnostic tests, survival rateOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-04-2910.34067/KID.00061820202641-76502021-02-04T13:57:27-08:002021-04-29Kidney360Original Investigation24666673
- Treatment Updates in Antineutrophil Cytoplasmic Autoantibodies (ANCA) VasculitisANCA vasculitis is a small-vessel vasculitis (SVV) resulting in inflammation of small- and medium-sized blood vessels. Since the initial description of SVV, there have been tremendous advances in our understanding of its pathogenesis. Over the last decade, we have made significant progress in understanding the pathogenesis and improving the treatment and prognosis of patients with ANCA vasculitis. Patient and renal survival has improved, and treatment is moving toward individualizing care, minimizing severe adverse events, and preventing relapse. This review focuses on treatment updates in ANCA vasculitis, duration of therapy, and management of relapses. We also describe the existing treatment protocols used at our institution.10.34067/KID.0007142020Fri, 05 Feb 2021 09:45:50 GMT-08:00Treatment Updates in Antineutrophil Cytoplasmic Autoantibodies (ANCA) VasculitisANCA vasculitis is a small-vessel vasculitis (SVV) resulting in inflammation of small- and medium-sized blood vessels. Since the initial description of SVV, there have been tremendous advances in our understanding of its pathogenesis. Over the last decade, we have made significant progress in understanding the pathogenesis and improving the treatment and prognosis of patients with ANCA vasculitis. Patient and renal survival has improved, and treatment is moving toward individualizing care, minimizing severe adverse events, and preventing relapse. This review focuses on treatment updates in ANCA vasculitis, duration of therapy, and management of relapses. We also describe the existing treatment protocols used at our institution.Jain, KoyalJawa, PankajDerebail, Vimal K.Falk, Ronald J.2021-02-05T09:45:50-08:00doi:10.34067/KID.0007142020hwp:resource-id:kidney360;2/4/763American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, ANCA, anti–neutrophil cytoplasmic autoantibodies, vasculitisReview ArticleReview Articlereview-article20212021-04-2910.34067/KID.00071420202641-76502021-02-05T09:45:50-08:002021-04-29Kidney360Review Article24763770
- Acute Dyspnea in a Young Woman Following Percutaneous Nephrostomy Tube Placement10.34067/KID.0006042020Thu, 29 Apr 2021 08:25:24 GMT-07:00Acute Dyspnea in a Young Woman Following Percutaneous Nephrostomy Tube PlacementKhin, EiMoreno, IttayPathak, Indu2021-04-29T08:25:24-07:00doi:10.34067/KID.0006042020hwp:resource-id:kidney360;2/4/773American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, catheterization, dyspnea, nephrostomy tube, percutaneous nephrostomy, pleural effusion, pyelonephritis, urinothoraxClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-04-2910.34067/KID.00060420202641-76502021-04-29T08:25:24-07:002021-04-29Kidney360Clinical Images in Nephrology and Dialysis24773775
- Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney Allografts10.34067/KID.0000042021Wed, 03 Feb 2021 11:36:20 GMT-08:00Dynamic Response of Donor-Derived Cell-Free DNA Following Treatment of Acute Rejection in Kidney AllograftsWolf-Doty, Theresa K.Mannon, Roslyn B.Poggio, Emilio D.Hinojosa, Randall J.Hiller, DavidBromberg, Jonathan S.Brennan, Daniel C.2021-02-03T11:36:20-08:00doi:10.34067/KID.0000042021hwp:resource-id:kidney360;2/4/729American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, allografts, cell-free nucleic acids, kidney, tissue donorsOriginal InvestigationTransplantationOriginal InvestigationTransplantationresearch-article20212021-04-2910.34067/KID.00000420212641-76502021-02-03T11:36:20-08:002021-04-29Kidney360Original Investigation24729736
- Implementation of an Electronic Catheter Checklist in Outpatient Hemodialysis Facilities: Results of a Pilot Quality Improvement Project10.34067/KID.0006772020Tue, 09 Feb 2021 11:16:43 GMT-08:00Implementation of an Electronic Catheter Checklist in Outpatient Hemodialysis Facilities: Results of a Pilot Quality Improvement ProjectMokrzycki, Michele H.Leigh, Kerry A.Kliger, Alan S.Niyyar, Vandana DuaBren Asp, VirginiaGolestaneh, LadanTaylor, QuinettaNovosad, Shannon A.2021-02-09T11:16:43-08:00doi:10.34067/KID.0006772020hwp:resource-id:kidney360;2/4/684American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, antisepsis, audit tool, bacteremia, catheter, checklist, hemodialysis, infection, outpatients, quality improvement, vascular accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-04-2910.34067/KID.00067720202641-76502021-02-09T11:16:43-08:002021-04-29Kidney360Original Investigation24684694
- Functional Status in CKD: What Measures to Use?10.34067/KID.0001462021Thu, 29 Apr 2021 08:25:24 GMT-07:00Functional Status in CKD: What Measures to Use?Schrauben, Sarah J.Chang, Alex R.2021-04-29T08:25:24-07:00doi:10.34067/KID.0001462021hwp:resource-id:kidney360;2/4/608American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, functional status, Short Physical Performance BatteryEditorialsEditorialseditorial20212021-04-2910.34067/KID.00014620212641-76502021-04-29T08:25:24-07:002021-04-29Kidney360Editorials24608610
- Clinical Spectrum and Renal Outcome of Cryoglobulinemia in Hong Kong10.34067/KID.0007532020Mon, 22 Feb 2021 07:26:47 GMT-08:00Clinical Spectrum and Renal Outcome of Cryoglobulinemia in Hong KongFung, Winston Wing-ShingYip, Terry Cheuk-FungWong, Vincent Wai-SunChow, Kai-MingWong, Grace Lai-HungSzeto, Cheuk-Chun2021-02-22T07:26:47-08:00doi:10.34067/KID.0007532020hwp:resource-id:kidney360;2/4/721American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, cryoglobulinemia, epidemiology and outcomes, glomerulonephritis, Hong Kong, kidney diseaseOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-04-2910.34067/KID.00075320202641-76502021-02-22T07:26:47-08:002021-04-29Kidney360Original Investigation24721728
- Associations of Performance-Based Functional Assessments and Adverse Outcomes in CKD10.34067/KID.0005802020Tue, 19 Jan 2021 12:41:10 GMT-08:00Associations of Performance-Based Functional Assessments and Adverse Outcomes in CKDBelkin, Mitchell D.Doerfler, Rebecca M.Wagner, Lee-AnnZhan, MinFink, Jeffrey C.2021-01-19T12:41:10-08:00doi:10.34067/KID.0005802020hwp:resource-id:kidney360;2/4/629American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, adverse outcomes, CKD, ESKD, functional assessments, IADL, MMSE, SPPBOriginal InvestigationChronic Kidney DiseaseOriginal InvestigationChronic Kidney Diseaseresearch-article20212021-04-2910.34067/KID.00058020202641-76502021-01-19T12:41:10-08:002021-04-29Kidney360Original Investigation24629638
- Targeting Patient and Health System Barriers To Improve Rates of Hemodialysis Initiation with an Arteriovenous Access10.34067/KID.0007812020Fri, 26 Feb 2021 12:04:31 GMT-08:00Targeting Patient and Health System Barriers To Improve Rates of Hemodialysis Initiation with an Arteriovenous AccessFlythe, Jennifer E.Narendra, Julia H.Yule, ChristinaManivannan, SuryaMurphy, ShannonLee, Shoou-Yih D.Strigo, Tara S.Peskoe, SarahPendergast, Jane F.Boulware, L. EbonyGreen, Jamie A.2021-02-26T12:04:31-08:00doi:10.34067/KID.0007812020hwp:resource-id:kidney360;2/4/708American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous access, barriers, hemodialysis, mixed methods, quality improvement, vascular accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-04-2910.34067/KID.00078120202641-76502021-02-26T12:04:31-08:002021-04-29Kidney360Original Investigation24708720
- AKI, Anemia, and Thrombocytopenia in a Patient with Leg and Flank Pain10.34067/KID.0006012020Thu, 29 Apr 2021 08:25:24 GMT-07:00AKI, Anemia, and Thrombocytopenia in a Patient with Leg and Flank PainLara Prado, Jesús IvánPazos Pérez, Fabiola2021-04-29T08:25:24-07:00doi:10.34067/KID.0006012020hwp:resource-id:kidney360;2/4/771American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, anemia, antiphospholipid syndrome, flank pain, leg, leukopenia, renal infarction, thrombocytopeniaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-04-2910.34067/KID.00060120202641-76502021-04-29T08:25:24-07:002021-04-29Kidney360Clinical Images in Nephrology and Dialysis24771772
- Center-Effect of Incident Hemodialysis Vascular Access Use: Analysis of a Bi-national Registry10.34067/KID.0005742020Tue, 09 Feb 2021 11:16:43 GMT-08:00Center-Effect of Incident Hemodialysis Vascular Access Use: Analysis of a Bi-national RegistryNg, SamanthaPascoe, Elaine M.Johnson, David W.Hawley, Carmel M.Polkinghorne, Kevan R.McDonald, StephenClayton, Philip A.Rabindranath, Kannaiyan S.Roberts, Matthew A.Irish, Ashley B.Viecelli, Andrea K.2021-02-09T11:16:43-08:00doi:10.34067/KID.0005742020hwp:resource-id:kidney360;2/4/674American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, arteriovenous access, arteriovenous fistula, center characteristics, center effect, center size, center variation, central venous catheter, hemodialysis, vascular accessOriginal InvestigationDialysisOriginal InvestigationDialysisresearch-article20212021-04-2910.34067/KID.00057420202641-76502021-02-09T11:16:43-08:002021-04-29Kidney360Original Investigation24674683
- Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux10.1681/ASN.2020050681Wed, 17 Feb 2021 08:19:08 GMT-08:00Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral RefluxVerbitsky, MiguelKrithivasan, PriyaBatourina, EkaterinaKhan, AtlasGraham, Sarah E.Marasà, MaddalenaKim, HyunwooLim, Tze Y.Weng, Patricia L.Sánchez-Rodríguez, ElenaMitrotti, AdeleAhram, Dina F.Zanoni, FrancescaFasel, David A.Westland, RikSampson, Matthew G.Zhang, Jun Y.Bodria, MonicaKil, Byum HeeShril, ShirleeGesualdo, LoretoTorri, FabioScolari, FrancescoIzzi, Claudiavan Wijk, Joanna A.E.Saraga, MarijanSantoro, DomenicoConti, GiovanniBarton, David E.Dobson, Mark G.Puri, PremFurth, Susan L.Warady, Bradley A.Pisani, IsabellaFiaccadori, EnricoAllegri, LandinoDegl'Innocenti, Maria LudovicaPiaggio, GiorgioAlam, ShumyleGigante, MaddalenaZaza, GianluigiEsposito, PasqualeLin, FangmingSimões-e-Silva, Ana CristinaBrodkiewicz, AndrzejDrozdz, DorotaZachwieja, KatarzynaMiklaszewska, MonikaSzczepanska, MariaAdamczyk, PiotrTkaczyk, MarcinTomczyk, DariaSikora, PrzemyslawMizerska-Wasiak, MalgorzataKrzemien, GrazynaSzmigielska, AgnieszkaZaniew, MarcinLozanovski, Vladimir J.Gucev, ZoranIonita-Laza, IulianaStanaway, Ian B.Crosslin, David R.Wong, Craig S.Hildebrandt, FriedhelmBarasch, JonathanKenny, Eimear E.Loos, Ruth J.F.Levy, BrynnGhiggeri, Gian MarcoHakonarson, HakonLatos-Bieleńska, AnnaMaterna-Kiryluk, AnnaDarlow, John M.Tasic, VeliborWiller, CristenKiryluk, KrzysztofSanna-Cherchi, SimoneMendelsohn, Cathy L.Gharavi, Ali G.2021-02-17T08:19:08-08:00doi:10.1681/ASN.2020050681hwp:resource-id:jnephrol;32/4/805American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyvesico-ureteral reflux, human genetics, genetics and development, pediatric nephrologyBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20200506811046-66731533-34502021-02-17T08:19:08-08:002021-04Journal of the American Society of NephrologyBasic Research324805820
- mtor Haploinsufficiency Ameliorates Renal Cysts and Cilia Abnormality in Adult Zebrafish tmem67 Mutants10.1681/ASN.2020070991Thu, 11 Feb 2021 11:40:06 GMT-08:00mtor Haploinsufficiency Ameliorates Renal Cysts and Cilia Abnormality in Adult Zebrafish tmem67 MutantsZhu, PingQiu, QiHarris, Peter C.Xu, XiaoleiLin, Xueying2021-02-11T11:40:06-08:00doi:10.1681/ASN.2020070991hwp:resource-id:jnephrol;32/4/822American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygenetics and development, molecular genetics, polycystic kidney disease, optical clearingBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20200709911046-66731533-34502021-02-11T11:40:06-08:002021-04Journal of the American Society of NephrologyBasic Research324822836
- Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study10.1681/ASN.2020060849Tue, 02 Mar 2021 06:36:17 GMT-08:00Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort StudyGreen, Daniel M.Wang, MingjuanKrasin, MatthewSrivastava, DeoKumarOnder, SongulJay, Dennis W.Ness, Kirsten K.Greene, WilliamLanctot, Jennifer Q.Shelton, Kyla C.Zhu, LiangMulrooney, Daniel A.Ehrhardt, Matthew J.Davidoff, Andrew M.Robison, Leslie L.Hudson, Melissa M.2021-03-02T06:36:17-08:00doi:10.1681/ASN.2020060849hwp:resource-id:jnephrol;32/4/983American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypediatric cancer, ifosfamide, cisplatin, carboplatin, amphotericin B, calcineurin inhibitor, hypertension, kidney irradiation, long-term survivorsClinical ResearchClinical Researchresearch-article20212021-04-01April 202110.1681/ASN.20200608491046-66731533-34502021-03-02T06:36:17-08:002021-04Journal of the American Society of NephrologyClinical Research324983993
- Association between Immunoglobulin M and Steroid Resistance in Children with Nephrotic Syndrome: A Retrospective Multicenter Study in Japan10.34067/KID.0004432020Tue, 19 Jan 2021 09:27:56 GMT-08:00Association between Immunoglobulin M and Steroid Resistance in Children with Nephrotic Syndrome: A Retrospective Multicenter Study in JapanUdagawa, TomohiroMatsuyama, YusukeOkutsu, MikaMotoyoshi, YaekoOkada, MariTada, NorimasaKikuchi, ErikoShimoda, MasuhiroKanamori, ToruOmori, TaeTakahashi, MasakiImai, KohsukeEndo, AkifumiFujiwara, TakeoMorio, Tomohiro2021-01-19T09:27:56-08:00doi:10.34067/KID.0004432020hwp:resource-id:kidney360;2/3/487American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, children, idiopathic nephrotic syndrome, logistic regression analysis, multivariate analysis, retrospective study, selectivity index, serum IgM, steroid resistantOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20212021-03-2510.34067/KID.00044320202641-76502021-01-19T09:27:56-08:002021-03-25Kidney360Original Investigations23487493
- Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis10.34067/KID.0005612020Tue, 01 Dec 2020 10:20:45 GMT-08:00Morphologic Analysis of Urinary Podocytes in Focal Segmental GlomerulosclerosisShirai, YokoMiura, KenichiroYokoyama, TakashiHorita, ShigeruNakayama, HidekiSeino, HiroshiAndo, TaroShiratori, AtsutoshiYabuuchi, TomooKaneko, NaotoIshiwa, ShoIshizuka, KiyonobuHara, MasanoriHattori, Motoshi2020-12-01T10:20:45-08:00doi:10.34067/KID.0005612020hwp:resource-id:kidney360;2/3/477American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, focal segmental glomerulosclerosis, hypertrophy, minimal change nephrotic syndrome, mitotic catastrophe, p21, podocyteOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20212021-03-2510.34067/KID.00056120202641-76502020-12-01T10:20:45-08:002021-03-25Kidney360Original Investigations23477486
- Childhood Cancer and the Risk of ESKD10.1681/ASN.2020071002Thu, 12 Nov 2020 10:51:18 GMT-08:00Childhood Cancer and the Risk of ESKDCalderon-Margalit, RonitPleniceanu, OrenTzur, DoritStern-Zimmer, MichalAfek, ArnonErlich, TomerVerhovsky, GuyKeinan-Boker, LitalSkorecki, KarlTwig, GiladVivante, Asaf2020-11-12T10:51:18-08:00doi:10.1681/ASN.2020071002hwp:resource-id:jnephrol;32/2/495American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyESKD, cancer, pediatric nephrologyClinical ResearchClinical Researchresearch-article20212021-02-01February 202110.1681/ASN.20200710021046-66731533-34502020-11-12T10:51:18-08:002021-02Journal of the American Society of NephrologyClinical Research322495501
- Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST Trial10.1681/ASN.2020050645Tue, 15 Dec 2020 09:50:57 GMT-08:00Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized, Controlled IVIST TrialAhlenstiel-Grunow, ThuridLiu, XiaofeiSchild, RaphaelOh, JunTaylan, ChristinaWeber, Lutz T.Staude, HagenVerboom, MurielleSchröder, ChristophSabau, RuxandraGroßhennig, AnikaPape, Lars2020-12-15T09:50:57-08:00doi:10.1681/ASN.2020050645hwp:resource-id:jnephrol;32/2/502American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypediatric kidney transplantation, kidney transplantation, immunosuppression, lymphocytesClinical ResearchClinical Researchresearch-article20212021-02-01February 202110.1681/ASN.20200506451046-66731533-34502020-12-15T09:50:57-08:002021-02Journal of the American Society of NephrologyClinical Research322502516
- Measuring Patient Experience with Home Dialysis in the United States10.2215/CJN.01990221Tue, 30 Mar 2021 07:25:40 GMT-07:00Measuring Patient Experience with Home Dialysis in the United StatesBrady, Brian M.Kurella Tamura, Manjula2021-03-30T07:25:40-07:00doi:10.2215/CJN.01990221hwp:resource-id:clinjasn;16/4/508American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologydialysisEditorialsEditorialseditorial20212021-04-07April 07, 202110.2215/CJN.019902211555-90411555-905X2021-03-30T07:25:40-07:002021-04-07Clinical Journal of the American Society of NephrologyEditorials16444508497588510498598
- Inherited Tubulopathies of the KidneyThe kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology.10.2215/CJN.14481119Wed, 01 Apr 2020 07:10:22 GMT-07:00Inherited Tubulopathies of the KidneyThe kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we focus on genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of genetically defined patients have shaped our understanding of kidney physiology.Downie, Mallory L.Lopez Garcia, Sergio C.Kleta, RobertBockenhauer, Detlef2020-04-01T07:10:22-07:00doi:10.2215/CJN.14481119hwp:resource-id:clinjasn;16/4/620American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney tubule, renal tubular acidosis, Bartter-s syndrome, tubulopathies, nephrogenic diabetes insipidus, magnesium wasting disorders, Water, Kidney Tubules, kidney, Urinary Tract Physiological Phenomena, Emotions, Homeostasis, Sensation, Kidney, Genomics, SeriesGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-04-07April 07, 202110.2215/CJN.144811191555-90411555-905X2020-04-01T07:10:22-07:002021-04-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease164762011006301100
- Patient Experiences with Home Dialysis10.2215/CJN.01570221Tue, 30 Mar 2021 07:25:40 GMT-07:00Patient Experiences with Home DialysisMyers, James2021-03-30T07:25:40-07:00doi:10.2215/CJN.01570221hwp:resource-id:clinjasn;16/4/497American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhome dialysis, criteria, patient experiencePatient VoicePatient Voiceeditorial20212021-04-07April 07, 202110.2215/CJN.015702211555-90411555-905X2021-03-30T07:25:40-07:002021-04-07Clinical Journal of the American Society of NephrologyPatient Voice16444497588508498598510
- Integrating Patient Perspectives into Medical Device Regulatory Decision Making to Advance Innovation in Kidney Disease10.2215/CJN.11510720Wed, 03 Mar 2021 06:28:25 GMT-08:00Integrating Patient Perspectives into Medical Device Regulatory Decision Making to Advance Innovation in Kidney DiseaseTarver, Michelle E.Neuland, Carolyn2021-03-03T06:28:25-08:00doi:10.2215/CJN.11510720hwp:resource-id:clinjasn;16/4/636American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient preference, patient-reported outcomes, patient engagement, Food and Drug Administration, regulatory, end stage kidney disease, decision makingPerspectivesPerspectivesresearch-article20212021-04-07April 07, 202110.2215/CJN.115107201555-90411555-905X2021-03-03T06:28:25-08:002021-04-07Clinical Journal of the American Society of NephrologyPerspectives1644444636634639642645638635641644647
- Incorporating Patient Preferences via Bayesian Decision Analysis10.2215/CJN.12110720Wed, 03 Mar 2021 06:28:26 GMT-08:00Incorporating Patient Preferences via Bayesian Decision AnalysisChaudhuri, Shomesh E.Lo, Andrew W.2021-03-03T06:28:26-08:00doi:10.2215/CJN.12110720hwp:resource-id:clinjasn;16/4/639American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, randomized controlled trials, quality of life, Bayesian decision analysis, patient preferencesPerspectivesPerspectivesresearch-article20212021-04-07April 07, 202110.2215/CJN.121107201555-90411555-905X2021-03-03T06:28:26-08:002021-04-07Clinical Journal of the American Society of NephrologyPerspectives1644444639634636642645641635638644647
- Using Patient Preference Information to Inform Regulatory Decision Making10.2215/CJN.11930720Wed, 03 Mar 2021 06:28:25 GMT-08:00Using Patient Preference Information to Inform Regulatory Decision MakingFlythe, Jennifer E.West, Melissa2021-03-03T06:28:25-08:00doi:10.2215/CJN.11930720hwp:resource-id:clinjasn;16/4/642American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient preference, dialysis, kidney replacement therapy, innovation, decision makingPerspectivesPerspectivesresearch-article20212021-04-07April 07, 202110.2215/CJN.119307201555-90411555-905X2021-03-03T06:28:25-08:002021-04-07Clinical Journal of the American Society of NephrologyPerspectives1644444642634636639645644635638641647
- Legitimization and Incorporation of Patient Preferences10.2215/CJN.11780720Wed, 03 Mar 2021 06:28:26 GMT-08:00Legitimization and Incorporation of Patient PreferencesConway, Paul T.Knight, Richard2021-03-03T06:28:26-08:00doi:10.2215/CJN.11780720hwp:resource-id:clinjasn;16/4/645American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient preference information, patient insights, Kidney Precision Medicine Project, FDA, Kidney Health Initiative, KidneyX, NIH, patient engagement, advancing American kidney healthPerspectivesPerspectivesresearch-article20212021-04-07April 07, 202110.2215/CJN.117807201555-90411555-905X2021-03-03T06:28:26-08:002021-04-07Clinical Journal of the American Society of NephrologyPerspectives1644444645634636639642647635638641644
- Overview of Various Components of the Science of Patient Input10.2215/CJN.11760720Wed, 03 Mar 2021 06:28:25 GMT-08:00Overview of Various Components of the Science of Patient InputSheldon, Murray2021-03-03T06:28:25-08:00doi:10.2215/CJN.11760720hwp:resource-id:clinjasn;16/4/634American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPerspectivesPerspectivesother20212021-04-07April 07, 202110.2215/CJN.117607201555-90411555-905X2021-03-03T06:28:25-08:002021-04-07Clinical Journal of the American Society of NephrologyPerspectives1644444634636639642645635638641644647
- Expression of CD147 and Cyclophilin A in Kidneys of Patients with COVID-1910.2215/CJN.09440620Wed, 02 Dec 2020 01:21:23 GMT-08:00Expression of CD147 and Cyclophilin A in Kidneys of Patients with COVID-19Su, HuaWan, ChengWang, Zhen-DiGao, YongLi, Yun-ChengTang, FangZhu, Hong-YanYi, Li-XiaZhang, Chun2020-12-02T13:21:23-08:00doi:10.2215/CJN.09440620hwp:resource-id:clinjasn;16/4/618American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCell Signaling, COVID-19, acute renal failure, Cyclophilin AResearch LettersResearch Lettersletter20212021-04-07April 07, 202110.2215/CJN.094406201555-90411555-905X2020-12-02T13:21:23-08:002021-04-07Clinical Journal of the American Society of NephrologyResearch Letters164618619
- Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients10.2215/CJN.09130620Tue, 23 Feb 2021 06:21:35 GMT-08:00Proteinuria and Clinical Outcomes in Hospitalized COVID-19 PatientsKarras, AlexandreLivrozet, MarineLazareth, HélèneBenichou, NicolasHulot, Jean-SébastienFayol, AntoineChauvet, SophieJannot, Anne-SophiePenet, Marie-AudeDiehl, Jean-LucGodier, AnneSanchez, OlivierMirault, TristanThervet, EricPallet, NicolasPinot, JérômeClerc, SébastienArlet, Jean-BenoîtGodier, AnneCholley, Bernard2021-02-23T06:21:35-08:00doi:10.2215/CJN.09130620hwp:resource-id:clinjasn;16/4/514American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, COVID-19, proteinuria, proximal tubule, tubular epithelium, prognosisOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-04-07April 07, 202110.2215/CJN.091306201555-90411555-905X2021-02-23T06:21:35-08:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles164514521
- A Longitudinal, 3-Month Serologic Assessment of SARS-CoV-2 Infections in a Belgian Hemodialysis Facility10.2215/CJN.12490720Wed, 18 Nov 2020 05:17:05 GMT-08:00A Longitudinal, 3-Month Serologic Assessment of SARS-CoV-2 Infections in a Belgian Hemodialysis FacilityLabriola, LauraScohy, AnaïsSeghers, FrançoisPerlot, QuentinDe Greef, JulienDesmet, ChristineRomain, CécileMorelle, JohannYombi, Jean-CyrKabamba, BenoîtRodriguez-Villalobos, HectorJadoul, Michel2020-11-18T05:17:05-08:00doi:10.2215/CJN.12490720hwp:resource-id:clinjasn;16/4/613American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, hemodialysis, longitudinal studiesResearch LettersResearch Lettersletter20212021-04-07April 07, 202110.2215/CJN.124907201555-90411555-905X2020-11-18T05:17:05-08:002021-04-07Clinical Journal of the American Society of NephrologyResearch Letters164613614
- SGLT2 Inhibitors in Diabetic Kidney Disease10.2215/CJN.18881220Wed, 03 Feb 2021 11:29:56 GMT-08:00SGLT2 Inhibitors in Diabetic Kidney DiseaseZoungas, Sophiade Boer, Ian H.2021-02-03T11:29:56-08:00doi:10.2215/CJN.18881220hwp:resource-id:clinjasn;16/4/631American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, diabetic kidney disease, sodium-glucose transporter 2 inhibitorsKidney Case Conferences: How I TreatKidney Case Conferences: How I Treatresearch-article20212021-04-07April 07, 202110.2215/CJN.188812201555-90411555-905X2021-02-03T11:29:56-08:002021-04-07Clinical Journal of the American Society of NephrologyKidney Case Conferences: How I Treat164631633
- Effect of Aerobic Exercise on Dialysis-Related Symptoms in Individuals Undergoing Maintenance Hemodialysis10.2215/CJN.15080920Thu, 25 Mar 2021 09:10:35 GMT-07:00Effect of Aerobic Exercise on Dialysis-Related Symptoms in Individuals Undergoing Maintenance HemodialysisHargrove, NicholasEl Tobgy, NadaZhou, OliviaPinder, MarkPlant, BrittanyAskin, NicoleBieber, LauraCollister, DavidWhitlock, ReidTangri, NavdeepBohm, Clara2021-03-25T09:10:35-07:00doi:10.2215/CJN.15080920hwp:resource-id:clinjasn;16/4/560American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyaerobic exercise, hemodialysis, dialysis-related symptoms, fatigue, quality of life, restless legs syndromeOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-04-07April 07, 202110.2215/CJN.150809201555-90411555-905X2021-03-25T09:10:35-07:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1644560505574507
- Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD Patients10.2215/CJN.15020920Thu, 18 Mar 2021 08:22:28 GMT-07:00Digital Applications Targeting Medication Safety in Ambulatory High-Risk CKD PatientsOng, Stephanie W.Jassal, Sarbjit V.Porter, Eveline C.Min, Kyoyoon K.Uddin, AkibCafazzo, Joseph A.Rac, Valeria E.Tomlinson, GeorgeLogan, Alexander G.2021-03-18T08:22:28-07:00doi:10.2215/CJN.15020920hwp:resource-id:clinjasn;16/4/532American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, medication reconciliation, medication discrepancy, digital health, patient engagement, chronic disease management, virtual care, patient-centered careOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-04-07April 07, 202110.2215/CJN.150209201555-90411555-905X2021-03-18T08:22:28-07:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1644532499542501
- Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine ProjectThe Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP. Patients with CKD and AKI and clinicians from the study sites are members of the Community Engagement Committee, with representation on other KPMP committees. They participate in KPMP deliberations to address scientific, clinical, logistic, analytic, ethical, and community engagement issues. The Community Engagement Committee guides KPMP research priorities from perspectives of patients and clinicians. Patients led development of essential study components, including the informed consent process, no-fault harm insurance coverage, the ethics statement, return of results plan, a “Patient Primer” for scientists and the public, and Community Advisory Boards. As members across other KPMP committees, the Community Engagement Committee assures that the science is developed and conducted in a manner relevant to study participants and the clinical community. Patients have guided the KPMP to produce research aligned with their priorities. The Community Engagement Committee partnership has set new benchmarks for patient leadership in precision medicine research.10.2215/CJN.10270620Mon, 30 Nov 2020 05:37:33 GMT-08:00Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine ProjectThe Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP. Patients with CKD and AKI and clinicians from the study sites are members of the Community Engagement Committee, with representation on other KPMP committees. They participate in KPMP deliberations to address scientific, clinical, logistic, analytic, ethical, and community engagement issues. The Community Engagement Committee guides KPMP research priorities from perspectives of patients and clinicians. Patients led development of essential study components, including the informed consent process, no-fault harm insurance coverage, the ethics statement, return of results plan, a “Patient Primer” for scientists and the public, and Community Advisory Boards. As members across other KPMP committees, the Community Engagement Committee assures that the science is developed and conducted in a manner relevant to study participants and the clinical community. Patients have guided the KPMP to produce research aligned with their priorities. The Community Engagement Committee partnership has set new benchmarks for patient leadership in precision medicine research.Tuttle, Katherine R.Knight, RichardAppelbaum, Paul S.Arora, TanimaBansal, ShwetaBebiak, JackBrown, KeithCampbell, CatherineCooperman, LeslieCorona-Villalobos, Celia P.Dighe, Ashveenade Boer, Ian H.Hall, Daniel E.Jefferson, NicholeJolly, StaceyKermani, AsraLee, Simon C.Mehl, KarlaMurugan, RaghavanRoberts, Glenda V.Rosas, Sylvia E.Himmelfarb, JonathanMiller, R. Tyler,,Knight, RichardLecker, StewartStillman, IsaacWaikar, SushrutColona, MiaKibblear, ZoeMcmahon, GearoidWeins, AstridHacohen, NirHoover, PaulAulisio, MarkCooperman, LeslieHerlitz, LealO’Toole, JohnPoggio, EmilioSedor, JohnAppelbaum, PaulBarasch, JonathanBalderes, OliviaBomback, AndrewD’agati, VivetteKiryluk, KrzysztofMehl, KarlaShang, Ning (Sunny)Weng, ChenhuaBarisoni, LauraAlexandrov, TheodoreAshkar, TarekBarwinska, DariaDagher, PierreDunn, KennethEadon, MichaelFerkowicz, MichaelKelly, KatherineSutton, TimothyWinfree, SethMenez, StevenParikh, ChiragRosenberg, AviVillalobos, PamSlack, AlisonRosas, SylviaWilliams, MarkAzeloglu, EvrenHansen, JensHe, Cijang (John)Iyengar, RaviParikh, SamirRovin, BradAnderton, ChrisPasa-Tolic, LjiljanaVelickovic, DusanOliver, George (Holt)Ardayfio, JosephBebiak, JackBrown, KeithCampbell, TaneishaCampbell, CatherineHayashi, LyndaJefferson, NicholeKoewler, RobertRoberts, GlendaSaul, JohnShpigel, AnnaStutzke, Edith ChristineWright, LorendaMiegs, LeslieSealfon, RachelTroyanskaya, OlgaTuttle, KatherineLake, BlueZhang, KunJoanes, MariaLaszik, ZoltanBalis, UlyssesHe, OliverHodgin, JeffreyKretzler, MatthiasMariani, LauraMenon, RajasreeOtto, EdgarSchaub, JenniferSteck, BeckyElder, MicheleHall, DanielKellum, JohnMurugan, RaghavPalevsky, PaulRandhawa, ParmjeetRosengart, MatthewSims-Lucas, SunnyStefanick, MaryTublin, MitchellAlpers, Charlesde Boer, IanFullerton, MaliaHimmelfarb, JonathanMcclelland, RobynMooney, SeanShankland, StuartWilliams, KayleenBlank, KristinaDighe, AshveenaCarson, JonasDowd, FrederickBansal, ShwetaSharma, KumarZhang, GuanshiKermani, AsraLee, SimonMiller, TylerMoe, OrsonPark, HaroldSanchez, FranciscoTorrealba, JoseToto, RobertVazquez, MiguelWang, NancyGaut, JoeJain, SanjayVijayan, AnithaArora, TanimaMoledina, DennisUgochukwu, UgwuowoWilson, Francis Perry2020-11-30T05:37:33-08:00doi:10.2215/CJN.10270620hwp:resource-id:clinjasn;16/4/660American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, kidney, kidney biopsy, kidney disease, renal biopsy, acute kidney injury, diabetic nephropathy, hypertensive nephropathy, Precision MedicineFeaturesFeaturesresearch-article20212021-04-07April 07, 202110.2215/CJN.102706201555-90411555-905X2020-11-30T05:37:33-08:002021-04-07Clinical Journal of the American Society of NephrologyFeatures164660668
- Risk Factors for CKD ProgressionThe Chronic Renal Insufficiency Cohort (CRIC) Study is an ongoing, multicenter, longitudinal study of nearly 5500 adults with CKD in the United States. Over the past 10 years, the CRIC Study has made significant contributions to the understanding of factors associated with CKD progression. This review summarizes findings from longitudinal studies evaluating risk factors associated with CKD progression in the CRIC Study, grouped into the following six thematic categories: (1) sociodemographic and economic (sex, race/ethnicity, and nephrology care); (2) behavioral (healthy lifestyle, diet, and sleep); (3) genetic (apoL1, genome-wide association study, and renin-angiotensin-aldosterone system pathway genes); (4) cardiovascular (atrial fibrillation, hypertension, and vascular stiffness); (5) metabolic (fibroblast growth factor 23 and urinary oxalate); and (6) novel factors (AKI and biomarkers of kidney injury). Additionally, we highlight areas where future research is needed, and opportunities for interdisciplinary collaboration.10.2215/CJN.07830520Wed, 11 Nov 2020 10:21:53 GMT-08:00Risk Factors for CKD ProgressionThe Chronic Renal Insufficiency Cohort (CRIC) Study is an ongoing, multicenter, longitudinal study of nearly 5500 adults with CKD in the United States. Over the past 10 years, the CRIC Study has made significant contributions to the understanding of factors associated with CKD progression. This review summarizes findings from longitudinal studies evaluating risk factors associated with CKD progression in the CRIC Study, grouped into the following six thematic categories: (1) sociodemographic and economic (sex, race/ethnicity, and nephrology care); (2) behavioral (healthy lifestyle, diet, and sleep); (3) genetic (apoL1, genome-wide association study, and renin-angiotensin-aldosterone system pathway genes); (4) cardiovascular (atrial fibrillation, hypertension, and vascular stiffness); (5) metabolic (fibroblast growth factor 23 and urinary oxalate); and (6) novel factors (AKI and biomarkers of kidney injury). Additionally, we highlight areas where future research is needed, and opportunities for interdisciplinary collaboration.Hannan, MaryAnsari, SajidMeza, NatalieAnderson, Amanda H.Srivastava, AnandWaikar, SushrutCharleston, JeanneWeir, Matthew R.Taliercio, JonathanHorwitz, EdwardSaunders, Milda R.Wolfrum, KatherineFeldman, Harold I.Lash, James P.Ricardo, Ana C.,,Appel, Lawrence J.Feldman, Harold I.Go, Alan S.He, JiangLash, James P.Nelson, Robert G.Rahman, MahboobRao, Panduranga S.Shah, Vallabh O.Townsend, Raymond R.Unruh, Mark L.2020-11-11T10:21:53-08:00doi:10.2215/CJN.07830520hwp:resource-id:clinjasn;16/4/648American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrisk factors, chronic kidney disease, progression of chronic renal failureFeaturesFeaturesresearch-article20212021-04-07April 07, 202110.2215/CJN.078305201555-90411555-905X2020-11-11T10:21:53-08:002021-04-07Clinical Journal of the American Society of NephrologyFeatures164648659
- Digital Solutions to Improve Medication Safety in CKD10.2215/CJN.01680221Thu, 18 Mar 2021 08:38:17 GMT-07:00Digital Solutions to Improve Medication Safety in CKDWagner, Lee-AnnFink, Jeffrey C.2021-03-18T08:38:17-07:00doi:10.2215/CJN.01680221hwp:resource-id:clinjasn;16/4/499American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologymHealth patient safety, smartphone, CKD, medication errors, chronic kidney diseaseEditorialsEditorialseditorial20212021-04-07April 07, 202110.2215/CJN.016802211555-90411555-905X2021-03-18T08:38:17-07:002021-04-07Clinical Journal of the American Society of NephrologyEditorials1644499532501542
- Nephronophthisis in Young Adults Phenocopying Thrombotic Microangiopathy and Severe Nephrosclerosis10.2215/CJN.11890720Wed, 02 Dec 2020 10:45:39 GMT-08:00Nephronophthisis in Young Adults Phenocopying Thrombotic Microangiopathy and Severe NephrosclerosisDoreille, AliceRaymond, LaureLebre, Anne-SophieLinster, CharelSaraeva Lamri, RadoslavaKarras, AlexandreKhayat, RatebMichel, Pierre-AntoineBuob, DavidLuque, YosuRafat, CédricMesnard, Laurent2020-12-02T10:45:39-08:00doi:10.2215/CJN.11890720hwp:resource-id:clinjasn;16/4/615American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, clinical hypertension, ciliopathy, whole exome sequencing, hypertension, nephrosclerosisResearch LettersResearch Lettersletter20212021-04-07April 07, 202110.2215/CJN.118907201555-90411555-905X2020-12-02T10:45:39-08:002021-04-07Clinical Journal of the American Society of NephrologyResearch Letters164615617
- Therapeutic Options to Improve Cardiovascular Outcomes with Long-Term Hemodialysis10.2215/CJN.02010221Mon, 29 Mar 2021 01:16:32 GMT-07:00Therapeutic Options to Improve Cardiovascular Outcomes with Long-Term HemodialysisClark-Cutaia, Maya N.Townsend, Raymond R.2021-03-29T13:16:32-07:00doi:10.2215/CJN.02010221hwp:resource-id:clinjasn;16/4/511American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, renal dialysis, randomized controlled trials, cardiovascular, hemodialysisEditorialsEditorialseditorial20212021-04-07April 07, 202110.2215/CJN.020102211555-90411555-905X2021-03-29T13:16:32-07:002021-04-07Clinical Journal of the American Society of NephrologyEditorials1644511575513587
- Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary Hyperparathyroidism10.2215/CJN.16601020Mon, 08 Mar 2021 08:01:13 GMT-08:00Comparative Effects of Etelcalcetide and Maxacalcitol on Serum Calcification Propensity in Secondary HyperparathyroidismShoji, TetsuoNakatani, ShinyaKabata, DaijiroMori, KatsuhitoShintani, AyumiYoshida, HisakoTakahashi, KanaeOta, KeikoFujii, HisakoUeda, ShinichiroNishi, ShinichiNakatani, TatsuyaYoshiyama, MinoruGoto, KiyoshiHamada, TakayoshiImanishi, MasahitoIshimura, EijiKagitani, SosukeKato, YoshikazuKumeda, YasuroMaekawa, KiyoshiMatsumura, TakayasuNagayama, HarumiObi, YasueOhno, YoshiteruSai, YoshinoriSakurai, MayumiSasaki, SatoshiShidara, KaoriShoji, ShigeichiTsujimoto, YoshihiroYamakawa, KenjiroYasuda, HideakiYodoi, ShozoInaba, MasaakiEmoto, Masanori2021-03-08T08:01:13-08:00doi:10.2215/CJN.16601020hwp:resource-id:clinjasn;16/4/599American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular calcification, mineral metabolism, hemodialysis, maxacalcitol, hyperparathyroidism, secondary, calcium receptor, vitamin D, clinical trialOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-04-07Month XX, 202110.2215/CJN.166010201555-90411555-905X2021-03-08T08:01:13-08:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles164599612
- Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis10.2215/CJN.12940820Mon, 29 Mar 2021 01:08:09 GMT-07:00Ramipril and Cardiovascular Outcomes in Patients on Maintenance HemodialysisRuggenenti, PieroPodestà, Manuel AlfredoTrillini, MatiasPerna, AnnalisaPeracchi, TobiaRubis, NadiaVilla, DavideMartinetti, DavideCortinovis, MonicaOndei, PatriziaCondemi, Carmela GiuseppinaGuastoni, Carlo MariaMeterangelis, AgneseGranata, AntonioMambelli, EmanuelePasquali, SoniaGenovesi, SimonettaPieruzzi, FedericoBertoli, Silvio VolmerDel Rosso, GoffredoGarozzo, MaurizioRigotti, AngeloPozzi, ClaudioDavid, SalvatoreDaidone, GiuseppeMingardi, GiulioMosconi, GiovanniGalfré, AndreaRomei Longhena, GiorgioPacitti, AlfonsoPani, AntonelloHidalgo Godoy, JorgeAnders, Hans-JoachimRemuzzi, Giuseppe,,Remuzzi, GiuseppeOndei, PatriziaCondemi, Carmela GiuseppinaRota, StefanoGuastoni, Carlo MariaBellotti, NicolettaNeri, Anna LisaMartina, ValentinaGidaro, BarbaraStasi, AntoniaMeterangelis, AgneseTamburello, SalvatriceRiva, Maria AlessandraCortinovis, EmanuelaGranata, AntonioSalamone, BenedettaMancini, ElenaPersici, ElisaSestigiani, ElenaMambelli, EmanuelePasquali, SoniaBovino, AchiropitaStella, AndreaGenovesi, SimonettaFabbrini, PaoloCasiraghi, ErikaBertoli, Silvio VolmerTedoldi, SilviaBigatti, GiadaDel Rosso, GoffredoMalandra, RosellaSassone, DarioGarozzo, MaurizioBattaglia, Giovanni GiorgioRigotti, AngeloCerretani, DavideBini, StefanoPozzi, ClaudioCorghi, EnzoDavid, SalvatoreCantarelli, ChiaraBlanco, ValentinaDaidone, GiuseppeOttaviano, GianniMingardi, GiulioRota, StefanoLedda, Giovanna FrancaMosconi, GiovanniZambianchi, LorettaBolasco, PiergiorgioGalfrè, AndreaMurtas, StefanoTeatini, UgoLonghena, Giorgio RomeiPacitti, AlfonsoInguaggiato, PaolaPani, AntonelloDessì, GiulianaScolari, FrancescoBove, SergioCozzolino, MarioPedone, MeriFarina, MarcoBarbisoni, FrancescoScanziani, RenzoSantorelli, GennaroSpotti, DonatellaAlibrandi, Maria Teresa SciarroneConte, FerruccioStefani, FrancescaBadalamenti, SalvatoreValentino, RossellaRubis, NadiaCalini, WallyDiadei, OlimpiaVilla, AlessandroVilla, DavideMartinetti, DavideCarminati, SergioGiuliano, Giovanni AntonioPerna, AnnalisaPeraro, FrancescoPeracchi, TobiaRuggenenti, PieroTrillini, MatiasPodestà, Manuel AlfredoBoccardo, PaolaPeracchi, SaraPorrini, EstebanSabadini, EttorePeraro, Francesco2021-03-29T13:08:09-07:00doi:10.2215/CJN.12940820hwp:resource-id:clinjasn;16/4/575American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRamipril, hemodialysis, ACE inhibitors, cardiovascular events, renin angiotensin systemOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-04-07April 07, 202110.2215/CJN.129408201555-90411555-905X2021-03-29T13:08:09-07:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1644575511587513
- The Promise and Challenge of Aerobic Exercise in People Undergoing Long-Term Hemodialysis10.2215/CJN.01960221Thu, 25 Mar 2021 09:25:11 GMT-07:00The Promise and Challenge of Aerobic Exercise in People Undergoing Long-Term HemodialysisJohansen, Kirsten L.2021-03-25T09:25:11-07:00doi:10.2215/CJN.01960221hwp:resource-id:clinjasn;16/4/505American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyexercise, hemodialysisEditorialsEditorialseditorial20212021-04-07April 07, 202110.2215/CJN.019602211555-90411555-905X2021-03-25T09:25:11-07:002021-04-07Clinical Journal of the American Society of NephrologyEditorials1644505560507574
- A New View of Iron Management in Heart Failure10.2215/CJN.01850221Mon, 29 Mar 2021 11:41:21 GMT-07:00A New View of Iron Management in Heart FailureUppal, Nupur N.Fishbane, Steven2021-03-29T11:41:21-07:00doi:10.2215/CJN.01850221hwp:resource-id:clinjasn;16/4/502American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia iron, heart failureEditorialsEditorialseditorial20212021-04-07April 07, 202110.2215/CJN.018502211555-90411555-905X2021-03-29T11:41:21-07:002021-04-07Clinical Journal of the American Society of NephrologyEditorials1644502522504531
- Heart Failure Hospitalization Risk associated with Iron Status in Veterans with CKD10.2215/CJN.15360920Mon, 29 Mar 2021 11:20:57 GMT-07:00Heart Failure Hospitalization Risk associated with Iron Status in Veterans with CKDCho, Monique E.Hansen, Jared L.Sauer, Brian C.Cheung, Alfred K.Agarwal, AdhishGreene, Tom2021-03-29T11:20:57-07:00doi:10.2215/CJN.15360920hwp:resource-id:clinjasn;16/4/522American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyiron, heart failure, veterans, hospitalization, chronic kidney disease, CKDOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-04-07Month XX, 202110.2215/CJN.153609201555-90411555-905X2021-03-29T11:20:57-07:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1644522502531504
- Development and Content Validity of a Patient-Reported Experience Measure for Home Dialysis10.2215/CJN.15570920Tue, 30 Mar 2021 07:25:41 GMT-07:00Development and Content Validity of a Patient-Reported Experience Measure for Home DialysisRivara, Matthew B.Edwards, ToddPatrick, DonaldAnderson, LisaHimmelfarb, JonathanMehrotra, Rajnish2021-03-30T07:25:41-07:00doi:10.2215/CJN.15570920hwp:resource-id:clinjasn;16/4/588American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, peritoneal dialysis, hemodialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-04-07April 07, 202110.2215/CJN.155709201555-90411555-905X2021-03-30T07:25:41-07:002021-04-07Clinical Journal of the American Society of NephrologyOriginal Articles16444588497508598498510
- Comparative Analysis of SARS-CoV-2 Reproduction Rates in the Dialysis and General Populations10.1681/ASN.2020121691Mon, 08 Mar 2021 12:11:25 GMT-08:00Comparative Analysis of SARS-CoV-2 Reproduction Rates in the Dialysis and General PopulationsCherif, AlhajiWilletts, Joanna L.Usvyat, LenWang, YuedongKotanko, Peter2021-03-08T12:11:25-08:00doi:10.1681/ASN.2020121691hwp:resource-id:jnephrol;32/4/791American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, chronic kidney disease, chronic kidney failure, chronic renal disease, chronic renal failure, dialysis, end stage kidney disease, epidemiology and outcomes, hemodialysis, COVID-19Research LettersResearch Lettersletter20212021-04-01April 202110.1681/ASN.20201216911046-66731533-34502021-03-08T12:11:25-08:002021-04Journal of the American Society of NephrologyResearch Letters324791794
- Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 201910.1681/ASN.2020071097Fri, 22 Jan 2021 07:39:08 GMT-08:00Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 2019Teoh, Jeremy Yuen-ChunYip, Terry Cheuk-FungLui, Grace Chung-YanWong, Vincent Wai-SunChow, Viola Chi-YingHo, Tracy Hang-YeeLi, Timothy Chun-ManTse, Yee-KitChiu, Peter Ka-FungNg, Chi-FaiHui, David Shu-CheongChan, Henry Lik-YuenSzeto, Cheuk-ChunWong, Grace Lai-Hung2021-01-22T07:39:08-08:00doi:10.1681/ASN.2020071097hwp:resource-id:jnephrol;32/4/961American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney, kidney disease, kidney dysfunction, renal dysfunction, renal injury, renal function decline, COVID-19Clinical ResearchClinical Researchresearch-article20212021-04-01April 202110.1681/ASN.20200710971046-66731533-34502021-01-22T07:39:08-08:002021-04Journal of the American Society of NephrologyClinical Research324961971
- A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids10.1681/ASN.2020101537Mon, 01 Feb 2021 07:16:13 GMT-08:00A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney OrganoidsWysocki, JanYe, MinghaoHassler, LuiseGupta, Ashwani KumarWang, YuguoNicoleascu, VladRandall, GlennWertheim, Jason A.Batlle, Daniel2021-02-01T07:16:13-08:00doi:10.1681/ASN.2020101537hwp:resource-id:jnephrol;32/4/795American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyACE2, SARS-CoV-2, soluble ACE2 proteins, ACE2 1-618-ABD, COVID-19, organoids, ACE2 decoyRapid CommunicationsRapid Communicationsother20212021-04-01April 202110.1681/ASN.20201015371046-66731533-34502021-02-01T07:16:13-08:002021-04Journal of the American Society of NephrologyRapid Communications324795803
- This Month's Highlights10.1681/ASN.2021020241Wed, 31 Mar 2021 11:00:43 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2021-03-31T11:00:43-07:00doi:10.1681/ASN.2021020241hwp:resource-id:jnephrol;32/4/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20212021-04-01April 202110.1681/ASN.20210202411046-66731533-34502021-03-31T11:00:43-07:002021-04Journal of the American Society of NephrologyThis Month's Highlights324ii
- Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and Glomerulosclerosis10.1681/ASN.2020050652Tue, 23 Feb 2021 10:57:49 GMT-08:00Automated Computational Detection of Interstitial Fibrosis, Tubular Atrophy, and GlomerulosclerosisGinley, BrandonJen, Kuang-YuHan, Seung SeokRodrigues, LuísJain, SanjayFogo, Agnes B.Zuckerman, JonathanWalavalkar, VighneshMiecznikowski, Jeffrey C.Wen, YumengYen, FeliciaYun, DonghwanMoon, Kyung ChulRosenberg, AviParikh, ChiragSarder, Pinaki2021-02-23T10:57:49-08:00doi:10.1681/ASN.2020050652hwp:resource-id:jnephrol;32/4/837American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyinterstitial fibrosis, tubular atrophy, glomerulosclerosis, prognostication, convolutional neural network, whole slide segmentation, diabetes, transplant, eGFR, machine learningBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20200506521046-66731533-34502021-02-23T10:57:49-08:002021-04Journal of the American Society of NephrologyBasic Research3244837767850768
- Automated Quantification of Chronic Changes in the Kidney Biopsy: Another Step in the Right Direction10.1681/ASN.2021020240Mon, 08 Mar 2021 01:34:02 GMT-08:00Automated Quantification of Chronic Changes in the Kidney Biopsy: Another Step in the Right DirectionHodgin, Jeffrey B.Mariani, Laura H.2021-03-08T13:34:02-08:00doi:10.1681/ASN.2021020240hwp:resource-id:jnephrol;32/4/767American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyinterstitial fibrosis, tubular atrophy, glomerulosclerosis convolutional neural networkUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-04-01April 202110.1681/ASN.20210202401046-66731533-34502021-03-08T13:34:02-08:002021-04Journal of the American Society of NephrologyUp Front Matters3244767837768850
- Failure to Advance Access to Kidney Transplantation over Two Decades in the United States10.1681/ASN.2020060888Thu, 11 Feb 2021 11:40:05 GMT-08:00Failure to Advance Access to Kidney Transplantation over Two Decades in the United StatesSchold, Jesse D.Mohan, SumitHuml, AnneBuccini, Laura D.Sedor, John R.Augustine, Joshua J.Poggio, Emilio D.2021-02-11T11:40:05-08:00doi:10.1681/ASN.2020060888hwp:resource-id:jnephrol;32/4/913American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, end-stage renal disease, risk factorsClinical EpidemiologyClinical Epidemiologyresearch-article20212021-04-01April 202110.1681/ASN.20200608881046-66731533-34502021-02-11T11:40:05-08:002021-04Journal of the American Society of NephrologyClinical Epidemiology324913926
- Passage of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act—a Chance to Celebrate and Reflect10.1681/ASN.2020121811Tue, 02 Mar 2021 06:36:18 GMT-08:00Passage of the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act—a Chance to Celebrate and ReflectGill, John S.Formica, Richard N.Murphy, Barbara2021-03-02T06:36:18-08:00doi:10.1681/ASN.2020121811hwp:resource-id:jnephrol;32/4/774American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, immunosuppression, kidney transplantationUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20212021-04-01April 202110.1681/ASN.20201218111046-66731533-34502021-03-02T06:36:18-08:002021-04Journal of the American Society of NephrologyUp Front Matters324677415407761540
- Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection10.1681/ASN.2020060850Wed, 03 Mar 2021 08:44:12 GMT-08:00Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant RejectionEl Fekih, RaniaHurley, JamesTadigotla, VasishtAlghamdi, AreejSrivastava, AnandCoticchia, ChristineChoi, JohnAllos, HazimYatim, KarimAlhaddad, JulianoEskandari, SiawoshChu, PhilipMihali, Albana B.Lape, Isadora T.Lima Filho, Mauricio P.Aoyama, Bruno T.Chandraker, AnilSafa, KassemMarkmann, James F.Riella, Leonardo V.Formica, Richard N.Skog, JohanAzzi, Jamil R.2021-03-03T08:44:12-08:00doi:10.1681/ASN.2020060850hwp:resource-id:jnephrol;32/4/994American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, urine exosome, mRNA, biomarker, rejectionClinical ResearchClinical Researchresearch-article20212021-04-01April 202110.1681/ASN.20200608501046-66731533-34502021-03-03T08:44:12-08:002021-04Journal of the American Society of NephrologyClinical Research3249941004
- The Preventable Productivity Burden of Kidney Disease in Australia10.1681/ASN.2020081148Tue, 09 Mar 2021 08:53:11 GMT-08:00The Preventable Productivity Burden of Kidney Disease in AustraliaSavira, FebyAdemi, ZanfinaWang, Bing H.Kompa, Andrew R.Owen, Alice J.Liew, DannyZomer, Ella2021-03-09T08:53:11-08:00doi:10.1681/ASN.2020081148hwp:resource-id:jnephrol;32/4/938American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, productivity, incidence, dynamic life table model, burdenClinical EpidemiologyClinical Epidemiologyresearch-article20212021-04-01April 202110.1681/ASN.20200811481046-66731533-34502021-03-09T08:53:11-08:002021-04Journal of the American Society of NephrologyClinical Epidemiology3244938771949773
- Cardiovascular Risk Based on ASCVD and KDIGO Categories in Chinese Adults: A Nationwide, Population-Based, Prospective Cohort Study10.1681/ASN.2020060856Thu, 04 Mar 2021 08:51:40 GMT-08:00Cardiovascular Risk Based on ASCVD and KDIGO Categories in Chinese Adults: A Nationwide, Population-Based, Prospective Cohort StudyXu, YuLi, MianQin, GuijunLu, JieliYan, LiXu, MinWang, TiangeZhao, ZhiyunDai, MengZhang, DiWan, QinHuo, YananChen, LuluShi, LixinHu, RuyingTang, XuleiSu, QingYu, XuefengQin, YingfenChen, GangGao, ZhengnanWang, GuixiaShen, FeixiaLuo, ZuojieChen, LiChen, YuhongZhang, YinfeiLiu, ChaoWang, YouminWu, ShengliYang, TaoLi, QiangBi, YufangZhao, JiajunMu, YimingWang, WeiqingNing, Guang,,Ning, GuangMu, YimingZhao, JiajunWang, WeiqingLiu, ChaoBi, YufangLi, DonghuiLai, ShenghanBloomgarden, Zachary T.,Wang, WeiqingBi, YufangLu, JieliLi, MianMu, YimingZhao, JiajunLiu, ChaoChen, LuluShi, LixinLi, QiangYang, TaoYan, LiWan, QinWu, ShengliWang, GuixiaLuo, ZuojieQin, YingfenTang, XuleiChen, GangHuo, YananGao, ZhengnanSu, QingYe, ZhenHu, RuyingWang, YouminQin, GuijunDeng, HuacongYu, XuefengShen, FeixiaChen, Li2021-03-04T08:51:40-08:00doi:10.1681/ASN.2020060856hwp:resource-id:jnephrol;32/4/927American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyestimated glomerular filtration rate, urinary albumin-to-creatinine ratio, atherosclerotic cardiovascular diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20212021-04-01April 202110.1681/ASN.20200608561046-66731533-34502021-03-04T08:51:40-08:002021-04Journal of the American Society of NephrologyClinical Epidemiology324927937
- Laxative Use and Risk of Dyskalemia in Patients with Advanced CKD Transitioning to Dialysis10.1681/ASN.2020081120Fri, 05 Feb 2021 10:53:21 GMT-08:00Laxative Use and Risk of Dyskalemia in Patients with Advanced CKD Transitioning to DialysisSumida, KeiichiDashputre, Ankur A.Potukuchi, Praveen K.Thomas, FridtjofObi, YoshitsuguMolnar, Miklos Z.Gatwood, Justin D.Streja, ElaniKalantar-Zadeh, KamyarKovesdy, Csaba P.2021-02-05T10:53:21-08:00doi:10.1681/ASN.2020081120hwp:resource-id:jnephrol;32/4/950American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, gastrointestinal medications, end-stage renal disease, electrolytes, hypokalemiaClinical EpidemiologyClinical Epidemiologyresearch-article20212021-04-01April 202110.1681/ASN.20200811201046-66731533-34502021-02-05T10:53:21-08:002021-04Journal of the American Society of NephrologyClinical Epidemiology324950959
- NBCn1 Increases NH4+ Reabsorption Across Thick Ascending Limbs, the Capacity for Urinary NH4+ Excretion, and Early Recovery from Metabolic Acidosis10.1681/ASN.2019060613Thu, 07 Jan 2021 09:45:44 GMT-08:00NBCn1 Increases NH4+ Reabsorption Across Thick Ascending Limbs, the Capacity for Urinary NH4+ Excretion, and Early Recovery from Metabolic AcidosisOlsen, Jeppe S. M.Svendsen, SamuelBerg, PederDam, Vibeke S.Sorensen, Mads V.Matchkov, Vladimir V.Leipziger, JensBoedtkjer, Ebbe2021-01-07T09:45:44-08:00doi:10.1681/ASN.2019060613hwp:resource-id:jnephrol;32/4/852American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis, cell & transport physiology, intracellular pH, ion transportBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20190606131046-66731533-34502021-01-07T09:45:44-08:002021-04Journal of the American Society of NephrologyBasic Research324852865
- QALYs, DALYs and Now PALYs: Strengthening the Argument for Prevention of CKD10.1681/ASN.2021020208Tue, 09 Mar 2021 08:40:31 GMT-08:00QALYs, DALYs and Now PALYs: Strengthening the Argument for Prevention of CKDCanney, MarkLevin, Adeera2021-03-09T08:40:31-08:00doi:10.1681/ASN.2021020208hwp:resource-id:jnephrol;32/4/771American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyprevention, CKD, burden, productivity, advocacyUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-04-01April 202110.1681/ASN.20210202081046-66731533-34502021-03-09T08:40:31-08:002021-04Journal of the American Society of NephrologyUp Front Matters3244771938773949
- Authors’ Reply10.1681/ASN.2021010051Mon, 01 Mar 2021 08:44:24 GMT-08:00Authors’ ReplyAkizawa, TadaoIwasaki, ManabuYamaguchi, YusukeMajikawa, YoshikatsuReusch, Michael2021-03-01T08:44:24-08:00doi:10.1681/ASN.2021010051hwp:resource-id:jnephrol;32/4/1005-aAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, hypoxia-inducible factor, erythropoiesis-stimulating agent, randomized controlled trial, hemodialysisLetters to the EditorLetters to the Editorletter20212021-04-01April 202110.1681/ASN.20210100511046-66731533-34502021-03-01T08:44:24-08:002021-04Journal of the American Society of NephrologyLetters to the Editor32474100516281005100716391005
- Me Or Your Own Eyes: RNA-Seq and the Kidney10.1681/ASN.2021010017Thu, 04 Mar 2021 09:17:20 GMT-08:00Me Or Your Own Eyes: RNA-Seq and the KidneyEllison, David H.2021-03-04T09:17:20-08:00doi:10.1681/ASN.2021010017hwp:resource-id:jnephrol;32/4/768American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologytranscriptional profiling, nephronUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-04-01April 202110.1681/ASN.20210100171046-66731533-34502021-03-04T09:17:20-08:002021-04Journal of the American Society of NephrologyUp Front Matters32444768886897771896912
- Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial10.1681/ASN.2020071091Mon, 01 Mar 2021 08:11:46 GMT-08:00Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized TrialScolari, FrancescoDelbarba, ElisaSantoro, DomenicoGesualdo, LoretoPani, AntonelloDallera, NadiaMani, Laila-YasminSantostefano, MarisaFeriozzi, SandroQuaglia, MarcoBoscutti, GiulianoFerrantelli, AngeloMarcantoni, CarmelitaPasserini, PatriziaMagistroni, RiccardoAlberici, FedericoGhiggeri, Gian MarcoPonticelli, ClaudioRavani, Pietro,,Scolari, FrancescoDelbarba, ElisaSantoro, DomenicoGesualdo, LoretoProtopapa, PaoloArgentiero, LuciaPani, AntonelloAngioi, AndreaLepore, NicolaDallera, NadiaMani, Laila-YasminVogts, BrunoSantostefano, MarisaFeriozzi, SandroQuaglia, MarcoBoscutti, GiulianoFerrantelli, AngeloMarcantoni, CarmelitaPasserini, PatriziaMagistroni, RiccardoAlberici, FedericoGhiggeri, Gian MarcoPonticelli, ClaudioRavani, Pietro2021-03-01T08:11:46-08:00doi:10.1681/ASN.2020071091hwp:resource-id:jnephrol;32/4/972American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, glomerulonephritis, nephrotic syndromeClinical ResearchClinical Researchresearch-article20212021-04-01April 202110.1681/ASN.20200710911046-66731533-34502021-03-01T08:11:46-08:002021-04Journal of the American Society of NephrologyClinical Research324972982
- Management of Obesity in Adults with CKDObesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.10.1681/ASN.2020101472Thu, 18 Feb 2021 06:49:58 GMT-08:00Management of Obesity in Adults with CKDObesity is a leading public health problem that currently affects over 650 million individuals worldwide. Although interest in the adverse effects of obesity has grown exponentially in recent years, less attention has been given to studying its management in individuals with CKD. This relatively unexplored area should be considered a high priority because of the rapid growth and high prevalence of obesity in the CKD population, its broad impact on health and outcomes, and its modifiable nature. This article begins to lay the groundwork in this field by providing a comprehensive overview that critically evaluates the available evidence related to obesity and kidney disease, identifies important gaps in our knowledge base, and integrates recent insights in the pathophysiology of obesity to help provide a way forward in establishing guidelines as a basis for managing obesity in CKD. Finally, the article includes a kidney-centric algorithm for management of obesity that can be used in clinical practice.Friedman, Allon N.Kaplan, Lee M.le Roux, Carel W.Schauer, Philip R.2021-02-18T06:49:58-08:00doi:10.1681/ASN.2020101472hwp:resource-id:jnephrol;32/4/777American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, chronic kidney disease, weight loss, kidney transplantation, quality of life, arteriovenous access, diabetes, bariatric surgery, metabolic surgery, GLP-1Up Front MattersReviewUp Front MattersReviewreview-article20212021-04-01April 202110.1681/ASN.20201014721046-66731533-34502021-02-18T06:49:58-08:002021-04Journal of the American Society of NephrologyUp Front Matters324777790
- 1α,25-Dihydroxyvitamin D3 Encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous Fistulas10.1681/ASN.2020060832Wed, 24 Feb 2021 06:58:00 GMT-08:001α,25-Dihydroxyvitamin D3 Encapsulated in Nanoparticles Prevents Venous Neointimal Hyperplasia and Stenosis in Porcine Arteriovenous FistulasSingh, Avishek K.Cai, ChuanqiKilari, SreenivasuluZhao, ChengleiSimeon, Michael L.Takahashi, EdwinEdelman, Elazer R.Kong, Hyunjoon (Joon)Macedo, ThanilaSingh, Ravinder J.Urban, Matthew W.Kumar, RajivMisra, Sanjay2021-02-24T06:58:00-08:00doi:10.1681/ASN.2020060832hwp:resource-id:jnephrol;32/4/866American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, vascular access, shear stress, restenosis, drug deliveryBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20200608321046-66731533-34502021-02-24T06:58:00-08:002021-04Journal of the American Society of NephrologyBasic Research324866885
- Roxadustat for Renal Anemia in ESRD from PKD Patients: Is It Safe Enough?10.1681/ASN.2020111664Mon, 01 Mar 2021 08:58:32 GMT-08:00Roxadustat for Renal Anemia in ESRD from PKD Patients: Is It Safe Enough?Liu, FeiWang, JingjingYe, QingFu, HaidongMao, Jianhua2021-03-01T08:58:32-08:00doi:10.1681/ASN.2020111664hwp:resource-id:jnephrol;32/4/1005American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia chronic kidney disease, polycystic kidney diseaseLetters to the EditorLetters to the Editorletter20212021-04-01April 202110.1681/ASN.20201116641046-66731533-34502021-03-01T08:58:32-08:002021-04Journal of the American Society of NephrologyLetters to the Editor32474100516281005100516391007
- A Comprehensive Map of mRNAs and Their Isoforms across All 14 Renal Tubule Segments of Mouse10.1681/ASN.2020101406Thu, 04 Mar 2021 09:32:56 GMT-08:00A Comprehensive Map of mRNAs and Their Isoforms across All 14 Renal Tubule Segments of MouseChen, LiheChou, Chun-LinKnepper, Mark A.2021-03-04T09:32:56-08:00doi:10.1681/ASN.2020101406hwp:resource-id:jnephrol;32/4/897American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyRNA-seq, alternative splicing, renal tubule, microdissectionBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20201014061046-66731533-34502021-03-04T09:32:56-08:002021-04Journal of the American Society of NephrologyBasic Research32444897768886912771896
- Targeted Single-Cell RNA-seq Identifies Minority Cell Types of Kidney Distal Nephron10.1681/ASN.2020101407Thu, 04 Mar 2021 09:32:57 GMT-08:00Targeted Single-Cell RNA-seq Identifies Minority Cell Types of Kidney Distal NephronChen, LiheChou, Chun-LinKnepper, Mark A.2021-03-04T09:32:57-08:00doi:10.1681/ASN.2020101407hwp:resource-id:jnephrol;32/4/886American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyscRNA-seq, distal convoluted tubule, thick ascending limb, macula densaBasic ResearchBasic Researchresearch-article20212021-04-01April 202110.1681/ASN.20201014071046-66731533-34502021-03-04T09:32:57-08:002021-04Journal of the American Society of NephrologyBasic Research32444886768897896771912
- A Call to Action for Addressing Disparities and Increasing Diversity in Academic Nephrology10.34067/KID.0006532020Wed, 27 Jan 2021 01:35:26 GMT-08:00A Call to Action for Addressing Disparities and Increasing Diversity in Academic NephrologyLyas, Claretha2021-01-27T13:35:26-08:00doi:10.34067/KID.0006532020hwp:resource-id:kidney360;2/3/532American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, academic, diversity, nephrologyPerspectivePerspectiveresearch-article20212021-03-2510.34067/KID.00065320202641-76502021-01-27T13:35:26-08:002021-03-25Kidney360Perspective23532533
- A Comparison Study of Coronavirus Disease 2019 Outcomes in Hospitalized Kidney Transplant Recipients10.34067/KID.0005652020Tue, 12 Jan 2021 08:06:07 GMT-08:00A Comparison Study of Coronavirus Disease 2019 Outcomes in Hospitalized Kidney Transplant RecipientsMansour, Sherry G.Malhotra, DivyanshuSimonov, MichaelYamamoto, YuArora, TanimaSubair, LabeebahAlausa, JameelMoledina, Dennis G.Greenberg, Jason H.Wilson, Francis PerryMarin, Ethan P.2021-01-12T08:06:07-08:00doi:10.34067/KID.0005652020hwp:resource-id:kidney360;2/3/494American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, causality, COVID-19, inpatient outcomes, kidney transplantationOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20212021-03-2510.34067/KID.00056520202641-76502021-01-12T08:06:07-08:002021-03-25Kidney360Original Investigations23494506
- Machine Learning for Prediction of Patients on Hemodialysis with an Undetected SARS-CoV-2 Infection10.34067/KID.0003802020Wed, 13 Jan 2021 01:56:25 GMT-08:00Machine Learning for Prediction of Patients on Hemodialysis with an Undetected SARS-CoV-2 InfectionMonaghan, Caitlin K.Larkin, John W.Chaudhuri, SheetalHan, HaoJiao, YueBermudez, Kristine M.Weinhandl, Eric D.Dahne-Steuber, Ines A.Belmonte, KathleenNeri, LucaKotanko, PeterKooman, Jeroen P.Hymes, Jeffrey L.Kossmann, Robert J.Usvyat, Len A.Maddux, Franklin W.2021-01-13T13:56:25-08:00doi:10.34067/KID.0003802020hwp:resource-id:kidney360;2/3/456American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, artificial intelligence, coronavirus, COVID-19, dialysis, end stage kidney disease, machine learning, prediction, SARS-CoV-2Original InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-03-2510.34067/KID.00038020202641-76502021-01-13T13:56:25-08:002021-03-25Kidney360Original Investigations23456468
- Progress toward the Clinical Application of Mesenchymal Stromal Cells and Other Disease-Modulating Regenerative Therapies: Examples from the Field of NephrologyDrawing from basic knowledge of stem-cell biology, embryonic development, wound healing, and aging, regenerative medicine seeks to develop therapeutic strategies that complement or replace conventional treatments by actively repairing diseased tissue or generating new organs and tissues. Among the various clinical-translational strategies within the field of regenerative medicine, several can be broadly described as promoting disease resolution indirectly through local or systemic interactions with a patient’s cells, without permanently integrating or directly forming new primary tissue. In this review, we focus on such therapies, which we term disease-modulating regenerative therapies (DMRT), and on the extent to which they have been translated into the clinical arena in four distinct areas of nephrology: renovascular disease (RVD), sepsis-associated AKI (SA-AKI), diabetic kidney disease (DKD), and kidney transplantation (KTx). As we describe, the DMRT that has most consistently progressed to human clinical trials for these indications is mesenchymal stem/stromal cells (MSCs), which potently modulate ischemic, inflammatory, profibrotic, and immune-mediated tissue injury through diverse paracrine mechanisms. In KTx, several early-phase clinical trials have also tested the potential for ex vivo–expanded regulatory immune cell therapies to promote donor-specific tolerance and prevent or resolve allograft injury. Other promising DMRT, including adult stem/progenitor cells, stem cell–derived extracellular vesicles, and implantable hydrogels/biomaterials remain at varying preclinical stages of translation for these renal conditions. To date (2021), no DMRT has gained market approval for use in patients with RVD, SA-AKI, DKD, or KTx, and clinical trials demonstrating definitive, cost-effective patient benefits are needed. Nonetheless, exciting progress in understanding the disease-specific mechanisms of action of MSCs and other DMRT, coupled with increasing knowledge of the pathophysiologic basis for renal-tissue injury and the experience gained from pioneering early-phase clinical trials provide optimism that influential, regenerative treatments for diverse kidney diseases will emerge in the years ahead.10.34067/KID.0005692020Wed, 27 Jan 2021 01:35:26 GMT-08:00Progress toward the Clinical Application of Mesenchymal Stromal Cells and Other Disease-Modulating Regenerative Therapies: Examples from the Field of NephrologyDrawing from basic knowledge of stem-cell biology, embryonic development, wound healing, and aging, regenerative medicine seeks to develop therapeutic strategies that complement or replace conventional treatments by actively repairing diseased tissue or generating new organs and tissues. Among the various clinical-translational strategies within the field of regenerative medicine, several can be broadly described as promoting disease resolution indirectly through local or systemic interactions with a patient’s cells, without permanently integrating or directly forming new primary tissue. In this review, we focus on such therapies, which we term disease-modulating regenerative therapies (DMRT), and on the extent to which they have been translated into the clinical arena in four distinct areas of nephrology: renovascular disease (RVD), sepsis-associated AKI (SA-AKI), diabetic kidney disease (DKD), and kidney transplantation (KTx). As we describe, the DMRT that has most consistently progressed to human clinical trials for these indications is mesenchymal stem/stromal cells (MSCs), which potently modulate ischemic, inflammatory, profibrotic, and immune-mediated tissue injury through diverse paracrine mechanisms. In KTx, several early-phase clinical trials have also tested the potential for ex vivo–expanded regulatory immune cell therapies to promote donor-specific tolerance and prevent or resolve allograft injury. Other promising DMRT, including adult stem/progenitor cells, stem cell–derived extracellular vesicles, and implantable hydrogels/biomaterials remain at varying preclinical stages of translation for these renal conditions. To date (2021), no DMRT has gained market approval for use in patients with RVD, SA-AKI, DKD, or KTx, and clinical trials demonstrating definitive, cost-effective patient benefits are needed. Nonetheless, exciting progress in understanding the disease-specific mechanisms of action of MSCs and other DMRT, coupled with increasing knowledge of the pathophysiologic basis for renal-tissue injury and the experience gained from pioneering early-phase clinical trials provide optimism that influential, regenerative treatments for diverse kidney diseases will emerge in the years ahead.Hickson, LaTonya J.Herrmann, Sandra M.McNicholas, Bairbre A.Griffin, Matthew D.2021-01-27T13:35:26-08:00doi:10.34067/KID.0005692020hwp:resource-id:kidney360;2/3/542American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, basic science, clinical trials, diabetic kidney disease, inflammation, mesenchymal stromal cells, regenerative medicine, regulatory T cells, renovascular disease, senescence, sepsis, stem cellsBasic Science for CliniciansBasic Science for Cliniciansother20212021-03-2510.34067/KID.00056920202641-76502021-01-27T13:35:26-08:002021-03-25Kidney360Basic Science for Clinicians23542557
- Sphingolipids and Kidney Disease: Possible Role of Preeclampsia and Intrauterine Growth Restriction (IUGR)Sphingolipids are now considered not only as constitutional components of the cellular membrane but also as essential bioactive factors regulating development and physiologic functions. Ceramide is a vital intermediate of sphingolipid metabolism, synthesized by de novo and salvage pathways, producing multiple types of sphingolipids and their metabolites. Although mutations in gene-encoding enzymes regulating sphingolipid synthesis and metabolism cause distinct diseases, an abnormal sphingolipid metabolism contributes to various pathologic conditions, including kidney diseases. Excessive accumulation of glycosphingolipids and promotion of the ceramide salvage and sphingosine-1-phosphate (S1P) pathways are found in the damaged kidney. Acceleration of the sphingosine kinase/S1P/S1P receptor (SphK/S1P/S1PR) axis plays a central role in deteriorating kidney functions. The SphK/S1P/S1PR signaling impairment is also found during pregnancy complications, such as preeclampsia and intrauterine growth restriction (IUGR). This mini-review discusses the current state of knowledge regarding the role of sphingolipid metabolism on kidney diseases, and the possible involvement of preeclampsia and IUGR conditions.10.34067/KID.0006322020Thu, 07 Jan 2021 11:41:55 GMT-08:00Sphingolipids and Kidney Disease: Possible Role of Preeclampsia and Intrauterine Growth Restriction (IUGR)Sphingolipids are now considered not only as constitutional components of the cellular membrane but also as essential bioactive factors regulating development and physiologic functions. Ceramide is a vital intermediate of sphingolipid metabolism, synthesized by de novo and salvage pathways, producing multiple types of sphingolipids and their metabolites. Although mutations in gene-encoding enzymes regulating sphingolipid synthesis and metabolism cause distinct diseases, an abnormal sphingolipid metabolism contributes to various pathologic conditions, including kidney diseases. Excessive accumulation of glycosphingolipids and promotion of the ceramide salvage and sphingosine-1-phosphate (S1P) pathways are found in the damaged kidney. Acceleration of the sphingosine kinase/S1P/S1P receptor (SphK/S1P/S1PR) axis plays a central role in deteriorating kidney functions. The SphK/S1P/S1PR signaling impairment is also found during pregnancy complications, such as preeclampsia and intrauterine growth restriction (IUGR). This mini-review discusses the current state of knowledge regarding the role of sphingolipid metabolism on kidney diseases, and the possible involvement of preeclampsia and IUGR conditions.Yokota, RodrigoBhunu, BenjaminToba, HiroeIntapad, Suttira2021-01-07T11:41:55-08:00doi:10.34067/KID.0006322020hwp:resource-id:kidney360;2/3/534American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, basic science, fetal growth retardation, intrauterine growth restriction, IUGR, kidney diseases, preeclampsia, small for gestational age infant, sphingolipidsBasic Science for CliniciansBasic Science for Cliniciansother20212021-03-2510.34067/KID.00063220202641-76502021-01-07T11:41:55-08:002021-03-25Kidney360Basic Science for Clinicians23534541
- Gut Microbiota-Immune System Interactions during Acute Kidney Injury10.34067/KID.0006792020Thu, 14 Jan 2021 01:27:37 GMT-08:00Gut Microbiota-Immune System Interactions during Acute Kidney InjuryNoel, SanjeevMohammad, FuadWhite, JamesLee, KyunghoGharaie, SepidehRabb, Hamid2021-01-14T13:27:37-08:00doi:10.34067/KID.0006792020hwp:resource-id:kidney360;2/3/528American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, basic science, cisplatin, dysbiosis, gastrointestinal microbiome, gut microbiota, immune system, ischemia reperfusion injury, transplantationPerspectivePerspectiveresearch-article20212021-03-2510.34067/KID.00067920202641-76502021-01-14T13:27:37-08:002021-03-25Kidney360Perspective23528531
- Impact of Casein- versus Grain-Based Diets on Rat Renal Sodium Transporters’ Abundance and Regulation10.34067/KID.0006702020Wed, 06 Jan 2021 01:46:58 GMT-08:00Impact of Casein- versus Grain-Based Diets on Rat Renal Sodium Transporters’ Abundance and RegulationMcDonough, Alicia A.Veiras, Luciana C.McFarlin, Brandon E.Ralph, Donna L.2021-01-06T13:46:58-08:00doi:10.34067/KID.0006702020hwp:resource-id:kidney360;2/3/519American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360renal physiology, acid/base and electrolyte disorders, basic science, casein diet, claudin, ENaC, grain diet, hypertension, NCC, NHE3, NKCC2, sodiumBrief CommunicationsRenal PhysiologyBrief CommunicationsRenal Physiologybrief-report20212021-03-2510.34067/KID.00067020202641-76502021-01-06T13:46:58-08:002021-03-25Kidney360Brief Communications23519523
- Patients with Hepatorenal Syndrome Should Be Dialyzed? COMMENTARY10.34067/KID.0006862020Wed, 16 Dec 2020 11:33:50 GMT-08:00Patients with Hepatorenal Syndrome Should Be Dialyzed? COMMENTARYRegner, Kevin R.2020-12-16T11:33:50-08:00doi:10.34067/KID.0006862020hwp:resource-id:kidney360;2/3/413American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, cirrhosis, hepatorenal syndrome, hyperammonemia, renal replacement therapyModerator CommentaryModerator Commentaryarticle-commentary20212021-03-2510.34067/KID.00068620202641-76502020-12-16T11:33:50-08:002021-03-25Kidney360Moderator Commentary23413414
- Patients with Hepatorenal Syndrome Should Be Dialyzed? PRO10.34067/KID.0006952020Wed, 16 Dec 2020 11:33:50 GMT-08:00Patients with Hepatorenal Syndrome Should Be Dialyzed? PROVelez, Juan Carlos Q.2020-12-16T11:33:50-08:00doi:10.34067/KID.0006952020hwp:resource-id:kidney360;2/3/406American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, cirrhosis, CRRT, decompensated, dialysis, end-of-life, futility, HRS-1, palliative, RRTDebates in NephrologyDebates in Nephrologyresearch-article20212021-03-2510.34067/KID.00069520202641-76502020-12-16T11:33:50-08:002021-03-25Kidney360Debates in Nephrology23406409
- Patients with Hepatorenal Syndrome Should Be Dialyzed? CON10.34067/KID.0006872020Wed, 16 Dec 2020 11:33:50 GMT-08:00Patients with Hepatorenal Syndrome Should Be Dialyzed? CONWadei, Hani M.2020-12-16T11:33:50-08:00doi:10.34067/KID.0006872020hwp:resource-id:kidney360;2/3/410American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, dialysis, hepatorenal syndrome, liver cirrhosis, renal replacement therapyDebates in NephrologyDebates in Nephrologyresearch-article20212021-03-2510.34067/KID.00068720202641-76502020-12-16T11:33:50-08:002021-03-25Kidney360Debates in Nephrology23410412
- Persistent Isolated Hematuria in a Japanese Woman10.34067/KID.0005642020Thu, 25 Mar 2021 05:00:29 GMT-07:00Persistent Isolated Hematuria in a Japanese WomanSato, MasayoMochizuki, ToshioNitta, Kosaku2021-03-25T05:00:29-07:00doi:10.34067/KID.0005642020hwp:resource-id:kidney360;2/3/602American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, Alport syndrome, electron microscopy, glomerular basement membrane, kidney biopsy, thin basement membrane nephropathy, type IV collagenClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-03-2510.34067/KID.00056420202641-76502021-03-25T05:00:29-07:002021-03-25Kidney360Clinical Images in Nephrology and Dialysis23602603
- Purple Urine in a Patient with Refractory Hypotension10.34067/KID.0005362020Thu, 25 Mar 2021 05:00:29 GMT-07:00Purple Urine in a Patient with Refractory HypotensionSriperumbuduri, SriramBrown, Pierre-AntoineClark, Edward G.2021-03-25T05:00:29-07:00doi:10.34067/KID.0005362020hwp:resource-id:kidney360;2/3/598American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, cyanocobalamin, methylene blue, purple urine, purple urine bag syndrome, shock, urine color, vasoplegiaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-03-2510.34067/KID.00053620202641-76502021-03-25T05:00:29-07:002021-03-25Kidney360Clinical Images in Nephrology and Dialysis23598599
- Acute Kidney Injury in a Patient following Percutaneous Kidney Biopsy10.34067/KID.0005252020Thu, 25 Mar 2021 05:00:29 GMT-07:00Acute Kidney Injury in a Patient following Percutaneous Kidney BiopsyParmar, Malvinder S.2021-03-25T05:00:29-07:00doi:10.34067/KID.0005252020hwp:resource-id:kidney360;2/3/600American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, complications, kidney biopsy, page kidney, perirenal hematoma, tamponadeClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-03-2510.34067/KID.00052520202641-76502021-03-25T05:00:29-07:002021-03-25Kidney360Clinical Images in Nephrology and Dialysis23600601
- Does Whom Patients Sit Next to during Hemodialysis Affect Whether They Request a Living Donation?10.34067/KID.0006682020Fri, 15 Jan 2021 05:59:29 GMT-08:00Does Whom Patients Sit Next to during Hemodialysis Affect Whether They Request a Living Donation?Gillespie, AvrumFink, Edward L.Gardiner, Heather M.Gadegbeku, Crystal A.Reese, Peter P.Obradovic, Zoran2021-01-15T05:59:29-08:00doi:10.34067/KID.0006682020hwp:resource-id:kidney360;2/3/507American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, clinical epidemiology, end stage kidney disease, hemodialysis, homophily, kidney transplantation, living donor, social contagion, social networks, survey research, transplantationOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20212021-03-2510.34067/KID.00066820202641-76502021-01-15T05:59:29-08:002021-03-25Kidney360Original Investigations23507518
- Social Networks in the Dialysis Unit: Can They Influence Patient Behavior?10.34067/KID.0000782021Thu, 25 Mar 2021 05:00:28 GMT-07:00Social Networks in the Dialysis Unit: Can They Influence Patient Behavior?Singh, Tripti2021-03-25T05:00:28-07:00doi:10.34067/KID.0000782021hwp:resource-id:kidney360;2/3/404American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, hospital departments, social networkEditorialEditorialeditorial20212021-03-2510.34067/KID.00007820212641-76502021-03-25T05:00:28-07:002021-03-25Kidney360Editorial23404405
- The Effectiveness of Depression Treatment for Adults with ESKD: A Systematic ReviewAdults with dialysis-dependent ESKD experience higher rates of depression than the general population, yet efficacy of depression treatments in this population is not well understood. We conducted a systematic review of the benefits and harms of depression treatment in adults with ESKD. We searched multiple data sources through June 2020 for English-language, controlled trials that compared interventions for depression in adults with ESKD to another intervention, placebo, or usual care, and reported depression treatment–related outcomes. Observational studies were included for harms. Two investigators independently screened all studies using prespecified criteria. One reviewer abstracted data on study design, interventions, implementation characteristics, and outcomes, and a second reviewer provided confirmation. Two reviewers independently assessed study quality and resolved any discords through discussion or a third reviewer. Strength of evidence (SOE) was assessed and agreed upon by review-team consensus. We qualitatively analyzed the data and present syntheses in text and tables. We included 26 RCTs and three observational studies. SSRIs were the most studied type of drug and the evidence was largely insufficient. We found moderate SOE that long-term, high-dose vitamin D3 is ineffective for reducing depression severity. Cognitive behavioral therapy is more effective than (undefined) psychotherapy and placebo for depression improvement and quality of life (low SOE), and acupressure is more effective than usual care or sham acupressure in reducing depression severity (low SOE). There is limited research evaluating treatment for depression in adults with ESKD, and existing studies may not be generalizable to adults in the United States. Studies suffer from limitations related to methodologic quality or reporting. More research replicating studies of promising interventions in US populations, with larger samples, is needed. Systematic Review registry name and registration number: PROSPERO, CRD4202014022710.34067/KID.0003142020Thu, 07 Jan 2021 09:59:20 GMT-08:00The Effectiveness of Depression Treatment for Adults with ESKD: A Systematic ReviewAdults with dialysis-dependent ESKD experience higher rates of depression than the general population, yet efficacy of depression treatments in this population is not well understood. We conducted a systematic review of the benefits and harms of depression treatment in adults with ESKD. We searched multiple data sources through June 2020 for English-language, controlled trials that compared interventions for depression in adults with ESKD to another intervention, placebo, or usual care, and reported depression treatment–related outcomes. Observational studies were included for harms. Two investigators independently screened all studies using prespecified criteria. One reviewer abstracted data on study design, interventions, implementation characteristics, and outcomes, and a second reviewer provided confirmation. Two reviewers independently assessed study quality and resolved any discords through discussion or a third reviewer. Strength of evidence (SOE) was assessed and agreed upon by review-team consensus. We qualitatively analyzed the data and present syntheses in text and tables. We included 26 RCTs and three observational studies. SSRIs were the most studied type of drug and the evidence was largely insufficient. We found moderate SOE that long-term, high-dose vitamin D3 is ineffective for reducing depression severity. Cognitive behavioral therapy is more effective than (undefined) psychotherapy and placebo for depression improvement and quality of life (low SOE), and acupressure is more effective than usual care or sham acupressure in reducing depression severity (low SOE). There is limited research evaluating treatment for depression in adults with ESKD, and existing studies may not be generalizable to adults in the United States. Studies suffer from limitations related to methodologic quality or reporting. More research replicating studies of promising interventions in US populations, with larger samples, is needed. Systematic Review registry name and registration number: PROSPERO, CRD42020140227Chopra, PavanAyers, Chelsea K.Antick, Jennifer R.Kansagara, DevanKondo, Karli2021-01-07T09:59:20-08:00doi:10.34067/KID.0003142020hwp:resource-id:kidney360;2/3/558American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, depression, depression treatment, ESKD, ESRD, systematic reviewReview ArticlesReview Articlesreview-article20212021-03-2510.34067/KID.00031420202641-76502021-01-07T09:59:20-08:002021-03-25Kidney360Review Articles23558585
- Longitudinal Changes in the Use of PD Assistance for Patients Maintained on Peritoneal Dialysis10.34067/KID.0006622020Tue, 12 Jan 2021 12:46:30 GMT-08:00Longitudinal Changes in the Use of PD Assistance for Patients Maintained on Peritoneal DialysisFonseca-Correa, Jorge I.Farragher, Janine F.Tomlinson, GeorgeOliver, Matthew J.Jain, ArshFlanagan, SusanKoyle, KathleenJassal, Sarbjit V.2021-01-12T12:46:30-08:00doi:10.34067/KID.0006622020hwp:resource-id:kidney360;2/3/469American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, chronic dialysis, dementia, geriatric nephrology, peritoneal dialysisOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-03-2510.34067/KID.00066220202641-76502021-01-12T12:46:30-08:002021-03-25Kidney360Original Investigations23469476
- Living Related Donor Kidney Transplantation in Atypical HUS: When Should It Be Considered?10.34067/KID.0007112020Thu, 21 Jan 2021 09:30:12 GMT-08:00Living Related Donor Kidney Transplantation in Atypical HUS: When Should It Be Considered?Kurup, MeghnaMandelbrot, DidierGarg, NeetikaSingh, Tripti2021-01-21T09:30:12-08:00doi:10.34067/KID.0007112020hwp:resource-id:kidney360;2/3/524American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, atypical HUS, donor evaluation, genetic testing, kidney transplantation, living donorsBrief CommunicationsTransplantationBrief CommunicationsTransplantationbrief-report20212021-03-2510.34067/KID.00071120202641-76502021-01-21T09:30:12-08:002021-03-25Kidney360Brief Communications23524527
- Biomarkers in ANCA-Associated Vasculitis: Potential Pitfalls and Future ProspectsOver the past 3 decades, significant advancements in the understanding of the pathophysiology of ANCA-associated vasculitis has led to the development of a multitude of potential candidate biomarkers. Accompanied by the advent of increasingly effective therapeutic strategies, the need for a dependable biomarker to help determine the extent of disease activity and risk of relapse is ever present. Implementation of such a biomarker would enable tailored therapy, optimizing disease control while helping to mitigate unnecessary exposure to therapy and potential treatment-related damage. Although far from perfect, ANCA serology and B-cell population are the two main staple biomarker tools widely used in practice to help supplement clinical assessment. Over recent years, the application and progress of more novel biomarker tools have arisen in both organ-limited and multisystem disease, including genomics, urinary proteins, degradation products of the alternative complement system, cytokines, metabolomics, and biospectroscopy. Validation studies and clinical translation of these tools are required, with serial assessment of disease activity and determination of therapy according to biomarker status correlated with patient outcomes.10.34067/KID.0006432020Tue, 19 Jan 2021 12:41:10 GMT-08:00Biomarkers in ANCA-Associated Vasculitis: Potential Pitfalls and Future ProspectsOver the past 3 decades, significant advancements in the understanding of the pathophysiology of ANCA-associated vasculitis has led to the development of a multitude of potential candidate biomarkers. Accompanied by the advent of increasingly effective therapeutic strategies, the need for a dependable biomarker to help determine the extent of disease activity and risk of relapse is ever present. Implementation of such a biomarker would enable tailored therapy, optimizing disease control while helping to mitigate unnecessary exposure to therapy and potential treatment-related damage. Although far from perfect, ANCA serology and B-cell population are the two main staple biomarker tools widely used in practice to help supplement clinical assessment. Over recent years, the application and progress of more novel biomarker tools have arisen in both organ-limited and multisystem disease, including genomics, urinary proteins, degradation products of the alternative complement system, cytokines, metabolomics, and biospectroscopy. Validation studies and clinical translation of these tools are required, with serial assessment of disease activity and determination of therapy according to biomarker status correlated with patient outcomes.Morris, Adam D.Rowbottom, Anthony W.Martin, Francis L.Woywodt, AlexanderDhaygude, Ajay P.2021-01-19T12:41:10-08:00doi:10.34067/KID.0006432020hwp:resource-id:kidney360;2/3/586American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, ANCA-associated vasculitis, biomarkers, disease activityReview ArticlesReview Articlesreview-article20212021-03-2510.34067/KID.00064320202641-76502021-01-19T12:41:10-08:002021-03-25Kidney360Review Articles23586597
- The Microbiome and p-Inulin in Hemodialysis: A Feasibility Study10.34067/KID.0006132020Fri, 15 Jan 2021 01:28:43 GMT-08:00The Microbiome and p-Inulin in Hemodialysis: A Feasibility StudyRaj, Dominic S.Sohn, Michael B.Charytan, David M.Himmelfarb, JonathanIkizler, T. AlpMehrotra, RajnishRamezani, AliRegunathan-Shenk, RenuHsu, Jesse Y.Landis, J. RichardLi, HongzheKimmel, Paul L.Kliger, Alan S.Dember, Laura M.,,Kliger, AlanCharytan, David M.Robinson, EmilyWilliams, MarkWeiner, Daniel E.Mc Causland, FinnianWaikar, SushrutAurien-Blajeni, EzraCinelli, AngelesNisam, TayyabaRim, SookyungSeok, PaulSmith, CarolineRollins, JasmineRaj, DominicRegunathan-Shenk, RenuSharma, ShailendraRamezani, AliAndrews, SarahDumadag, MichelleFranco, ChristinaWing, MariaHimmelfarb, JonathanMehrotra, RajnishAnderson, LisaLinke, LoriManahan, LindaIkizler, T. AlpHung, AdrianaCavanaugh, KerriBooker, CindyBrannon, BrigitteClagett, AdrienneEllis, CharlesDember, Laura M.Landis, J. RichardAnderson, AmandaHsu, JesseCifelli, DeniseBallard, ShawnDurborow, MarieHoward, TamaraKuzla, NatalieNessel, LisaTierney, AnnSkali, HichamSolomon, ScottRad, AriaDi Carli, MarceloGaber, MashaFoster, CourtneyKimmel, PaulKusek, JohnAbbott, KevinPalevsky, PaulGoldstein, StuartHibberd, PatriciaKaysen, GeorgeKorzenik, JoshuaLima, JoaoNissenson, AllenRamachandran, VasanRaboussin, DavidSiegel, JeffreyVaziri, NosratolaVigliani, GloriaWittes, Janet2021-01-15T13:28:43-08:00doi:10.34067/KID.0006132020hwp:resource-id:kidney360;2/3/445American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, crossover trial, feasibility studies, hemodialysis, microbiome, p-inulin, prebioticOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-03-2510.34067/KID.00061320202641-76502021-01-15T13:28:43-08:002021-03-25Kidney360Original Investigations23445455
- Estimating Kidney Failure Risk Using Electronic Medical Records10.34067/KID.0005592020Wed, 06 Jan 2021 01:46:58 GMT-08:00Estimating Kidney Failure Risk Using Electronic Medical RecordsNaranjo, Felipe S.Sang, YingyingBallew, Shoshana H.Stempniewicz, NikitaDunning, Stephan C.Levey, Andrew S.Coresh, JosefGrams, Morgan E.2021-01-06T13:46:58-08:00doi:10.34067/KID.0005592020hwp:resource-id:kidney360;2/3/415American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, albuminuria, electronic health records, kidney failureOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-03-2510.34067/KID.00055920202641-76502021-01-06T13:46:58-08:002021-03-25Kidney360Original Investigations23415424
- Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial10.34067/KID.0006782020Fri, 15 Jan 2021 01:28:43 GMT-08:00Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER TrialAgarwal, RajivRossignol, PatrickBudden, JeffreyMayo, Martha R.Arthur, SusanWilliams, BryanWhite, William B.2021-01-15T13:28:43-08:00doi:10.34067/KID.0006782020hwp:resource-id:kidney360;2/3/425American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, chronic renal insufficiency, hyperkalemia, patiromer, resistant hypertension, spironolactoneOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-03-2510.34067/KID.00067820202641-76502021-01-15T13:28:43-08:002021-03-25Kidney360Original Investigations23425434
- Mindfulness-based Virtual Reality Intervention in Hemodialysis Patients: A Pilot Study on End-user Perceptions and Safety10.34067/KID.0005522020Fri, 08 Jan 2021 10:59:02 GMT-08:00Mindfulness-based Virtual Reality Intervention in Hemodialysis Patients: A Pilot Study on End-user Perceptions and SafetyHernandez, RosalbaBurrows, BrettBrowning, Matthew H.E.M.Solai, KillivalavanFast, DrewLitbarg, Natalia O.Wilund, Kenneth R.Moskowitz, Judith T.2021-01-08T10:59:02-08:00doi:10.34067/KID.0005522020hwp:resource-id:kidney360;2/3/435American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, alternative therapies, hemodialysis, mindfulness/meditation, psychological wellbeing, symptom management, virtual realityOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-03-2510.34067/KID.00055220202641-76502021-01-08T10:59:02-08:002021-03-25Kidney360Original Investigations23435444
- Steroid Regimen for Children with Nephrotic Syndrome Relapse10.2215/CJN.19201220Thu, 21 Jan 2021 08:10:09 GMT-08:00Steroid Regimen for Children with Nephrotic Syndrome RelapseWilliams, Anna ElizabethGbadegesin, Rasheed A.2021-01-21T08:10:09-08:00doi:10.2215/CJN.19201220hwp:resource-id:clinjasn;16/2/179American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, children, glomerular disease, idiopathic nephrotic syndromeEditorialsEditorialseditorial20212021-02-08February 08, 202110.2215/CJN.192012201555-90411555-905X2021-01-21T08:10:09-08:002021-02-08Clinical Journal of the American Society of NephrologyEditorials1622179225181232
- Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse10.2215/CJN.06140420Thu, 21 Jan 2021 08:10:10 GMT-08:00Short-Duration Prednisolone in Children with Nephrotic Syndrome RelapseKainth, DeepikaHari, PankajSinha, AditiPandey, ShivamBagga, Arvind2021-01-21T08:10:10-08:00doi:10.2215/CJN.06140420hwp:resource-id:clinjasn;16/2/225American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinfrequently relapsing nephrotic syndrome, short regimen, frequent relapses, prednisolone, nephrotic syndromeOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20212021-02-08February 08, 202110.2215/CJN.061404201555-90411555-905X2021-01-21T08:10:10-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles1622225179232181
- Variability in Culture-Negative Peritonitis Rates in Pediatric Peritoneal Dialysis Programs in the United States10.2215/CJN.09190620Mon, 18 Jan 2021 08:39:38 GMT-08:00Variability in Culture-Negative Peritonitis Rates in Pediatric Peritoneal Dialysis Programs in the United StatesDavis, T. KeefeBryant, Kristina A.Rodean, JonathanRichardson, TroySelvarangan, RangarajQin, XuanNeu, AliciaWarady, Bradley A.2021-01-18T08:39:38-08:00doi:10.2215/CJN.09190620hwp:resource-id:clinjasn;16/2/233American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, pediatric nephrologyOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-02-08February 08, 202110.2215/CJN.091906201555-90411555-905X2021-01-18T08:39:38-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles1622233191240193
- Opportunities for Improvement in Quality of Care of PD-Related Peritonitis in Children10.2215/CJN.19461220Mon, 18 Jan 2021 08:39:38 GMT-08:00Opportunities for Improvement in Quality of Care of PD-Related Peritonitis in ChildrenVidal, Enrico2021-01-18T08:39:38-08:00doi:10.2215/CJN.19461220hwp:resource-id:clinjasn;16/2/191American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitonitis, children, quality of health careEditorialsEditorialseditorial20212021-02-08February 08, 202110.2215/CJN.194612201555-90411555-905X2021-01-18T08:39:38-08:002021-02-08Clinical Journal of the American Society of NephrologyEditorials1622191233193240
- Clinical Utility of Genetic Testing in the Precision Diagnosis and Management of Pediatric Patients with Kidney and Urinary Tract Diseases10.34067/KID.0002272020Fri, 30 Oct 2020 06:15:32 GMT-07:00Clinical Utility of Genetic Testing in the Precision Diagnosis and Management of Pediatric Patients with Kidney and Urinary Tract DiseasesBekheirnia, NasimGlinton, Kevin E.Rossetti, LindaManor, JoshuaChen, WuyanLamb, Dolores J.Braun, Michael C.Bekheirnia, Mir Reza2020-10-30T06:15:32-07:00doi:10.34067/KID.0002272020hwp:resource-id:kidney360;2/1/90American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360genetics, data collection, genetic testing, kidney disease, Renal Genetics Clinic, urologic diseasesOriginal InvestigationsGeneticsOriginal InvestigationsGeneticsresearch-article20212021-01-2810.34067/KID.00022720202641-76502020-10-30T06:15:32-07:002021-01-28Kidney360Original Investigations2190104
- Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression10.34067/KID.0006172020Tue, 01 Dec 2020 10:20:45 GMT-08:00Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to ImmunosuppressionForster, Benjamin M.Nee, RobertLittle, Dustin J.Greasley, Peter J.Hughes, James B.Gordon, Sarah M.Olson, Stephen W.2020-12-01T10:20:45-08:00doi:10.34067/KID.0006172020hwp:resource-id:kidney360;2/1/105American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, end stage kidney disease, estimated glomerular filtration rate, focal segmental glomerulosclerosis, immunosuppression, proteinuria, renal survival, risk factorsOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20212021-01-2810.34067/KID.00061720202641-76502020-12-01T10:20:45-08:002021-01-28Kidney360Original Investigations21105113
- Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease–Associated Kidney Failure10.2215/CJN.02720320Thu, 25 Feb 2021 08:17:45 GMT-08:00Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease–Associated Kidney FailureBae, SunjaeJohnson, MorganMassie, Allan B.Luo, XunHaywood, CarltonLanzkron, Sophie M.Grams, Morgan E.Segev, Dorry L.Purnell, Tanjala S.2021-02-25T08:17:45-08:00doi:10.2215/CJN.02720320hwp:resource-id:clinjasn;16/3/407American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, sickle cell disease, access to care, survival benefit, anemia, sickle cell, kidney failure, mortalityOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-03-08March 08, 202110.2215/CJN.027203201555-90411555-905X2021-02-25T08:17:45-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles1633407335414336
- Time to Procurement and Post-Kidney Transplant Outcomes10.2215/CJN.01340121Fri, 26 Feb 2021 11:10:54 GMT-08:00Time to Procurement and Post-Kidney Transplant OutcomesHaakinson, Danielle J.2021-02-26T11:10:54-08:00doi:10.2215/CJN.01340121hwp:resource-id:clinjasn;16/3/340American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, kidney transplantation, transplantation, transplant outcomes, end stage kidney disease, kidney donation, organ procurementEditorialsEditorialseditorial20212021-03-08March 08, 202110.2215/CJN.013401211555-90411555-905X2021-02-26T11:10:54-08:002021-03-08Clinical Journal of the American Society of NephrologyEditorials1633340427342436
- Correction: Infection-Related Acute Care Events among Patients with Glomerular Disease10.2215/CJN.00550121Mon, 01 Mar 2021 06:01:35 GMT-08:00Correction: Infection-Related Acute Care Events among Patients with Glomerular DiseaseAmerican Society of Nephrology2021-03-01T06:01:35-08:00doi:10.2215/CJN.00550121hwp:resource-id:clinjasn;16/3/456American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCorrection, erratum, infection, hospitalization, glomerular disease, nephrotic syndrome, kidney disease, immunosuppression, pediatric nephrology, acute care eventsErratumErratumcorrection20212021-03-08March 08, 202110.2215/CJN.005501211555-90411555-905X2021-03-01T06:01:35-08:002021-03-08Clinical Journal of the American Society of NephrologyErratum1615312124561749174945717611761
- Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria10.2215/CJN.15260920Mon, 22 Feb 2021 07:19:34 GMT-08:00Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline AlbuminuriaJardine, MegZhou, ZienLambers Heerspink, Hiddo J.Hockham, CarinnaLi, QiangAgarwal, RajivBakris, George L.Cannon, Christopher P.Charytan, David M.Greene, TomLevin, AdeeraLi, Jing-WeiNeuen, Brendon L.Neal, BruceOh, RichardOshima, MegumiPollock, CarolWheeler, David C.de Zeeuw, DickZhang, HongZinman, BernardMahaffey, Kenneth W.Perkovic, Vlado2021-02-22T07:19:34-08:00doi:10.2215/CJN.15260920hwp:resource-id:clinjasn;16/3/384American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologySGLT2 inhibitors, canagliflozin, chronic kidney disease progression, albuminuria, randomized controlled trials, cardiovascular system, diabetesOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20212021-03-08March 08, 202110.2215/CJN.152609201555-90411555-905X2021-02-22T07:19:34-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles163384395
- Life with Sickle Cell Disease and Kidney Failure10.2215/CJN.00500121Thu, 25 Feb 2021 08:31:19 GMT-08:00Life with Sickle Cell Disease and Kidney FailureCouch, Sasha2021-02-25T08:31:19-08:00doi:10.2215/CJN.00500121hwp:resource-id:clinjasn;16/3/335American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysickle cell disease, kidney failurePatient VoicePatient Voiceeditorial20212021-03-08March 08, 202110.2215/CJN.005001211555-90411555-905X2021-02-25T08:31:19-08:002021-03-08Clinical Journal of the American Society of NephrologyPatient Voice1633335407336414
- Challenges with Providing Hospice Care for Patients Undergoing Long-Term Dialysis10.2215/CJN.10710720Fri, 09 Oct 2020 08:50:46 GMT-07:00Challenges with Providing Hospice Care for Patients Undergoing Long-Term DialysisSchell, Jane O.Johnson, Douglas S.2020-10-09T08:50:46-07:00doi:10.2215/CJN.10710720hwp:resource-id:clinjasn;16/3/473American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end of life, hospice carePerspectivesPerspectivesresearch-article20212021-03-08March 08, 202110.2215/CJN.107107201555-90411555-905X2020-10-09T08:50:46-07:002021-03-08Clinical Journal of the American Society of NephrologyPerspectives163473475
- Uric Acid and CKD Progression Matures with Lessons for CKD Risk Factor Discovery10.2215/CJN.10650620Wed, 14 Oct 2020 08:51:07 GMT-07:00Uric Acid and CKD Progression Matures with Lessons for CKD Risk Factor DiscoveryOluwo, OluwaseunScialla, Julia J.2020-10-14T08:51:07-07:00doi:10.2215/CJN.10650620hwp:resource-id:clinjasn;16/3/476American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, uric acid, allopurinol, febuxostat, epidemiology and outcomes, risk factorsPerspectivesPerspectivesresearch-article20212021-03-08March 08, 202110.2215/CJN.106506201555-90411555-905X2020-10-14T08:51:07-07:002021-03-08Clinical Journal of the American Society of NephrologyPerspectives163476478
- Children with CKD Are Not Little Adults with CKD10.2215/CJN.11540720Thu, 15 Oct 2020 06:51:39 GMT-07:00Children with CKD Are Not Little Adults with CKDKula, Alexander J.Somers, Michael J.G.,2020-10-15T06:51:39-07:00doi:10.2215/CJN.11540720hwp:resource-id:clinjasn;16/3/470American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAAKH, pediatric nephrology, advocacy, chronic kidney disease, childrenPerspectivesPerspectivesresearch-article20212021-03-08March 08, 202110.2215/CJN.115407201555-90411555-905X2020-10-15T06:51:39-07:002021-03-08Clinical Journal of the American Society of NephrologyPerspectives163470472
- Resistant Hypertension in CKD10.2215/CJN.14610920Mon, 08 Feb 2021 09:47:52 GMT-08:00Resistant Hypertension in CKDThomas, GeorgeRahman, Mahboob2021-02-08T09:47:52-08:00doi:10.2215/CJN.14610920hwp:resource-id:clinjasn;16/3/467American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, chronic kidney disease, blood pressureKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20212021-03-08March 08, 202110.2215/CJN.146109201555-90411555-905X2021-02-08T09:47:52-08:002021-03-08Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat163467469
- Outcomes of Patients on Maintenance Dialysis Hospitalized with COVID-1910.2215/CJN.12360720Fri, 30 Oct 2020 10:50:33 GMT-07:00Outcomes of Patients on Maintenance Dialysis Hospitalized with COVID-19Chan, LiliJaladanki, Suraj K.Somani, SulaimanParanjpe, IshanKumar, ArvindZhao, ShanKaufman, LewisLeisman, StaciSharma, ShuchitaHe, John CijiangMurphy, BarbaraFayad, Zahi A.Levin, Matthew A.Bottinger, Erwin P.Charney, Alexander W.Glicksberg, Benjamin S.Coca, Steven G.Nadkarni, Girish N.,,Just, Allan C.Huckins, LauraO'Reilly, PaulMiotto, RiccardoRussak, Adam J.Rahman, AdeebVaid, AkhilLe Dobbyn, AmandaLeader, AndrewMoscati, ArdenKapoor, ArjunChang, ChristieBellaire, ChristopherCarrion, DanielChaudhry, FayzanRichter, FelixSoultanidis, GeorgiosParanjpe, IshanNabeel, IsmailDe Freitas, JessicaXu, JiayiRush, JohnathanJohnson, KippVemuri, KrishnaChaudhary, KumardeepLepow, LaurenCotter, LiamLiharska, LoraPereanez, MarcoBicak, MesudeDeFelice, NicholasNaik, NidhiBeckmann, NoamNadukuru, RajivO'Hagan, RossVan Vleck, Tielman T.Mutetwa, TinayeWanyan, TingyiFauveau, ValentinYang, YangLavin, YonitLanksy, AlonaAtreja, AshishDel Valle, DianeMeyer, DaraGolden, EddyeFasihuddin, FarahWen, Huei HsunRogers, JasonGutierrez, Jennifer LillyWalker, LauraSingh, ManbirDanieletto, MatteoNieves, Melissa A.Zweig, MicolPyzik, RenataFayad, RimaGlowe, PatriciaCalorossi, SharleneKaur, SparshdeepAscolillo, StevenRoa, YovannaLala-Trindade, AnuradhaPercha, BethanySigel, KeithPolak, PazHirten, RobertSwartz, TaliaCharney, DennisRosenberg, Murray M.Reich, DavidChatani, KumarNestler, EricKovatch, PatriciaFinkelstein, JosephBuxbaum, JosephCho, JudyKasarskis, AndrewHorowitz, CarolCordon-Cardo, CarlosMartin, Monica Sohn GlennGarcia-Sastre, AdolfoBagiella, EmiliaKrammer, FlorianAberg, JudithNarula, JagatWright, RobertLium, ErikWright, RosalindGelijns, AnnetineFuster, ValentinMerad, Miriam2020-10-30T10:50:33-07:00doi:10.2215/CJN.12360720hwp:resource-id:clinjasn;16/3/452American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, COVID-19, end-stage kidney diseaseResearch LettersResearch Lettersletter20212021-03-08March 08, 202110.2215/CJN.123607201555-90411555-905X2020-10-30T10:50:33-07:002021-03-08Clinical Journal of the American Society of NephrologyResearch Letters163452455
- Preliminary Assessment of Acute Kidney Injury in Critically Ill Children Associated with SARS-CoV-2 Infection10.2215/CJN.11470720Tue, 03 Nov 2020 06:52:42 GMT-08:00Preliminary Assessment of Acute Kidney Injury in Critically Ill Children Associated with SARS-CoV-2 InfectionBjornstad, Erica C.Krallman, Kelli A.Askenazi, DavidZappitelli, MichaelGoldstein, Stuart L.Basu, Rajit K.,,Irby, KatherineKhandhar, ParasMorgan, CatherineBrown, Erica Blenderde Leon, Sarah VelazquezAwojoodu, RonkeChakraborty, BarshaPeters, MarkYarlagadda, VamsiTigges, CodyShroff, RukshanaDaCar, Allie MichelleSu, FeliceArikan, AyseTala, JoanaKwiatkowski, DavidDuffey, EmilyOcampo, RosarioHammack, RebeccaBhalala, Utpalde Carvalho, Werther BrunowHefley, GlendaSheppard, CathyGupta, RonishChadha, VimalLiu, DianeGoilav, BeatriceDuong, Minh DienMazo, AlexandraShetty, NayanO’Malley, LauraJones, DawnBatchelder, ChristineBarhight, MatthewKring, ElizabethHassinger, AmandaRoss, CatherineStraka, NadineNawathe, PoojaGoulin, GaryGorga, StephenJayachandran, ChaandiniAyalon, ItayKamath, SameerHarward, MelissaMartin, SusanStajic, NatasaGist, KatjaJetton, JenniferVan Wyk, BrynnaBailey, DwightLamothe, JenniferPolikoff, LeeKirla, NavyaChanchlani, RahulSelewski, DavidFuhrman, DanaFormeck, CassandraNourbakhsh, NoureddinStarr, MichelleMenon, ShinaKitayama, HirotsuguParshuram, ChrisLee, JasmineSutherland, ScottSu, FeliceWoroniecki, RobertSirignano, RachelHuard, LeannaSpasojevic, BrankicaRsovac, SnezanaFrazier, JoshuaBortcosh, WilliamWilliams, DuaneFaustino, E. Vincent S.Stulce, CaseyGhanam, AvenehChong, GraceDharnidharka, VikasNeumayr, TaraGarros, DanielFong, LydiaGuerra, GonzaloDeep, AkashHackbarth, RichardKudchadkar, SapnaFitzgerald, JulieO’Campo, RosarioKhatri, AnujWalther, LesliePacheco, IreneAwadhare, PranaliCerovic, IvanaMedjo, BijanaRicci, ZaccariaAlobaidi, RashidBagshaw, SeanCrawford, BrendanBlaszak, RichardCollado Caparros, Juan FranciscoFeinstein, YaelMoss, Michelle2020-11-03T06:52:42-08:00doi:10.2215/CJN.11470720hwp:resource-id:clinjasn;16/3/446American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, critically ill children, acute kidney injuryResearch LettersResearch Lettersletter20212021-03-08March 08, 202110.2215/CJN.114707201555-90411555-905X2020-11-03T06:52:42-08:002021-03-08Clinical Journal of the American Society of NephrologyResearch Letters163446448
- Impact of COVID-19 Pandemic in Children with CKD or Immunosuppression10.2215/CJN.13120820Mon, 14 Dec 2020 08:31:23 GMT-08:00Impact of COVID-19 Pandemic in Children with CKD or ImmunosuppressionMastrangelo, AntonioMorello, WilliamVidal, EnricoGuzzo, IsabellaAnnicchiarico Petruzzelli, LuigiBenetti, ElisaMaterassi, MarcoGiordano, MarioPasini, AndreaCorrado, CiroPuccio, GiuseppeChimenz, RobertoPecoraro, CarmineMassella, LauraPeruzzi, LiciaMontini, Giovanni,,Peruzzi, LiciaBenetti, ElisaBenevenuta, ChiaraBrugnara, MilenaCasadio, LucaChimenz, RobertoConti, GiovanniCorrado, CiroDall’Amico, RobertoGianoglio, BrunoGiordano, MarioGualeni, ChiaraGuarino, StefanoGuzzo, IsabellaLa Manna, AngelaLa Scola, ClaudioMartelli, LauraMassella, LauraMastrangelo, AntonioMontini, GiovanniMorello, WilliamPani, AntonelloPapalia, TeresaPasini, AndreaPecoraro, CarminePelliccia, PiernicolaPennesi, MarcoAnnicchiarico Petruzzelli, LuigiPugliese, FabrizioRatsch, Ilse MariaRomagnani, PaolaMaterassi, MarcoRoperto, Rosa MariaTamburello, ChiaraVergine, GianlucaVergori, AntonioVianello, Federica AlessandraVidal, Enrico2020-12-14T08:31:23-08:00doi:10.2215/CJN.13120820hwp:resource-id:clinjasn;16/3/449American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, COVID-19, immunosuppression, kidney transplantation, glomerular disease, childrenResearch LettersResearch Lettersletter20212021-03-08March 08, 202110.2215/CJN.131208201555-90411555-905X2020-12-14T08:31:23-08:002021-03-08Clinical Journal of the American Society of NephrologyResearch Letters163449451
- GWAS-Based Discoveries in IgA Nephropathy, Membranous Nephropathy, and Steroid-Sensitive Nephrotic SyndromeOver the past decade, genome-wide association studies (GWAS) have emerged as a powerful tool to understand the genetic basis of complex traits in humans. The GWAS approach has been successfully applied to primary glomerular disorders, providing numerous novel insights into the genetic architecture of IgA nephropathy, membranous nephropathy, and steroid-sensitive nephrotic syndrome. IgA nephropathy appears to have a highly complex polygenic architecture, with nearly 20 genome-wide significant loci of small-to-moderate effects discovered to date. In contrast, the genetic susceptibility to membranous nephropathy and steroid-sensitive nephrotic syndrome appears to be driven by a small number of large-effect loci. The MHC locus on chromosome 6p21 is strongly associated with genetic susceptibility to all major types of immune-mediated glomerulopathies. However, a distinct set of classical HLA alleles is associated with each individual disease type, pinpointing to specific immune mechanisms underlying each of these conditions. Additional insights from the discovery of non-HLA risk loci reinforced the role of innate and adaptive immunity in the pathogenesis of these disorders, and highlighted important susceptibility overlaps between glomerular and other autoimmune and inflammatory conditions. Despite these initial successes, much larger GWAS and sequencing studies are still needed for each individual glomerular disease type. Increased power will be critical to comprehensively test for genetic effects across the full spectrum of allelic frequencies, to detect gene-gene and gene-environment interactions, and to potentially improve the performance of polygenic risk predictors. Moreover, the existing studies are limited mostly to European and East Asian populations, stressing the urgency to expand genetic discovery efforts to more diverse populations worldwide.10.2215/CJN.14031119Fri, 17 Jul 2020 07:54:21 GMT-07:00GWAS-Based Discoveries in IgA Nephropathy, Membranous Nephropathy, and Steroid-Sensitive Nephrotic SyndromeOver the past decade, genome-wide association studies (GWAS) have emerged as a powerful tool to understand the genetic basis of complex traits in humans. The GWAS approach has been successfully applied to primary glomerular disorders, providing numerous novel insights into the genetic architecture of IgA nephropathy, membranous nephropathy, and steroid-sensitive nephrotic syndrome. IgA nephropathy appears to have a highly complex polygenic architecture, with nearly 20 genome-wide significant loci of small-to-moderate effects discovered to date. In contrast, the genetic susceptibility to membranous nephropathy and steroid-sensitive nephrotic syndrome appears to be driven by a small number of large-effect loci. The MHC locus on chromosome 6p21 is strongly associated with genetic susceptibility to all major types of immune-mediated glomerulopathies. However, a distinct set of classical HLA alleles is associated with each individual disease type, pinpointing to specific immune mechanisms underlying each of these conditions. Additional insights from the discovery of non-HLA risk loci reinforced the role of innate and adaptive immunity in the pathogenesis of these disorders, and highlighted important susceptibility overlaps between glomerular and other autoimmune and inflammatory conditions. Despite these initial successes, much larger GWAS and sequencing studies are still needed for each individual glomerular disease type. Increased power will be critical to comprehensively test for genetic effects across the full spectrum of allelic frequencies, to detect gene-gene and gene-environment interactions, and to potentially improve the performance of polygenic risk predictors. Moreover, the existing studies are limited mostly to European and East Asian populations, stressing the urgency to expand genetic discovery efforts to more diverse populations worldwide.Sanchez-Rodriguez, ElenaSouthard, Christopher T.Kiryluk, Krzysztof2020-07-17T07:54:21-07:00doi:10.2215/CJN.14031119hwp:resource-id:clinjasn;16/3/458American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, IgA nephropathy, membranous nephropathy, steroid sensitive nephrotic syndrome, GWAS, human genetics, kidney genomics series, nephrotic syndrome, glomerulonephritisGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-03-08March 08, 202110.2215/CJN.140311191555-90411555-905X2020-07-17T07:54:21-07:002021-03-08Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease163458466
- Acute Kidney Injury among Black Patients with Sickle Cell Trait and Sickle Cell Disease10.2215/CJN.06960520Mon, 01 Mar 2021 06:01:35 GMT-08:00Acute Kidney Injury among Black Patients with Sickle Cell Trait and Sickle Cell DiseaseOlaniran, Kabir O.Allegretti, Andrew S.Zhao, Sophia H.Nigwekar, Sagar U.Kalim, Sahir2021-03-01T06:01:35-08:00doi:10.2215/CJN.06960520hwp:resource-id:clinjasn;16/3/348American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysickle cell trait, sickle cell disease, AKI, Black race, hazard ratio, incidence, eGFR declineOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-03-08March 08, 202110.2215/CJN.069605201555-90411555-905X2021-03-01T06:01:35-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles163348355
- Pathophysiology and Treatment of Enteric HyperoxaluriaEnteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative–sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.10.2215/CJN.08000520Tue, 08 Sep 2020 08:21:41 GMT-07:00Pathophysiology and Treatment of Enteric HyperoxaluriaEnteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative–sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.Witting, CelesteLangman, Craig B.Assimos, DeanBaum, Michelle A.Kausz, AnnamariaMilliner, DawnTasian, GregWorcester, ElaineAllain, MeaghanWest, MelissaKnauf, FelixLieske, John C.2020-09-08T08:21:41-07:00doi:10.2215/CJN.08000520hwp:resource-id:clinjasn;16/3/487American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hyperoxaluria, fat malabsorption, nephrolithiasisReviewReviewreview-article20212021-03-08March 08, 202110.2215/CJN.080005201555-90411555-905X2020-09-08T08:21:41-07:002021-03-08Clinical Journal of the American Society of NephrologyReview163487495
- Source of Post-Transplant Care and Mortality among Kidney Transplant Recipients Dually Enrolled in VA and Medicare10.2215/CJN.10020620Thu, 18 Feb 2021 09:43:53 GMT-08:00Source of Post-Transplant Care and Mortality among Kidney Transplant Recipients Dually Enrolled in VA and MedicareCashion, WinnGellad, Walid F.Sileanu, Florentina E.Mor, Maria K.Fine, Michael J.Hale, JenniferHall, Daniel E.Rogal, ShariSwitzer, GalenRamkumar, MohanWang, VirginiaBronson, Douglas A.Wilson, MarkGunnar, WilliamWeisbord, Steven D.2021-02-18T09:43:53-08:00doi:10.2215/CJN.10020620hwp:resource-id:clinjasn;16/3/437American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, transplant outcomes, survival, veterans, MedicareOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-03-08March 08, 202110.2215/CJN.100206201555-90411555-905X2021-02-18T09:43:53-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles1633437337445339
- Recurrent Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) Treatment10.2215/CJN.00950121Fri, 19 Feb 2021 10:57:44 GMT-08:00Recurrent Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor (RAASi) TreatmentBolaños, Jonathan A.Seliger, Stephen L.2021-02-19T10:57:44-08:00doi:10.2215/CJN.00950121hwp:resource-id:clinjasn;16/3/345American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, renin angiotensin system, cardiovascular diseaseEditorialsEditorialseditorial20212021-03-08March 08, 202110.2215/CJN.009501211555-90411555-905X2021-02-19T10:57:44-08:002021-03-08Clinical Journal of the American Society of NephrologyEditorials1633345365347373
- Ambulatory Treatments for RAAS Inhibitor–Related Hyperkalemia and the 1-Year Risk of Recurrence10.2215/CJN.12990820Fri, 19 Feb 2021 10:46:54 GMT-08:00Ambulatory Treatments for RAAS Inhibitor–Related Hyperkalemia and the 1-Year Risk of RecurrenceHundemer, Gregory L.Talarico, RobertTangri, NavdeepLeon, Silvia J.Bota, Sarah E.Rhodes, EmilyKnoll, Greg A.Sood, Manish M.2021-02-19T10:46:54-08:00doi:10.2215/CJN.12990820hwp:resource-id:clinjasn;16/3/365American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, epidemiology and outcomes, electrolytes, renin, clinical nephrology, hyperkalemia, renin-angiotensin system, recurrenceOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-03-08March 08, 202110.2215/CJN.129908201555-90411555-905X2021-02-19T10:46:54-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles1633365345373347
- The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney Transplantation10.2215/CJN.11420720Fri, 26 Feb 2021 11:02:18 GMT-08:00The Association of Time to Organ Procurement on Short- and Long-Term Outcomes in Kidney TransplantationEerola, VernerHelanterä, IlkkaBut, AnnaLempinen, MarkoMäkisalo, HeikkiNordin, ArnoIsoniemi, HelenaSallinen, Ville2021-02-26T11:02:18-08:00doi:10.2215/CJN.11420720hwp:resource-id:clinjasn;16/3/427American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydelayed graft function, chronic allograft failure, acute rejection, kidney transplantation, Tissue and Organ ProcurementOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-03-08March 08, 202110.2215/CJN.114207201555-90411555-905X2021-02-26T11:02:18-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles1633427340436342
- Deep Learning Model for Real-Time Prediction of Intradialytic Hypotension10.2215/CJN.09280620Thu, 11 Feb 2021 12:11:00 GMT-08:00Deep Learning Model for Real-Time Prediction of Intradialytic HypotensionLee, HojunYun, DonghwanYoo, JayeonYoo, KiyoonKim, Yong ChulKim, Dong KiOh, Kook-HwanJoo, Kwon WookKim, Yon SuKwak, NojunHan, Seung Seok2021-02-11T12:11:00-08:00doi:10.2215/CJN.09280620hwp:resource-id:clinjasn;16/3/396American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyartificial intelligence, deep learning, hemodialysis, intradialytic hypotension, machine learning, hypotensionOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-03-08March 08, 202110.2215/CJN.092806201555-90411555-905X2021-02-11T12:11:00-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles1633396343406344
- Patients with Protein-Truncating PKD1 Mutations and Mild ADPKD10.2215/CJN.11100720Thu, 18 Feb 2021 09:17:36 GMT-08:00Patients with Protein-Truncating PKD1 Mutations and Mild ADPKDLanktree, Matthew B.Guiard, ElsaAkbari, PedramPourafkari, MarinaIliuta, Ioan-AndreiAhmed, SyedHaghighi, AmirrezaHe, NingSong, XuewenPaterson, Andrew D.Khalili, KoroshPei, York P.C.2021-02-18T09:17:36-08:00doi:10.2215/CJN.11100720hwp:resource-id:clinjasn;16/3/374American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypolycystic kidney disease, genetic kidney disease, ADPKD, human genetics, mutationOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20212021-03-08March 08, 202110.2215/CJN.111007201555-90411555-905X2021-02-18T09:17:36-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles163374383
- Nocturnal Systolic Hypertension and Adverse Prognosis in Patients with CKD10.2215/CJN.14420920Wed, 10 Feb 2021 08:08:30 GMT-08:00Nocturnal Systolic Hypertension and Adverse Prognosis in Patients with CKDWang, QinWang, YuWang, JinweiZhang, LuxiaZhao, Ming-Hui,,Zhao, Ming-HuiZhang, LuxiaWang, XiaoqinYuan, JunZhou, QiaolingYuan, QiongjingChen, MenghuaZhou, XiaolingFu, ShuxiaLi, ShaomeiZha, YanHuang, RongsaiLiu, ZhangsuoZhang, JunJunWang, LiPu, LeiLiu, JianLi, SuhuaXiong, ZuyingLiang, WeiZhao, JinghongMu, JiaoLian, XiyanLiao, YunjuanGan, HuaWang, RongLv, ZhimeiLiao, YunhuaPan, LingYang, XiaopingLin, ZhifengTong, ZongwuZhu, YunHe, QiangWu, FuquanLi, RongRong, KaiWang, CailiZhang, YanhuiWang, YueTang, WenWu, HuaZhao, BanLi, RongshanWang, LihuaLi, DetianDu, FengWu, YongguiZhang, WeiLin, ShanXu, PengchengLin, HongliHu, ZhaoPei, FeiZhang, HaisongGao, YanSun, LuyingLi, XiaWang, WenkeLv, FenglingWang, DeguangWang, XuerongXu, DongmeiTang, LijunMa, YingchunWang, TingtingFu, PingWang, TingliXing, ChangyingZhang, ChengningXu, XudongHe, HaidongLiao, XiaohuiXie, ShuqinHu, GuicaiHuang, Lan2021-02-10T08:08:30-08:00doi:10.2215/CJN.14420920hwp:resource-id:clinjasn;16/3/356American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyambulatory blood pressure monitoring, nocturnal systolic hypertension, chronic kidney disease, end-stage renal disease, cardiovascular events, hypertensionOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-03-08March 08, 202110.2215/CJN.144209201555-90411555-905X2021-02-10T08:08:30-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles163356364
- Acute Kidney Injury, Microvascular Rarefaction, and Estimated Glomerular Filtration Rate in Kidney Transplant Recipients10.2215/CJN.07270520Mon, 01 Mar 2021 06:01:34 GMT-08:00Acute Kidney Injury, Microvascular Rarefaction, and Estimated Glomerular Filtration Rate in Kidney Transplant RecipientsDoreille, AliceAzzi, FéryelLarivière-Beaudoin, StéphanieKarakeussian-Rimbaud, AnnieTrudel, DominiqueHébert, Marie-JoséeDieudé, MélaniePatey, NatachaCardinal, Héloïse2021-03-01T06:01:34-08:00doi:10.2215/CJN.07270520hwp:resource-id:clinjasn;16/3/415American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, chronic kidney failure, delayed graft function, pathophysiology of renal disease and progression, microvascular rarefaction, kidney transplantation, acute kidney injuryOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-03-08March 08, 202110.2215/CJN.072705201555-90411555-905X2021-03-01T06:01:34-08:002021-03-08Clinical Journal of the American Society of NephrologyOriginal Articles163415426
- Post-Kidney Transplant Care and Health Outcomes of US Veterans10.2215/CJN.00580121Thu, 18 Feb 2021 09:51:56 GMT-08:00Post-Kidney Transplant Care and Health Outcomes of US VeteransKrishnan, NamrataCrowley, Susan T.2021-02-18T09:51:56-08:00doi:10.2215/CJN.00580121hwp:resource-id:clinjasn;16/3/337American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplant, health outcomes, dual care, health equity, veteransEditorialsEditorialseditorial20212021-03-08March 08, 202110.2215/CJN.005801211555-90411555-905X2021-02-18T09:51:56-08:002021-03-08Clinical Journal of the American Society of NephrologyEditorials1633337437339445
- Preprint Servers in Kidney Disease ResearchPreprint servers, such as arXiv and bioRxiv, have disrupted the scientific communication landscape by providing rapid access to research before peer review. medRxiv was launched as a free online repository for preprints in the medical, clinical, and related health sciences in 2019. In this review, we present the uptake of preprint server use in nephrology and discuss specific considerations regarding preprint server use in medicine. Distribution of kidney-related research on preprint servers is rising at an exponential rate. Survey of nephrology journals identified that 15 of 17 (88%) are publishing original research accepted submissions that have been uploaded to preprint servers. After reviewing 52 clinically impactful trials in nephrology discussed in the online Nephrology Journal Club (NephJC), an average lag of 300 days was found between study completion and publication, indicating an opportunity for faster research dissemination. Rapid review of papers discussing benefits and risks of preprint server use from the researcher, publisher, or end user perspective identified 53 papers that met criteria. Potential benefits of biomedical preprint servers included rapid dissemination, improved transparency of the peer review process, greater visibility and recognition, and collaboration. However, these benefits come at the risk of rapid spread of results not yet subjected to the rigors of peer review. Preprint servers shift the burden of critical appraisal to the reader. Media may be especially at risk due to their focus on “late-breaking” information. Preprint servers have played an even larger role when late-breaking research results are of special interest, such as during the global coronavirus disease 2019 pandemic. Coronavirus disease 2019 has brought both the benefits and risks of preprint servers to the forefront. Given the prominent online presence of the nephrology community, it is poised to lead the medicine community in appropriate use of preprint servers.10.2215/CJN.03800320Fri, 17 Jul 2020 07:54:21 GMT-07:00Preprint Servers in Kidney Disease ResearchPreprint servers, such as arXiv and bioRxiv, have disrupted the scientific communication landscape by providing rapid access to research before peer review. medRxiv was launched as a free online repository for preprints in the medical, clinical, and related health sciences in 2019. In this review, we present the uptake of preprint server use in nephrology and discuss specific considerations regarding preprint server use in medicine. Distribution of kidney-related research on preprint servers is rising at an exponential rate. Survey of nephrology journals identified that 15 of 17 (88%) are publishing original research accepted submissions that have been uploaded to preprint servers. After reviewing 52 clinically impactful trials in nephrology discussed in the online Nephrology Journal Club (NephJC), an average lag of 300 days was found between study completion and publication, indicating an opportunity for faster research dissemination. Rapid review of papers discussing benefits and risks of preprint server use from the researcher, publisher, or end user perspective identified 53 papers that met criteria. Potential benefits of biomedical preprint servers included rapid dissemination, improved transparency of the peer review process, greater visibility and recognition, and collaboration. However, these benefits come at the risk of rapid spread of results not yet subjected to the rigors of peer review. Preprint servers shift the burden of critical appraisal to the reader. Media may be especially at risk due to their focus on “late-breaking” information. Preprint servers have played an even larger role when late-breaking research results are of special interest, such as during the global coronavirus disease 2019 pandemic. Coronavirus disease 2019 has brought both the benefits and risks of preprint servers to the forefront. Given the prominent online presence of the nephrology community, it is poised to lead the medicine community in appropriate use of preprint servers.Vlasschaert, CaitlynGiles, CameronHiremath, SwapnilLanktree, Matthew B.2020-07-17T07:54:21-07:00doi:10.2215/CJN.03800320hwp:resource-id:clinjasn;16/3/479American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPreprint, social media, peer review, kidney disease, educationFeatureFeatureresearch-article20212021-03-08March 08, 202110.2215/CJN.038003201555-90411555-905X2020-07-17T07:54:21-07:002021-03-08Clinical Journal of the American Society of NephrologyFeature163479486
- Leveraging Deep Learning to Improve Safety of Outpatient Hemodialysis10.2215/CJN.00450121Thu, 11 Feb 2021 12:21:07 GMT-08:00Leveraging Deep Learning to Improve Safety of Outpatient HemodialysisCorrea, SimonMc Causland, Finnian R.2021-02-11T12:21:07-08:00doi:10.2215/CJN.00450121hwp:resource-id:clinjasn;16/3/343American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, hypotension, outpatients, deep learningEditorialsEditorialseditorial20212021-03-08March 08, 202110.2215/CJN.004501211555-90411555-905X2021-02-11T12:21:07-08:002021-03-08Clinical Journal of the American Society of NephrologyEditorials1633343396344406
- Ensuring the Equitable Advancement of American Kidney Health—the Need to Account for Socioeconomic Disparities in the ESRD Treatment Choices Model10.1681/ASN.2020101466Wed, 30 Dec 2020 07:39:40 GMT-08:00Ensuring the Equitable Advancement of American Kidney Health—the Need to Account for Socioeconomic Disparities in the ESRD Treatment Choices ModelReddy, Yuvaram N.V.Tummalapalli, Sri LekhaMendu, Mallika L.2020-12-30T07:39:40-08:00doi:10.1681/ASN.2020101466hwp:resource-id:jnephrol;32/2/265American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyAdvancing American Kidney Health initiative, social determinants of health, health policy, home dialysis, ESRD Treatment Choices modelUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20212021-02-01February 202110.1681/ASN.20201014661046-66731533-34502020-12-30T07:39:40-08:002021-02Journal of the American Society of NephrologyUp Front Matters322265267
- Separate and Unequal: Race-Based Algorithms and Implications for Nephrology10.1681/ASN.2020081175Thu, 28 Jan 2021 09:35:55 GMT-08:00Separate and Unequal: Race-Based Algorithms and Implications for NephrologySchmidt, Insa M.Waikar, Sushrut S.2021-01-28T09:35:55-08:00doi:10.1681/ASN.2020081175hwp:resource-id:jnephrol;32/3/529American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrace-based algorithms, medicine, racism, nephrologyPerspectivesPerspectivesresearch-article20212021-03-01March 202110.1681/ASN.20200811751046-66731533-34502021-01-28T09:35:55-08:002021-03Journal of the American Society of NephrologyPerspectives323529533
- Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study10.1681/ASN.2020030239Mon, 18 Jan 2021 09:18:39 GMT-08:00Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) StudyZheng, ZiheWaikar, Sushrut S.Schmidt, Insa M.Landis, J. RichardHsu, Chi-yuanShafi, TariqFeldman, Harold I.Anderson, Amanda H.Wilson, Francis P.Chen, JingRincon-Choles, HernanRicardo, Ana C.Saab, GeorgesIsakova, TamaraKallem, RadhakrishnaFink, Jeffrey C.Rao, Panduranga S.Xie, DaweiYang, Wei,,Appel, Lawrence J.Go, Alan S.He, JiangLash, James P.Rahman, MahboobTownsend, Raymond R.2021-01-18T09:18:39-08:00doi:10.1681/ASN.2020030239hwp:resource-id:jnephrol;32/3/639American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCKD subgroups, clustering analysis, patient heterogeneity, survivalClinical EpidemiologyClinical Epidemiologyresearch-article20212021-03-01March 202110.1681/ASN.20200302391046-66731533-34502021-01-18T09:18:39-08:002021-03Journal of the American Society of NephrologyClinical Epidemiology323639653
- Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA Nephropathy10.1681/ASN.2020060823Tue, 16 Feb 2021 08:29:16 GMT-08:00Interaction between GALNT12 and C1GALT1 Associates with Galactose-Deficient IgA1 and IgA NephropathyWang, Yan-NaZhou, Xu-JieChen, PeiYu, Gui-ZhenZhang, XueHou, PingLiu, Li-JunShi, Su-FangLv, Ji-ChengZhang, Hong2021-02-16T08:29:16-08:00doi:10.1681/ASN.2020060823hwp:resource-id:jnephrol;32/3/545American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhuman genetics, IgA nephropathy, glomerulonephritis, IgA, immune complexesRapid CommunicationsRapid Communicationsother20212021-03-01March 202110.1681/ASN.20200608231046-66731533-34502021-02-16T08:29:16-08:002021-03Journal of the American Society of NephrologyRapid Communications323545552
- Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury10.1681/ASN.2020050717Fri, 29 Jan 2021 09:37:00 GMT-08:00Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion InjuryChiba, TakutoCerqueira, Débora M.Li, YaoBodnar, Andrew J.Mukherjee, ElinaPfister, KatherinePhua, Yu LengShaikh, KaiSanders, Brandon T.Hemker, Shelby L.Pagano, Patrick J.Wu, Yijen L.Ho, JacquelineSims-Lucas, Sunder2021-01-29T09:37:00-08:00doi:10.1681/ASN.2020050717hwp:resource-id:jnephrol;32/3/553American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologymicroRNA, acute kidney injury, renal microvasculatureRapid CommunicationsRapid Communicationsresearch-article20212021-03-01March 202110.1681/ASN.20200507171046-66731533-34502021-01-29T09:37:00-08:002021-03Journal of the American Society of NephrologyRapid Communications323553562
- Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients10.1681/ASN.2020050598Fri, 05 Feb 2021 11:37:45 GMT-08:00Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis PatientsIsaka, YoshitakaHamano, TakayukiFujii, HidekiTsujimoto, YoshihiroKoiwa, FumihikoSakaguchi, YusukeTanaka, RyoichiTomiyama, NoriyukiTatsugami, FuminariTeramukai, Satoshi2021-02-05T11:37:45-08:00doi:10.1681/ASN.2020050598hwp:resource-id:jnephrol;32/3/723American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperphosphatemia, dialysis, coronary calcification, phosphate bindersClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200505981046-66731533-34502021-02-05T11:37:45-08:002021-03Journal of the American Society of NephrologyClinical Research3233723526735528
- Heterozygosity for a Pathogenic Variant in SLC12A3 That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum Potassium10.1681/ASN.2020071030Thu, 04 Feb 2021 08:54:27 GMT-08:00Heterozygosity for a Pathogenic Variant in SLC12A3 That Causes Autosomal Recessive Gitelman Syndrome Is Associated with Lower Serum PotassiumWan, XuesiPerry, JamesZhang, HaichenJin, FengRyan, Kathleen A.Van Hout, CristopherReid, JeffreyOverton, JohnBaras, ArisHan, ZheStreeten, ElizabethLi, YanbingMitchell, Braxton D.Shuldiner, Alan R.Fu, Mao,,Abecasis, GoncaloBaras, ArisCantor, MichaelCoppola, GiovanniEconomides, ArisOverton, John D.Reid, Jeffrey G.Shuldiner, AlanBeechert, ChristinaForsythe, CaitlinFuller, Erin D.Gu, ZhenhuaLattari, MichaelLopez, AlexanderSchleicher, Thomas D.Padilla, Maria SotiropoulosToledo, KarinaWidom, LouisWolf, Sarah E.Pradhan, ManasiManoochehri, KiaUlloa, Ricardo H.Bai, XiaodongBalasubramanian, SuganthiBarnard, LelandBlumenfeld, AndrewChai, YatingEom, GisuHabegger, LukasHahn, YoungHawes, AliciaKhalid, ShareefMaxwell, Evan K.Penn, JohnStaples, Jeffrey C.Yadav, AshishGuzzardo, Paloma M.Jones, Marcus B.Mitnaul, Lyndon J.2021-02-04T08:54:27-08:00doi:10.1681/ASN.2020071030hwp:resource-id:jnephrol;32/3/756American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypotassium, Gitelman syndrome, heterozygosity, whole-exome sequencing, genetic renal diseaseClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200710301046-66731533-34502021-02-04T08:54:27-08:002021-03Journal of the American Society of NephrologyClinical Research323756765
- In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes10.1681/ASN.2020081181Thu, 21 Jan 2021 10:45:06 GMT-08:00In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different PhenotypesRavindran, AishwaryaCasal Moura, MartaFervenza, Fernando C.Nasr, Samih H.Alexander, Mariam P.Fidler, Mary E.Herrera Hernandez, Loren P.Zhang, PingchuanGrande, Joseph P.Cornell, Lynn D.Gross, Lou AnnNegron, VivianJenson, Grace E.Madden, Benjamin J.Charlesworth, M. CristineSethi, Sanjeev2021-01-21T10:45:06-08:00doi:10.1681/ASN.2020081181hwp:resource-id:jnephrol;32/3/695American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, renal biopsy, lupus nephritisClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200811811046-66731533-34502021-01-21T10:45:06-08:002021-03Journal of the American Society of NephrologyClinical Research3233695525706526
- Effect of Kidney Function on Relationships between Lifestyle Behaviors and Mortality or Cardiovascular Outcomes: A Pooled Cohort Analysis10.1681/ASN.2020040394Fri, 05 Feb 2021 10:53:20 GMT-08:00Effect of Kidney Function on Relationships between Lifestyle Behaviors and Mortality or Cardiovascular Outcomes: A Pooled Cohort AnalysisSchrauben, Sarah J.Hsu, Jesse Y.Amaral, SandraAnderson, Amanda H.Feldman, Harold I.Dember, Laura M.2021-02-05T10:53:20-08:00doi:10.1681/ASN.2020040394hwp:resource-id:jnephrol;32/3/663American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, chronic renal failure, mortality risk, heart failure, health behaviors, lifestyleClinical EpidemiologyClinical Epidemiologyresearch-article20212021-03-01March 202110.1681/ASN.20200403941046-66731533-34502021-02-05T10:53:20-08:002021-03Journal of the American Society of NephrologyClinical Epidemiology323663675
- SRGAP1 Controls Small Rho GTPases To Regulate Podocyte Foot Process Maintenance10.1681/ASN.2020081126Fri, 29 Jan 2021 09:37:01 GMT-08:00SRGAP1 Controls Small Rho GTPases To Regulate Podocyte Foot Process MaintenanceRogg, ManuelMaier, Jasmin I.Dotzauer, RobertArtelt, NadineKretz, OliverHelmstädter, MartinAbed, AhmedSammarco, AlenaSigle, AugustSellung, DominikDinse, PatrickReiche, KarolineYasuda-Yamahara, MakoBiniossek, Martin L.Walz, GerdWerner, MartinEndlich, NicoleSchilling, OliverHuber, Tobias B.Schell, Christoph2021-01-29T09:37:01-08:00doi:10.1681/ASN.2020081126hwp:resource-id:jnephrol;32/3/563American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycell adhesion, cell signaling, focal segmental glomerulosclerosis, glomerular epithelial cells, nephrotic syndrome, podocyte, Rho GTPase, RhoGAP, Srgap1Basic ResearchBasic Researchresearch-article20212021-03-01March 202110.1681/ASN.20200811261046-66731533-34502021-01-29T09:37:01-08:002021-03Journal of the American Society of NephrologyBasic Research323563579
- Urinary Single-Cell Profiling Captures the Cellular Diversity of the Kidney10.1681/ASN.2020050757Tue, 02 Feb 2021 11:20:56 GMT-08:00Urinary Single-Cell Profiling Captures the Cellular Diversity of the KidneyAbedini, AminZhu, Yuan O.Chatterjee, ShataksheeHalasz, GaborDevalaraja-Narashimha, KishorShrestha, RojeshS. Balzer, MichaelPark, JihwanZhou, TongMa, ZiyuanSullivan, Katie MarieHu, HailongSheng, XinLiu, HongboWei, YiBoustany-Kari, Carine M.Patel, UptalAlmaani, SalemPalmer, MatthewTownsend, RaymondBlady, ShiraHogan, Jonathan,Morton, LoriSusztak, Katalin,Susztak, KatalinTownsend, RaymondBlady, ShiraPalmer, MatthewBoustany, CarineUrquhart, RichardGuarnieri, PaoloSarov-Blat, LeaHu, ErdingMorton, LoriDevalaraja, KishorPatel, UptalBadal, ShawnLiles, JohnRosen, JonathanKarihaloo, AnilLuciano, RandyHogan, JonathanMottl, AmyBansal, ShwetaAlmaani, SalemArgyropoulos, ChristosCampbell, KirkIsakova, TamaraLenz, OliverSzerlip, HaroldKretzler, MatthiasCanetta, PietroSchelling, JefferyAvasare, RupaliBrosius, FrankRoss, MichaelKopyt, NelsonTumlin, JamesScialla, JuliaLafayette, RichardSingh, ManishaZhong, Yan2021-02-02T11:20:56-08:00doi:10.1681/ASN.2020050757hwp:resource-id:jnephrol;32/3/614American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic kidney disease, urine, single-cell transcriptomics, RNA sequencingBasic ResearchBasic Researchresearch-article20212021-03-01March 202110.1681/ASN.20200507571046-66731533-34502021-02-02T11:20:56-08:002021-03Journal of the American Society of NephrologyBasic Research323614627
- Impairment of Proteasome Function in Podocytes Leads to CKD10.1681/ASN.2019101025Thu, 28 Jan 2021 09:35:55 GMT-08:00Impairment of Proteasome Function in Podocytes Leads to CKDMakino, Shin-ichiShirata, NaritoshiOliva Trejo, Juan AlejandroYamamoto-Nonaka, KanaeYamada, HiroyukiMiyake, TakafumiMori, KiyoshiNakagawa, TakahikoTashiro, YoshitakaYamashita, HirofumiYanagita, MotokoTakahashi, RyosukeAsanuma, Katsuhiko2021-01-28T09:35:55-08:00doi:10.1681/ASN.2019101025hwp:resource-id:jnephrol;32/3/597American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, ubiquitin-proteasome system, autophagy-lysosomal system, oxidative stress, apoptosisBasic ResearchBasic Researchresearch-article20212021-03-01March 202110.1681/ASN.20191010251046-66731533-34502021-01-28T09:35:55-08:002021-03Journal of the American Society of NephrologyBasic Research323597613
- A Randomized Clinical Trial of Anti–IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection10.1681/ASN.2020071106Fri, 18 Dec 2020 11:57:35 GMT-08:00A Randomized Clinical Trial of Anti–IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant RejectionDoberer, KonstantinDuerr, MichaelHalloran, Philip F.Eskandary, FarsadBudde, KlemensRegele, HeinzReeve, JeffBorski, AnitaKozakowski, NicolasReindl-Schwaighofer, RomanWaiser, JohannesLachmann, NilsSchranz, SabineFirbas, ChristaMühlbacher, JakobGelbenegger, GeorgPerkmann, ThomasWahrmann, MarkusKainz, AlexanderRistl, RobinHalleck, FabianBond, GregorChong, EdwardJilma, BerndBöhmig, Georg A.2020-12-18T11:57:35-08:00doi:10.1681/ASN.2020071106hwp:resource-id:jnephrol;32/3/708American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyantibody-mediated rejection, chronic rejection, interleukin-6, monoclonal antibody, renal transplantation, randomized controlled trialClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200711061046-66731533-34502020-12-18T11:57:35-08:002021-03Journal of the American Society of NephrologyClinical Research323708722
- This Month's Highlights10.1681/ASN.2021010073Fri, 26 Feb 2021 11:00:25 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2021-02-26T11:00:25-08:00doi:10.1681/ASN.2021010073hwp:resource-id:jnephrol;32/3/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20212021-03-01March 202110.1681/ASN.20210100731046-66731533-34502021-02-26T11:00:25-08:002021-03Journal of the American Society of NephrologyThis Month's Highlights323ii
- In Search of the Optimal Target for Phosphate Control: Episode 110.1681/ASN.2021010027Fri, 05 Feb 2021 11:24:40 GMT-08:00In Search of the Optimal Target for Phosphate Control: Episode 1Wald, RonWalsh, Michael W.2021-02-05T11:24:40-08:00doi:10.1681/ASN.2021010027hwp:resource-id:jnephrol;32/3/526American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate binders, randomized controlled trials, vascular calcificationEditorialsEditorialseditorial20212021-03-01March 202110.1681/ASN.20210100271046-66731533-34502021-02-05T11:24:40-08:002021-03Journal of the American Society of NephrologyEditorials3233526723528735
- Glomerular Exostosin Deposits in Membranous Lupus Nephritis—a Dialogue10.1681/ASN.2020121810Mon, 25 Jan 2021 07:55:48 GMT-08:00Glomerular Exostosin Deposits in Membranous Lupus Nephritis—a DialogueHilhorst, MarcAnders, Hans-Joachim2021-01-25T07:55:48-08:00doi:10.1681/ASN.2020121810hwp:resource-id:jnephrol;32/3/525American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, membranous nephropathy, lupus nephritis, systemic lupus erythematosusEditorialsEditorialseditorial20212021-03-01March 202110.1681/ASN.20201218101046-66731533-34502021-01-25T07:55:48-08:002021-03Journal of the American Society of NephrologyEditorials3233525695526706
- Reflections of a Naïve Trainee to Barnes Jewish Hospital/Washington University in 1970—My First 25 Years10.1681/ASN.2020101516Thu, 28 Jan 2021 09:35:54 GMT-08:00Reflections of a Naïve Trainee to Barnes Jewish Hospital/Washington University in 1970—My First 25 YearsMorrison, Aubrey R.2021-01-28T09:35:54-08:00doi:10.1681/ASN.2020101516hwp:resource-id:jnephrol;32/3/543American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologysocial justice, under represented minoritiesSpecial ArticleSpecial Articleresearch-article20212021-03-01March 202110.1681/ASN.20201015161046-66731533-34502021-01-28T09:35:54-08:002021-03Journal of the American Society of NephrologySpecial Article323543544
- Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 Study10.1681/ASN.2020081150Wed, 10 Feb 2021 08:13:45 GMT-08:00Roxadustat for Treating Anemia in Patients with CKD Not on Dialysis: Results from a Randomized Phase 3 StudyFishbane, StevenEl-Shahawy, Mohamed A.Pecoits-Filho, RobertoVan, Bui PhamHouser, Mark T.Frison, LarsLittle, Dustin J.Guzman, Nicolas J.Pergola, Pablo E.2021-02-10T08:13:45-08:00doi:10.1681/ASN.2020081150hwp:resource-id:jnephrol;32/3/737American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic kidney disease, clinical nephrology, randomized controlled trials, clinical trialClinical ResearchClinical Researchresearch-article20212021-03-01March 202110.1681/ASN.20200811501046-66731533-34502021-02-10T08:13:45-08:002021-03Journal of the American Society of NephrologyClinical Research323667371537153775515371538
- Autoimmunity in Acute Poststreptococcal GN: A Neglected Aspect of the DiseaseAcute poststreptococcal GN (APSGN) is the prototype of immune complex GN and is associated with manifestations of autoimmune reactivity that have been neglected as epiphenomena. Recently, studies have demonstrated transient antifactor B autoantibodies that activate the alternative complement pathway, bringing self-immunity to a central position in the pathogenesis of APSGN. Therefore, examining other manifestations of autoimmunity that have been reported in association with poststreptococcal GN is of interest. This article reviews the renal and extrarenal manifestations of autoimmune reactivity in APSGN and considers their potential relevance in modifying the usually benign clinical course of the disease. It also discusses related aspects of the nephritogenic antigens, complement activation, and genetic elements associated with immune reactivity and their potential relevance to the familial incidence of the disease.10.1681/ASN.2020081228Tue, 02 Feb 2021 11:20:56 GMT-08:00Autoimmunity in Acute Poststreptococcal GN: A Neglected Aspect of the DiseaseAcute poststreptococcal GN (APSGN) is the prototype of immune complex GN and is associated with manifestations of autoimmune reactivity that have been neglected as epiphenomena. Recently, studies have demonstrated transient antifactor B autoantibodies that activate the alternative complement pathway, bringing self-immunity to a central position in the pathogenesis of APSGN. Therefore, examining other manifestations of autoimmunity that have been reported in association with poststreptococcal GN is of interest. This article reviews the renal and extrarenal manifestations of autoimmune reactivity in APSGN and considers their potential relevance in modifying the usually benign clinical course of the disease. It also discusses related aspects of the nephritogenic antigens, complement activation, and genetic elements associated with immune reactivity and their potential relevance to the familial incidence of the disease.Rodriguez-Iturbe, Bernardo2021-02-02T11:20:56-08:00doi:10.1681/ASN.2020081228hwp:resource-id:jnephrol;32/3/534American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, poststreptococcal nephritis, autoimmunity, complement, anti-immunoglobulinsReviewsReviewsreview-article20212021-03-01March 202110.1681/ASN.20200812281046-66731533-34502021-02-02T11:20:56-08:002021-03Journal of the American Society of NephrologyReviews323534542
- Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC Study10.1681/ASN.2020030301Thu, 28 Jan 2021 09:35:55 GMT-08:00Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC StudyKim, Esther D.Soliman, Elsayed Z.Coresh, JosefMatsushita, KunihiroChen, Lin Yee2021-01-28T09:35:55-08:00doi:10.1681/ASN.2020030301hwp:resource-id:jnephrol;32/3/629American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, cardiac arrhythmia, atrial fibrillationClinical EpidemiologyClinical Epidemiologyresearch-article20212021-03-01March 202110.1681/ASN.20200303011046-66731533-34502021-01-28T09:35:55-08:002021-03Journal of the American Society of NephrologyClinical Epidemiology323629638
- From Infancy to Fancy: A Glimpse into the Evolutionary Journey of Podocytes in CulturePodocytes are critical components of the filtration barrier and responsible for maintaining healthy kidney function. An assault on podocytes is generally associated with progression of chronic glomerular diseases. Therefore, podocyte pathophysiology is a favorite research subject for nephrologists. Despite this, podocyte research has lagged because of the unavailability of techniques for culturing such specialized cells ex vivo in quantities that are adequate for mechanistic studies. In recent years, this problem was circumvented by the efforts of researchers, who successfully developed several in vitro podocyte cell culture model systems that paved the way for incredible discoveries in the field of nephrology. This review sets us on a journey that provides a comprehensive insight into the groundbreaking breakthroughs and novel technologic advances made in the field of podocyte cell culture so far, beginning from its inception, evolution, and progression. In this study, we also describe in detail the pros and cons of different models that are being used to culture podocytes. Our extensive and exhaustive deliberation on the status of podocyte cell culture will facilitate researchers to choose wisely an appropriate model for their own research to avoid potential pitfalls in the future.10.34067/KID.0006492020Tue, 22 Dec 2020 09:45:36 GMT-08:00From Infancy to Fancy: A Glimpse into the Evolutionary Journey of Podocytes in CulturePodocytes are critical components of the filtration barrier and responsible for maintaining healthy kidney function. An assault on podocytes is generally associated with progression of chronic glomerular diseases. Therefore, podocyte pathophysiology is a favorite research subject for nephrologists. Despite this, podocyte research has lagged because of the unavailability of techniques for culturing such specialized cells ex vivo in quantities that are adequate for mechanistic studies. In recent years, this problem was circumvented by the efforts of researchers, who successfully developed several in vitro podocyte cell culture model systems that paved the way for incredible discoveries in the field of nephrology. This review sets us on a journey that provides a comprehensive insight into the groundbreaking breakthroughs and novel technologic advances made in the field of podocyte cell culture so far, beginning from its inception, evolution, and progression. In this study, we also describe in detail the pros and cons of different models that are being used to culture podocytes. Our extensive and exhaustive deliberation on the status of podocyte cell culture will facilitate researchers to choose wisely an appropriate model for their own research to avoid potential pitfalls in the future.Agarwal, ShivangiSudhini, Yashwanth R.Reiser, JochenAltintas, Mehmet M.2020-12-22T09:45:36-08:00doi:10.34067/KID.0006492020hwp:resource-id:kidney360;2/2/385American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360renal physiology, basic science, cell culture techniques, glomerulonephritis, podocytes, proteinuriaReview ArticlesReview Articlesreview-article20212021-02-2510.34067/KID.00064920202641-76502020-12-22T09:45:36-08:002021-02-25Kidney360Review Articles22385397
- In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite Urolithiasis10.34067/KID.0006942020Wed, 23 Dec 2020 02:00:03 GMT-08:00In Vivo Entombment of Bacteria and Fungi during Calcium Oxalate, Brushite, and Struvite UrolithiasisSaw, Jessica J.Sivaguru, MayandiWilson, Elena M.Dong, YiranSanford, Robert A.Fields, Chris J.Cregger, Melissa A.Merkel, Annette C.Bruce, William J.Weber, Joseph R.Lieske, John C.Krambeck, Amy E.Rivera, Marcelino E.Large, TimothyLange, DirkBhattacharjee, Ananda S.Romero, Michael F.Chia, NicholasFouke, Bruce W.2020-12-23T14:00:03-08:00doi:10.34067/KID.0006942020hwp:resource-id:kidney360;2/2/298American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360nephrolithiasis, bacteria, basic science, fungi entombment, geomicrobiology, kidney stone mineralogy, microbiome, nephrolithiasis, Raman spectroscopy, super-resolution autofluorescence (SRAF) microscopy, urolithiasisOriginal InvestigationsNephrolithiasisOriginal InvestigationsNephrolithiasisresearch-article20212021-02-2510.34067/KID.00069420202641-76502020-12-23T14:00:03-08:002021-02-25Kidney360Original Investigations22298311
- Proximal Tubular Oxidative Metabolism in Acute Kidney Injury and the Transition to CKDThe proximal tubule relies on oxidative mitochondrial metabolism to meet its energy needs and has limited capacity for glycolysis, which makes it uniquely susceptible to damage during AKI, especially after ischemia and anoxia. Under these conditions, mitochondrial ATP production is initially decreased by several mechanisms, including fatty acid–induced uncoupling and inhibition of respiration related to changes in the shape and volume of mitochondria. Glycolysis is initially insufficient as a source of ATP to protect the cells and mitochondrial function, but supplementation of tricarboxylic acid cycle intermediates augments anaerobic ATP production, and improves recovery of mitochondrial oxidative metabolism. Incomplete recovery is characterized by defects of respiratory enzymes and lipid metabolism. During the transition to CKD, tubular cells atrophy but maintain high expression of glycolytic enzymes, and there is decreased fatty acid oxidation. These metabolic changes may be amenable to a number of therapeutic interventions.10.34067/KID.0004772020Tue, 22 Dec 2020 09:45:36 GMT-08:00Proximal Tubular Oxidative Metabolism in Acute Kidney Injury and the Transition to CKDThe proximal tubule relies on oxidative mitochondrial metabolism to meet its energy needs and has limited capacity for glycolysis, which makes it uniquely susceptible to damage during AKI, especially after ischemia and anoxia. Under these conditions, mitochondrial ATP production is initially decreased by several mechanisms, including fatty acid–induced uncoupling and inhibition of respiration related to changes in the shape and volume of mitochondria. Glycolysis is initially insufficient as a source of ATP to protect the cells and mitochondrial function, but supplementation of tricarboxylic acid cycle intermediates augments anaerobic ATP production, and improves recovery of mitochondrial oxidative metabolism. Incomplete recovery is characterized by defects of respiratory enzymes and lipid metabolism. During the transition to CKD, tubular cells atrophy but maintain high expression of glycolytic enzymes, and there is decreased fatty acid oxidation. These metabolic changes may be amenable to a number of therapeutic interventions.Schaub, Jennifer A.Venkatachalam, Manjeri A.Weinberg, Joel M.2020-12-22T09:45:36-08:00doi:10.34067/KID.0004772020hwp:resource-id:kidney360;2/2/355American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, aTP, basic science, CKD, glycolysis, metabolism, mitochondria, tricarboxylic acid cycleBasic Science for CliniciansBasic Science for Cliniciansresearch-article20212021-02-2510.34067/KID.00047720202641-76502020-12-22T09:45:36-08:002021-02-25Kidney360Basic Science for Clinicians22355364
- Meeting the Demand for Renal Replacement Therapy during the COVID-19 Pandemic: A Manufacturer’s Perspective10.34067/KID.0006192020Tue, 29 Dec 2020 01:46:37 GMT-08:00Meeting the Demand for Renal Replacement Therapy during the COVID-19 Pandemic: A Manufacturer’s PerspectiveAnger, Michael S.Mullon, ClaudyFicociello, Linda H.Thompson, DavidKraus, Michael A.Newcomb, PeteKossmann, Robert J.2020-12-29T13:46:37-08:00doi:10.34067/KID.0006192020hwp:resource-id:kidney360;2/2/350American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, AKI, COVID-19, CRRT, dialysis, dialysis machines, emergency response, manufacturer, manufacturingPerspectivePerspectiveresearch-article20212021-02-2510.34067/KID.00061920202641-76502020-12-29T13:46:37-08:002021-02-25Kidney360Perspective22350354
- COVID-19 Antibodies and Outcomes among Outpatient Maintenance Hemodialysis Patients10.34067/KID.0006292020Wed, 09 Dec 2020 02:28:11 GMT-08:00COVID-19 Antibodies and Outcomes among Outpatient Maintenance Hemodialysis PatientsKhatri, MineshIslam, ShahidulDutka, PaulaCarson, JohnDrakakis, JamesImbriano, LouisJawaid, ImranMehta, TapanMiyawaki, NobuyukiWu, ElainYang, StephenAli, NicoleDivers, JasminGrant, CandaceMasani, Naveed2020-12-09T14:28:11-08:00doi:10.34067/KID.0006292020hwp:resource-id:kidney360;2/2/263American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, antibodies, COVID-19, end stage renal disease, hemodialysis, outpatients, SARS-CoV-2Original InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-02-2510.34067/KID.00062920202641-76502020-12-09T14:28:11-08:002021-02-25Kidney360Original Investigations22263269
- Global Dialysis Perspective: Spain10.34067/KID.0005722020Wed, 30 Dec 2020 11:27:19 GMT-08:00Global Dialysis Perspective: SpainRoca-Tey, RamonIbeas, JoseSánchez Alvarez, J. Emilio2020-12-30T11:27:19-08:00doi:10.34067/KID.0005722020hwp:resource-id:kidney360;2/2/344American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, hemodialysis, home dialysis, home hemodialysis, mortality, online hemodiafiltration, peritoneal dialysis, reimbursement, survival, transplantation, vascular accessGlobal PerspectivesGlobal Perspectivesresearch-article20212021-02-2510.34067/KID.00057220202641-76502020-12-30T11:27:19-08:002021-02-25Kidney360Global Perspectives22344349
- Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory Analysis10.34067/KID.0005852020Tue, 08 Dec 2020 01:29:19 GMT-08:00Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory AnalysisTuttle, Katherine R.Rayner, BrianLakshmanan, Mark C.Kwan, Anita Y.M.Konig, ManigeShurzinske, LindaBotros, Fady T.2020-12-08T13:29:19-08:00doi:10.34067/KID.0005852020hwp:resource-id:kidney360;2/2/254American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360diabetes and the kidney, end-stage kidney disease, ESKD, glomerular filtration rate, GLP-1 receptor agonist, kidney failure, macroalbuminuriaOriginal InvestigationsDiabetes and the KidneyOriginal InvestigationsDiabetes and the Kidneyresearch-article20212021-02-2510.34067/KID.00058520202641-76502020-12-08T13:29:19-08:002021-02-25Kidney360Original Investigations22254262
- A Transplant Patient with Blue Lips, Tongue, and Fingertips10.34067/KID.0005102020Thu, 25 Feb 2021 06:00:33 GMT-08:00A Transplant Patient with Blue Lips, Tongue, and FingertipsSriperumbuduri, SriramHesketh, CaitlinClark, Edward G.2021-02-25T06:00:33-08:00doi:10.34067/KID.0005102020hwp:resource-id:kidney360;2/2/398American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, dapsone, hypoxia, kidney transplant, methemoglobinemia, pneumocystisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-02-2510.34067/KID.00051020202641-76502021-02-25T06:00:33-08:002021-02-25Kidney360Clinical Images in Nephrology and Dialysis22398399
- Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Nondiabetic Patients on Hemodialysis Using Metabolomic Profiling10.34067/KID.0004422020Fri, 04 Dec 2020 09:48:06 GMT-08:00Identification of Novel Biomarkers and Pathways for Coronary Artery Calcification in Nondiabetic Patients on Hemodialysis Using Metabolomic ProfilingChen, WeiFitzpatrick, JessicaSozio, Stephen M.Jaar, Bernard G.Estrella, Michelle M.Riascos-Bernal, Dario F.Wu, Tong TongQiu, YunpingKurland, Irwin J.Dubin, Ruth F.Chen, YabingParekh, Rulan S.Bushinsky, David A.Sibinga, Nicholas E.S.2020-12-04T09:48:06-08:00doi:10.34067/KID.0004422020hwp:resource-id:kidney360;2/2/279American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360mineral metabolism, arginine and proline metabolism, arterial calcification, bile acid, coronary artery disease, dialysis, metabolomicsOriginal InvestigationsMineral MetabolismOriginal InvestigationsMineral Metabolismresearch-article20212021-02-2510.34067/KID.00044220202641-76502020-12-04T09:48:06-08:002021-02-25Kidney360Original Investigations22279289
- Mayo Imaging Classification May Be Useful in Determining the Need for Nephrectomy in ADPKD10.34067/KID.0003902020Wed, 30 Dec 2020 06:19:49 GMT-08:00Mayo Imaging Classification May Be Useful in Determining the Need for Nephrectomy in ADPKDRosenberg, StephanieVirmani, SarthakKlarman, SharonSantovasi, SamanthaDai, FengDahl, Neera K.2020-12-30T06:19:49-08:00doi:10.34067/KID.0003902020hwp:resource-id:kidney360;2/2/325American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, autosomal dominant polycystic kidney, diagnostic imaging, kidney transplantation, Mayo class, nephrectomyBrief CommunicationsCystic Kidney DiseaseBrief CommunicationsCystic Kidney Diseasebrief-report20212021-02-2510.34067/KID.00039020202641-76502020-12-30T06:19:49-08:002021-02-25Kidney360Brief Communications22325330
- How To Prescribe And Troubleshoot Continuous Renal Replacement Therapy: A Case-Based ReviewContinuous RRT (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in patients who are critically ill with AKI in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population, such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk, and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized, or do not have solid evidence-based foundations. In this study, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to patients who are critically ill. Specific focus is on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation, and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves, and is on the basis of step-wise decisions made during the care of this patient, according to the specific patient’s needs and the logistics available at the corresponding institution.10.34067/KID.0004912020Mon, 14 Dec 2020 09:25:45 GMT-08:00How To Prescribe And Troubleshoot Continuous Renal Replacement Therapy: A Case-Based ReviewContinuous RRT (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in patients who are critically ill with AKI in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population, such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk, and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized, or do not have solid evidence-based foundations. In this study, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to patients who are critically ill. Specific focus is on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation, and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves, and is on the basis of step-wise decisions made during the care of this patient, according to the specific patient’s needs and the logistics available at the corresponding institution.Neyra, Javier A.Yessayan, LenarThompson Bastin, Melissa L.Wille, Keith MTolwani, Ashita J2020-12-14T09:25:45-08:00doi:10.34067/KID.0004912020hwp:resource-id:kidney360;2/2/371American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acid-base disorder, AKI, anticoagulation, citrate, CRRT, ECMO, fluid removal, hyponatremia, ICU, kidney, renal replacement therapyReview ArticlesReview Articlesreview-article20212021-02-2510.34067/KID.00049120202641-76502020-12-14T09:25:45-08:002021-02-25Kidney360Review Articles22371384
- Unexpected Complication in an ESKD Patient during AVG Thrombectomy10.34067/KID.0004272020Thu, 25 Feb 2021 06:00:33 GMT-08:00Unexpected Complication in an ESKD Patient during AVG ThrombectomyGill, JasmeetAkinfolarin, AkinwandeSzerlip, Harold M.2021-02-25T06:00:33-08:00doi:10.34067/KID.0004272020hwp:resource-id:kidney360;2/2/400American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, hemodialysis, pulmonary artery, stent migrationClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-02-2510.34067/KID.00042720202641-76502021-02-25T06:00:33-08:002021-02-25Kidney360Clinical Images in Nephrology and Dialysis22400401
- AKI in a Patient with Pyuria and an Alkaline Urine10.34067/KID.0003832020Thu, 25 Feb 2021 06:00:33 GMT-08:00AKI in a Patient with Pyuria and an Alkaline UrineAnthonissen, BlaiseLengelé, Jean-PhilippeCambier, Jean-François2021-02-25T06:00:33-08:00doi:10.34067/KID.0003832020hwp:resource-id:kidney360;2/2/402American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, encrusted cystitis, encrusted pyelitis, microbiology, obstructive nephropathy, urologyClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-02-2510.34067/KID.00038320202641-76502021-02-25T06:00:33-08:002021-02-25Kidney360Clinical Images in Nephrology and Dialysis22402403
- Multidisciplinary Team versus a “Phosphate-Counting” App for Serum Phosphate Control: A Randomized Controlled Trial10.34067/KID.0007132020Tue, 15 Dec 2020 01:29:55 GMT-08:00Multidisciplinary Team versus a “Phosphate-Counting” App for Serum Phosphate Control: A Randomized Controlled TrialFarfan-Ruiz, Ana CeciliaCzikk, DanielLeidecker, JulieRamsay, TimMcCormick, BrendanWilson, KumananZimmerman, Deborah2020-12-15T13:29:55-08:00doi:10.34067/KID.0007132020hwp:resource-id:kidney360;2/2/290American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360mineral metabolism, hyperphosphatemia, peritoneal dialysis, phosphate, phosphate binders, randomized controlled trialOriginal InvestigationsMineral MetabolismOriginal InvestigationsMineral Metabolismresearch-article20212021-02-2510.34067/KID.00071320202641-76502020-12-15T13:29:55-08:002021-02-25Kidney360Original Investigations22290297
- Sedentary Behavior and Change in Kidney Function: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)10.34067/KID.0006202020Wed, 09 Dec 2020 02:28:11 GMT-08:00Sedentary Behavior and Change in Kidney Function: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)Hannan, MaryRicardo, Ana C.Cai, JianwenFranceschini, NoraKaplan, RobertMarquez, David X.Rosas, Sylvia E.Schneiderman, NeilSotres-Alvarez, DanielaTalavera, Gregory A.Daviglus, Martha L.Lash, James P.2020-12-09T14:28:11-08:00doi:10.34067/KID.0006202020hwp:resource-id:kidney360;2/2/245American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, clinical epidemiology, Hispanic Americans, public health, risk factors, sedentary behaviorOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20212021-02-2510.34067/KID.00062020202641-76502020-12-09T14:28:11-08:002021-02-25Kidney360Original Investigations22245253
- Comparison of Equations To Estimate Glomerular Filtration Rate and Their Impact on Frequency of Cisplatin-associated Acute Kidney Injury10.34067/KID.0000572020Tue, 29 Dec 2020 12:05:14 GMT-08:00Comparison of Equations To Estimate Glomerular Filtration Rate and Their Impact on Frequency of Cisplatin-associated Acute Kidney InjuryMotwani, Shveta S.Choueiri, Toni K.Partridge, Ann H.Hu, JianiKaymakcalan, Marina D.Waikar, Sushrut S.Curhan, Gary C.2020-12-29T12:05:14-08:00doi:10.34067/KID.0000572020hwp:resource-id:kidney360;2/2/205American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, chemotherapy toxicity, cisplatin nephrotoxicity, cisplatin-associated AKI, CKD-EPI, creatinine, eGFR, GFR, kidney function, kidney function testing, MDRD, nephrotoxicity, onco-nephrology, prevention of nephrotoxicityOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20212021-02-2510.34067/KID.00005720202641-76502020-12-29T12:05:14-08:002021-02-25Kidney360Original Investigations22205214
- Development and Validation of a Web-Based Prediction Model for AKI after Surgery10.34067/KID.0004732020Tue, 29 Dec 2020 01:46:37 GMT-08:00Development and Validation of a Web-Based Prediction Model for AKI after SurgeryWoo, Sang H.Zavodnick, JillianAckermann, LilyMaarouf, Omar H.Zhang, JingjingCowan, Scott W.2020-12-29T13:46:37-08:00doi:10.34067/KID.0004732020hwp:resource-id:kidney360;2/2/215American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, morbidity, postoperative period, renal dialysis, renal replacement therapy, risk assessment, web-basedOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20212021-02-2510.34067/KID.00047320202641-76502020-12-29T13:46:37-08:002021-02-25Kidney360Original Investigations22215223
- Factors Associated with Dialysis Discontinuation Outside of the Acute Care Setting10.34067/KID.0004312020Wed, 09 Dec 2020 02:28:11 GMT-08:00Factors Associated with Dialysis Discontinuation Outside of the Acute Care SettingRoberts, Matthew J.Johansen, Kirsten L.Copeland, Timothy P.McCulloch, Charles E.Coufal, SarahKu, Elaine2020-12-09T14:28:11-08:00doi:10.34067/KID.0004312020hwp:resource-id:kidney360;2/2/331American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, discontinuation, ESKD, hemodialysis, peritoneal dialysis, withdrawalBrief CommunicationsDialysisBrief CommunicationsDialysisbrief-report20212021-02-2510.34067/KID.00043120202641-76502020-12-09T14:28:11-08:002021-02-25Kidney360Brief Communications22331335
- A Phase 1 Randomized Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in CKD10.34067/KID.0005862020Fri, 04 Dec 2020 09:48:06 GMT-08:00A Phase 1 Randomized Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in CKDNowak, Kristen L.Kakkar, RahulDevalaraja, MattLo, LarryPark, WansuGobburu, JogaKling, DouglasDavidson, MichaelChonchol, Michel2020-12-04T09:48:06-08:00doi:10.34067/KID.0005862020hwp:resource-id:kidney360;2/2/224American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, cardiovascular disease, chronic inflammation, CKD, clinical trial, interleukin-6, nephrology, phase 1, ziltivekimabOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-02-2510.34067/KID.00058620202641-76502020-12-04T09:48:06-08:002021-02-25Kidney360Original Investigations22224235
- Novel Use of Premixed Dialysate Bags during Water Supply Interruption in Acute Hospital SettingPatients on dialysis are exposed to large amounts of water during conventional intermittent hemodialysis; hence, there are strict regulations regarding the quality of water used to prepare dialysate. Occasionally, water systems fail due to natural disasters or structural supply issues, such as water-main breaks or unplanned changes in municipal or facility water quality. It is critical to regularly monitor and immediately recognize such a failure and take steps to avoid exposing the patients to contaminants. In addition to the recognition of the problem, the ability to pivot and continue to provide safe treatment to inpatients who are dependent on dialysis is essential, both from an ultrafiltration and a clearance standpoint. At our hospital, an unforeseen water disruption occurred and we were able to continue to provide KRT with premade, bagged dialysate to mitigate the effect on our patients on dialysis. This is a novel method using available machines and dialysate, which we normally stock for continuous KRT, for short dialysis sessions. The methodology is similar to that which has been widely used for short daily home hemodialysis with low dialysate flow rate. Because this situation occurred in the midst of the SARS-CoV-2 pandemic, we had to be mindful of dialysate volumes and staffing time. Here, we present our investigation into the cause of the water-system failure and how we quickly implemented the alternative dialysis method. Short dialysis with low-flow dialysate will not deliver the same Kt/V per session as standard dialysis; however, this method was successfully implemented and tailored with adjustments for patients requiring higher clearance for specific indications, such as severe hyperkalemia.10.34067/KID.0004762020Wed, 09 Dec 2020 09:54:50 GMT-08:00Novel Use of Premixed Dialysate Bags during Water Supply Interruption in Acute Hospital SettingPatients on dialysis are exposed to large amounts of water during conventional intermittent hemodialysis; hence, there are strict regulations regarding the quality of water used to prepare dialysate. Occasionally, water systems fail due to natural disasters or structural supply issues, such as water-main breaks or unplanned changes in municipal or facility water quality. It is critical to regularly monitor and immediately recognize such a failure and take steps to avoid exposing the patients to contaminants. In addition to the recognition of the problem, the ability to pivot and continue to provide safe treatment to inpatients who are dependent on dialysis is essential, both from an ultrafiltration and a clearance standpoint. At our hospital, an unforeseen water disruption occurred and we were able to continue to provide KRT with premade, bagged dialysate to mitigate the effect on our patients on dialysis. This is a novel method using available machines and dialysate, which we normally stock for continuous KRT, for short dialysis sessions. The methodology is similar to that which has been widely used for short daily home hemodialysis with low dialysate flow rate. Because this situation occurred in the midst of the SARS-CoV-2 pandemic, we had to be mindful of dialysate volumes and staffing time. Here, we present our investigation into the cause of the water-system failure and how we quickly implemented the alternative dialysis method. Short dialysis with low-flow dialysate will not deliver the same Kt/V per session as standard dialysis; however, this method was successfully implemented and tailored with adjustments for patients requiring higher clearance for specific indications, such as severe hyperkalemia.Kohn, Orly F.Plascencia, MiguelTaylor, YolandaKoyner, Jay L.2020-12-09T09:54:50-08:00doi:10.34067/KID.0004762020hwp:resource-id:kidney360;2/2/339American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, acute dialysis, acute hospital, dialysis solutions, patient safety, pre-mixed dialysate, water quality for dialysis, water supplyInnovative Technology and MethodologyDialysisInnovative Technology and MethodologyDialysisother20212021-02-2510.34067/KID.00047620202641-76502020-12-09T09:54:50-08:002021-02-25Kidney360Innovative Technology and Methodology22339343
- Inhibition of Lysyl Oxidase with β-aminopropionitrile Improves Venous Adaptation after Arteriovenous Fistula Creation10.34067/KID.0005012020Fri, 18 Dec 2020 11:43:24 GMT-08:00Inhibition of Lysyl Oxidase with β-aminopropionitrile Improves Venous Adaptation after Arteriovenous Fistula CreationHernandez, Diana R.Applewhite, BrandonMartinez, LaiselLaurito, TylerTabbara, MarwanRojas, Miguel G.Wei, YuntaoSelman, GuillermoKnysheva, MarinaVelazquez, Omaida C.Salman, Loay H.Andreopoulos, Fotios M.Shiu, Yan-TingVazquez-Padron, Roberto I.2020-12-18T11:43:24-08:00doi:10.34067/KID.0005012020hwp:resource-id:kidney360;2/2/270American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, animal model, arteriovenous fistula, collagen crosslinking, crosslinking, lysyl oxidaseOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-02-2510.34067/KID.00050120202641-76502020-12-18T11:43:24-08:002021-02-25Kidney360Original Investigations22270278
- Low-dose Rituximab Monotherapy or in Combination with Tacrolimus Is Effective in Primary Membranous Nephropathy10.34067/KID.0004672020Fri, 18 Dec 2020 09:28:45 GMT-08:00Low-dose Rituximab Monotherapy or in Combination with Tacrolimus Is Effective in Primary Membranous NephropathyPathak, VivekVenkatesan, MadhavRegunathan-Shenk, Renu2020-12-18T09:28:45-08:00doi:10.34067/KID.0004672020hwp:resource-id:kidney360;2/2/336American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, cyclosporine, membranous glomerulonephritis, remission induction, rituximab, tacrolimusBrief CommunicationsGlomerular and Tubulointerstitial DiseasesBrief CommunicationsGlomerular and Tubulointerstitial Diseasesbrief-report20212021-02-2510.34067/KID.00046720202641-76502020-12-18T09:28:45-08:002021-02-25Kidney360Brief Communications22336338
- The Impact of CKD on Perioperative Risk and Mortality after Bariatric Surgery10.34067/KID.0004832020Mon, 14 Dec 2020 06:09:39 GMT-08:00The Impact of CKD on Perioperative Risk and Mortality after Bariatric SurgeryCarvalho Silveira, FlaviaMartin, William P.Maranga, Gabriellele Roux, Carel W.Ren-Fielding, Christine J.2020-12-14T06:09:39-08:00doi:10.34067/KID.0004832020hwp:resource-id:kidney360;2/2/236American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, bariatric surgery, complication, loss, obesity, risk factor, weightOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-02-2510.34067/KID.00048320202641-76502020-12-14T06:09:39-08:002021-02-25Kidney360Original Investigations22236244
- Improving on the Adrogué–Madias FormulaThe Adrogué–Madias (A-M) formula is correct as written, but technically, it only works when adding 1 L of an intravenous (IV) fluid. For all other volumes, the A-M algorithm gives an approximate answer, one that diverges further from the truth as the IV volume is increased. If 1 L of an IV fluid is calculated to change the serum sodium by some amount, then it was long assumed that giving a fraction of the liter would change the serum sodium by a proportional amount. We challenged that assumption and now prove that the A-M change in [sodium] ([Na]) is not scalable in a linear way. Rather, the Δ[Na] needs to be scaled in a way that accounts for the actual volume of IV fluid being given. This is accomplished by our improved version of the A-M formula in a mathematically rigorous way. Our equation accepts any IV fluid volume, eliminates the illogical infinities, and most importantly, incorporates the scaling step so that it cannot be forgotten. However, the nonlinear scaling makes it harder to obtain a desired Δ[Na]. Therefore, we reversed the equation so that clinicians can enter the desired Δ[Na], keeping the rate of sodium correction safe, and then get an answer in terms of the volume of IV fluid to infuse. The improved equation can also unify the A-M formula with the corollary A-M loss equation wherein 1 L of urine is lost. The method is to treat loss as a negative volume. Because the new equation is just as straightforward as the original formula, we believe that the improved form of A-M is ready for immediate use, alongside frequent [Na] monitoring.10.34067/KID.0005882020Fri, 04 Dec 2020 01:38:27 GMT-08:00Improving on the Adrogué–Madias FormulaThe Adrogué–Madias (A-M) formula is correct as written, but technically, it only works when adding 1 L of an intravenous (IV) fluid. For all other volumes, the A-M algorithm gives an approximate answer, one that diverges further from the truth as the IV volume is increased. If 1 L of an IV fluid is calculated to change the serum sodium by some amount, then it was long assumed that giving a fraction of the liter would change the serum sodium by a proportional amount. We challenged that assumption and now prove that the A-M change in [sodium] ([Na]) is not scalable in a linear way. Rather, the Δ[Na] needs to be scaled in a way that accounts for the actual volume of IV fluid being given. This is accomplished by our improved version of the A-M formula in a mathematically rigorous way. Our equation accepts any IV fluid volume, eliminates the illogical infinities, and most importantly, incorporates the scaling step so that it cannot be forgotten. However, the nonlinear scaling makes it harder to obtain a desired Δ[Na]. Therefore, we reversed the equation so that clinicians can enter the desired Δ[Na], keeping the rate of sodium correction safe, and then get an answer in terms of the volume of IV fluid to infuse. The improved equation can also unify the A-M formula with the corollary A-M loss equation wherein 1 L of urine is lost. The method is to treat loss as a negative volume. Because the new equation is just as straightforward as the original formula, we believe that the improved form of A-M is ready for immediate use, alongside frequent [Na] monitoring.Chen, SheldonShieh, MichaelChiaramonte, RobertShey, Jason2020-12-04T13:38:27-08:00doi:10.34067/KID.0005882020hwp:resource-id:kidney360;2/2/365American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, Adrogué-Madias algorithm, algorithm, delta [sodium], dysnatremia, general equation, hypernatremia, hyponatremia, infinity, non-linear, scalingReview ArticlesReview Articlesreview-article20212021-02-2510.34067/KID.00058820202641-76502020-12-04T13:38:27-08:002021-02-25Kidney360Review Articles22365370
- Regional Citrate Anticoagulation Protocol for Patients with Presumed Absent Citrate Metabolism10.34067/KID.0005342020Fri, 18 Dec 2020 01:56:30 GMT-08:00Regional Citrate Anticoagulation Protocol for Patients with Presumed Absent Citrate MetabolismSzamosfalvi, BalazsPuri, VidhitSohaney, RyannWagner, BenjaminRiddle, AmyDickinson, SharonNapolitano, LenaHeung, MichaelHumes, DavidYessayan, Lenar2020-12-18T13:56:30-08:00doi:10.34067/KID.0005342020hwp:resource-id:kidney360;2/2/192American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, citrate anticoagulation, citrate toxicity, CKRT, CRRT, filter life, hypocalcemia, lactic acidosis, liver failure, veno-venous hemodiafiltrationOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20212021-02-2510.34067/KID.00053420202641-76502020-12-18T13:56:30-08:002021-02-25Kidney360Original Investigations22192204
- Diagnostic Utility of Serial Microscopic Examination of the Urinary Sediment in Acute Kidney Injury10.34067/KID.0004022020Fri, 11 Dec 2020 02:29:54 GMT-08:00Diagnostic Utility of Serial Microscopic Examination of the Urinary Sediment in Acute Kidney InjuryVarghese, VipinRivera, Maria SoledadAlalwan, Ali A.Alghamdi, Ayman M.Gonzalez, Manuel E.Velez, Juan Carlos Q.2020-12-11T14:29:54-08:00doi:10.34067/KID.0004022020hwp:resource-id:kidney360;2/2/182American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury, ICU nephrology, acute tubular necrosis, granular casts, urinary casts, urine microscopy, urine sedimentOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20212021-02-2510.34067/KID.00040220202641-76502020-12-11T14:29:54-08:002021-02-25Kidney360Original Investigations22182191
- Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney Disease10.34067/KID.0001182019Fri, 04 Dec 2020 01:38:27 GMT-08:00Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney DiseaseBhutani, GauriAstor, Brad C.Mandelbrot, Didier A.Mankowski-Gettle, LoriZiemlewicz, TimothyWells, Shane A.Frater-Rubsam, LeahHorner, VanessaBoyer, CourtneyLaffin, JenniferDjamali, Arjang2020-12-04T13:38:27-08:00doi:10.34067/KID.0001182019hwp:resource-id:kidney360;2/2/312American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360transplantation, calcineurin inhibitor, coronary artery disease, death, graft survival, human leukocyte antigen (HLA), kidney transplant, nephrectomy, obesity, polycystic kidney disease, post-transplant diabetes mellitusOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20212021-02-2510.34067/KID.00011820192641-76502020-12-04T13:38:27-08:002021-02-25Kidney360Original Investigations22312324
- Overview of The Human Heredity and Health in Africa Kidney Disease Research Network (H3A-KDRN)10.34067/KID.0002592020Tue, 08 Dec 2020 01:29:19 GMT-08:00Overview of The Human Heredity and Health in Africa Kidney Disease Research Network (H3A-KDRN)Adu, DwomoaOjo, Akinlolu,2020-12-08T13:29:19-08:00doi:10.34067/KID.0002592020hwp:resource-id:kidney360;2/1/129American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, Africa, apolipoprotein L1, chronic kidney disease, geneticsGlobal PerspectiveGlobal Perspectiveresearch-article20212021-01-2810.34067/KID.00025920202641-76502020-12-08T13:29:19-08:002021-01-28Kidney360Global Perspective21129133
- Resident Macrophages in Cystic Kidney DiseaseInterstitial inflammation is an important feature of cystic kidney disease. Renal macrophages are the most well-studied inflammatory cell in the kidney, and their involvement in cyst formation has been reported in different animal models and patients with cystic kidney disease. Originally, it was believed that renal macrophages were maintained from a constant supply of bone marrow–derived circulating monocytes, and could be recruited to the kidney in response to local inflammation. However, this idea has been challenged using fate-mapping methods, by showing that at least two distinct developmental origins of macrophages are present in the adult mouse kidney. The first type, infiltrating macrophages, are recruited from circulating monocytes and gradually develop macrophage properties on entering the kidney. The second, resident macrophages, predominantly originate from embryonic precursors, colonize the kidney during its development, and proliferate in situ to maintain their population throughout adulthood. Infiltrating and resident macrophages work together to maintain homeostasis and properly respond to pathologic conditions, such as AKI, cystic kidney disease, or infection. This review will briefly summarize current knowledge of resident macrophages in cystic kidney disease.10.34067/KID.0006052020Fri, 11 Dec 2020 10:08:43 GMT-08:00Resident Macrophages in Cystic Kidney DiseaseInterstitial inflammation is an important feature of cystic kidney disease. Renal macrophages are the most well-studied inflammatory cell in the kidney, and their involvement in cyst formation has been reported in different animal models and patients with cystic kidney disease. Originally, it was believed that renal macrophages were maintained from a constant supply of bone marrow–derived circulating monocytes, and could be recruited to the kidney in response to local inflammation. However, this idea has been challenged using fate-mapping methods, by showing that at least two distinct developmental origins of macrophages are present in the adult mouse kidney. The first type, infiltrating macrophages, are recruited from circulating monocytes and gradually develop macrophage properties on entering the kidney. The second, resident macrophages, predominantly originate from embryonic precursors, colonize the kidney during its development, and proliferate in situ to maintain their population throughout adulthood. Infiltrating and resident macrophages work together to maintain homeostasis and properly respond to pathologic conditions, such as AKI, cystic kidney disease, or infection. This review will briefly summarize current knowledge of resident macrophages in cystic kidney disease.Li, ZhangZimmerman, Kurt A.Yoder, Bradley K.2020-12-11T10:08:43-08:00doi:10.34067/KID.0006052020hwp:resource-id:kidney360;2/1/167American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360cystic kidney disease, chronic kidney disease, macrophages, mouse models, renal injury, Basic ScienceReview ArticlesReview Articlesreview-article20212021-01-2810.34067/KID.00060520202641-76502020-12-11T10:08:43-08:002021-01-28Kidney360Review Articles21167175
- The Relationship between APOL1 Structure and Function: Clinical ImplicationsCommon variants in the APOL1 gene are associated with an increased risk of nondiabetic kidney disease in individuals of African ancestry. Mechanisms by which APOL1 variants mediate kidney disease pathogenesis are not well understood. Amino acid changes resulting from the kidney disease–associated APOL1 variants alter the three-dimensional structure and conformational dynamics of the C-terminal α-helical domain of the protein, which can rationalize the functional consequences. Understanding the three-dimensional structure of the protein, with and without the risk variants, can provide insights into the pathogenesis of kidney diseases mediated by APOL1 variants.10.34067/KID.0002482020Wed, 04 Nov 2020 01:31:03 GMT-08:00The Relationship between APOL1 Structure and Function: Clinical ImplicationsCommon variants in the APOL1 gene are associated with an increased risk of nondiabetic kidney disease in individuals of African ancestry. Mechanisms by which APOL1 variants mediate kidney disease pathogenesis are not well understood. Amino acid changes resulting from the kidney disease–associated APOL1 variants alter the three-dimensional structure and conformational dynamics of the C-terminal α-helical domain of the protein, which can rationalize the functional consequences. Understanding the three-dimensional structure of the protein, with and without the risk variants, can provide insights into the pathogenesis of kidney diseases mediated by APOL1 variants.Madhavan, Sethu M.Buck, Matthias2020-11-04T13:31:03-08:00doi:10.34067/KID.0002482020hwp:resource-id:kidney360;2/1/134American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, amino acids, APOL1, apolipoprotein L1, genetics, human APOL1 protein, kidney diseases, protein structure, Basic ScienceBasic Science for CliniciansBasic Science for Cliniciansother20212021-01-2810.34067/KID.00024820202641-76502020-11-04T13:31:03-08:002021-01-28Kidney360Basic Science for Clinicians21134140
- Jump-Starting Kidney Research10.2215/CJN.06570520Mon, 10 Aug 2020 04:47:46 GMT-07:00Jump-Starting Kidney ResearchNorton, Jenna M.Star, Robert A.2020-08-10T16:47:46-07:00doi:10.2215/CJN.06570520hwp:resource-id:clinjasn;16/2/313American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic kidney failure, acute renal failure, acute kidney injury, end stage kidney disease, end-stage renal diseasePerspectivesPerspectivesresearch-article20212021-02-08February 08, 202110.2215/CJN.065705201555-90411555-905X2020-08-10T16:47:46-07:002021-02-08Clinical Journal of the American Society of NephrologyPerspectives162313315
- Metabolic Acidosis and CKD Progression10.2215/CJN.07990520Fri, 07 Aug 2020 12:27:56 GMT-07:00Metabolic Acidosis and CKD ProgressionMadias, Nicolaos E.2020-08-07T12:27:56-07:00doi:10.2215/CJN.07990520hwp:resource-id:clinjasn;16/2/310American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, CKD progression, metabolic acidosis, bicarbonate concentration, H+ retentionPerspectivesPerspectivesresearch-article20212021-02-08February 08, 202110.2215/CJN.079905201555-90411555-905X2020-08-07T12:27:56-07:002021-02-08Clinical Journal of the American Society of NephrologyPerspectives162310312
- PEXIVAS10.2215/CJN.10550620Tue, 22 Sep 2020 12:25:26 GMT-07:00PEXIVASDe Vriese, An S.Fervenza, Fernando C.2020-09-22T12:25:26-07:00doi:10.2215/CJN.10550620hwp:resource-id:clinjasn;16/2/307American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, Plasmapheresis, PEXIVAS, renal, pulmonary hemorrhage, severePerspectivesPerspectivesresearch-article20212021-02-08February 08, 202110.2215/CJN.105506201555-90411555-905X2020-09-22T12:25:26-07:002021-02-08Clinical Journal of the American Society of NephrologyPerspectives162307309
- Mind the Gap10.2215/CJN.19321220Tue, 19 Jan 2021 08:43:41 GMT-08:00Mind the GapGoldberg, Aviva M.Bignall, O. N. Ray2021-01-19T08:43:41-08:00doi:10.2215/CJN.19321220hwp:resource-id:clinjasn;16/2/185American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparity, pediatric kidney transplantation, pediatric nephrology, equity, ethnicity, childrenEditorialsEditorialseditorial20212021-02-08February 08, 202110.2215/CJN.193212201555-90411555-905X2021-01-19T08:43:41-08:002021-02-08Clinical Journal of the American Society of NephrologyEditorials1622185194187203
- Social Determinants of Health and Race Disparities in Kidney Transplant10.2215/CJN.04860420Thu, 28 Jan 2021 01:37:03 GMT-08:00Social Determinants of Health and Race Disparities in Kidney TransplantWesselman, HannahFord, Christopher GrahamLeyva, YuridiaLi, XingyuanChang, Chung-Chou H.Dew, Mary AmandaKendall, KelleeCroswell, EmileePleis, John R.Ng, Yue HarnUnruh, Mark L.Shapiro, RonMyaskovsky, Larissa2021-01-28T13:37:03-08:00doi:10.2215/CJN.04860420hwp:resource-id:clinjasn;16/2/262American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, social determinants of health, disparitiesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-02-08February 08, 202110.2215/CJN.048604201555-90411555-905X2021-01-28T13:37:03-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles1622262177274178
- Associations between Deprivation, Geographic Location, and Access to Pediatric Kidney Care in the United Kingdom10.2215/CJN.11020720Tue, 19 Jan 2021 08:43:41 GMT-08:00Associations between Deprivation, Geographic Location, and Access to Pediatric Kidney Care in the United KingdomPlumb, Lucy A.Sinha, Manish D.Casula, AnnaInward, Carol D.Marks, Stephen D.Caskey, Fergus J.Ben-Shlomo, Yoav2021-01-19T08:43:41-08:00doi:10.2215/CJN.11020720hwp:resource-id:clinjasn;16/2/194American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, kidney transplantation, epidemiology and outcomes, pediatric kidney transplantation, pediatric nephrology, pediatrics, transplantation, clinical epidemiology, childrenOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20212021-02-08Month XX, 202010.2215/CJN.110207201555-90411555-905X2021-01-19T08:43:41-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles1622194185203187
- Sex Disparity in Deceased-Donor Kidney Transplant Access by Cause of Kidney Disease10.2215/CJN.09140620Tue, 26 Jan 2021 06:35:26 GMT-08:00Sex Disparity in Deceased-Donor Kidney Transplant Access by Cause of Kidney DiseaseAhearn, PatrickJohansen, Kirsten L.Tan, Jane C.McCulloch, Charles E.Grimes, Barbara A.Ku, Elaine2021-01-26T06:35:26-08:00doi:10.2215/CJN.09140620hwp:resource-id:clinjasn;16/2/241American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, chronic dialysis, disparity, kidney transplantation, kidney failureOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-02-08February 08, 202110.2215/CJN.091406201555-90411555-905X2021-01-26T06:35:26-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles162241250
- Advancing NephrologyNew treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology—from value-based care to prize competitions—will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, such as the American Society of Nephrology, the National Kidney Foundation, and the Renal Physicians Association, and international nephrologists and organizations, such as the International Society of Nephrology and the European Renal Association–European Dialysis and Transplant Association, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Recognizing the timeliness of this opportunity, the American Society of Nephrology convened a Division Chief Retreat in Dallas, Texas, in June 2019 to address five key issues: (1) asserting the value of nephrology to the health system; (2) productivity and compensation; (3) financial support of faculty’s and divisions’ educational efforts; (4) faculty recruitment, retention, diversity, and inclusion; and (5) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology. Herein, we highlight the outcomes of these discussions and recommendations to the American Society of Nephrology.10.2215/CJN.01550220Wed, 12 Aug 2020 05:47:51 GMT-07:00Advancing NephrologyNew treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology—from value-based care to prize competitions—will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, such as the American Society of Nephrology, the National Kidney Foundation, and the Renal Physicians Association, and international nephrologists and organizations, such as the International Society of Nephrology and the European Renal Association–European Dialysis and Transplant Association, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Recognizing the timeliness of this opportunity, the American Society of Nephrology convened a Division Chief Retreat in Dallas, Texas, in June 2019 to address five key issues: (1) asserting the value of nephrology to the health system; (2) productivity and compensation; (3) financial support of faculty’s and divisions’ educational efforts; (4) faculty recruitment, retention, diversity, and inclusion; and (5) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology. Herein, we highlight the outcomes of these discussions and recommendations to the American Society of Nephrology.Braden, Gregory L.Chapman, ArleneEllison, David H.Gadegbeku, Crystal A.Gurley, Susan B.Igarashi, PeterKelepouris, EllieMoxey-Mims, Marva M.Okusa, Mark D.Plumb, Troy J.Quaggin, Susan E.Salant, David J.Segal, Mark S.Shankland, Stuart J.Somlo, Stefan2020-08-12T05:47:51-07:00doi:10.2215/CJN.01550220hwp:resource-id:clinjasn;16/2/319American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyWork Force, Nephrology Fellowship, Medical Education, KidneyX, Physician Productivity, DiversityFeaturesFeaturesresearch-article20212021-02-08February 08, 202110.2215/CJN.015502201555-90411555-905X2020-08-12T05:47:51-07:002021-02-08Clinical Journal of the American Society of NephrologyFeatures162319327
- Is It Time for Precision Dialysis?10.2215/CJN.08610520Fri, 18 Sep 2020 10:25:18 GMT-07:00Is It Time for Precision Dialysis?Gupta, NupurWish, Jay B.2020-09-18T10:25:18-07:00doi:10.2215/CJN.08610520hwp:resource-id:clinjasn;16/2/316American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney replacement therapy, payment models, chronic kidney disease, shared decision making, end stage kidney disease, dialysisPerspectivesPerspectivesresearch-article20212021-02-08February 08, 202110.2215/CJN.086105201555-90411555-905X2020-09-18T10:25:18-07:002021-02-08Clinical Journal of the American Society of NephrologyPerspectives162316318
- Characteristics of Acute Kidney Injury in Hospitalized COVID-19 Patients in an Urban Academic Medical Center10.2215/CJN.07440520Fri, 18 Sep 2020 10:25:18 GMT-07:00Characteristics of Acute Kidney Injury in Hospitalized COVID-19 Patients in an Urban Academic Medical CenterLee, John R.Silberzweig, JeffreyAkchurin, OlehChoi, Mary E.Srivatana, VeshLin, JonathanLiu, FrankMalha, LineLubetzky, MichelleDadhania, Darshana M.Shankaranarayanan, DivyaShimonov, DaniilNeupane, SanjaySalinas, ThaliaBhasin, AartiVarma, EllyLeuprecht, LorenzGerardine, SupriyaLamba, PerolaGoyal, ParagCaliendo, EricTiase, VictoriaSharma, RahulPark, Joel C.Steel, Peter A.D.Suthanthiran, ManikkamZhang, Yiye2020-09-18T10:25:18-07:00doi:10.2215/CJN.07440520hwp:resource-id:clinjasn;16/2/284American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, COVID-19, acute kidney injury, Academic Medical CentersResearch LettersResearch Lettersletter20212021-02-08February 08, 202110.2215/CJN.074405201555-90411555-905X2020-09-18T10:25:18-07:002021-02-08Clinical Journal of the American Society of NephrologyResearch Letters162284286
- Prolonged SARS-CoV-2 Viral RNA Shedding and IgG Antibody Response to SARS-CoV-2 in Patients on Hemodialysis10.2215/CJN.11120720Wed, 14 Oct 2020 08:51:07 GMT-07:00Prolonged SARS-CoV-2 Viral RNA Shedding and IgG Antibody Response to SARS-CoV-2 in Patients on HemodialysisShaikh, AishaZeldis, EttiCampbell, Kirk N.Chan, Lili2020-10-14T08:51:07-07:00doi:10.2215/CJN.11120720hwp:resource-id:clinjasn;16/2/290American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, hemodialysis, RNA, viral, immunoglobulin GResearch LettersResearch Lettersletter20212021-02-08February 08, 202110.2215/CJN.111207201555-90411555-905X2020-10-14T08:51:07-07:002021-02-08Clinical Journal of the American Society of NephrologyResearch Letters162290292
- Barriers to Kidney Transplantation in Racial/Ethnic Minorities10.2215/CJN.19371220Thu, 28 Jan 2021 01:51:58 GMT-08:00Barriers to Kidney Transplantation in Racial/Ethnic MinoritiesFox, Monica2021-01-28T13:51:58-08:00doi:10.2215/CJN.19371220hwp:resource-id:clinjasn;16/2/177American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic kidney failure, dialysis, disparity, end stage kidney disease, ESKD, kidney donation, transplant outcomes, kidney transplantation, kidney diseasePatient VoicePatient Voiceeditorial20212021-02-08February 08, 202110.2215/CJN.193712201555-90411555-905X2021-01-28T13:51:58-08:002021-02-08Clinical Journal of the American Society of NephrologyPatient Voice1622177262178274
- APOL1 Nephropathy: From Genetics to Clinical ApplicationsRates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic variants in the apoL1 (APOL1) gene found only in individuals with recent African ancestry. These variants greatly increase rates of hypertension-associated ESKD, FSGS, HIV-associated nephropathy, and other forms of nondiabetic kidney disease. We discuss the population genetics of APOL1 risk variants and the clinical spectrum of APOL1 nephropathy. We then consider clinical issues that arise for the practicing nephrologist caring for the patient who may have APOL1 kidney disease.10.2215/CJN.15161219Thu, 02 Jul 2020 07:48:59 GMT-07:00APOL1 Nephropathy: From Genetics to Clinical ApplicationsRates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic variants in the apoL1 (APOL1) gene found only in individuals with recent African ancestry. These variants greatly increase rates of hypertension-associated ESKD, FSGS, HIV-associated nephropathy, and other forms of nondiabetic kidney disease. We discuss the population genetics of APOL1 risk variants and the clinical spectrum of APOL1 nephropathy. We then consider clinical issues that arise for the practicing nephrologist caring for the patient who may have APOL1 kidney disease.Friedman, David J.Pollak, Martin R.2020-07-02T07:48:59-07:00doi:10.2215/CJN.15161219hwp:resource-id:clinjasn;16/2/294American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAPOL1, chronic kidney disease, genetic kidney disease, Kidney Genomics Series, APOL1 protein, human, Apolipoprotein L1, HIV-Associated Nephropathy, African Americans, Glomerulosclerosis, Focal Segmental, kidney, hypertension, Genetics, Population, diabetes mellitusGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-02-08February 08, 202110.2215/CJN.151612191555-90411555-905X2020-07-02T07:48:59-07:002021-02-08Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease162294303
- Use of Gadolinium in Individuals with Reduced Kidney Function10.2215/CJN.13950820Mon, 11 Jan 2021 09:23:21 GMT-08:00Use of Gadolinium in Individuals with Reduced Kidney FunctionKalantari, KambizSwaminathan, Sundararaman2021-01-11T09:23:21-08:00doi:10.2215/CJN.13950820hwp:resource-id:clinjasn;16/2/304American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygadolinium, reduced kidney function, NSFKidney Case Conferences: How I TreatKidney Case Conferences: How I Treatresearch-article20212021-02-08February 08, 202110.2215/CJN.139508201555-90411555-905X2021-01-11T09:23:21-08:002021-02-08Clinical Journal of the American Society of NephrologyKidney Case Conferences: How I Treat162304306
- Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD Progression10.2215/CJN.10470620Wed, 27 Jan 2021 06:55:29 GMT-08:00Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD ProgressionHeida, Judith E.Gansevoort, Ron T.Messchendorp, A. LianneMeijer, EstherCasteleijn, Niek F.Boertien, Wendy E.Zittema, Debbie,,Drenth, Joost P.H.de Fijter, Johan W.van Gastel, Maatje D.A.Losekoot, MoniquePeters, Dorien J.M.Visser, Folkert W.Wetzels, Jack F.Zietse, Robert2021-01-27T06:55:29-08:00doi:10.2215/CJN.10470620hwp:resource-id:clinjasn;16/2/204American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, urea, renal function decline, urine-to-plasma urea ratio, autosomal dominant polycystic kidney diseaseOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20212021-02-08February 08, 202110.2215/CJN.104706201555-90411555-905X2021-01-27T06:55:29-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles162204212
- Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States10.2215/CJN.10960720Fri, 15 Jan 2021 06:58:50 GMT-08:00Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United StatesChang, Su-HsinMerzkani, MassiniLentine, Krista L.Wang, MeiAxelrod, David A.Anwar, SiddiqSchnitzler, Mark A.Wellen, JasonChapman, William C.Alhamad, Tarek2021-01-15T06:58:50-08:00doi:10.2215/CJN.10960720hwp:resource-id:clinjasn;16/2/251American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHepatitis C virus, kidney discard, nucleic acid amplification testing, deceased donorOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-02-08February 08, 202110.2215/CJN.109607201555-90411555-905X2021-01-15T06:58:50-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles1622251188261190
- Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival10.2215/CJN.13640820Mon, 25 Jan 2021 07:53:46 GMT-08:00Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft SurvivalLan, James H.Kadatz, MatthewChang, Doris T.Gill, JagbirGebel, Howard M.Gill, John S.2021-01-25T07:53:46-08:00doi:10.2215/CJN.13640820hwp:resource-id:clinjasn;16/2/275American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, acute rejection, risk factors, antibodiesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20212021-02-08February 08, 202110.2215/CJN.136408201555-90411555-905X2021-01-25T07:53:46-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles162275283
- Exome Chip Analyses and Genetic Risk for IgA Nephropathy among Han Chinese10.2215/CJN.06910520Mon, 18 Jan 2021 08:39:38 GMT-08:00Exome Chip Analyses and Genetic Risk for IgA Nephropathy among Han ChineseZhou, Xu-jieTsoi, Lam C.Hu, YongPatrick, Matthew T.He, KevinBerthier, Celine C.Li, YanmingWang, Yan-naQi, Yuan-yuanZhang, Yue-miaoGan, TingLi, YangHou, PingLiu, Li-junShi, Su-fangLv, Ji-chengXu, Hu-jiZhang, Hong2021-01-18T08:39:38-08:00doi:10.2215/CJN.06910520hwp:resource-id:clinjasn;16/2/213American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, exome, exome-wide association study, genetic variants, differential expression, gene networkOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20212021-02-08February 08, 202110.2215/CJN.069105201555-90411555-905X2021-01-18T08:39:38-08:002021-02-08Clinical Journal of the American Society of NephrologyOriginal Articles1622213182224184
- Strategies to Reduce Rehospitalization in Patients with CKD and Kidney FailureReadmissions in patients with nondialysis-dependent CKD and kidney failure are common and are associated with significant morbidity, mortality, and economic consequences. In 2013, the Centers for Medicare and Medicaid Services implemented the Hospital Readmissions Reduction Program in an attempt to reduce high hospitalization-associated costs. Up to 50% of all readmissions are deemed avoidable and present an opportunity for intervention. We describe factors that are specific to the patient, the index hospitalization, and underlying conditions that help identify the “high-risk” patient. Early follow-up care, developing volume management strategies, optimizing nutrition, obtaining palliative care consultations for seriously ill patients during hospitalization and conducting goals-of-care discussions with them, instituting systematic advance care planning during outpatient visits to avoid unwanted hospitalizations and intensive treatment at the end of life, and developing protocols for patients with incident or prevalent cardiovascular conditions may help prevent avoidable readmissions in patients with kidney disease.10.2215/CJN.02300220Mon, 13 Jul 2020 06:59:20 GMT-07:00Strategies to Reduce Rehospitalization in Patients with CKD and Kidney FailureReadmissions in patients with nondialysis-dependent CKD and kidney failure are common and are associated with significant morbidity, mortality, and economic consequences. In 2013, the Centers for Medicare and Medicaid Services implemented the Hospital Readmissions Reduction Program in an attempt to reduce high hospitalization-associated costs. Up to 50% of all readmissions are deemed avoidable and present an opportunity for intervention. We describe factors that are specific to the patient, the index hospitalization, and underlying conditions that help identify the “high-risk” patient. Early follow-up care, developing volume management strategies, optimizing nutrition, obtaining palliative care consultations for seriously ill patients during hospitalization and conducting goals-of-care discussions with them, instituting systematic advance care planning during outpatient visits to avoid unwanted hospitalizations and intensive treatment at the end of life, and developing protocols for patients with incident or prevalent cardiovascular conditions may help prevent avoidable readmissions in patients with kidney disease.Doshi, SimitWish, Jay B.2020-07-13T06:59:20-07:00doi:10.2215/CJN.02300220hwp:resource-id:clinjasn;16/2/328American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, rehospitalization, kidney failure, Patient Readmission, Palliative Care, Medicare, Medicaid, Outpatients, hospitalization, Hospital Costs, Renal Insufficiency, Renal Insufficiency, Chronic, Patient Care PlanningFeaturesFeaturesresearch-article20212021-02-08February 08, 202110.2215/CJN.023002201555-90411555-905X2020-07-13T06:59:20-07:002021-02-08Clinical Journal of the American Society of NephrologyFeatures162328334
- Assessing Genetic Risk for IgA Nephropathy10.2215/CJN.19491220Mon, 18 Jan 2021 08:39:38 GMT-08:00Assessing Genetic Risk for IgA NephropathyPrakash, SindhuriGharavi, Ali G.2021-01-18T08:39:38-08:00doi:10.2215/CJN.19491220hwp:resource-id:clinjasn;16/2/182American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathyEditorialsEditorialseditorial20212021-02-08February 08, 202110.2215/CJN.194912201555-90411555-905X2021-01-18T08:39:38-08:002021-02-08Clinical Journal of the American Society of NephrologyEditorials1622182213184224
- Correction: Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications10.2215/CJN.18391120Wed, 06 Jan 2021 09:39:02 GMT-08:00Correction: Systematic Review and Meta-Analysis of Native Kidney Biopsy ComplicationsAmerican Society of Nephrology2021-01-06T09:39:02-08:00doi:10.2215/CJN.18391120hwp:resource-id:clinjasn;16/2/293American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, chronic kidney disease, kidney biopsyErratumErratumcorrection20212021-02-08February 08, 202110.2215/CJN.183911201555-90411555-905X2021-01-06T09:39:02-08:002021-02-08Clinical Journal of the American Society of NephrologyErratum161521129315952931602
- Effect of Sickle Cell Trait and APOL1 Genotype on the Association of Soluble uPAR with Kidney Function Measures in Black Americans10.2215/CJN.12100720Wed, 02 Dec 2020 10:45:39 GMT-08:00Effect of Sickle Cell Trait and APOL1 Genotype on the Association of Soluble uPAR with Kidney Function Measures in Black AmericansReiner, Alexander P.Raffield, Laura M.Franceschini, NoraAuer, Paul L.Lange, Ethan M.Nickerson, Deborah A.Zakai, Neil A.Correa, AdolfoOlson, Nels,,Abe, NamikoAbecasis, GonçaloAguet, FrancoisAlbert, ChristineAlmasy, LauraAlonso, AlvaroAment, SethAnderson, PeterAnugu, PramodApplebaum-Bowden, DeborahArdlie, KristinArking, DanArnett, Donna K.Ashley-Koch, AllisonAslibekyan, StellaAssimes, TimAuer, PaulAvramopoulos, DimitriosBarnard, JohnBarnes, KathleenBarr, R. GrahamBarron-Casella, EmilyBarwick, LucasBeaty, TerriBeck, GeraldBecker, DianeBecker, LewisBeer, RebeccaBeitelshees, AmberBenjamin, EmeliaBenos, TakisBezerra, MarcosBielak, LarryBis, JoshuaBlackwell, ThomasBlangero, JohnBoerwinkle, EricBowden, Donald W.Bowler, RussellBrody, JenniferBroeckel, UlrichBroome, JaiBunting, KarenBurchard, EstebanBustamante, CarlosButh, ErinCade, BrianCardwell, JonathanCarey, VincentCarty, CaraCasaburi, RichardCasella, JamesCastaldi, PeterChaffin, MarkChang, ChristyChang, Yi-ChengChasman, DanielChavan, SameerChen, Bo-JuenChen, Wei-MinChen, Yii-Der IdaCho, MichaelChoi, Seung HoanChuang, Lee-MingChung, MinaChung, Ren-HuaClish, ClaryComhair, SuzyConomos, MatthewCornell, ElaineCorrea, AdolfoCrandall, CarolynCrapo, JamesCupples, L. AdrienneCurran, JoanneCurtis, JeffreyCuster, BrianDamcott, ColeenDarbar, DawoodDas, SayantanDavid, SeanDavis, ColleenDaya, Michellede Andrade, Marizade las Fuentes, LisaDeBaun, MichaelDeka, RanjanDeMeo, DawnDevine, ScottDuan, QingDuggirala, RaviDurda, Jon PeterDutcher, SusanEaton, CharlesEkunwe, LynetteEl Boueiz, AdelEllinor, PatrickEmery, LeslieErzurum, SerpilFarber, CharlesFingerlin, TashaFlickinger, MatthewFornage, MyriamFranceschini, NoraFrazar, ChrisFu, MaoFullerton, Stephanie M.Fulton, LucindaGabriel, StaceyGan, WeiniuGao, ShanshanGao, YanGass, MargeryGelb, BruceGeng, Xiaoqi PriscillaGeraci, MarkGermer, SorenGerszten, RobertGhosh, AuyonGibbs, RichardGignoux, ChrisGladwin, MarkGlahn, DavidGogarten, StephanieGong, Da-WeiGoring, HaraldGraw, SharonGrine, DanielGu, C. CharlesGuan, YueGuo, XiuqingGupta, NamrataHaessler, JeffHall, MichaelHarris, DanielHawley, Nicola L.He, JiangHeavner, BenHeckbert, SusanHernandez, RyanHerrington, DavidHersh, CraigHidalgo, BerthaHixson, JamesHobbs, BrianHokanson, JohnHong, ElliottHoth, KarinHsiung, Chao AgnesHung, Yi-JenHuston, HaleyHwu, Chii MinIrvin, Marguerite RyanJackson, RebeccaJain, DeeptiJaquish, CashellJhun, Min AJohnsen, JillJohnson, AndrewJohnson, CraigJohnston, RichJones, KimberlyKang, Hyun MinKaplan, RobertKardia, SharonKathiresan, SekarKelly, ShannonKenny, EimearKessler, MichaelKhan, AlynaKim, WonjiKinney, GregKonkle, BarbaraKooperberg, CharlesKramer, HollyLange, ChristophLange, EthanLange, LeslieLaurie, CathyLaurie, CeceliaLeBoff, MerylLee, JiwonLee, Seunggeun ShawnLee, Wen-JaneLeFaive, JonathonLevine, DavidLevy, DanLewis, JoshuaLi, XiaohuiLi, YunLin, HenryLin, HonghuangLin, Keng HanLin, XihongLiu, SiminLiu, YongmeiLiu, YuLoos, Ruth J.F.Lubitz, StevenLunetta, KathrynLuo, JamesMahaney, MichaelMake, BarryManichaikul, AniManson, JoAnnMargolin, LaurenMartin, LisaMathai, SusanMathias, RasikaMay, SusanneMcArdle, PatrickMcDonald, Merry-LynnMcFarland, SeanMcGarvey, StephenMcGoldrick, DanielMcHugh, CaitlinMei, HaoMestroni, LuisaMeyers, Deborah AMikulla, JulieMin, NancyMinear, MollieMinster, Ryan L.Mitchell, Braxton D.Moll, MattMontasser, May E.Montgomery, CourtneyMoscati, ArdenMusani, SolomonMwasongwe, StanfordMychaleckyj, Josyf C.Nadkarni, GirishNaik, RakhiNaseri, TakeNatarajan, PradeepNekhai, SergeiNelson, Sarah C.Neltner, BonnieNickerson, DeborahNorth, KariO'Connell, JeffO'Connor, TimOchs-Balcom, HeatherPaik, DavidPalmer, NicholettePankow, JamesPapanicolaou, GeorgeParsa, AfshinPeralta, Juan ManuelPerez, MarcoPerry, JamesPeters, UlrikePeyser, PatriciaPhillips, Lawrence S.Pollin, ToniPost, WendyBecker, Julia PowersBoorgula, Meher PreethiPreuss, MichaelPsaty, BruceQasba, PankajQiao, DandiQin, ZhaohuiRafaels, NicholasRaffield, LauraRamachandran, Vasan S.Rao, D.C.Rasmussen-Torvik, LauraRatan, AakroshRedline, SusanReed, RobertRegan, ElizabethReiner, AlexReupena, Muagututi‘a SefuivaRice, KenRich, StephenRoden, DanRoselli, CarolinaRotter, JeromeRuczinski, IngoRussell, PamelaRuuska, SarahRyan, KathleenSabino, Ester CerdeiraSaleheen, DanishSalimi, ShabnamSalzberg, StevenSandow, KevinSankaran, Vijay G.Scheller, ChristopherSchmidt, EllenSchwander, KarenSchwartz, DavidSciurba, FrankSeidman, ChristineSeidman, JonathanSheehan, VivienSherman, Stephanie L.Shetty, AmolShetty, AniketSheu, Wayne Hui-HengShoemaker, M. BenjaminSilver, BrianSilverman, EdwinSmith, JenniferSmith, JoshSmith, NicholasSmith, TanjaSmoller, SylviaSnively, BeverlySnyder, MichaelSofer, TamarSotoodehnia, NonaStilp, Adrienne M.Storm, GarrettStreeten, ElizabethSu, Jessica LaskySung, Yun JuSylvia, JodySzpiro, AdamSztalryd, CaroleTaliun, DanielTang, HuaTaub, MargaretTaylor, Kent D.Taylor, MatthewTaylor, SimeonTelen, MarilynThornton, Timothy A.Threlkeld, MachikoTinker, LesleyTirschwell, DavidTishkoff, SarahTiwari, HemantTong, CatherineTracy, RussellTsai, MichaelVaidya, DhananjayVan Den Berg, DavidVandeHaar, PeterVrieze, ScottWalker, TarikWallace, RobertWalts, AvramWang, Fei FeiWang, HemingWatson, KarolWeeks, Daniel E.Weir, BruceWeiss, ScottWeng, Lu-ChenWessel, JenniferWiller, CristenWilliams, KayleenWilliams, L. KeokiWilson, CarlaWilson, JamesWong, QuennaWu, JosephXu, HuichunYanek, LisaYang, IvanaYang, RongzeZaghloul, NorannZekavat, MaryamZhang, YingzeZhao, Snow XueyanZhao, WeiZhi, DeguiZhou, XiangZhu, XiaofengZody, MichaelZoellner, Sebastian2020-12-02T10:45:39-08:00doi:10.2215/CJN.12100720hwp:resource-id:clinjasn;16/2/287American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, genetic renal disease, sickle cell traitResearch LettersResearch Lettersletter20212021-02-08February 08, 202110.2215/CJN.121007201555-90411555-905X2020-12-02T10:45:39-08:002021-02-08Clinical Journal of the American Society of NephrologyResearch Letters162287289
- Optimizing Utilization of Kidneys from Hepatitis C–Positive Kidney Donors10.2215/CJN.19431220Fri, 15 Jan 2021 06:58:50 GMT-08:00Optimizing Utilization of Kidneys from Hepatitis C–Positive Kidney DonorsAriyamuthu, Venkatesh K.Tanriover, Bekir2021-01-15T06:58:50-08:00doi:10.2215/CJN.19431220hwp:resource-id:clinjasn;16/2/188American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhepatitis, kidney transplantation, cadaver organ transplantation, glomerular filtration rate, kidney failureEditorialsEditorialseditorial20212021-02-08February 08, 202110.2215/CJN.194312201555-90411555-905X2021-01-15T06:58:50-08:002021-02-08Clinical Journal of the American Society of NephrologyEditorials1622188251190261
- Authors' Reply10.1681/ASN.2020091276Tue, 29 Sep 2020 11:07:03 GMT-07:00Authors' ReplyClarke, Candice L.Prendecki, MariaMcAdoo, Stephen P.Willicombe, Michelle2020-09-29T11:07:03-07:00doi:10.1681/ASN.2020091276hwp:resource-id:jnephrol;31/12/2968-aAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologySeroprevalence, COVID-19Letters to the EditorLetters to the Editorletter20202020-12-01December 202010.1681/ASN.20200912761046-66731533-34502020-09-29T11:07:03-07:002020-12Journal of the American Society of NephrologyLetters to the Editor3112122968296729682967
- TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling10.1681/ASN.2020040424Wed, 30 Dec 2020 07:39:40 GMT-08:00TrkC Is Essential for Nephron Function and Trans-Activates Igf1R SignalingLepa, CarolinHoppe, SaschaStöber, AntjeSkryabin, Boris V.Sievers, Laura KatharinaHeitplatz, BarbaraCiarimboli, GiulianoNeugebauer, UteLindenmeyer, Maja T.Cohen, Clemens D.Drexler, Hannes C.A.Boor, PeterWeide, ThomasPavenstädt, HermannGeorge, Britta2020-12-30T07:39:40-08:00doi:10.1681/ASN.2020040424hwp:resource-id:jnephrol;32/2/357American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyTrkC, Ntrk3, signaling, Igf1R, podocyteBasic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200404241046-66731533-34502020-12-30T07:39:40-08:002021-02Journal of the American Society of NephrologyBasic Research322357374
- Remdesivir in COVID-19 Patients with Impaired Renal Function10.1681/ASN.2020101535Thu, 21 Jan 2021 10:45:06 GMT-08:00Remdesivir in COVID-19 Patients with Impaired Renal FunctionGevers, SannaWelink, Janvan Nieuwkoop, Cees2021-01-21T10:45:06-08:00doi:10.1681/ASN.2020101535hwp:resource-id:jnephrol;32/2/518American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotoxicity, COVID-19Letters to the EditorLetters to the Editorletter20212021-02-01February 202110.1681/ASN.20201015351046-66731533-34502021-01-21T10:45:06-08:002021-02Journal of the American Society of NephrologyLetters to the Editor3222751851913845195201386
- Authors’ Reply10.1681/ASN.2020121692Thu, 21 Jan 2021 10:45:07 GMT-08:00Authors’ ReplyAdamsick, Meagan L.Bhattacharyya, Roby P.Sise, Meghan E.,2021-01-21T10:45:07-08:00doi:10.1681/ASN.2020121692hwp:resource-id:jnephrol;32/2/519American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, COVID-19Letters to the EditorLetters to the Editorletter20212021-02-01February 202110.1681/ASN.20201216921046-66731533-34502021-01-21T10:45:07-08:002021-02Journal of the American Society of NephrologyLetters to the Editor3222751951813845205191386
- Incidence, Characteristics, and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry Study10.1681/ASN.2020060875Thu, 05 Nov 2020 08:49:17 GMT-08:00Incidence, Characteristics, and Outcome of COVID-19 in Adults on Kidney Replacement Therapy: A Regionwide Registry StudyDe Meester, JohanDe Bacquer, DirkNaesens, MaartenMeijers, BjornCouttenye, Marie M.De Vriese, An S.,,Gheuens, Ericde Jonge, HylkeDe Meyer, VickyDe Moor, BartEvenepoel, PieterHenckes, ManuLemahieu, WimStas, KoenVan Biesen, WimWissing, Karl Martin2020-11-05T08:49:17-08:00doi:10.1681/ASN.2020060875hwp:resource-id:jnephrol;32/2/385American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, kidney transplantation, clinical epidemiology, mortality, virology, COVID-19Clinical EpidemiologyClinical Epidemiologyresearch-article20212021-02-01February 202110.1681/ASN.20200608751046-66731533-34502020-11-05T08:49:17-08:002021-02Journal of the American Society of NephrologyClinical Epidemiology322385396
- Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes10.1681/ASN.2020040464Tue, 15 Dec 2020 09:50:57 GMT-08:00Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and OutcomesReese, Peter P.Aubert, OlivierNaesens, MaartenHuang, EdmundPotluri, VishnuKuypers, DirkBouquegneau, AntoineDivard, GillianRaynaud, MarcBouatou, YassineVo, AshleyGlotz, DenisLegendre, ChristopheLefaucheur, CarmenJordan, StanleyEmpana, Jean-PhilippeJouven, XavierLoupy, Alexandre2020-12-15T09:50:57-08:00doi:10.1681/ASN.2020040464hwp:resource-id:jnephrol;32/2/397American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, transplant outcomes, kidney transplantation, epidemiology and outcomes, pathologyClinical EpidemiologyClinical Epidemiologyresearch-article20212021-02-01February 202110.1681/ASN.20200404641046-66731533-34502020-12-15T09:50:57-08:002021-02Journal of the American Society of NephrologyClinical Epidemiology322553971263126440912641265
- Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5p10.1681/ASN.2020060775Thu, 21 Jan 2021 10:45:07 GMT-08:00Renal AAV2-Mediated Overexpression of Long Non-Coding RNA H19 Attenuates Ischemic Acute Kidney Injury Through Sponging of microRNA-30a-5pHaddad, GeorgeKölling, MalteWegmann, Urs A.Dettling, AngelaSeeger, HaraldSchmitt, RolandSoerensen-Zender, IngaHaller, HermannKistler, Andreas D.Dueck, AnneEngelhardt, StefanThum, ThomasMueller, Thomas F.Wüthrich, Rudolf P.Lorenzen, Johan M.2021-01-21T10:45:07-08:00doi:10.1681/ASN.2020060775hwp:resource-id:jnephrol;32/2/323American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyischemic acute kidney injury, lncRNA, H19Basic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200607751046-66731533-34502021-01-21T10:45:07-08:002021-02Journal of the American Society of NephrologyBasic Research322323341
- Long-Term Exposure to Ambient PM2.5 and Increased Risk of CKD Prevalence in China10.1681/ASN.2020040517Thu, 17 Dec 2020 07:15:33 GMT-08:00Long-Term Exposure to Ambient PM2.5 and Increased Risk of CKD Prevalence in ChinaLi, GuoxingHuang, JingWang, JinweiZhao, MinghuiLiu, YangGuo, XinbiaoWu, ShaoweiZhang, Luxia2020-12-17T07:15:33-08:00doi:10.1681/ASN.2020040517hwp:resource-id:jnephrol;32/2/448American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, prevalence, ambient PM2.5, long-term exposureClinical EpidemiologyClinical Epidemiologyresearch-article20212021-02-01Month XX, 202010.1681/ASN.20200405171046-66731533-34502020-12-17T07:15:33-08:002021-02Journal of the American Society of NephrologyClinical Epidemiology323222844826021014582622101
- Authors’ Reply10.1681/ASN.2020111615Thu, 17 Dec 2020 07:15:34 GMT-08:00Authors’ ReplyDenic, AleksandarRule, Andrew D.2020-12-17T07:15:34-08:00doi:10.1681/ASN.2020111615hwp:resource-id:jnephrol;32/2/517-aAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephron, renal morphology, glomerulusLetters to the EditorLetters to the Editorletter20212021-02-01February 202110.1681/ASN.20201116151046-66731533-34502020-12-17T07:15:34-08:002021-02Journal of the American Society of NephrologyLetters to the Editor32221151751726425185172652
- Can Total Nephron Number Predict Progressive CKD after Radical Nephrectomy?10.1681/ASN.2020111585Thu, 17 Dec 2020 07:15:34 GMT-08:00Can Total Nephron Number Predict Progressive CKD after Radical Nephrectomy?Seibel, JeanRebibou, Jean-MichelLegendre, Mathieu2020-12-17T07:15:34-08:00doi:10.1681/ASN.2020111585hwp:resource-id:jnephrol;32/2/517American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologynephrectomy, Pathophysiology of Renal Disease and Progression, hyperfiltration, nephronLetters to the EditorLetters to the Editorletter20212021-02-01February 202110.1681/ASN.20201115851046-66731533-34502020-12-17T07:15:34-08:002021-02Journal of the American Society of NephrologyLetters to the Editor32221151751726425175182652
- Missing Self-Induced Activation of NK Cells Combines with Non-Complement-Fixing Donor-Specific Antibodies to Accelerate Kidney Transplant Loss in Chronic Antibody-Mediated Rejection10.1681/ASN.2020040433Wed, 25 Nov 2020 01:16:05 GMT-08:00Missing Self-Induced Activation of NK Cells Combines with Non-Complement-Fixing Donor-Specific Antibodies to Accelerate Kidney Transplant Loss in Chronic Antibody-Mediated RejectionKoenig, AliceMezaache, SarahCallemeyn, JasperBarba, ThomasMathias, VirginieSicard, AntoineCharreau, BéatriceRabeyrin, MaudDijoud, FrédériquePicard, CécileMeas-Yedid, VannaryOlivo-Marin, Jean-ChristopheMorelon, EmmanuelNaesens, MaartenDubois, ValérieThaunat, Olivier2020-11-25T13:16:05-08:00doi:10.1681/ASN.2020040433hwp:resource-id:jnephrol;32/2/479American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, chronic rejection, NK cells, donor specific antibodies, missing selfClinical ResearchClinical Researchresearch-article20212021-02-01Month XX, 202010.1681/ASN.20200404331046-66731533-34502020-11-25T13:16:05-08:002021-02Journal of the American Society of NephrologyClinical Research3222479262494264
- A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD10.1681/ASN.2020050556Mon, 07 Dec 2020 08:43:40 GMT-08:00A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKDToto, RobertPetersen, JeffreyBerns, Jeffrey S.Lewis, Eldrin FosterTran, QuiWeir, Matthew R.2020-12-07T08:43:40-08:00doi:10.1681/ASN.2020050556hwp:resource-id:jnephrol;32/2/469American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, darbepoetin, dosing strategy, blood transfusionClinical ResearchClinical Researchresearch-article20212021-02-01February 202110.1681/ASN.20200505561046-66731533-34502020-12-07T08:43:40-08:002021-02Journal of the American Society of NephrologyClinical Research322469478
- Changes in NAD and Lipid Metabolism Drive Acidosis-Induced Acute Kidney Injury10.1681/ASN.2020071003Thu, 21 Jan 2021 10:45:07 GMT-08:00Changes in NAD and Lipid Metabolism Drive Acidosis-Induced Acute Kidney InjuryBugarski, MilicaGhazi, SusanPolesel, MarcelloMartins, Joana R.Hall, Andrew M.2021-01-21T10:45:07-08:00doi:10.1681/ASN.2020071003hwp:resource-id:jnephrol;32/2/342American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis, acute renal failure, metabolism, mitochondria, proximal tubuleBasic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200710031046-66731533-34502021-01-21T10:45:07-08:002021-02Journal of the American Society of NephrologyBasic Research322342356
- Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury10.1681/ASN.2020020127Wed, 06 Jan 2021 08:44:24 GMT-08:00Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion InjuryGillis, Ellen E.Brands, Michael W.Sullivan, Jennifer C.2021-01-06T08:44:24-08:00doi:10.1681/ASN.2020020127hwp:resource-id:jnephrol;32/2/375American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, intrauterine growth, animal model, acute kidney injury, pregnancyBasic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200201271046-66731533-34502021-01-06T08:44:24-08:002021-02Journal of the American Society of NephrologyBasic Research3222375259384260
- Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD and Risk of Adverse Outcomes: A Nationwide Study10.1681/ASN.2020050682Mon, 28 Dec 2020 09:08:14 GMT-08:00Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD and Risk of Adverse Outcomes: A Nationwide StudyFu, Edouard L.Evans, MarieClase, Catherine M.Tomlinson, Laurie A.van Diepen, MerelDekker, Friedo W.Carrero, Juan J.2020-12-28T09:08:14-08:00doi:10.1681/ASN.2020050682hwp:resource-id:jnephrol;32/2/424American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyACE inhibitors, mortality risk, dialysis, cardiovascular events, kidney disease, renin-angiotensin systemClinical EpidemiologyClinical Epidemiologyresearch-article20212021-02-01February 202110.1681/ASN.20200506821046-66731533-34502020-12-28T09:08:14-08:002021-02Journal of the American Society of NephrologyClinical Epidemiology322424435
- Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy10.1681/ASN.2020030349Wed, 23 Dec 2020 08:27:25 GMT-08:00Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA NephropathyCanney, MarkBarbour, Sean J.Zheng, YuyanCoppo, RosannaZhang, HongLiu, Zhi-HongMatsuzaki, KeiichiSuzuki, YusukeKatafuchi, RitsukoReich, Heather N.Cattran, Daniel,,Russo, M.L.Troyanov, S.Cook, H.T.Roberts, I.Tesar, V.Maixnerova, D.Lundberg, S.Emma, F.Fuiano, L.Beltrame, G.Rollino, C.Amore, A.Camilla, R.Peruzzi, L.Praga, M.Feriozzi, S.Polci, R.Segoloni, G.Colla, L.Pani, A.Piras, D.Angioi, A.Cancarini, G.Ravera, S.Durlik, M.Moggia, E.Ballarin, J.Di Giulio, S.Pugliese, F.Serriello, I.Caliskan, Y.Sever, M.Kilicaslan, I.Locatelli, F.Del Vecchio, L.Wetzels, J.F.M.Peters, H.Berg, U.Carvalho, F.da Costa Ferreira, A.C.Maggio, M.Wiecek, A.Ots-Rosenberg, M.Magistroni, R.Topaloglu, R.Bilginer, Y.D’Amico, M.Stangou, M.Giacchino, F.Goumenos, D.Kalliakmani, P.Gerolymos, M.Galesic, K.Geddes, C.Siamopoulos, K.Balafa, O.Galliani, M.Stratta, P.Quaglia, M.Bergia, R.Cravero, R.Salvadori, M.Cirami, L.Fellstrom, B.Smerud, H. KlosterFerrario, F.Stellato, T.Egido, J.Martin, C.Floege, J.Eitner, F.Lupo, A.Bernich, P.Menè, P.Morosetti, M.van Kooten, C.Rabelink, T.Reinders, M.E.J.Grinyo, J.M. BoriaCusinato, S.Benozzi, L.Savoldi, S.Licata, C.Mizerska-Wasiak, M.Martina, G.Messuerotti, A.Dal Canton, A.Esposito, C.Migotto, C.Triolo, G.Mariano, F.Pozzi, C.Boero, R.Bellur, S.Mazzucco, G.Giannakakis, C.Honsova, E.Sundelin, B.Di Palma, A.M.Ferrario, F.Gutiérrez, E.Asunis, A.M.Barratt, J.Tardanico, R.Perkowska-Ptasinska, A.Terroba, J. ArceFortunato, M.Pantzaki, A.Ozluk, Y.Steenbergen, E.Soderberg, M.Riispere, Z.Furci, L.Orhan, D.Kipgen, D.Casartelli, D.Ljubanovic, D. GalesicGakiopoulou, HBertoni, E.Ortiz, P. CannataKarkoszka, H.Groene, H.J.Stoppacciaro, A.Bajema, I.Bruijn, J.Oliveras, X. FulladosaMaldyk, J.Ioachim, E.Bavbek, N.Cook, T.Troyanov, S.Alpers, C.Amore, A.Barratt, J.Feehally, J.Berthoux, F.Bonsib, S.Bruijn, J.D’Agati, V.D’Amico, G.Emancipator, S.Emmal, F.Ferrario, F.Fervenza, F.Florquin, S.Fogo, A.Geddes, C.Groene, H.Haas, M.Hill, P.Hogg, R.Hsu, S.Hunley, T.Hladunewich, M.Jennette, C.Joh, K.Julian, B.Kawamura, T.Lai, F.Leung, C.Li, L.Li, P.Liu, Z.Massat, A.Mackinnon, B.Mezzano, S.Schena, F.Tomino, Y.Walker, P.Wang, H.Weening, J.Yoshikawa, N.Zeng, Cai-HongShi, SufangSuzuki, H.Koike, K.Hirano, K.Kawamura, T.Yokoo, T.Hanai, M.Fukami, K.Takahashi, K.Yuzawa, Y.Niwa, M.Yasuda, Y.Maruyama, S.Ichikawa, D.Suzuki, T.Shirai, S.Fukuda, A.Fujimoto, S.Trimarchi, H.2020-12-23T08:27:25-08:00doi:10.1681/ASN.2020030349hwp:resource-id:jnephrol;32/2/436American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, end stage kidney disease, proteinuria, renal pathology, renal function decline, glomerular disease, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20212021-02-01February 202110.1681/ASN.20200303491046-66731533-34502020-12-23T08:27:25-08:002021-02Journal of the American Society of NephrologyClinical Epidemiology322436447
- Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study10.1681/ASN.2020060848Wed, 11 Nov 2020 10:18:24 GMT-08:00Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort StudyRehnberg, JohannaSymreng, AdinaLudvigsson, Jonas F.Emilsson, Louise2020-11-11T10:18:24-08:00doi:10.1681/ASN.2020060848hwp:resource-id:jnephrol;32/2/411American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, clinical epidemiology, end stage kidney disease, ESKDClinical EpidemiologyClinical Epidemiologyresearch-article20212021-02-01February 202110.1681/ASN.20200608481046-66731533-34502020-11-11T10:18:24-08:002021-02Journal of the American Society of NephrologyClinical Epidemiology322411423
- Erratum10.1681/ASN.2020111609Fri, 29 Jan 2021 11:00:41 GMT-08:00ErratumAmerican Society of Nephrology2021-01-29T11:00:41-08:00doi:10.1681/ASN.2020111609hwp:resource-id:jnephrol;32/2/521American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyJASN, erratum, correctionErrataErratacorrection20212021-02-01February 202110.1681/ASN.20201116091046-66731533-34502021-01-29T11:00:41-08:002021-02Journal of the American Society of NephrologyErrata3231211115212573257352125872587
- Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration Rate10.1681/ASN.2020060833Wed, 25 Nov 2020 01:16:04 GMT-08:00Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration RateChen, YanZelnick, Leila R.Hoofnagle, Andrew N.Yeung, Catherine K.Shireman, Laura M.Phillips, BrianBrauchla, Calder C.de Boer, IanManahan, LindaHeckbert, Susan R.Himmelfarb, JonathanKestenbaum, Bryan R.2020-11-25T13:16:04-08:00doi:10.1681/ASN.2020060833hwp:resource-id:jnephrol;32/2/459American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney medication clearance, glomerular filtration rate, secretory solutes clearances, furosemide, penciclovirClinical ResearchClinical Researchresearch-article20212021-02-01February 202110.1681/ASN.20200608331046-66731533-34502020-11-25T13:16:04-08:002021-02Journal of the American Society of NephrologyClinical Research322459468
- The Road Ahead for Research on Air Pollution and Kidney Disease10.1681/ASN.2020121713Mon, 18 Jan 2021 09:18:38 GMT-08:00The Road Ahead for Research on Air Pollution and Kidney DiseaseAl-Aly, ZiyadBowe, Benjamin2021-01-18T09:18:38-08:00doi:10.1681/ASN.2020121713hwp:resource-id:jnephrol;32/2/260American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, pollution, air pollution, chronic kidney disease, particulate matter, burden of disease, global health, environment, clinical epidemiologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-02-01February 202110.1681/ASN.20201217131046-66731533-34502021-01-18T09:18:38-08:002021-02Journal of the American Society of NephrologyUp Front Matters3222260448262458
- This Month's Highlights10.1681/ASN.2020121749Fri, 29 Jan 2021 11:00:40 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2021-01-29T11:00:40-08:00doi:10.1681/ASN.2020121749hwp:resource-id:jnephrol;32/2/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20212021-02-01February 202110.1681/ASN.20201217491046-66731533-34502021-01-29T11:00:40-08:002021-02Journal of the American Society of NephrologyThis Month’s Highlights322ii
- The Mineralocorticoid Receptor in Salt-Sensitive Hypertension and Renal InjuryHypertension and its comorbidities pose a major public health problem associated with disease-associated factors related to a modern lifestyle, such high salt intake or obesity. Accumulating evidence has demonstrated that aldosterone and its receptor, the mineralocorticoid receptor (MR), have crucial roles in the development of salt-sensitive hypertension and coexisting cardiovascular and renal injuries. Accordingly, clinical trials have repetitively shown the promising effects of MR blockers in these diseases. We and other researchers have identified novel mechanisms of MR activation involved in salt-sensitive hypertension and renal injury, including the obesity-derived overproduction of aldosterone and ligand-independent signaling. Moreover, recent advances in the analysis of cell-specific and context-dependent mechanisms of MR activation in various tissues—including a classic target of aldosterone, aldosterone-sensitive distal nephrons—are now providing new insights. In this review, we summarize recent updates to our understanding of aldosterone-MR signaling, focusing on its role in salt-sensitive hypertension and renal injury.10.1681/ASN.2020071041Mon, 04 Jan 2021 09:13:31 GMT-08:00The Mineralocorticoid Receptor in Salt-Sensitive Hypertension and Renal InjuryHypertension and its comorbidities pose a major public health problem associated with disease-associated factors related to a modern lifestyle, such high salt intake or obesity. Accumulating evidence has demonstrated that aldosterone and its receptor, the mineralocorticoid receptor (MR), have crucial roles in the development of salt-sensitive hypertension and coexisting cardiovascular and renal injuries. Accordingly, clinical trials have repetitively shown the promising effects of MR blockers in these diseases. We and other researchers have identified novel mechanisms of MR activation involved in salt-sensitive hypertension and renal injury, including the obesity-derived overproduction of aldosterone and ligand-independent signaling. Moreover, recent advances in the analysis of cell-specific and context-dependent mechanisms of MR activation in various tissues—including a classic target of aldosterone, aldosterone-sensitive distal nephrons—are now providing new insights. In this review, we summarize recent updates to our understanding of aldosterone-MR signaling, focusing on its role in salt-sensitive hypertension and renal injury.Ayuzawa, NobuhiroFujita, Toshiro2021-01-04T09:13:31-08:00doi:10.1681/ASN.2020071041hwp:resource-id:jnephrol;32/2/279American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymineralocorticoid receptor, aldosterone, pendrin, obesity, salt, hypertensionUp Front MattersReviewsUp Front MattersReviewsreview-article20212021-02-01February 202110.1681/ASN.20200710411046-66731533-34502021-01-04T09:13:31-08:002021-02Journal of the American Society of NephrologyUp Front Matters322279289
- Dysregulated Dynein-Mediated Trafficking of Nephrin Causes INF2-related Podocytopathy10.1681/ASN.2020081109Tue, 22 Dec 2020 05:54:56 GMT-08:00Dysregulated Dynein-Mediated Trafficking of Nephrin Causes INF2-related PodocytopathySun, HuaPerez-Gill, ChandraSchlöndorff, Johannes SSubramanian, BalajikarthickPollak, Martin R.2020-12-22T05:54:56-08:00doi:10.1681/ASN.2020081109hwp:resource-id:jnephrol;32/2/307American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, podocyte, cytoskeletonBasic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200811091046-66731533-34502020-12-22T05:54:56-08:002021-02Journal of the American Society of NephrologyBasic Research322307322
- Missing Self and DSA—Synergy of Two NK Cell Activation Pathways in Kidney Transplantation10.1681/ASN.2020121731Thu, 07 Jan 2021 09:45:43 GMT-08:00Missing Self and DSA—Synergy of Two NK Cell Activation Pathways in Kidney TransplantationHidalgo, Luis G.2021-01-07T09:45:43-08:00doi:10.1681/ASN.2020121731hwp:resource-id:jnephrol;32/2/262American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic allograft rejection, immunology, kidney transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-02-01February 202110.1681/ASN.20201217311046-66731533-34502021-01-07T09:45:43-08:002021-02Journal of the American Society of NephrologyUp Front Matters3222262479264494
- New ‘Antigens’ in Membranous NephropathyMembranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account for approximately 60% of all MN, both primary and secondary. In the remaining MN, target antigens were unknown. Use of laser microdissection and mass spectrometry enabled identification of new “antigens.” This approach led to the identification of four novel types of MN: exotosin 1 (EXT1)– and exotosin 2 (EXT2)–associated MN, NELL1-associated MN, Sema3B-associated MN, and PCDH7-associated MN. Each of these represents a distinct disease entity, with different clinical and pathologic findings. In this review, the structure of the proteins and the clinical and pathologic findings of the new types of MN are discussed. The role of mass spectrometry for accurate diagnosis of MN cannot be overemphasized. Finally, any classification of MN should be made on the basis of the antigens that are detected. Further studies are required to understand the pathophysiology, response to treatment, and outcomes of these new MNs.10.1681/ASN.2020071082Wed, 30 Dec 2020 07:39:40 GMT-08:00New ‘Antigens’ in Membranous NephropathyMembranous nephropathy (MN) occurs due to deposition of immune complexes along the subepithelial region of glomerular basement membrane. Two previously identified target antigens for the immune complexes, PLA2R (identified in 2009) and THSD7A (in 2014), account for approximately 60% of all MN, both primary and secondary. In the remaining MN, target antigens were unknown. Use of laser microdissection and mass spectrometry enabled identification of new “antigens.” This approach led to the identification of four novel types of MN: exotosin 1 (EXT1)– and exotosin 2 (EXT2)–associated MN, NELL1-associated MN, Sema3B-associated MN, and PCDH7-associated MN. Each of these represents a distinct disease entity, with different clinical and pathologic findings. In this review, the structure of the proteins and the clinical and pathologic findings of the new types of MN are discussed. The role of mass spectrometry for accurate diagnosis of MN cannot be overemphasized. Finally, any classification of MN should be made on the basis of the antigens that are detected. Further studies are required to understand the pathophysiology, response to treatment, and outcomes of these new MNs.Sethi, Sanjeev2020-12-30T07:39:40-08:00doi:10.1681/ASN.2020071082hwp:resource-id:jnephrol;32/2/268American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, membranous nephropathy, nephrotic syndromeUp Front MattersReviewsUp Front MattersReviewsreview-article20212021-02-01February 202110.1681/ASN.20200710821046-66731533-34502020-12-30T07:39:40-08:002021-02Journal of the American Society of NephrologyUp Front Matters322268278
- Animal Model of Pregnancy after Acute Kidney Injury Mirrors the Human Observations10.1681/ASN.2020121734Wed, 06 Jan 2021 08:44:24 GMT-08:00Animal Model of Pregnancy after Acute Kidney Injury Mirrors the Human ObservationsTangren, Jessica SheehanThadhani, Ravi2021-01-06T08:44:24-08:00doi:10.1681/ASN.2020121734hwp:resource-id:jnephrol;32/2/259American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-02-01February 202110.1681/ASN.20201217341046-66731533-34502021-01-06T08:44:24-08:002021-02Journal of the American Society of NephrologyUp Front Matters3222259375260384
- Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality Gradients10.1681/ASN.2020070930Wed, 25 Nov 2020 01:16:05 GMT-08:00Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality GradientsHinze, ChristianKaraiskos, NikosBoltengagen, AnastasiyaWalentin, KatharinaRedo, KleaHimmerkus, NinaBleich, MarkusPotter, S. StevenPotter, Andrew S.Eckardt, Kai-UweKocks, ChristineRajewsky, NikolausSchmidt-Ott, Kai M.2020-11-25T13:16:05-08:00doi:10.1681/ASN.2020070930hwp:resource-id:jnephrol;32/2/291American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologymicroenvironment, spatial resolution single-cell transcriptomics, osmolality gradient, osmogenes, cell typesBasic ResearchBasic Researchresearch-article20212021-02-01February 202110.1681/ASN.20200709301046-66731533-34502020-11-25T13:16:05-08:002021-02Journal of the American Society of NephrologyBasic Research322291306
- The Arteriovenous Fistula and Progression of Kidney Disease10.34067/KID.0006262020Thu, 28 Jan 2021 05:00:28 GMT-08:00The Arteriovenous Fistula and Progression of Kidney DiseaseGolper, Thomas A.2021-01-28T05:00:28-08:00doi:10.34067/KID.0006262020hwp:resource-id:kidney360;2/1/4American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, adherence, basic science, eGFR, fistula, graft, hemodialysis, preconditioning, progression, stiffness, vasoactivityEditorialsEditorialseditorial20212021-01-2810.34067/KID.00062620202641-76502021-01-28T05:00:28-08:002021-01-28Kidney360Editorials2146
- Hypomagnesemia in the Cancer PatientHypomagnesemia is a common medical problem that contributes to the morbidity and mortality of patients with cancer. This review summarizes magnesium physiology and highlights the mechanisms underlying magnesium disturbances due to cancer and cancer treatment. The causes of hypomagnesemia can be categorized according to the pathophysiologic mechanism: decreased intake, transcellular shift, gastrointestinal losses, and kidney losses. Patients with cancer are at risk for opportunistic infections, frequently experience cardiovascular complications, and often receive classes of medications that cause or exacerbate hypomagnesemia. Also, cancer-specific therapies are responsible for hypomagnesemia, including platinum-based chemotherapy, anti-EGF receptor mAbs, human EGF receptor-2 target inhibitors (HER2), and calcineurin inhibitors. Urinary indices, such as the fractional excretion of magnesium, can provide useful information about the etiology. The management of hypomagnesemia depends on the magnitude of hypomagnesemia and the underlying cause. We recommended checking serum magnesium at the beginning of treatment and as part of routine monitoring throughout cancer treatment. Opportunities exist for potential research and practice improvement, including further characterization of hypomagnesemia regarding the clinical effect on cancer outcomes, preventing hypomagnesemia in patients receiving high-risk anticancer agents, and developing effective therapeutic strategies.10.34067/KID.0005622020Wed, 11 Nov 2020 01:24:25 GMT-08:00Hypomagnesemia in the Cancer PatientHypomagnesemia is a common medical problem that contributes to the morbidity and mortality of patients with cancer. This review summarizes magnesium physiology and highlights the mechanisms underlying magnesium disturbances due to cancer and cancer treatment. The causes of hypomagnesemia can be categorized according to the pathophysiologic mechanism: decreased intake, transcellular shift, gastrointestinal losses, and kidney losses. Patients with cancer are at risk for opportunistic infections, frequently experience cardiovascular complications, and often receive classes of medications that cause or exacerbate hypomagnesemia. Also, cancer-specific therapies are responsible for hypomagnesemia, including platinum-based chemotherapy, anti-EGF receptor mAbs, human EGF receptor-2 target inhibitors (HER2), and calcineurin inhibitors. Urinary indices, such as the fractional excretion of magnesium, can provide useful information about the etiology. The management of hypomagnesemia depends on the magnitude of hypomagnesemia and the underlying cause. We recommended checking serum magnesium at the beginning of treatment and as part of routine monitoring throughout cancer treatment. Opportunities exist for potential research and practice improvement, including further characterization of hypomagnesemia regarding the clinical effect on cancer outcomes, preventing hypomagnesemia in patients receiving high-risk anticancer agents, and developing effective therapeutic strategies.Workeneh, Biruh T.Uppal, Nupur N.Jhaveri, Kenar D.Rondon-Berrios, Helbert2020-11-11T13:24:25-08:00doi:10.34067/KID.0005622020hwp:resource-id:kidney360;2/1/154American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, cetuximab, cisplatin, electrolytes, hypomagnesemia, magnesium, neoplasms, onconephrology, TRPM6Review ArticlesReview Articlesreview-article20212021-01-2810.34067/KID.00056220202641-76502020-11-11T13:24:25-08:002021-01-28Kidney360Review Articles21154166
- Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: CON10.34067/KID.0005572020Thu, 03 Dec 2020 06:20:01 GMT-08:00Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: CONPun, Patrick H.Crowley, Susan T.2020-12-03T06:20:01-08:00doi:10.34067/KID.0005572020hwp:resource-id:kidney360;2/1/13American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, Gadolinium, nephrogenic systemic fibrosis, safetyDebates in NephrologyDebates in Nephrologyresearch-article20212021-01-2810.34067/KID.00055720202641-76502020-12-03T06:20:01-08:002021-01-28Kidney360Debates in Nephrology211315
- Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: PRO10.34067/KID.0005792020Thu, 03 Dec 2020 06:20:01 GMT-08:00Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: PRORodby, Roger A.2020-12-03T06:20:01-08:00doi:10.34067/KID.0005792020hwp:resource-id:kidney360;2/1/10American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, CKD 4/5, gadolinium, nephrogenic systemic fibrosisDebates in NephrologyDebates in Nephrologyresearch-article20212021-01-2810.34067/KID.00057920202641-76502020-12-03T06:20:01-08:002021-01-28Kidney360Debates in Nephrology211012
- Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: COMMENTARY10.34067/KID.0006002020Thu, 03 Dec 2020 06:20:01 GMT-08:00Group II GBCM Can Be Used Safely for Imaging in Stage 4/5 CKD Patients: COMMENTARYAbu-Alfa, Ali K.2020-12-03T06:20:01-08:00doi:10.34067/KID.0006002020hwp:resource-id:kidney360;2/1/16American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, gadolinium, magnetic resonance imaging, nephrogenic systemic fibrosisModerator CommentaryModerator Commentaryarticle-commentary20212021-01-2810.34067/KID.00060020202641-76502020-12-03T06:20:01-08:002021-01-28Kidney360Moderator Commentary211619
- Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury: An Observational Study10.34067/KID.0006452020Fri, 20 Nov 2020 01:23:35 GMT-08:00Niacinamide May Be Associated with Improved Outcomes in COVID-19-Related Acute Kidney Injury: An Observational StudyRaines, Nathan H.Ganatra, SarjuNissaisorakarn, PitchaphonPandit, AmarMorales, AlexAsnani, AartiSadrolashrafi, MehrnazMaheshwari, RahulPatel, RushinBang, VigyanShreyder, KatherineBrar, SimarjeetSingh, AmitojDani, Sourbha S.Knapp, SarahPoyan Mehr, AliBrown, Robert S.Zeidel, Mark L.Bhargava, RheaSchlondorff, JohannesSteinman, Theodore I.Mukamal, Kenneth J.Parikh, Samir M.2020-11-20T13:23:35-08:00doi:10.34067/KID.0006452020hwp:resource-id:kidney360;2/1/33American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, acute renal failure, clinical trial, COVID-19, NAD+, niacinamide, outcomes, SARS-CoV-2, vitamin B3Original InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20212021-01-2810.34067/KID.00064520202641-76502020-11-20T13:23:35-08:002021-01-28Kidney360Original Investigations213341
- Living behind the Mask amid Two Pandemics: COVID-19 and Social Injustice10.34067/KID.0006422020Tue, 08 Dec 2020 01:29:19 GMT-08:00Living behind the Mask amid Two Pandemics: COVID-19 and Social InjusticeGee, Patrick O.2020-12-08T13:29:19-08:00doi:10.34067/KID.0006422020hwp:resource-id:kidney360;2/1/7American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, COVID-19, pandemics, patient, social injusticePatient PerspectivePatient Perspectiveresearch-article20212021-01-2810.34067/KID.00064220202641-76502020-12-08T13:29:19-08:002021-01-28Kidney360Patient Perspective2179
- COVID-19 in Patients with CKD in New York City10.34067/KID.0004142020Thu, 26 Nov 2020 05:30:15 GMT-08:00COVID-19 in Patients with CKD in New York CityAkchurin, OlehMeza, KellyBiswas, SharmiGreenbaum, MichaelaLicona-Freudenstein, Alexandra P.Goyal, ParagChoi, Justin J.Choi, Mary E.2020-11-26T05:30:15-08:00doi:10.34067/KID.0004142020hwp:resource-id:kidney360;2/1/63American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, acute kidney injury, COVID-19, hyperphosphatemia, in-hospital mortality, SARS-CoV-2Original InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-01-2810.34067/KID.00041420202641-76502020-11-26T05:30:15-08:002021-01-28Kidney360Original Investigations216370
- SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-1910.34067/KID.0006102020Tue, 01 Dec 2020 10:20:45 GMT-08:00SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19Wang, XiaolingPatel, AmrishTisdale, LelaHaq, ZahinYe, XiaolingLasky, RachelPreciado, PriscilaTao, XiaDias, Gabriela FerreiraChao, Joshua E.Hakim, MohamadHan, MaggieThwin, OhnmarRaimann, JochenChatoth, DineshKotanko, PeterGrobe, Nadja2020-12-01T10:20:45-08:00doi:10.34067/KID.0006102020hwp:resource-id:kidney360;2/1/86American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, COVID-19, dialysis solutions, peritoneal dialysis, RT-PCR, SARS-CoV-2Original InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20212021-01-2810.34067/KID.00061020202641-76502020-12-01T10:20:45-08:002021-01-28Kidney360Original Investigations218689
- Effect of COVID-19 on Kidney Disease Incidence and ManagementThe COVID-19 outbreak has had substantial effects on the incidence and management of kidney diseases, including AKI, ESKD, GN, and kidney transplantation. Initial reports from China suggested a lower AKI incidence in patients with COVID-19, but more recent studies from North America reveal a much higher incidence, likely due to the higher prevalence of comorbid conditions, such as hypertension, diabetes, and CKD. AKI in this setting is associated with worse outcomes, including the requirement for vasopressors or mechanical ventilation and death. Performing RRT in those with AKI poses challenges, such as limiting exposure of staff, preserving PPE, coagulopathy, and hypoxemia due to acute respiratory distress syndrome. Continuous RRT is the preferred modality, with sustained low-efficiency dialysis also an option, both managed without 1:1 hemodialysis nursing support. Regional citrate is the preferred anticoagulation, but systemic unfractionated heparin may be used in patients with coagulopathy. The ultrafiltration rate has to be set carefully, taking into consideration hypotension, hypoxemia, and responsiveness to presser and ventilatory support. The chance of transmission puts in-center chronic hemodialysis and other immunosuppressed patients at particularly increased risk. Limited data show that patients with CKD are also at increased risk for more severe disease, if infected. Little is known about the virus’s effects on immunocompromised patients with glomerular diseases and kidney transplants, which introduces challenges for management of immunosuppressant regimens. Although there are no standardized guidelines regarding the management of immunosuppression, several groups recommend stopping the antimetabolite in hospitalized transplant patients and continuing a reduced dose of calcineurin inhibitors. This comprehensive review critically appraises the best available evidence regarding the effect of COVID-19 on the incidence and management of kidney diseases. Where evidence is lacking, current expert opinion and clinical guidelines are reviewed, and knowledge gaps worth investigation are identified.10.34067/KID.0006362020Tue, 24 Nov 2020 10:19:10 GMT-08:00Effect of COVID-19 on Kidney Disease Incidence and ManagementThe COVID-19 outbreak has had substantial effects on the incidence and management of kidney diseases, including AKI, ESKD, GN, and kidney transplantation. Initial reports from China suggested a lower AKI incidence in patients with COVID-19, but more recent studies from North America reveal a much higher incidence, likely due to the higher prevalence of comorbid conditions, such as hypertension, diabetes, and CKD. AKI in this setting is associated with worse outcomes, including the requirement for vasopressors or mechanical ventilation and death. Performing RRT in those with AKI poses challenges, such as limiting exposure of staff, preserving PPE, coagulopathy, and hypoxemia due to acute respiratory distress syndrome. Continuous RRT is the preferred modality, with sustained low-efficiency dialysis also an option, both managed without 1:1 hemodialysis nursing support. Regional citrate is the preferred anticoagulation, but systemic unfractionated heparin may be used in patients with coagulopathy. The ultrafiltration rate has to be set carefully, taking into consideration hypotension, hypoxemia, and responsiveness to presser and ventilatory support. The chance of transmission puts in-center chronic hemodialysis and other immunosuppressed patients at particularly increased risk. Limited data show that patients with CKD are also at increased risk for more severe disease, if infected. Little is known about the virus’s effects on immunocompromised patients with glomerular diseases and kidney transplants, which introduces challenges for management of immunosuppressant regimens. Although there are no standardized guidelines regarding the management of immunosuppression, several groups recommend stopping the antimetabolite in hospitalized transplant patients and continuing a reduced dose of calcineurin inhibitors. This comprehensive review critically appraises the best available evidence regarding the effect of COVID-19 on the incidence and management of kidney diseases. Where evidence is lacking, current expert opinion and clinical guidelines are reviewed, and knowledge gaps worth investigation are identified.McAdams, MeredithOstrosky-Frid, MauricioRajora, NilumHedayati, Susan2020-11-24T10:19:10-08:00doi:10.34067/KID.0006362020hwp:resource-id:kidney360;2/1/141American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury, ICU nephrology, chronic kidney disease, COVID-19, dialysis, end stage kidney diseaseReview ArticlesReview Articlesreview-article20212021-01-2810.34067/KID.00063620202641-76502020-11-24T10:19:10-08:002021-01-28Kidney360Review Articles21141153
- Skin Rash in a Stage 4 CKD Patient Treated for Hyperkalemia10.34067/KID.0003992020Thu, 28 Jan 2021 05:00:28 GMT-08:00Skin Rash in a Stage 4 CKD Patient Treated for HyperkalemiaBoge, HannaAlmehmi, SloanAlmehmi, Ammar2021-01-28T05:00:28-08:00doi:10.34067/KID.0003992020hwp:resource-id:kidney360;2/1/176American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, chronic renal insufficiency, CKD, exanthema, hyperkalemia, patiromer, skin rashClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-01-2810.34067/KID.00039920202641-76502021-01-28T05:00:28-08:002021-01-28Kidney360Clinical Images in Nephrology and Dialysis21176177
- Arteriovenous Fistula Creation and Estimated Glomerular Filtration Rate Decline in Advanced CKD: A Matched Cohort Study10.34067/KID.0005072020Thu, 19 Nov 2020 01:38:50 GMT-08:00Arteriovenous Fistula Creation and Estimated Glomerular Filtration Rate Decline in Advanced CKD: A Matched Cohort StudyDupuis, Marie-ÈveLaurin, Louis-PhilippeGoupil, RémiBénard, ValériePichette, MaudeLafrance, Jean-PhilippeElftouh, NaoualPichette, VincentNadeau-Fredette, Annie-Claire2020-11-19T13:38:50-08:00doi:10.34067/KID.0005072020hwp:resource-id:kidney360;2/1/42American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, arteriovenous fistula, chronic renal insufficiency, cohort studies, estimated glomerular filtration rate, peritoneal dialysis, predialysis, propensity score matchingOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-01-2810.34067/KID.00050720202641-76502020-11-19T13:38:50-08:002021-01-28Kidney360Original Investigations214249
- Glomerular Filtration Function Decline, Mortality, and Cardiovascular Events: Data from the Strong Heart Study10.34067/KID.0000782020Thu, 26 Nov 2020 05:30:12 GMT-08:00Glomerular Filtration Function Decline, Mortality, and Cardiovascular Events: Data from the Strong Heart StudySuchy-Dicey, Astrid M.Zhang, YingMcPherson, SterlingTuttle, Katherine R.Howard, Barbara V.Umans, JasonBuchwald, Dedra S.2020-11-26T05:30:12-08:00doi:10.34067/KID.0000782020hwp:resource-id:kidney360;2/1/71American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, cardiovascular diseases, chronic renal insufficiency, glomerular filtration rate, hypertensive nephropathy, nephritis, North American IndiansOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20212021-01-2810.34067/KID.00007820202641-76502020-11-26T05:30:12-08:002021-01-28Kidney360Original Investigations217178
- Association of Diet Quality Indices with Longitudinal Changes in Kidney Function in U.S. Hispanics/Latinos: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)10.34067/KID.0004552020Tue, 24 Nov 2020 10:19:10 GMT-08:00Association of Diet Quality Indices with Longitudinal Changes in Kidney Function in U.S. Hispanics/Latinos: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)Missikpode, CelestinRicardo, Ana C.Durazo-Arvizu, Ramon A.Manoharan, AnjellaMattei, JosiemerIsasi, Carmen R.Mossavar-Rahmani, YasminTalavera, Gregory A.Sotres-Alvarez, DanielaDaviglus, Martha L.Lash, James P.2020-11-24T10:19:10-08:00doi:10.34067/KID.0004552020hwp:resource-id:kidney360;2/1/50American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, diet, diet quality, Hispanic Americans, public health, AHEI-2010, Mediterranean diet, DASH, eGFR, UACROriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20212021-01-2810.34067/KID.00045520202641-76502020-11-24T10:19:10-08:002021-01-28Kidney360Original Investigations215062
- Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching Sessions10.34067/KID.0006282020Wed, 02 Dec 2020 10:33:24 GMT-08:00Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching SessionsChancay, JorgeEswarappa, MeghanaSanchez Russo, LuisSparks, Matthew A.Farouk, Samira S.2020-12-02T10:33:24-08:00doi:10.34067/KID.0006282020hwp:resource-id:kidney360;2/1/79American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, internal medicine residents, medical education, nephrology, residents, trainees, urine, urine microscopy, video conferencing, virtualOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20212021-01-2810.34067/KID.00062820202641-76502020-12-02T10:33:24-08:002021-01-28Kidney360Original Investigations217985
- An Unexpected Imaging Finding in a CKD Patient on Lithium Therapy10.34067/KID.0003642020Thu, 28 Jan 2021 05:00:28 GMT-08:00An Unexpected Imaging Finding in a CKD Patient on Lithium TherapyAnthonissen, BlaiseDanse, EtienneGoffin, Eric2021-01-28T05:00:28-08:00doi:10.34067/KID.0003642020hwp:resource-id:kidney360;2/1/180American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360chronic kidney disease, lithium nephropathy, nephrogenic diabetes insipidus, renal micro-cysts, small cysts formationClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-01-2810.34067/KID.00036420202641-76502021-01-28T05:00:28-08:002021-01-28Kidney360Clinical Images in Nephrology and Dialysis21180181
- Kidney360: Year 1 in Review10.34067/KID.0007042020Thu, 28 Jan 2021 05:00:28 GMT-08:00Kidney360: Year 1 in ReviewAllon, Michael2021-01-28T05:00:28-08:00doi:10.34067/KID.0007042020hwp:resource-id:kidney360;2/1/1American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360clinical nephrologyEditorialsEditorialseditorial20212021-01-2810.34067/KID.00070420202641-76502021-01-28T05:00:28-08:002021-01-28Kidney360Editorials2113
- CKD in a Patient Treated with Adefovir for Chronic Hepatitis B Virus Infection10.34067/KID.0004242020Thu, 28 Jan 2021 05:00:28 GMT-08:00CKD in a Patient Treated with Adefovir for Chronic Hepatitis B Virus InfectionKudose, SatoruLunenfeld, EllenMarkowitz, Glen S.2021-01-28T05:00:28-08:00doi:10.34067/KID.0004242020hwp:resource-id:kidney360;2/1/178American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, adefovir, adenine, chronic hepatitis B, chronic renal insufficiency, giant mitochondria, organophosphonatesClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20212021-01-2810.34067/KID.00042420202641-76502021-01-28T05:00:28-08:002021-01-28Kidney360Clinical Images in Nephrology and Dialysis21178179
- The Δ Anion Gap/Δ Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta?10.34067/KID.0000842019Tue, 10 Nov 2020 10:18:39 GMT-08:00The Δ Anion Gap/Δ Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta?Rudkin, Scott E.Grogan, Tristan R.Treger, Richard M.2020-11-10T10:18:39-08:00doi:10.34067/KID.0000842019hwp:resource-id:kidney360;2/1/20American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, acid-base equilibrium, bicarbonates, blood gas, lactic acidosisOriginal InvestigationsAcid/Base and Electrolyte DisordersOriginal InvestigationsAcid/Base and Electrolyte Disordersresearch-article20212021-01-2810.34067/KID.00008420192641-76502020-11-10T10:18:39-08:002021-01-28Kidney360Original Investigations212025
- Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill Patients10.34067/KID.0003552020Wed, 04 Nov 2020 09:28:08 GMT-08:00Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill PatientsFlannery, Alexander H.Bosler, KatherineOrtiz-Soriano, Victor M.Gianella, FabiolaPrado, VictorLambert, JoshuaToto, Robert D.Moe, Orson W.Neyra, Javier A.2020-11-04T09:28:08-08:00doi:10.34067/KID.0003552020hwp:resource-id:kidney360;2/1/26American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, biomarker, critical care, critical illness, intensive care, major adverse kidney event, outcomeOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20212021-01-2810.34067/KID.00035520202641-76502020-11-04T09:28:08-08:002021-01-28Kidney360Original Investigations212632
- Pathways Project: Development of a Multimodal Innovation To Improve Kidney Supportive Care in Dialysis CentersCurrent care models for older patients with kidney failure in the United States do not incorporate supportive care approaches. The absence of supportive care contributes to poor symptom management and unwanted forms of care at the end of life. Using an Institute for Healthcare Improvement Collaborative Model for Achieving Breakthrough Improvement, we conducted a focused literature review, interviewed implementation experts, and convened a technical expert panel to distill existing evidence into an evidence-based supportive care change package. The change package consists of 14 best-practice recommendations for the care of patients seriously ill with kidney failure, emphasizing three key practices: systematic identification of patients who are seriously ill, goals-of-care conversations with identified patients, and care options to respond to patient wishes. Implementation will be supported through a collaborative consisting of three intensive learning sessions, monthly learning and collaboration calls, site data feedback, and quality-improvement technical assistance. To evaluate the change package’s implementation and effectiveness, we designed a mixed-methods hybrid study involving the following: (1) effectiveness evaluation (including patient outcomes and staff perception of the effectiveness of the implementation of the change package); (2) quality-improvement monitoring via monthly tracking of a suite of quality-improvement indicators tied to the change package; and (3) implementation evaluation conducted by the external evaluator using mixed methods to assess implementation of the collaborative processes. Ten dialysis centers across the country, treating approximately 1550 patients, will participate. This article describes the process informing the intervention design, components of the intervention, evaluation design and measurements, and preliminary feasibility assessments.10.34067/KID.0005892020Mon, 23 Nov 2020 01:32:22 GMT-08:00Pathways Project: Development of a Multimodal Innovation To Improve Kidney Supportive Care in Dialysis CentersCurrent care models for older patients with kidney failure in the United States do not incorporate supportive care approaches. The absence of supportive care contributes to poor symptom management and unwanted forms of care at the end of life. Using an Institute for Healthcare Improvement Collaborative Model for Achieving Breakthrough Improvement, we conducted a focused literature review, interviewed implementation experts, and convened a technical expert panel to distill existing evidence into an evidence-based supportive care change package. The change package consists of 14 best-practice recommendations for the care of patients seriously ill with kidney failure, emphasizing three key practices: systematic identification of patients who are seriously ill, goals-of-care conversations with identified patients, and care options to respond to patient wishes. Implementation will be supported through a collaborative consisting of three intensive learning sessions, monthly learning and collaboration calls, site data feedback, and quality-improvement technical assistance. To evaluate the change package’s implementation and effectiveness, we designed a mixed-methods hybrid study involving the following: (1) effectiveness evaluation (including patient outcomes and staff perception of the effectiveness of the implementation of the change package); (2) quality-improvement monitoring via monthly tracking of a suite of quality-improvement indicators tied to the change package; and (3) implementation evaluation conducted by the external evaluator using mixed methods to assess implementation of the collaborative processes. Ten dialysis centers across the country, treating approximately 1550 patients, will participate. This article describes the process informing the intervention design, components of the intervention, evaluation design and measurements, and preliminary feasibility assessments.Lupu, Dale E.Aldous, AnnetteHarbert, GlendaKurella Tamura, ManjulaHoldsworth, Laura M.Nicklas, AmandaVinson, BrandyMoss, Alvin H.2020-11-23T13:32:22-08:00doi:10.34067/KID.0005892020hwp:resource-id:kidney360;2/1/114American Society of NephrologyCopyright © 2021 by the American Society of NephrologyKidney360geriatric and palliative nephrology, advance care planning, communication, end of life, goals of care, implementation science, palliative care, shared decision-making, supportive careInnovative Technology and MethodologyGeriatric and Palliative NephrologyInnovative Technology and MethodologyGeriatric and Palliative Nephrologyresearch-article20212021-01-2810.34067/KID.00058920202641-76502020-11-23T13:32:22-08:002021-01-28Kidney360Innovative Technology and Methodology21114128
- Dietary Therapy for Managing Hyperphosphatemia10.2215/CJN.18171120Wed, 30 Dec 2020 07:10:55 GMT-08:00Dietary Therapy for Managing HyperphosphatemiaNarasaki, YokoRhee, Connie M.2020-12-30T07:10:55-08:00doi:10.2215/CJN.18171120hwp:resource-id:clinjasn;16/1/9American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperphosphatemia, hemodialysis, nutritionEditorialsEditorialseditorial20212021-01-07January 07, 202110.2215/CJN.181711201555-90411555-905X2020-12-30T07:10:55-08:002021-01-07Clinical Journal of the American Society of NephrologyEditorials1611910711120
- Mobile Health in Dialysis: The Best Engagement Medium Is the One that’s with Patients10.2215/CJN.18051120Tue, 22 Dec 2020 08:10:24 GMT-08:00Mobile Health in Dialysis: The Best Engagement Medium Is the One that’s with PatientsSingh, Karandeep2020-12-22T08:10:24-08:00doi:10.2215/CJN.18051120hwp:resource-id:clinjasn;16/1/12American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymobile health, smartphone apps, dialysis, patient engagementEditorialsEditorialseditorial20212021-01-07January 07, 202110.2215/CJN.180511201555-90411555-905X2020-12-22T08:10:24-08:002021-01-07Clinical Journal of the American Society of NephrologyEditorials1611112981131062
- Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance Hemodialysis10.2215/CJN.10070620Fri, 18 Dec 2020 08:59:26 GMT-08:00Zolpidem Versus Trazodone Initiation and the Risk of Fall-Related Fractures among Individuals Receiving Maintenance HemodialysisAssimon, Magdalene M.Flythe, Jennifer E.2020-12-18T08:59:26-08:00doi:10.2215/CJN.10070620hwp:resource-id:clinjasn;16/1/88American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfall, fracture, hemodialysis, insomnia, trazodone, zolpidemOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-01-07January 07, 202110.2215/CJN.100706201555-90411555-905X2020-12-18T08:59:26-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1618897
- Forever Starts Now10.2215/CJN.18141120Tue, 29 Dec 2020 08:13:41 GMT-08:00Forever Starts NowKotwal, SradhaPerkovic, Vlado2020-12-29T08:13:41-08:00doi:10.2215/CJN.18141120hwp:resource-id:clinjasn;16/1/6American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, diabetes, randomized controlled trials, glucoseEditorialsEditorialseditorial20212021-01-07January 07, 202110.2215/CJN.181411201555-90411555-905X2020-12-29T08:13:41-08:002021-01-07Clinical Journal of the American Society of NephrologyEditorials1611670878
- Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury10.2215/CJN.11220720Tue, 29 Dec 2020 08:13:40 GMT-08:00Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney InjuryZhao, MinSun, ShusenHuang, ZhenguangWang, TianshengTang, Huilin2020-12-29T08:13:40-08:00doi:10.2215/CJN.11220720hwp:resource-id:clinjasn;16/1/70American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, diabetes, diabetic nephropathy, drug nephrotoxicity, acute kidney injury, glucose, network meta-analysisOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20212021-01-07January 07, 202110.2215/CJN.112207201555-90411555-905X2020-12-29T08:13:40-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1611706788
- Klotho in Clinical NephrologyαKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.10.2215/CJN.02840320Wed, 22 Jul 2020 10:03:26 GMT-07:00Klotho in Clinical NephrologyαKlotho (called Klotho here) is a membrane protein that serves as the coreceptor for the circulating hormone fibroblast growth factor 23 (FGF23). Klotho is also cleaved and released as a circulating substance originating primarily from the kidney and exerts a myriad of housekeeping functions in just about every organ. The vital role of Klotho is shown by the multiorgan failure with genetic deletion in rodents, with certain features reminiscent of human disease. The most common causes of systemic Klotho deficiency are AKI and CKD. Preclinical data on Klotho biology have advanced considerably and demonstrated its potential diagnostic and therapeutic value; however, multiple knowledge gaps exist in the regulation of Klotho expression, release, and metabolism; its target organs; and mechanisms of action. In the translational and clinical fronts, progress has been more modest. Nonetheless, Klotho has potential clinical applications in the diagnosis of AKI and CKD, in prognosis of progression and extrarenal complications, and finally, as replacement therapy for systemic Klotho deficiency. The overall effect of Klotho in clinical nephrology requires further technical advances and additional large prospective human studies.Neyra, Javier A.Hu, Ming ChangMoe, Orson W.2020-07-22T10:03:26-07:00doi:10.2215/CJN.02840320hwp:resource-id:clinjasn;16/1/162American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyKlotho;, nephrology;, kidney;, diagnosis;, therapyReviewReviewreview-article20212021-01-07January 07, 202110.2215/CJN.028403201555-90411555-905X2020-07-22T10:03:26-07:002021-01-07Clinical Journal of the American Society of NephrologyReview161162176
- The Mobile Health Readiness of People Receiving In-Center Hemodialysis and Home Dialysis10.2215/CJN.11690720Tue, 22 Dec 2020 08:10:24 GMT-08:00The Mobile Health Readiness of People Receiving In-Center Hemodialysis and Home DialysisHussein, Wael F.Bennett, Paul N.Pace, SloaneChen, ShijieLegg, VeronicaAtwal, JugjeetSun, SumiSchiller, Brigitte2020-12-22T08:10:24-08:00doi:10.2215/CJN.11690720hwp:resource-id:clinjasn;16/1/98American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, hemodialysis, mHealth, mobile health, telehealth, telemedicineOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-01-07January 07, 202110.2215/CJN.116907201555-90411555-905X2020-12-22T08:10:24-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1611198112106213
- Long-Term Safety of Tolvaptan in ADPKD10.2215/CJN.17981120Tue, 29 Dec 2020 08:13:40 GMT-08:00Long-Term Safety of Tolvaptan in ADPKDPatel, Dipal M.Dahl, Neera K.2020-12-29T08:13:40-08:00doi:10.2215/CJN.17981120hwp:resource-id:clinjasn;16/1/3American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, safety, clinical trial, Tolvaptan, autosomal dominant polycystic kidney diseaseEditorialsEditorialseditorial20212021-01-07January 07, 202110.2215/CJN.179811201555-90411555-905X2020-12-29T08:13:40-08:002021-01-07Clinical Journal of the American Society of NephrologyEditorials1611348558
- Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.10250620Tue, 29 Dec 2020 08:13:40 GMT-08:00Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney DiseaseTorres, Vicente E.Chapman, Arlene B.Devuyst, OlivierGansevoort, Ron T.Perrone, Ronald D.Lee, JenniferHoke, Molly E.Estilo, AlvinSergeyeva, Olga2020-12-29T08:13:40-08:00doi:10.2215/CJN.10250620hwp:resource-id:clinjasn;16/1/48American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, cystic kidney, tolvaptanOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20212021-01-07January 07, 202110.2215/CJN.102506201555-90411555-905X2020-12-29T08:13:40-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1611483585
- Effect of Phosphate-Specific Diet Therapy on Phosphate Levels in Adults Undergoing Maintenance Hemodialysis10.2215/CJN.09360620Wed, 30 Dec 2020 07:10:55 GMT-08:00Effect of Phosphate-Specific Diet Therapy on Phosphate Levels in Adults Undergoing Maintenance HemodialysisSt-Jules, David E.Rozga, Mary R.Handu, DeepaCarrero, Juan Jesus2020-12-30T07:10:55-08:00doi:10.2215/CJN.09360620hwp:resource-id:clinjasn;16/1/107American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperphosphatemia, nutrition, chronic kidney disease, ESRD, hemodialysis, phosphorusOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20212021-01-07January 07, 202110.2215/CJN.093606201555-90411555-905X2020-12-30T07:10:55-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1611107912011
- Correction10.2215/CJN.16851020Wed, 25 Nov 2020 01:28:53 GMT-08:00CorrectionAmerican Society of Nephrology2020-11-25T13:28:53-08:00doi:10.2215/CJN.16851020hwp:resource-id:clinjasn;16/1/127American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correctionErratumErratumcorrection20212021-01-07January 07, 202110.2215/CJN.168510201555-90411555-905X2020-11-25T13:28:53-08:002021-01-07Clinical Journal of the American Society of NephrologyErratum1615110101271386138612713881388
- NAT8 Variants, N-Acetylated Amino Acids, and Progression of CKD10.2215/CJN.08600520Wed, 30 Dec 2020 07:10:55 GMT-08:00NAT8 Variants, N-Acetylated Amino Acids, and Progression of CKDLuo, ShengyuanSurapaneni, AdityaZheng, ZiheRhee, Eugene P.Coresh, JosefHung, Adriana M.Nadkarni, Girish N.Yu, BingBoerwinkle, EricTin, AdrienneArking, Dan E.Steinbrenner, IngaSchlosser, PascalKöttgen, AnnaGrams, Morgan E.2020-12-30T07:10:55-08:00doi:10.2215/CJN.08600520hwp:resource-id:clinjasn;16/1/37American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, end-stage renal disease, human genetics, metabolism, amino acids, acetylationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20212021-01-07January 07, 202110.2215/CJN.086005201555-90411555-905X2020-12-30T07:10:55-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1613747
- What Does Uromodulin Do?10.2215/CJN.06390420Mon, 24 Aug 2020 05:50:22 GMT-07:00What Does Uromodulin Do?Kipp, AnneOlinger, Eric2020-08-24T05:50:22-07:00doi:10.2215/CJN.06390420hwp:resource-id:clinjasn;16/1/150American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, cell & transport physiology, chronic kidney disease, distal tubule, genetic renal disease, water-electrolyte balance, uromodulinPerspectivesPerspectivesresearch-article20212021-01-07January 07, 202110.2215/CJN.063904201555-90411555-905X2020-08-24T05:50:22-07:002021-01-07Clinical Journal of the American Society of NephrologyPerspectives161150153
- Prospective Cohort Study of Renin-Angiotensin System Blocker Usage after Hospitalized Acute Kidney Injury10.2215/CJN.10840720Thu, 03 Dec 2020 09:20:24 GMT-08:00Prospective Cohort Study of Renin-Angiotensin System Blocker Usage after Hospitalized Acute Kidney InjuryBrar, SandeepLiu, Kathleen D.Go, Alan S.Hsu, Raymond K.Chinchilli, Vernon M.Coca, Steven G.Garg, Amit X.Himmelfarb, JonathanIkizler, T. AlpKaufman, JamesKimmel, Paul L.Parikh, Chirag R.Siew, Edward D.Ware, Lorraine B.Zeng, HuiHsu, Chi-yuan,,Ghahramani, NasrollahReeves, W. BrianKong, LanWang, MingFarace, ElanaTan, ThidaOrdonez, Juan D.Zheng, SijieLewis, Julia B.Moledina, Dennis G.Devarajan, PrasadZappitelli, MichaelWurfel, MarkEggers, Paul W.Moxey-Mims, Marva M.2020-12-03T09:20:24-08:00doi:10.2215/CJN.10840720hwp:resource-id:clinjasn;16/1/26American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, renin angiotensin system, epidemiology and outcomes, acute kidney injuryOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-01-07January 07, 202110.2215/CJN.108407201555-90411555-905X2020-12-03T09:20:24-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1612636
- Optimizing Peritoneal Dialysis–Associated Peritonitis Prevention in the United StatesPeritoneal dialysis (PD)–associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.10.2215/CJN.11280919Thu, 06 Aug 2020 12:05:06 GMT-07:00Optimizing Peritoneal Dialysis–Associated Peritonitis Prevention in the United StatesPeritoneal dialysis (PD)–associated peritonitis is the leading cause of permanent transition to hemodialysis among patients receiving PD. Peritonitis is associated with higher mortality risk and added treatment costs and limits more widespread PD utilization. Optimizing the prevention of peritonitis in the United States will first require standardization of peritonitis definitions, key data elements, and outcomes in an effort to facilitate nationwide reporting. Standardized reporting can also help describe the variability in peritonitis rates and outcomes across facilities in the United States in an effort to identify potential peritonitis prevention strategies and engage with stakeholders to develop strategies for their implementation. Here, we will highlight considerations and challenges in developing standardized definitions and implementation of national reporting of peritonitis rates by PD facilities. We will describe existing peritonitis prevention evidence gaps, highlight successful infection-reporting initiatives among patients receiving in-center hemodialysis or PD, and provide an overview of nationwide quality improvement initiatives, both in the United States and elsewhere, that have translated into a reduction in peritonitis incidence. We will discuss opportunities for collaboration and expansion of the Nephrologists Transforming Dialysis Safety (NTDS) initiative to develop knowledge translation pathways that will lead to dissemination of best practices in an effort to reduce peritonitis incidence.Perl, JeffreyFuller, Douglas S.Boudville, NeilKliger, Alan S.Schaubel, Douglas E.Teitelbaum, IsaacWarady, Bradley A.Neu, Alicia M.Patel, Priti R.Piraino, BethSchreiber, MartinPisoni, Ronald L.2020-08-06T12:05:06-07:00doi:10.2215/CJN.11280919hwp:resource-id:clinjasn;16/1/154American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis-associated peritonitis, dialysis, Incidence, Quality Improvement, Translational Medical Research, peritoneal dialysis, Peritonitis, Health Care CostsFeatureFeatureresearch-article20212021-01-07January 07, 202110.2215/CJN.112809191555-90411555-905X2020-08-06T12:05:06-07:002021-01-07Clinical Journal of the American Society of NephrologyFeature161154161
- Addressing Polypharmacy in Outpatient Dialysis Units10.2215/CJN.05270420Thu, 13 Aug 2020 11:13:49 GMT-07:00Addressing Polypharmacy in Outpatient Dialysis UnitsBattistella, MarisaNg, Patrick2020-08-13T11:13:49-07:00doi:10.2215/CJN.05270420hwp:resource-id:clinjasn;16/1/144American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPerspectivesPerspectivesresearch-article20212021-01-07January 07, 202110.2215/CJN.052704201555-90411555-905X2020-08-13T11:13:49-07:002021-01-07Clinical Journal of the American Society of NephrologyPerspectives161144146
- Availability, Accessibility, and Quality of Conservative Kidney Management Worldwide10.2215/CJN.09070620Tue, 15 Dec 2020 07:48:19 GMT-08:00Availability, Accessibility, and Quality of Conservative Kidney Management WorldwideLunney, MeaghanBello, Aminu K.Levin, AdeeraTam-Tham, HelenThomas, ChandraOsman, Mohamed A.Ye, FengBellorin-Font, EzequielBenghanem Gharbi, MohammedGhnaimat, MohammadHtay, HtayCho, YeoungjeeJha, VivekanandOssareh, ShahrzadRondeau, EricSola, LauraTchokhonelidze, IrmaTesar, VladimirTungsanga, KriangKazancioglu, Rumeyza TuranWang, Angela Yee-MoonYang, Chih-WeiZemchenkov, AlexanderZhao, Ming-huiJager, Kitty J.Jindal, Kailash K.Okpechi, Ikechi G.Brown, Edwina A.Brown, MarkTonelli, MarcelloHarris, David C.Johnson, David W.Caskey, Fergus J.Davison, Sara N.2020-12-15T07:48:19-08:00doi:10.2215/CJN.09070620hwp:resource-id:clinjasn;16/1/79American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney failure, conservative kidney management, global health, survey, capacityOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20212021-01-07January 07, 202110.2215/CJN.090706201555-90411555-905X2020-12-15T07:48:19-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1617987
- Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary TractRevolutions in genetics, epigenetics, and bioinformatics are currently changing the outline of diagnostics and clinical medicine. From a nephrologist’s perspective, individuals with congenital anomalies of the kidney and urinary tract (CAKUT) are an important patient category: not only is CAKUT the predominant cause of kidney failure in children and young adults, but the strong phenotypic and genotypic heterogeneity of kidney and urinary tract malformations has hampered standardization of clinical decision making until now. However, patients with CAKUT may benefit from precision medicine, including an integrated diagnostics trajectory, genetic counseling, and personalized management to improve clinical outcomes of developmental kidney and urinary tract defects. In this review, we discuss the present understanding of the molecular etiology of CAKUT and the currently available genome diagnostic modalities in the clinical care of patients with CAKUT. Finally, we discuss how clinical integration of findings from large-scale genetic, epigenetic, and gene-environment interaction studies may improve the prognosis of all individuals with CAKUT.10.2215/CJN.14661119Mon, 20 Apr 2020 04:58:25 GMT-07:00Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary TractRevolutions in genetics, epigenetics, and bioinformatics are currently changing the outline of diagnostics and clinical medicine. From a nephrologist’s perspective, individuals with congenital anomalies of the kidney and urinary tract (CAKUT) are an important patient category: not only is CAKUT the predominant cause of kidney failure in children and young adults, but the strong phenotypic and genotypic heterogeneity of kidney and urinary tract malformations has hampered standardization of clinical decision making until now. However, patients with CAKUT may benefit from precision medicine, including an integrated diagnostics trajectory, genetic counseling, and personalized management to improve clinical outcomes of developmental kidney and urinary tract defects. In this review, we discuss the present understanding of the molecular etiology of CAKUT and the currently available genome diagnostic modalities in the clinical care of patients with CAKUT. Finally, we discuss how clinical integration of findings from large-scale genetic, epigenetic, and gene-environment interaction studies may improve the prognosis of all individuals with CAKUT.Westland, RikRenkema, Kirsten Y.Knoers, Nine V.A.M.2020-04-20T04:58:25-07:00doi:10.2215/CJN.14661119hwp:resource-id:clinjasn;16/1/128American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetics and development, kidney development, clinical nephrology, molecular genetics, chronic kidney disease, gene-environment interaction, precision medicine, genetic counseling, clinical decision-making, computational biology, urogenital abnormalities, vesico-ureteral reflux, renal insufficiency, prognosis, epigenesis, geneticGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20212021-01-07January 07, 202110.2215/CJN.146611191555-90411555-905X2020-04-20T04:58:25-07:002021-01-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease161128137
- Acute Kidney Injury in a National Cohort of Hospitalized US Veterans with COVID-1910.2215/CJN.09610620Mon, 16 Nov 2020 06:51:29 GMT-08:00Acute Kidney Injury in a National Cohort of Hospitalized US Veterans with COVID-19Bowe, BenjaminCai, MiaoXie, YanGibson, Andrew K.Maddukuri, GeethaAl-Aly, Ziyad2020-11-16T06:51:29-08:00doi:10.2215/CJN.09610620hwp:resource-id:clinjasn;16/1/14American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, acute kidney injury, mortality, kidney function, respiratory failure, Length of stay, racial disparities, obesity, diabetes, Black raceOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20212021-01-07January 07, 202110.2215/CJN.096106201555-90411555-905X2020-11-16T06:51:29-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1611425
- COVID-19 in Peritoneal Dialysis Patients10.2215/CJN.07200520Tue, 08 Sep 2020 08:21:41 GMT-07:00COVID-19 in Peritoneal Dialysis PatientsJiang, Hua-JunTang, HuiXiong, FeiChen, Wen-LiTian, Jian-BoSun, JingDong, Jun-WuWang, Xiao-HuiJin, Xiao-FeiDing, Yan-QiongXu, LiMiao, Xiao-PingZhang, Chun2020-09-08T08:21:41-07:00doi:10.2215/CJN.07200520hwp:resource-id:clinjasn;16/1/121American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, ESKD, peritoneal dialysisResearch LettersResearch Letterseditorial20212021-01-07January 07, 202110.2215/CJN.072005201555-90411555-905X2020-09-08T08:21:41-07:002021-01-07Clinical Journal of the American Society of NephrologyResearch Letters161121123
- Anticoagulation Strategies and Filter Life in COVID-19 Patients Receiving Continuous Renal Replacement Therapy10.2215/CJN.08430520Thu, 17 Sep 2020 10:18:33 GMT-07:00Anticoagulation Strategies and Filter Life in COVID-19 Patients Receiving Continuous Renal Replacement TherapyShankaranarayanan, DivyaMuthukumar, ThangamaniBarbar, TarekBhasin, AartiGerardine, SupriyaLamba, PerolaLeuprecht, LorenzNeupane, Sanjay P.Salinas, ThaliaShimonov, DaniilVarma, EllyLiu, Frank2020-09-17T10:18:33-07:00doi:10.2215/CJN.08430520hwp:resource-id:clinjasn;16/1/124American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, anticoagulation, CRRT, continuous renal replacement therapyResearch LettersResearch Lettersletter20212021-01-07January 07, 202110.2215/CJN.084305201555-90411555-905X2020-09-17T10:18:33-07:002021-01-07Clinical Journal of the American Society of NephrologyResearch Letters161124126
- Walkaway PIRRT (as SLED) for Acute Kidney Injury10.2215/CJN.07510520Fri, 11 Sep 2020 07:07:30 GMT-07:00Walkaway PIRRT (as SLED) for Acute Kidney InjuryBurgner, AnnaGolper, Thomas2020-09-11T07:07:30-07:00doi:10.2215/CJN.07510520hwp:resource-id:clinjasn;16/1/138American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPIRRT, SLED, acute kidney injuryKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20212021-01-07January 07, 202110.2215/CJN.075105201555-90411555-905X2020-09-11T07:07:30-07:002021-01-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat161138140
- Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney Disease10.2215/CJN.08410520Wed, 16 Dec 2020 08:21:00 GMT-08:00Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney DiseaseHanrahan, John P.de Boer, Ian H.Bakris, George L.Wilson, Phebe J.Wakefield, James D.Seferovic, Jelena P.Chickering, Jennifer G.Chien, Yueh-tyngCarlson, KennethCressman, Michael D.Currie, Mark G.Milne, G. ToddProfy, Albert T.2020-12-16T08:21:00-08:00doi:10.2215/CJN.08410520hwp:resource-id:clinjasn;16/1/59American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, diabetes, albuminuria, hypertensionOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20212021-01-07January 07, 202110.2215/CJN.084105201555-90411555-905X2020-12-16T08:21:00-08:002021-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1615969
- Incremental and Twice-Weekly Hemodialysis Program in Practice10.2215/CJN.04170320Tue, 22 Sep 2020 12:25:26 GMT-07:00Incremental and Twice-Weekly Hemodialysis Program in PracticeMurea, MarianaKalantar-Zadeh, Kamyar2020-09-22T12:25:26-07:00doi:10.2215/CJN.04170320hwp:resource-id:clinjasn;16/1/147American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyincremental dialysis, residual kidney function, precision medicine, patient centeredness, hemodialysis, acute kidney injuryPerspectivesPerspectivesresearch-article20212021-01-07January 07, 202110.2215/CJN.041703201555-90411555-905X2020-09-22T12:25:26-07:002021-01-07Clinical Journal of the American Society of NephrologyPerspectives161147149
- Patients with Kidney Disease: Ready to Use Smartphones for Health Care Delivery?10.2215/CJN.17771120Tue, 22 Dec 2020 08:10:24 GMT-08:00Patients with Kidney Disease: Ready to Use Smartphones for Health Care Delivery?Schmidt, Lana2020-12-22T08:10:24-08:00doi:10.2215/CJN.17771120hwp:resource-id:clinjasn;16/1/1American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic kidney failure, kidney failure, dialysis, Delivery of Health Care, smartphonePatient VoicePatient Voiceeditorial20212021-01-07January 7, 202110.2215/CJN.177711201555-90411555-905X2020-12-22T08:10:24-08:002021-01-07Clinical Journal of the American Society of NephrologyPatient Voice1611119812210613
- Gender and CKD10.2215/CJN.03030320Fri, 07 Aug 2020 12:27:56 GMT-07:00Gender and CKDAhmed, Sofia B.Saad, NathalieDumanski, Sandra M.2020-08-07T12:27:56-07:00doi:10.2215/CJN.03030320hwp:resource-id:clinjasn;16/1/141American Society of NephrologyCopyright © 2021 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, gender, disparity, inclusion, sex hormones, gender-affirming therapyPerspectivesPerspectivesresearch-article20212021-01-07January 07, 202110.2215/CJN.030303201555-90411555-905X2020-08-07T12:27:56-07:002021-01-07Clinical Journal of the American Society of NephrologyPerspectives161141143
- A Model To Estimate Glucose Absorption in Peritoneal Dialysis: A Pilot Study10.34067/KID.0004722020Tue, 29 Sep 2020 10:36:18 GMT-07:00A Model To Estimate Glucose Absorption in Peritoneal Dialysis: A Pilot StudyKotla, Suman KrishnaSaxena, AshishSaxena, Ramesh2020-09-29T10:36:18-07:00doi:10.34067/KID.0004722020hwp:resource-id:kidney360;1/12/1373American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, glucose, glucose absorption, peritoneal dialysis, pilot projectsOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-12-3110.34067/KID.00047220202641-76502020-09-29T10:36:18-07:002020-12-31Kidney360Original Investigations11213731379
- Abnormal Imaging Findings of the Kidneys in a Patient with Shock10.34067/KID.0003692020Thu, 31 Dec 2020 05:30:28 GMT-08:00Abnormal Imaging Findings of the Kidneys in a Patient with ShockLuo, XinyiCielo, Aileen GraceVelez, Juan Carlos Q.2020-12-31T05:30:28-08:00doi:10.34067/KID.0003692020hwp:resource-id:kidney360;1/12/1462American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute cortical necrosis, acute hemorrhage, acute kidney injury, ATN, bilateral, gunshot wound, hemorrhagic shock, renal cortical necrosisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-12-3110.34067/KID.00036920202641-76502020-12-31T05:30:28-08:002020-12-31Kidney360Clinical Images in Nephrology and Dialysis11214621463
- Patency of ePTFE Arteriovenous Graft Placements in Hemodialysis Patients: Systematic Literature Review and Meta-AnalysisArteriovenous grafts (AVGs) are an appropriate option for vascular access in certain hemodialysis patients. Expanded polytetrafluoroethylene (ePTFE) has become the dominant material for such grafts, due in part to innovations in graft design and surgical interventions to reduce complications and improve patency rates. Comprehensive evidence syntheses have not been conducted to update AVG performance in an era in which both access choice and ePTFE graft functioning may have changed. We conducted a systematic review and meta-analysis summarizing outcomes from recent studies of ePTFE AVGs in hemodialysis, following PRISMA standards. Literature searches were conducted in multiple databases to identify observational and interventional studies of AVG patency and infection risk. Primary, primary-assisted, and secondary patency rates were analyzed at 6, 12, 18, and 24 months postplacement. Kaplan–Meier graft survival plots were digitized to recreate individual patient-level data. Patency rates were pooled using a random effects model. We identified 32 studies meeting our selection criteria that were published from 2004 through 2019. A total of 38 study arms of ePTFE grafts were included, representing 3381 AVG accesses placed. The mean primary, primary-assisted, and secondary patency rates at 1 year were 41% (95% CI, 35% to 47%), 46% (95% CI, 41% to 51%), and 70% (95% CI, 64% to 75%), respectively. Mean 24-month patency rates were 28% (95% CI, 22% to 33%), 34% (95% CI, 27% to 41%), and 54% (95% CI, 47% to 61%), respectively. A high degree of heterogeneity across studies was observed. Overall risk of infection was not consistently reported, but among available studies the pooled estimate was 9% per patient-year (95% CI, 6% to 12%). This meta-analysis provides an up-to-date estimate of the performance of ePTFE AVGs, within the context of improved graft designs and improved interventional techniques.10.34067/KID.0003502020Thu, 15 Oct 2020 09:15:37 GMT-07:00Patency of ePTFE Arteriovenous Graft Placements in Hemodialysis Patients: Systematic Literature Review and Meta-AnalysisArteriovenous grafts (AVGs) are an appropriate option for vascular access in certain hemodialysis patients. Expanded polytetrafluoroethylene (ePTFE) has become the dominant material for such grafts, due in part to innovations in graft design and surgical interventions to reduce complications and improve patency rates. Comprehensive evidence syntheses have not been conducted to update AVG performance in an era in which both access choice and ePTFE graft functioning may have changed. We conducted a systematic review and meta-analysis summarizing outcomes from recent studies of ePTFE AVGs in hemodialysis, following PRISMA standards. Literature searches were conducted in multiple databases to identify observational and interventional studies of AVG patency and infection risk. Primary, primary-assisted, and secondary patency rates were analyzed at 6, 12, 18, and 24 months postplacement. Kaplan–Meier graft survival plots were digitized to recreate individual patient-level data. Patency rates were pooled using a random effects model. We identified 32 studies meeting our selection criteria that were published from 2004 through 2019. A total of 38 study arms of ePTFE grafts were included, representing 3381 AVG accesses placed. The mean primary, primary-assisted, and secondary patency rates at 1 year were 41% (95% CI, 35% to 47%), 46% (95% CI, 41% to 51%), and 70% (95% CI, 64% to 75%), respectively. Mean 24-month patency rates were 28% (95% CI, 22% to 33%), 34% (95% CI, 27% to 41%), and 54% (95% CI, 47% to 61%), respectively. A high degree of heterogeneity across studies was observed. Overall risk of infection was not consistently reported, but among available studies the pooled estimate was 9% per patient-year (95% CI, 6% to 12%). This meta-analysis provides an up-to-date estimate of the performance of ePTFE AVGs, within the context of improved graft designs and improved interventional techniques.Halbert, Ronald J.Nicholson, GinaNordyke, Robert J.Pilgrim, AlisonNiklason, Laura2020-10-15T09:15:37-07:00doi:10.34067/KID.0003502020hwp:resource-id:kidney360;1/12/1437American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, arteriovenous graft, hemodialysis, infection, patency, renal dialysis, vascular accessReview ArticlesReview Articlesreview-article20202020-12-3110.34067/KID.00035020202641-76502020-10-15T09:15:37-07:002020-12-31Kidney360Review Articles11214371446
- Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot Trial10.34067/KID.0004342020Thu, 15 Oct 2020 09:15:37 GMT-07:00Combination Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD (HIDE): A Randomized, Placebo-Controlled, Pilot TrialCharytan, David M.Hsu, Jesse Y.Mc Causland, Finnian R.Waikar, Sushrut S.Ikizler, T. AlpRaj, Dominic S.Landis, J. RichardMehrotra, RajnishWilliams, MarkDiCarli, MarceloSkali, HichamKimmel, Paul L.Kliger, Alan S.Dember, Laura M.,,Himmelfarb, JonathanAnderson, Amanda HHung, Adriana MSharma, ShailendraWeiner, Daniel E.2020-10-15T09:15:37-07:00doi:10.34067/KID.0004342020hwp:resource-id:kidney360;1/12/1380American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, chronic kidney failure, hemodialysis, hydralazine, isosorbide dinitrate, pilot projects, randomized controlled trial, renal dialysisOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-12-3110.34067/KID.00043420202641-76502020-10-15T09:15:37-07:002020-12-31Kidney360Original Investigations11213801389
- Self-Referral Patterns of Living Kidney Donors via Social Media: Examining an Expanding Platform10.34067/KID.0005732020Thu, 31 Dec 2020 05:30:28 GMT-08:00Self-Referral Patterns of Living Kidney Donors via Social Media: Examining an Expanding PlatformJoachim, Emily2020-12-31T05:30:28-08:00doi:10.34067/KID.0005732020hwp:resource-id:kidney360;1/12/1337American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, kidney transplantation, living donor, referral and consultation, social mediaEditorialsEditorialseditorial20202020-12-3110.34067/KID.00057320202641-76502020-12-31T05:30:28-08:002020-12-31Kidney360Editorials11213371338
- Induction and Donor Specific Antibodies in Low Immunologic Risk Kidney Transplant Recipients10.34067/KID.0000122020Thu, 01 Oct 2020 09:37:53 GMT-07:00Induction and Donor Specific Antibodies in Low Immunologic Risk Kidney Transplant RecipientsBath, Natalie M.Djamali, ArjangParajuli, SandeshMandelbrot, DidierLeverson, GlenHidalgo, LuisEllis, ThomasDescourouez, Jillian L.Jorgenson, Margaret R.Hager, DaveKaufman, Dixon B.Redfield, Robert R.2020-10-01T09:37:53-07:00doi:10.34067/KID.0000122020hwp:resource-id:kidney360;1/12/1407American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, antibodies, donor specific antibody, induction, kidney transplantation, tissue donorsOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-12-3110.34067/KID.00001220202641-76502020-10-01T09:37:53-07:002020-12-31Kidney360Original Investigations11214071418
- Severe Hypertension in a 3-Month-Old Infant10.34067/KID.0003602020Thu, 31 Dec 2020 05:30:28 GMT-08:00Severe Hypertension in a 3-Month-Old InfantChawla, JonathanManning, DavidAshoor, Isa2020-12-31T05:30:28-08:00doi:10.34067/KID.0003602020hwp:resource-id:kidney360;1/12/1464American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, hydronephrosis, hypertension, pediatric nephrology, UPJ obstructionClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-12-3110.34067/KID.00036020202641-76502020-12-31T05:30:28-08:002020-12-31Kidney360Clinical Images in Nephrology and Dialysis11214641465
- Impact of Social Media on Self-Referral Patterns for Living Kidney Donation10.34067/KID.0003212020Fri, 30 Oct 2020 09:26:53 GMT-07:00Impact of Social Media on Self-Referral Patterns for Living Kidney DonationDuBray, Bernard J.Shawar, Saed H.Rega, Scott A.Smith, Kristin M.Centanni, Kaylin M.Warmke, KaraConcepcion, Beatrice P.Edwards, Gretchen C.Schaefer, Heidi M.Feurer, Irene D.Forbes, Rachel C.2020-10-30T09:26:53-07:00doi:10.34067/KID.0003212020hwp:resource-id:kidney360;1/12/1419American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, kidney transplantation, living donation, referral and consultation, social media, tissue and organ harvestingOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-12-3110.34067/KID.00032120202641-76502020-10-30T09:26:53-07:002020-12-31Kidney360Original Investigations11214191425
- Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical Trial10.34067/KID.0004002020Wed, 23 Sep 2020 09:50:08 GMT-07:00Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical TrialSeliger, Stephen L.Watnick, TerryAlthouse, Andrew D.Perrone, Ronald D.Abebe, Kaleab Z.Hallows, Kenneth R.Miskulin, Dana C.Bae, Kyongtae T.2020-09-23T09:50:08-07:00doi:10.34067/KID.0004002020hwp:resource-id:kidney360;1/12/1363American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360cystic kidney disease, autosomal dominant polycystic kidney, clinical trial, health-related quality of life, metformin, patient-reported outcomes, polycystic kidney disease, total kidney volumeOriginal InvestigationsCystic Kidney DiseaseOriginal InvestigationsCystic Kidney Diseaseresearch-article20202020-12-3110.34067/KID.00040020202641-76502020-09-23T09:50:08-07:002020-12-31Kidney360Original Investigations11213631372
- Risk Factors for Kidney Stone Formation following Bariatric SurgeryKidney stones are painful, common, and increasing in incidence. Obesity and bariatric surgery rates are also on the rise in the United States. Although bariatric surgery is associated with improvements in metabolic outcomes, malabsorptive bariatric surgery procedures are also associated with increased risk of kidney stones. Restrictive bariatric surgeries have not been associated with kidney-stone risk. Higher risk of kidney stones after malabsorptive procedures is associated with postsurgical changes in urine composition, including high urine oxalate, low urine citrate, and low urine volume. Certain dietary recommendations after surgery may help mitigate these urine changes and reduce risk of kidney stones. Understanding risk of kidney stones after surgery is essential to improving patient outcomes after bariatric surgery.10.34067/KID.0004982020Thu, 01 Oct 2020 09:37:53 GMT-07:00Risk Factors for Kidney Stone Formation following Bariatric SurgeryKidney stones are painful, common, and increasing in incidence. Obesity and bariatric surgery rates are also on the rise in the United States. Although bariatric surgery is associated with improvements in metabolic outcomes, malabsorptive bariatric surgery procedures are also associated with increased risk of kidney stones. Restrictive bariatric surgeries have not been associated with kidney-stone risk. Higher risk of kidney stones after malabsorptive procedures is associated with postsurgical changes in urine composition, including high urine oxalate, low urine citrate, and low urine volume. Certain dietary recommendations after surgery may help mitigate these urine changes and reduce risk of kidney stones. Understanding risk of kidney stones after surgery is essential to improving patient outcomes after bariatric surgery.Prochaska, MeganWorcester, Elaine2020-10-01T09:37:53-07:00doi:10.34067/KID.0004982020hwp:resource-id:kidney360;1/12/1456American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360nephrolithiasis, bariatric surgery, kidney calculi, risk factorsReview ArticlesReview Articlesreview-article20202020-12-3110.34067/KID.00049820202641-76502020-10-01T09:37:53-07:002020-12-31Kidney360Review Articles11214561461
- Back Pain and Lower Extremity Sensory Loss in an ESKD Patient10.34067/KID.0003322020Thu, 31 Dec 2020 05:30:28 GMT-08:00Back Pain and Lower Extremity Sensory Loss in an ESKD PatientMaalouly, ChristianVô, BernardLabriola, Laura2020-12-31T05:30:28-08:00doi:10.34067/KID.0003322020hwp:resource-id:kidney360;1/12/1466American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, back pain, brown tumor, end stage kidney disease, hemodialysis, hyperparathyroidism, lower extremityClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-12-3110.34067/KID.00033220202641-76502020-12-31T05:30:28-08:002020-12-31Kidney360Clinical Images in Nephrology and Dialysis11214661467
- Cognitive Function and Uremic Toxins after Kidney Transplantation: An Exploratory Study10.34067/KID.0000272020Mon, 21 Sep 2020 01:25:17 GMT-07:00Cognitive Function and Uremic Toxins after Kidney Transplantation: An Exploratory Studyte Linde, Elsemiekevan Roij, Claudette J.M.Meijers, Bjӧrn K.I.De Loor, HenrietteKessels, Roy P.C.Wetzels, Jack F.M.2020-09-21T13:25:17-07:00doi:10.34067/KID.0000272020hwp:resource-id:kidney360;1/12/1398American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, biological toxins, cognition, kidney transplantationOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-12-3110.34067/KID.00002720202641-76502020-09-21T13:25:17-07:002020-12-31Kidney360Original Investigations11213981406
- Dialysis Filter Life in COVID-19: Early Lessons from the Pandemic10.34067/KID.0006212020Thu, 31 Dec 2020 05:30:28 GMT-08:00Dialysis Filter Life in COVID-19: Early Lessons from the PandemicPortales-Castillo, IgnacioAllegretti, Andrew S.2020-12-31T05:30:28-08:00doi:10.34067/KID.0006212020hwp:resource-id:kidney360;1/12/1334American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, continuous venovenous hemofiltration, coronavirus, COVID-19, CRRT, CVVH, end stage renal disease, hemodialysis, hemofiltration, hypercoagulability, SARS, SARS-CoV-2, thrombosisEditorialsEditorialseditorial20202020-12-3110.34067/KID.00062120202641-76502020-12-31T05:30:28-08:002020-12-31Kidney360Editorials11213341336
- Acute Peritoneal Dialysis During the COVID-19 Pandemic at Bellevue Hospital in New York City10.34067/KID.0005192020Fri, 16 Oct 2020 10:42:40 GMT-07:00Acute Peritoneal Dialysis During the COVID-19 Pandemic at Bellevue Hospital in New York CityCaplin, Nina J.Zhdanova, OlgaTandon, ManishThompson, NathanPatel, DhwanilSoomro, QandeelRanjeeta, FnuJoseph, LeianScherer, JenniferJoshi, ShivamDyal, BettyChawla, HarminderIyer, SitalakshmiBails, DouglasBenstein, JudithGoldfarb, David S.Gelb, BruceAmerling, RichardCharytan, David M.2020-10-16T10:42:40-07:00doi:10.34067/KID.0005192020hwp:resource-id:kidney360;1/12/1345American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, continuous kidney replacement therapy, COVID-19, hemodialysis, hospital, intensive care unit, New York City, pandemic, peritoneal dialysis, prone ventilationOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-12-3110.34067/KID.00051920202641-76502020-10-16T10:42:40-07:002020-12-31Kidney360Original Investigations11213451352
- Psychosocial Impact of COVID-19 Pandemic on Patients with End-Stage Kidney Disease on Hemodialysis10.34067/KID.0004662020Tue, 20 Oct 2020 01:31:37 GMT-07:00Psychosocial Impact of COVID-19 Pandemic on Patients with End-Stage Kidney Disease on HemodialysisLee, JacquelineSteel, JenniferRoumelioti, Maria-EleniErickson, SarahMyaskovsky, LarissaYabes, Jonathan G.Rollman, Bruce L.Weisbord, StevenUnruh, MarkJhamb, Manisha2020-10-20T13:31:37-07:00doi:10.34067/KID.0004662020hwp:resource-id:kidney360;1/12/1390American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, anxiety, COVID-19, depression, dialysis, pandemic, psychosocial, sleep, stressOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-12-3110.34067/KID.00046620202641-76502020-10-20T13:31:37-07:002020-12-31Kidney360Original Investigations11213901397
- Characteristics, Outcomes and 60-Day Hospital Mortality of ICU Patients with COVID-19 and Acute Kidney Injury10.34067/KID.0004282020Fri, 02 Oct 2020 06:04:16 GMT-07:00Characteristics, Outcomes and 60-Day Hospital Mortality of ICU Patients with COVID-19 and Acute Kidney InjuryThakkar, JyotsanaChand, SudhamAboodi, Michael S.Gone, Anirudh R.Alahiri, EmadSchecter, David E.Grand, DavidSharma, DeepAbramowitz, Matthew K.Ross, Michael J.Dicpinigaitis, PeterKapoor, Sumit2020-10-02T06:04:16-07:00doi:10.34067/KID.0004282020hwp:resource-id:kidney360;1/12/1339American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, AKI, COVID-19, hospital mortality, intensive care unitsOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-12-3110.34067/KID.00042820202641-76502020-10-02T06:04:16-07:002020-12-31Kidney360Original Investigations11213391344
- Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney Injury10.34067/KID.0004322020Tue, 20 Oct 2020 10:00:12 GMT-07:00Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney InjuryWen, YuangLeDoux, Jason R.Mohamed, MunerRamanand, AkankshScharwath, KevinMundy, DestineyLukitsch, IvoVelez, Juan Carlos Q.2020-10-20T10:00:12-07:00doi:10.34067/KID.0004322020hwp:resource-id:kidney360;1/12/1426American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute renal failure, circuit, clinical nephrology, clogging, clotting, COVID-19, CRP, CRRT, dialysis, heparin, inflammation, PIRRT, renal replacement therapy, SLED, thrombosis, transmembrane pressure, virologyBrief CommunicationBrief Communicationbrief-report20202020-12-3110.34067/KID.00043220202641-76502020-10-20T10:00:12-07:002020-12-31Kidney360Brief Communication11214261431
- Global Dialysis Perspective: South Africa10.34067/KID.0005152020Tue, 20 Oct 2020 10:00:12 GMT-07:00Global Dialysis Perspective: South AfricaJardine, ThabietDavids, Mogamat Razeen2020-10-20T10:00:12-07:00doi:10.34067/KID.0005152020hwp:resource-id:kidney360;1/12/1432American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, chronic kidney disease, disease registries, hemodialysis, kidney failure, peritoneal dialysis, South AfricaGlobal PerspectiveGlobal Perspectiveresearch-article20202020-12-3110.34067/KID.00051520202641-76502020-10-20T10:00:12-07:002020-12-31Kidney360Global Perspective11214321436
- APOL1 Risk Variants Impair Multiple Mitochondrial Pathways in a Metabolomics Analysis10.34067/KID.0003592020Wed, 30 Sep 2020 10:03:22 GMT-07:00APOL1 Risk Variants Impair Multiple Mitochondrial Pathways in a Metabolomics AnalysisMa, LijunPalmer, Nicholette D.Choi, Young AMurea, MarianaSnipes, James A.Parks, John S.Langefeld, Carl D.Freedman, Barry I.2020-09-30T10:03:22-07:00doi:10.34067/KID.0003592020hwp:resource-id:kidney360;1/12/1353American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, African Americans, APOL1, CKD, FSGS, genetics, kidney, metabolomics, mitochondria, Basic ScienceOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-12-3110.34067/KID.00035920202641-76502020-09-30T10:03:22-07:002020-12-31Kidney360Original Investigations11213531362
- Beta-2 Microglobulin Amyloidosis: Past, Present, and FutureAlmost half a century has elapsed since the first description of dialysis-related amyloidosis (DRA), a disorder caused by excessive accumulation of β-2 microglobulin (B2M). Within that period, substantial advances in RRT occurred. These improvements have led to a decrease in the incidence of DRA. In many countries, DRA is considered a “disappearing act” or complication. Although the prevalence of patients living with RRT increases, not all will have access to kidney transplantation. Consequently, the number of patients requiring interventions for treatment of DRA is postulated to increase. This postulate has been borne out in Japan, where the number of patients with ESKD requiring surgery for carpal tunnel continues to increase. Clinicians treating patients with ESKD have treatment options to improve B2M clearance; however, there is a need to identify ways to translate improved B2M clearance into improved quality of life for patients undergoing long-term dialysis.10.34067/KID.0004922020Wed, 21 Oct 2020 11:24:32 GMT-07:00Beta-2 Microglobulin Amyloidosis: Past, Present, and FutureAlmost half a century has elapsed since the first description of dialysis-related amyloidosis (DRA), a disorder caused by excessive accumulation of β-2 microglobulin (B2M). Within that period, substantial advances in RRT occurred. These improvements have led to a decrease in the incidence of DRA. In many countries, DRA is considered a “disappearing act” or complication. Although the prevalence of patients living with RRT increases, not all will have access to kidney transplantation. Consequently, the number of patients requiring interventions for treatment of DRA is postulated to increase. This postulate has been borne out in Japan, where the number of patients with ESKD requiring surgery for carpal tunnel continues to increase. Clinicians treating patients with ESKD have treatment options to improve B2M clearance; however, there is a need to identify ways to translate improved B2M clearance into improved quality of life for patients undergoing long-term dialysis.Portales-Castillo, IgnacioYee, JerryTanaka, HiroshiFenves, Andrew Z.2020-10-21T11:24:32-07:00doi:10.34067/KID.0004922020hwp:resource-id:kidney360;1/12/1447American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, advanced glycosylation, amyloidosis, beta-2-microglobulin, carpal tunnel, dialysis, hemofiltration, microglobulin, spondyloarthropathy, tenosynovitisReview ArticlesReview Articlesreview-article20202020-12-3110.34067/KID.00049220202641-76502020-10-21T11:24:32-07:002020-12-31Kidney360Review Articles11214471455
- Transcriptomes of Major Proximal Tubule Cell Culture Models10.1681/ASN.2020010009Thu, 29 Oct 2020 09:51:15 GMT-07:00Transcriptomes of Major Proximal Tubule Cell Culture ModelsKhundmiri, Syed J.Chen, LiheLederer, Eleanor D.Yang, Chin-RangKnepper, Mark A.2020-10-29T09:51:15-07:00doi:10.1681/ASN.2020010009hwp:resource-id:jnephrol;32/1/86American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyRNA-Seq, proximal tubule, cell culture, proteomicsBasic ResearchBasic Researchresearch-article20212021-01-01January 202110.1681/ASN.20200100091046-66731533-34502020-10-29T09:51:15-07:002021-01Journal of the American Society of NephrologyBasic Research3215886126520999712672100
- Will Targeting Interleukin-6 in the Anemia of CKD Change Our Treatment Paradigm?10.1681/ASN.2020101476Thu, 03 Dec 2020 07:35:19 GMT-08:00Will Targeting Interleukin-6 in the Anemia of CKD Change Our Treatment Paradigm?Coyne, Daniel W.Fleming, Robert2020-12-03T07:35:19-08:00doi:10.1681/ASN.2020101476hwp:resource-id:jnephrol;32/1/6American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, erythropoietin, hemodialysisUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-01-01January 202110.1681/ASN.20201014761046-66731533-34502020-12-03T07:35:19-08:002021-01Journal of the American Society of NephrologyUp Front Matters321162118222
- The Aftermath of AKI: Recurrent AKI, Acute Kidney Disease, and CKD Progression10.1681/ASN.2020091317Fri, 09 Oct 2020 11:47:01 GMT-07:00The Aftermath of AKI: Recurrent AKI, Acute Kidney Disease, and CKD ProgressionWen, YumengParikh, Chirag R.2020-10-09T11:47:01-07:00doi:10.1681/ASN.2020091317hwp:resource-id:jnephrol;32/1/2American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes mellitus, acute kidney injury, acute kidney disease, chronic kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20212021-01-01January 202110.1681/ASN.20200913171046-66731533-34502020-10-09T11:47:01-07:002021-01Journal of the American Society of NephrologyUp Front Matters321121384150
- This Month's Highlights10.1681/ASN.2020111605Tue, 29 Dec 2020 11:00:29 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2020-12-29T11:00:29-08:00doi:10.1681/ASN.2020111605hwp:resource-id:jnephrol;32/1/iAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20212021-01-01January 202110.1681/ASN.20201116051046-66731533-34502020-12-29T11:00:29-08:002021-01Journal of the American Society of NephrologyThis Month's Highlights321ii
- Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study10.1681/ASN.2020050625Wed, 28 Oct 2020 07:18:33 GMT-07:00Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic StudyHsu, SimonZelnick, Leila R.Lin, Yvonne S.Best, Cora M.Kestenbaum, BryanThummel, Kenneth E.Rose, Lynn M.Hoofnagle, Andrew N.de Boer, Ian H.2020-10-28T07:18:33-07:00doi:10.1681/ASN.2020050625hwp:resource-id:jnephrol;32/1/188American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, catabolism, clearance, end stage kidney disease, racial differences, vitamin DClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200506251046-66731533-34502020-10-28T07:18:33-07:002021-01Journal of the American Society of NephrologyClinical Research321188198
- Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease10.1681/ASN.2020040511Mon, 12 Oct 2020 12:14:48 GMT-07:00Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney DiseaseZhang, ChaoBalbo, BrunoMa, MingZhao, JunTian, XinKluger, YuvalSomlo, Stefan2020-10-12T12:14:48-07:00doi:10.1681/ASN.2020040511hwp:resource-id:jnephrol;32/1/41American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, proliferation, transcriptional profilingBasic ResearchBasic Researchresearch-article20212021-01-01Month XX, 202110.1681/ASN.20200405111046-66731533-34502020-10-12T12:14:48-07:002021-01Journal of the American Society of NephrologyBasic Research3214151
- Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis10.1681/ASN.2020030384Mon, 31 Aug 2020 06:41:38 GMT-07:00Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-AnalysisKelly, Jaimon T.Su, GuobinZhang, LaQin, XindongMarshall, SkyeGonzález-Ortiz, AilemaClase, Catherine M.Campbell, Katrina L.Xu, HongCarrero, Juan-Jesus2020-08-31T06:41:38-07:00doi:10.1681/ASN.2020030384hwp:resource-id:jnephrol;32/1/239American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydiet, exercise, smoking, alcohol, lifestyle, chronic kidney diseaseMeta-AnalysisMeta-Analysisresearch-article20212021-01-01January 202110.1681/ASN.20200303841046-66731533-34502020-08-31T06:41:38-07:002021-01Journal of the American Society of NephrologyMeta-Analysis321239253
- Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in Adults10.1681/ASN.2019050546Mon, 09 Nov 2020 01:32:09 GMT-08:00Comparison of the Efficacy and Safety of Tacrolimus and Low-Dose Corticosteroid with High-Dose Corticosteroid for Minimal Change Nephrotic Syndrome in AdultsChin, Ho JunChae, Dong-WanKim, Yong ChulAn, Won SukIhm, ChunGyooJin, Dong-ChanKim, Sung GyunKim, Yong-LimKim, Yong-SooKim, Yoon-GooKoo, Ho SeokLee, Jung EunLee, Kang WookOh, JieunPark, Jung HwanJiang, HongsiLee, HyuncheolLee, Sang Koo2020-11-09T13:32:09-08:00doi:10.1681/ASN.2019050546hwp:resource-id:jnephrol;32/1/199American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologycorticosteroid, glomerulonephritis, nephrotic syndrome, immunosuppression, tacrolimus, remissionClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20190505461046-66731533-34502020-11-09T13:32:09-08:002021-01Journal of the American Society of NephrologyClinical Research321199210
- Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial10.1681/ASN.2020050595Thu, 03 Dec 2020 07:35:20 GMT-08:00Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled TrialPergola, Pablo E.Devalaraja, MattFishbane, StevenChonchol, MichelMathur, Vandana S.Smith, Mark T.Lo, LarryHerzog, KurtKakkar, RahulDavidson, Michael H.2020-12-03T07:35:20-08:00doi:10.1681/ASN.2020050595hwp:resource-id:jnephrol;32/1/211American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, anemia, chronic kidney disease, cardiovascular disease, erythropoietin stimulating agents, inflammationClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200505951046-66731533-34502020-12-03T07:35:20-08:002021-01Journal of the American Society of NephrologyClinical Research321121162228
- Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis10.1681/ASN.2020030362Wed, 04 Nov 2020 05:53:01 GMT-08:00Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental PyelonephritisRuiz-Rosado, Juan de DiosRobledo-Avila, FrankCortado, HannaRangel-Moreno, JavierJustice, Sheryl S.Yang, ChingSpencer, John DavidBecknell, BrianPartida-Sanchez, Santiago2020-11-04T05:53:01-08:00doi:10.1681/ASN.2020030362hwp:resource-id:jnephrol;32/1/69American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyurinary tract infection, acute pyelonephritis, inflammation, renal scarring, macrophages, neutrophilsBasic ResearchBasic Researchresearch-article20212021-01-01January 202110.1681/ASN.20200303621046-66731533-34502020-11-04T05:53:01-08:002021-01Journal of the American Society of NephrologyBasic Research3216985
- Deep Learning–Based Segmentation and Quantification in Experimental Kidney Histopathology10.1681/ASN.2020050597Thu, 05 Nov 2020 08:49:17 GMT-08:00Deep Learning–Based Segmentation and Quantification in Experimental Kidney HistopathologyBouteldja, NassimKlinkhammer, Barbara M.Bülow, Roman D.Droste, PatrickOtten, Simon W.Freifrau von Stillfried, SaskiaMoellmann, JuliaSheehan, Susan M.Korstanje, RonMenzel, SylviaBankhead, PeterMietsch, MatthiasDrummer, CharisLehrke, MichaelKramann, RafaelFloege, JürgenBoor, PeterMerhof, Dorit2020-11-05T08:49:17-08:00doi:10.1681/ASN.2020050597hwp:resource-id:jnephrol;32/1/52American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologydigital pathology, segmentation, histopathology, animal model, machine learning collectionBasic ResearchBasic Researchresearch-article20212021-01-01January 202110.1681/ASN.20200505971046-66731533-34502020-11-05T08:49:17-08:002021-01Journal of the American Society of NephrologyBasic Research3215268
- Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis10.1681/ASN.2020040478Mon, 05 Oct 2020 07:54:37 GMT-07:00Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal AgenesisArora, VeronicaKhan, SulimanW. El-Hattab, AymanDua Puri, RatnaRocha, Maria EugeniaMerdzanic, RijadPaknia, OmidBeetz, ChristianRolfs, ArndtBertoli-Avella, Aida M.Bauer, PeterVerma, Ishwar C.2020-10-05T07:54:37-07:00doi:10.1681/ASN.2020040478hwp:resource-id:jnephrol;32/1/223American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal agenesis, gene expression, genetics and developmentClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200404781046-66731533-34502020-10-05T07:54:37-07:002021-01Journal of the American Society of NephrologyClinical Research321223228
- Intracellular Phosphate and ATP Depletion Measured by Magnetic Resonance Spectroscopy in Patients Receiving Maintenance Hemodialysis10.1681/ASN.2020050716Thu, 22 Oct 2020 01:26:42 GMT-07:00Intracellular Phosphate and ATP Depletion Measured by Magnetic Resonance Spectroscopy in Patients Receiving Maintenance HemodialysisChazot, GuillaumeLemoine, SandrineKocevar, GabrielKalbacher, EmilieSappey-Marinier, DominiqueRouvière, OlivierJuillard, Laurent2020-10-22T13:26:42-07:00doi:10.1681/ASN.2020050716hwp:resource-id:jnephrol;32/1/229American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, hyperphosphatemia, cell transferClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200507161046-66731533-34502020-10-22T13:26:42-07:002021-01Journal of the American Society of NephrologyClinical Research321229237
- Conventional and Genetic Evidence on the Association between Adiposity and CKD10.1681/ASN.2020050679Fri, 30 Oct 2020 11:51:04 GMT-07:00Conventional and Genetic Evidence on the Association between Adiposity and CKDZhu, PengfeiHerrington, William G.Haynes, RichardEmberson, JonathanLandray, Martin J.Sudlow, Cathie L.M.Woodward, MarkBaigent, ColinLewington, SarahStaplin, Natalie2020-10-30T11:51:04-07:00doi:10.1681/ASN.2020050679hwp:resource-id:jnephrol;32/1/127American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, body mass index, central adiposity, chronic kidney disease, epidemiology and outcomes, Mendelian randomizationClinical EpidemiologyClinical Epidemiologyresearch-article20212021-01-01January 202110.1681/ASN.20200506791046-66731533-34502020-10-30T11:51:04-07:002021-01Journal of the American Society of NephrologyClinical Epidemiology321127137
- Humanized C3 Mouse: A Novel Accelerated Model of C3 Glomerulopathy10.1681/ASN.2020050698Mon, 07 Dec 2020 08:43:40 GMT-08:00Humanized C3 Mouse: A Novel Accelerated Model of C3 GlomerulopathyDevalaraja-Narashimha, KishorMeagher, KarolineLuo, YifanHuang, CongKaplan, TheodoreMuthuswamy, AnantharamanHalasz, GaborCasanova, SarahO’Brien, JohnPeyser Boiarsky, RebeccaMcWhirter, JohnGartner, HansBai, YuMacDonnell, ScottLiu, ChienHu, YingLatuszek, AdriannaWei, YiPrasad, SrinivasaHuang, TammyYancopoulos, GeorgeMurphy, AndrewOlson, WilliamZambrowicz, BrianMacdonald, LynnMorton, Lori G.2020-12-07T08:43:40-08:00doi:10.1681/ASN.2020050698hwp:resource-id:jnephrol;32/1/99American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyC3 glomerulopathy, mouse model, humanized C3 mice, accelerated kidney disease, C2 KO, liver phenotype, C5, C3b, CFH mAbsBasic ResearchBasic Researchresearch-article20212021-01-01Month XX, 202010.1681/ASN.20200506981046-66731533-34502020-12-07T08:43:40-08:002021-01Journal of the American Society of NephrologyBasic Research32199114
- Complexities of eGFRs in a Study of Glomerular Physiology10.1681/ASN.2020091364Mon, 09 Nov 2020 01:43:31 GMT-08:00Complexities of eGFRs in a Study of Glomerular PhysiologySteiner, Robert W.2020-11-09T13:43:31-08:00doi:10.1681/ASN.2020091364hwp:resource-id:jnephrol;32/1/256American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rateLetter to the EditorLetter to the Editorletter20212021-01-01January 202110.1681/ASN.20200913641046-66731533-34502020-11-09T13:43:31-08:002021-01Journal of the American Society of NephrologyLetter to the Editor3211825625719052572581914
- Authors’ Reply10.1681/ASN.2020101478Mon, 09 Nov 2020 01:43:31 GMT-08:00Authors’ ReplyCollard, Didiervan de Velde, LennartVogt, Liffertvan den Born, Bert-Jan H.2020-11-09T13:43:31-08:00doi:10.1681/ASN.2020101478hwp:resource-id:jnephrol;32/1/257American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular hyperfiltration, glomerular filtration rate, renal hemodynamicsLetter to the EditorLetter to the Editorletter20212021-01-01January 202110.1681/ASN.20201014781046-66731533-34502020-11-09T13:43:31-08:002021-01Journal of the American Society of NephrologyLetter to the Editor3211825725619052582571914
- Sphingosine-1-Phosphate Metabolism and Signaling in Kidney DiseasesIn the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.10.1681/ASN.2020050697Fri, 18 Dec 2020 11:57:35 GMT-08:00Sphingosine-1-Phosphate Metabolism and Signaling in Kidney DiseasesIn the past few decades, sphingolipids and sphingolipid metabolites have gained attention because of their essential role in the pathogenesis and progression of kidney diseases. Studies in models of experimental and clinical nephropathies have described accumulation of sphingolipids and sphingolipid metabolites, and it has become clear that the intracellular sphingolipid composition of renal cells is an important determinant of renal function. Proper function of the glomerular filtration barrier depends heavily on the integrity of lipid rafts, which include sphingolipids as key components. In addition to contributing to the structural integrity of membranes, sphingolipid metabolites, such as sphingosine-1-phosphate (S1P), play important roles as second messengers regulating biologic processes, such as cell growth, differentiation, migration, and apoptosis. This review will focus on the role of S1P in renal cells and how aberrant extracellular and intracellular S1P signaling contributes to the pathogenesis and progression of kidney diseases.Drexler, YelenaMolina, JudithMitrofanova, AllaFornoni, AlessiaMerscher, Sandra2020-12-18T11:57:35-08:00doi:10.1681/ASN.2020050697hwp:resource-id:jnephrol;32/1/9American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, sphingosine-1-phosphate, ceramide, sphingolipid metabolism, sphingolipidsUp Front MattersReviewUp Front MattersReviewother20212021-01-01January 202110.1681/ASN.20200506971046-66731533-34502020-12-18T11:57:35-08:002021-01Journal of the American Society of NephrologyUp Front Matters321931
- Normalization of Cerebral Blood Flow, Neurochemicals, and White Matter Integrity after Kidney Transplantation10.1681/ASN.2020050584Fri, 16 Oct 2020 10:47:42 GMT-07:00Normalization of Cerebral Blood Flow, Neurochemicals, and White Matter Integrity after Kidney TransplantationLepping, Rebecca J.Montgomery, Robert N.Sharma, PalashMahnken, Jonathan D.Vidoni, Eric D.Choi, In-YoungSarnak, Mark J.Brooks, William M.Burns, Jeffrey M.Gupta, Aditi2020-10-16T10:47:42-07:00doi:10.1681/ASN.2020050584hwp:resource-id:jnephrol;32/1/177American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyESKD, kidney transplantation, cerebral blood flow, neurochemicals, white matter integrity, ASL, MRSI, DTIClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200505841046-66731533-34502020-10-16T10:47:42-07:002021-01Journal of the American Society of NephrologyClinical Research321177187
- AKI in Hospitalized Patients with COVID-1910.1681/ASN.2020050615Thu, 03 Sep 2020 12:26:11 GMT-07:00AKI in Hospitalized Patients with COVID-19Chan, LiliChaudhary, KumardeepSaha, AparnaChauhan, KinsukVaid, AkhilZhao, ShanParanjpe, IshanSomani, SulaimanRichter, FelixMiotto, RiccardoLala, AnuradhaKia, ArashTimsina, PremLi, LiFreeman, RobertChen, RongNarula, JagatJust, Allan C.Horowitz, CarolFayad, ZahiCordon-Cardo, CarlosSchadt, EricLevin, Matthew A.Reich, David L.Fuster, ValentinMurphy, BarbaraHe, John C.Charney, Alexander W.Böttinger, Erwin P.Glicksberg, Benjamin S.Coca, Steven G.Nadkarni, Girish N.,Chan, LiliChaudhary, KumardeepSaha, AparnaChauhan, KinsukVaid, AkhilZhao, ShanParanjpe, IshanSomani, SulaimanRichter, FelixMiotto, RiccardoLala, AnuradhaKia, ArashTimsina, PremLi, LiFreeman, RobertChen, RongNarula, JagatJust, Allan C.Horowitz, CarolFayad, ZahiCordon-Cardo, CarlosSchadt, EricLevin, Matthew A.Reich, David L.Fuster, ValentinMurphy, BarbaraHe, John C.Charney, Alexander W.Böttinger, Erwin P.Glicksberg, Benjamin S.Coca, Steven G.Nadkarni, Girish N.2020-09-03T12:26:11-07:00doi:10.1681/ASN.2020050615hwp:resource-id:jnephrol;32/1/151American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, dialysis, COVID-19Clinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200506151046-66731533-34502020-09-03T12:26:11-07:002021-01Journal of the American Society of NephrologyClinical Research3211115141611606176
- AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-1910.1681/ASN.2020060897Fri, 16 Oct 2020 10:47:43 GMT-07:00AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19Gupta, ShrutiCoca, Steven G.Chan, LiliMelamed, Michal L.Brenner, Samantha K.Hayek, Salim S.Sutherland, AnnePuri, SonikaSrivastava, AnandLeonberg-Yoo, AmandaShehata, Alexandre M.Flythe, Jennifer E.Rashidi, ArashSchenck, Edward J.Goyal, NitenderHedayati, S. SusanDy, RajanyBansal, AnipAthavale, AmbarishNguyen, H. BryantVijayan, AnithaCharytan, David M.Schulze, Carl E.Joo, Min J.Friedman, Allon N.Zhang, JingjingSosa, Marie AnneJudd, EricVelez, Juan Carlos Q.Mallappallil, MaryRedfern, Roberta E.Bansal, Amar D.Neyra, Javier A.Liu, Kathleen D.Renaghan, Amanda D.Christov, MartaMolnar, Miklos Z.Sharma, ShreyakKamal, OmerBoateng, Jeffery OwusuShort, Samuel A.P.Admon, Andrew J.Sise, Meghan E.Wang, WeiParikh, Chirag R.Leaf, David E.,Walther, Carl P.Anumudu, Samaya J.Arunthamakun, JustinKopecky, Kathleen F.Milligan, Gregory P.McCullough, Peter A.Nguyen, Thuy-DuyenShaefi, ShahzadKrajewski, Megan L.Shankar, SidharthPannu, AmeekaValencia, Juan D.Waikar, Sushrut S.Kibbelaar, Zoe A.Hart, PeterUpadhyay, ShristiVohra, IshaanGreen, AdamRachoin, Jean-SebastienSchorr, Christa A.Shea, LisaEdmonston, Daniel L.Mosher, Christopher L.Cohen, ZazaAllusson, ValerieBambrick-Santoyo, GabrielaBhatti, Noor ul aainMehta, BijalWilliams, AquinoWalters, PatriciaGo, Ronaldo C.Rose, Keith M.Lisk, RebeccaZhou, Amy M.Kim, Ethan C.Mathews, Kusum S.Altman, Deena R.Saha, AparnaSoh, HowardWen, Huei HsunBose, SonaliLeven, Emily A.Wang, Jing G.Mosoyan, GoharNadkarni, Girish N.Pattharanitima, PattharawinGallagher, Emily J.Guirguis, JohnKapoor, RajatMeshberger, ChristopherKelly, Katherine J.Garibaldi, Brian T.Corona-Villalobos, Celia P.Wen, YumengMenez, StevenMalik, Rubab F.Cervantes, Carmen ElenaGautam, Samir C.Ouyang, JieJohn, SabuYap, ErnieMelaku, YohannesMohamed, IbrahimBajracharya, SiddharthaPuri, IshaThaxton, MariahBhattacharya, JyotsnaWagner, JohnBoudourakis, LeonAhoubim, AfshinThomas, Leslie F.Sirganagari, Dheeraj ReddyGuru, Pramod K.Zhou, YanBergl, Paul A.Rodriguez, JesusShah, Jatan A.Gupta, Mrigank S.Kumar, Princy N.Lazarous, Deepa G.Kassaye, Seble G.Johns, Tanya S.Mocerino, RyanPrudhvi, KalyanZhu, DenzelLevy, Rebecca V.Azzi, YorgFisher, MollyYunes, MilagrosSedaliu, KaltrinaGolestaneh, LadanBrogan, MaureenKumar, NeeljaChang, MichaelThakkar, JyotsanaRaichoudhury, RiteshAthreya, AkshayFarag, MohamedCho, Soo JungPlataki, MariaAlvarez-Mulett, Sergio L.Gomez-Escobar, Luis G.Pan, DiLee, StefiKrishnan, JamunaWhalen, WilliamMacina, AshleyChaudhry, SobaataWu, BenjaminModersitzki, FrankBhivshet, AmeyLeidner, Alexander S.Martinez, CarlosKruser, Jacqueline M.Wunderink, Richard G.Hodakowski, Alexander J.Price-Haywood, Eboni G.Matute-Trochez, Luis A.Hasty, Anna E.Mohamed, Muner M.B.Avasare, Rupali S.Zonies, DavidNewman, Erik T.Omar, Samah AbuPokharel, Kapil K.Singh, HarkarandeepCorrea, SimonShaukat, TanveerMeghan Lee, Heather YangStrohbehn, Ian A.Li, JiahuaMueller, Ariel L.Cairl, Nicholas S.Naimy, GabrielAbu-Saif, AbeerHall, DanyellBickley, LauraRowan, ChrisMadhani-Lovely, FarahPeev, VasilReiser, JochenByun, John J.Vissing, AndrewKapania, Esha M.Post, ZoePatel, Nilam P.Hermes, Joy-MariePatrawalla, AmeeFinkel, Diana G.Danek, Barbara A.Arikapudi, SowminyaPaer, Jeffrey M.Cangialosi, PeterLiotta, MarkRadbel, JaredSunderram, JagScharf, Matthew T.Ahmed, AyeshaBerim, IlyaVatson, Jayanth S.Anand, ShuchiLevitt, Joseph E.Garcia, PabloBoyle, Suzanne M.Song, RuiArif, AliWoo, Sang HoonDeng, XiaoyingKatz-Greenberg, GoniSenter, KatharineSharshir, Moh’d A.Rusnak, Vadym V.Imran Ali, MuhammadPeters, TerriHughes, KathyPodoll, Amber S.Chonchol, MichelSharma, SunitaBurnham, Ellen L.Hejal, RanaLatta, LauraTolwani, AshitaAlbertson, Timothy E.Adams, Jason Y.Chang, Steven Y.Beutler, Rebecca M.Macedo, EtienneRhee, HarinJotwani, Vasantha K.Koyner, Jay L.Shah, Chintan V.Jaikaransingh, VishalToth-Manikowski, Stephanie M.Lash, James P.Chaaban, NourhanAhmad, YahyaElias, MadonaIardino, AlfredoAu, Elizabeth H.Sharma, Jill H.Taldone, SabrinaContreras, GabrielDe La Zerda, DavidFornoni, AlessiaGershengorn, Hayley B.Blakely, PennelopeBerlin, HannaAzam, Tariq U.Shadid, HusamPan, MichaelHayer, Patrick O.’Meloche, ChelseaFeroze, RafeyPadalia, Kishan J.Bitar, AbbasAnderson, ElizabethDonnelly, John P.Tugman, Matthew J.Chang, Emily H.Brown, Brent R.Spiardi, Ryan C.Miano, Todd A.Roche, Meaghan S.Vasquez, Charles R.Ernecoff, Natalie C.Kapoor, SanjanaVerma, SiddharthChen, HuiwenKovesdy, Csaba P.Azhar, AmbreenNadamuni, Mridula V.Shastri, ShaniWillett, Duwayne L.Enfield, Kyle B.Bhatraju, Pavan K.Malik, A. BilalSemler, Matthew W.Mariyam Joy, ChristinaLi, TingtingGoldberg, SethKao, Patricia F.Schumaker, Greg L.Faugno, Anthony J.Schumaker, Greg L.Hsu, Caroline M.Tariq, AsmaMeyer, LeahKshirsagar, Ravi K.Weiner, Daniel E.Griffiths, JenniferGupta, SanjeevKapoor, ArommaWilson, PerryArora, TanimaUgwuowo, Ugochukwu2020-10-16T10:47:43-07:00doi:10.1681/ASN.2020060897hwp:resource-id:jnephrol;32/1/161American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical epidemiology, dialysis, risk factors, COVID-19, renal replacement therapy, acute kidney injuryClinical ResearchClinical Researchresearch-article20212021-01-01January 202110.1681/ASN.20200608971046-66731533-34502020-10-16T10:47:43-07:002021-01Journal of the American Society of NephrologyClinical Research3211171614151182317661601824
- COVID-19–Associated Glomerular Disease10.1681/ASN.2020060804Thu, 19 Nov 2020 06:52:32 GMT-08:00COVID-19–Associated Glomerular DiseaseShetty, Aneesha A.Tawhari, IbrahimSafar-Boueri, LuisaSeif, NayAlahmadi, AmeenGargiulo, RichardAggarwal, VikramUsman, IrtazaKisselev, SergeyGharavi, Ali G.Kanwar, YahspalQuaggin, Susan E.2020-11-19T06:52:32-08:00doi:10.1681/ASN.2020060804hwp:resource-id:jnephrol;32/1/33American Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, collapsing glomerulopathy, APOL1Rapid CommunicationRapid Communicationresearch-article20212021-01-01Month XX, 202010.1681/ASN.20200608041046-66731533-34502020-11-19T06:52:32-08:002021-01Journal of the American Society of NephrologyRapid Communication3211331402
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- Authors’ Reply10.1681/ASN.2020101479Thu, 05 Nov 2020 08:49:16 GMT-08:00Authors’ ReplyRosenstock, Jordan L.Bijol, Vanesa2020-11-05T08:49:16-08:00doi:10.1681/ASN.2020101479hwp:resource-id:jnephrol;32/1/255-aAmerican Society of NephrologyCopyright © 2021 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID AKI, COVID-19Letter to the EditorLetter to the Editorletter20212021-01-01Month XX, 202010.1681/ASN.20201014791046-66731533-34502020-11-05T08:49:16-08:002021-01Journal of the American Society of NephrologyLetter to the Editor3211925525519442562551947
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- Authors’ Reply10.1681/ASN.2020071096Fri, 04 Sep 2020 09:16:32 GMT-07:00Authors’ ReplyAkizawa, TadaoIwasaki, ManabuYamaguchi, YusukeMajikawa, YoshikatsuReusch, Michael2020-09-04T09:16:32-07:00doi:10.1681/ASN.2020071096hwp:resource-id:jnephrol;31/11/2738American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, hemodialysis, hypoxia-inducible factor, erythropoiesis-stimulating agent, randomized controlled trialsLetters to the EditorLetters to the Editorletter20202020-11-01November 202010.1681/ASN.20200710961046-66731533-34502020-09-04T09:16:32-07:002020-11Journal of the American Society of NephrologyLetters to the Editor3111112738273727402737
- Much to Fear about MUCH10.1681/ASN.2020091270Tue, 06 Oct 2020 10:25:15 GMT-07:00Much to Fear about MUCHAgarwal, Rajiv2020-10-06T10:25:15-07:00doi:10.1681/ASN.2020091270hwp:resource-id:jnephrol;31/11/2496American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, chronic kidney disease, clinical epidemiology, clinical hypertension, blood pressure, cardiovascular eventsUp Front MattersEditorialsUp Front MattersEditorialseditorial20202020-11-01November 202010.1681/ASN.20200912701046-66731533-34502020-10-06T10:25:15-07:002020-11Journal of the American Society of NephrologyUp Front Matters3111112496260924992621
- Thematic Analysis of Hospice Mentions in the Health Records of Veterans with Advanced Kidney Disease10.1681/ASN.2020040473Thu, 06 Aug 2020 12:22:22 GMT-07:00Thematic Analysis of Hospice Mentions in the Health Records of Veterans with Advanced Kidney DiseaseO’Hare, Ann M.Butler, Catherine R.Taylor, Janelle S.Wong, Susan P.Y.Vig, Elizabeth K.Laundry, Ryan S.Wachterman, Melissa W.Hebert, Paul L.Liu, Chuan-FenRios-Burrows, NilkaRichards, Claire A.2020-08-06T12:22:22-07:00doi:10.1681/ASN.2020040473hwp:resource-id:jnephrol;31/11/2667American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyhospice, end-of-life, advanced kidney disease, concurrent care, concurrent dialysis, veteranClinical ResearchClinical Researchresearch-article20202020-11-01November 202010.1681/ASN.20200404731046-66731533-34502020-08-06T12:22:22-07:002020-11Journal of the American Society of NephrologyClinical Research311126672677
- Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 Interaction10.1681/ASN.2020040401Tue, 04 Aug 2020 08:49:33 GMT-07:00Nephron Progenitor Maintenance Is Controlled through Fibroblast Growth Factors and Sprouty1 InteractionHuh, Sung-HoHa, LigyeomJang, Hee-Seong2020-08-04T08:49:33-07:00doi:10.1681/ASN.2020040401hwp:resource-id:jnephrol;31/11/2559American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyFGF signal, Spry1, nephron progenitor cells, kidney developmentBasic ResearchBasic Researchresearch-article20202020-11-01November 202010.1681/ASN.20200404011046-66731533-34502020-08-04T08:49:33-07:002020-11Journal of the American Society of NephrologyBasic Research311125592572
- This Month's Highlights10.1681/ASN.2020091382Fri, 30 Oct 2020 10:00:32 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2020-10-30T10:00:32-07:00doi:10.1681/ASN.2020091382hwp:resource-id:jnephrol;31/11/iAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20202020-11-01November 202010.1681/ASN.20200913821046-66731533-34502020-10-30T10:00:32-07:002020-11Journal of the American Society of NephrologyThis Month’s Highlights3111ii
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- Authors’ Reply10.1681/ASN.2020081171Fri, 11 Sep 2020 07:23:35 GMT-07:00Authors’ ReplyShin, Jung-ImSang, YingyingDunning, Stephan C.Grams, Morgan E.2020-09-11T07:23:35-07:00doi:10.1681/ASN.2020081171hwp:resource-id:jnephrol;31/11/2740-aAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rateLetters to the EditorLetters to the Editorletter20202020-11-01November 202010.1681/ASN.20200811711046-66731533-34502020-09-11T07:23:35-07:002020-11Journal of the American Society of NephrologyLetters to the Editor3111112740274027412740
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- A New Dimension to the Mechanisms Causing Muscle Loss in CKD10.1681/ASN.2020091341Fri, 09 Oct 2020 11:47:02 GMT-07:00A New Dimension to the Mechanisms Causing Muscle Loss in CKDPrice, S. RussBailey, James L.2020-10-09T11:47:02-07:00doi:10.1681/ASN.2020091341hwp:resource-id:jnephrol;31/11/2495American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, skeletal muscle, muscle atrophy, cachexiaEditorialsEditorialseditorial20202020-11-01November 202010.1681/ASN.20200913411046-66731533-34502020-10-09T11:47:02-07:002020-11Journal of the American Society of NephrologyEditorials3111112495257324962587
- Mechanisms Regulating Muscle Protein Synthesis in CKD10.1681/ASN.2019121277Thu, 06 Aug 2020 12:22:23 GMT-07:00Mechanisms Regulating Muscle Protein Synthesis in CKDZhang, LipingChen, QinChen, ZihongWang, YingGamboa, Jorge L.Ikizler, Talat AlpGaribotto, GiacomoMitch, William E.2020-08-06T12:22:23-07:00doi:10.1681/ASN.2019121277hwp:resource-id:jnephrol;31/11/2573American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyprotein synthesis, chronic kidney disease, muscle wasting, protein metabolism, ribosomal RNA transcription, epigeneticsBasic ResearchBasic Researchresearch-article20202020-11-01November 202010.1681/ASN.20191212771046-66731533-34502020-08-06T12:22:23-07:002020-11Journal of the American Society of NephrologyBasic Research31321111222573249552152125872496521521
- Binder Blunder in CKD10.1681/ASN.2020081182Fri, 11 Sep 2020 07:23:35 GMT-07:00Binder Blunder in CKDIx, Joachim H.2020-09-11T07:23:35-07:00doi:10.1681/ASN.2020081182hwp:resource-id:jnephrol;31/11/2499American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologymineral metabolismUp Front MattersEditorialsUp Front MattersEditorialseditorial20202020-11-01November 202010.1681/ASN.20200811821046-66731533-34502020-09-11T07:23:35-07:002020-11Journal of the American Society of NephrologyUp Front Matters3111112499265325012666
- Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney Disease10.1681/ASN.2019111197Fri, 21 Aug 2020 07:56:25 GMT-07:00Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney DiseaseCasal Moura, MartaIrazabal, Maria V.Eirin, AlfonsoZand, LadanSethi, SanjeevBorah, Bijan J.Winters, Jeffrey L.Moriarty, James P.Cartin-Ceba, RodrigoBerti, AlviseBaqir, MisbahThompson, Gwen E.Makol, AshimaWarrington, Kenneth J.Thao, ViengneeseeSpecks, UlrichFervenza, Fernando C.2020-08-21T07:56:25-07:00doi:10.1681/ASN.2019111197hwp:resource-id:jnephrol;31/11/2688American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, glomerulonephritis, rituximab, cyclophosphamide, PlasmapheresisClinical ResearchClinical Researchresearch-article20202020-11-01November 202010.1681/ASN.20191111971046-66731533-34502020-08-21T07:56:25-07:002020-11Journal of the American Society of NephrologyClinical Research311126882704
- Live Imaging of Monocyte Subsets in Immune Complex-Mediated Glomerulonephritis Reveals Distinct Phenotypes and Effector Functions10.1681/ASN.2019121326Mon, 31 Aug 2020 06:41:39 GMT-07:00Live Imaging of Monocyte Subsets in Immune Complex-Mediated Glomerulonephritis Reveals Distinct Phenotypes and Effector FunctionsTurner-Stokes, TabithaGarcia Diaz, AnaPinheiro, DamilolaPrendecki, MariaMcAdoo, Stephen P.Roufosse, CandiceCook, H. TerencePusey, Charles D.Woollard, Kevin J.2020-08-31T06:41:39-07:00doi:10.1681/ASN.2019121326hwp:resource-id:jnephrol;31/11/2523American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, immune complexes, macrophages, immunologyBasic ResearchBasic Researchresearch-article20202020-11-01November 202010.1681/ASN.20191213261046-66731533-34502020-08-31T06:41:39-07:002020-11Journal of the American Society of NephrologyBasic Research311125232542
- Role of Roxadustat for ESA-Resistant Renal Anemia? —Read with Caution10.1681/ASN.2020060821Fri, 04 Sep 2020 09:16:31 GMT-07:00Role of Roxadustat for ESA-Resistant Renal Anemia? —Read with CautionTanaka, MototsuguShinohara, KayoOno, AkikoIkuma, Mutsuhiro2020-09-04T09:16:31-07:00doi:10.1681/ASN.2020060821hwp:resource-id:jnephrol;31/11/2737American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, hemodialysis, hypoxia-inducible factor, erythropoiesis-stimulating agent, randomized controlled trialLetters to the EditorLetters to the Editorletter20202020-11-01November 202010.1681/ASN.20200608211046-66731533-34502020-09-04T09:16:31-07:002020-11Journal of the American Society of NephrologyLetters to the Editor3111112737273827372740
- A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD)10.1681/ASN.2020040411Fri, 11 Sep 2020 07:23:36 GMT-07:00A Randomized Trial on the Effect of Phosphate Reduction on Vascular End Points in CKD (IMPROVE-CKD)Toussaint, Nigel D.Pedagogos, EugeniaLioufas, Nicole M.Elder, Grahame J.Pascoe, Elaine M.Badve, Sunil V.Valks, AndreaBlock, Geoffrey A.Boudville, NeilCameron, James D.Campbell, Katrina L.Chen, Sylvia S.M.Faull, Randall J.Holt, Stephen G.Jackson, DanaJardine, Meg J.Johnson, David W.Kerr, Peter G.Lau, Kenneth K.Hooi, Lai-SeongNarayan, OmPerkovic, VladoPolkinghorne, Kevan R.Pollock, Carol A.Reidlinger, DonnaRobison, LauraSmith, Edward R.Walker, Robert J.Wang, Angela Yee MoonHawley, Carmel M.,2020-09-11T07:23:36-07:00doi:10.1681/ASN.2020040411hwp:resource-id:jnephrol;31/11/2653American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyarterial compliance, cardiovascular disease, phosphate, phosphate binders, vascular calcification, lanthanum carbonateClinical ResearchClinical Researchresearch-article20202020-11-01November 202010.1681/ASN.20200404111046-66731533-34502020-09-11T07:23:36-07:002020-11Journal of the American Society of NephrologyClinical Research3111112653249926662501
- Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 Expression10.1681/ASN.2019121289Fri, 28 Aug 2020 08:10:43 GMT-07:00Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 ExpressionBrandt, SabineBallhause, Tobias M.Bernhardt, AnjaBecker, AnnikaSalaru, DeliaLe-Deffge, Hien MinhFehr, AlexanderFu, YanPhilipsen, LarsDjudjaj, SonjaMüller, Andreas J.Kramann, RafaelIbrahim, MahmoudGeffers, RobertSiebel, ChrisIsermann, BerendHeidel, Florian H.Lindquist, Jonathan A.Mertens, Peter R.2020-08-28T08:10:43-07:00doi:10.1681/ASN.2019121289hwp:resource-id:jnephrol;31/11/2589American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, chronic kidney disease, cell signaling, chronic inflammation, cell adhesionBasic ResearchBasic Researchresearch-article20202020-11-01November 202010.1681/ASN.20191212891046-66731533-34502020-08-28T08:10:43-07:002020-11Journal of the American Society of NephrologyBasic Research311125892608
- Extracellular Matrix Injury of Kidney Allografts in Antibody-Mediated Rejection: A Proteomics Study10.1681/ASN.2020030286Tue, 08 Sep 2020 12:13:48 GMT-07:00Extracellular Matrix Injury of Kidney Allografts in Antibody-Mediated Rejection: A Proteomics StudyClotet-Freixas, SergiMcEvoy, Caitriona M.Batruch, IhorPastrello, ChiaraKotlyar, MaxVan, Julie Anh DungArambewela, MadhurangiBoshart, AlexFarkona, SofiaNiu, YunLi, YanhongFamure, OlusegunBozovic, AndreaKulasingam, VathanyChen, PeixuenKim, S. JosephChan, EmilieMoshkelgosha, SajadRahman, Syed AshiqurDas, JishnuMartinu, TerezaJuvet, StephenJurisica, IgorChruscinski, AndrzejJohn, RohanKonvalinka, Ana2020-09-08T12:13:48-07:00doi:10.1681/ASN.2020030286hwp:resource-id:jnephrol;31/11/2705American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, extracellular matrix, glomerular endothelial cells, proximal tubule, renal biopsy, kidney transplantationClinical ResearchClinical Researchresearch-article20202020-11-01November 202010.1681/ASN.20200302861046-66731533-34502020-09-08T12:13:48-07:002020-11Journal of the American Society of NephrologyClinical Research311127052724
- Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse Kidney10.1681/ASN.2020020184Thu, 06 Aug 2020 12:22:26 GMT-07:00Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse KidneyMarable, Sierra S.Chung, EunahPark, Joo-Seop2020-08-06T12:22:26-07:00doi:10.1681/ASN.2020020184hwp:resource-id:jnephrol;31/11/2543American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, Hnf4a, kidney development, Fanconi renotubular syndromeBasic ResearchBasic Researchresearch-article20202020-11-01November 202010.1681/ASN.20200201841046-66731533-34502020-08-06T12:22:26-07:002020-11Journal of the American Society of NephrologyBasic Research311125432558
- Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A Post Hoc Analysis from the CREDENCE Trial10.1681/ASN.2020050723Wed, 30 Sep 2020 10:43:47 GMT-07:00Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A Post Hoc Analysis from the CREDENCE TrialOshima, MegumiNeuen, Brendon L.Li, JingWeiPerkovic, VladoCharytan, David M.de Zeeuw, DickEdwards, RobertGreene, TomLevin, AdeeraMahaffey, Kenneth W.De Nicola, LucaPollock, CarolRosenthal, NormanWheeler, David C.Jardine, Meg J.Heerspink, Hiddo J.L.2020-09-30T10:43:47-07:00doi:10.1681/ASN.2020050723hwp:resource-id:jnephrol;31/12/2925American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, canagliflozin, SGLT2 inhibitor, kidney and cardiovascular outcomesClinical ResearchClinical Researchresearch-article20202020-12-01December 202010.1681/ASN.20200507231046-66731533-34502020-09-30T10:43:47-07:002020-12Journal of the American Society of NephrologyClinical Research311229252936
- This Month's Highlights10.1681/ASN.2020101487Wed, 25 Nov 2020 10:00:27 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2020-11-25T10:00:27-08:00doi:10.1681/ASN.2020101487hwp:resource-id:jnephrol;31/12/iAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20202020-12-01December 202010.1681/ASN.20201014871046-66731533-34502020-11-25T10:00:27-08:002020-12Journal of the American Society of NephrologyThis Month's Highlights3112ii
- A Single Point-in-Time eGFR Is Not Associated with Increased Risk of Dementia in the Elderly10.1681/ASN.2020081119Fri, 11 Sep 2020 07:23:36 GMT-07:00A Single Point-in-Time eGFR Is Not Associated with Increased Risk of Dementia in the ElderlyGupta, AditiBurns, Jeffrey M.2020-09-11T07:23:36-07:00doi:10.1681/ASN.2020081119hwp:resource-id:jnephrol;31/12/2965American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyeGFR, dementia, decline in eGFR, cognitionLetters to the EditorLetters to the Editorletter20202020-12-01December 202010.1681/ASN.20200811191046-66731533-34502020-09-11T07:23:36-07:002020-12Journal of the American Society of NephrologyLetters to the Editor3112122965296629652966
- Slope of Kidney Function and Its Association with Longitudinal Mortality and Cardiovascular Disease among Individuals with CKD10.1681/ASN.2020040476Tue, 06 Oct 2020 10:25:16 GMT-07:00Slope of Kidney Function and Its Association with Longitudinal Mortality and Cardiovascular Disease among Individuals with CKDOrlandi, Paula F.Xie, DaweiYang, WeiCohen, Jordana B.Deo, RajatRicardo, Ana C.Schrauben, SarahWang, XueHamm, L. LeeHe, JiangSondheimer, James H.Kallem, KrishnaTownsend, RaymondRaj, DominicParsa, AfshinAnderson, Amanda H.Feldman, Harold I.,,Appel, Lawrence J.Go, Alan S.Lash, James P.Rao, Panduranga S.Rahman, Mahboob2020-10-06T10:25:16-07:00doi:10.1681/ASN.2020040476hwp:resource-id:jnephrol;31/12/2912American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, epidemiology and outcomes, glomerular filtration rate, risk factors, mortality risk, cardiovascular eventsClinical EpidemiologyClinical Epidemiologyresearch-article20202020-12-01December 202010.1681/ASN.20200404761046-66731533-34502020-10-06T10:25:16-07:002020-12Journal of the American Society of NephrologyClinical Epidemiology311229122923
- Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis10.1681/ASN.2020050580Mon, 12 Oct 2020 12:14:49 GMT-07:00Spatiotemporal ATP Dynamics during AKI Predict Renal PrognosisYamamoto, ShinyaYamamoto, MasamichiNakamura, JinMii, AkikoYamamoto, ShigenoriTakahashi, MasahiroKaneko, KeiichiUchino, EiichiroSato, YukiFukuma, ShingoImamura, HiromiMatsuda, MichiyukiYanagita, Motoko2020-10-12T12:14:49-07:00doi:10.1681/ASN.2020050580hwp:resource-id:jnephrol;31/12/2855American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyATP, energy dynamics, imaging, AKI, fibrosis, hypothermiaBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200505801046-66731533-34502020-10-12T12:14:49-07:002020-12Journal of the American Society of NephrologyBasic Research311228552869
- Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy10.1681/ASN.2019080799Thu, 10 Sep 2020 06:58:25 GMT-07:00Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA NephropathyLi, MingWang, LingShi, Dian-ChunFoo, Jia-NeeZhong, ZhongKhor, Chiea-ChuenLanzani, ChiaraCitterio, LorenaSalvi, ErikaYin, Pei-RanBei, Jin-XinWang, LiLiao, Yun-HuaChen, JianChen, Qin-KaiXu, GangJiang, Geng-RuWan, Jian-XinChen, Meng-HuaChen, NanZhang, HongZeng, Yi-XinLiu, Zhi-HongLiu, Jian-JunYu, Xue-Qing2020-09-10T06:58:25-07:00doi:10.1681/ASN.2019080799hwp:resource-id:jnephrol;31/12/2949American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, meta-analysis, genome-wide association study, common variantsMeta-AnalysisMeta-Analysisresearch-article20202020-12-01December 202010.1681/ASN.20190807991046-66731533-34502020-09-10T06:58:25-07:002020-12Journal of the American Society of NephrologyMeta-Analysis311229492963
- Short or Long Sleep Duration and CKD: A Mendelian Randomization Study10.1681/ASN.2020050666Thu, 01 Oct 2020 07:14:50 GMT-07:00Short or Long Sleep Duration and CKD: A Mendelian Randomization StudyPark, SehoonLee, SoojinKim, YaerimLee, YeonheeKang, Min WooKim, KwangsooKim, Yong ChulHan, Seung SeokLee, HajeongLee, Jung PyoJoo, Kwon WookLim, Chun SooKim, Yon SuKim, Dong Ki2020-10-01T07:14:50-07:00doi:10.1681/ASN.2020050666hwp:resource-id:jnephrol;31/12/2937American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologysleep, chronic kidney disease, Mendelian randomization, genetic risk score, end-stage kidney diseaseClinical ResearchClinical Researchresearch-article20202020-12-01December 202010.1681/ASN.20200506661046-66731533-34502020-10-01T07:14:50-07:002020-12Journal of the American Society of NephrologyClinical Research311229372947
- Mix for Regeneration: Nephron Replacement by Transplanted Cells10.1681/ASN.2020091350Thu, 05 Nov 2020 08:49:17 GMT-08:00Mix for Regeneration: Nephron Replacement by Transplanted CellsSchmidt-Ott, Kai M.2020-11-05T08:49:17-08:00doi:10.1681/ASN.2020091350hwp:resource-id:jnephrol;31/12/2743American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycell-based regenerative therapy, chronic kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20202020-12-01December 202010.1681/ASN.20200913501046-66731533-34502020-11-05T08:49:17-08:002020-12Journal of the American Society of NephrologyUp Front Matters3112122743275727452772
- Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury10.1681/ASN.2020050572Wed, 16 Sep 2020 11:55:34 GMT-07:00Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte InjuryNing, LiangSuleiman, Hani Y.Miner, Jeffrey H.2020-09-16T11:55:34-07:00doi:10.1681/ASN.2020050572hwp:resource-id:jnephrol;31/12/2815American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulus podocyte, cytoskeleton, actin, glomerular filtration barrierBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200505721046-66731533-34502020-09-16T11:55:34-07:002020-12Journal of the American Society of NephrologyBasic Research311228152832
- Single-Cell Profiling of AKI in a Murine Model Reveals Novel Transcriptional Signatures, Profibrotic Phenotype, and Epithelial-to-Stromal Crosstalk10.1681/ASN.2020010052Wed, 28 Oct 2020 07:18:33 GMT-07:00Single-Cell Profiling of AKI in a Murine Model Reveals Novel Transcriptional Signatures, Profibrotic Phenotype, and Epithelial-to-Stromal CrosstalkRudman-Melnick, ValeriaAdam, MikePotter, AndrewChokshi, Saagar M.Ma, QingDrake, Keri A.Schuh, Meredith P.Kofron, J. MatthewDevarajan, PrasadPotter, S. Steven2020-10-28T07:18:33-07:00doi:10.1681/ASN.2020010052hwp:resource-id:jnephrol;31/12/2793American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, single-cell, renal developmental genes, cellular crosstalkBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200100521046-66731533-34502020-10-28T07:18:33-07:002020-12Journal of the American Society of NephrologyBasic Research311227932814
- Murine Epsins Play an Integral Role in Podocyte Function10.1681/ASN.2020050691Tue, 13 Oct 2020 06:52:14 GMT-07:00Murine Epsins Play an Integral Role in Podocyte FunctionWang, YingPedigo, Christopher E.Inoue, KazunoriTian, XuefeiCross, ElizabethEbenezer, KarenLi, WeiWang, ZhenShin, Jee WonSchwartze, EikeGroener, MarwinIshibe, Shuta2020-10-13T06:52:14-07:00doi:10.1681/ASN.2020050691hwp:resource-id:jnephrol;31/12/2870American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycell adhesion, glomerulosclerosis, podocyteBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200506911046-66731533-34502020-10-13T06:52:14-07:002020-12Journal of the American Society of NephrologyBasic Research311228702886
- The Imposed Obscurity of Richard W. Lippman, MD (1916–1959), Revered Renal Researcher and Physician10.1681/ASN.2020060769Thu, 29 Oct 2020 09:51:15 GMT-07:00The Imposed Obscurity of Richard W. Lippman, MD (1916–1959), Revered Renal Researcher and PhysicianStrauss, Franklin G.Fine, Leon G.2020-10-29T09:51:15-07:00doi:10.1681/ASN.2020060769hwp:resource-id:jnephrol;31/12/2749American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyhistory of nephrology, Richard W Lippman, Linus Pauling, Thomas Addis, House Un-American Committee, Harry GoldblattPerspectivesPerspectivesresearch-article20202020-12-01December 202010.1681/ASN.20200607691046-66731533-34502020-10-29T09:51:15-07:002020-12Journal of the American Society of NephrologyPerspectives311227492751
- Authors’ Reply10.1681/ASN.2020081189Fri, 11 Sep 2020 07:23:35 GMT-07:00Authors’ ReplyKurella Tamura, ManjulaPajewski, NicholasWeiner, Daniel E.2020-09-11T07:23:35-07:00doi:10.1681/ASN.2020081189hwp:resource-id:jnephrol;31/12/2966American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney diseaseLetters to the EditorLetters to the Editorletter20202020-12-01December 202010.1681/ASN.20200811891046-66731533-34502020-09-11T07:23:35-07:002020-12Journal of the American Society of NephrologyLetters to the Editor3112122966296529662965
- Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney Disease10.1681/ASN.2020060806Fri, 25 Sep 2020 05:42:23 GMT-07:00Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney DiseaseConway, Bryan R.O’Sullivan, Eoin D.Cairns, CarolynnO’Sullivan, JamesSimpson, Daniel J.Salzano, AngelaConnor, KatieDing, PengHumphries, DuncanStewart, KevinTeenan, OliverPius, RiinuHenderson, Neil C.Bénézech, CécileRamachandran, PrakashFerenbach, DavidHughes, JeremyChandra, TamirDenby, Laura2020-09-25T05:42:23-07:00doi:10.1681/ASN.2020060806hwp:resource-id:jnephrol;31/12/2833American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, kidney disease, scRNA sequencing, myeloid cellsBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200608061046-66731533-34502020-09-25T05:42:23-07:002020-12Journal of the American Society of NephrologyBasic Research311228332854
- Death after Kidney Transplantation: An Analysis by Era and Time Post-Transplant10.1681/ASN.2020050566Wed, 09 Sep 2020 07:36:13 GMT-07:00Death after Kidney Transplantation: An Analysis by Era and Time Post-TransplantYing, TraceyShi, BreeKelly, Patrick J.Pilmore, HelenClayton, Philip A.Chadban, Steven J.2020-09-09T07:36:13-07:00doi:10.1681/ASN.2020050566hwp:resource-id:jnephrol;31/12/2887American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologymortality, kidney transplantation, cardiovascular disease, cancer, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20202020-12-01December 202010.1681/ASN.20200505661046-66731533-34502020-09-09T07:36:13-07:002020-12Journal of the American Society of NephrologyClinical Epidemiology311228872899
- Successful Introduction of Human Renovascular Units into the Mammalian Kidney10.1681/ASN.2019050508Tue, 04 Aug 2020 08:49:34 GMT-07:00Successful Introduction of Human Renovascular Units into the Mammalian KidneyPleniceanu, OrenHarari-Steinberg, OritOmer, DoritGnatek, YehuditLachmi, Bat-ElCohen-Zontag, OsnatManevitz-Mendelson, EugeniaBarzilai, AvivYampolsky, MatanFuchs, YaronRosenzweig, BarakEisner, AlonDotan, ZoharFine, Leon G.Dekel, BenjaminGreenberger, Shoshana2020-08-04T08:49:34-07:00doi:10.1681/ASN.2019050508hwp:resource-id:jnephrol;31/12/2757American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal stem cell, vascular endothelial growth factor, renal tubular epithelial cells, kidney spheres, organoids, mesenchymal stem cell (MSC)Basic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20190505081046-66731533-34502020-08-04T08:49:34-07:002020-12Journal of the American Society of NephrologyBasic Research3112122757274327722745
- Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney Disease10.1681/ASN.2020040523Wed, 16 Sep 2020 11:55:34 GMT-07:00Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney DiseaseSellmayr, MarkusHernandez Petzsche, Moritz RomanMa, QiuyueKrüger, NilsLiapis, HelenBrink, AndreasLenz, BarbaraAngelotti, Maria LuciaGnemmi, VivianeKuppe, ChristophKim, HyojinBindels, Eric Moniqué JohannesTajti, FerencSaez-Rodriguez, JulioLech, MaciejKramann, RafaelRomagnani, PaolaAnders, Hans-JoachimSteiger, Stefanie2020-09-16T11:55:34-07:00doi:10.1681/ASN.2020040523hwp:resource-id:jnephrol;31/12/2773American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyuric acid, granuloma, macrophages, inflammation, fibrosis, chronic kidney diseaseBasic ResearchBasic Researchresearch-article20202020-12-01December 202010.1681/ASN.20200405231046-66731533-34502020-09-16T11:55:34-07:002020-12Journal of the American Society of NephrologyBasic Research311227732792
- A Comparison of Different Estimates of Albuminuria in Association with Mortality in Epidemiologic Research10.2215/CJN.07290520Mon, 14 Sep 2020 07:53:03 GMT-07:00A Comparison of Different Estimates of Albuminuria in Association with Mortality in Epidemiologic ResearchKoopman, Jacob J.E.Scherzer, RebeccaIx, Joachim H.Shlipak, Michael G.Waikar, Sushrut S.2020-09-14T07:53:03-07:00doi:10.2215/CJN.07290520hwp:resource-id:clinjasn;15/12/1814American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, biomarker, albumin-creatinine ratio, albumin-osmolality ratio, urine, mortality, clinical epidemiologyResearch LetterResearch Letterletter20202020-12-07December 07, 202010.2215/CJN.072905201555-90411555-905X2020-09-14T07:53:03-07:002020-12-07Clinical Journal of the American Society of NephrologyResearch Letter151218141816
- Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m210.2215/CJN.10140620Thu, 19 Nov 2020 06:44:08 GMT-08:00Effects of Canagliflozin in Patients with Baseline eGFR <30 ml/min per 1.73 m2Bakris, GeorgeOshima, MegumiMahaffey, Kenneth W.Agarwal, RajivCannon, Christopher P.Capuano, GeorgeCharytan, David M.de Zeeuw, DickEdwards, RobertGreene, TomHeerspink, Hiddo J.L.Levin, AdeeraNeal, BruceOh, RichardPollock, CarolRosenthal, NormanWheeler, David C.Zhang, HongZinman, BernardJardine, Meg J.Perkovic, Vlado2020-11-19T06:44:08-08:00doi:10.2215/CJN.10140620hwp:resource-id:clinjasn;15/12/1705American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, diabetes, diabetic nephropathy, canagliflozinOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20202020-12-07December 07, 202010.2215/CJN.101406201555-90411555-905X2020-11-19T06:44:08-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1512121705169417141695
- Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKD10.2215/CJN.08310520Wed, 25 Nov 2020 01:28:55 GMT-08:00Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKDMuanda, Flory T.Weir, Matthew A.Bathini, LavanyaClemens, Kristin K.Perkovic, VladoSood, Manish M.McArthur, EricSontrop, Jessica M.Kim, Richard B.Garg, Amit X.2020-11-25T13:28:55-08:00doi:10.2215/CJN.08310520hwp:resource-id:clinjasn;15/12/1728American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysitagliptin, chronic kidney disease, dosage, toxicity, heart failureOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20202020-12-07December 07, 202010.2215/CJN.083105201555-90411555-905X2020-11-25T13:28:55-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles151217281739
- Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated Glomerulonephritis10.2215/CJN.07210520Tue, 17 Nov 2020 12:26:04 GMT-08:00Urinary Soluble CD163 and Disease Activity in Biopsy-Proven ANCA-Associated GlomerulonephritisAendekerk, Joop P.Timmermans, Sjoerd A.M.E.G.Busch, Matthias H.Potjewijd, JudithHeeringa, PeterDamoiseaux, Jan G.M.C.Reutelingsperger, Chris P.van Paassen, Pieter,Christiaans, M.Fung, T.Gelens, M.Kooman, J.Leunissen, K.Litjens, E.van der Sande, F.Duijnhoven, E.Boorsma, S.Huitema, J.Wirtz, J.de Heer, F.Krekels, M.Stifft, F.Verseput, G.ter Braak, N.Frenken, L.Gaertner, S.2020-11-17T12:26:04-08:00doi:10.2215/CJN.07210520hwp:resource-id:clinjasn;15/12/1740American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, glomerulonephritis, vasculitis, kidney biopsy, macrophages, Acute kidney injury, kidney pathology, BiopsyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-12-07December 07, 202010.2215/CJN.072105201555-90411555-905X2020-11-17T12:26:04-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles151217401748
- Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy10.2215/CJN.02500220Mon, 30 Nov 2020 05:37:33 GMT-08:00Multi-Autoantibody Signature and Clinical Outcome in Membranous NephropathyGhiggeri, Gian MarcoSeitz-Polski, BarbaraJustino, JoanaZaghrini, ChristellePayré, ChristineBrglez, VesnaDolla, GuillaumeSinico, AlbertoScolari, FrancescoVaglio, AugustoPrunotto, MarcoCandiano, GiovanniRadice, AntonellaBruschi, MaurizioLambeau, Gérard,,Ghiggeri, Gian MarcoRadice, AntonellaSinico, AlbertoScolari, FrancescoGesualdo, LoretoMoroni, GabriellaMagistroni, RiccardoSantoro, DomenicoPani, AntonelloVaglio, AugustoAllegri, LandinoPisani, IsabellaGranata, AntonioGrandagliano, GiuseppeRolla, DavieBoscutti, GiulianoBianco, Lucia MardinBruschi, MaurizioRavani, PietroBodria, MonicaCandiano, Giovanni2020-11-30T05:37:33-08:00doi:10.2215/CJN.02500220hwp:resource-id:clinjasn;15/12/1762American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, glomerulonephritis, membranous nephropathy, autoantibodiesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-12-07December 07, 202010.2215/CJN.025002201555-90411555-905X2020-11-30T05:37:33-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles151217621776
- Depression Screening Tools for Patients with Kidney Failure10.2215/CJN.05540420Tue, 17 Nov 2020 12:26:05 GMT-08:00Depression Screening Tools for Patients with Kidney FailureKondo, KarliAntick, Jennifer R.Ayers, Chelsea K.Kansagara, DevanChopra, Pavan2020-11-17T12:26:05-08:00doi:10.2215/CJN.05540420hwp:resource-id:clinjasn;15/12/1785American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepression, ESRD, end stage kidney disease, screening, assessment tool, systematic reviewOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-12-07December 07, 202010.2215/CJN.055404201555-90411555-905X2020-11-17T12:26:05-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles15121212178516921702179516931704
- Screening for Depression in People with Kidney Failure10.2215/CJN.16381020Tue, 17 Nov 2020 12:26:04 GMT-08:00Screening for Depression in People with Kidney FailureGregg, L. ParkerHedayati, S. Susan2020-11-17T12:26:04-08:00doi:10.2215/CJN.16381020hwp:resource-id:clinjasn;15/12/1702American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyscreening, depression, CKD, ESRD, dialysisEditorialsEditorialseditorial20202020-12-07December 07, 202010.2215/CJN.163810201555-90411555-905X2020-11-17T12:26:04-08:002020-12-07Clinical Journal of the American Society of NephrologyEditorials15121212170216921785170416931795
- ACOs and Bending the Cost Curve for Health Care Spending for People with Kidney Failure10.2215/CJN.16521020Tue, 24 Nov 2020 08:11:46 GMT-08:00ACOs and Bending the Cost Curve for Health Care Spending for People with Kidney FailureAwan, Ahmed A.Erickson, Kevin F.2020-11-24T08:11:46-08:00doi:10.2215/CJN.16521020hwp:resource-id:clinjasn;15/12/1699American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyeconomic analysis, health expenditures, kidney failureEditorialsEditorialseditorial20202020-12-07December 07, 202010.2215/CJN.165210201555-90411555-905X2020-11-24T08:11:46-08:002020-12-07Clinical Journal of the American Society of NephrologyEditorials1512121699177717011784
- Infection-Related Acute Care Events among Patients with Glomerular Disease10.2215/CJN.05900420Tue, 20 Oct 2020 11:06:04 GMT-07:00Infection-Related Acute Care Events among Patients with Glomerular DiseaseGlenn, Dorey A.Henderson, Candace D.O’Shaughnessy, MichelleHu, YichunBomback, AndrewGibson, KeishaGreenbaum, Larry A.Zee, JarcyMariani, LauraFalk, RonaldHogan, SusanMottl, Amy,2020-10-20T11:06:04-07:00doi:10.2215/CJN.05900420hwp:resource-id:clinjasn;15/12/1749American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinfection, hospitalization, glomerular disease, nephrotic syndrome, kidney disease, immunosuppression, pediatric nephrology, acute care eventsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-12-07December 07, 202010.2215/CJN.059004201555-90411555-905X2020-10-20T11:06:04-07:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1516123317494564561761457457
- Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients10.2215/CJN.02560220Tue, 10 Nov 2020 06:07:35 GMT-08:00Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant RecipientsLetellier, ThibaultLeborgne, FlorentKerleau, ClarisseGaultier, AurélieDantal, JacquesVille, Simon,,Blancho, GillesBranchereau, JulienCantarovich, DiegoChapelet, AgnèsDeltombe, ClémentFakhouri, FadiFigueres, LucileGarandeau, ClaireGiral, MagaliGourraud-Vercel, CarolineHourmant, MaryvonneJacquemont, LolaLe Bot, SabineMeurette, Aurélie2020-11-10T06:07:35-08:00doi:10.2215/CJN.02560220hwp:resource-id:clinjasn;15/12/1804American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, diuretics, transplantation, kidney transplantation, skin cancer, squamous cell carcinoma, thiazide diuretics, HydrochlorothiazideOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-12-07December 07, 202010.2215/CJN.025602201555-90411555-905X2020-11-10T06:07:35-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles151218041813
- Correction10.2215/CJN.16691020Mon, 09 Nov 2020 11:46:46 GMT-08:00CorrectionAmerican Society of Nephrology2020-11-09T11:46:46-08:00doi:10.2215/CJN.16691020hwp:resource-id:clinjasn;15/12/1817American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCorrection, erratumErratumErratumcorrection20202020-12-07December 07, 202010.2215/CJN.166910201555-90411555-905X2020-11-09T11:46:46-08:002020-12-07Clinical Journal of the American Society of NephrologyErratum151218171817
- Metabolic AlkalosisMetabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s. Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.10.2215/CJN.16041219Thu, 25 Jun 2020 10:36:32 GMT-07:00Metabolic AlkalosisMetabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s. Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.Emmett, Michael2020-06-25T10:36:32-07:00doi:10.2215/CJN.16041219hwp:resource-id:clinjasn;15/12/1848American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyelectrolytes, alkalosis, musculoskeletal abnormalities, bicarbonatesReviewsReviewsreview-article20202020-12-07December 07, 202010.2215/CJN.160412191555-90411555-905X2020-06-25T10:36:32-07:002020-12-07Clinical Journal of the American Society of NephrologyReviews151218481856
- AKI!Now Initiative: Recommendations for Awareness, Recognition, and Management of AKIThe American Society of Nephrology has established a new initiative, AKI!Now, with the goal of promoting excellence in the prevention and treatment of AKI by building a foundational program that transforms education and delivery of AKI care, aiming to reduce morbidity and associated mortality and to improve long-term outcomes. In this article, we describe our current efforts to improve early recognition and management involving inclusive interdisciplinary collaboration between providers, patients, and their families; discuss the ongoing need to change some of our current AKI paradigms and diagnostic methods; and provide specific recommendations to improve AKI recognition and care. In the hospital and the community, AKI is a common and increasingly frequent condition that generates risks of adverse events and high costs. Unfortunately, patients with AKI may frequently have received less than optimal quality of care. New classifications have facilitated understanding of AKI incidence and its impact on outcomes, but they are not always well aligned with AKI pathophysiology. Despite ongoing research efforts, treatments to promote or hasten kidney recovery remain ineffective. To avoid progression, the current approach to AKI emphasizes the promotion of early recognition and timely response. However, a lack of awareness of the importance of early recognition and treatment among health care team members and the heterogeneity of approaches within the health care teams assessing the patient remains a major challenge. Early identification is further complicated by differences in settings where AKI occurs (the community or the hospital), and by differences in patient populations and cultures between the intensive care unit and ward environments. To address these obstacles, we discuss the need to improve education at all levels of care and to generate specific guidance on AKI evaluation and management, including the development of a widely applicable education and an AKI management toolkit, engaging hospital administrators to incorporate AKI as a quality initiative, and raising awareness of AKI as a complication of other disease processes.10.2215/CJN.15611219Tue, 21 Apr 2020 04:51:19 GMT-07:00AKI!Now Initiative: Recommendations for Awareness, Recognition, and Management of AKIThe American Society of Nephrology has established a new initiative, AKI!Now, with the goal of promoting excellence in the prevention and treatment of AKI by building a foundational program that transforms education and delivery of AKI care, aiming to reduce morbidity and associated mortality and to improve long-term outcomes. In this article, we describe our current efforts to improve early recognition and management involving inclusive interdisciplinary collaboration between providers, patients, and their families; discuss the ongoing need to change some of our current AKI paradigms and diagnostic methods; and provide specific recommendations to improve AKI recognition and care. In the hospital and the community, AKI is a common and increasingly frequent condition that generates risks of adverse events and high costs. Unfortunately, patients with AKI may frequently have received less than optimal quality of care. New classifications have facilitated understanding of AKI incidence and its impact on outcomes, but they are not always well aligned with AKI pathophysiology. Despite ongoing research efforts, treatments to promote or hasten kidney recovery remain ineffective. To avoid progression, the current approach to AKI emphasizes the promotion of early recognition and timely response. However, a lack of awareness of the importance of early recognition and treatment among health care team members and the heterogeneity of approaches within the health care teams assessing the patient remains a major challenge. Early identification is further complicated by differences in settings where AKI occurs (the community or the hospital), and by differences in patient populations and cultures between the intensive care unit and ward environments. To address these obstacles, we discuss the need to improve education at all levels of care and to generate specific guidance on AKI evaluation and management, including the development of a widely applicable education and an AKI management toolkit, engaging hospital administrators to incorporate AKI as a quality initiative, and raising awareness of AKI as a complication of other disease processes.Liu, Kathleen D.Goldstein, Stuart L.Vijayan, AnithaParikh, Chirag R.Kashani, KianoushOkusa, Mark D.Agarwal, AnupamCerdá, Jorge,2020-04-21T04:51:19-07:00doi:10.2215/CJN.15611219hwp:resource-id:clinjasn;15/12/1838American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, critical care nephrology, AKI recognition, AKI awareness, AKI biomarkers, artificial intelligence, electronic alerts, AKI multidisciplinary management, AKI urinalysis, AKI pathology, incidence, goals, morbidity, kidney, hospital administrators, patient care team, quality of health care, intensive care units, longitudinal studiesReviewsReviewsresearch-article20202020-12-07December 07, 202010.2215/CJN.156112191555-90411555-905X2020-04-21T04:51:19-07:002020-12-07Clinical Journal of the American Society of NephrologyReviews151218381847
- Racial Disparities in the Arteriovenous Fistula Care Continuum in Hemodialysis Patients10.2215/CJN.03600320Tue, 20 Oct 2020 11:06:03 GMT-07:00Racial Disparities in the Arteriovenous Fistula Care Continuum in Hemodialysis PatientsQian, JoyceLee, TimmyThamer, MaeZhang, YiCrews, Deidra C.Allon, Michael2020-10-20T11:06:03-07:00doi:10.2215/CJN.03600320hwp:resource-id:clinjasn;15/12/1796American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, arteriovenous access, dialysis access, hemodialysis access, disparityOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-12-07December 07, 202010.2215/CJN.036003201555-90411555-905X2020-10-20T11:06:03-07:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles151217961803
- Genetic Disorders of the Glomerular Filtration BarrierThe glomerular filtration barrier is a highly specialized capillary wall comprising fenestrated endothelial cells, podocytes, and an intervening basement membrane. In glomerular disease, this barrier loses functional integrity, allowing the passage of macromolecules and cells, and there are associated changes in both cell morphology and the extracellular matrix. Over the past 3 decades, there has been a transformation in our understanding about glomerular disease, fueled by genetic discovery, and this is leading to exciting advances in our knowledge about glomerular biology and pathophysiology. In current clinical practice, a genetic diagnosis already has important implications for management, ranging from estimating the risk of disease recurrence post-transplant to the life-changing advances in the treatment of atypical hemolytic uremic syndrome. Improving our understanding about the mechanistic basis of glomerular disease is required for more effective and personalized therapy options. In this review, we describe genotype and phenotype correlations for genetic disorders of the glomerular filtration barrier, with a particular emphasis on how these gene defects cluster by both their ontology and patterns of glomerular pathology.10.2215/CJN.11440919Mon, 23 Mar 2020 05:27:10 GMT-07:00Genetic Disorders of the Glomerular Filtration BarrierThe glomerular filtration barrier is a highly specialized capillary wall comprising fenestrated endothelial cells, podocytes, and an intervening basement membrane. In glomerular disease, this barrier loses functional integrity, allowing the passage of macromolecules and cells, and there are associated changes in both cell morphology and the extracellular matrix. Over the past 3 decades, there has been a transformation in our understanding about glomerular disease, fueled by genetic discovery, and this is leading to exciting advances in our knowledge about glomerular biology and pathophysiology. In current clinical practice, a genetic diagnosis already has important implications for management, ranging from estimating the risk of disease recurrence post-transplant to the life-changing advances in the treatment of atypical hemolytic uremic syndrome. Improving our understanding about the mechanistic basis of glomerular disease is required for more effective and personalized therapy options. In this review, we describe genotype and phenotype correlations for genetic disorders of the glomerular filtration barrier, with a particular emphasis on how these gene defects cluster by both their ontology and patterns of glomerular pathology.Li, Anna S.Ingham, Jack F.Lennon, Rachel2020-03-23T05:27:10-07:00doi:10.2215/CJN.11440919hwp:resource-id:clinjasn;15/12/1818American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular filtration barrier, glomerular basement membrane, podocyte, endothelium, focal segmental glomerulosclerosis, Kidney Genomics SeriesGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-12-07December 07, 202010.2215/CJN.114409191555-90411555-905X2020-03-23T05:27:10-07:002020-12-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease151218181828
- Depression: A Side Effect of CKD10.2215/CJN.16411020Tue, 17 Nov 2020 12:26:04 GMT-08:00Depression: A Side Effect of CKDJones, Jennifer2020-11-17T12:26:04-08:00doi:10.2215/CJN.16411020hwp:resource-id:clinjasn;15/12/1692American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepression, chronic kidney disease, mortality risk, kidney transplantation, mental health, pre-existing conditions, screening, kidney failure, assessment tool, dialysisPatient VoicesPatient Voiceseditorial20202020-12-07December 07, 202010.2215/CJN.164110201555-90411555-905X2020-11-17T12:26:04-08:002020-12-07Clinical Journal of the American Society of NephrologyPatient Voices15121212169217021785169317041795
- Peritoneal Dialysis for Acute Kidney Injury during the COVID-19 Pandemic10.2215/CJN.09240620Fri, 14 Aug 2020 05:51:02 GMT-07:00Peritoneal Dialysis for Acute Kidney Injury during the COVID-19 PandemicShimonov, DaniilSrivatana, Vesh2020-08-14T05:51:02-07:00doi:10.2215/CJN.09240620hwp:resource-id:clinjasn;15/12/1829American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, acute kidney injury, COVID-19Kidney Case Conferences: How I TreatKidney Case Conferences: How I Treatresearch-article20202020-12-07December 07, 202010.2215/CJN.092406201555-90411555-905X2020-08-14T05:51:02-07:002020-12-07Clinical Journal of the American Society of NephrologyKidney Case Conferences: How I Treat151218291831
- Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN)10.2215/CJN.06870520Wed, 25 Nov 2020 01:28:54 GMT-08:00Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN)Ito, SadayoshiKashihara, NaokiShikata, KenichiNangaku, MasaomiWada, TakashiOkuda, YasuyukiSawanobori, Tomoko2020-11-25T13:28:54-08:00doi:10.2215/CJN.06870520hwp:resource-id:clinjasn;15/12/1715American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyesaxerenone, diabetes mellitus, microalbuminuriaOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20202020-12-07December 07, 202010.2215/CJN.068705201555-90411555-905X2020-11-25T13:28:54-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1512121715169617271698
- Mineralocorticoid Receptor Antagonists for Diabetic Kidney Disease10.2215/CJN.16201020Wed, 25 Nov 2020 01:28:54 GMT-08:00Mineralocorticoid Receptor Antagonists for Diabetic Kidney DiseaseRossing, Peter2020-11-25T13:28:54-08:00doi:10.2215/CJN.16201020hwp:resource-id:clinjasn;15/12/1696American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, chronic kidney disease, aldosterone, microalbuminuria, mineralocorticoid receptor antagonistsEditorialsEditorialseditorial20202020-12-07December 07, 202010.2215/CJN.162010201555-90411555-905X2020-11-25T13:28:54-08:002020-12-07Clinical Journal of the American Society of NephrologyEditorials1512121696171516981727
- Are SGLT2 Inhibitors Safe and Effective in Advanced Diabetic Kidney Disease?10.2215/CJN.16351020Thu, 19 Nov 2020 06:44:08 GMT-08:00Are SGLT2 Inhibitors Safe and Effective in Advanced Diabetic Kidney Disease?Zoungas, SophiaPolkinghorne, Kevan R.2020-11-19T06:44:08-08:00doi:10.2215/CJN.16351020hwp:resource-id:clinjasn;15/12/1694American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, kidney disease, sodium-glucose transporter 2 inhibitorsEditorialsEditorialseditorial20202020-12-07December 07, 202010.2215/CJN.163510201555-90411555-905X2020-11-19T06:44:08-08:002020-12-07Clinical Journal of the American Society of NephrologyEditorials1512121694170516951714
- The Role of Incremental Peritoneal Dialysis in the Era of the Advancing American Kidney Health Initiative10.2215/CJN.03960320Fri, 24 Jul 2020 07:39:49 GMT-07:00The Role of Incremental Peritoneal Dialysis in the Era of the Advancing American Kidney Health InitiativeReddy, Yuvaram N.V.Mendu, Mallika L.2020-07-24T07:39:49-07:00doi:10.2215/CJN.03960320hwp:resource-id:clinjasn;15/12/1835American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, economic impact, end stage kidney disease, end-stage renal disease, peritoneal dialysis, peritoneal membrane, kidneyPerspectivesPerspectivesresearch-article20202020-12-07December 07, 202010.2215/CJN.039603201555-90411555-905X2020-07-24T07:39:49-07:002020-12-07Clinical Journal of the American Society of NephrologyPerspectives151218351837
- Stepping into the Void10.2215/CJN.04660420Thu, 09 Jul 2020 07:55:51 GMT-07:00Stepping into the VoidAgarwal, AnupamIbrahim, Tod2020-07-09T07:55:51-07:00doi:10.2215/CJN.04660420hwp:resource-id:clinjasn;15/12/1832American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNephrologists physician compensation, kidney organizationsPerspectivesPerspectivesresearch-article20202020-12-07December 07, 202010.2215/CJN.046604201555-90411555-905X2020-07-09T07:55:51-07:002020-12-07Clinical Journal of the American Society of NephrologyPerspectives151271832105318341055
- Advancing American Kidney Health (AAKH): Catalyst for Investment in Kidney Diseases Clinical Trials and Precision Medicine10.2215/CJN.03660320Wed, 05 Aug 2020 10:14:28 GMT-07:00Advancing American Kidney Health (AAKH): Catalyst for Investment in Kidney Diseases Clinical Trials and Precision MedicineFowler, Kevin John2020-08-05T10:14:28-07:00doi:10.2215/CJN.03660320hwp:resource-id:clinjasn;15/12/1689American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyACE inhibitors, African Americans, African American Study of Kidney Disease and Hypertension, clinical trials, precision medicine, upstream interventions, in-center hemodialysisPatient VoicesPatient Voicesresearch-article20202020-12-07December 07, 202010.2215/CJN.036603201555-90411555-905X2020-08-05T10:14:28-07:002020-12-07Clinical Journal of the American Society of NephrologyPatient Voices151216891691
- Accountable Care Organizations and Spending for Patients Undergoing Long-Term Dialysis10.2215/CJN.02150220Tue, 24 Nov 2020 08:11:47 GMT-08:00Accountable Care Organizations and Spending for Patients Undergoing Long-Term DialysisBakre, ShivaniHollingsworth, John M.Yan, Phyllis L.Lawton, Emily J.Hirth, Richard A.Shahinian, Vahakn B.2020-11-24T08:11:47-08:00doi:10.2215/CJN.02150220hwp:resource-id:clinjasn;15/12/1777American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylong-term dialysis, Medicare, Accountable Care OrganizationsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-12-07December 07, 202010.2215/CJN.021502201555-90411555-905X2020-11-24T08:11:47-08:002020-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1512121777169917841701
- Prevalence of COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening10.1681/ASN.2020081193Tue, 29 Sep 2020 11:07:02 GMT-07:00Prevalence of COVID-19 Infection in Hemodialysis Patients Detected Using Serologic ScreeningRodríguez-Espinosa, DianaBroseta, José JesúsCuadrado, ElenaMaduell, Francisco2020-09-29T11:07:02-07:00doi:10.1681/ASN.2020081193hwp:resource-id:jnephrol;31/12/2967American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologySARS-CoV-2, hemodialysis, prevalence, COVID-19Letters to the EditorLetters to the Editorletter20202020-12-01December 202010.1681/ASN.20200811931046-66731533-34502020-09-29T11:07:02-07:002020-12Journal of the American Society of NephrologyLetters to the Editor3112122967296829672968
- Detection of SARS-CoV-2 Antibodies in Kidney Transplant Recipients10.1681/ASN.2020081152Thu, 29 Oct 2020 09:51:14 GMT-07:00Detection of SARS-CoV-2 Antibodies in Kidney Transplant RecipientsPrendecki, MariaClarke, CandiceGleeson, SarahGreathead, LouiseSantos, EvaMcLean, AdamRandell, PaulMoore, Luke S.P.Mughal, NabeelaGuckian, MaryKelleher, PeterMcadoo, Stephen P.Willicombe, Michelle2020-10-29T09:51:14-07:00doi:10.1681/ASN.2020081152hwp:resource-id:jnephrol;31/12/2753American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunosuppression, immunology, virology, kidney transplantation, COVID-19Research LetterResearch Letterother20202020-12-01December 202010.1681/ASN.20200811521046-66731533-34502020-10-29T09:51:14-07:002020-12Journal of the American Society of NephrologyResearch Letter311227532756
- Does SARS-CoV-2 Infect the Kidney?10.1681/ASN.2020081229Tue, 13 Oct 2020 06:52:13 GMT-07:00Does SARS-CoV-2 Infect the Kidney?Khan, ShazaChen, LiheYang, Chin-RangRaghuram, ViswanathanKhundmiri, Syed J.Knepper, Mark A.2020-10-13T06:52:13-07:00doi:10.1681/ASN.2020081229hwp:resource-id:jnephrol;31/12/2746American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, COVID-19, proximal tubule, podocyte, ACE2Up Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20202020-12-01December 202010.1681/ASN.20200812291046-66731533-34502020-10-13T06:52:13-07:002020-12Journal of the American Society of NephrologyUp Front Matters311227462748
- Major Variation across Local Transplant Centers in Probability of Kidney Transplant for Wait-Listed Patients10.1681/ASN.2020030335Fri, 09 Oct 2020 11:47:02 GMT-07:00Major Variation across Local Transplant Centers in Probability of Kidney Transplant for Wait-Listed PatientsKing, Kristen L.Husain, S. AliSchold, Jesse D.Patzer, Rachel E.Reese, Peter P.Jin, ZhezhenRatner, Lloyd E.Cohen, David J.Pastan, Stephen O.Mohan, Sumit2020-10-09T11:47:02-07:00doi:10.1681/ASN.2020030335hwp:resource-id:jnephrol;31/12/2900American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, organ allocation, patient preferences, shared decision-making, health policyClinical EpidemiologyClinical Epidemiologyresearch-article20202020-12-01December 202010.1681/ASN.20200303351046-66731533-34502020-10-09T11:47:02-07:002020-12Journal of the American Society of NephrologyClinical Epidemiology311229002911
- Long-Term Living Kidney Donor Risk: A Web-Based Calculator10.1681/ASN.2020081238Fri, 30 Oct 2020 11:51:04 GMT-07:00Long-Term Living Kidney Donor Risk: A Web-Based CalculatorPalzer, Elise F.Vempati, ShrutiHelgeson, Erika S.Matas, Arthur J.2020-10-30T11:51:04-07:00doi:10.1681/ASN.2020081238hwp:resource-id:jnephrol;31/12/2968American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney donation, mortality risk, risk factorsLetters to the EditorLetters to the Editorletter20202020-12-01December 202010.1681/ASN.20200812381046-66731533-34502020-10-30T11:51:04-07:002020-12Journal of the American Society of NephrologyLetters to the Editor311299296828852749296928932755
- The Role of Telenephrology in the Management of CKD10.34067/KID.0000802019Mon, 21 Sep 2020 01:25:17 GMT-07:00The Role of Telenephrology in the Management of CKDBelcher, Justin M.2020-09-21T13:25:17-07:00doi:10.34067/KID.0000802019hwp:resource-id:kidney360;1/11/1310American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, chronic renal insufficiency, telehealth, telemedicine, telenephrologyPerspectivesPerspectivesresearch-article20202020-11-2510.34067/KID.00008020192641-76502020-09-21T13:25:17-07:002020-11-25Kidney360Perspectives11113101315
- Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins and Inflammation in CKD10.34067/KID.0003942020Fri, 04 Sep 2020 01:26:42 GMT-07:00Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins and Inflammation in CKDKimber, CassandraZhang, ShiqinJohnson, CassandraWest, Raymond E.Prokopienko, Alexander J.Mahnken, Jonathan D.Yu, Alan S.Hoofnagle, Andrew N.Ir, DianaRobertson, Charles E.Miyazaki, MakotoChonchol, MichelJovanovich, AnnaKestenbaum, BryanFrank, Daniel N.Nolin, Thomas D.Stubbs, Jason R.2020-09-04T13:26:42-07:00doi:10.34067/KID.0003942020hwp:resource-id:kidney360;1/11/1206American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, cardiovascular disease, chronic renal insufficiency, clinical trial, gastrointestinal microbiome, gut microbiome, indoxyl sulfate, inflammation, p-cresol sulfate, rifaximin, TMAO, uremiaOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-11-2510.34067/KID.00039420202641-76502020-09-04T13:26:42-07:002020-11-25Kidney360Original Investigations11112061216
- Characteristics and Effectiveness of Dedicated Care Programs for Patients Starting Dialysis: A Systematic Review10.34067/KID.0004052020Tue, 08 Sep 2020 01:30:40 GMT-07:00Characteristics and Effectiveness of Dedicated Care Programs for Patients Starting Dialysis: A Systematic ReviewAttalla, MirnaFriedman, ZoeMcKeown, SandraHarel, ZivHingwala, JayMolnar, Amber O.Norman, PatrickSilver, Samuel A.2020-09-08T13:30:40-07:00doi:10.34067/KID.0004052020hwp:resource-id:kidney360;1/11/1244American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, chronic dialysis, chronic hemodialysis, chronic kidney failure, end stage kidney disease, mortality, vascular accessOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-11-2510.34067/KID.00040520202641-76502020-09-08T13:30:40-07:002020-11-25Kidney360Original Investigations11112441253
- Global Perspectives in Dialysis: Singapore10.34067/KID.0004382020Fri, 18 Sep 2020 11:25:51 GMT-07:00Global Perspectives in Dialysis: SingaporeLeo, Christopher Cheang HanChan, Gek Cher2020-09-18T11:25:51-07:00doi:10.34067/KID.0004382020hwp:resource-id:kidney360;1/11/1306American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, dialysis, global, hemodialysis, peritoneal dialysis, SingaporeGlobal PerspectivesGlobal Perspectivesresearch-article20202020-11-2510.34067/KID.00043820202641-76502020-09-18T11:25:51-07:002020-11-25Kidney360Global Perspectives11113061309
- AKI and Hypercalcemia in a Patient with Weakness and Fatigue10.34067/KID.0002282020Wed, 25 Nov 2020 05:30:27 GMT-08:00AKI and Hypercalcemia in a Patient with Weakness and FatigueRahimi, CheyenneStroemel, MathiasAndeen, Nicole K.2020-11-25T05:30:27-08:00doi:10.34067/KID.0002282020hwp:resource-id:kidney360;1/11/1328American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, acute kidney injury, fatigue, frailty, hypercalcemia, lysozyme, sarcoidosis, tubulointerstitialClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-11-2510.34067/KID.00022820202641-76502020-11-25T05:30:27-08:002020-11-25Kidney360Clinical Images in Nephrology and Dialysis11113281329
- Interhospital Transfer and Outcomes in Patients with AKI: A Population-Based Cohort Study10.34067/KID.0003612020Thu, 17 Sep 2020 11:11:58 GMT-07:00Interhospital Transfer and Outcomes in Patients with AKI: A Population-Based Cohort StudyKitchlu, AbhijatShapiro, JoshuaSlater, JustinBrimble, K. ScottDirk, Jade S.Jeyakumar, NivethikaDixon, Stephanie N.Garg, Amit X.Harel, ZivHarvey, AndreaKim, S. JosephSilver, Samuel A.Wald, Ron2020-09-17T11:11:58-07:00doi:10.34067/KID.0003612020hwp:resource-id:kidney360;1/11/1195American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, cohort studies, critical illness, outcomes, patient transfer, renal replacement therapyOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-11-2510.34067/KID.00036120202641-76502020-09-17T11:11:58-07:002020-11-25Kidney360Original Investigations11111951205
- Long-Term Beneficial Effects of Tonsillectomy on Patients with Immunoglobulin A Nephropathy10.34067/KID.0003932020Wed, 02 Sep 2020 09:32:53 GMT-07:00Long-Term Beneficial Effects of Tonsillectomy on Patients with Immunoglobulin A NephropathyMoriyama, TakahitoKarasawa, KazunoriMiyabe, YoeiAkiyama, KenichiIwabuchi, YukoOgura, ShotaTakabe, TomoSugiura, NaokoSeki, MomokoHanafusa, NorioUchida, KeikoNitta, Kosaku2020-09-02T09:32:53-07:00doi:10.34067/KID.0003932020hwp:resource-id:kidney360;1/11/1270American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, IgA glomerulonephritis, IgA nephropathy, prognosis, tonsillectomyOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-11-2510.34067/KID.00039320202641-76502020-09-02T09:32:53-07:002020-11-25Kidney360Original Investigations11112701283
- Renal Infarction in a Patient Found to Have a Dysproteinemia10.34067/KID.0003082020Wed, 25 Nov 2020 05:30:27 GMT-08:00Renal Infarction in a Patient Found to Have a DysproteinemiaPatel, JayeshHolman, Carol J.Fraer, Mony2020-11-25T05:30:27-08:00doi:10.34067/KID.0003082020hwp:resource-id:kidney360;1/11/1332American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, disseminated intravascular coagulation, dysproteinemia, multiple myeloma, renal infarction, rouleaux, schistocytesClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-11-2510.34067/KID.00030820202641-76502020-11-25T05:30:27-08:002020-11-25Kidney360Clinical Images in Nephrology and Dialysis11113321333
- Apparent AKI in a Patient with Ascites Following Laparoscopic Hysterectomy10.34067/KID.0002852020Wed, 25 Nov 2020 05:30:27 GMT-08:00Apparent AKI in a Patient with Ascites Following Laparoscopic HysterectomyCervantes, Carmen ElenaMenez, StevenHanouneh, Mohamad2020-11-25T05:30:27-08:00doi:10.34067/KID.0002852020hwp:resource-id:kidney360;1/11/1330American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, ascites, bladder rupture, hysterectomy, laparoscopy, pseudo-azotemiaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-11-2510.34067/KID.00028520202641-76502020-11-25T05:30:27-08:002020-11-25Kidney360Clinical Images in Nephrology and Dialysis11113301331
- A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC)10.34067/KID.0001522020Thu, 03 Sep 2020 01:28:00 GMT-07:00A Prospective, Double-Blind, Randomized, Placebo-Controlled, Crossover Study Using an Orally Administered Oxalate Decarboxylase (OxDC)Quintero, EmilyBird, Victoria YvonneLiu, HowardStevens, GaryRyan, Alan S.Buzzerd, SabrinaKlimberg, Ira W.2020-09-03T13:28:00-07:00doi:10.34067/KID.0001522020hwp:resource-id:kidney360;1/11/1284American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360nephrolithiasis, Carboxy-Lyases, chronic kidney disease, cross-over studies, double-blind method, hyperoxaluria, kidney stone, nephrolithiasis, oxalate, oxalate decarboxylase, oxalate nephrophathy, oxalate-rich foods, prospective studies, urinary oxalate, urinary oxalate reductionOriginal InvestigationsNephrolithiasisOriginal InvestigationsNephrolithiasisresearch-article20202020-11-2510.34067/KID.00015220202641-76502020-09-03T13:28:00-07:002020-11-25Kidney360Original Investigations11112841290
- Predictors of Arteriovenous Fistula Failure: A Post Hoc Analysis of the FAVOURED Study10.34067/KID.0002732020Mon, 14 Sep 2020 09:23:25 GMT-07:00Predictors of Arteriovenous Fistula Failure: A Post Hoc Analysis of the FAVOURED StudySee, Yong PeyCho, YeoungjeePascoe, Elaine M.Cass, AlanIrish, AshleyVoss, DavidPolkinghorne, Kevan R.Hooi, Lai SeongOng, Loke-MengPaul-Brent, Peta-AnneKerr, Peter G.Mori, Trevor A.Hawley, Carmel M.Johnson, David W.Viecelli, Andrea K.2020-09-14T09:23:25-07:00doi:10.34067/KID.0002732020hwp:resource-id:kidney360;1/11/1259American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, arteriovenous access, arteriovenous fistula, hemodialysis, hemodialysis access, vascular accessOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-11-2510.34067/KID.00027320202641-76502020-09-14T09:23:25-07:002020-11-25Kidney360Original Investigations11112591269
- Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming Barriers10.34067/KID.0004592020Thu, 03 Sep 2020 08:30:09 GMT-07:00Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming BarriersLentine, Krista L.Peipert, John D.Alhamad, TarekCaliskan, YasarConcepcion, Beatrice P.Forbes, RachelSchnitzler, MarkChang, Su-HsinCooper, MatthewBloom, Roy D.Mannon, Roslyn B.Axelrod, David A.2020-09-03T08:30:09-07:00doi:10.34067/KID.0004592020hwp:resource-id:kidney360;1/11/1291American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, direct acting antiviral therapy, donation, hepatitis C virus, infection, kidney transplantation, practices, surveys and questionnaires, tissue donorsOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-11-2510.34067/KID.00045920202641-76502020-09-03T08:30:09-07:002020-11-25Kidney360Original Investigations11112911299
- Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective from the Spanish Nephrology10.34067/KID.0002602020Fri, 11 Sep 2020 09:31:44 GMT-07:00Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective from the Spanish NephrologySánchez-Alvarez, EmilioMacía, Manuelde Sequera Ortiz, Patricia2020-09-11T09:31:44-07:00doi:10.34067/KID.0002602020hwp:resource-id:kidney360;1/11/1254American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, COVID-19, hemodialysis, pandemic, renal dialysis, SpainOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-11-2510.34067/KID.00026020202641-76502020-09-11T09:31:44-07:002020-11-25Kidney360Original Investigations11112541258
- Beware the Ides of March: A Fellow’s Perspective on Surviving the COVID-19 Pandemic10.34067/KID.0005442020Thu, 24 Sep 2020 01:29:45 GMT-07:00Beware the Ides of March: A Fellow’s Perspective on Surviving the COVID-19 PandemicHindi, JudyFuca, NicholasSanchez Russo, Luis2020-09-24T13:29:45-07:00doi:10.34067/KID.0005442020hwp:resource-id:kidney360;1/11/1316American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, COVID-19, pandemics, severe acute respiratory syndrome coronavirus 2PerspectivesPerspectivesresearch-article20202020-11-2510.34067/KID.00054420202641-76502020-09-24T13:29:45-07:002020-11-25Kidney360Perspectives11113161318
- The Characteristics, Dynamics, and the Risk of Death in COVID-19 Positive Dialysis Patients in London, UK10.34067/KID.0004502020Thu, 10 Sep 2020 08:21:38 GMT-07:00The Characteristics, Dynamics, and the Risk of Death in COVID-19 Positive Dialysis Patients in London, UKKular, DalvirChis Ster, IrinaSarnowski, AlexanderLioudaki, EiriniBraide-Azikiwe, Dandisonba C.B.Ford, Martin L.Makanjuola, DavidRankin, AlexandraCairns, HughPopoola, JoyceCole, NicholasPhanish, MysoreHull, RichardSwift, Pauline A.Banerjee, Debasish2020-09-10T08:21:38-07:00doi:10.34067/KID.0004502020hwp:resource-id:kidney360;1/11/1226American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, frailty, hemodialysis, London, mortality, mortality risk, peritoneal dialysis, United KingdomOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-11-2510.34067/KID.00045020202641-76502020-09-10T08:21:38-07:002020-11-25Kidney360Original Investigations11112261243
- Global Dialysis Perspective: Guatemala10.34067/KID.0004092020Thu, 17 Sep 2020 11:11:58 GMT-07:00Global Dialysis Perspective: GuatemalaGarcia, PabloSánchez-Polo, Vicente2020-09-17T11:11:58-07:00doi:10.34067/KID.0004092020hwp:resource-id:kidney360;1/11/1300American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, end-stage kidney disease, global health, global kidney care, Guatemala, Latin America, nephrologyGlobal PerspectivesGlobal Perspectivesresearch-article20202020-11-2510.34067/KID.00040920202641-76502020-09-17T11:11:58-07:002020-11-25Kidney360Global Perspectives11113001305
- mTOR Signaling in Kidney DiseasesThe mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, is crucial in regulating cell growth, metabolism, proliferation, and survival. Under physiologic conditions, mTOR signaling maintains podocyte and tubular cell homeostasis. In AKI, activation of mTOR signaling in tubular cells and interstitial fibroblasts promotes renal regeneration and repair. However, constitutive activation of mTOR signaling in kidneys results in the initiation and progression of glomerular hypertrophy, interstitial fibrosis, polycystic kidney disease, and renal cell carcinoma. Here, we summarize the recent studies about mTOR signaling in renal physiology and injury, and discuss the possibility of its use as a therapeutic target for kidney diseases.10.34067/KID.0003782020Thu, 03 Sep 2020 09:46:01 GMT-07:00mTOR Signaling in Kidney DiseasesThe mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, is crucial in regulating cell growth, metabolism, proliferation, and survival. Under physiologic conditions, mTOR signaling maintains podocyte and tubular cell homeostasis. In AKI, activation of mTOR signaling in tubular cells and interstitial fibroblasts promotes renal regeneration and repair. However, constitutive activation of mTOR signaling in kidneys results in the initiation and progression of glomerular hypertrophy, interstitial fibrosis, polycystic kidney disease, and renal cell carcinoma. Here, we summarize the recent studies about mTOR signaling in renal physiology and injury, and discuss the possibility of its use as a therapeutic target for kidney diseases.Gui, YuanDai, Chunsun2020-09-03T09:46:01-07:00doi:10.34067/KID.0003782020hwp:resource-id:kidney360;1/11/1319American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, glomerular hypertrophy, kidney fibrosis, mTOR, polycystic kidney disease, renal cell carcinoma, TOR serine-threonine kinases, Basic ScienceReview ArticleReview Articlereview-article20202020-11-2510.34067/KID.00037820202641-76502020-09-03T09:46:01-07:002020-11-25Kidney360Review Article11113191327
- Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: CON10.34067/KID.0005112020Wed, 23 Sep 2020 01:37:51 GMT-07:00Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: CONGuthrie, Bruce2020-09-23T13:37:51-07:00doi:10.34067/KID.0005112020hwp:resource-id:kidney360;1/11/1189American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, analgesia, chronic renal insufficiency, hypesthesia, non-steroidal anti-inflammatory agents, pain managementDebates in NephrologyDebates in Nephrologyresearch-article20202020-11-2510.34067/KID.00051120202641-76502020-09-23T13:37:51-07:002020-11-25Kidney360Debates in Nephrology11111891191
- Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: COMMENTARY10.34067/KID.0004652020Wed, 23 Sep 2020 01:37:51 GMT-07:00Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: COMMENTARYBaker, Megan L.Perazella, Mark A.2020-09-23T13:37:51-07:00doi:10.34067/KID.0004652020hwp:resource-id:kidney360;1/11/1192American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, analgesia, chronic kidney disease, chronic renal insufficiency, hyperkalemia, hypesthesia, nephrotoxicity, non-steroidal anti-inflammatory drugs, pain managementModerator CommentaryModerator Commentaryarticle-commentary20202020-11-2510.34067/KID.00046520202641-76502020-09-23T13:37:51-07:002020-11-25Kidney360Moderator Commentary11111921194
- Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: PRO10.34067/KID.0004582020Wed, 23 Sep 2020 01:37:51 GMT-07:00Can NSAIDs Be Used Safely for Analgesia in Patients with CKD?: PROBarreto, Erin F.Feely, Molly A.2020-09-23T13:37:51-07:00doi:10.34067/KID.0004582020hwp:resource-id:kidney360;1/11/1184American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360nephro-pharmacology, acute kidney injury, analgesia, nephrotoxicity, NSAID, opioids, pharmacodynamic, pharmacokineticDebates in NephrologyDebates in Nephrologyresearch-article20202020-11-2510.34067/KID.00045820202641-76502020-09-23T13:37:51-07:002020-11-25Kidney360Debates in Nephrology11111841188
- Histopathologic and Clinical Features in Patients with Diabetes and Kidney Disease10.34067/KID.0003962020Fri, 11 Sep 2020 07:13:38 GMT-07:00Histopathologic and Clinical Features in Patients with Diabetes and Kidney DiseaseSanghavi, Sarah F.Roark, TravisZelnick, Leila R.Najafian, BehzadAndeen, Nicole K.Alpers, Charles E.Pichler, RaimundAyers, Ernestde Boer, Ian H.2020-09-11T07:13:38-07:00doi:10.34067/KID.0003962020hwp:resource-id:kidney360;1/11/1217American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360diabetes and the kidney, diabetes mellitus, diabetic kidney disease, diabetic retinopathy, focal segmental glomerulosclerosis, histopathology, proteinuriaOriginal InvestigationsDiabetes and the KidneyOriginal InvestigationsDiabetes and the Kidneyresearch-article20202020-11-2510.34067/KID.00039620202641-76502020-09-11T07:13:38-07:002020-11-25Kidney360Original Investigations11112171225
- Moving the Science of Patient-Reported Outcome Measures Forward10.2215/CJN.14900920Thu, 22 Oct 2020 12:29:05 GMT-07:00Moving the Science of Patient-Reported Outcome Measures ForwardRamer, Sarah J.Scherer, Jennifer S.2020-10-22T12:29:05-07:00doi:10.2215/CJN.14900920hwp:resource-id:clinjasn;15/11/1546American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfatigue, hemodialysisEditorialsEditorialseditorial20202020-11-06November 06, 202010.2215/CJN.149009201555-90411555-905X2020-10-22T12:29:05-07:002020-11-06Clinical Journal of the American Society of NephrologyEditorials15111111154615391614154815401621
- Systematic Review and Meta-Analysis of Native Kidney Biopsy Complications10.2215/CJN.04710420Thu, 15 Oct 2020 06:51:39 GMT-07:00Systematic Review and Meta-Analysis of Native Kidney Biopsy ComplicationsPoggio, Emilio D.McClelland, Robyn L.Blank, Kristina N.Hansen, SpencerBansal, ShwetaBomback, Andrew S.Canetta, Pietro A.Khairallah, PascaleKiryluk, KrzysztofLecker, Stewart H.McMahon, Gearoid M.Palevsky, Paul M.Parikh, SamirRosas, Sylvia E.Tuttle, KatherineVazquez, Miguel A.Vijayan, AnithaRovin, Brad H.,2020-10-15T06:51:39-07:00doi:10.2215/CJN.04710420hwp:resource-id:clinjasn;15/11/1595American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, chronic kidney disease, acute renal failureOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20202020-11-06November 06, 202010.2215/CJN.047104201555-90411555-905X2020-10-15T06:51:39-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles15161111112159515411587293160215421594293
- Major Bleeding and Risk of Death after Percutaneous Native Kidney Biopsies10.2215/CJN.14721219Thu, 15 Oct 2020 06:51:39 GMT-07:00Major Bleeding and Risk of Death after Percutaneous Native Kidney BiopsiesHalimi, Jean-MichelGatault, PhilippeLonguet, HélèneBarbet, ChristelleBisson, ArnaudSautenet, BénédicteHerbert, JulienBuchler, MatthiasGrammatico-Guillon, LeslieFauchier, Laurent2020-10-15T06:51:39-07:00doi:10.2215/CJN.14721219hwp:resource-id:clinjasn;15/11/1587American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, bleeding, Epidemiology and outcomes, nationwide data, score, Diabetic Nephropathies, Thrombocytopenia, Frailty, Hemorrhage, Hematoma, Amyloidosis, Nephrectomy, Thrombotic Microangiopathies, Blood Transfusion, anemiaOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20202020-11-06November 06, 202010.2215/CJN.147212191555-90411555-905X2020-10-15T06:51:39-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles1516111111815871541159512611594154216021261
- How Safe Is a Native Kidney Biopsy?10.2215/CJN.14890920Thu, 15 Oct 2020 06:51:39 GMT-07:00How Safe Is a Native Kidney Biopsy?Koirala, AbbalJefferson, J. Ashley2020-10-15T06:51:39-07:00doi:10.2215/CJN.14890920hwp:resource-id:clinjasn;15/11/1541American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, blood transfusion, acute kidney injury, chronic kidney diseaseEditorialsEditorialseditorial20202020-11-06November 06, 202010.2215/CJN.148909201555-90411555-905X2020-10-15T06:51:39-07:002020-11-06Clinical Journal of the American Society of NephrologyEditorials15111111154115871595154215941602
- Trends in Use and In-Hospital Outcomes of Subcutaneous Implantable Cardioverter Defibrillators in Patients Undergoing Long-Term Dialysis10.2215/CJN.07920520Wed, 23 Sep 2020 07:43:00 GMT-07:00Trends in Use and In-Hospital Outcomes of Subcutaneous Implantable Cardioverter Defibrillators in Patients Undergoing Long-Term DialysisPun, Patrick H.Parzynski, Craig S.Friedman, Daniel J.Sanders, GillianCurtis, Jeptha P.Al-Khatib, Sana M.2020-09-23T07:43:00-07:00doi:10.2215/CJN.07920520hwp:resource-id:clinjasn;15/11/1622American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous access, cardiovascular, cardiovascular disease, dialysis, dialysis access, end stage kidney disease, epidemiology and outcomes, hospitals, defibrillators, implantableOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-11-06November 06, 202010.2215/CJN.079205201555-90411555-905X2020-09-23T07:43:00-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles151116221630
- Utilization of Deep Learning for Subphenotype Identification in Sepsis-Associated Acute Kidney Injury10.2215/CJN.09330819Thu, 08 Oct 2020 07:58:32 GMT-07:00Utilization of Deep Learning for Subphenotype Identification in Sepsis-Associated Acute Kidney InjuryChaudhary, KumardeepVaid, AkhilDuffy, ÁineParanjpe, IshanJaladanki, SurajParanjpe, ManishJohnson, KippGokhale, AvanteePattharanitima, PattharawinChauhan, KinsukO’Hagan, RossVan Vleck, TielmanCoca, Steven G.Cooper, RichardGlicksberg, BenjaminBottinger, Erwin P.Chan, LiliNadkarni, Girish N.2020-10-08T07:58:32-07:00doi:10.2215/CJN.09330819hwp:resource-id:clinjasn;15/11/1557American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, dialysis, mortality, AKI, deep learning, subtypes, acute kidney injuryOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20202020-11-06November 06, 202010.2215/CJN.093308191555-90411555-905X2020-10-08T07:58:32-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles1511111557154315651545
- Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD10.2215/CJN.02020220Tue, 06 Oct 2020 09:47:17 GMT-07:00Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKDChen, JingHamm, L. LeeBundy, Joshua D.Kumbala, Damodar R.Bodana, ShirishaChandra, SehgalChen, Chung-ShiuanStarcke, Charlton C.Guo, YajunSchaefer, Caroline M.Lustigova, EvaMahone, ErinVadalia, Aarti M.Livingston, TerraObst, KatherineHernandez, JesusBokhari, Syed RizwanKleinpeter, MyraAlper, Arnold B.Lukitsch, IvoHe, HuaNieman, David C.He, Jiang2020-10-06T09:47:17-07:00doi:10.2215/CJN.02020220hwp:resource-id:clinjasn;15/11/1566American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyendothelial dysfunction, chronic inflammation, oxidative stress, chronic kidney disease, sodium nitrite, isoquercetinOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-11-06November 06, 202010.2215/CJN.020202201555-90411555-905X2020-10-06T09:47:17-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles151115661575
- Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United States10.2215/CJN.04350420Mon, 12 Oct 2020 07:26:52 GMT-07:00Trends in Mineral Metabolism Treatment Strategies in Patients Receiving Hemodialysis in the United StatesHall, RasheedaPlatt, AlyssaWilson, JonathanEphraim, Patti L.Hwang, Angelina S.Chen, AngelWeiner, Daniel E.Boulware, L. EbonyPendergast, JaneScialla, Julia J.,2020-10-12T07:26:52-07:00doi:10.2215/CJN.04350420hwp:resource-id:clinjasn;15/11/1603American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycinacalcet, calcimimetic, vitamin D, pharmacoepidemiology, dialysis, phosphate binders, hemodialysis, mineral metabolismOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-11-06November 06, 202010.2215/CJN.043504201555-90411555-905X2020-10-12T07:26:52-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles151116031613
- Revisiting Filtration Fraction as an Index of the Risk of Hemofilter Clotting in Continuous Venovenous Hemofiltration10.2215/CJN.02410220Wed, 13 May 2020 07:48:48 GMT-07:00Revisiting Filtration Fraction as an Index of the Risk of Hemofilter Clotting in Continuous Venovenous HemofiltrationHatamizadeh, PartaTolwani, AshitaPalevsky, Paul2020-05-13T07:48:48-07:00doi:10.2215/CJN.02410220hwp:resource-id:clinjasn;15/11/1660American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfiltration fraction, extracorporeal circuit clotting, extracorporeal circuit malfunction, circuit clotting, continuous venovenous hemofiltration, continuous renal replacement therapy, critical care medicine, critical care nephrology, acute kidney injury, renal replacement therapy, ICU nephrology, blood coagulation, ultrafiltrationPerspectivesPerspectivesresearch-article20202020-11-06November 06, 202010.2215/CJN.024102201555-90411555-905X2020-05-13T07:48:48-07:002020-11-06Clinical Journal of the American Society of NephrologyPerspectives151116601662
- The Curious Story of Cerebral Salt Wasting10.2215/CJN.00070120Wed, 01 Jul 2020 08:26:23 GMT-07:00The Curious Story of Cerebral Salt WastingVerbalis, Joseph G.2020-07-01T08:26:23-07:00doi:10.2215/CJN.00070120hwp:resource-id:clinjasn;15/11/1666American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvasopressin, volume regulation, Inappropriate ADH Syndrome, hyponatremiaPerspectivesPerspectivesresearch-article20202020-11-06November 06, 202010.2215/CJN.000701201555-90411555-905X2020-07-01T08:26:23-07:002020-11-06Clinical Journal of the American Society of NephrologyPerspectives151116661668
- Association of VA Payment Reform for Dialysis with Spending, Access to Care, and Outcomes for Veterans with ESKD10.2215/CJN.02100220Tue, 22 Sep 2020 12:25:27 GMT-07:00Association of VA Payment Reform for Dialysis with Spending, Access to Care, and Outcomes for Veterans with ESKDWang, VirginiaSwaminathan, ShailenderCorneau, Emily A.Maciejewski, Matthew L.Trivedi, Amal N.O’Hare, Ann M.Mor, Vincent2020-09-22T12:25:27-07:00doi:10.2215/CJN.02100220hwp:resource-id:clinjasn;15/11/1631American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, mortality, Veterans, Health Services AccessibilityOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-11-06November 06, 202010.2215/CJN.021002201555-90411555-905X2020-09-22T12:25:27-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles151116311639
- Effect of Urate-Lowering Therapy on Cardiovascular and Kidney Outcomes10.2215/CJN.05190420Wed, 14 Oct 2020 08:51:08 GMT-07:00Effect of Urate-Lowering Therapy on Cardiovascular and Kidney OutcomesChen, QiWang, ZiZhou, JingweiChen, ZhenjieLi, YanLi, ShichaoZhao, HukangBadve, Sunil V.Lv, Jicheng2020-10-14T08:51:08-07:00doi:10.2215/CJN.05190420hwp:resource-id:clinjasn;15/11/1576American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyurate-lowering therapy, prevention, cardiovascular, mortality, kidney, meta-analysisOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-11-06November 06, 202010.2215/CJN.051904201555-90411555-905X2020-10-14T08:51:08-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles151115761586
- Validation of a Core Patient-Reported Outcome Measure for Fatigue in Patients Receiving Hemodialysis10.2215/CJN.05880420Thu, 22 Oct 2020 12:29:05 GMT-07:00Validation of a Core Patient-Reported Outcome Measure for Fatigue in Patients Receiving HemodialysisJu, AngelaTeixeira-Pinto, ArmandoTong, AllisonSmith, Alice C.Unruh, MarkDavison, Sara N.Dapueto, JuanDew, Mary AmandaFluck, RichardGermain, Michael J.Jassal, Sarbjit V.Obrador, Gregorio T.O’Donoghue, DonalViecelli, Andrea K.Strippoli, GiovanniRuospo, MarinellaTimofte, DeliaSharma, AnkitAu, EricHowell, MartinCosta, Daniel S.J.Anumudu, SamayaCraig, Jonathan C.Rutherford, Claudia2020-10-22T12:29:05-07:00doi:10.2215/CJN.05880420hwp:resource-id:clinjasn;15/11/1614American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, fatigue, patient reported outcome measuresOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-11-06November 06, 202010.2215/CJN.058804201555-90411555-905X2020-10-22T12:29:05-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles15111111161415391546162115401548
- QT Interval in Adult with Chronic Hypokalemia due to Gitelman Syndrome10.2215/CJN.07540520Wed, 12 Aug 2020 05:47:51 GMT-07:00QT Interval in Adult with Chronic Hypokalemia due to Gitelman SyndromeCourand, Pierre-YvesMarques, PedroVargas-Poussou, RosaAzizi, MichelBlanchard, Anne,2020-08-12T05:47:51-07:00doi:10.2215/CJN.07540520hwp:resource-id:clinjasn;15/11/1640American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGitelman-s syndrome, QT interval, electrocardiogram, potassium, magnesium, hypokalemiaResearch LetterResearch Letterletter20202020-11-06November 06, 202010.2215/CJN.075405201555-90411555-905X2020-08-12T05:47:51-07:002020-11-06Clinical Journal of the American Society of NephrologyResearch Letter151116401642
- Not All Sepsis-Associated Acute Kidney Injury Is the Same10.2215/CJN.14860920Thu, 08 Oct 2020 07:58:32 GMT-07:00Not All Sepsis-Associated Acute Kidney Injury Is the SameGunning, SamanthaKoyner, Jay L.2020-10-08T07:58:32-07:00doi:10.2215/CJN.14860920hwp:resource-id:clinjasn;15/11/1543American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, artificial intelligence, sepsis, electronic medical record, phenotypes, risk factorsEditorialsEditorialseditorial20202020-11-06November 06, 202010.2215/CJN.148609201555-90411555-905X2020-10-08T07:58:32-07:002020-11-06Clinical Journal of the American Society of NephrologyEditorials1511111543155715451565
- Delivering High-Quality Peritoneal Dialysis10.2215/CJN.02930320Thu, 11 Jun 2020 07:10:24 GMT-07:00Delivering High-Quality Peritoneal DialysisTeitelbaum, Isaac2020-06-11T07:10:24-07:00doi:10.2215/CJN.02930320hwp:resource-id:clinjasn;15/11/1663American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, electrolytes, blood pressure, mineral metabolism, Kidney Failure, ChronicPerspectivesPerspectivesresearch-article20202020-11-06November 06, 202010.2215/CJN.029303201555-90411555-905X2020-06-11T07:10:24-07:002020-11-06Clinical Journal of the American Society of NephrologyPerspectives151116631665
- Pain Management in a Patient with Kidney Failure10.2215/CJN.01440220Fri, 10 Apr 2020 09:20:10 GMT-07:00Pain Management in a Patient with Kidney FailureMoist, Louise2020-04-10T09:20:10-07:00doi:10.2215/CJN.01440220hwp:resource-id:clinjasn;15/11/1657American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypain management, kidney failure, Renal InsufficiencyKidney Case Conference: Nephrology Quiz & QuestionnaireKidney Case Conference: Nephrology Quiz & Questionnaireresearch-article20202020-11-06November 06, 202010.2215/CJN.014402201555-90411555-905X2020-04-10T09:20:10-07:002020-11-06Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz & Questionnaire151116571659
- Health Policy for Dialysis Care in Canada and the United StatesContemporary dialysis treatment for chronic kidney failure is complex, is associated with poor clinical outcomes, and leads to high health costs, all of which pose substantial policy challenges. Despite similar policy goals and universal access for their kidney failure programs, the United States and Canada have taken very different approaches to dealing with these challenges. While US dialysis care is primarily government funded and delivered predominantly by private for-profit providers, Canadian dialysis care is also government funded but delivered almost exclusively in public facilities. Differences also exist for regulatory mechanisms and the policy incentives that may influence the behavior of providers and facilities. These differences in health policy are associated with significant variation in clinical outcomes: mortality among patients on dialysis is consistently lower in Canada than in the United States, although the gap has narrowed in recent years. The observed heterogeneity in policy and outcomes offers important potential opportunities for each health system to learn from the other. This article compares and contrasts transnational dialysis-related health policies, focusing on key levers including payment, finance, regulation, and organization. We also describe how policy levers can incentivize favorable practice patterns to support high-quality/high-value, person-centered care and to catalyze the emergence of transformative technologies for alternative kidney replacement strategies.10.2215/CJN.14961219Thu, 25 Jun 2020 10:36:32 GMT-07:00Health Policy for Dialysis Care in Canada and the United StatesContemporary dialysis treatment for chronic kidney failure is complex, is associated with poor clinical outcomes, and leads to high health costs, all of which pose substantial policy challenges. Despite similar policy goals and universal access for their kidney failure programs, the United States and Canada have taken very different approaches to dealing with these challenges. While US dialysis care is primarily government funded and delivered predominantly by private for-profit providers, Canadian dialysis care is also government funded but delivered almost exclusively in public facilities. Differences also exist for regulatory mechanisms and the policy incentives that may influence the behavior of providers and facilities. These differences in health policy are associated with significant variation in clinical outcomes: mortality among patients on dialysis is consistently lower in Canada than in the United States, although the gap has narrowed in recent years. The observed heterogeneity in policy and outcomes offers important potential opportunities for each health system to learn from the other. This article compares and contrasts transnational dialysis-related health policies, focusing on key levers including payment, finance, regulation, and organization. We also describe how policy levers can incentivize favorable practice patterns to support high-quality/high-value, person-centered care and to catalyze the emergence of transformative technologies for alternative kidney replacement strategies.Tonelli, MarcelloVanholder, RaymondHimmelfarb, Jonathan2020-06-25T10:36:32-07:00doi:10.2215/CJN.14961219hwp:resource-id:clinjasn;15/11/1669American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, health policy, innovation, transnational comparisons, Kidney Failure, Chronic, peritoneal dialysis, Renal Insufficiency, Health Care Costs, GovernmentFeatureFeatureresearch-article20202020-11-06November 06, 202010.2215/CJN.149612191555-90411555-905X2020-06-25T10:36:32-07:002020-11-06Clinical Journal of the American Society of NephrologyFeature151116691677
- Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney DiseaseDiabetic kidney disease and its comorbid conditions, including atherosclerotic cardiovascular disease, heart failure, diabetes, and obesity, are interconnected conditions that compound the risk of kidney failure and cardiovascular mortality, and exponentiate health care costs. Sodium glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1 RA) are novel diabetes medications that prevent cardiovascular events and kidney failure. Clinical trials exploring the cardiovascular and kidney outcomes of SGLT2i and GLP-1 RA have fundamentally shifted the treatment paradigm of diabetes. Clinical guidelines for diabetes management recommend a more holistic approach beyond glycemic control and emphasize heart and kidney protection of SGLT2i and GLP-1 RA. However, the adoption of prescribing SGLT2i and GLP-1 RA for patients with diabetes and high cardiovascular and kidney risk has been slow. In this review, we provide a decision-making tool to help clinicians determine when to consider SGLT2i and GLP-1 RA for heart and kidney protection. First, we discuss a comprehensive risk assessment for patients with diabetic kidney disease. We compare the effectiveness of SGLT2i and GLP-1 RA for different risk categories. Then, we present a decision algorithm using cardiovascular and kidney failure risk stratification and the strength of current evidence for the use of SGLT2i and GLP-1 RA. Lastly, we review the adverse effects of SGLT2i and GLP-1 RA and propose mitigation strategies.10.2215/CJN.02690320Tue, 09 Jun 2020 06:29:26 GMT-07:00Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney DiseaseDiabetic kidney disease and its comorbid conditions, including atherosclerotic cardiovascular disease, heart failure, diabetes, and obesity, are interconnected conditions that compound the risk of kidney failure and cardiovascular mortality, and exponentiate health care costs. Sodium glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1 RA) are novel diabetes medications that prevent cardiovascular events and kidney failure. Clinical trials exploring the cardiovascular and kidney outcomes of SGLT2i and GLP-1 RA have fundamentally shifted the treatment paradigm of diabetes. Clinical guidelines for diabetes management recommend a more holistic approach beyond glycemic control and emphasize heart and kidney protection of SGLT2i and GLP-1 RA. However, the adoption of prescribing SGLT2i and GLP-1 RA for patients with diabetes and high cardiovascular and kidney risk has been slow. In this review, we provide a decision-making tool to help clinicians determine when to consider SGLT2i and GLP-1 RA for heart and kidney protection. First, we discuss a comprehensive risk assessment for patients with diabetic kidney disease. We compare the effectiveness of SGLT2i and GLP-1 RA for different risk categories. Then, we present a decision algorithm using cardiovascular and kidney failure risk stratification and the strength of current evidence for the use of SGLT2i and GLP-1 RA. Lastly, we review the adverse effects of SGLT2i and GLP-1 RA and propose mitigation strategies.Li, JiahuaAlbajrami, OltjonZhuo, MinHawley, Chelsea E.Paik, Julie M.2020-06-09T06:29:26-07:00doi:10.2215/CJN.02690320hwp:resource-id:clinjasn;15/11/1678American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, sodium-glucose cotransporter 2 inhibitor, glucagon-like peptide-1 receptor agonist, prescribing algorithm, diabetic kidney disease, Glucagon-Like Peptide 1, Diabetic Nephropathies, Glucagon-Like Peptide-1 Receptor, Cardiovascular Diseases, Blood Glucose, obesity, heart failure, kidney, Renal Insufficiency, Risk Assessment, Health Care Costs, Algorithms, Decision Making, SymportersReviewReviewreview-article20202020-11-06November 06, 202010.2215/CJN.026903201555-90411555-905X2020-06-09T06:29:26-07:002020-11-06Clinical Journal of the American Society of NephrologyReview151116781688
- Fatigue While Undergoing Long-Term Hemodialysis10.2215/CJN.14870920Thu, 22 Oct 2020 12:29:05 GMT-07:00Fatigue While Undergoing Long-Term HemodialysisSondergaard, Henning2020-10-22T12:29:05-07:00doi:10.2215/CJN.14870920hwp:resource-id:clinjasn;15/11/1539American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfatigue, hemodialysisPatient VoicePatient Voiceeditorial20202020-11-06November 06, 202010.2215/CJN.148709201555-90411555-905X2020-10-22T12:29:05-07:002020-11-06Clinical Journal of the American Society of NephrologyPatient Voice15111111153915461614154015481621
- Prevalence of Kidney Injury and Associations with Critical Illness and Death in Patients with COVID-1910.2215/CJN.04780420Thu, 17 Sep 2020 10:18:33 GMT-07:00Prevalence of Kidney Injury and Associations with Critical Illness and Death in Patients with COVID-19Zheng, XiziYang, HongyuLi, XiaolongLi, HaichaoXu, LingyiYu, QiDong, YapingZhao, YouluWang, JinweiHou, WanyinZhang, XinLi, YangHu, FengGao, HongLv, JichengYang, Li2020-09-17T10:18:33-07:00doi:10.2215/CJN.04780420hwp:resource-id:clinjasn;15/11/1549American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, acute kidney injury, proteinuria, hematuria, critical illnessOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20202020-11-06November 06, 202010.2215/CJN.047804201555-90411555-905X2020-09-17T10:18:33-07:002020-11-06Clinical Journal of the American Society of NephrologyOriginal Articles151115491556
- Genome-Wide Association Studies of CKD and Related TraitsThe past few years have seen major advances in genome-wide association studies (GWAS) of CKD and kidney function–related traits in several areas: increases in sample size from >100,000 to >1 million, enabling the discovery of >250 associated genetic loci that are highly reproducible; the inclusion of participants not only of European but also of non-European ancestries; and the use of advanced computational methods to integrate additional genomic and other unbiased, high-dimensional data to characterize the underlying genetic architecture and prioritize potentially causal genes and variants. Together with other large-scale biobank and genetic association studies of complex traits, these GWAS of kidney function–related traits have also provided novel insight into the relationship of kidney function to other diseases with respect to their genetic associations, genetic correlation, and directional relationships. A number of studies also included functional experiments using model organisms or cell lines to validate prioritized potentially causal genes and/or variants. In this review article, we will summarize these recent GWAS of CKD and kidney function–related traits, explain approaches for downstream characterization of associated genetic loci and the value of such computational follow-up analyses, and discuss related challenges along with potential solutions to ultimately enable improved treatment and prevention of kidney diseases through genetics.10.2215/CJN.00020120Thu, 14 May 2020 08:27:27 GMT-07:00Genome-Wide Association Studies of CKD and Related TraitsThe past few years have seen major advances in genome-wide association studies (GWAS) of CKD and kidney function–related traits in several areas: increases in sample size from >100,000 to >1 million, enabling the discovery of >250 associated genetic loci that are highly reproducible; the inclusion of participants not only of European but also of non-European ancestries; and the use of advanced computational methods to integrate additional genomic and other unbiased, high-dimensional data to characterize the underlying genetic architecture and prioritize potentially causal genes and variants. Together with other large-scale biobank and genetic association studies of complex traits, these GWAS of kidney function–related traits have also provided novel insight into the relationship of kidney function to other diseases with respect to their genetic associations, genetic correlation, and directional relationships. A number of studies also included functional experiments using model organisms or cell lines to validate prioritized potentially causal genes and/or variants. In this review article, we will summarize these recent GWAS of CKD and kidney function–related traits, explain approaches for downstream characterization of associated genetic loci and the value of such computational follow-up analyses, and discuss related challenges along with potential solutions to ultimately enable improved treatment and prevention of kidney diseases through genetics.Tin, AdrienneKöttgen, Anna2020-05-14T08:27:27-07:00doi:10.2215/CJN.00020120hwp:resource-id:clinjasn;15/11/1643American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, genetic renal disease, Kidney Genomics Series, Genome-Wide Association Study, Multifactorial Inheritance, Sample Size, Biological Specimen Banks, Follow-Up Studies, Genetic Loci, Genome, Genomics, Genetic Association Studies, Cell Line, Renal Insufficiency, ChronicGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-11-06November 06, 202010.2215/CJN.000201201555-90411555-905X2020-05-14T08:27:27-07:002020-11-06Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease151116431656
- Donor-Derived Cell-Free DNA: Is It All the Same? The Jury Is Still Out10.34067/KID.0004412020Mon, 21 Sep 2020 06:11:21 GMT-07:00Donor-Derived Cell-Free DNA: Is It All the Same? The Jury Is Still OutGarg, Neetika2020-09-21T06:11:21-07:00doi:10.34067/KID.0004412020hwp:resource-id:kidney360;1/10/1038American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, allosure, biomarker, donor-derived cell-free DNA, kidney transplant, prospera, rejectionEditorialsEditorialseditorial20202020-10-2910.34067/KID.00044120202641-76502020-09-21T06:11:21-07:002020-10-29Kidney360Editorials11010381039
- Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic ParadigmNearly seven decades have elapsed since the clinical and biochemical features of primary hyperaldosteronism (PA) were described by Conn. PA is now widely recognized as the most common form of secondary hypertension. PA has a strong correlation with cardiovascular disease and failure to recognize and/or properly diagnose this condition has profound health consequences. With proper identification and management, PA has the potential to be surgically cured in a proportion of affected individuals. The diagnostic pursuit for PA is not a simplistic endeavor, particularly because an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm. These new concepts have emerged in all areas of this clinical condition, including identification, diagnosis, and treatment. Here, we review the recent advances in this field and summarize the effect these advances have on both diagnostic and therapeutic modalities.10.34067/KID.0000922020Thu, 23 Jul 2020 02:20:07 GMT-07:00Hyperaldosteronism: How Current Concepts Are Transforming the Diagnostic and Therapeutic ParadigmNearly seven decades have elapsed since the clinical and biochemical features of primary hyperaldosteronism (PA) were described by Conn. PA is now widely recognized as the most common form of secondary hypertension. PA has a strong correlation with cardiovascular disease and failure to recognize and/or properly diagnose this condition has profound health consequences. With proper identification and management, PA has the potential to be surgically cured in a proportion of affected individuals. The diagnostic pursuit for PA is not a simplistic endeavor, particularly because an enhanced understanding of the disease process is continually redefining the diagnostic and treatment algorithm. These new concepts have emerged in all areas of this clinical condition, including identification, diagnosis, and treatment. Here, we review the recent advances in this field and summarize the effect these advances have on both diagnostic and therapeutic modalities.Lattanzio, Michael R.Weir, Matthew R.2020-07-23T14:20:07-07:00doi:10.34067/KID.0000922020hwp:resource-id:kidney360;1/10/1148American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360hypertension, adrenal vein sampling, adrenalectomy, aldosterone renin ratio, cardiovascular disease, confirmatory testing, eplerenone, hyperaldosteronism, hypertension, hypokalemia, spironolactoneReview ArticlesReview Articlesreview-article20202020-10-2910.34067/KID.00009220202641-76502020-07-23T14:20:07-07:002020-10-29Kidney360Review Articles11011481156
- Parathyroid Hormone Serum Levels and Mortality among Hemodialysis Patients in the Gulf Cooperation Council Countries: Results from the DOPPS (2012–2018)10.34067/KID.0000772020Wed, 26 Aug 2020 12:18:42 GMT-07:00Parathyroid Hormone Serum Levels and Mortality among Hemodialysis Patients in the Gulf Cooperation Council Countries: Results from the DOPPS (2012–2018)Al Salmi, IssaBieber, BrianAl Rukhaimi, MonaAlSahow, AliShaheen, FaissalAl-Ghamdi, Saeed M.G.Al Wakeel, JamalAl Ali, FadwaAl-Aradi, AliHejaili, Fayez AlMaimani, Yacoub AlFouly, EssamRobinson, Bruce M.Pisoni, Ronald L.2020-08-26T12:18:42-07:00doi:10.34067/KID.0000772020hwp:resource-id:kidney360;1/10/1083American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, DOPPS, Gulf Cooperation Council, hemodialysis, mortality, parathyroid hormone, Basic ScienceOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-10-2910.34067/KID.00007720202641-76502020-08-26T12:18:42-07:002020-10-29Kidney360Original Investigations11010831090
- From Theory to Reality: Establishing a Successful Kidney Genetics Clinic in the Outpatient Setting10.34067/KID.0004262020Wed, 12 Aug 2020 09:27:27 GMT-07:00From Theory to Reality: Establishing a Successful Kidney Genetics Clinic in the Outpatient SettingLundquist, Andrew L.Pelletier, Renee C.Leonard, Courtney E.Williams, Winfred W.Armstrong, Katrina A.Rehm, Heidi L.Rhee, Eugene P.2020-08-12T09:27:27-07:00doi:10.34067/KID.0004262020hwp:resource-id:kidney360;1/10/1099American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360genetics, ambulatory care facilities, familial nephropathy, genetic kidney disease, kidney dysfunction, outpatientsOriginal InvestigationsGeneticsOriginal InvestigationsGeneticsresearch-article20202020-10-2910.34067/KID.00042620202641-76502020-08-12T09:27:27-07:002020-10-29Kidney360Original Investigations11010991106
- The Nephrology Immersion Classroom for Internal Medicine Residents10.34067/KID.0001882020Thu, 20 Aug 2020 09:22:39 GMT-07:00The Nephrology Immersion Classroom for Internal Medicine ResidentsRoberts, John K.Seay, Norman W.Mohottige, DinushikaZaas, AimeeWolf, Myles2020-08-20T09:22:39-07:00doi:10.34067/KID.0001882020hwp:resource-id:kidney360;1/10/1060American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, digital learning, digital videos, education, internship and residency, pencastsOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20202020-10-2910.34067/KID.00018820202641-76502020-08-20T09:22:39-07:002020-10-29Kidney360Original Investigations11010601067
- Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane Workers10.34067/KID.0003392020Wed, 19 Aug 2020 01:29:34 GMT-07:00Kidney Function, Self-Reported Symptoms, and Urine Findings in Nicaraguan Sugarcane WorkersPetropoulos, Zoe E.Laws, Rebecca L.Amador, Juan JoséLópez-Pilarte, DamarisKaufman, James S.Weiner, Daniel E.Ramirez-Rubio, OrianaBrooks, Daniel R.McClean, Michael D.Scammell, Madeleine K.2020-08-19T13:29:34-07:00doi:10.34067/KID.0003392020hwp:resource-id:kidney360;1/10/1042American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, kidney injury biomarkers, medications, Mesoamerican nephropathy, occupational and environmental health, symptoms, urinary tract infection, Basic ScienceOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-10-2910.34067/KID.00033920202641-76502020-08-19T13:29:34-07:002020-10-29Kidney360Original Investigations11010421051
- Abdominal Distention in a Patient on Peritoneal Dialysis10.34067/KID.0002412020Mon, 02 Nov 2020 09:20:40 GMT-08:00Abdominal Distention in a Patient on Peritoneal DialysisLi, John WingSud, Kamal2020-11-02T09:20:40-08:00doi:10.34067/KID.0002412020hwp:resource-id:kidney360;1/10/1182American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, digestive system abnormalities, lipomatosis, peritoneal dialysis, retroperitonealClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-10-2910.34067/KID.00024120202641-76502020-11-02T09:20:40-08:002020-10-29Kidney360Clinical Images in Nephrology and Dialysis11011821183
- Donor-Derived Cell Free DNA: Is It All the Same?10.34067/KID.0003512020Fri, 19 Jun 2020 09:12:27 GMT-07:00Donor-Derived Cell Free DNA: Is It All the Same?Melancon, Joseph K.Khalil, AliLerman, Mark J.2020-06-19T09:12:27-07:00doi:10.34067/KID.0003512020hwp:resource-id:kidney360;1/10/1118American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, allografts, biomarker, cell-free nucleic acids, dd-cfDNA, diagnostic tests, routine, donor derived cell free DNA, kidney transplantation, tissue donors, transplantationOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-10-2910.34067/KID.00035120202641-76502020-06-19T09:12:27-07:002020-10-29Kidney360Original Investigations11011181123
- Calcimimetic Use in Dialysis-Dependent Medicare Fee-for-Service Beneficiaries and Implications for Bundled Payment10.34067/KID.0003042020Tue, 25 Aug 2020 01:28:18 GMT-07:00Calcimimetic Use in Dialysis-Dependent Medicare Fee-for-Service Beneficiaries and Implications for Bundled PaymentGooding, MarkDesai, PoojaOwens, HollyPetrilla, Allison A.Kambhampati, MaheshLevine, ZachYoung, JoannaFagan, JackRubin, Robert2020-08-25T13:28:18-07:00doi:10.34067/KID.0003042020hwp:resource-id:kidney360;1/10/1091American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360nephro-pharmacology, calcimimetics, chronic kidney failure, fee-for-service plans, Medicare, parathyroid hormone, Prospective Payment System, renal dialysis, secondary hyperparathyroidism, United States, Basic ScienceOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-10-2910.34067/KID.00030420202641-76502020-08-25T13:28:18-07:002020-10-29Kidney360Original Investigations11010911098
- Internal Medicine Residents’ Perceptions of Nephrology as a Career: A Focus Group Study10.34067/KID.0003652020Wed, 19 Aug 2020 01:29:34 GMT-07:00Internal Medicine Residents’ Perceptions of Nephrology as a Career: A Focus Group StudyBeck, NatalieFurgeson, SethChonchol, MichelKendrick, Jessica2020-08-19T13:29:34-07:00doi:10.34067/KID.0003652020hwp:resource-id:kidney360;1/10/1052American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, career choice, focus groups, internship and residency, nephrologyOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20202020-10-2910.34067/KID.00036520202641-76502020-08-19T13:29:34-07:002020-10-29Kidney360Original Investigations11010521059
- How To Build a Successful Urgent-Start Peritoneal Dialysis ProgramIn-center hemodialysis (HD) remains the predominant dialysis therapy in patients with ESKD. Many patients with ESKD present in late stage, requiring urgent dialysis initiation, and the majority start HD with central venous catheters (CVCs), which are associated with poor outcomes and high cost of care. Peritoneal dialysis (PD) catheters can be safely placed in such patients with late-presenting ESKD, obviating the need for CVCs. PD can begin almost immediately in the recumbent position, using low fill volumes. Such PD initiations, commencing within 2 weeks of the catheter placement, are termed urgent-start PD (USPD). Most patients with an intact peritoneal cavity and stable home situation are eligible for USPD. Although there is a small risk of PD catheter–related mechanical complications, most can be managed conservatively. Moreover, overall outcomes of USPD are comparable to those with planned PD initiations, in contrast to the high rate of catheter-related infections and bacteremia associated with urgent-start HD. The ongoing coronavirus disease 2019 pandemic has further exposed the vulnerability of patients with ESKD getting in-center HD. PD can mitigate the risk of infection by reducing environmental exposure to the virus. Thus, USPD is a safe and cost-effective option for unplanned dialysis initiation in patients with late-presenting ESKD. To develop a successful USPD program, a strong infrastructure with clear pathways is essential. Coordination of care between nephrologists, surgeons or interventionalists, and hospital and PD center staff is imperative so that patient education, home visits, PD catheter placements, and urgent PD initiations are accomplished expeditiously. Implementation of urgent-start PD will help to increase PD use, reduce cost, and improve patient outcomes, and will be a step forward in fostering the goal set by the Advancing American Kidney Health initiative.10.34067/KID.0002392020Tue, 11 Aug 2020 06:18:52 GMT-07:00How To Build a Successful Urgent-Start Peritoneal Dialysis ProgramIn-center hemodialysis (HD) remains the predominant dialysis therapy in patients with ESKD. Many patients with ESKD present in late stage, requiring urgent dialysis initiation, and the majority start HD with central venous catheters (CVCs), which are associated with poor outcomes and high cost of care. Peritoneal dialysis (PD) catheters can be safely placed in such patients with late-presenting ESKD, obviating the need for CVCs. PD can begin almost immediately in the recumbent position, using low fill volumes. Such PD initiations, commencing within 2 weeks of the catheter placement, are termed urgent-start PD (USPD). Most patients with an intact peritoneal cavity and stable home situation are eligible for USPD. Although there is a small risk of PD catheter–related mechanical complications, most can be managed conservatively. Moreover, overall outcomes of USPD are comparable to those with planned PD initiations, in contrast to the high rate of catheter-related infections and bacteremia associated with urgent-start HD. The ongoing coronavirus disease 2019 pandemic has further exposed the vulnerability of patients with ESKD getting in-center HD. PD can mitigate the risk of infection by reducing environmental exposure to the virus. Thus, USPD is a safe and cost-effective option for unplanned dialysis initiation in patients with late-presenting ESKD. To develop a successful USPD program, a strong infrastructure with clear pathways is essential. Coordination of care between nephrologists, surgeons or interventionalists, and hospital and PD center staff is imperative so that patient education, home visits, PD catheter placements, and urgent PD initiations are accomplished expeditiously. Implementation of urgent-start PD will help to increase PD use, reduce cost, and improve patient outcomes, and will be a step forward in fostering the goal set by the Advancing American Kidney Health initiative.Rajora, NilumShastri, ShaniPirwani, GulzarSaxena, Ramesh2020-08-11T06:18:52-07:00doi:10.34067/KID.0002392020hwp:resource-id:kidney360;1/10/1165American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, end stage kidney disease, peritoneal dialysis, unplanned dialysis initiations, urgent-start peritoneal dialysisReview ArticlesReview Articlesreview-article20202020-10-2910.34067/KID.00023920202641-76502020-08-11T06:18:52-07:002020-10-29Kidney360Review Articles11011651177
- Functionally Essential Tubular Proteins Are Lost to Urine-Excreted, Large Extracellular Vesicles during Chronic Renal Insufficiency10.34067/KID.0001212020Tue, 25 Aug 2020 09:34:17 GMT-07:00Functionally Essential Tubular Proteins Are Lost to Urine-Excreted, Large Extracellular Vesicles during Chronic Renal InsufficiencyAdam, Ryan J.Paterson, Mark R.Wardecke, LukusHoffmann, Brian R.Kriegel, Alison J.2020-08-25T09:34:17-07:00doi:10.34067/KID.0001212020hwp:resource-id:kidney360;1/10/1107American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, chronic renal insufficiency, extracellular vesicles, proteomics, proximal tubule, rats, urinary biomarkers, Basic ScienceOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-10-2910.34067/KID.00012120202641-76502020-08-25T09:34:17-07:002020-10-29Kidney360Original Investigations11011071117
- Assessing Polycystic Kidney Disease in Rodents: Comparison of Robotic 3D Ultrasound and Magnetic Resonance ImagingPolycystic kidney disease (PKD) is an inherited disorder characterized by renal cyst formation and enlargement of the kidney. PKD severity can be staged noninvasively by measuring total kidney volume (TKV), a promising biomarker that has recently received regulatory qualification. In preclinical mouse models, where the disease is studied and potential therapeutics are evaluated, the most popular noninvasive method of measuring TKV is magnetic resonance imaging (MRI). Although MRI provides excellent 3D resolution and contrast, these systems are expensive to operate, have long acquisition times, and, consequently, are not heavily used in preclinical PKD research. In this study, a new imaging instrument, based on robotic ultrasound (US), was evaluated as a complementary approach for assessing PKD in rodent models. The objective was to determine the extent to which TKV measurements on the robotic US scanner correlated with both in vivo and ex vivo reference standards (MRI and Vernier calipers, respectively). A cross-sectional study design was implemented that included both PKD-affected mice and healthy wild types, spanning sex and age for a wide range of kidney volumes. It was found that US-derived TKV measurements and kidney lengths were strongly associated with both in vivo MRI and ex vivo Vernier caliper measurements (R2=0.94 and 0.90, respectively). In addition to measuring TKV, renal vascular density was assessed using acoustic angiography (AA), a novel contrast-enhanced US methodology. AA image intensity, indicative of volumetric vascularity, was seen to have a strong negative correlation with TKV (R2=0.82), suggesting impaired renal vascular function in mice with larger kidneys. These studies demonstrate that robotic US can provide a rapid and accurate approach for noninvasively evaluating PKD in rodent models.10.34067/KID.0003912020Tue, 18 Aug 2020 09:35:48 GMT-07:00Assessing Polycystic Kidney Disease in Rodents: Comparison of Robotic 3D Ultrasound and Magnetic Resonance ImagingPolycystic kidney disease (PKD) is an inherited disorder characterized by renal cyst formation and enlargement of the kidney. PKD severity can be staged noninvasively by measuring total kidney volume (TKV), a promising biomarker that has recently received regulatory qualification. In preclinical mouse models, where the disease is studied and potential therapeutics are evaluated, the most popular noninvasive method of measuring TKV is magnetic resonance imaging (MRI). Although MRI provides excellent 3D resolution and contrast, these systems are expensive to operate, have long acquisition times, and, consequently, are not heavily used in preclinical PKD research. In this study, a new imaging instrument, based on robotic ultrasound (US), was evaluated as a complementary approach for assessing PKD in rodent models. The objective was to determine the extent to which TKV measurements on the robotic US scanner correlated with both in vivo and ex vivo reference standards (MRI and Vernier calipers, respectively). A cross-sectional study design was implemented that included both PKD-affected mice and healthy wild types, spanning sex and age for a wide range of kidney volumes. It was found that US-derived TKV measurements and kidney lengths were strongly associated with both in vivo MRI and ex vivo Vernier caliper measurements (R2=0.94 and 0.90, respectively). In addition to measuring TKV, renal vascular density was assessed using acoustic angiography (AA), a novel contrast-enhanced US methodology. AA image intensity, indicative of volumetric vascularity, was seen to have a strong negative correlation with TKV (R2=0.82), suggesting impaired renal vascular function in mice with larger kidneys. These studies demonstrate that robotic US can provide a rapid and accurate approach for noninvasively evaluating PKD in rodent models.Beaumont, Nathan J.Holmes, Heather L.Gregory, Adriana V.Edwards, Marie E.Rojas, Juan D.Gessner, Ryan C.Dayton, Paul A.Kline, Timothy L.Romero, Michael F.Czernuszewicz, Tomasz J.2020-08-18T09:35:48-07:00doi:10.34067/KID.0003912020hwp:resource-id:kidney360;1/10/1128American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360cystic kidney disease, magnetic resonance imaging, murine, noninvasive, polycystic kidney disease, preclinical imaging, robotics, rodentia, total kidney volume, ultrasonography, Basic ScienceInnovative Technology and MethodologyInnovative Technology and Methodologyresearch-article20202020-10-2910.34067/KID.00039120202641-76502020-08-18T09:35:48-07:002020-10-29Kidney360Innovative Technology and Methodology11011281136
- Organelle Stress and Crosstalk in Kidney DiseaseOrganelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.10.34067/KID.0002442020Fri, 07 Aug 2020 09:22:52 GMT-07:00Organelle Stress and Crosstalk in Kidney DiseaseOrganelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.Hasegawa, ShoInagi, Reiko2020-08-07T09:22:52-07:00doi:10.34067/KID.0002442020hwp:resource-id:kidney360;1/10/1157American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, acute kidney injury, AKI-to-CKD transition, ER stress, lipid metabolism, mitochondria, organelle crosstalk, organelle stress, tubular inflammation, unfolded protein response (UPR), Basic ScienceReview ArticlesReview Articlesreview-article20202020-10-2910.34067/KID.00024420202641-76502020-08-07T09:22:52-07:002020-10-29Kidney360Review Articles11011571164
- Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease10.34067/KID.0002522020Wed, 02 Sep 2020 09:32:53 GMT-07:00Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver DiseaseBesse, WhitneyRoosendaal, CharlotteTuccillo, LuigiGhosh Roy, SounakGallagher, Anna-RachelSomlo, Stefan2020-09-02T09:32:53-07:00doi:10.34067/KID.0002522020hwp:resource-id:kidney360;1/10/1068American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360cystic kidney disease, ADPKD, ARPKD, cysts, ductal plate, fibrocystin, mouse model, PKD1, PKHD1, polycystic liver, polycystin, Basic ScienceOriginal InvestigationsCystic Kidney DiseaseOriginal InvestigationsCystic Kidney Diseaseresearch-article20202020-10-2910.34067/KID.00025220202641-76502020-09-02T09:32:53-07:002020-10-29Kidney360Original Investigations11010681076
- Global Dialysis Perspective: India10.34067/KID.0003982020Wed, 19 Aug 2020 09:34:22 GMT-07:00Global Dialysis Perspective: IndiaBharati, JoyitaJha, Vivekanand2020-08-19T09:34:22-07:00doi:10.34067/KID.0003982020hwp:resource-id:kidney360;1/10/1143American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, health economics, IndiaGlobal PerspectivesGlobal Perspectivesresearch-article20202020-10-2910.34067/KID.00039820202641-76502020-08-19T09:34:22-07:002020-10-29Kidney360Global Perspectives11011431147
- Abdominal Pain and Fever in an Elderly Patient with Diabetes Mellitus10.34067/KID.0002402020Thu, 29 Oct 2020 05:30:23 GMT-07:00Abdominal Pain and Fever in an Elderly Patient with Diabetes MellitusKhetan, PrakashRamteke, VishalAshtekar, Jitendra2020-10-29T05:30:23-07:00doi:10.34067/KID.0002402020hwp:resource-id:kidney360;1/10/1180American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, abdominal pain, acute kidney injury, aged, bacterial infections, diabetes mellitus, emphysematous aortitis, emphysematous cystitisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-10-2910.34067/KID.00024020202641-76502020-10-29T05:30:23-07:002020-10-29Kidney360Clinical Images in Nephrology and Dialysis11011801181
- Global Dialysis Perspective: United States10.34067/KID.0001602020Fri, 14 Aug 2020 01:41:13 GMT-07:00Global Dialysis Perspective: United StatesHan, YunSaran, Rajiv2020-08-14T13:41:13-07:00doi:10.34067/KID.0001602020hwp:resource-id:kidney360;1/10/1137American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, Centers for Medicaid and Medicare, kidney registry, prospective payment system, surveillance, United States Renal Data SystemGlobal PerspectivesGlobal Perspectivesresearch-article20202020-10-2910.34067/KID.00016020202641-76502020-08-14T13:41:13-07:002020-10-29Kidney360Global Perspectives11011371142
- How Hemodialysis Patients Perceive the SARS-CoV-2 Health Crisis: Lessons from Austria10.34067/KID.0003582020Tue, 25 Aug 2020 09:34:17 GMT-07:00How Hemodialysis Patients Perceive the SARS-CoV-2 Health Crisis: Lessons from AustriaDavidovic, TamaraSprenger-Mähr, HanneloreAbbassi-Nik, ArminZitt, EmanuelLhotta, Karl2020-08-25T09:34:17-07:00doi:10.34067/KID.0003582020hwp:resource-id:kidney360;1/10/1077American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, Austria, COVID-19, hemodialysis, mental health, pandemic, renal Dialysis, SARS-CoV-2Original InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-10-2910.34067/KID.00035820202641-76502020-08-25T09:34:17-07:002020-10-29Kidney360Original Investigations11010771082
- Moving beyond COVID-19 Surge—Caring for Patients with Kidney Disease throughout the Pandemic10.34067/KID.0005452020Fri, 18 Sep 2020 06:01:48 GMT-07:00Moving beyond COVID-19 Surge—Caring for Patients with Kidney Disease throughout the PandemicBelani, SharinaPravoverov, LeonidGoes, Nelson B.Zheng, SijieAsovskaya, Anna V.Kroupa, PaulPoyan Mehr, Ali2020-09-18T06:01:48-07:00doi:10.34067/KID.0005452020hwp:resource-id:kidney360;1/10/1124American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, acute kidney injury, chronic kidney disease, COVID-19, end-stage kidney diseaseBrief CommunicationBrief Communicationbrief-report20202020-10-2910.34067/KID.00054520202641-76502020-09-18T06:01:48-07:002020-10-29Kidney360Brief Communication11011241127
- Leveraging the Capabilities of the FDA’s Sentinel System To Improve Kidney CareThe Sentinel System is a national electronic postmarketing resource established by the US Food and Drug Administration to support assessment of the safety and effectiveness of marketed medical products. It has built a large, multi-institutional, distributed data network that contains comprehensive electronic health data, covering about 700 million person-years of longitudinal observation time nationwide. With its sophisticated infrastructure and a large selection of flexible analytic tools, the Sentinel System permits rapid and secure analyses, while preserving patient privacy and health-system autonomy. The Sentinel System also offers enhanced capabilities, including accessing full-text medical records, supporting randomized clinical trials embedded in healthcare delivery systems, and facilitating effective collection of patient-reported data using mobile devices, among many other research programs. The nephrology research community can use the infrastructure, tools, and data that this national resource offers for evidence generation. This review summarizes the Sentinel System and its ability to rapidly generate high-quality, real-world evidence; discusses the program’s experience in, and potential for, addressing gaps in kidney care; and outlines avenues for conducting research, leveraging this national resource in collaboration with Sentinel investigators.10.1681/ASN.2020040526Mon, 19 Oct 2020 08:04:34 GMT-07:00Leveraging the Capabilities of the FDA’s Sentinel System To Improve Kidney CareThe Sentinel System is a national electronic postmarketing resource established by the US Food and Drug Administration to support assessment of the safety and effectiveness of marketed medical products. It has built a large, multi-institutional, distributed data network that contains comprehensive electronic health data, covering about 700 million person-years of longitudinal observation time nationwide. With its sophisticated infrastructure and a large selection of flexible analytic tools, the Sentinel System permits rapid and secure analyses, while preserving patient privacy and health-system autonomy. The Sentinel System also offers enhanced capabilities, including accessing full-text medical records, supporting randomized clinical trials embedded in healthcare delivery systems, and facilitating effective collection of patient-reported data using mobile devices, among many other research programs. The nephrology research community can use the infrastructure, tools, and data that this national resource offers for evidence generation. This review summarizes the Sentinel System and its ability to rapidly generate high-quality, real-world evidence; discusses the program’s experience in, and potential for, addressing gaps in kidney care; and outlines avenues for conducting research, leveraging this national resource in collaboration with Sentinel investigators.Adimadhyam, SruthiBarreto, Erin F.Cocoros, Noelle M.Toh, SengweeBrown, Jeffrey S.Maro, Judith C.Corrigan-Curay, JacquelineDal Pan, Gerald J.Ball, RobertMartin, DavidNguyen, MichaelPlatt, RichardLi, Xiaojuan2020-10-19T08:04:34-07:00doi:10.1681/ASN.2020040526hwp:resource-id:jnephrol;31/11/2506American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyU.S. Food and Drug Administration, Sentinel Initiative, epidemiology, outcomes research, real-world evidence, electronic health dataUp Front MattersReviewUp Front MattersReviewreview-article20202020-11-01November 202010.1681/ASN.20200405261046-66731533-34502020-10-19T08:04:34-07:002020-11Journal of the American Society of NephrologyUp Front Matters311125062516
- COVID-19 Infection in ESKD: Findings from a Prospective Disease Surveillance Program at Dialysis Facilities in New York City and Long Island10.1681/ASN.2020070932Mon, 19 Oct 2020 08:04:33 GMT-07:00COVID-19 Infection in ESKD: Findings from a Prospective Disease Surveillance Program at Dialysis Facilities in New York City and Long IslandWeiss, StevenBhat, Premiladel Pilar Fernandez, MariaBhat, J. GaneshCoritsidis, George N.2020-10-19T08:04:33-07:00doi:10.1681/ASN.2020070932hwp:resource-id:jnephrol;31/11/2517American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, New York City, hospitalization, mortality, undocumented, COVID-19Research LettersResearch Lettersletter20202020-11-01November 202010.1681/ASN.20200709321046-66731533-34502020-10-19T08:04:33-07:002020-11Journal of the American Society of NephrologyResearch Letters311125172521
- Soluble Urokinase Receptor (SuPAR) in COVID-19–Related AKI10.1681/ASN.2020060829Tue, 22 Sep 2020 06:29:12 GMT-07:00Soluble Urokinase Receptor (SuPAR) in COVID-19–Related AKIAzam, Tariq U.Shadid, Husam R.Blakely, PennelopeO’Hayer, PatrickBerlin, HannaPan, MichaelZhao, PeiyaoZhao, LiliPennathur, SubramaniamPop-Busui, RodicaAltintas, IzzetTingleff, JensStauning, Marius A.Andersen, OveAdami, Maria-EvangeliaSolomonidi, NickyTsilika, MariaTober-Lau, PinkusArnaoutoglou, EleniKeitel, VerenaTacke, FrankChalkias, AthanasiosLoosen, Sven H.Giamarellos-Bourboulis, Evangelos J.Eugen-Olsen, JesperReiser, JochenHayek, Salim S.,Hayek, Salim S.Blakely, PennelopeBerlin, HannaAzam, Tariq U.Shadid, HusamPan, MichaelO’Hayer, PatrickMeloche, ChelseaFeroze, RafeyPadalia, Kishan J.Anderson, ElizabethPerry, DannyBitar, AbbasKaakati, RayanZhao, LiliZhao, PeiyaoEugen-Olsen, JesperAltintas, IzzetTingleff, JensStauning, MariusHoulind, Morten BaltzerLindstrøm, Mette B.Andersen, OveGamst-Jensen, HejdiRasmussen, Line Jee HartmannRasmussen, ChristianNehlin, Jan O.Kallemose, ThomasParvaiz, ImranGiamarellos-Bourboulis, Evangelos J.Adami, Maria-EvangeliaSolomonidi, NickyTsilika, MariaSaridaki, MariaLekakis, VasileiosLoosen, SvenLuedde, TomKeitel, VerenaChalkias, AthanasiosArnaoutoglou, EleniPantazopoulos, IoannisLaou, EleniKolonia, KonstantinaSkoulakis, AnargyrosTacke, FrankTober-Lau, PinkusMohr, RaphaelKurth, FlorianSander, Leif ErikJochum, Christoph2020-09-22T06:29:12-07:00doi:10.1681/ASN.2020060829hwp:resource-id:jnephrol;31/11/2725American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, AKI, urokinase, SuPAR, SARS-CoV-2, coronavirus, dialysis, renal replacement therapy, CRP, COVID-19Clinical ResearchClinical Researchresearch-article20202020-11-01November 202010.1681/ASN.20200608291046-66731533-34502020-09-22T06:29:12-07:002020-11Journal of the American Society of NephrologyClinical Research311127252735
- The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD Injury10.1681/ASN.2020071061Fri, 11 Sep 2020 07:23:36 GMT-07:00The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD InjuryRutkowski, Mark Peter2020-09-11T07:23:36-07:00doi:10.1681/ASN.2020071061hwp:resource-id:jnephrol;31/11/2740American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, FDA drug label, creatinine, disparities, estimated glomerular filtration rate, metforminLetters to the EditorLetters to the Editorletter20202020-11-01November 202010.1681/ASN.20200710611046-66731533-34502020-09-11T07:23:36-07:002020-11Journal of the American Society of NephrologyLetters to the Editor3111112740274027402741
- The Mechanism of Kidney Disease Due to APOL1 Risk Variants10.1681/ASN.2020070954Thu, 17 Sep 2020 10:20:54 GMT-07:00The Mechanism of Kidney Disease Due to APOL1 Risk VariantsPays, Etienne2020-09-17T10:20:54-07:00doi:10.1681/ASN.2020070954hwp:resource-id:jnephrol;31/11/2502American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic glomerulonephritis, chronic kidney disease, cytoskeleton, end stage kidney disease, focal segmental glomerulosclerosis, APOL1 risk variants, APOL3, PI4KB, Golgi PI(4)PUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20202020-11-01November 202010.1681/ASN.20200709541046-66731533-34502020-09-17T10:20:54-07:002020-11Journal of the American Society of NephrologyUp Front Matters311125022505
- Multicenter Study to Transplant Hepatitis C–Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection10.1681/ASN.2020050686Tue, 25 Aug 2020 07:10:34 GMT-07:00Multicenter Study to Transplant Hepatitis C–Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus InfectionSise, Meghan E.Goldberg, David S.Kort, Jens J.Schaubel, Douglas E.Alloway, Rita R.Durand, Christine M.Fontana, Robert J.Brown, Robert S.Friedewald, John J.Prenner, StaceyLandis, J. RichardFernando, MelissaPhillips, Caitlin C.Woodle, E. SteveRike-Shields, AdeleSherman, Kenneth E.Elias, NahelWilliams, Winfred W.Gustafson, Jenna L.Desai, Niraj M.Barnaba, BrittanyNorman, Silas P.Doshi, MonaSultan, Samuel T.Aull, Meredith J.Levitsky, JoshBelshe, Dianne S.Chung, Raymond T.Reese, Peter P.2020-08-25T07:10:34-07:00doi:10.1681/ASN.2020050686hwp:resource-id:jnephrol;31/11/2678American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyhepatitis C virus, kidney transplantation, direct-acting antivirals, organ allocationClinical ResearchClinical Researchresearch-article20202020-11-01November 202010.1681/ASN.20200506861046-66731533-34502020-08-25T07:10:34-07:002020-11Journal of the American Society of NephrologyClinical Research311126782687
- Moving Nephrology Genetics into Clinical Care10.34067/KID.0005142020Thu, 29 Oct 2020 05:30:22 GMT-07:00Moving Nephrology Genetics into Clinical CareLanktree, Matthew B.2020-10-29T05:30:22-07:00doi:10.34067/KID.0005142020hwp:resource-id:kidney360;1/10/1040American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360genetics, chronic kidney disease, genetic testing, genetics, polycystic kidney diseaseEditorialsEditorialseditorial20202020-10-2910.34067/KID.00051420202641-76502020-10-29T05:30:22-07:002020-10-29Kidney360Editorials11010401041
- Abnormal Kidney Ultrasound in a Transplant Patient with AKI10.34067/KID.0002022020Thu, 29 Oct 2020 05:30:23 GMT-07:00Abnormal Kidney Ultrasound in a Transplant Patient with AKISy-Go, Janina Paula T.Thirunavukkarasu, SorkkoBentall, Andrew J.2020-10-29T05:30:23-07:00doi:10.34067/KID.0002022020hwp:resource-id:kidney360;1/10/1178American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, extra-renal pelvis, hydronephrosis, kidney ultrasoundClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-10-2910.34067/KID.00020220202641-76502020-10-29T05:30:23-07:002020-10-29Kidney360Clinical Images in Nephrology and Dialysis11011781179
- Authors' Reply10.1681/ASN.2020060854Mon, 06 Jul 2020 11:32:31 GMT-07:00Authors' ReplyFarrington, CrystalAllon, Michael2020-07-06T11:32:31-07:00doi:10.1681/ASN.2020060854hwp:resource-id:jnephrol;31/9/2228American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, arteriovenous fistula, vascular mappingLetter to the EditorLetter to the Editorletter20202020-09-01September 202010.1681/ASN.20200608541046-66731533-34502020-07-06T11:32:31-07:002020-09Journal of the American Society of NephrologyLetter to the Editor31992228222622292228
- Gentamicin-Induced Acute Kidney Injury in an Animal Model Involves Programmed Necrosis of the Collecting Duct10.1681/ASN.2019020204Wed, 08 Jul 2020 09:11:04 GMT-07:00Gentamicin-Induced Acute Kidney Injury in an Animal Model Involves Programmed Necrosis of the Collecting DuctHuang, HuihuiJin, William W.Huang, MingJi, HeyuCapen, Diane E.Xia, YinYuan, JunyingPăunescu, Teodor G.Lu, Hua A. Jenny2020-07-08T09:11:04-07:00doi:10.1681/ASN.2019020204hwp:resource-id:jnephrol;31/9/2097American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologygentamicin, collecting duct, necroptosis, inflammation, fibrosisBasic ResearchBasic Researchresearch-article20202020-09-01September 202010.1681/ASN.20190202041046-66731533-34502020-07-08T09:11:04-07:002020-09Journal of the American Society of NephrologyBasic Research31920972115
- Kidney Disease, Intensive Hypertension Treatment, and Risk for Dementia and Mild Cognitive Impairment: The Systolic Blood Pressure Intervention Trial10.1681/ASN.2020010038Fri, 26 Jun 2020 07:17:32 GMT-07:00Kidney Disease, Intensive Hypertension Treatment, and Risk for Dementia and Mild Cognitive Impairment: The Systolic Blood Pressure Intervention TrialKurella Tamura, ManjulaGaussoin, Sarah A.Pajewski, Nicholas M.Chelune, Gordon J.Freedman, Barry I.Gure, Tanya R.Haley, William E.Killeen, Anthony A.Oparil, SuzanneRapp, Stephen R.Rifkin, Dena E.Supiano, MarkWilliamson, Jeff D.Weiner, Daniel E.,Kurella Tamura, ManjulaGaussoin, Sarah A.Pajewski, Nicholas M.Chelune, Gordon J.Freedman, Barry I.Gure, Tanya R.Haley, William E.Killeen, Anthony A.Oparil, SuzanneRapp, Stephen R.Rifkin, DenaSupiano, MarkWilliamson, Jeff D.Weiner, Daniel E.2020-06-26T07:17:32-07:00doi:10.1681/ASN.2020010038hwp:resource-id:jnephrol;31/9/2122American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologysystolic blood pressure, Epidemiology and outcomes, glomerular filtration rate, hypertensionClinical EpidemiologyClinical Epidemiologyresearch-article20202020-09-01September 202010.1681/ASN.20200100381046-66731533-34502020-06-26T07:17:32-07:002020-09Journal of the American Society of NephrologyClinical Epidemiology31921222132
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- Rate and Predictors of Finding Monoclonal Gammopathy of Renal Significance (MGRS) Lesions on Kidney Biopsy in Patients with Monoclonal Gammopathy10.1681/ASN.2020010054Mon, 03 Aug 2020 08:33:52 GMT-07:00Rate and Predictors of Finding Monoclonal Gammopathy of Renal Significance (MGRS) Lesions on Kidney Biopsy in Patients with Monoclonal GammopathyKlomjit, NattawatLeung, NelsonFervenza, FernandoSethi, SanjeevZand, Ladan2020-08-03T08:33:52-07:00doi:10.1681/ASN.2020010054hwp:resource-id:jnephrol;31/10/2400American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyMGUS, MGRS, monoclonal gammopathy of renal significance, monoclonal gammopathy of undetermined significance, renal biopsy, kidney biopsyClinical EpidemiologyClinical Epidemiologyresearch-article20202020-10-01October 202010.1681/ASN.20200100541046-66731533-34502020-08-03T08:33:52-07:002020-10Journal of the American Society of NephrologyClinical Epidemiology311024002411
- Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu Mesenchyme10.1681/ASN.2019101075Fri, 21 Aug 2020 07:56:25 GMT-07:00Differentiation of a Contractile, Ureter-Like Tissue, from Embryonic Stem Cell–Derived Ureteric Bud and Ex Fetu MesenchymeSallam, MayPalakkan, Anwar A.Mills, Christopher G.Tarnick, JuliaElhendawi, MonaMarson, LornaDavies, Jamie A.2020-08-21T07:56:25-07:00doi:10.1681/ASN.2019101075hwp:resource-id:jnephrol;31/10/2253American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologystem cell, renal stem cell, ureteric bud, kidney developmentRapid CommunicationRapid Communicationresearch-article20202020-10-01October 202010.1681/ASN.20191010751046-66731533-34502020-08-21T07:56:25-07:002020-10Journal of the American Society of NephrologyRapid Communication311010722532231i22622232i
- This Month’s Highlights10.1681/ASN.2020081221Wed, 30 Sep 2020 10:00:27 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2020-09-30T10:00:27-07:00doi:10.1681/ASN.2020081221hwp:resource-id:jnephrol;31/10/iAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20202020-10-01October 202010.1681/ASN.20200812211046-66731533-34502020-09-30T10:00:27-07:002020-10Journal of the American Society of NephrologyThis Month’s Highlights3110ii
- Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to Injury10.1681/ASN.2020020220Fri, 10 Jul 2020 10:44:14 GMT-07:00Single-Cell Transcriptome Profiling of the Kidney Glomerulus Identifies Key Cell Types and Reactions to InjuryChung, Jun-JaeGoldstein, LeonardChen, Ying-Jiun J.Lee, JiyeonWebster, Joshua D.Roose-Girma, MeronePaudyal, Sharad C.Modrusan, ZoraDey, AnweshaShaw, Andrey S.2020-07-10T10:44:14-07:00doi:10.1681/ASN.2020020220hwp:resource-id:jnephrol;31/10/2341American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, chronic kidney disease, diabetic glomerulopathy, glomerular disease, transcriptional profilingBasic ResearchBasic Researchresearch-article20202020-10-01October 202010.1681/ASN.20200202201046-66731533-34502020-07-10T10:44:14-07:002020-10Journal of the American Society of NephrologyBasic Research311023412354
- Two Tales of Single-Cell RNA Sequencing: Gene Expression and Alternative Splicing in Mouse Kidney Development10.1681/ASN.2020081180Thu, 03 Sep 2020 12:26:12 GMT-07:00Two Tales of Single-Cell RNA Sequencing: Gene Expression and Alternative Splicing in Mouse Kidney DevelopmentChen, Lihe2020-09-03T12:26:12-07:00doi:10.1681/ASN.2020081180hwp:resource-id:jnephrol;31/10/2234American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, single-cell RNA-seq, alternative splicingEditorialsEditorialseditorial20202020-10-01October 202010.1681/ASN.20200811801046-66731533-34502020-09-03T12:26:12-07:002020-10Journal of the American Society of NephrologyEditorials3110102234227822362291
- Cell-Free DNA: Proceed, but with Caution10.1681/ASN.2020060915Mon, 10 Aug 2020 04:48:48 GMT-07:00Cell-Free DNA: Proceed, but with CautionCrew, R. JohnKhairallah, PascaleHusain, S. Ali2020-08-10T16:48:48-07:00doi:10.1681/ASN.2020060915hwp:resource-id:jnephrol;31/10/2491American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute rejection, kidney transplantation, renal biopsy, immunosuppressionLetters to the EditorLetters to the Editorletter20202020-10-01October 202010.1681/ASN.20200609151046-66731533-34502020-08-10T16:48:48-07:002020-10Journal of the American Society of NephrologyLetters to the Editor311024912492
- Use of Do-Not-Resuscitate Orders for Critically Ill Patients with ESKD10.1681/ASN.2020010088Thu, 27 Aug 2020 07:33:43 GMT-07:00Use of Do-Not-Resuscitate Orders for Critically Ill Patients with ESKDDanziger, JohnÁngel Armengol de la Hoz, MiguelCeli, Leo AnthonyCohen, Robert A.Mukamal, Kenneth J.2020-08-27T07:33:43-07:00doi:10.1681/ASN.2020010088hwp:resource-id:jnephrol;31/10/2393American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologypalliative care, goals of care, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20202020-10-01October 202010.1681/ASN.20200100881046-66731533-34502020-08-27T07:33:43-07:002020-10Journal of the American Society of NephrologyClinical Epidemiology3110102393223223992234
- Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial10.1681/ASN.2020020225Thu, 13 Aug 2020 05:53:42 GMT-07:00Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled TrialWitham, Miles D.Lees, Jennifer S.White, MyraBand, MargaretBell, SamiraChantler, Donna J.Ford, IanFulton, Roberta L.Kennedy, GwenLittleford, Roberta C.McCrea, Ian V.McGlynn, DeborahPanarelli, MaurizioRalston, Maximilian R.Rutherford, ElaineSevern, AlisonThomson, NicolaTraynor, Jamie P.Struthers, Allan D.Wetherall, KirstyMark, Patrick B.2020-08-13T05:53:42-07:00doi:10.1681/ASN.2020020225hwp:resource-id:jnephrol;31/10/2434American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyvitamin K, chronic kidney disease, vascular calcification, arterial stiffnessClinical ResearchClinical Researchresearch-article20202020-10-01October 202010.1681/ASN.20200202251046-66731533-34502020-08-13T05:53:42-07:002020-10Journal of the American Society of NephrologyClinical Research311024342445
- Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy10.1681/ASN.2019111160Fri, 07 Aug 2020 10:51:02 GMT-07:00Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD TherapyMidgley, Adam C.Wei, YongzhenZhu, DashuaiGao, FangliYan, HongyuKhalique, AnilaLuo, WenyaJiang, HuanLiu, XiangshengGuo, JiasenZhang, ChuangnianFeng, GuoweiWang, KaiBai, XueyuanNing, WenYang, ChaoZhao, QiangKong, Deling2020-08-07T10:51:02-07:00doi:10.1681/ASN.2019111160hwp:resource-id:jnephrol;31/10/2292American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, fibrosis, nanoparticles, gene therapy, regenerative medicineBasic ResearchBasic Researchresearch-article20202020-10-01October 202010.1681/ASN.20191111601046-66731533-34502020-08-07T10:51:02-07:002020-10Journal of the American Society of NephrologyBasic Research311022922311
- Do-Not-Resuscitate Orders among Patients with ESKD Admitted to the Intensive Care Unit: A Bird’s Eye View10.1681/ASN.2020081160Thu, 27 Aug 2020 07:33:42 GMT-07:00Do-Not-Resuscitate Orders among Patients with ESKD Admitted to the Intensive Care Unit: A Bird’s Eye ViewScherer, Jennifer S.O’Hare, Ann M.2020-08-27T07:33:42-07:00doi:10.1681/ASN.2020081160hwp:resource-id:jnephrol;31/10/2232American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyESKDEditorialsEditorialseditorial20202020-10-01October 202010.1681/ASN.20200811601046-66731533-34502020-08-27T07:33:42-07:002020-10Journal of the American Society of NephrologyEditorials3110102232239322342399
- Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program10.1681/ASN.2019121312Tue, 21 Jul 2020 02:54:18 GMT-07:00Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS ProgramOshima, MegumiNeal, BruceToyama, TadashiOhkuma, ToshiakiLi, Qiangde Zeeuw, DickHeerspink, Hiddo J.L.Mahaffey, Kenneth W.Fulcher, GregoryCanovatchel, WilliamMatthews, David R.Perkovic, Vlado2020-07-21T14:54:18-07:00doi:10.1681/ASN.2019121312hwp:resource-id:jnephrol;31/10/2446American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyType 2 diabetes, eGFR decline, canagliflozin, SGLT2 inhibitorsClinical ResearchClinical Researchresearch-article20202020-10-01October 202010.1681/ASN.20191213121046-66731533-34502020-07-21T14:54:18-07:002020-10Journal of the American Society of NephrologyClinical Research311024462456
- Correction10.2215/CJN.13090820Mon, 14 Sep 2020 07:53:03 GMT-07:00CorrectionAmerican Society of Nephrology2020-09-14T07:53:03-07:00doi:10.2215/CJN.13090820hwp:resource-id:clinjasn;15/10/1496American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumeditorial20202020-10-07October 07, 202010.2215/CJN.130908201555-90411555-905X2020-09-14T07:53:03-07:002020-10-07Clinical Journal of the American Society of NephrologyErratum151014961496
- Improving the Evaluation Process for Potential Living Kidney Donor Candidates10.2215/CJN.13470820Thu, 24 Sep 2020 05:36:55 GMT-07:00Improving the Evaluation Process for Potential Living Kidney Donor CandidatesFranks, Karol2020-09-24T05:36:55-07:00doi:10.2215/CJN.13470820hwp:resource-id:clinjasn;15/10/1381American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, living donors, process assessment, health carePatient VoicePatient Voiceeditorial20202020-10-07October 07, 202010.2215/CJN.134708201555-90411555-905X2020-09-24T05:36:55-07:002020-10-07Clinical Journal of the American Society of NephrologyPatient Voice1510101381146413821473
- SGLT2 Inhibitors across the Spectrum of Severity of CKD10.2215/CJN.13430820Tue, 29 Sep 2020 11:35:11 GMT-07:00SGLT2 Inhibitors across the Spectrum of Severity of CKDZiaolhagh, AliArgyropoulos, Christos2020-09-29T11:35:11-07:00doi:10.2215/CJN.13430820hwp:resource-id:clinjasn;15/10/1386American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyempaglflozin, KDIGO risk category, SGLT2 inhibitors, chronic kidney diseaseEditorialsEditorialseditorial20202020-10-07October 07, 202010.2215/CJN.134308201555-90411555-905X2020-09-29T11:35:11-07:002020-10-07Clinical Journal of the American Society of NephrologyEditorials15161010111386143312712713881444127127
- IgE-Mediated Immune Response and Antibody-Mediated Rejection10.2215/CJN.02870320Wed, 09 Sep 2020 07:33:56 GMT-07:00IgE-Mediated Immune Response and Antibody-Mediated RejectionRascio, FedericaPontrelli, PaolaNetti, Giuseppe StefanoManno, ElisabettaInfante, BarbaraSimone, SimonaCastellano, GiuseppeRanieri, ElenaSeveso, MichelaCozzi, EmanueleGesualdo, LoretoStallone, GiovanniGrandaliano, Giuseppe2020-09-09T07:33:56-07:00doi:10.2215/CJN.02870320hwp:resource-id:clinjasn;15/10/1474American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic rejection, mast cells, basophils, interferon alpha, IgEOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-10-07October 07, 202010.2215/CJN.028703201555-90411555-905X2020-09-09T07:33:56-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1510101474139214831393
- IgE in Antibody-Mediated Rejection10.2215/CJN.13000820Wed, 09 Sep 2020 07:33:56 GMT-07:00IgE in Antibody-Mediated RejectionAdam, Benjamin A.Gebel, Howard M.2020-09-09T07:33:56-07:00doi:10.2215/CJN.13000820hwp:resource-id:clinjasn;15/10/1392American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgE, antibody-mediated rejectionEditorialsEditorialseditorial20202020-10-07October 07, 202010.2215/CJN.130008201555-90411555-905X2020-09-09T07:33:56-07:002020-10-07Clinical Journal of the American Society of NephrologyEditorials1510101392147413931483
- Artificial Intelligence10.2215/CJN.13450820Wed, 16 Sep 2020 08:47:53 GMT-07:00Artificial IntelligenceHou, JeanNast, Cynthia C.2020-09-16T08:47:53-07:00doi:10.2215/CJN.13450820hwp:resource-id:clinjasn;15/10/1389American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, nephrology, renal biopsy, renal morphology, renal pathology, artificial intelligenceEditorialsEditorialseditorial20202020-10-07October 07, 202010.2215/CJN.134508201555-90411555-905X2020-09-16T08:47:53-07:002020-10-07Clinical Journal of the American Society of NephrologyEditorials1510101389144513911454
- Donor Age, Donor-Recipient Size Mismatch, and Kidney Graft Survival10.2215/CJN.02310220Tue, 25 Aug 2020 07:08:34 GMT-07:00Donor Age, Donor-Recipient Size Mismatch, and Kidney Graft SurvivalLepeytre, FannyDelmas-Frenette, CatherineZhang, XunLarivière-Beaudoin, StéphanieSapir-Pichhadze, RuthFoster, Bethany J.Cardinal, Héloïse2020-08-25T07:08:34-07:00doi:10.2215/CJN.02310220hwp:resource-id:clinjasn;15/10/1455American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, kidney transplantation, graft survival, donor, organ transplantOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-10-07October 07, 202010.2215/CJN.023102201555-90411555-905X2020-08-25T07:08:34-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles151014551463
- Evaluation of the Classification Accuracy of the Kidney Biopsy Direct Immunofluorescence through Convolutional Neural Networks10.2215/CJN.03210320Wed, 16 Sep 2020 08:47:53 GMT-07:00Evaluation of the Classification Accuracy of the Kidney Biopsy Direct Immunofluorescence through Convolutional Neural NetworksLigabue, GiuliaPollastri, FedericoFontana, FrancescoLeonelli, MarcoFurci, LucianaGiovanella, SilviaAlfano, GaetanoCappelli, GianniTesta, FrancescaBolelli, FedericoGrana, CostantinoMagistroni, Riccardo2020-09-16T08:47:53-07:00doi:10.2215/CJN.03210320hwp:resource-id:clinjasn;15/10/1445American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal pathology, renal biopsy, immunofluorescence, Convoluted Neural Network, artificial intelligenceOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-10-07October 07, 202010.2215/CJN.032103201555-90411555-905X2020-09-16T08:47:53-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1510101445138914541391
- Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk Categories10.2215/CJN.14901219Tue, 29 Sep 2020 11:35:12 GMT-07:00Empagliflozin and Cardiovascular and Kidney Outcomes across KDIGO Risk CategoriesLevin, AdeeraPerkovic, VladoWheeler, David C.Hantel, StefanGeorge, Jyothis T.von Eynatten, MaximilianKoitka-Weber, AudreyWanner, Christoph,2020-09-29T11:35:12-07:00doi:10.2215/CJN.14901219hwp:resource-id:clinjasn;15/10/1433American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, empagliflozin, glomerular filtration rate, KDIGO, kidney disease, SGLT2 inhibitionOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20202020-10-07October 07, 202010.2215/CJN.149012191555-90411555-905X2020-09-29T11:35:12-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1510101433138614441388
- A RAND-Modified Delphi on Key Indicators to Measure the Efficiency of Living Kidney Donor Candidate Evaluations10.2215/CJN.03780320Thu, 24 Sep 2020 05:36:56 GMT-07:00A RAND-Modified Delphi on Key Indicators to Measure the Efficiency of Living Kidney Donor Candidate EvaluationsHabbous, StevenBarnieh, LianneLitchfield, KennethMcKenzie, SusanReich, MarianLam, Ngan N.Mucsi, IstvanBugeja, AnnYohanna, SeychelleMainra, RahulChong, KateFantus, DanielPrasad, G V RameshDipchand, ChristineGill, JagbirGetchell, LeahGarg, Amit X.2020-09-24T05:36:56-07:00doi:10.2215/CJN.03780320hwp:resource-id:clinjasn;15/10/1464American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, kidney transplantation, living donorsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-10-07October 07, 202010.2215/CJN.037803201555-90411555-905X2020-09-24T05:36:56-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1510101464138114731382
- Performance of the Kidney Failure Risk Equation by Disease Etiology in Advanced CKD10.2215/CJN.03940320Mon, 14 Sep 2020 07:53:04 GMT-07:00Performance of the Kidney Failure Risk Equation by Disease Etiology in Advanced CKDHundemer, Gregory L.Tangri, NavdeepSood, Manish M.Ramsay, TimBugeja, AnnBrown, Pierre A.Clark, Edward G.Biyani, MohanWhite, Christine A.Akbari, Ayub2020-09-14T07:53:04-07:00doi:10.2215/CJN.03940320hwp:resource-id:clinjasn;15/10/1424American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic kidney failure, kidney failure, progression of chronic renal failure, kidney failure risk equation, KFRE, end-stage kidney diseaseOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-10-07October 07, 202010.2215/CJN.039403201555-90411555-905X2020-09-14T07:53:04-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles151014241432
- Cuffless Blood Pressure MonitoringCurrent BP measurements are on the basis of traditional BP cuff approaches. Ambulatory BP monitoring, at 15- to 30-minute intervals usually over 24 hours, provides sufficiently continuous readings that are superior to the office-based snapshot, but this system is not suitable for frequent repeated use. A true continuous BP measurement that could collect BP passively and frequently would require a cuffless method that could be worn by the patient, with the data stored electronically much the same way that heart rate and heart rhythm are already done routinely. Ideally, BP should be measured continuously and frequently during diverse activities during both daytime and nighttime in the same subject by means of novel devices. There is increasing excitement for newer methods to measure BP on the basis of sensors and algorithm development. As new devices are refined and their accuracy is improved, it will be possible to better assess masked hypertension, nocturnal hypertension, and the severity and variability of BP. In this review, we discuss the progression in the field, particularly in the last 5 years, ending with sensor-based approaches that incorporate machine learning algorithms to personalized medicine.10.2215/CJN.03680320Fri, 17 Jul 2020 07:54:22 GMT-07:00Cuffless Blood Pressure MonitoringCurrent BP measurements are on the basis of traditional BP cuff approaches. Ambulatory BP monitoring, at 15- to 30-minute intervals usually over 24 hours, provides sufficiently continuous readings that are superior to the office-based snapshot, but this system is not suitable for frequent repeated use. A true continuous BP measurement that could collect BP passively and frequently would require a cuffless method that could be worn by the patient, with the data stored electronically much the same way that heart rate and heart rhythm are already done routinely. Ideally, BP should be measured continuously and frequently during diverse activities during both daytime and nighttime in the same subject by means of novel devices. There is increasing excitement for newer methods to measure BP on the basis of sensors and algorithm development. As new devices are refined and their accuracy is improved, it will be possible to better assess masked hypertension, nocturnal hypertension, and the severity and variability of BP. In this review, we discuss the progression in the field, particularly in the last 5 years, ending with sensor-based approaches that incorporate machine learning algorithms to personalized medicine.Pandit, Jay A.Lores, EnriqueBatlle, Daniel2020-07-17T07:54:22-07:00doi:10.2215/CJN.03680320hwp:resource-id:clinjasn;15/10/1531American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBlood Pressure Monitoring, Ambulatory, blood pressure, Masked Hypertension, Heart Rate, Blood Pressure Determination, Machine Learning, Blood Pressure MonitorsReviewReviewresearch-article20202020-10-07October 07, 202010.2215/CJN.036803201555-90411555-905X2020-07-17T07:54:22-07:002020-10-07Clinical Journal of the American Society of NephrologyReview151015311538
- Acute Kidney Injury and Risk of CKD and Hypertension after Pediatric Cardiac Surgery10.2215/CJN.00150120Fri, 18 Sep 2020 10:25:18 GMT-07:00Acute Kidney Injury and Risk of CKD and Hypertension after Pediatric Cardiac SurgeryZappitelli, MichaelParikh, Chirag R.Kaufman, James S.Go, Alan S.Kimmel, Paul L.Hsu, Chi-yuanCoca, Steven G.Chinchilli, Vernon M.Greenberg, Jason H.Moxey-Mims, Marva M.Ikizler, T. AlpCockovski, VedranDyer, Anne-MarieDevarajan, Prasad,2020-09-18T10:25:18-07:00doi:10.2215/CJN.00150120hwp:resource-id:clinjasn;15/10/1403American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, chronic kidney disease, clinical hypertension, pediatric nephrology, pediatric intensive care medicine, epidemiology and outcomes, acute kidney injuryOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20202020-10-07October 07, 202010.2215/CJN.001501201555-90411555-905X2020-09-18T10:25:18-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles151014031412
- Intrauterine Growth Restriction and Risk of Diverse Forms of Kidney Disease during the First 50 Years of Life10.2215/CJN.04080320Mon, 17 Aug 2020 07:03:53 GMT-07:00Intrauterine Growth Restriction and Risk of Diverse Forms of Kidney Disease during the First 50 Years of LifeGjerde, AnnaReisæter, Anna VarbergSkrunes, RannveigMarti, Hans-PeterVikse, Bjørn Egil2020-08-17T07:03:53-07:00doi:10.2215/CJN.04080320hwp:resource-id:clinjasn;15/10/1413American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, intrauterine growth, renal development, risk factorsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-10-07October 07, 202010.2215/CJN.040803201555-90411555-905X2020-08-17T07:03:53-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles151014131423
- The Histological Picture of Indication Biopsies in the First 2 Weeks after Kidney Transplantation10.2215/CJN.04230320Mon, 10 Aug 2020 04:47:46 GMT-07:00The Histological Picture of Indication Biopsies in the First 2 Weeks after Kidney TransplantationVan Loon, ElisabetLerut, EvelyneSenev, AleksandarCoemans, MaartenPirenne, JacquesMonbaliu, DiethardJochmans, InaSainz Barriga, MauricioDe Vusser, KatrienVan Craenenbroeck, Amaryllis H.Sprangers, BenEmonds, Marie-PauleKuypers, DirkNaesens, Maarten2020-08-10T16:47:46-07:00doi:10.2215/CJN.04230320hwp:resource-id:clinjasn;15/10/1484American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute allograft rejection, ischemia-reperfusion injury, delayed graft function, kidney biopsy, kidney transplantationOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-10-07October 07, 202010.2215/CJN.042303201555-90411555-905X2020-08-10T16:47:46-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles151014841493
- The Incidence, Risk Factors, and Prognosis of Acute Kidney Injury in Adult Patients with Coronavirus Disease 201910.2215/CJN.04650420Tue, 22 Sep 2020 12:25:27 GMT-07:00The Incidence, Risk Factors, and Prognosis of Acute Kidney Injury in Adult Patients with Coronavirus Disease 2019Cheng, YichunLuo, RanWang, XuWang, KunZhang, NanhuiZhang, MengWang, ZhixiangDong, LeiLi, JunhuaZeng, RuiYao, YingGe, ShuwangXu, Gang2020-09-22T12:25:27-07:00doi:10.2215/CJN.04650420hwp:resource-id:clinjasn;15/10/1394American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, COVID-19, mortality, prognosis, risk factorsOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20202020-10-07October 07, 202010.2215/CJN.046504201555-90411555-905X2020-09-22T12:25:27-07:002020-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1510101394138314021385
- COVID-19 in Children with Nephrotic Syndrome on Anti-CD20 Chronic Immunosuppression10.2215/CJN.06400420Fri, 10 Jul 2020 10:47:44 GMT-07:00COVID-19 in Children with Nephrotic Syndrome on Anti-CD20 Chronic ImmunosuppressionAngeletti, AndreaDrovandi, StefaniaSanguineri, FrancescaSantaniello, MariaFerrando, GiuliaForno, RobertoCipresso, GaiaCaridi, GianlucaRiella, Leonardo V.Cravedi, PaoloGhiggeri, Gian Marco2020-07-10T10:47:44-07:00doi:10.2215/CJN.06400420hwp:resource-id:clinjasn;15/10/1494American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunology, rheumatology, chronic glomerulonephritis, immunosuppression, lymphocytes, COVID-19, nephrotic syndromeResearch LetterResearch Letterletter20202020-10-07October 07, 202010.2215/CJN.064004201555-90411555-905X2020-07-10T10:47:44-07:002020-10-07Clinical Journal of the American Society of NephrologyResearch Letter151014941495
- COVID-19–Associated Acute Kidney Injury10.2215/CJN.13600820Tue, 22 Sep 2020 12:25:26 GMT-07:00COVID-19–Associated Acute Kidney InjurySiew, Edward D.Birkelo, Bethany C.2020-09-22T12:25:26-07:00doi:10.2215/CJN.13600820hwp:resource-id:clinjasn;15/10/1383American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal, COVID-19, epidemiology and outcomes, acute kidney injuryEditorialsEditorialseditorial20202020-10-07October 07, 202010.2215/CJN.136008201555-90411555-905X2020-09-22T12:25:26-07:002020-10-07Clinical Journal of the American Society of NephrologyEditorials1510101383139413851402
- Management Consideration in Drug-Induced Lactic Acidosis10.2215/CJN.14781219Fri, 22 May 2020 05:48:44 GMT-07:00Management Consideration in Drug-Induced Lactic AcidosisMorales, AlexanderDanziger, John2020-05-22T05:48:44-07:00doi:10.2215/CJN.14781219hwp:resource-id:clinjasn;15/10/1511American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacidosis, lactic, metformin, hypoglycemic agentsKidney Case Conferences: How I TreatKidney Case Conferences: How I Treatresearch-article20202020-10-07October 07, 202010.2215/CJN.147812191555-90411555-905X2020-05-22T05:48:44-07:002020-10-07Clinical Journal of the American Society of NephrologyKidney Case Conferences: How I Treat151015111512
- Offering Better Standards of Dialysis Care for Immigrants10.2215/CJN.01190120Fri, 22 May 2020 05:48:44 GMT-07:00Offering Better Standards of Dialysis Care for ImmigrantsCervantes, LiliaJohnson, TracyHill, AubreyEarnest, Mark2020-05-22T05:48:44-07:00doi:10.2215/CJN.01190120hwp:resource-id:clinjasn;15/10/1516American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal dialysis, Colorado, Emigrants and Immigrants, Reference StandardsPerspectivesPerspectivesresearch-article20202020-10-07October 07, 202010.2215/CJN.011901201555-90411555-905X2020-05-22T05:48:44-07:002020-10-07Clinical Journal of the American Society of NephrologyPerspectives151015161518
- Treatment of Granulomatosis with Polyangiitis and Microscopic Polyangiitis10.2215/CJN.15861219Fri, 29 May 2020 08:25:03 GMT-07:00Treatment of Granulomatosis with Polyangiitis and Microscopic PolyangiitisTesar, VladimirHruskova, Zdenka2020-05-29T08:25:03-07:00doi:10.2215/CJN.15861219hwp:resource-id:clinjasn;15/10/1519American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil CytoplasmicPerspectivesPerspectivesresearch-article20202020-10-07October 07, 202010.2215/CJN.158612191555-90411555-905X2020-05-29T08:25:03-07:002020-10-07Clinical Journal of the American Society of NephrologyPerspectives151015191521
- Can We Mend the Broken Clock by Timing Antihypertensive Therapy Sensibly?10.2215/CJN.00360120Mon, 11 May 2020 08:13:20 GMT-07:00Can We Mend the Broken Clock by Timing Antihypertensive Therapy Sensibly?Georgianos, Panagiotis I.Agarwal, Rajiv2020-05-11T08:13:20-07:00doi:10.2215/CJN.00360120hwp:resource-id:clinjasn;15/10/1513American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, hypertension, antihypertensive agentsPerspectivesPerspectivesresearch-article20202020-10-07October 07, 202010.2215/CJN.003601201555-90411555-905X2020-05-11T08:13:20-07:002020-10-07Clinical Journal of the American Society of NephrologyPerspectives151015131515
- Clinical Genetic Screening in Adult Patients with Kidney DiseaseExpanded accessibility of genetic sequencing technologies, such as chromosomal microarray and massively parallel sequencing approaches, is changing the management of hereditary kidney diseases. Genetic causes account for a substantial proportion of pediatric kidney disease cases, and with increased utilization of diagnostic genetic testing in nephrology, they are now also detected at appreciable frequencies in adult populations. Establishing a molecular diagnosis can have many potential benefits for patient care, such as guiding treatment, familial testing, and providing deeper insights on the molecular pathogenesis of kidney diseases. Today, with wider clinical use of genetic testing as part of the diagnostic evaluation, nephrologists have the challenging task of selecting the most suitable genetic test for each patient, and then applying the results into the appropriate clinical contexts. This review is intended to familiarize nephrologists with the various technical, logistical, and ethical considerations accompanying the increasing utilization of genetic testing in nephrology care.10.2215/CJN.15141219Thu, 09 Jul 2020 07:55:51 GMT-07:00Clinical Genetic Screening in Adult Patients with Kidney DiseaseExpanded accessibility of genetic sequencing technologies, such as chromosomal microarray and massively parallel sequencing approaches, is changing the management of hereditary kidney diseases. Genetic causes account for a substantial proportion of pediatric kidney disease cases, and with increased utilization of diagnostic genetic testing in nephrology, they are now also detected at appreciable frequencies in adult populations. Establishing a molecular diagnosis can have many potential benefits for patient care, such as guiding treatment, familial testing, and providing deeper insights on the molecular pathogenesis of kidney diseases. Today, with wider clinical use of genetic testing as part of the diagnostic evaluation, nephrologists have the challenging task of selecting the most suitable genetic test for each patient, and then applying the results into the appropriate clinical contexts. This review is intended to familiarize nephrologists with the various technical, logistical, and ethical considerations accompanying the increasing utilization of genetic testing in nephrology care.Cocchi, EnricoNestor, Jordan GabrielaGharavi, Ali G.2020-07-09T07:55:51-07:00doi:10.2215/CJN.15141219hwp:resource-id:clinjasn;15/10/1497American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, genomics, genetics, medical genetics, human genetics, kidney disease, familial kidney disease, referral and consultation, chronic kidney disease, Sanger sequencing, microarray techniques, array techniques, CGH array, whole exome sequencing, whole genome sequencing, massive parallel sequencing, translations, human genetic testing, genetic renal disease, familial nephropathy, Kidney Genomics Series, Genetic Testing, High-Throughput Nucleotide Sequencing, Patient Care, Renal Insufficiency, ChronicGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-10-07October 07, 202010.2215/CJN.151412191555-90411555-905X2020-07-09T07:55:51-07:002020-10-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease151014971510
- Toward Patient-Centered InnovationIndividuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall well-being. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle (i.e., from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to (1) develop a conceptual framework for a health-related quality of life PROM; (2) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and (3) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices.10.2215/CJN.00110120Fri, 10 Apr 2020 09:20:11 GMT-07:00Toward Patient-Centered InnovationIndividuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall well-being. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle (i.e., from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to (1) develop a conceptual framework for a health-related quality of life PROM; (2) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and (3) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices.Flythe, Jennifer E.Hilliard, Tandrea S.Ikeler, KourtneyKeller, SanGipson, Debbie S.Grandinetti, Amanda C.Nordyke, Robert J.Perrone, Ronald D.Roy-Chaudhury, PrabirUnruh, MarkWest, MelissaBocell, FraserHurst, Frank P.2020-04-10T09:20:11-07:00doi:10.2215/CJN.00110120hwp:resource-id:clinjasn;15/10/1522American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-reported outcomes, medical devices, innovation, dialysis, hemodialysis, end-stage renal disease, patient priorities, clinical trial, renal dialysis, quality of life, Public-Private Sector Partnerships, United States Food and Drug Administration, Patient Reported Outcome Measures, Renal Insufficiency, Renal Replacement Therapy, kidney, Patient-Centered CareFeaturesFeaturesresearch-article20202020-10-07October 07, 202010.2215/CJN.001101201555-90411555-905X2020-04-10T09:20:11-07:002020-10-07Clinical Journal of the American Society of NephrologyFeatures151015221530
- Reversal of Donor Hepatitis C Virus–Related Mesangial Proliferative GN in a Kidney Transplant Recipient10.1681/ASN.2020060820Wed, 16 Sep 2020 11:55:33 GMT-07:00Reversal of Donor Hepatitis C Virus–Related Mesangial Proliferative GN in a Kidney Transplant RecipientKhairallah, PascaleKudose, SatoruMorris, Heather K.Ratner, Lloyd E.Mohan, SumitRadhakrishnan, JaiChang, Jae-Hyung2020-09-16T11:55:33-07:00doi:10.1681/ASN.2020060820hwp:resource-id:jnephrol;31/10/2246American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, hepatitis, glomerulonephritis, transplant outcomesResearch LettersResearch Lettersletter20202020-10-01October 202010.1681/ASN.20200608201046-66731533-34502020-09-16T11:55:33-07:002020-10Journal of the American Society of NephrologyResearch Letters311022462249
- End-of-Life Care among US Adults with ESKD Who Were Waitlisted or Received a Kidney Transplant, 2005–201410.1681/ASN.2020030342Wed, 09 Sep 2020 07:36:13 GMT-07:00End-of-Life Care among US Adults with ESKD Who Were Waitlisted or Received a Kidney Transplant, 2005–2014Butler, Catherine R.Reese, Peter P.Perkins, James D.Hall, Yoshio N.Curtis, J. RandallKurella Tamura, ManjulaO'Hare, Ann M.2020-09-09T07:36:13-07:00doi:10.1681/ASN.2020030342hwp:resource-id:jnephrol;31/10/2424American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, kidney transplantation, quality of life, United States Renal Data SystemClinical ResearchClinical Researchresearch-article20202020-10-01October 202010.1681/ASN.20200303421046-66731533-34502020-09-09T07:36:13-07:002020-10Journal of the American Society of NephrologyClinical Research311024242433
- Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney Transplantation10.1681/ASN.2020030320Tue, 28 Jul 2020 10:45:12 GMT-07:00Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney TransplantationLouis, KevinMacedo, CamilaBailly, ElodieLau, LouisRamaswami, BalaMarrari, MarilynLandsittel, DouglasChang, AlexanderChandran, UmaFadakar, PaulYamada, MasakiChalasani, GeethaRandhawa, ParmjeetZeevi, AdrianaSingh, HarinderLefaucheur, CarmenMetes, Diana2020-07-28T10:45:12-07:00doi:10.1681/ASN.2020030320hwp:resource-id:jnephrol;31/10/2457American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, lymphocytes, immunology, kidney transplantation, transcriptional profiling, transplant outcomesClinical ResearchClinical Researchresearch-article20202020-10-01October 202010.1681/ASN.20200303201046-66731533-34502020-07-28T10:45:12-07:002020-10Journal of the American Society of NephrologyClinical Research311024572474
- COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical Outcomes10.1681/ASN.2020050639Wed, 26 Aug 2020 10:27:44 GMT-07:00COVID-19 Infection in Kidney Transplant Recipients: Disease Incidence and Clinical OutcomesElias, MichellePievani, DanieleRandoux, ChristineLouis, KevinDenis, BlandineDelion, AlexandraLe Goff, OcéaneAntoine, CorinneGreze, ClarissePillebout, EvangelineAbboud, ImadGlotz, DenisDaugas, EricLefaucheur, Carmen2020-08-26T10:27:44-07:00doi:10.1681/ASN.2020050639hwp:resource-id:jnephrol;31/10/2413American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, coronavirus, pandemic, kidney transplantation, SARS-CoV-2Clinical ResearchClinical Researchresearch-article20202020-10-01October 202010.1681/ASN.20200506391046-66731533-34502020-08-26T10:27:44-07:002020-10Journal of the American Society of NephrologyClinical Research311024132423
- Correction10.1681/ASN.2020081117Wed, 30 Sep 2020 10:00:27 GMT-07:00CorrectionAmerican Society of Nephrology2020-09-30T10:00:27-07:00doi:10.1681/ASN.2020081117hwp:resource-id:jnephrol;31/10/2494American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19CorrectionCorrectioncorrection20202020-10-01October 202010.1681/ASN.20200811171046-66731533-34502020-09-30T10:00:27-07:002020-10Journal of the American Society of NephrologyCorrection31311082494168324941687
- The Exclusion of Patients with CKD in Prospectively Registered Interventional Trials for COVID-19—a Rapid Review of International Registry Data10.1681/ASN.2020060877Tue, 08 Sep 2020 12:13:47 GMT-07:00The Exclusion of Patients with CKD in Prospectively Registered Interventional Trials for COVID-19—a Rapid Review of International Registry DataMajor, RupertSelvaskandan, HareshMakkeyah, Yahya MostafaHull, KatherineKuverji, ApexaGraham-Brown, Matthew2020-09-08T12:13:47-07:00doi:10.1681/ASN.2020060877hwp:resource-id:jnephrol;31/10/2250American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical trial, chronic kidney disease, COVID-19Research LettersResearch Lettersletter20202020-10-01October 202010.1681/ASN.20200608771046-66731533-34502020-09-08T12:13:47-07:002020-10Journal of the American Society of NephrologyResearch Letters311022502252
- Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup10.1681/ASN.2020050564Tue, 22 Sep 2020 06:29:13 GMT-07:00Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP WorkgroupBerling, IngridKing, Joshua D.Shepherd, GreeneHoffman, Robert S.Alhatali, BadriaLavergne, ValeryRoberts, Darren M.Gosselin, SophieWilson, GabrielleNolin, Thomas D.Ghannoum, Marc,Anseeuw, KurtBird, StevenBunchman, TimothyBouchard, JoséeCalello, DianeChin, PaulDoi, KentGalvao, TaisGoldfarb, DavidHassanian, HosseinHoegberg, LotteKallab, SibaKebede, SofiaKielstein, JanLewington, AndrewLi, YiMacedo, EtienneMacLaren, RobMégarbane, BrunoMowry, JamesOstermann, MarliesPeng, AiRoy, Jean-PhilippeVijayan, AnithaWalsh, StevenWong, AnselmWood, DavidYates, Christopher2020-09-22T06:29:13-07:00doi:10.1681/ASN.2020050564hwp:resource-id:jnephrol;31/10/2475American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyQuinine, Chloroquine, Hydroxychloroquine, hemodialysis, hemofiltration, COVID-19Meta-AnalysisMeta-Analysisresearch-article20202020-10-01October 202010.1681/ASN.20200505641046-66731533-34502020-09-22T06:29:13-07:002020-10Journal of the American Society of NephrologyMeta-Analysis311024752489
- Perspectives on COVID-19 from Singapore: Impact on ESKD Care and Medical Education10.1681/ASN.2020050721Tue, 18 Aug 2020 05:47:30 GMT-07:00Perspectives on COVID-19 from Singapore: Impact on ESKD Care and Medical EducationCoffman, Thomas M.Chan, Choong MengChoong, Lina Hui-LinCurran, IanTan, Hak KoonTan, Chorh Chuan2020-08-18T05:47:30-07:00doi:10.1681/ASN.2020050721hwp:resource-id:jnephrol;31/10/2242American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, education, ESKD Care, AsiaPerspectivesPerspectivesresearch-article20202020-10-01October 202010.1681/ASN.20200507211046-66731533-34502020-08-18T05:47:30-07:002020-10Journal of the American Society of NephrologyPerspectives311022422245
- Improving Care for Patients after Hospitalization with AKI10.1681/ASN.2020040397Thu, 10 Sep 2020 06:58:25 GMT-07:00Improving Care for Patients after Hospitalization with AKISiew, Edward D.Liu, Kathleen D.Bonn, JohnChinchilli, VernonDember, Laura M.Girard, Timothy D.Greene, TomHernandez, Adrian F.Ikizler, T. AlpJames, Matthew T.Kampschroer, KevinKopp, Jeffrey B.Levy, MarlaPalevsky, Paul M.Pannu, NeeshParikh, Chirag R.Rocco, Michael V.Silver, Samuel A.Thiessen-Philbrook, HeatherWald, RonXie, YiningKimmel, Paul L.Star, Robert A.2020-09-10T06:58:25-07:00doi:10.1681/ASN.2020040397hwp:resource-id:jnephrol;31/10/2237American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, epidemiology and outcomesPerspectivesPerspectivesresearch-article20202020-10-01October 202010.1681/ASN.20200403971046-66731533-34502020-09-10T06:58:25-07:002020-10Journal of the American Society of NephrologyPerspectives311022372241
- Heterozygous Urinary Abnormality–Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome10.34067/KID.0000372019Thu, 16 Jul 2020 01:33:03 GMT-07:00Heterozygous Urinary Abnormality–Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport SyndromeHorinouchi, TomokoYamamura, TomohikoNagano, ChinaSakakibara, NanaIshiko, ShinyaAoto, YuyaRossanti, RiniNakanishi, KoichiShima, YukoMorisada, NaoyaIijima, KazumotoNozu, Kandai2020-07-16T13:33:03-07:00doi:10.34067/KID.0000372019hwp:resource-id:kidney360;1/9/936American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360genetics, autosomal recessive Alport syndrome, genotype-phenotype correlation, hematuria, benign familial, heterozygous mutation, kidney failure, chronic, nephritis, hereditary, prognosis, prognostic predicting factor, retrospective studies, urinary abnormalitiesOriginal InvestigationsGeneticsOriginal InvestigationsGeneticsresearch-article20202020-09-2410.34067/KID.00003720192641-76502020-07-16T13:33:03-07:002020-09-24Kidney360Original Investigations19936942
- Fibrillary Glomerulonephritis and DnaJ Homolog Subfamily B Member 9 (DNAJB9)Fibrillary GN (FGN) is a rare glomerular disease that is diagnosed based on the presence of fibrils in glomeruli. The fibrils are typically noncongophilic, randomly oriented, and measure 12–24 nm. Traditionally, electron microscopy (EM) has been an important tool to aid in the diagnosis of FGN by identifying the fibrils and to distinguish it from other entities that could mimic FGN. However, recently DnaJ homolog subfamily B member 9 (DNAJB9) has emerged as both a specific and sensitive biomarker in patients with FGN. It allows prompt diagnosis and alleviates reliance on EM. DNAJB9 is a cochaperone of heat shock protein 70 and is involved in endoplasmic reticulum protein-folding pathways. But its role in the pathogenesis of FGN remains elusive. DNAJB9 may act as a putative antigen or alternatively it may secondarily bind to misfolded IgG in the glomeruli. These hypotheses need future studies to elucidate the role of DNAJB9 in the pathogenesis of FGN. The treatment regimen for FGN has been limited due to paucity of studies. Most patients receive combination immunosuppressive regimens. Rituximab has been studied the most in FGN and it may delay disease progression. Prognosis of FGN remains poor and 50% require dialysis within 2 years of diagnosis. Despite its poor prognosis in native kidneys, the rate of recurrence post-transplantation is low (20%) and patient as well as allograft outcomes are similar to patients without FGN.10.34067/KID.0002532020Wed, 08 Jul 2020 09:45:26 GMT-07:00Fibrillary Glomerulonephritis and DnaJ Homolog Subfamily B Member 9 (DNAJB9)Fibrillary GN (FGN) is a rare glomerular disease that is diagnosed based on the presence of fibrils in glomeruli. The fibrils are typically noncongophilic, randomly oriented, and measure 12–24 nm. Traditionally, electron microscopy (EM) has been an important tool to aid in the diagnosis of FGN by identifying the fibrils and to distinguish it from other entities that could mimic FGN. However, recently DnaJ homolog subfamily B member 9 (DNAJB9) has emerged as both a specific and sensitive biomarker in patients with FGN. It allows prompt diagnosis and alleviates reliance on EM. DNAJB9 is a cochaperone of heat shock protein 70 and is involved in endoplasmic reticulum protein-folding pathways. But its role in the pathogenesis of FGN remains elusive. DNAJB9 may act as a putative antigen or alternatively it may secondarily bind to misfolded IgG in the glomeruli. These hypotheses need future studies to elucidate the role of DNAJB9 in the pathogenesis of FGN. The treatment regimen for FGN has been limited due to paucity of studies. Most patients receive combination immunosuppressive regimens. Rituximab has been studied the most in FGN and it may delay disease progression. Prognosis of FGN remains poor and 50% require dialysis within 2 years of diagnosis. Despite its poor prognosis in native kidneys, the rate of recurrence post-transplantation is low (20%) and patient as well as allograft outcomes are similar to patients without FGN.Klomjit, NattawatAlexander, Mariam PriyaZand, Ladan2020-07-08T09:45:26-07:00doi:10.34067/KID.0002532020hwp:resource-id:kidney360;1/9/1002American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, DNAJB9, fibrillary glomerulonephritis, kidney glomerulus, proteinuria, rituximabReview ArticlesReview Articlesreview-article20202020-09-2410.34067/KID.00025320202641-76502020-07-08T09:45:26-07:002020-09-24Kidney360Review Articles1910021013
- Penile Pain in a Hemodialysis Patient10.34067/KID.0001472020Thu, 24 Sep 2020 05:30:22 GMT-07:00Penile Pain in a Hemodialysis PatientCabrera Fermin, Clara MiguelinaSingh, ShashankKoratala, Abhilash2020-09-24T05:30:22-07:00doi:10.34067/KID.0001472020hwp:resource-id:kidney360;1/9/1032American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, calcific uremic arteriolopathy, penile calciphylaxisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-09-2410.34067/KID.00014720202641-76502020-09-24T05:30:22-07:002020-09-24Kidney360Clinical Images in Nephrology and Dialysis1910321033
- A Systematic Approach To Promoting Home Hemodialysis during End Stage Kidney DiseaseHome dialysis has garnered much attention since the advent of the Advancing American Kidney Health initiative. For many patients and nephrologists, home dialysis and peritoneal dialysis are synonymous. However, home hemodialysis (HHD) should not be forgotten. Since 2004, HHD has grown more rapidly than other dialytic modalities. The cardinal feature of HHD is customizability of treatment intensity, which can be titrated to address the vexing problems of volume and pressure loading during interdialytic gaps and ultrafiltration intensity during each hemodialysis session. Growing HHD utilization requires commitment to introducing patients to the modality throughout the course of ESKD. In this article, we describe a set of strategies for introducing HHD concepts and equipment. First, patients initiating dialysis may attend a transitional care unit, which offers an educational program about all dialytic modalities during 3–5 weeks of in-facility hemodialysis, possibly using HHD equipment. Second, prevalent patients on hemodialysis may participate in “trial-run” programs, which allow patients to experience increased treatment frequency and HHD equipment for several weeks, but without the overt commitment of initiating HHD training. In both models, perceived barriers to HHD—including fear of equipment, anxiety about self-cannulation, catheter dependence, and the absence of a care partner—can be addressed in a supportive setting. Third, patients on peritoneal dialysis who are nearing a transition to hemodialysis may be encouraged to consider a home-to-home transition (i.e., from peritoneal dialysis to HHD). Taken together, these strategies represent a systematic approach to growing HHD utilization in multiple phenotypes of patients on dialysis. With the feature of facilitating intensive hemodialysis, HHD can be a key not only to satiating demand for home dialysis, but also to improving the health of patients on dialysis.10.34067/KID.0003132020Wed, 08 Jul 2020 09:45:26 GMT-07:00A Systematic Approach To Promoting Home Hemodialysis during End Stage Kidney DiseaseHome dialysis has garnered much attention since the advent of the Advancing American Kidney Health initiative. For many patients and nephrologists, home dialysis and peritoneal dialysis are synonymous. However, home hemodialysis (HHD) should not be forgotten. Since 2004, HHD has grown more rapidly than other dialytic modalities. The cardinal feature of HHD is customizability of treatment intensity, which can be titrated to address the vexing problems of volume and pressure loading during interdialytic gaps and ultrafiltration intensity during each hemodialysis session. Growing HHD utilization requires commitment to introducing patients to the modality throughout the course of ESKD. In this article, we describe a set of strategies for introducing HHD concepts and equipment. First, patients initiating dialysis may attend a transitional care unit, which offers an educational program about all dialytic modalities during 3–5 weeks of in-facility hemodialysis, possibly using HHD equipment. Second, prevalent patients on hemodialysis may participate in “trial-run” programs, which allow patients to experience increased treatment frequency and HHD equipment for several weeks, but without the overt commitment of initiating HHD training. In both models, perceived barriers to HHD—including fear of equipment, anxiety about self-cannulation, catheter dependence, and the absence of a care partner—can be addressed in a supportive setting. Third, patients on peritoneal dialysis who are nearing a transition to hemodialysis may be encouraged to consider a home-to-home transition (i.e., from peritoneal dialysis to HHD). Taken together, these strategies represent a systematic approach to growing HHD utilization in multiple phenotypes of patients on dialysis. With the feature of facilitating intensive hemodialysis, HHD can be a key not only to satiating demand for home dialysis, but also to improving the health of patients on dialysis.Lockridge, RobertWeinhandl, EricKraus, MichaelSchreiber, MartinSpry, LeslieTailor, PrayusCarver, MichelleGlickman, JoelMiller, Brent2020-07-08T09:45:26-07:00doi:10.34067/KID.0003132020hwp:resource-id:kidney360;1/9/993American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, cardiovascular disease, education, hemodialysis, home, kidney failure, chronic, peritoneal dialysis, renal dialysis, transitional care unit, volumeReview ArticlesReview Articlesreview-article20202020-09-2410.34067/KID.00031320202641-76502020-07-08T09:45:26-07:002020-09-24Kidney360Review Articles199931001
- Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy10.34067/KID.0002802020Fri, 07 Aug 2020 06:11:58 GMT-07:00Substitution of Oral for Intravenous Cyclophosphamide in Membranous NephropathyLuzardo, LeonellaOttati, GabrielaCabrera, JimenaTrujillo, HernandoGarau, MarielaGonzález Bedat, CarlotaCoitiño, RubenAunchayna, María H.Santiago, JoséBaldovinos, GracielaSilvariño, RicardoFerreiro, AlejandroGonzález-Martínez, FranciscoGadola, LilianaNoboa, OscarCaorsi, Hena2020-08-07T06:11:58-07:00doi:10.34067/KID.0002802020hwp:resource-id:kidney360;1/9/943American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, glomerulopathies, intravenous cyclophosphamide, membranous glomerulonephritis, membranous nephropathy, nephrotic syndrome, relapse, remissionOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-09-2410.34067/KID.00028020202641-76502020-08-07T06:11:58-07:002020-09-24Kidney360Original Investigations19943949
- Unexpected FDG-PET Scan Finding in an ESKD Patient with Weight Loss10.34067/KID.0001582020Thu, 24 Sep 2020 05:30:22 GMT-07:00Unexpected FDG-PET Scan Finding in an ESKD Patient with Weight LossPonlot, EléonoreGoffin, Eric2020-09-24T05:30:22-07:00doi:10.34067/KID.0001582020hwp:resource-id:kidney360;1/9/1034American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, catheter, FDG-PET scan, peritoneal dialysis, peritonitis, Staphylococcus aureus, vancomycinClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-09-2410.34067/KID.00015820202641-76502020-09-24T05:30:22-07:002020-09-24Kidney360Clinical Images in Nephrology and Dialysis1910341035
- Single Lumen Alternating Micro-Batch Hemodiafiltration (SLAMB-HDF): A Device for Minimally Invasive Renal Replacement TherapyBlood-based RRT, such as hemodialysis, requires access to the bloodstream and adequate blood flow to enable the requisite clearance. As such, nearly all RRT systems require two lumens, enabling a blood circuit that pulls blood from one lumen or needle and returns it via another lumen or needle. The proposed single lumen alternating micro-batch (SLAMB) technique uses a small single lumen to draw a “micro” batch of blood into a single reservoir. In the reservoir, the “batch” of blood is circulated at a high blood flow rate through a hemofilter or hemodialyzer, enabling efficient small- and middle-molecule clearance. Thereafter, the “purified” blood is returned to the patient and the cycle is repeated. Each batch comprises 20–300 ml of blood, which is adjusted to the vascular access, hemodynamic status, and size of the patient. Up to 15 cycles can be done per hour, allowing this system to achieve a blood clearance level comparable to modern continuous RRT systems. Because the system can function with a small-bore single lumen, this device can work with existing central lines, thus allowing for less invasive vascular access. Because of their size and relative simplicity, SLAMB-based systems are less expensive, smaller, and have improved portability. Lastly, a similar, manual SLAMB-hemofiltration kit, which requires no electricity or battery, can be developed at low cost (<$25) for use in austere medical conditions, thus expanding the availability of RRT for patients with AKI.10.34067/KID.0001462020Fri, 31 Jul 2020 10:21:53 GMT-07:00Single Lumen Alternating Micro-Batch Hemodiafiltration (SLAMB-HDF): A Device for Minimally Invasive Renal Replacement TherapyBlood-based RRT, such as hemodialysis, requires access to the bloodstream and adequate blood flow to enable the requisite clearance. As such, nearly all RRT systems require two lumens, enabling a blood circuit that pulls blood from one lumen or needle and returns it via another lumen or needle. The proposed single lumen alternating micro-batch (SLAMB) technique uses a small single lumen to draw a “micro” batch of blood into a single reservoir. In the reservoir, the “batch” of blood is circulated at a high blood flow rate through a hemofilter or hemodialyzer, enabling efficient small- and middle-molecule clearance. Thereafter, the “purified” blood is returned to the patient and the cycle is repeated. Each batch comprises 20–300 ml of blood, which is adjusted to the vascular access, hemodynamic status, and size of the patient. Up to 15 cycles can be done per hour, allowing this system to achieve a blood clearance level comparable to modern continuous RRT systems. Because the system can function with a small-bore single lumen, this device can work with existing central lines, thus allowing for less invasive vascular access. Because of their size and relative simplicity, SLAMB-based systems are less expensive, smaller, and have improved portability. Lastly, a similar, manual SLAMB-hemofiltration kit, which requires no electricity or battery, can be developed at low cost (<$25) for use in austere medical conditions, thus expanding the availability of RRT for patients with AKI.Chawla, Lakhmir S.2020-07-31T10:21:53-07:00doi:10.34067/KID.0001462020hwp:resource-id:kidney360;1/9/969American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, 0by25, batch dialysis, dialysis, hemodiafiltration, hemoperfusion, home dialysis, manual dialysis, renal replacement therapy, single needle, SLAMBInnovative Technology and MethodologyInnovative Technology and Methodologyother20202020-09-2410.34067/KID.00014620202641-76502020-07-31T10:21:53-07:002020-09-24Kidney360Innovative Technology and Methodology19969973
- Sudden Coma and Quadriplegia in a Hemodialysis Patient10.34067/KID.0001622020Thu, 24 Sep 2020 05:30:22 GMT-07:00Sudden Coma and Quadriplegia in a Hemodialysis PatientYu, Chih-HenHuang, Han-WeiSung, Junne-Ming2020-09-24T05:30:22-07:00doi:10.34067/KID.0001622020hwp:resource-id:kidney360;1/9/1036American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, brain, catheterization, cerebral air embolism, embolism, air, long-term hemodialysis catheter, renal dialysisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-09-2410.34067/KID.00016220202641-76502020-09-24T05:30:22-07:002020-09-24Kidney360Clinical Images in Nephrology and Dialysis1910361037
- Elevated Plasma Free Sialic Acid Levels in Individuals with Reduced Glomerular Filtration Rates10.34067/KID.0002122020Thu, 09 Jul 2020 10:01:15 GMT-07:00Elevated Plasma Free Sialic Acid Levels in Individuals with Reduced Glomerular Filtration RatesFuentes, FedericoCarrillo, NuriaWilkins, Kenneth J.Blake, JodiLeoyklang, PetcharatGahl, William A.Kopp, Jeffrey B.Huizing, Marjan2020-07-09T10:01:15-07:00doi:10.34067/KID.0002122020hwp:resource-id:kidney360;1/9/957American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular disease, N-acetylmannosamine (ManNAc), N-acetylneuraminic acid (Neu5Ac), podocyte, proteinuria, sialic acid, sialylationBrief CommunicationsBrief Communicationsbrief-report20202020-09-2410.34067/KID.00021220202641-76502020-07-09T10:01:15-07:002020-09-24Kidney360Brief Communications19957961
- Patency Outcomes of Arteriovenous Fistulas and Grafts for Hemodialysis Access: A Trade-Off between Nonmaturation and Long-Term Complications10.34067/KID.0000462020Thu, 23 Jul 2020 09:35:56 GMT-07:00Patency Outcomes of Arteriovenous Fistulas and Grafts for Hemodialysis Access: A Trade-Off between Nonmaturation and Long-Term ComplicationsVoorzaat, Bram M.Janmaat, Cynthia J.van der Bogt, Koen E.A.Dekker, Friedo W.Rotmans, Joris I.2020-07-23T09:35:56-07:00doi:10.34067/KID.0000462020hwp:resource-id:kidney360;1/9/916American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, arteriovenous graft, patency, vascular accessOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-09-2410.34067/KID.00004620202641-76502020-07-23T09:35:56-07:002020-09-24Kidney360Original Investigations19916924
- Approach to Persistent Microscopic Hematuria in ChildrenPersistent isolated microscopic hematuria is relatively common in pediatric practice, affecting around 0.25% of children. Isolated microscopic hematuria can be caused by a myriad of potentially benign or serious causes, including urologic issues; kidney stones; glomerular diseases, including disorders of the glomerular basement membrane; hematologic abnormalities; and others. The challenge for the pediatrician or pediatric nephrologist is to distinguish children with potentially progressive forms of kidney disease versus other causes while minimizing cost and inconvenience for the child and family. This manuscript will review the multiple potential causes of microscopic hematuria and provide a framework for the initial evaluation and monitoring of such patients.10.34067/KID.0003222020Fri, 10 Jul 2020 01:22:46 GMT-07:00Approach to Persistent Microscopic Hematuria in ChildrenPersistent isolated microscopic hematuria is relatively common in pediatric practice, affecting around 0.25% of children. Isolated microscopic hematuria can be caused by a myriad of potentially benign or serious causes, including urologic issues; kidney stones; glomerular diseases, including disorders of the glomerular basement membrane; hematologic abnormalities; and others. The challenge for the pediatrician or pediatric nephrologist is to distinguish children with potentially progressive forms of kidney disease versus other causes while minimizing cost and inconvenience for the child and family. This manuscript will review the multiple potential causes of microscopic hematuria and provide a framework for the initial evaluation and monitoring of such patients.Kallash, MahmoudRheault, Michelle N.2020-07-10T13:22:46-07:00doi:10.34067/KID.0003222020hwp:resource-id:kidney360;1/9/1014American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, Alport syndrome, hematuria, hypercalciuria, IgA nephropathy, IgA vasculitis, pediatric nephrologyReview ArticlesReview Articlesreview-article20202020-09-2410.34067/KID.00032220202641-76502020-07-10T13:22:46-07:002020-09-24Kidney360Review Articles1910141020
- The Geometry of Arteriovenous Fistulas Using Endothelial Nitric Oxide Synthase Mouse Models10.34067/KID.0001832020Fri, 31 Jul 2020 10:21:53 GMT-07:00The Geometry of Arteriovenous Fistulas Using Endothelial Nitric Oxide Synthase Mouse ModelsFalzon, IsabelleNorthrup, HannahGuo, LinglingTotenhagen, JohnLee, TimmyShiu, Yan-Ting2020-07-31T10:21:53-07:00doi:10.34067/KID.0001832020hwp:resource-id:kidney360;1/9/925American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, arteriovenous fistulas, endothelial nitric oxide synthase, NOS3 protein, Basic ScienceOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-09-2410.34067/KID.00018320202641-76502020-07-31T10:21:53-07:002020-09-24Kidney360Original Investigations19925935
- Hypoxia-Inducible Factor and Oxygen Biology in the KidneyKidney tissue hypoxia is detected in various kidney diseases and is considered to play an important role in the pathophysiology of both AKI and CKD. Because of the characteristic vascular architecture and high energy demand to drive tubular solute transport, the renal medulla is especially prone to hypoxia. Injured kidneys often present capillary rarefaction, inflammation, and fibrosis, which contribute to sustained kidney hypoxia, forming a vicious cycle promoting progressive CKD. Hypoxia-inducible factor (HIF), a transcription factor responsible for cellular adaptation to hypoxia, is generally considered to protect against AKI. On the contrary, consequences of sustained HIF activation in CKD may be either protective, neutral, or detrimental. The kidney outcomes seem to be affected by various factors, such as cell types in which HIF is activated/inhibited, disease models, balance between two HIF isoforms, and time and methods of intervention. This suggests multifaceted functions of HIF and highlights the importance of understanding its role within each specific context. Prolyl-hydroxylase domain (PHD) inhibitors, which act as HIF stabilizers, have been developed to treat anemia of CKD. Although many preclinical studies demonstrated renoprotective effects of PHD inhibitors in CKD models, there may be some situations in which they lead to deleterious effects. Further studies are needed to identify patients who would gain additional benefits from PHD inhibitors and those who may need to avoid them.10.34067/KID.0001302020Wed, 22 Jul 2020 01:47:16 GMT-07:00Hypoxia-Inducible Factor and Oxygen Biology in the KidneyKidney tissue hypoxia is detected in various kidney diseases and is considered to play an important role in the pathophysiology of both AKI and CKD. Because of the characteristic vascular architecture and high energy demand to drive tubular solute transport, the renal medulla is especially prone to hypoxia. Injured kidneys often present capillary rarefaction, inflammation, and fibrosis, which contribute to sustained kidney hypoxia, forming a vicious cycle promoting progressive CKD. Hypoxia-inducible factor (HIF), a transcription factor responsible for cellular adaptation to hypoxia, is generally considered to protect against AKI. On the contrary, consequences of sustained HIF activation in CKD may be either protective, neutral, or detrimental. The kidney outcomes seem to be affected by various factors, such as cell types in which HIF is activated/inhibited, disease models, balance between two HIF isoforms, and time and methods of intervention. This suggests multifaceted functions of HIF and highlights the importance of understanding its role within each specific context. Prolyl-hydroxylase domain (PHD) inhibitors, which act as HIF stabilizers, have been developed to treat anemia of CKD. Although many preclinical studies demonstrated renoprotective effects of PHD inhibitors in CKD models, there may be some situations in which they lead to deleterious effects. Further studies are needed to identify patients who would gain additional benefits from PHD inhibitors and those who may need to avoid them.Sugahara, MaiTanaka, TetsuhiroNangaku, Masaomi2020-07-22T13:47:16-07:00doi:10.34067/KID.0001302020hwp:resource-id:kidney360;1/9/1021American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, acute kidney injury, anemia, fibrosis, hypoxia, inflammation, microvascular rarefaction, prolyl-hydroxylase inhibitors, renal insufficiency, chronic, transcription factors, Basic ScienceReview ArticlesReview Articlesreview-article20202020-09-2410.34067/KID.00013020202641-76502020-07-22T13:47:16-07:002020-09-24Kidney360Review Articles1910211031
- Loss of Cilia Does Not Slow Liver Disease Progression in Mouse Models of Autosomal Recessive Polycystic Kidney Disease10.34067/KID.0001022019Fri, 10 Jul 2020 01:22:46 GMT-07:00Loss of Cilia Does Not Slow Liver Disease Progression in Mouse Models of Autosomal Recessive Polycystic Kidney DiseaseGallagher, Anna RachelSomlo, Stefan2020-07-10T13:22:46-07:00doi:10.34067/KID.0001022019hwp:resource-id:kidney360;1/9/962American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360cilia, cystic disease, Pkd1, polycystic kidney, autosomal dominant, autosomal recessive, liver cystic disease, hepatorenal disorders, Basic ScienceBrief CommunicationsBrief Communicationsbrief-report20202020-09-2410.34067/KID.00010220192641-76502020-07-10T13:22:46-07:002020-09-24Kidney360Brief Communications19962968
- Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: The Con View10.34067/KID.0003262020Mon, 13 Jul 2020 01:27:35 GMT-07:00Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: The Con ViewBobart, Shane A.Fervenza, Fernando C.2020-07-13T13:27:35-07:00doi:10.34067/KID.0003262020hwp:resource-id:kidney360;1/9/890American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, biopsy, glomerulonephritis, membranous, membranous nephropathy, nephrotic syndrome, PLA2R1 protein, human, receptors, PhospholipaseA2Debates in NephrologyDebates in Nephrologyresearch-article20202020-09-2410.34067/KID.00032620202641-76502020-07-13T13:27:35-07:002020-09-24Kidney360Debates in Nephrology19890893
- Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: Pro10.34067/KID.0003752020Mon, 13 Jul 2020 01:27:35 GMT-07:00Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: ProHogan, Jonathan J.2020-07-13T13:27:35-07:00doi:10.34067/KID.0003752020hwp:resource-id:kidney360;1/9/887American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, glomerulonephritis, membranous, kidney biopsy, membranous nephropathy, PLA2R1 protein, humanDebates in NephrologyDebates in Nephrologyresearch-article20202020-09-2410.34067/KID.00037520202641-76502020-07-13T13:27:35-07:002020-09-24Kidney360Debates in Nephrology19887889
- Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: Commentary10.34067/KID.0004012020Mon, 13 Jul 2020 01:27:35 GMT-07:00Kidney Biopsy Is Required for Nephrotic Syndrome with PLA2R+ and Normal Kidney Function: CommentaryGlassock, Richard J.2020-07-13T13:27:35-07:00doi:10.34067/KID.0004012020hwp:resource-id:kidney360;1/9/894American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, glomerulonephritis, kidney biopsy, membranous nephropathy, PLA2R antibody, PLA2R1 protein, humanModerator CommentaryModerator Commentaryarticle-commentary20202020-09-2410.34067/KID.00040120202641-76502020-07-13T13:27:35-07:002020-09-24Kidney360Moderator Commentary19894896
- Gerhard Giebisch and the Gift of Mentorship10.34067/KID.0004402020Tue, 21 Jul 2020 09:48:39 GMT-07:00Gerhard Giebisch and the Gift of MentorshipAronson, Peter S.2020-07-21T09:48:39-07:00doi:10.34067/KID.0004402020hwp:resource-id:kidney360;1/9/977American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360renal physiology, biography, mentors, tribute, Basic SciencePerspectivePerspectiveresearch-article20202020-09-2410.34067/KID.00044020202641-76502020-07-21T09:48:39-07:002020-09-24Kidney360Perspective19977981
- Global Dialysis Perspective: Vietnam10.34067/KID.0002872020Tue, 21 Jul 2020 06:53:17 GMT-07:00Global Dialysis Perspective: VietnamPham Van, BuiVo Duc, Chien2020-07-21T06:53:17-07:00doi:10.34067/KID.0002872020hwp:resource-id:kidney360;1/9/974American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, dialysis, nephrology, peritoneal dialysis, transplantation, VietnamGlobal PerspectiveGlobal Perspectiveresearch-article20202020-09-2410.34067/KID.00028720202641-76502020-07-21T06:53:17-07:002020-09-24Kidney360Global Perspective19974976
- Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Prospective Observational Study10.34067/KID.0001272020Thu, 09 Jul 2020 10:01:15 GMT-07:00Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Prospective Observational StudyHong, SusanaPresswala, LubainaHarris, Yael T.Romao, IsabelaRoss, Daniel W.Andrade Paz, HugoZhang, MengJhaveri, Kenar D.Sakhiya, VipulFishbane, Steven2020-07-09T10:01:15-07:00doi:10.34067/KID.0001272020hwp:resource-id:kidney360;1/9/897American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, complications, diabetes mellitus, type 2, glucose, glycated hemoglobin A, hypoglycemia, hypoglycemic agents, prospective studies, risk factorsOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-09-2410.34067/KID.00012720202641-76502020-07-09T10:01:15-07:002020-09-24Kidney360Original Investigations19897903
- Shaping Up Mitochondria in Diabetic NephropathyMitochondrial medicine has experienced significant progress in recent years and is expected to grow significantly in the near future, yielding many opportunities to translate novel bench discoveries into clinical medicine. Multiple lines of evidence have linked mitochondrial dysfunction to a variety of metabolic diseases, including diabetic nephropathy (DN). Mitochondrial dysfunction presumably precedes the emergence of key histologic and biochemical features of DN, which provides the rationale to explore mitochondrial fitness as a novel therapeutic target in patients with DN. Ultimately, the success of mitochondrial medicine is dependent on a better understanding of the underlying biology of mitochondrial fitness and function. To this end, recent advances in mitochondrial biology have led to new understandings of the potential effect of mitochondrial dysfunction in a myriad of human pathologies. We have proposed that molecular mechanisms that modulate mitochondrial dynamics contribute to the alterations of mitochondrial fitness and progression of DN. In this comprehensive review, we highlight the possible effects of mitochondrial dysfunction in DN, with the hope that targeting specific mitochondrial signaling pathways may lead to the development of new drugs that mitigate DN progression. We will outline potential tools to improve mitochondrial fitness in DN as a novel therapeutic strategy. These emerging views suggest that the modulation of mitochondrial fitness could serve as a key target in ameliorating progression of kidney disease in patients with diabetes.10.34067/KID.0002352020Thu, 30 Jul 2020 10:36:47 GMT-07:00Shaping Up Mitochondria in Diabetic NephropathyMitochondrial medicine has experienced significant progress in recent years and is expected to grow significantly in the near future, yielding many opportunities to translate novel bench discoveries into clinical medicine. Multiple lines of evidence have linked mitochondrial dysfunction to a variety of metabolic diseases, including diabetic nephropathy (DN). Mitochondrial dysfunction presumably precedes the emergence of key histologic and biochemical features of DN, which provides the rationale to explore mitochondrial fitness as a novel therapeutic target in patients with DN. Ultimately, the success of mitochondrial medicine is dependent on a better understanding of the underlying biology of mitochondrial fitness and function. To this end, recent advances in mitochondrial biology have led to new understandings of the potential effect of mitochondrial dysfunction in a myriad of human pathologies. We have proposed that molecular mechanisms that modulate mitochondrial dynamics contribute to the alterations of mitochondrial fitness and progression of DN. In this comprehensive review, we highlight the possible effects of mitochondrial dysfunction in DN, with the hope that targeting specific mitochondrial signaling pathways may lead to the development of new drugs that mitigate DN progression. We will outline potential tools to improve mitochondrial fitness in DN as a novel therapeutic strategy. These emerging views suggest that the modulation of mitochondrial fitness could serve as a key target in ameliorating progression of kidney disease in patients with diabetes.Mise, KokiGalvan, Daniel L.Danesh, Farhad R.2020-07-30T10:36:47-07:00doi:10.34067/KID.0002352020hwp:resource-id:kidney360;1/9/982American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360diabetes and the kidney, diabetic nephropathy, ETC, mitochondria, mitochondrial biogenesis, mitochondrial complex activity, mitochondrial dynamics, mitochondrial fitness, mitophagy, OXPHOS, ROS, Basic ScienceBasic Science for CliniciansBasic Science for Cliniciansresearch-article20202020-09-2410.34067/KID.00023520202641-76502020-07-30T10:36:47-07:002020-09-24Kidney360Basic Science for Clinicians19982992
- Screening and Recognition of Chronic Kidney Disease in VA Health Care System Primary Care Clinics10.34067/KID.0000532020Thu, 09 Jul 2020 10:01:15 GMT-07:00Screening and Recognition of Chronic Kidney Disease in VA Health Care System Primary Care ClinicsBansal, ShwetaMader, MichaelPugh, Jacqueline A.2020-07-09T10:01:15-07:00doi:10.34067/KID.0000532020hwp:resource-id:kidney360;1/9/904American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, awareness, diuretics, glomerular filtration rate, hypertension, International Classification of Diseases, kidney function tests, renal insufficiency, chronic, retrospective studies, screening, urinalysis, proteinuria, albuminuriaOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-09-2410.34067/KID.00005320202641-76502020-07-09T10:01:15-07:002020-09-24Kidney360Original Investigations19904915
- Association of FGF23 with Incident Sepsis in Community-Dwelling Adults: A Cohort Study10.34067/KID.0000942020Wed, 29 Jul 2020 05:51:20 GMT-07:00Association of FGF23 with Incident Sepsis in Community-Dwelling Adults: A Cohort StudyPaul, ShejutiJudd, Suzanne E.Wang, Henry E.Gutiérrez, Orlando M.2020-07-29T05:51:20-07:00doi:10.34067/KID.0000942020hwp:resource-id:kidney360;1/9/950American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360mineral metabolism, cohort studies, community-dwelling adults, diagnostic tests, routine, fibroblast growth factor 23, independent living, sepsisOriginal InvestigationsMineral MetabolismOriginal InvestigationsMineral Metabolismresearch-article20202020-09-2410.34067/KID.00009420202641-76502020-07-29T05:51:20-07:002020-09-24Kidney360Original Investigations19950956
- Factors Associated with Nephrology Fellowship Program Fill Rates10.2215/CJN.01120120Mon, 18 May 2020 12:58:57 GMT-07:00Factors Associated with Nephrology Fellowship Program Fill RatesMatchett, Caroline L.Astor, Brad C.Maursetter, Laura J.2020-05-18T12:58:57-07:00doi:10.2215/CJN.01120120hwp:resource-id:clinjasn;15/9/1340American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFellowships and Scholarships, nephrologyResearch LetterResearch Letterresearch-article20202020-09-07September 07, 202010.2215/CJN.011201201555-90411555-905X2020-05-18T12:58:57-07:002020-09-07Clinical Journal of the American Society of NephrologyResearch Letter15913401341
- A Step in the Right Direction10.2215/CJN.12350720Tue, 25 Aug 2020 07:08:33 GMT-07:00A Step in the Right DirectionSchell, Jane OgdenLupu, Dale Ellen2020-08-25T07:08:33-07:00doi:10.2215/CJN.12350720hwp:resource-id:clinjasn;15/9/1228American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-reported outcomes, symptom management, hemodialysis, patient-centered careEditorialsEditorialseditorial20202020-09-07September 07, 202010.2215/CJN.123507201555-90411555-905X2020-08-25T07:08:33-07:002020-09-07Clinical Journal of the American Society of NephrologyEditorials15991228129912301309
- Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 Dialyzer10.2215/CJN.01210120Tue, 25 Aug 2020 07:08:33 GMT-07:00Efficacy and Safety of Expanded Hemodialysis with the Theranova 400 DialyzerWeiner, Daniel E.Falzon, LukeSkoufos, LineBernardo, AngelitoBeck, WernerXiao, MengqiTran, Ha2020-08-25T07:08:33-07:00doi:10.2215/CJN.01210120hwp:resource-id:clinjasn;15/9/1310American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, dialysis, maintenance dialysis, chronic inflammation, chronic dialysis, end-stage kidney disease, randomized controlled trials, renal dialysis, ESKDOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-09-07September 07, 202010.2215/CJN.012101201555-90411555-905X2020-08-25T07:08:33-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15913101319
- Genetic Testing Is Beneficial to the Entire Family10.2215/CJN.11360720Thu, 27 Aug 2020 07:22:45 GMT-07:00Genetic Testing Is Beneficial to the Entire FamilyVerma, Meghna2020-08-27T07:22:45-07:00doi:10.2215/CJN.11360720hwp:resource-id:clinjasn;15/9/1224American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic testing, kidney diseasesPatient VoicesPatient Voiceseditorial20202020-09-07September 07, 202010.2215/CJN.113607201555-90411555-905X2020-08-27T07:22:45-07:002020-09-07Clinical Journal of the American Society of NephrologyPatient Voices15999122412791231122412861233
- Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation10.2215/CJN.15651219Tue, 25 Aug 2020 07:08:34 GMT-07:00Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney DonationPrice, Anna M.Greenhall, George H. B.Moody, William E.Steeds, Richard P.Mark, Patrick B.Edwards, Nicola C.Hayer, Manvir K.Pickup, Luke C.Radhakrishnan, AshwinLaw, Jonathan P.Banerjee, DebasishCampbell, TundeTomson, Charles R. V.Cockcroft, John R.Shrestha, BadriWilkinson, Ian B.Tomlinson, Laurie A.Ferro, Charles J.Townend, Jonathan N.,2020-08-25T07:08:34-07:00doi:10.2215/CJN.15651219hwp:resource-id:clinjasn;15/9/1330American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, arterial stiffness, hypertension, living kidney donors, chronic kidney disease, pulse wave velocity, arteries, hemodynamicsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-09-07September 07, 202010.2215/CJN.156512191555-90411555-905X2020-08-25T07:08:34-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15991330123713391239
- Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement10.2215/CJN.13661119Tue, 25 Aug 2020 07:08:32 GMT-07:00Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver InvolvementHogan, Marie C.Chamberlin, Julie A.Vaughan, Lisa E.Waits, Angela L.Banks, CarlyLeistikow, KathleenOftsie, TroyMadsen, ChuckEdwards, MarieGlockner, JamesKremers, Walter K.Harris, Peter C.LaRusso, Nicholas F.Torres, Vicente E.Masyuk, Tatyana V.2020-08-25T07:08:32-07:00doi:10.2215/CJN.13661119hwp:resource-id:clinjasn;15/9/1267American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhepatic cyst, somatostatin analog, polycystic kidney disease, liver diseaseOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20202020-09-07September 07, 202010.2215/CJN.136611191555-90411555-905X2020-08-25T07:08:32-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15912671278
- Preimplantation Genetic Testing for Genetic Kidney Disease10.2215/CJN.11790720Thu, 27 Aug 2020 07:22:45 GMT-07:00Preimplantation Genetic Testing for Genetic Kidney DiseaseBurke, WylieWest, Kathleen M.2020-08-27T07:22:45-07:00doi:10.2215/CJN.11790720hwp:resource-id:clinjasn;15/9/1231American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypreimplantation genetic testing, genetic kidney diseaseEditorialsEditorialseditorial20202020-09-07September 07, 202010.2215/CJN.117907201555-90411555-905X2020-08-27T07:22:45-07:002020-09-07Clinical Journal of the American Society of NephrologyEditorials15999123112791224123312861224
- Contrast-Associated Acute Kidney Injury10.2215/CJN.11960720Mon, 24 Aug 2020 05:50:22 GMT-07:00Contrast-Associated Acute Kidney InjuryMeraz-Muñoz, AlejandroWald, Ron2020-08-24T05:50:22-07:00doi:10.2215/CJN.11960720hwp:resource-id:clinjasn;15/9/1225American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycontrast-associated acute kidney injury, biomarkers, angiographyEditorialsEditorialseditorial20202020-09-07September 07, 202010.2215/CJN.119607201555-90411555-905X2020-08-24T05:50:22-07:002020-09-07Clinical Journal of the American Society of NephrologyEditorials15991225124012271250
- Arterial Mechanics following Living Kidney Donation10.2215/CJN.12280720Tue, 25 Aug 2020 07:08:34 GMT-07:00Arterial Mechanics following Living Kidney DonationPeixoto, Aldo J.2020-08-25T07:08:34-07:00doi:10.2215/CJN.12280720hwp:resource-id:clinjasn;15/9/1237American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarterial mechanics, chronic kidney disease, blood pressureEditorialsEditorialseditorial20202020-09-07September 07, 202010.2215/CJN.122807201555-90411555-905X2020-08-25T07:08:34-07:002020-09-07Clinical Journal of the American Society of NephrologyEditorials15991237133012391339
- Preimplantation Genetic Testing for Monogenic Kidney Disease10.2215/CJN.03550320Thu, 27 Aug 2020 07:22:45 GMT-07:00Preimplantation Genetic Testing for Monogenic Kidney DiseaseSnoek, RozemarijnStokman, Marijn F.Lichtenbelt, Klaske D.van Tilborg, Theodora C.Simcox, Cindy E.Paulussen, Aimée D.C.Dreesen, Jos C.M.F.van Reekum, FrankaLely, A. TitiaKnoers, Nine V.A.M.de Die-Smulders, Christine E.M.van Eerde, Albertien M.2020-08-27T07:22:45-07:00doi:10.2215/CJN.03550320hwp:resource-id:clinjasn;15/9/1279American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, ADPKD, Alport syndrome, Genetic Testing, Kidney DiseasesOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20202020-09-07September 07, 202010.2215/CJN.035503201555-90411555-905X2020-08-27T07:22:45-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15999127912241231128612241233
- Implementing a Patient-Reported Outcome Measure for Hemodialysis Patients in Routine Clinical Care10.2215/CJN.01840220Tue, 25 Aug 2020 07:08:33 GMT-07:00Implementing a Patient-Reported Outcome Measure for Hemodialysis Patients in Routine Clinical CareEvans, Jenna M.Glazer, AlyshaLum, RebeccaHeale, EstiMacKinnon, MarnieBlake, Peter G.Walsh, Michael2020-08-25T07:08:33-07:00doi:10.2215/CJN.01840220hwp:resource-id:clinjasn;15/9/1299American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-reported outcomes, symptom screening, symptom management, renal, chronic kidney disease, end stage kidney disease, nephrologyOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-09-07September 07, 202010.2215/CJN.018402201555-90411555-905X2020-08-25T07:08:33-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15991299122813091230
- Mycophenolate Mofetil Treatment of C3 Glomerulopathy10.2215/CJN.11740720Wed, 19 Aug 2020 07:28:50 GMT-07:00Mycophenolate Mofetil Treatment of C3 GlomerulopathyPeleg, YonatanAppel, Gerald B.2020-08-19T07:28:50-07:00doi:10.2215/CJN.11740720hwp:resource-id:clinjasn;15/9/1234American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymycophenolate mofetilEditorialsEditorialseditorial20202020-09-07September 07, 202010.2215/CJN.117407201555-90411555-905X2020-08-19T07:28:50-07:002020-09-07Clinical Journal of the American Society of NephrologyEditorials15991234128712361298
- Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease10.2215/CJN.15241219Wed, 19 Aug 2020 07:28:51 GMT-07:00Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the DiseaseCaravaca-Fontán, FernandoDíaz-Encarnación, Montserrat M.Lucientes, LauraCavero, TeresaCabello, VirginiaAriceta, GemaQuintana, Luis F.Marco, HelenaBarros, XoanaRamos, NataliaRodríguez-Mendiola, NuriaCruz, SoniaFernández-Juárez, GemaRodríguez, AdelaPérez de José, AnaRabasco, CristinaRodado, RaquelFernández, LoretoPérez Gómez, VanessaÁvila, Ana I.Bravo, LuisLumbreras, JavierAllende, NataliaSanchez de la Nieta, Maria DoloresRodríguez, EvaOlea, TeresaMelgosa, MartaHuerta, AnaMiquel, RosaMon, CarmenFraga, Gloriade Lorenzo, AlbertoDraibe, JulianaCano-Megías, MartaGonzález, FaynaShabaka, AmirLópez-Rubio, Maria EsperanzaFenollosa, María ÁngelesMartín-Penagos, LuisDa Silva, IaraAlonso Titos, JuanaRodríguez de Córdoba, SantiagoGoicoechea de Jorge, ElenaPraga, Manuel,2020-08-19T07:28:51-07:00doi:10.2215/CJN.15241219hwp:resource-id:clinjasn;15/9/1287American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlternative complement pathway, C3 glomerulopathy, mycophenolate mofetilOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-09-07September 07, 202010.2215/CJN.152412191555-90411555-905X2020-08-19T07:28:51-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15991287123412981236
- Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD10.2215/CJN.15291219Tue, 21 Jul 2020 02:33:40 GMT-07:00Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKDWomack, RebeccaBerru, FabianPanwar, BhupeshGutiérrez, Orlando M.2020-07-21T14:33:40-07:00doi:10.2215/CJN.15291219hwp:resource-id:clinjasn;15/9/1251American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, clinical trial, mineral metabolism, anemia, ferrous sulfate, ferric citrate, Iron DeficiencyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-09-07September 07, 202010.2215/CJN.152912191555-90411555-905X2020-07-21T14:33:40-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15912511258
- Therapeutic Plasma Exchange Using Membrane Plasma SeparationTherapeutic plasma exchange is a blood purification technique designed for the removal of large molecular weight toxins such as pathogenic antibodies and lipoproteins. Plasma exchange can be performed either by membrane separation or centrifugation. Centrifugal plasma exchange is more common in the United States, while membrane separation is more popular in Germany and Japan. The membrane separation technique is similar to the ultrafiltration procedures performed with a standard dialysis machine but in which the membrane’s pores are large enough to allow removal of all circulating molecules while retaining the cellular components. The current availability of plasma separation membranes compatible with CRRT systems has dramatically increased the potential for almost all nephrologists to perform these treatments. This review describes the membrane separation techniques available in the United States, the practical aspects of ordering and operating a membrane separation plasma exchange procedure, and its possible complications.10.2215/CJN.12501019Mon, 20 Apr 2020 04:58:25 GMT-07:00Therapeutic Plasma Exchange Using Membrane Plasma SeparationTherapeutic plasma exchange is a blood purification technique designed for the removal of large molecular weight toxins such as pathogenic antibodies and lipoproteins. Plasma exchange can be performed either by membrane separation or centrifugation. Centrifugal plasma exchange is more common in the United States, while membrane separation is more popular in Germany and Japan. The membrane separation technique is similar to the ultrafiltration procedures performed with a standard dialysis machine but in which the membrane’s pores are large enough to allow removal of all circulating molecules while retaining the cellular components. The current availability of plasma separation membranes compatible with CRRT systems has dramatically increased the potential for almost all nephrologists to perform these treatments. This review describes the membrane separation techniques available in the United States, the practical aspects of ordering and operating a membrane separation plasma exchange procedure, and its possible complications.Ahmed, SadiqKaplan, Andre2020-04-20T04:58:25-07:00doi:10.2215/CJN.12501019hwp:resource-id:clinjasn;15/9/1364American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, Plasmapheresis, Plasma Exchange, ultrafiltration, Nephrologists, Molecular Weight, Centrifugation, Kidneys, Artificial, Antibodies, Lipoproteins, renal dialysisReviewsReviewsreview-article20202020-09-07September 07, 202010.2215/CJN.125010191555-90411555-905X2020-04-20T04:58:25-07:002020-09-07Clinical Journal of the American Society of NephrologyReviews15913641370
- Updates in Diagnosis and Management of Preeclampsia in Women with CKDIt is estimated that women with CKD are ten times more likely to develop preeclampsia than women without CKD, with preeclampsia affecting up to 40% of pregnancies in women with CKD. However, the shared phenotype of hypertension, proteinuria, and impaired excretory kidney function complicates the diagnosis of superimposed preeclampsia in women with CKD who have hypertension and/or proteinuria that predates pregnancy. This article outlines the diagnoses of preeclampsia and superimposed preeclampsia. It discusses the pathogenesis of preeclampsia, including abnormal placentation and angiogenic dysfunction. The clinical use of angiogenic markers as diagnostic adjuncts for women with suspected preeclampsia is described, and the limited data on the use of these markers in women with CKD are presented. The role of kidney biopsy in pregnancy is examined. The management of preeclampsia is outlined, including important advances and controversies in aspirin prophylaxis, BP treatment targets, and the timing of delivery.10.2215/CJN.15121219Thu, 02 Apr 2020 01:32:20 GMT-07:00Updates in Diagnosis and Management of Preeclampsia in Women with CKDIt is estimated that women with CKD are ten times more likely to develop preeclampsia than women without CKD, with preeclampsia affecting up to 40% of pregnancies in women with CKD. However, the shared phenotype of hypertension, proteinuria, and impaired excretory kidney function complicates the diagnosis of superimposed preeclampsia in women with CKD who have hypertension and/or proteinuria that predates pregnancy. This article outlines the diagnoses of preeclampsia and superimposed preeclampsia. It discusses the pathogenesis of preeclampsia, including abnormal placentation and angiogenic dysfunction. The clinical use of angiogenic markers as diagnostic adjuncts for women with suspected preeclampsia is described, and the limited data on the use of these markers in women with CKD are presented. The role of kidney biopsy in pregnancy is examined. The management of preeclampsia is outlined, including important advances and controversies in aspirin prophylaxis, BP treatment targets, and the timing of delivery.Wiles, KateChappell, Lucy C.Lightstone, LizBramham, Kate2020-04-02T13:32:20-07:00doi:10.2215/CJN.15121219hwp:resource-id:clinjasn;15/9/1371American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypre-eclampsia, chronic renal insufficiency, glomerulus, proteinuria, pregnancy, Placentation, blood pressure, Renal Insufficiency, Chronic, hypertension, Renal Elimination, Phenotype, Prednisolone, BiopsyReviewsReviewsreview-article20202020-09-07September 07, 202010.2215/CJN.151212191555-90411555-905X2020-04-02T13:32:20-07:002020-09-07Clinical Journal of the American Society of NephrologyReviews15913711380
- Reimagining Institutional Research Training10.2215/CJN.14741219Fri, 03 Apr 2020 06:00:09 GMT-07:00Reimagining Institutional Research TrainingSpruance, Victoria M.Rankin, Tracy L.2020-04-03T06:00:09-07:00doi:10.2215/CJN.14741219hwp:resource-id:clinjasn;15/9/1361American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyworkforce, institutional training, research training, Research Personnel, ResearchPerspectivesPerspectivesresearch-article20202020-09-07September 07, 202010.2215/CJN.147412191555-90411555-905X2020-04-03T06:00:09-07:002020-09-07Clinical Journal of the American Society of NephrologyPerspectives15913611363
- Defining Early Recovery of Acute Kidney Injury10.2215/CJN.13381019Wed, 01 Apr 2020 07:10:21 GMT-07:00Defining Early Recovery of Acute Kidney InjuryDuff, StephenMurray, Patrick T.2020-04-01T07:10:21-07:00doi:10.2215/CJN.13381019hwp:resource-id:clinjasn;15/9/1358American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, AKI, Acute kidney injury, AKI Recovery, Acute kidney injury recovery, Acute kidney disease, AKI recovery criteria, KDIGO criteria, Recovering AKI, AKI Reversal, ADQI, creatinineIntroductionPerspectivesPerspectivesresearch-article20202020-09-07September 07, 202010.2215/CJN.133810191555-90411555-905X2020-04-01T07:10:21-07:002020-09-07Clinical Journal of the American Society of NephrologyPerspectives15913581360
- Fibroblast Growth Factor 23 and the Last Mile10.2215/CJN.13631119Fri, 10 Apr 2020 09:20:10 GMT-07:00Fibroblast Growth Factor 23 and the Last MileGutiérrez, Orlando M.2020-04-10T09:20:10-07:00doi:10.2215/CJN.13631119hwp:resource-id:clinjasn;15/9/1355American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperphosphatemia, mineral metabolism, cardiovascular disease, fibroblast growth factor 23, Fibroblast Growth Factors, Diagnostic Tests, RoutinePerspectivesPerspectivesresearch-article20202020-09-07September 07, 202010.2215/CJN.136311191555-90411555-905X2020-04-10T09:20:10-07:002020-09-07Clinical Journal of the American Society of NephrologyPerspectives15913551357
- The Use of Genomics to Drive Kidney Disease Drug Discovery and DevelopmentAs opposed to diseases such as cancer, autoimmune disease, and diabetes, identifying drugs to treat CKD has proven significantly more challenging. Over the past 2 decades, new potential therapeutic targets have been identified as genetically altered proteins involved in rare monogenetic kidney diseases. Other possible target genes have been implicated through common genetic polymorphisms associated with CKD in the general population. Significant challenges remain before translating these genetic insights into clinical therapies for CKD. This paper will discuss how genetic variants may be leveraged to develop drugs and will especially focus on those genes associated with CKD to exemplify the value and challenges in including genetic information in the drug development pipeline.10.2215/CJN.11070919Thu, 19 Mar 2020 08:35:42 GMT-07:00The Use of Genomics to Drive Kidney Disease Drug Discovery and DevelopmentAs opposed to diseases such as cancer, autoimmune disease, and diabetes, identifying drugs to treat CKD has proven significantly more challenging. Over the past 2 decades, new potential therapeutic targets have been identified as genetically altered proteins involved in rare monogenetic kidney diseases. Other possible target genes have been implicated through common genetic polymorphisms associated with CKD in the general population. Significant challenges remain before translating these genetic insights into clinical therapies for CKD. This paper will discuss how genetic variants may be leveraged to develop drugs and will especially focus on those genes associated with CKD to exemplify the value and challenges in including genetic information in the drug development pipeline.Reilly, Dermot F.Breyer, Matthew D.2020-03-19T08:35:42-07:00doi:10.2215/CJN.11070919hwp:resource-id:clinjasn;15/9/1342American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, drug transporter, genetic renal disease, drug discovery, kidney, renal insufficiency, chronic, diabetes mellitus, genomics, drug development, polymorphism, genetic, autoimmune diseases, neoplasmsGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-09-07September 07, 202010.2215/CJN.110709191555-90411555-905X2020-03-19T08:35:42-07:002020-09-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease15913421351
- How We Manage Hypertension in a Patient with a Recent Stroke10.2215/CJN.00030120Mon, 11 May 2020 08:13:20 GMT-07:00How We Manage Hypertension in a Patient with a Recent StrokeChang, Tara I.Bhalla, Vivek2020-05-11T08:13:20-07:00doi:10.2215/CJN.00030120hwp:resource-id:clinjasn;15/9/1352American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, blood pressure, stroke, Disease ManagementKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20202020-09-07September 07, 202010.2215/CJN.000301201555-90411555-905X2020-05-11T08:13:20-07:002020-09-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat15913521354
- COVID-19 Outbreak and Management Approach for Families with Children on Long-Term Kidney Replacement Therapy10.2215/CJN.03630320Tue, 14 Jul 2020 09:26:46 GMT-07:00COVID-19 Outbreak and Management Approach for Families with Children on Long-Term Kidney Replacement TherapyZhao, RuiZhou, QingWang, Xiao-WenLiu, Cui-HuaWang, MoYang, QingZhai, Yi-HuiZhu, Da-QianChen, JingFang, Xiao-YanTang, Xiao-ShanZhang, HuiShen, QianXu, Hong2020-07-14T09:26:46-07:00doi:10.2215/CJN.03630320hwp:resource-id:clinjasn;15/9/1259American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal replacement therapy, COVID-19, SARS-CoV-2, End-stage kidney disease, Caregivers, Families, Mainland China, ChildrenOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20202020-09-07September 07, 202010.2215/CJN.036303201555-90411555-905X2020-07-14T09:26:46-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15912591266
- Postangiography Increases in Serum Creatinine and Biomarkers of Injury and Repair10.2215/CJN.15931219Mon, 24 Aug 2020 05:50:23 GMT-07:00Postangiography Increases in Serum Creatinine and Biomarkers of Injury and RepairLiu, CarolineMor, Maria K.Palevsky, Paul M.Kaufman, James S.Thiessen Philbrook, HeatherWeisbord, Steven D.Parikh, Chirag R.2020-08-24T05:50:23-07:00doi:10.2215/CJN.15931219hwp:resource-id:clinjasn;15/9/1240American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycontrast media, prognostic biomarker, tubular injury, urinary biomarkers, plasma biomarkers, clinical trial, renal hemodynamics, intrinsic injury, creatinine, Biomarkers, AngiographyOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20202020-09-07September 07, 202010.2215/CJN.159312191555-90411555-905X2020-08-24T05:50:23-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15991240122512501227
- The Early Days10.2215/CJN.08780620Wed, 29 Jul 2020 08:58:42 GMT-07:00The Early DaysRoberts, Glenda V.Gee, Patrick O.2020-07-29T08:58:42-07:00doi:10.2215/CJN.08780620hwp:resource-id:clinjasn;15/9/1221American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, Postkidney transplant recipientPatient VoicesPatient Voiceseditorial20202020-09-07September 07, 202010.2215/CJN.087806201555-90411555-905X2020-07-29T08:58:42-07:002020-09-07Clinical Journal of the American Society of NephrologyPatient Voices15912211223
- Utilization and Outcomes of Single and Dual Kidney Transplants from Older Deceased Donors in the United Kingdom10.2215/CJN.02060220Mon, 20 Jul 2020 02:00:19 GMT-07:00Utilization and Outcomes of Single and Dual Kidney Transplants from Older Deceased Donors in the United KingdomIbrahim, MariaGreenhall, George H.B.Summers, Dominic M.Mumford, LisaJohnson, RachelBaker, Richard J.Forsythe, JohnPettigrew, Gavin J.Ahmad, NiazCallaghan, Chris J.2020-07-20T14:00:19-07:00doi:10.2215/CJN.02060220hwp:resource-id:clinjasn;15/9/1320American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, transplantation, survival, renal transplantation, organ transplant, kidney transplantation, kidney donation, kidney donor, utilization, deceased donorOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-09-07September 07, 202010.2215/CJN.020602201555-90411555-905X2020-07-20T14:00:19-07:002020-09-07Clinical Journal of the American Society of NephrologyOriginal Articles15913201329
- Early Detection of CKD: Implications for Low-Income, Middle-Income, and High-Income CountriesCKD is common, costly, and associated with adverse health outcomes. Because inexpensive treatments can slow the rate of kidney function loss, and because CKD is asymptomatic until its later stages, the idea of early detection of CKD to improve outcomes ignites enthusiasm, especially in low- and middle-income countries where renal replacement is often unavailable or unaffordable. Available data and prior experience suggest that the benefits of population-based screening for CKD are uncertain; that there is potential for harms; that screening is not a wise use of resources, even in high-income countries; and that screening has substantial opportunity costs in low- and middle-income countries that offset its hypothesized benefits. In contrast, some of the factors that diminish the value of population-based screening (such as markedly higher prevalence of CKD in people with diabetes, hypertension, and cardiovascular disease, as well as high preexisting use of kidney testing in such patients) substantially increase the appeal of searching for CKD in people with known kidney risk factors (case finding) in high-income countries as well as in low- and middle-income countries. For both screening and case finding, detection of new cases is the easiest component; the real challenge is ensuring appropriate management for a chronic disease, usually for years or even decades. This review compares and contrasts the benefits, harms, and opportunity costs associated with these two approaches to early detection of CKD. We also suggest criteria (discussed separately for high-income countries and for low- and middle-income countries) to use in assessing when countries should consider case finding versus when they should consider foregoing systematic attempts at early detection and focus on management of known cases.10.1681/ASN.2020030277Mon, 24 Aug 2020 05:56:14 GMT-07:00Early Detection of CKD: Implications for Low-Income, Middle-Income, and High-Income CountriesCKD is common, costly, and associated with adverse health outcomes. Because inexpensive treatments can slow the rate of kidney function loss, and because CKD is asymptomatic until its later stages, the idea of early detection of CKD to improve outcomes ignites enthusiasm, especially in low- and middle-income countries where renal replacement is often unavailable or unaffordable. Available data and prior experience suggest that the benefits of population-based screening for CKD are uncertain; that there is potential for harms; that screening is not a wise use of resources, even in high-income countries; and that screening has substantial opportunity costs in low- and middle-income countries that offset its hypothesized benefits. In contrast, some of the factors that diminish the value of population-based screening (such as markedly higher prevalence of CKD in people with diabetes, hypertension, and cardiovascular disease, as well as high preexisting use of kidney testing in such patients) substantially increase the appeal of searching for CKD in people with known kidney risk factors (case finding) in high-income countries as well as in low- and middle-income countries. For both screening and case finding, detection of new cases is the easiest component; the real challenge is ensuring appropriate management for a chronic disease, usually for years or even decades. This review compares and contrasts the benefits, harms, and opportunity costs associated with these two approaches to early detection of CKD. We also suggest criteria (discussed separately for high-income countries and for low- and middle-income countries) to use in assessing when countries should consider case finding versus when they should consider foregoing systematic attempts at early detection and focus on management of known cases.Tonelli, MarcelloDickinson, James A.2020-08-24T05:56:14-07:00doi:10.1681/ASN.2020030277hwp:resource-id:jnephrol;31/9/1931American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyscreening, chronic kidney disease, low and middle income country, noncommunicable diseasesReviewsReviewsreview-article20202020-09-01September 202010.1681/ASN.20200302771046-66731533-34502020-08-24T05:56:14-07:002020-09Journal of the American Society of NephrologyReviews31991931192119401922
- AKI in Hospitalized Patients with and without COVID-19: A Comparison Study10.1681/ASN.2020040509Wed, 15 Jul 2020 12:55:08 GMT-07:00AKI in Hospitalized Patients with and without COVID-19: A Comparison StudyFisher, MollyNeugarten, JoelBellin, EranYunes, MilagrosStahl, LindsayJohns, Tanya S.Abramowitz, Matthew K.Levy, RebeccaKumar, NeeljaMokrzycki, Michele H.Coco, MariaDominguez, MaryPrudhvi, KalyanGolestaneh, Ladan2020-07-15T12:55:08-07:00doi:10.1681/ASN.2020040509hwp:resource-id:jnephrol;31/9/2145American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, COVID-19, sex, race, outcomes, risk factorsClinical ResearchClinical Researchresearch-article20202020-09-01September 202010.1681/ASN.20200405091046-66731533-34502020-07-15T12:55:08-07:002020-09Journal of the American Society of NephrologyClinical Research31921452157
- Caution in Identifying Coronaviruses by Electron Microscopy10.1681/ASN.2020050755Fri, 10 Jul 2020 10:44:14 GMT-07:00Caution in Identifying Coronaviruses by Electron MicroscopyMiller, Sarah E.Goldsmith, Cynthia S.2020-07-10T10:44:14-07:00doi:10.1681/ASN.2020050755hwp:resource-id:jnephrol;31/9/2223American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologySARS-CoV-2, electron microscopy, clathrin-coated vesicles, COVID-19, multivesicular bodiesLetters to the EditorLetters to the Editorletter20202020-09-01September 202010.1681/ASN.20200507551046-66731533-34502020-07-10T10:44:14-07:002020-09Journal of the American Society of NephrologyLetters to the Editor31999222322242225222422252226
- Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective Cohort10.1681/ASN.2020040426Fri, 21 Aug 2020 07:56:26 GMT-07:00Clinicopathological Features and Outcomes of Acute Kidney Injury in Critically Ill COVID-19 with Prolonged Disease Course: A Retrospective CohortXia, PengWen, YubingDuan, YaqiSu, HuaCao, WeiXiao, MengMa, JieZhou, YangzhongChen, GangJiang, WeiWu, HuanwenHu, YanXu, SanpengCai, HanghangLiu, ZhengyinZhou, XiangDu, BinWang, JinglanLi, TaishengYan, XiaoweiChen, LimengLiang, ZhiyongZhang, ShuyangZhang, ChunQin, YanWang, GuopingLi, Xuemei2020-08-21T07:56:26-07:00doi:10.1681/ASN.2020040426hwp:resource-id:jnephrol;31/9/2205American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal pathology, acute renal failure, kidney disease, COVID-19, critically illClinical ResearchClinical Researchresearch-article20202020-09-01September 202010.1681/ASN.20200404261046-66731533-34502020-08-21T07:56:26-07:002020-09Journal of the American Society of NephrologyClinical Research31922052221
- Postmortem Kidney Pathology Findings in Patients with COVID-1910.1681/ASN.2020050744Wed, 29 Jul 2020 09:04:12 GMT-07:00Postmortem Kidney Pathology Findings in Patients with COVID-19Santoriello, DominickKhairallah, PascaleBomback, Andrew S.Xu, KatherineKudose, SatoruBatal, IbrahimBarasch, JonathanRadhakrishnan, JaiD’Agati, VivetteMarkowitz, Glen2020-07-29T09:04:12-07:00doi:10.1681/ASN.2020050744hwp:resource-id:jnephrol;31/9/2158American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, pathology, acute tubular injury, COVID-19, SARS-CoV-2, acute kidney injuryClinical ResearchClinical Researchresearch-article20202020-09-01September 202010.1681/ASN.20200507441046-66731533-34502020-07-29T09:04:12-07:002020-09Journal of the American Society of NephrologyClinical Research31921582167
- Kidney and Lung ACE2 Expression after an ACE Inhibitor or an Ang II Receptor Blocker: Implications for COVID-1910.1681/ASN.2020050667Wed, 15 Jul 2020 12:55:08 GMT-07:00Kidney and Lung ACE2 Expression after an ACE Inhibitor or an Ang II Receptor Blocker: Implications for COVID-19Wysocki, JanLores, EnriqueYe, MinghaoSoler, Maria JoseBatlle, Daniel2020-07-15T12:55:08-07:00doi:10.1681/ASN.2020050667hwp:resource-id:jnephrol;31/9/1941American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyACE2, angiotensin converting enzyme 2, ACE inhibitors, angiotensin receptor blockers, COVID-19Research LettersResearch Lettersletter20202020-09-01September 202010.1681/ASN.20200506671046-66731533-34502020-07-15T12:55:08-07:002020-09Journal of the American Society of NephrologyResearch Letters31919411943
- Authors’ Reply10.1681/ASN.2020060847Wed, 12 Aug 2020 05:49:14 GMT-07:00Authors’ ReplyFarkash, Evan A.Wilson, Allecia M.Jentzen, Jeffrey M.2020-08-12T05:49:14-07:00doi:10.1681/ASN.2020060847hwp:resource-id:jnephrol;31/9/2225American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, SARS-CoV-2, acute kidney failure, autopsy, electron microscopyLetters to the EditorLetters to the Editorletter20202020-09-01September 202010.1681/ASN.20200608471046-66731533-34502020-08-12T05:49:14-07:002020-09Journal of the American Society of NephrologyLetters to the Editor31999222522242223222622252224
- Kidney Involvement in COVID-19: Need for Better Definitions10.1681/ASN.2020050630Thu, 09 Jul 2020 07:56:55 GMT-07:00Kidney Involvement in COVID-19: Need for Better DefinitionsDelsante, MarcoRossi, Giovanni M.Gandolfini, IlariaBagnasco, Serena M.Rosenberg, Avi Z.2020-07-09T07:56:55-07:00doi:10.1681/ASN.2020050630hwp:resource-id:jnephrol;31/9/2224American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, histopathology, electron microscopy, COVID-19Letters to the EditorLetters to the Editorletter20202020-09-01September 202010.1681/ASN.20200506301046-66731533-34502020-07-09T07:56:55-07:002020-09Journal of the American Society of NephrologyLetters to the Editor31999222422232225222522242226
- Kidney Biopsy Findings in Patients with COVID-1910.1681/ASN.2020060802Fri, 17 Jul 2020 08:06:30 GMT-07:00Kidney Biopsy Findings in Patients with COVID-19Kudose, SatoruBatal, IbrahimSantoriello, DominickXu, KatherineBarasch, JonathanPeleg, YonatanCanetta, PietroRatner, Lloyd E.Marasa, MaddalenaGharavi, Ali G.Stokes, M. BarryMarkowitz, Glen S.D’Agati, Vivette D.2020-07-17T08:06:30-07:00doi:10.1681/ASN.2020060802hwp:resource-id:jnephrol;31/9/1959American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, renal pathology, COVID-19Rapid CommunicationRapid Communicationresearch-article20202020-09-01September 202010.1681/ASN.20200608021046-66731533-34502020-07-17T08:06:30-07:002020-09Journal of the American Society of NephrologyRapid Communication31919591968
- High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic Screening10.1681/ASN.2020060827Thu, 30 Jul 2020 11:56:33 GMT-07:00High Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients Detected Using Serologic ScreeningClarke, CandicePrendecki, MariaDhutia, AmritaAli, Mahrukh A.Sajjad, HiraShivakumar, OshiniLightstone, LizKelleher, PeterPickering, Matthew C.Thomas, DavidCharif, RawyaGriffith, MeganMcAdoo, Stephen P.Willicombe, Michelle2020-07-30T11:56:33-07:00doi:10.1681/ASN.2020060827hwp:resource-id:jnephrol;31/9/1969American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, serology, COVID-19Rapid CommunicationRapid Communicationresearch-article20202020-09-01September 202010.1681/ASN.20200608271046-66731533-34502020-07-30T11:56:33-07:002020-09Journal of the American Society of NephrologyRapid Communication31919691975
- COVID-19–Associated Kidney Injury: A Case Series of Kidney Biopsy Findings10.1681/ASN.2020050699Mon, 13 Jul 2020 11:02:23 GMT-07:00COVID-19–Associated Kidney Injury: A Case Series of Kidney Biopsy FindingsSharma, PurvaUppal, Nupur N.Wanchoo, RimdaShah, Hitesh H.Yang, YiheParikh, RushangKhanin, YuriyMadireddy, VarunLarsen, Christopher P.Jhaveri, Kenar D.Bijol, Vanesa,Abate, MersemaPaz Andrade, HugoBarnett, Richard L.Bellucci, AlessandroBhaskaran, Madhu C.Corona, Antonio G.Flores Chang, Bessy SuyinFinger, MarkFishbane, StevenGitman, MichaelHalinski, CandiceHasan, ShamirHazzan, Azzour D.Hirsch, Jamie S.Hong, SusanaJhaveri, Kenar D.Khanin, YuriyKuan, AireenMadireddy, VarunMalieckal, DeepaMuzib, AbdulrahmanNair, GayatriNair, Vinay V.Ng, Jia H.Parikh, RushangRoss, Daniel W.Sakhiya, VipulbhaiSachdeva, MalaSchwarz, RichardShah, Hitesh H.Sharma, PurvaSinghal, Pravin C.Uppal, Nupur N.Wanchoo, Rimda2020-07-13T11:02:23-07:00doi:10.1681/ASN.2020050699hwp:resource-id:jnephrol;31/9/1948American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney pathology, kidney biopsy, acute kidney injury, AKI, ATN, COVID-19, SARS-CoV-2Rapid CommunicationRapid Communicationresearch-article20202020-09-01September 202010.1681/ASN.20200506991046-66731533-34502020-07-13T11:02:23-07:002020-09Journal of the American Society of NephrologyRapid Communication31919481958
- Histopathologic and Ultrastructural Findings in Postmortem Kidney Biopsy Material in 12 Patients with AKI and COVID-1910.1681/ASN.2020050683Thu, 16 Jul 2020 09:45:49 GMT-07:00Histopathologic and Ultrastructural Findings in Postmortem Kidney Biopsy Material in 12 Patients with AKI and COVID-19Golmai, PounehLarsen, Christopher P.DeVita, Maria V.Wahl, Samuel J.Weins, AstridRennke, Helmut G.Bijol, VanesaRosenstock, Jordan L.2020-07-16T09:45:49-07:00doi:10.1681/ASN.2020050683hwp:resource-id:jnephrol;31/9/1944American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyAcute kidney injury, COVID-19, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, pathology, biopsy, virionResearch LettersResearch Lettersresearch-article20202020-09-01September 202010.1681/ASN.20200506831046-66731533-34502020-07-16T09:45:49-07:002020-09Journal of the American Society of NephrologyResearch Letters3191119442552551947255256
- Racial and Ethnic Disparities in Seasonal Influenza Vaccination among Dialysis Facilities in the United States10.1681/ASN.2020040483Thu, 13 Aug 2020 05:53:41 GMT-07:00Racial and Ethnic Disparities in Seasonal Influenza Vaccination among Dialysis Facilities in the United StatesDanziger, JohnWeinhandl, EricFriedman, DavidMukamal, Kenneth J.2020-08-13T05:53:41-07:00doi:10.1681/ASN.2020040483hwp:resource-id:jnephrol;31/9/2117American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyvaccination, disparities, COVID-19Clinical EpidemiologyClinical Epidemiologyresearch-article20202020-09-01September 202010.1681/ASN.20200404831046-66731533-34502020-08-13T05:53:41-07:002020-09Journal of the American Society of NephrologyClinical Epidemiology31921172121
- Rationing Scarce Resources: The Potential Impact of COVID-19 on Patients with Chronic Kidney Disease10.1681/ASN.2020050704Wed, 15 Jul 2020 12:55:08 GMT-07:00Rationing Scarce Resources: The Potential Impact of COVID-19 on Patients with Chronic Kidney DiseaseSilberzweig, JeffreyIkizler, T. AlpKramer, HollyPalevsky, Paul M.Vassalotti, JosephKliger, Alan S.2020-07-15T12:55:08-07:00doi:10.1681/ASN.2020050704hwp:resource-id:jnephrol;31/9/1926American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, rationing, COVID-19PerspectivesPerspectivesresearch-article20202020-09-01September 202010.1681/ASN.20200507041046-66731533-34502020-07-15T12:55:08-07:002020-09Journal of the American Society of NephrologyPerspectives31919261928
- Molecular Mismatch—the Renaissance of HLA in Kidney Transplantation10.1681/ASN.2020071011Thu, 06 Aug 2020 12:22:24 GMT-07:00Molecular Mismatch—the Renaissance of HLA in Kidney TransplantationWiebe, ChrisNickerson, Peter W.2020-08-06T12:22:24-07:00doi:10.1681/ASN.2020071011hwp:resource-id:jnephrol;31/9/1922American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, chronic allograft rejection, acute allograft rejectionEditorialsEditorialseditorial20202020-09-01September 202010.1681/ASN.20200710111046-66731533-34502020-08-06T12:22:24-07:002020-09Journal of the American Society of NephrologyEditorials31991922219319252204
- Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study10.1681/ASN.2020010019Thu, 06 Aug 2020 12:22:25 GMT-07:00Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort StudySenev, AleksandarCoemans, MaartenLerut, EvelyneVan Sandt, VickyKerkhofs, JohanDaniëls, LiesbethDriessche, Marleen VandenCompernolle, VeerleSprangers, BenVan Loon, ElisabetCallemeyn, JasperClaas, FransTambur, Anat R.Verbeke, GeertKuypers, DirkEmonds, Marie-PauleNaesens, Maarten2020-08-06T12:22:25-07:00doi:10.1681/ASN.2020010019hwp:resource-id:jnephrol;31/9/2193American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, kidney transplantation, HLA, histocompatibility, organ allocationClinical ResearchClinical Researchresearch-article20202020-09-01September 202010.1681/ASN.20200100191046-66731533-34502020-08-06T12:22:25-07:002020-09Journal of the American Society of NephrologyClinical Research31992193192222041925
- Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney Transplant10.1681/ASN.2020030326Wed, 15 Jul 2020 12:55:09 GMT-07:00Harnessing Expressed Single Nucleotide Variation and Single Cell RNA Sequencing To Define Immune Cell Chimerism in the Rejecting Kidney TransplantMalone, Andrew F.Wu, HaojiaFronick, CatrinaFulton, RobertGaut, Joseph P.Humphreys, Benjamin D.2020-07-15T12:55:09-07:00doi:10.1681/ASN.2020030326hwp:resource-id:jnephrol;31/9/1977American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologygene expression, transplantation, transcriptional profilingBasic ResearchBasic Researchresearch-article20202020-09-01September 202010.1681/ASN.20200303261046-66731533-34502020-07-15T12:55:09-07:002020-09Journal of the American Society of NephrologyBasic Research31919771986
- Increasing Peritoneal Dialysis Use in Response to the COVID-19 Pandemic: Will It Go Viral?10.1681/ASN.2020050729Mon, 03 Aug 2020 08:33:52 GMT-07:00Increasing Peritoneal Dialysis Use in Response to the COVID-19 Pandemic: Will It Go Viral?Brown, Edwina A.Perl, Jeffrey2020-08-03T08:33:52-07:00doi:10.1681/ASN.2020050729hwp:resource-id:jnephrol;31/9/1928American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, COVID-19, home dialysisPerspectivesPerspectivesresearch-article20202020-09-01September 202010.1681/ASN.20200507291046-66731533-34502020-08-03T08:33:52-07:002020-09Journal of the American Society of NephrologyPerspectives31919281930
- Genetic Analysis in Kidney Disease: Advancing Clinical Diagnosis and Research Discovery10.34067/KID.0003632020Thu, 27 Aug 2020 05:30:21 GMT-07:00Genetic Analysis in Kidney Disease: Advancing Clinical Diagnosis and Research DiscoveryBesse, Whitney2020-08-27T05:30:21-07:00doi:10.34067/KID.0003632020hwp:resource-id:kidney360;1/8/720American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360genetics, aHUS, atypical hemolytic uremic syndrome, exome sequencing, gene panel, genetic diagnosis, genetic kidney disease, MLPA, WESEditorialsEditorialseditorial20202020-08-2710.34067/KID.00036320202641-76502020-08-27T05:30:21-07:002020-08-27Kidney360Editorials18720723
- Apparent Treatment-Resistant Hypertension Assessed by Office and Ambulatory Blood Pressure in Chronic Kidney Disease—A Report from the Chronic Renal Insufficiency Cohort Study10.34067/KID.0002072020Wed, 24 Jun 2020 09:32:29 GMT-07:00Apparent Treatment-Resistant Hypertension Assessed by Office and Ambulatory Blood Pressure in Chronic Kidney Disease—A Report from the Chronic Renal Insufficiency Cohort StudyThomas, GeorgeFelts, JesseBrecklin, Carolyn S.Chen, JingDrawz, Paul E.Lustigova, EvaMehta, RupalMiller, Edgar R.Sozio, Stephen M.Weir, Matthew R.Xie, DaweiWang, XueRahman, MahboobAppel, Lawrence J.Feldman, Harold I.Go, Alan S.He, JiangLash, James P.Nelson, Robert G.Shah, Vallabh O.Townsend, Raymond R.Unruh, Mark L.2020-06-24T09:32:29-07:00doi:10.34067/KID.0002072020hwp:resource-id:kidney360;1/8/810American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360hypertension, resistant hypertension, chronic kidney disease, CRIC, ambulatory blood pressure monitoring, cardiovascular diseaseOriginal InvestigationsHypertensionOriginal InvestigationsHypertensionresearch-article20202020-08-2710.34067/KID.00020720202641-76502020-06-24T09:32:29-07:002020-08-27Kidney360Original Investigations18810818
- Supply and Distribution of Vascular Access Physicians in the United States: A Cross-Sectional Study10.34067/KID.0002722020Wed, 01 Jul 2020 06:00:11 GMT-07:00Supply and Distribution of Vascular Access Physicians in the United States: A Cross-Sectional StudyLee, Shoou-Yih D.Xiang, JieKshirsagar, Abhijit V.Steffick, DianeSaran, RajivWang, Virginia2020-07-01T06:00:11-07:00doi:10.34067/KID.0002722020hwp:resource-id:kidney360;1/8/763American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, arteriovenous fistula, arteriovenous graft, demography, distribution, health care sector, health resources, kidney failure, chronic, physicians, primary care, referral and consultation, registries, renal dialysis, supply, vascular accessOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-08-2710.34067/KID.00027220202641-76502020-07-01T06:00:11-07:002020-08-27Kidney360Original Investigations18763771
- Understanding the Link between Neighborhoods and Kidney DiseaseNeighborhoods are where we live, learn, work, pray, and play. Growing evidence indicates that neighborhoods are an important determinant of health. The built features of our neighborhoods, such as the ways in which the streets are designed and connected and the availability of green spaces and transit stops, as well as the social features, such as the trust among neighbors and the perceptions of safety, may influence health through multiple pathways, such as access to important resources, psychosocial stress, and health behaviors. In particular, the extant literature consistently documents an association between neighborhood features and renal-associated conditions, such as cardiovascular disease, hypertension, diabetes, and obesity. There is also some evidence suggesting an association between neighborhood poverty and ESKD. The link between neighborhood and earlier stages of CKD, however, has been less clear, with most studies documenting no association. It may be that the neighborhood measures used in previous studies do not capture features of the neighborhood important for earlier stages of disease development and progression. It may also be that our current biomarkers (e.g., eGFR) and urine protein are not able to pick up very early forms of renal damage because of the kidney’s overall high reserve capacity. This paper critically reviews the state of the literature on neighborhood and renal disease, with recommendations for neighborhood measures in future research. Neighborhoods are designed, built, and informed by policy, and thus, they are amenable to intervention, making them a potentially powerful way to improve renal health and reduce health inequalities at the population level.10.34067/KID.0001202019Tue, 23 Jun 2020 01:24:05 GMT-07:00Understanding the Link between Neighborhoods and Kidney DiseaseNeighborhoods are where we live, learn, work, pray, and play. Growing evidence indicates that neighborhoods are an important determinant of health. The built features of our neighborhoods, such as the ways in which the streets are designed and connected and the availability of green spaces and transit stops, as well as the social features, such as the trust among neighbors and the perceptions of safety, may influence health through multiple pathways, such as access to important resources, psychosocial stress, and health behaviors. In particular, the extant literature consistently documents an association between neighborhood features and renal-associated conditions, such as cardiovascular disease, hypertension, diabetes, and obesity. There is also some evidence suggesting an association between neighborhood poverty and ESKD. The link between neighborhood and earlier stages of CKD, however, has been less clear, with most studies documenting no association. It may be that the neighborhood measures used in previous studies do not capture features of the neighborhood important for earlier stages of disease development and progression. It may also be that our current biomarkers (e.g., eGFR) and urine protein are not able to pick up very early forms of renal damage because of the kidney’s overall high reserve capacity. This paper critically reviews the state of the literature on neighborhood and renal disease, with recommendations for neighborhood measures in future research. Neighborhoods are designed, built, and informed by policy, and thus, they are amenable to intervention, making them a potentially powerful way to improve renal health and reduce health inequalities at the population level.Lapedis, Cathryn J.Mariani, Laura H.Jang, Bohyun JoyHodgin, JeffreyHicken, Margaret T.2020-06-23T13:24:05-07:00doi:10.34067/KID.0001202019hwp:resource-id:kidney360;1/8/845American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Chronic Kidney Disease, Health Behavior, Health Status Disparities, Kidney, Failure Chronic, Poverty, Renal Insufficiency, Chronic, Residence Characteristics, Socioeconomic Factors, Stress, PsychologicalReview ArticlesReview Articlesreview-article20202020-08-2710.34067/KID.00012020192641-76502020-06-23T13:24:05-07:002020-08-27Kidney360Review Articles18845854
- Initial Validation of a Machine Learning-Derived Prognostic Test (KidneyIntelX) Integrating Biomarkers and Electronic Health Record Data To Predict Longitudinal Kidney Outcomes10.34067/KID.0002252020Tue, 30 Jun 2020 06:07:28 GMT-07:00Initial Validation of a Machine Learning-Derived Prognostic Test (KidneyIntelX) Integrating Biomarkers and Electronic Health Record Data To Predict Longitudinal Kidney OutcomesChauhan, KinsukNadkarni, Girish N.Fleming, FergusMcCullough, JamesHe, Cijiang J.Quackenbush, JohnMurphy, BarbaraDonovan, Michael J.Coca, Steven G.Bonventre, Joseph V.2020-06-30T06:07:28-07:00doi:10.34067/KID.0002252020hwp:resource-id:kidney360;1/8/731American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, APOL1 protein, human, apolipoprotein L1, area under curve, biologic specimen banks, diabetes mellitus, type 2, electronic health records, follow-up studies, glomerular filtration rate, HAVCR1 protein, human, hepatitis A virus cellular receptor 1, prognosis, receptors, tumor necrosis factor, type I, TNFRSF1A protein, human, tumor necrosis factorsOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20202020-08-2710.34067/KID.00022520202641-76502020-06-30T06:07:28-07:002020-08-27Kidney360Original Investigations18731739
- Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease10.34067/KID.0002262020Tue, 16 Jun 2020 01:31:23 GMT-07:00Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney DiseaseInoue, ReikoNishi, HiroshiInoue, DaisukeHonda, KenjiroNangaku, Masaomi2020-06-16T13:31:23-07:00doi:10.34067/KID.0002262020hwp:resource-id:kidney360;1/8/740American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360cystic kidney disease, Japan, polycystic kidney, autosomal dominant, population density, regional variance, tolvaptanOriginal InvestigationsCystic Kidney DiseaseOriginal InvestigationsCystic Kidney Diseaseresearch-article20202020-08-2710.34067/KID.00022620202641-76502020-06-16T13:31:23-07:002020-08-27Kidney360Original Investigations18740745
- Value of Immediate Post-Kidney Biopsy Ultrasound in Excluding Late Hemorrhagic Complications10.34067/KID.0002212020Tue, 23 Jun 2020 09:29:55 GMT-07:00Value of Immediate Post-Kidney Biopsy Ultrasound in Excluding Late Hemorrhagic ComplicationsAl-Balas, AlianAlmehmi, AmmarAllon, Michael2020-06-23T09:29:55-07:00doi:10.34067/KID.0002212020hwp:resource-id:kidney360;1/8/797American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, biopsy, hemoglobins, hemorrhage, kidney, outpatients, retrospective studiesOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-08-2710.34067/KID.00022120202641-76502020-06-23T09:29:55-07:002020-08-27Kidney360Original Investigations18797800
- Beyond Panel-Based Testing: Exome Analysis Increases Sensitivity for Diagnosis of Genetic Kidney Disease10.34067/KID.0001342020Wed, 13 May 2020 01:27:03 GMT-07:00Beyond Panel-Based Testing: Exome Analysis Increases Sensitivity for Diagnosis of Genetic Kidney DiseaseWilson, Parker C.Love-Gregory, LatishaCorliss, MeaganMcNulty, SamanthaHeusel, Jonathan W.Gaut, Joseph P.2020-05-13T13:27:03-07:00doi:10.34067/KID.0001342020hwp:resource-id:kidney360;1/8/772American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360genetics, clinical, exome, genetics, medical, genomics, high-throughput nucleotide sequencing, kidney, kidney diseases, cystic, next generation sequencing, panel, retrospective studiesOriginal InvestigationsGeneticsOriginal InvestigationsGeneticsresearch-article20202020-08-2710.34067/KID.00013420202641-76502020-05-13T13:27:03-07:002020-08-27Kidney360Original Investigations18772780
- REDUcing the burden of dialysis Catheter ComplicaTIOns: a National approach (REDUCCTION) – design and baseline results10.34067/KID.0001132020Tue, 02 Jun 2020 02:13:45 GMT-07:00REDUcing the burden of dialysis Catheter ComplicaTIOns: a National approach (REDUCCTION) – design and baseline resultsKotwal, SradhaCoggan, SarahMcDonald, StephenTalaulikar, GirishCass, AlanJan, StephenPolkinghorne, Kevan R.Gray, Nicholas A.Gallagher, Martin2020-06-02T14:13:45-07:00doi:10.34067/KID.0001132020hwp:resource-id:kidney360;1/8/746American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, Australia, bacteremia, catheterization, central venous catheters, crossinfection, dialysis catheter, evidence-based medicine, health care costs, longitudinal studies, renal dialysis, vascular accessOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-08-2710.34067/KID.00011320202641-76502020-06-02T14:13:45-07:002020-08-27Kidney360Original Investigations18746754
- Cystic Kidneys in a Patient with Craniofacial Abnormalities10.34067/KID.0001332020Thu, 27 Aug 2020 05:30:21 GMT-07:00Cystic Kidneys in a Patient with Craniofacial AbnormalitiesTsao, Allison L.Sperati, C. John2020-08-27T05:30:21-07:00doi:10.34067/KID.0001332020hwp:resource-id:kidney360;1/8/882American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360genetics, brain, cilia, cystic kidney disease, diagnosis, differential, face, genetic testing, kidney, mouth, nephromegaly, oro-facial-digital syndromeClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-08-2710.34067/KID.00013320202641-76502020-08-27T05:30:21-07:002020-08-27Kidney360Clinical Images in Nephrology and Dialysis18882883
- Management of Anemia in Nondialysis Chronic Kidney Disease: Current Recommendations, Real-World Practice, and Patient PerspectivesIn nondialysis CKD (ND-CKD), anemia is a multifactorial and complex condition in which several dysfunctions dynamically contribute to a reduction in circulating hemoglobin (Hb) levels in red blood cells. Anemia is common in CKD and represents an important and modifiable risk factor for poor clinical outcomes. Importantly, symptoms related to anemia, including reduced physical functioning and fatigue, have been identified as high priorities by patients with CKD. The current management of anemia in ND-CKD (i.e., parameters to initiate treatment, Hb and iron indexes targets, choice of therapies, and effect of treatment on clinical and patient-reported outcomes) remains controversial. In this review article, we explore the epidemiology of anemia in ND-CKD and revise current recommendations and controversies in its management. Exploring data from real-world clinical practices, particularly from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps), we highlight the current challenges to translating current recommendations to clinical practice, providing patients’ perspectives of anemia and how it affects their quality of life. Finally, we summarize recent advances in the field of anemia that may change the way this condition will be managed in the future.10.34067/KID.0001442020Wed, 01 Jul 2020 06:00:11 GMT-07:00Management of Anemia in Nondialysis Chronic Kidney Disease: Current Recommendations, Real-World Practice, and Patient PerspectivesIn nondialysis CKD (ND-CKD), anemia is a multifactorial and complex condition in which several dysfunctions dynamically contribute to a reduction in circulating hemoglobin (Hb) levels in red blood cells. Anemia is common in CKD and represents an important and modifiable risk factor for poor clinical outcomes. Importantly, symptoms related to anemia, including reduced physical functioning and fatigue, have been identified as high priorities by patients with CKD. The current management of anemia in ND-CKD (i.e., parameters to initiate treatment, Hb and iron indexes targets, choice of therapies, and effect of treatment on clinical and patient-reported outcomes) remains controversial. In this review article, we explore the epidemiology of anemia in ND-CKD and revise current recommendations and controversies in its management. Exploring data from real-world clinical practices, particularly from the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps), we highlight the current challenges to translating current recommendations to clinical practice, providing patients’ perspectives of anemia and how it affects their quality of life. Finally, we summarize recent advances in the field of anemia that may change the way this condition will be managed in the future.Guedes, MuriloRobinson, Bruce M.Obrador, GregorioTong, AllisonPisoni, Ronald L.Pecoits-Filho, Roberto2020-07-01T06:00:11-07:00doi:10.34067/KID.0001442020hwp:resource-id:kidney360;1/8/855American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, anemia, erythrocyte count, erythrocytes, fatigue, hemoglobins, iron, patient reported outcome measures, quality of life, renal insufficiency, chronic, risk factorsReview ArticlesReview Articlesreview-article20202020-08-2710.34067/KID.00014420202641-76502020-07-01T06:00:11-07:002020-08-27Kidney360Review Articles18855862
- Multi-Organ Infarction in a Patient Receiving Infliximab10.34067/KID.0001192020Thu, 27 Aug 2020 05:30:21 GMT-07:00Multi-Organ Infarction in a Patient Receiving InfliximabCampbell, DeanKalra, KartikDesilva, Ranil2020-08-27T05:30:21-07:00doi:10.34067/KID.0001192020hwp:resource-id:kidney360;1/8/880American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, biomarkers, biopsy, polyarteritis nodosa, psoriatic arthritis, tumor necrosis factor inhibitors, tumor necrosis factor-alpha, vasculitisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-08-2710.34067/KID.00011920202641-76502020-08-27T05:30:21-07:002020-08-27Kidney360Clinical Images in Nephrology and Dialysis18880881
- Bioenergetic Evolution Explains Prevalence of Low Nephron Number at Birth: Risk Factor for CKDThere is greater than tenfold variation in nephron number of the human kidney at birth. Although low nephron number is a recognized risk factor for CKD, its determinants are poorly understood. Evolutionary medicine represents a new discipline that seeks evolutionary explanations for disease, broadening perspectives on research and public health initiatives. Evolution of the kidney, an organ rich in mitochondria, has been driven by natural selection for reproductive fitness constrained by energy availability. Over the past 2 million years, rapid growth of an energy-demanding brain in Homo sapiens enabled hominid adaptation to environmental extremes through selection for mutations in mitochondrial and nuclear DNA epigenetically regulated by allocation of energy to developing organs. Maternal undernutrition or hypoxia results in intrauterine growth restriction or preterm birth, resulting in low birth weight and low nephron number. Regulated through placental transfer, environmental oxygen and nutrients signal nephron progenitor cells to reprogram metabolism from glycolysis to oxidative phosphorylation. These processes are modulated by counterbalancing anabolic and catabolic metabolic pathways that evolved from prokaryote homologs and by hypoxia-driven and autophagy pathways that evolved in eukaryotes. Regulation of nephron differentiation by histone modifications and DNA methyltransferases provide epigenetic control of nephron number in response to energy available to the fetus. Developmental plasticity of nephrogenesis represents an evolved life history strategy that prioritizes energy to early brain growth with adequate kidney function through reproductive years, the trade-off being increasing prevalence of CKD delayed until later adulthood. The research implications of this evolutionary analysis are to identify regulatory pathways of energy allocation directing nephrogenesis while accounting for the different life history strategies of animal models such as the mouse. The clinical implications are to optimize nutrition and minimize hypoxic/toxic stressors in childbearing women and children in early postnatal development.10.34067/KID.0002012020Tue, 07 Jul 2020 10:12:04 GMT-07:00Bioenergetic Evolution Explains Prevalence of Low Nephron Number at Birth: Risk Factor for CKDThere is greater than tenfold variation in nephron number of the human kidney at birth. Although low nephron number is a recognized risk factor for CKD, its determinants are poorly understood. Evolutionary medicine represents a new discipline that seeks evolutionary explanations for disease, broadening perspectives on research and public health initiatives. Evolution of the kidney, an organ rich in mitochondria, has been driven by natural selection for reproductive fitness constrained by energy availability. Over the past 2 million years, rapid growth of an energy-demanding brain in Homo sapiens enabled hominid adaptation to environmental extremes through selection for mutations in mitochondrial and nuclear DNA epigenetically regulated by allocation of energy to developing organs. Maternal undernutrition or hypoxia results in intrauterine growth restriction or preterm birth, resulting in low birth weight and low nephron number. Regulated through placental transfer, environmental oxygen and nutrients signal nephron progenitor cells to reprogram metabolism from glycolysis to oxidative phosphorylation. These processes are modulated by counterbalancing anabolic and catabolic metabolic pathways that evolved from prokaryote homologs and by hypoxia-driven and autophagy pathways that evolved in eukaryotes. Regulation of nephron differentiation by histone modifications and DNA methyltransferases provide epigenetic control of nephron number in response to energy available to the fetus. Developmental plasticity of nephrogenesis represents an evolved life history strategy that prioritizes energy to early brain growth with adequate kidney function through reproductive years, the trade-off being increasing prevalence of CKD delayed until later adulthood. The research implications of this evolutionary analysis are to identify regulatory pathways of energy allocation directing nephrogenesis while accounting for the different life history strategies of animal models such as the mouse. The clinical implications are to optimize nutrition and minimize hypoxic/toxic stressors in childbearing women and children in early postnatal development.Chevalier, Robert L.2020-07-07T10:12:04-07:00doi:10.34067/KID.0002012020hwp:resource-id:kidney360;1/8/863American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, evolutionary bioenergetics, kidney development, developmental plasticity, epigenetics, evolutionary medicine, kidney metabolism, mitochondria, nephron number, placenta, Basic ScienceReview ArticlesReview Articlesreview-article20202020-08-2710.34067/KID.00020120202641-76502020-07-07T10:12:04-07:002020-08-27Kidney360Review Articles18863879
- Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty Acids10.34067/KID.0000772019Wed, 03 Jun 2020 10:15:34 GMT-07:00Advanced Oxidation Protein Products Contribute to Renal Tubulopathy via Perturbation of Renal Fatty AcidsImafuku, TadashiWatanabe, HiroshiSatoh, TakaoMatsuzaka, TakashiInazumi, TomoakiKato, HiromasaTanaka, ShomaNakamura, YukaNakano, TakehiroTokumaru, KaiMaeda, HitoshiMukunoki, AyumiTakeo, ToruNakagata, NaomiTanaka, MotokoMatsushita, KazutakaTsuchiya, SokenSugimoto, YukihikoShimano, HitoshiFukagawa, MasafumiMaruyama, Toru2020-06-03T10:15:34-07:00doi:10.34067/KID.0000772019hwp:resource-id:kidney360;1/8/781American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, advanced oxidation protein products, albumin, Elovl6, epithelial cells, ER stress, fatty acid metabolism, mechanistic target of rapamycin complex 1, mice, mTORC1, proximal tubulopathy, renal fatty acids perturbation, SREBP1, stearate, Basic ScienceOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-08-2710.34067/KID.00007720192641-76502020-06-03T10:15:34-07:002020-08-27Kidney360Original Investigations18781796
- Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection10.34067/KID.0003792020Mon, 22 Jun 2020 01:37:01 GMT-07:00Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 InfectionChaudhri, ImranKoraishy, Farrukh M.Bolotova, OlenaYoo, JeanwooMarcos, Luis A.Taub, ErinSahib, HaseenaBloom, MichelleAhmad, SaharSkopicki, HalMallipattu, Sandeep K.2020-06-22T13:37:01-07:00doi:10.34067/KID.0003792020hwp:resource-id:kidney360;1/8/801American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360hypertension, ACE inhibitors, angiotensin II receptor blocker, cohort studies, COVID-19, hospitalization, hypertension, inflammation, renin angiotensin system, respirationOriginal InvestigationsHypertensionOriginal InvestigationsHypertensionresearch-article20202020-08-2710.34067/KID.00037920202641-76502020-06-22T13:37:01-07:002020-08-27Kidney360Original Investigations18801809
- Urinary Sediment Microscopy in Acute Kidney Injury Associated with COVID-1910.34067/KID.0003352020Tue, 02 Jun 2020 02:13:45 GMT-07:00Urinary Sediment Microscopy in Acute Kidney Injury Associated with COVID-19Hernandez-Arroyo, Cesar F.Varghese, VipinMohamed, Muner M.B.Velez, Juan Carlos Q.2020-06-02T14:13:45-07:00doi:10.34067/KID.0003352020hwp:resource-id:kidney360;1/8/819American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Clinical Nephrology, Acute Kidney Injury, acute tubular injury, acute tubular necrosis, coronavirus, COVID-19, diagnosis, granular casts, Microscopy, SARS-CoV-2, urine sedimentBrief CommunicationsBrief Communicationsbrief-report20202020-08-2710.34067/KID.00033520202641-76502020-06-02T14:13:45-07:002020-08-27Kidney360Brief Communications18819823
- Chronic Hemodialysis Patients Hospitalized with COVID-19: Short-term Outcomes in the Bronx, New York10.34067/KID.0003672020Thu, 18 Jun 2020 09:50:03 GMT-07:00Chronic Hemodialysis Patients Hospitalized with COVID-19: Short-term Outcomes in the Bronx, New YorkFisher, MollyYunes, MilagrosMokrzycki, Michele H.Golestaneh, LadanAlahiri, EmadCoco, Maria2020-06-18T09:50:03-07:00doi:10.34067/KID.0003672020hwp:resource-id:kidney360;1/8/755American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, cardiovascular diseases, coronavirus infections, COVID-19, hospital mortality, kidney failure, chronic, New York City, renal dialysis, respiration, artificial, retrospective studies, severe acute respiratory syndrome coronavirus 2Original InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-08-2710.34067/KID.00036720202641-76502020-06-18T09:50:03-07:002020-08-27Kidney360Original Investigations18755762
- Appearances Can Be Deceiving - Viral-like Inclusions in COVID-19 Negative Renal Biopsies by Electron Microscopy10.34067/KID.0002692020Tue, 30 Jun 2020 06:07:27 GMT-07:00Appearances Can Be Deceiving - Viral-like Inclusions in COVID-19 Negative Renal Biopsies by Electron MicroscopyCassol, Clarissa A.Gokden, NerimanLarsen, Christopher P.Bourne, Thomas D.2020-06-30T06:07:27-07:00doi:10.34067/KID.0002692020hwp:resource-id:kidney360;1/8/824American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, endosomes, exosomes, inclusions, microscopy, electron, microscopy, immunoelectron, pandemics, reverse transcriptase polymerase chain reaction, RNA, viral, SARS-CoV-2, ultrastructure, virionsBrief CommunicationsBrief Communicationsbrief-report20202020-08-2710.34067/KID.00026920202641-76502020-06-30T06:07:27-07:002020-08-27Kidney360Brief Communications18824828
- Technology, Telehealth, and Nephrology: The Time Is Now10.34067/KID.0002382020Wed, 03 Jun 2020 10:15:34 GMT-07:00Technology, Telehealth, and Nephrology: The Time Is NowJain, GauravAhmad, MasoodWallace, Eric L.2020-06-03T10:15:34-07:00doi:10.34067/KID.0002382020hwp:resource-id:kidney360;1/8/834American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, access to care, apps, COVID-19, health services accessibility, kidney failure, chronic, monitoring, physiologic, pandemics, renal dialysis, renal insufficiency, chronic, telehealth, telemedicine, telenephrology, videoPerspectivePerspectiveresearch-article20202020-08-2710.34067/KID.00023820202641-76502020-06-03T10:15:34-07:002020-08-27Kidney360Perspective18834836
- Response to COVID-19 Infection in Hemodialysis Patients: An Australian Perspective10.34067/KID.0002492020Fri, 19 Jun 2020 09:12:27 GMT-07:00Response to COVID-19 Infection in Hemodialysis Patients: An Australian PerspectivePolkinghorne, Kevan R.Kerr, Peter G.Boudville, Neil2020-06-19T09:12:27-07:00doi:10.34067/KID.0002492020hwp:resource-id:kidney360;1/8/829American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, acute kidney injury, Australia, COVID-19, dialysis, government, New Zealand, severe acute respiratory syndrome coronavirus 2Global PerspectiveGlobal Perspectiveresearch-article20202020-08-2710.34067/KID.00024920202641-76502020-06-19T09:12:27-07:002020-08-27Kidney360Global Perspective18829833
- Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury10.34067/KID.0001632020Wed, 24 Jun 2020 01:26:36 GMT-07:00Impaired Tubular Secretion of Organic Solutes in Acute Kidney InjuryO’Brien, Frank J.Mair, Robert D.Plummer, Natalie S.Meyer, Timothy W.Sutherland, Scott M.Sirich, Tammy L.2020-06-24T13:26:36-07:00doi:10.34067/KID.0001632020hwp:resource-id:kidney360;1/8/724American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Acute Kidney Injury and ICU Nephrology, 4-cresol sulfate, Acute Kidney Injury, Blood Proteins, Creatinine, Cresols, Glutamine, Hippurates, Indican, phenylacetylglutamine, Sulfates, Sulfuric Acid EstersOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-08-2710.34067/KID.00016320202641-76502020-06-24T13:26:36-07:002020-08-27Kidney360Original Investigations18724730
- Unusual Dialysis Catheter Location in a Transplant Patient10.34067/KID.0001252020Thu, 27 Aug 2020 05:30:21 GMT-07:00Unusual Dialysis Catheter Location in a Transplant PatientVia Reque Cortes, Daniela del PilarAndrade Vale, PabloGessolo Lins, Paulo Ricardo2020-08-27T05:30:21-07:00doi:10.34067/KID.0001252020hwp:resource-id:kidney360;1/8/884American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, heart defects, congenital, hemodialysis, hemodynamics, persistent left superior vena cava, renal dialysis, vascular access, vascular malformations, vena cavaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-08-2710.34067/KID.00012520202641-76502020-08-27T05:30:21-07:002020-08-27Kidney360Clinical Images in Nephrology and Dialysis18884886
- An Approach to Neurological Disorders in a Kidney Transplant RecipientKidney transplantation is the preferred treatment modality in patients with ESKD. However, there are associated complications that arise from immunosuppressive medications, infections, and associated comorbidities. Neurologic disorders frequently develop in patients who have received a kidney transplant, which in turn increases the associated morbidity and mortality. This review discusses the common neurologic disorders after kidney transplantation, including infections, cognitive decline, drug-related conditions, malignancy, seizure, and other neurologic complications.10.34067/KID.0002052020Tue, 16 Jun 2020 10:37:41 GMT-07:00An Approach to Neurological Disorders in a Kidney Transplant RecipientKidney transplantation is the preferred treatment modality in patients with ESKD. However, there are associated complications that arise from immunosuppressive medications, infections, and associated comorbidities. Neurologic disorders frequently develop in patients who have received a kidney transplant, which in turn increases the associated morbidity and mortality. This review discusses the common neurologic disorders after kidney transplantation, including infections, cognitive decline, drug-related conditions, malignancy, seizure, and other neurologic complications.Meena, PritiBhargava, VinantRana, DevinderBhalla, AnilGupta, Ashwani2020-06-16T10:37:41-07:00doi:10.34067/KID.0002052020hwp:resource-id:kidney360;1/8/837American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, calcineurin inhibitors, cognitive dysfunction, comorbidity, ESKD, immunosuppression, infections, kidney failure, chronic, kidney transplantation, neurological complications, seizuresReview ArticlesReview Articlesreview-article20202020-08-2710.34067/KID.00020520202641-76502020-06-16T10:37:41-07:002020-08-27Kidney360Review Articles18837844
- What It Means to Live with Focal Segmental Glomerulosclerosis10.2215/CJN.02890320Thu, 30 Apr 2020 07:33:45 GMT-07:00What It Means to Live with Focal Segmental GlomerulosclerosisBressler, Kent2020-04-30T07:33:45-07:00doi:10.2215/CJN.02890320hwp:resource-id:clinjasn;15/5/587American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGlomerulosclerosis, Focal Segmental, Biopsy, kidney patientPatient VoicePatient Voiceeditorial20202020-05-07May 07, 202010.2215/CJN.028903201555-90411555-905X2020-04-30T07:33:45-07:002020-05-07Clinical Journal of the American Society of NephrologyPatient Voice15555587594673588596684
- Ask and It Shall Be Given10.2215/CJN.03180320Thu, 30 Apr 2020 07:33:45 GMT-07:00Ask and It Shall Be GivenCanetta, Pietro A.Bomback, Andrew S.2020-04-30T07:33:45-07:00doi:10.2215/CJN.03180320hwp:resource-id:clinjasn;15/5/594American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, clinical trial, Epidemiology and outcomes, Kidney Diseases, Outcome Assessment, Health Care, Glomerular DiseasesEditorialsEditorialseditorial20202020-05-07May 07, 202010.2215/CJN.031803201555-90411555-905X2020-04-30T07:33:45-07:002020-05-07Clinical Journal of the American Society of NephrologyEditorials15555594587673596588684
- Walking while Talking in Older Adults with Chronic Kidney Disease10.2215/CJN.12401019Fri, 06 Mar 2020 07:58:09 GMT-08:00Walking while Talking in Older Adults with Chronic Kidney DiseaseHo, Jim Q.Verghese, JoeAbramowitz, Matthew K.2020-03-06T07:58:09-08:00doi:10.2215/CJN.12401019hwp:resource-id:clinjasn;15/5/665American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, Aged, Walking Speed, Walking, Accidental Falls, Independent Living, Frailty, Gait Analysis, Factor Analysis, Statistical, glomerular filtration rate, Gait, Cognitive Dysfunction, Linear Models, EGFR protein, human, ErbB Receptors, Renal Insufficiency, Chronic, CognitionOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20202020-05-07May 07, 202010.2215/CJN.124010191555-90411555-905X2020-03-06T07:58:09-08:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles155665672
- Circulating Uromodulin and Risk of Cardiovascular Events and Kidney Failure10.2215/CJN.03580320Tue, 14 Apr 2020 10:16:17 GMT-07:00Circulating Uromodulin and Risk of Cardiovascular Events and Kidney FailurePonte, BelenDevuyst, Olivier2020-04-14T10:16:17-07:00doi:10.2215/CJN.03580320hwp:resource-id:clinjasn;15/5/589American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUromodulin, Renal Insufficiency, Cardiovascular Diseases, BiomarkersEditorialsEditorialsresearch-article20202020-05-07May 07, 202010.2215/CJN.035803201555-90411555-905X2020-04-14T10:16:17-07:002020-05-07Clinical Journal of the American Society of NephrologyEditorials1555589616591624
- Identifying Outcomes Important to Patients with Glomerular Disease and Their Caregivers10.2215/CJN.13101019Thu, 30 Apr 2020 07:33:44 GMT-07:00Identifying Outcomes Important to Patients with Glomerular Disease and Their CaregiversCarter, Simon A.Gutman, TaliaLogeman, CharlotteCattran, DanLightstone, LizBagga, ArvindBarbour, Sean J.Barratt, JonathanBoletis, JohnCaster, DawnCoppo, RosannaFervenza, Fernando C.Floege, JürgenHladunewich, MichelleHogan, Jonathan J.Kitching, A. RichardLafayette, Richard A.Malvar, AnaRadhakrishnan, JaiRovin, Brad H.Scholes-Robertson, NicoleTrimarchi, HérnanZhang, HongAzukaitis, KarolisCho, YeoungjeeViecelli, Andrea K.Dunn, LoueseHarris, DavidJohnson, David W.Kerr, Peter G.Laboi, PaulRyan, JessicaShen, Jenny I.Ruiz, LorenaWang, Angela Yee-MoonLee, Achilles Hoi KanFung, SamuelTong, Matthew Ka-HangTeixeira-Pinto, ArmandoWilkie, MartinAlexander, Stephen I.Craig, Jonathan C.Tong, Allison,2020-04-30T07:33:44-07:00doi:10.2215/CJN.13101019hwp:resource-id:clinjasn;15/5/673American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFocus Groups, Caregivers, renal dialysis, blood pressure, Decision Making, Shared, Data Accuracy, Blood Pressure Determination, Family Relations, Anxiety, Fatigue, InfectionsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-05-07May 07, 202010.2215/CJN.131010191555-90411555-905X2020-04-30T07:33:44-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles15555673587594684588596
- Benefits of Continuing RAAS Inhibitors in Advanced CKD10.2215/CJN.02920320Mon, 06 Apr 2020 08:22:57 GMT-07:00Benefits of Continuing RAAS Inhibitors in Advanced CKDGaudreault-Tremblay, Marie-MichèleFoster, Bethany J.2020-04-06T08:22:57-07:00doi:10.2215/CJN.02920320hwp:resource-id:clinjasn;15/5/592American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyACE inhibitors, chronic kidney disease, chronic kidney failure, chronic renal insufficiency, clinical nephrology, pediatric nephrology, progression of chronic renal failure, progression of renal failure, proteinuria, renal protection, renin angiotensin system, Renal Insufficiency, Chronic, Renin-Angiotensin System, Angiotensin-Converting Enzyme InhibitorsEditorialsEditorialseditorial20202020-05-07May 07, 202010.2215/CJN.029203201555-90411555-905X2020-04-06T08:22:57-07:002020-05-07Clinical Journal of the American Society of NephrologyEditorials1555592625593632
- The Elusive Promise of Bioimpedance in Fluid Management of Patients Undergoing Dialysis10.2215/CJN.01770220Wed, 29 Apr 2020 08:37:30 GMT-07:00The Elusive Promise of Bioimpedance in Fluid Management of Patients Undergoing DialysisDavies, Simon J.2020-04-29T08:37:30-07:00doi:10.2215/CJN.01770220hwp:resource-id:clinjasn;15/5/597American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, dialysis, randomized controlled trials, left ventricular hypertrophy, renal dialysis, Fluid Therapy, Electric ImpedanceEditorialsEditorialseditorial20202020-05-07May 07, 202010.2215/CJN.017702201555-90411555-905X2020-04-29T08:37:30-07:002020-05-07Clinical Journal of the American Society of NephrologyEditorials1555597685599694
- Bioimpedance Guided Fluid Management in Peritoneal Dialysis10.2215/CJN.06480619Wed, 29 Apr 2020 08:37:30 GMT-07:00Bioimpedance Guided Fluid Management in Peritoneal DialysisTian, NaYang, XiaoGuo, QunyingZhou, QianYi, ChunyanLin, JianxiongCao, PeiyiYe, HongjianChen, MenghuaYu, Xueqing2020-04-29T08:37:30-07:00doi:10.2215/CJN.06480619hwp:resource-id:clinjasn;15/5/685American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfluid overload, bioelectrical impedance analysis, fluid control, short-term outcome, Control Groups, Cardiovascular Diseases, Electric Impedance, Body Water, Survival Rate, peritoneal dialysis, dialysis, Water-Electrolyte Imbalance, Maintenance, diabetes mellitusOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-05-07May 07, 202010.2215/CJN.064806191555-90411555-905X2020-04-29T08:37:30-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1555685597694599
- Trajectories of Serum Sodium on In-Hospital and 1-Year Survival among Hospitalized Patients10.2215/CJN.12281019Wed, 25 Mar 2020 06:32:37 GMT-07:00Trajectories of Serum Sodium on In-Hospital and 1-Year Survival among Hospitalized PatientsChewcharat, ApiThongprayoon, CharatCheungpasitporn, WisitMao, Michael A.Thirunavukkarasu, SorkkoKashani, Kianoush B.2020-03-25T06:32:37-07:00doi:10.2215/CJN.12281019hwp:resource-id:clinjasn;15/5/600American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysodium, survival, hospitalized patients, hyponatremia, hypernatremia, hospital mortality, cohort studies, hospitalization, hospitalsOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20202020-05-07May 07, 202010.2215/CJN.122810191555-90411555-905X2020-03-25T06:32:37-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles155600607
- Pilot Study of Return of Genetic Results to Patients in Adult Nephrology10.2215/CJN.12481019Thu, 16 Apr 2020 02:04:02 GMT-07:00Pilot Study of Return of Genetic Results to Patients in Adult NephrologyNestor, Jordan G.Marasa, MaddalenaMilo-Rasouly, HilaGroopman, Emily E.Husain, S. AliMohan, SumitFernandez, HildaAggarwal, Vimla S.Ahram, Dina F.Vena, NatalieBogyo, KelsieBomback, Andrew S.Radhakrishnan, JaiAppel, Gerald B.Ahn, WooinCohen, David J.Canetta, Pietro A.Dube, Geoffrey K.Rao, Maya K.Morris, Heather K.Crew, Russell J.Sanna-Cherchi, SimoneKiryluk, KrzysztofGharavi, Ali G.2020-04-16T14:04:02-07:00doi:10.2215/CJN.12481019hwp:resource-id:clinjasn;15/5/651American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, human genetics, chronic kidney disease, familial nephropathy, adult, humans, nephrology, retrospective studies, pilot projects, workflow, medical genetics, exome, biological specimen banks, whole exome sequencing, kidney diseases, genetic testing, genomics, referral and consultation, patient care, cohort studiesOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20202020-05-07May 07, 202010.2215/CJN.124810191555-90411555-905X2020-04-16T14:04:02-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles155651664
- A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal Trials10.2215/CJN.08170719Thu, 02 Apr 2020 01:32:20 GMT-07:00A Post Hoc Analysis of Statin Use in Tolvaptan Autosomal Dominant Polycystic Kidney Disease Pivotal TrialsShoaf, Susan E.Ouyang, JohnSergeyeva, OlgaEstilo, AlvinLi, HuiLeung, Deborah2020-04-02T13:32:20-07:00doi:10.2215/CJN.08170719hwp:resource-id:clinjasn;15/5/643American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, chronic renal disease, polycystic kidney disease, statins, pharmacokinetics, Alanine Transaminase, Polycystic Kidney, Autosomal Dominant, Aspartate Aminotransferases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Tolvaptan, Allopurinol, Confidence Intervals, Incidence, Abdominal Pain, Research Design, Organic Anion Transporters, Antidiuretic Hormone Receptor Antagonists, chronic kidney diseaseOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20202020-05-07May 07, 202010.2215/CJN.081707191555-90411555-905X2020-04-02T13:32:20-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles155643650
- Effects of Intensive Blood Pressure Control in Patients with and without Albuminuria10.2215/CJN.12371019Wed, 15 Jul 2020 12:02:46 GMT-07:00Effects of Intensive Blood Pressure Control in Patients with and without AlbuminuriaChang, Alex R.Kramer, HollyWei, GuoBoucher, RobertGrams, Morgan E.Berlowitz, DanBhatt, UdayanCohen, Debbie L.Drawz, PaulPunzi, HenryFreedman, Barry I.Haley, WilliamHawfield, AmretHorwitz, EdwardMcLouth, ChristopherMorisky, DonPapademetriou, VasiliosRocco, Michael V.Wall, BarryWeiner, Daniel E.Zias, AthenaBeddhu, Srinivasan,2020-07-15T12:02:46-07:00doi:10.2215/CJN.12371019hwp:resource-id:clinjasn;15/8/1121American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, hypertension, albuminuria, chronic kidney disease, cardiovascular disease, mortality, systolic blood pressure, clinical trialOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20202020-08-07August 07, 202010.2215/CJN.123710191555-90411555-905X2020-07-15T12:02:46-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15881121108111281083
- Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia10.2215/CJN.16011219Tue, 28 Jul 2020 10:43:58 GMT-07:00Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with AnemiaAkizawa, TadaoNangaku, MasaomiYonekawa, TaekoOkuda, NobuhikoKawamatsu, ShinyaOnoue, TomohiroEndo, YukihiroHara, KatsutoshiCobitz, Alexander R.2020-07-28T10:43:58-07:00doi:10.2215/CJN.16011219hwp:resource-id:clinjasn;15/8/1155American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, anemia, hemodialysis, Erythropoiesis, hypoxia-inducible factor prolyl hydroxylase inhibitor, daprodustat, HIF, clinical trial, double-blind, hemoglobin, hepcidinOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-08-07August 07, 202010.2215/CJN.160112191555-90411555-905X2020-07-28T10:43:58-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15811551165
- Intensive Blood Pressure Lowering Should Be the Goal for Most Individuals at High Risk of Cardiovascular Disease Irrespective of Albuminuria10.2215/CJN.09410620Wed, 15 Jul 2020 12:02:46 GMT-07:00Intensive Blood Pressure Lowering Should Be the Goal for Most Individuals at High Risk of Cardiovascular Disease Irrespective of AlbuminuriaAscher, Simon B.Ix, Joachim H.2020-07-15T12:02:46-07:00doi:10.2215/CJN.09410620hwp:resource-id:clinjasn;15/8/1081American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, proteinuria, albuminuria, chronic kidney disease, cardiovascular disease, randomized controlled trials, hypertensionEditorialsEditorialseditorial20202020-08-07August 07, 202010.2215/CJN.094106201555-90411555-905X2020-07-15T12:02:46-07:002020-08-07Clinical Journal of the American Society of NephrologyEditorials15881081112110831128
- Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China10.2215/CJN.04160320Fri, 22 May 2020 05:48:43 GMT-07:00Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, ChinaWu, JunLi, JushuangZhu, GeliZhang, YanxiaBi, ZhiminYu, YeanHuang, BoFu, ShouzhiTan, YiqingSun, JianbinLi, Xiangyou2020-05-22T05:48:43-07:00doi:10.2215/CJN.04160320hwp:resource-id:clinjasn;15/8/1139American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysevere acute respiratory syndrome coronavirus 2, OVID-19, kidney failure, maintenance hemodialysis, CoronavirusOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-08-07August 07, 202010.2215/CJN.041603201555-90411555-905X2020-05-22T05:48:43-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15888113910731087114510741089
- Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis10.2215/CJN.14561119Tue, 28 Jul 2020 10:43:59 GMT-07:00Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritisvan Daalen, Emma E.Wester Trejo, Maria A.C.Göçeroğlu, ArdaFerrario, FrancoJoh, KensukeNoël, Laure-HélèneOgawa, YayoiWilhelmus, SuzanneBall, Miriam J.Honsova, EvaHruskova, ZdenkaKain, RenateKimura, TomoyoshiKollar, MarekKronbichler, AndreasLindhard, KristinePuéchal, XavierSalvatore, StevenSzpirt, WladimirTakizawa, HidekiTesar, VladimirBerden, Annelies E.Dekkers, Olaf M.Hagen, E. ChristiaanOosting, JanRahmattulla, ChinarWolterbeek, RonBos, Willem JanBruijn, Jan A.Bajema, Ingeborg M.2020-07-28T10:43:59-07:00doi:10.2215/CJN.14561119hwp:resource-id:clinjasn;15/8/1103American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, kidney biopsy, Antibodies, Antineutrophil Cytoplasmic, Confidence Intervals, Observer Variation, glomerulonephritis, Renal Insufficiency, Cohort Studies, Prognosis, BiopsyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-08-07August 07, 202010.2215/CJN.145611191555-90411555-905X2020-07-28T10:43:59-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15881103107811111080
- Drug Selection for Treating Hypertension in Dialysis Patients10.2215/CJN.09910620Thu, 16 Jul 2020 07:30:40 GMT-07:00Drug Selection for Treating Hypertension in Dialysis PatientsShafi, TariqMiskulin, Dana C.2020-07-16T07:30:40-07:00doi:10.2215/CJN.09910620hwp:resource-id:clinjasn;15/8/1084American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, antihypertensive drug class, dialysisEditorialsEditorialseditorial20202020-08-07August 07, 202010.2215/CJN.099106201555-90411555-905X2020-07-16T07:30:40-07:002020-08-07Clinical Journal of the American Society of NephrologyEditorials15881084112910861138
- External Validation of the International IgA Nephropathy Prediction Tool10.2215/CJN.16021219Thu, 02 Jul 2020 07:49:00 GMT-07:00External Validation of the International IgA Nephropathy Prediction ToolZhang, JunjunHuang, BoLiu, ZhangsuoWang, XutongXie, MinhuaGuo, RuxueWang, YongliYu, DanWang, PanfeiZhu, YuzeRen, Jingjing2020-07-02T07:49:00-07:00doi:10.2215/CJN.16021219hwp:resource-id:clinjasn;15/8/1112American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, external validation, international prediction tool, glomerular filtration rate, Glomerulonephritis, IGA, Calibration, Kidney Failure, Chronic, Cohort Studies, BiopsyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-08-07August 07, 202010.2215/CJN.160212191555-90411555-905X2020-07-02T07:49:00-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15811121120
- Comparative Efficacy and Safety of BP-Lowering Pharmacotherapy in Patients Undergoing Maintenance Dialysis10.2215/CJN.12201019Thu, 16 Jul 2020 07:30:40 GMT-07:00Comparative Efficacy and Safety of BP-Lowering Pharmacotherapy in Patients Undergoing Maintenance DialysisShaman, Ahmed M.Smyth, BrendanArnott, ClarePalmer, Suetonia C.Mihailidou, Anastasia S.Jardine, Meg J.Gallagher, Martin P.Perkovic, VladoJun, Min2020-07-16T07:30:40-07:00doi:10.2215/CJN.12201019hwp:resource-id:clinjasn;15/8/1129American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, systolic blood pressure, chronic kidney disease, renal dialysis, Antihypertensive agents, Adverse events, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Renin, Calcium Channel Blockers, blood pressure, Mineralocorticoid Receptor Antagonists, Peptidyl-Dipeptidase A, Cardiovascular Diseases, hypotension, risk factorsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-08-07August 07, 202010.2215/CJN.122010191555-90411555-905X2020-07-16T07:30:40-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15881129108411381086
- Keeping Up with the Times10.2215/CJN.09600620Tue, 28 Jul 2020 10:43:59 GMT-07:00Keeping Up with the TimesBrix, Silke R.Geetha, Duvuru2020-07-28T10:43:59-07:00doi:10.2215/CJN.09600620hwp:resource-id:clinjasn;15/8/1078American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, glomerulonephritis, outcomesEditorialsEditorialseditorial20202020-08-07August 07, 202010.2215/CJN.096006201555-90411555-905X2020-07-28T10:43:59-07:002020-08-07Clinical Journal of the American Society of NephrologyEditorials15881078110310801111
- Apixaban versus No Anticoagulation in Patients Undergoing Long-Term Dialysis with Incident Atrial Fibrillation10.2215/CJN.11650919Fri, 22 May 2020 05:48:45 GMT-07:00Apixaban versus No Anticoagulation in Patients Undergoing Long-Term Dialysis with Incident Atrial FibrillationMavrakanas, Thomas A.Garlo, KatherineCharytan, David M.2020-05-22T05:48:45-07:00doi:10.2215/CJN.11650919hwp:resource-id:clinjasn;15/8/1146American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyapixaban, atrial fibrillation, dialysis, mortality, ischemic stroke, hemorrhagic stroke, Ischemic Attack, Transient, Stroke, Propensity Score, Incidence, Retrospective Studies, Brain Ischemia, Pyridones, Pyrazoles, Anticoagulants, Thromboembolism, Myocardial InfarctionOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-08-07August 07, 202010.2215/CJN.116509191555-90411555-905X2020-05-22T05:48:45-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15811461154
- Racial Differences in Risk Factors for Kidney Stone Formation10.2215/CJN.12671019Fri, 19 Jun 2020 10:04:56 GMT-07:00Racial Differences in Risk Factors for Kidney Stone FormationZisman, Anna L.Coe, Fredric L.Cohen, Andrew J.Riedinger, Christopher B.Worcester, Elaine M.2020-06-19T10:04:56-07:00doi:10.2215/CJN.12671019hwp:resource-id:clinjasn;15/8/1166American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, ethnicity, Calcium Oxalate, Uric Acid, African Americans, Kidney Calculi, risk factors, calcium phosphateOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20202020-08-07August 07, 202010.2215/CJN.126710191555-90411555-905X2020-06-19T10:04:56-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15811661173
- Adverse Drug Effects in Patients with CKD10.2215/CJN.08890620Wed, 01 Jul 2020 08:26:23 GMT-07:00Adverse Drug Effects in Patients with CKDPerazella, Mark A.Nolin, Thomas D.2020-07-01T08:26:23-07:00doi:10.2215/CJN.08890620hwp:resource-id:clinjasn;15/8/1075American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, acute kidney injury, drug toxicity, pharmacology, renin-angiotensin system blockers, hemorrhage, drug-related side effects and adverse reactions, renal insufficiency, chronic, glomerular filtration rateEditorialsEditorialseditorial20202020-08-07August 07, 202010.2215/CJN.088906201555-90411555-905X2020-07-01T08:26:23-07:002020-08-07Clinical Journal of the American Society of NephrologyEditorials15881075109010771102
- Kidney Disease, Race, and GFR EstimationAssessment of GFR is central to clinical practice, research, and public health. Current Kidney Disease Improving Global Outcomes guidelines recommend measurement of serum creatinine to estimate GFR as the initial step in GFR evaluation. Serum creatinine is influenced by creatinine metabolism as well as GFR; hence, all equations to estimate GFR from serum creatinine include surrogates for muscle mass, such as age, sex, race, height, or weight. The guideline-recommended equation in adults (the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation) includes a term for race (specified as black versus nonblack), which improves the accuracy of GFR estimation by accounting for differences in non-GFR determinants of serum creatinine by race in the study populations used to develop the equation. In that study, blacks had a 16% higher average measured GFR compared with nonblacks with the same age, sex, and serum creatinine. The reasons for this difference are only partly understood, and the use of race in GFR estimation has limitations. Some have proposed eliminating the race coefficient, but this would induce a systematic underestimation of measured GFR in blacks, with potential unintended consequences at the individual and population levels. We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group. We suggest full disclosure of use of race in GFR estimation, accommodation of those who decline to identify their race, and shared decision making between health care providers and patients. We also suggest mindful use of cystatin C as a confirmatory test as well as clearance measurements. It would be preferable to avoid specification of race in GFR estimation if there was a superior, evidence-based substitute. The goal of future research should be to develop more accurate methods for GFR estimation that do not require use of race or other demographic characteristics.10.2215/CJN.12791019Mon, 11 May 2020 08:13:20 GMT-07:00Kidney Disease, Race, and GFR EstimationAssessment of GFR is central to clinical practice, research, and public health. Current Kidney Disease Improving Global Outcomes guidelines recommend measurement of serum creatinine to estimate GFR as the initial step in GFR evaluation. Serum creatinine is influenced by creatinine metabolism as well as GFR; hence, all equations to estimate GFR from serum creatinine include surrogates for muscle mass, such as age, sex, race, height, or weight. The guideline-recommended equation in adults (the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation) includes a term for race (specified as black versus nonblack), which improves the accuracy of GFR estimation by accounting for differences in non-GFR determinants of serum creatinine by race in the study populations used to develop the equation. In that study, blacks had a 16% higher average measured GFR compared with nonblacks with the same age, sex, and serum creatinine. The reasons for this difference are only partly understood, and the use of race in GFR estimation has limitations. Some have proposed eliminating the race coefficient, but this would induce a systematic underestimation of measured GFR in blacks, with potential unintended consequences at the individual and population levels. We propose a more cautious approach that maintains and improves accuracy of GFR estimates and avoids disadvantaging any racial group. We suggest full disclosure of use of race in GFR estimation, accommodation of those who decline to identify their race, and shared decision making between health care providers and patients. We also suggest mindful use of cystatin C as a confirmatory test as well as clearance measurements. It would be preferable to avoid specification of race in GFR estimation if there was a superior, evidence-based substitute. The goal of future research should be to develop more accurate methods for GFR estimation that do not require use of race or other demographic characteristics.Levey, Andrew S.Titan, Silvia M.Powe, Neil R.Coresh, JosefInker, Lesley A.2020-05-11T08:13:20-07:00doi:10.2215/CJN.12791019hwp:resource-id:clinjasn;15/8/1203American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhuman, Cystatin C, creatinine, glomerular filtration rate, African Americans, Public Health, Decision Making, Shared, Body Weights and Measures, Renal Insufficiency, Chronic, Health Personnel, Demography, Kidney Function TestsFeaturesFeaturesresearch-article20202020-08-07August 07, 202010.2215/CJN.127910191555-90411555-905X2020-05-11T08:13:20-07:002020-08-07Clinical Journal of the American Society of NephrologyFeatures15881203120112121202
- Adverse Drug Reactions in Patients with CKD10.2215/CJN.01030120Wed, 01 Jul 2020 08:26:24 GMT-07:00Adverse Drug Reactions in Patients with CKDLaville, Solène M.Gras-Champel, ValérieMoragny, JulienMetzger, MarieJacquelinet, ChristianCombe, ChristianFouque, DenisLaville, MauriceFrimat, LucRobinson, Bruce M.Stengel, BénédicteMassy, Ziad A.Liabeuf, Sophie,2020-07-01T08:26:24-07:00doi:10.2215/CJN.01030120hwp:resource-id:clinjasn;15/8/1090American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, pharmacoepidemiology, antithrombotic agents, adverse drug reactions, risk factors, diuretics, Renin-Angiotensin System, glomerular filtration rate, Cohort Studies, Renal Insufficiency, Chronic, Drug-Related Side Effects and Adverse Reactions, hospitalization, Medical RecordsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-08-07August 07, 202010.2215/CJN.010301201555-90411555-905X2020-07-01T08:26:24-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15881090107511021077
- COVID-19 in Patients with Kidney Disease10.2215/CJN.09730620Tue, 07 Jul 2020 07:17:46 GMT-07:00COVID-19 in Patients with Kidney DiseaseAjaimy, MariaMelamed, Michal L.2020-07-07T07:17:46-07:00doi:10.2215/CJN.09730620hwp:resource-id:clinjasn;15/8/1087American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, transplantation, COVID-19EditorialsEditorialseditorial20202020-08-07August 07, 202010.2215/CJN.097306201555-90411555-905X2020-07-07T07:17:46-07:002020-08-07Clinical Journal of the American Society of NephrologyEditorials15888810871139117410731089114511781074
- Long-Term Hemodialysis during the COVID-19 Pandemic10.2215/CJN.09100620Thu, 02 Jul 2020 07:49:00 GMT-07:00Long-Term Hemodialysis during the COVID-19 PandemicGedney, Nieltje2020-07-02T07:49:00-07:00doi:10.2215/CJN.09100620hwp:resource-id:clinjasn;15/8/1073American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, chronic dialysis, chronic kidney disease, chronic kidney failure, chronic renal failure, COVID-19, dialysis, end stage kidney disease, end-stage renal disease, kidney disease, kidney failurePatient VoicePatient Voiceresearch-article20202020-08-07August 07, 202010.2215/CJN.091006201555-90411555-905X2020-07-02T07:49:00-07:002020-08-07Clinical Journal of the American Society of NephrologyPatient Voice15888107311391087107411451089
- Precision in GFR Reporting10.2215/CJN.00690120Mon, 11 May 2020 08:13:20 GMT-07:00Precision in GFR ReportingGrubbs, Vanessa2020-05-11T08:13:20-07:00doi:10.2215/CJN.00690120hwp:resource-id:clinjasn;15/8/1201American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrace-based medicine, GFR reporting, precision, glomerular filtration rate, Cystatin CPerspectivesPerspectivesresearch-article20202020-08-07August 07, 202010.2215/CJN.006901201555-90411555-905X2020-05-11T08:13:20-07:002020-08-07Clinical Journal of the American Society of NephrologyPerspectives15881201120312021212
- I Love Nephrology, but Should I Be a Nephrologist?10.2215/CJN.01490220Tue, 12 May 2020 07:02:16 GMT-07:00I Love Nephrology, but Should I Be a Nephrologist?Arora, Tanima2020-05-12T07:02:16-07:00doi:10.2215/CJN.01490220hwp:resource-id:clinjasn;15/8/1193American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, Education, Career Trainee, Initiatives, nephrologistsPerspectivesPerspectivesresearch-article20202020-08-07August 07, 202010.2215/CJN.014902201555-90411555-905X2020-05-12T07:02:16-07:002020-08-07Clinical Journal of the American Society of NephrologyPerspectives15811931194
- Careers in Critical Care Nephrology10.2215/CJN.10500919Thu, 09 Jul 2020 07:55:51 GMT-07:00Careers in Critical Care NephrologySanghavi, Sarah F.Campbell, Kirk N.2020-07-09T07:55:51-07:00doi:10.2215/CJN.10500919hwp:resource-id:clinjasn;15/8/1198American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycritical care, workforce, recruitment, training, intensivist, intensive care, Career Choice, Fellowships and ScholarshipsPerspectivesPerspectivesresearch-article20202020-08-07August 07, 202010.2215/CJN.105009191555-90411555-905X2020-07-09T07:55:51-07:002020-08-07Clinical Journal of the American Society of NephrologyPerspectives15811981200
- Ensuring Gender-Affirming Care in Nephrology10.2215/CJN.14471119Thu, 05 Mar 2020 06:30:38 GMT-08:00Ensuring Gender-Affirming Care in NephrologyMohottige, DinushikaLunn, Mitchell R.2020-03-05T06:30:38-08:00doi:10.2215/CJN.14471119hwp:resource-id:clinjasn;15/8/1195American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTransgender Persons, Transsexualism, nephrology, Gender Identity, Improving Care, Gender ExpansivePerspectivesPerspectivesresearch-article20202020-08-07August 07, 202010.2215/CJN.144711191555-90411555-905X2020-03-05T06:30:38-08:002020-08-07Clinical Journal of the American Society of NephrologyPerspectives15811951197
- At the Research-Clinical InterfaceWhether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (APOL1), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions.10.2215/CJN.09670819Mon, 10 Feb 2020 08:18:15 GMT-08:00At the Research-Clinical InterfaceWhether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (APOL1), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions.West, Kathleen M.Blacksher, ErikaCavanaugh, Kerri L.Fullerton, Stephanie M.Umeukeje, Ebele M.Young, Bessie A.Burke, Wylie2020-02-10T08:18:15-08:00doi:10.2215/CJN.09670819hwp:resource-id:clinjasn;15/8/1181American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, research results, ethics, humans, consensus, apolipoprotein L1, genetic research, disclosure, knowledge, kidney, diseases, Kidney Genomics SeriesGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-08-07August 07, 202010.2215/CJN.096708191555-90411555-905X2020-02-10T08:18:15-08:002020-08-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease15811811189
- Presidential Address Kidney Week 2019The American Society of Nephrology Presidential Address was delivered by Mark Rosenberg at Kidney Week 2019 on November 7, 2019 in Washington, DC. The Address describes a remarkable alignment—a syzygy of policy, science, innovation accelerators, clinical trials, clinical care delivery, and activated patients—that exists today in the kidney space. As a community, we must ensure that the strategies developed to take advantage of this alignment, such as Advancing American Kidney Health, succeed. We must overcome our current challenges to thrive as a meaningful specialty. We have an incredible opportunity to come together as a kidney community to ensure success that realigns the priorities and incentives in kidney medicine to better achieve kidney health for all people throughout the world. The time is now to act.10.2215/CJN.15011219Tue, 24 Mar 2020 07:47:32 GMT-07:00Presidential Address Kidney Week 2019The American Society of Nephrology Presidential Address was delivered by Mark Rosenberg at Kidney Week 2019 on November 7, 2019 in Washington, DC. The Address describes a remarkable alignment—a syzygy of policy, science, innovation accelerators, clinical trials, clinical care delivery, and activated patients—that exists today in the kidney space. As a community, we must ensure that the strategies developed to take advantage of this alignment, such as Advancing American Kidney Health, succeed. We must overcome our current challenges to thrive as a meaningful specialty. We have an incredible opportunity to come together as a kidney community to ensure success that realigns the priorities and incentives in kidney medicine to better achieve kidney health for all people throughout the world. The time is now to act.Rosenberg, Mark E.2020-03-24T07:47:32-07:00doi:10.2215/CJN.15011219hwp:resource-id:clinjasn;15/8/1213American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, kidney, kidney failure, nephrology, transplantation, policy, kidney diseases, patientparticipationFeaturesFeaturesresearch-article20202020-08-07August 07, 202010.2215/CJN.150112191555-90411555-905X2020-03-24T07:47:32-07:002020-08-07Clinical Journal of the American Society of NephrologyFeatures15812131219
- Association of Race and Risk of Graft Loss among Kidney Transplant Recipients in the US Military Health System10.2215/CJN.01200120Thu, 30 Apr 2020 07:33:45 GMT-07:00Association of Race and Risk of Graft Loss among Kidney Transplant Recipients in the US Military Health SystemForman, Crystal J.Yuan, Christina M.Jindal, Rahul M.Agodoa, Lawrence Y.Abbott, Kevin C.Nee, Robert2020-04-30T07:33:45-07:00doi:10.2215/CJN.01200120hwp:resource-id:clinjasn;15/8/1179American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, transplant outcomes, United States Renal Data System, end stage kidney disease, Military Health System, Medical Assistance, Graft Survival, Graft RejectionResearch LettersResearch Lettersresearch-article20202020-08-07August 07, 202010.2215/CJN.012001201555-90411555-905X2020-04-30T07:33:45-07:002020-08-07Clinical Journal of the American Society of NephrologyResearch Letters15811791180
- Early Outcomes of Outpatient Management of Kidney Transplant Recipients with Coronavirus Disease 201910.2215/CJN.05170420Mon, 18 May 2020 12:58:57 GMT-07:00Early Outcomes of Outpatient Management of Kidney Transplant Recipients with Coronavirus Disease 2019Husain, S. AliDube, GeoffreyMorris, HeatherFernandez, HildaChang, Jae-HyungPaget, KathrynSritharan, SharlineePatel, ShefaliPawliczak, OlgaBoehler, MiaTsapepas, DemetraCrew, R. JohnCohen, David J.Mohan, Sumit2020-05-18T12:58:57-07:00doi:10.2215/CJN.05170420hwp:resource-id:clinjasn;15/8/1174American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, COVID-19, SARS-CoV2, coronavirus, Outpatients, Statistics, Nonparametric, creatinine, severe acute respiratory syndrome coronavirus 2, Cohort Studies, hospitalization, DyspneaOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-08-07August 07, 202010.2215/CJN.051704201555-90411555-905X2020-05-18T12:58:57-07:002020-08-07Clinical Journal of the American Society of NephrologyOriginal Articles15881174108711781089
- Use of Checkpoint Inhibitors in a Kidney Transplant Recipient with Metastatic Cancer10.2215/CJN.15941219Mon, 23 Mar 2020 05:27:10 GMT-07:00Use of Checkpoint Inhibitors in a Kidney Transplant Recipient with Metastatic CancerOng, Song ChingMannon, Roslyn B.2020-03-23T05:27:10-07:00doi:10.2215/CJN.15941219hwp:resource-id:clinjasn;15/8/1190American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, renal transplantation, rejection, kidney transplantation, Neoplasms, Neoplasms, Second PrimaryKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20202020-08-07August 07, 202010.2215/CJN.159412191555-90411555-905X2020-03-23T05:27:10-07:002020-08-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire15811901192
- Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? PRO10.34067/KID.0003172020Wed, 17 Jun 2020 01:34:06 GMT-07:00Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? PRODe Broe, Marc E.Vervaet, Bejamin A.2020-06-17T13:34:06-07:00doi:10.34067/KID.0003172020hwp:resource-id:kidney360;1/7/591American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, agriculture, agrochemicals, atrophy, calcineurin inhibition, Central America, CKDu, lysosome, Mesoamerican nephropathy, nephritis, interstitial, nephrotoxicity, pesticide, proximal tubule, renal insufficiency, chronic, Sri Lanka, toxinDebates in NephrologyDebates in Nephrologyresearch-article20202020-07-3010.34067/KID.00031720202641-76502020-06-17T13:34:06-07:002020-07-30Kidney360Debates in Nephrology17591595
- AKI in a Patient Engaged in Vegetable Juicing10.34067/KID.0001182020Thu, 30 Jul 2020 05:30:20 GMT-07:00AKI in a Patient Engaged in Vegetable JuicingObadan, Odianosen I.Yudd, Michael2020-07-30T05:30:20-07:00doi:10.34067/KID.0001182020hwp:resource-id:kidney360;1/7/716American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Acute Kidney Injury, Biopsy, Casts, Creatinine, Hyperoxaluria, Juicing, Kidney, Nephropathy, PolarizedClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-07-3010.34067/KID.00011820202641-76502020-07-30T05:30:20-07:002020-07-30Kidney360Clinical Images in Nephrology and Dialysis17716717
- Renal Safety of Nonsteroidal Anti-Inflammatory Drugs and Opioids in Hospitalized Patients on Renin-Angiotensin System Inhibitors10.34067/KID.0003682020Thu, 30 Jul 2020 05:30:20 GMT-07:00Renal Safety of Nonsteroidal Anti-Inflammatory Drugs and Opioids in Hospitalized Patients on Renin-Angiotensin System InhibitorsHung, Adriana M.Chung, Cecilia P.2020-07-30T05:30:20-07:00doi:10.34067/KID.0003682020hwp:resource-id:kidney360;1/7/586American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, analgesics, opioid, angiotensins, anti-inflammatory agents, non-steroidal, drug interactions, hospitalization, pain management, renin, vascular resistanceEditorialsEditorialseditorial20202020-07-3010.34067/KID.00036820202641-76502020-07-30T05:30:20-07:002020-07-30Kidney360Editorials17586587
- Interactions between FGF23 and Genotype in Autosomal Dominant Polycystic Kidney Disease10.34067/KID.0001692020Tue, 12 May 2020 01:40:04 GMT-07:00Interactions between FGF23 and Genotype in Autosomal Dominant Polycystic Kidney DiseaseGrau, LauraGitomer, BereniceMcNair, BryanWolf, MylesHarris, PeterBrosnahan, GodelaTorres, VicenteSteinman, TheodoreYu, AlanChapman, ArleneChonchol, MichelNowak, Kristen L.2020-05-12T13:40:04-07:00doi:10.34067/KID.0001692020hwp:resource-id:kidney360;1/7/648American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360cystic kidney disease, FGF23, fibroblast growth factors, genotype, kidney failure, chronic, mineral metabolism, mutation, polycystic kidney disease, polycystic kidney, autosomal dominant, vitamin DOriginal InvestigationsCystic Kidney DiseaseOriginal InvestigationsCystic Kidney Diseaseresearch-article20202020-07-3010.34067/KID.00016920202641-76502020-05-12T13:40:04-07:002020-07-30Kidney360Original Investigations17648656
- A Night Float System in Nephrology Fellowship: A Mixed Methods Evaluation10.34067/KID.0001572020Fri, 08 May 2020 01:27:20 GMT-07:00A Night Float System in Nephrology Fellowship: A Mixed Methods EvaluationPlotkin, Jennifer B.Xu, Eric J.Fine, Derek M.Knicely, Daphne H.Sperati, C. JohnSozio, Stephen M.2020-05-08T13:27:20-07:00doi:10.34067/KID.0001572020hwp:resource-id:kidney360;1/7/631American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, analysis of variance, assessment, continuity of patient care, education, faculty, fellowship, focus groups, mixed methods, nephrology, night float, surveys and questionnaires, work-life balanceOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20202020-07-3010.34067/KID.00015720202641-76502020-05-08T13:27:20-07:002020-07-30Kidney360Original Investigations17631639
- Janus-Faced: Molecular Mechanisms and Versatile Nature of Renal FibrosisRenal fibrosis is a major hallmark of CKD, regardless of the underlying etiology. In fibrosis development and progression, myofibroblasts play a pivotal role, producing extracellular matrix and interacting with various resident cells in the kidney. Over the past decade, the origin of myofibroblasts has been thoroughly investigated. Emerging evidence suggests that renal myofibroblasts originate from several cellular sources, including resident fibroblasts, pericytes, and bone marrow–derived cells. The contribution of resident fibroblasts is most crucial, and currently available data strongly suggest the importance of functional heterogeneity and plasticity of fibroblasts in kidney disease progression. Resident fibroblasts acquire distinct phenotypes based on their local microenvironment and exert multifactorial functions. For example, age-dependent alterations of renal fibroblasts make a significant contribution to the formation of tertiary lymphoid tissues, which promote local inflammation after injury in the aged kidney. In conjunction with fibrosis development, dysfunction of resident fibroblasts provokes unique pathologic conditions including renal anemia and peritubular capillary loss, both of which are major complications of CKD. Although renal fibrosis is considered detrimental in general, recent studies suggest it has beneficial roles, such as maintaining functional crosstalk with injured proximal tubular cells and supporting their regeneration. These findings provide novel insight into the mechanisms of renal fibrosis, which could be regarded as an adaptive process of kidney injury and repair. Precise understanding of the functional heterogeneity of resident fibroblasts and myofibroblasts has the potential to facilitate the development of novel therapeutics against kidney diseases. In this review, we describe the current perspective on the origin of myofibroblasts and fibroblast heterogeneity, with special emphasis on the dual aspects of renal fibrosis, both beneficial and detrimental, in CKD progression.10.34067/KID.0001972020Fri, 15 May 2020 09:56:42 GMT-07:00Janus-Faced: Molecular Mechanisms and Versatile Nature of Renal FibrosisRenal fibrosis is a major hallmark of CKD, regardless of the underlying etiology. In fibrosis development and progression, myofibroblasts play a pivotal role, producing extracellular matrix and interacting with various resident cells in the kidney. Over the past decade, the origin of myofibroblasts has been thoroughly investigated. Emerging evidence suggests that renal myofibroblasts originate from several cellular sources, including resident fibroblasts, pericytes, and bone marrow–derived cells. The contribution of resident fibroblasts is most crucial, and currently available data strongly suggest the importance of functional heterogeneity and plasticity of fibroblasts in kidney disease progression. Resident fibroblasts acquire distinct phenotypes based on their local microenvironment and exert multifactorial functions. For example, age-dependent alterations of renal fibroblasts make a significant contribution to the formation of tertiary lymphoid tissues, which promote local inflammation after injury in the aged kidney. In conjunction with fibrosis development, dysfunction of resident fibroblasts provokes unique pathologic conditions including renal anemia and peritubular capillary loss, both of which are major complications of CKD. Although renal fibrosis is considered detrimental in general, recent studies suggest it has beneficial roles, such as maintaining functional crosstalk with injured proximal tubular cells and supporting their regeneration. These findings provide novel insight into the mechanisms of renal fibrosis, which could be regarded as an adaptive process of kidney injury and repair. Precise understanding of the functional heterogeneity of resident fibroblasts and myofibroblasts has the potential to facilitate the development of novel therapeutics against kidney diseases. In this review, we describe the current perspective on the origin of myofibroblasts and fibroblast heterogeneity, with special emphasis on the dual aspects of renal fibrosis, both beneficial and detrimental, in CKD progression.Arai, HiroyukiYanagita, Motoko2020-05-15T09:56:42-07:00doi:10.34067/KID.0001972020hwp:resource-id:kidney360;1/7/697American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, bone marrow, disease progression, extracellular matrix, fibrosis, kidney, myofibroblasts, pericytes, phenotype, renal insufficiency, chronic, Basic ScienceReview ArticlesReview Articlesreview-article20202020-07-3010.34067/KID.00019720202641-76502020-05-15T09:56:42-07:002020-07-30Kidney360Review Articles17697704
- Incidence, Risk Factors, and Outcomes of Neonatal Renal Vein Thrombosis in Ontario: Population-Based Cohort Study10.34067/KID.0000912019Wed, 27 May 2020 01:36:08 GMT-07:00Incidence, Risk Factors, and Outcomes of Neonatal Renal Vein Thrombosis in Ontario: Population-Based Cohort StudyOuellette, Allison C.Darling, Elizabeth K.Sivapathasundaram, BranavanBabe, GlendaPerez, RichardChan, Anthony K.C.Chanchlani, Rahul2020-05-27T13:36:08-07:00doi:10.34067/KID.0000912019hwp:resource-id:kidney360;1/7/640American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, cohort studies, infant, newborn, neonatology, nephrology, Ontario, pediatrics, population, pre-eclampsia, renal veins, thrombosisOriginal InvestigationsClinical NephrologyOriginal InvestigationsClinical Nephrologyresearch-article20202020-07-3010.34067/KID.00009120192641-76502020-05-27T13:36:08-07:002020-07-30Kidney360Original Investigations17640647
- Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? CON10.34067/KID.0002922020Wed, 17 Jun 2020 01:34:06 GMT-07:00Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? CONWesseling, Catharina2020-06-17T13:34:06-07:00doi:10.34067/KID.0002922020hwp:resource-id:kidney360;1/7/596American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, CKDnt, CKDu, etiology, heat stress, India, Mesoamerican nephropathy, metals, occupation, pesticides, Sri LankaDebates in NephrologyDebates in Nephrologyresearch-article20202020-07-3010.34067/KID.00029220202641-76502020-06-17T13:34:06-07:002020-07-30Kidney360Debates in Nephrology17596601
- Right Arm Pain and Swelling in an End-Stage Kidney Disease Patient10.34067/KID.0001242020Thu, 30 Jul 2020 05:30:20 GMT-07:00Right Arm Pain and Swelling in an End-Stage Kidney Disease PatientJdiaa, Sara S.Gebrael, Diala I.Koubar, Sahar H.2020-07-30T05:30:20-07:00doi:10.34067/KID.0001242020hwp:resource-id:kidney360;1/7/714American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360bone mineral disease, brown tumors, hyperparathyroidism, chronic kidney disease, ESKD, osteitis fibrosa cystica, renalosteodystrophyClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-07-3010.34067/KID.00012420202641-76502020-07-30T05:30:20-07:002020-07-30Kidney360Clinical Images in Nephrology and Dialysis17714715
- Attitudes to Clinical Pig Kidney Xenotransplantation among Medical Providers and Patients10.34067/KID.0002082020Wed, 27 May 2020 01:36:08 GMT-07:00Attitudes to Clinical Pig Kidney Xenotransplantation among Medical Providers and PatientsPadilla, Luz A.Hurst, DanielLopez, RaymondKumar, VineetaCooper, David K.C.Paris, Wayne2020-05-27T13:36:08-07:00doi:10.34067/KID.0002082020hwp:resource-id:kidney360;1/7/657American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, attitude, genetic engineering, heterografts, kidney, kidney transplantation, logistic models, patient, personality, provider, religion, surveys and questionnaires, transplantation, heterologous, xenotransplantationOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-07-3010.34067/KID.00020820202641-76502020-05-27T13:36:08-07:002020-07-30Kidney360Original Investigations17657662
- Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? Commentary10.34067/KID.0003412020Wed, 17 Jun 2020 01:34:06 GMT-07:00Is an Environmental Nephrotoxin the Primary Cause of CKDu (Mesoamerican Nephropathy)? CommentaryMadero, Magdalena2020-06-17T13:34:06-07:00doi:10.34067/KID.0003412020hwp:resource-id:kidney360;1/7/602American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, CKDu, environmental toxins, Mesoamerican NephropathyModerator CommentaryModerator Commentaryarticle-commentary20202020-07-3010.34067/KID.00034120202641-76502020-06-17T13:34:06-07:002020-07-30Kidney360Moderator Commentary17602603
- No Zoom Required: Meeting at the β-Intercalated Cells10.1681/ASN.2020060844Thu, 23 Jul 2020 12:29:42 GMT-07:00No Zoom Required: Meeting at the β-Intercalated CellsLin, Wie-YinMuallem, Shmuel2020-07-23T12:29:42-07:00doi:10.1681/ASN.2020060844hwp:resource-id:jnephrol;31/8/1655American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologypendrin, CFTR, bicarbonate, excretionUp Front MattersEditorialsUp Front MattersEditorialseditorial20202020-08-01August 202010.1681/ASN.20200608441046-66731533-34502020-07-23T12:29:42-07:002020-08Journal of the American Society of NephrologyUp Front Matters31881655171116571727
- Fibroblast Growth Factor 23 and Risk of Hospitalization with Infection in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study10.1681/ASN.2019101106Tue, 23 Jun 2020 08:10:25 GMT-07:00Fibroblast Growth Factor 23 and Risk of Hospitalization with Infection in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) StudyIshigami, JunichiTaliercio, Jonathan T.Feldman, Harold I.Srivastava, AnandTownsend, Raymond R.Cohen, Debbie L.Horwitz, Edward J.Rao, PandurangaCharleston, JeanneFink, Jeffrey C.Ricardo, Ana C.Sondheimer, JamesChen, Teresa K.Wolf, MylesIsakova, TamaraAppel, Lawrence J.Matsushita, Kunihiro,Go, Alan S.He, JiangLash, James P.Rahman, Mahboob2020-06-23T08:10:25-07:00doi:10.1681/ASN.2019101106hwp:resource-id:jnephrol;31/8/1836American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Chronic inflammation, fibroblastClinical EpidemiologyClinical Epidemiologyresearch-article20202020-08-01August 202010.1681/ASN.20191011061046-66731533-34502020-06-23T08:10:25-07:002020-08Journal of the American Society of NephrologyClinical Epidemiology31818361846
- Improving Equity in Medication Use through Better Kidney Function Measurement10.1681/ASN.2020060880Mon, 13 Jul 2020 11:02:23 GMT-07:00Improving Equity in Medication Use through Better Kidney Function MeasurementTuot, Delphine S.2020-07-13T11:02:23-07:00doi:10.1681/ASN.2020060880hwp:resource-id:jnephrol;31/8/1657American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydisparities, diabetes, eGFR, metforminUp Front MattersEditorialsUp Front MattersEditorialseditorial20202020-08-01August 202010.1681/ASN.20200608801046-66731533-34502020-07-13T11:02:23-07:002020-08Journal of the American Society of NephrologyUp Front Matters31881657184716581858
- This Month's Highlights10.1681/ASN.2020060907Fri, 31 Jul 2020 10:00:32 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2020-07-31T10:00:32-07:00doi:10.1681/ASN.2020060907hwp:resource-id:jnephrol;31/8/iAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20202020-08-01August 202010.1681/ASN.20200609071046-66731533-34502020-07-31T10:00:32-07:002020-08Journal of the American Society of NephrologyThis Month's Highlights318ii
- Impaired Renal HCO3- Excretion in Cystic Fibrosis10.1681/ASN.2020010053Thu, 23 Jul 2020 12:29:43 GMT-07:00Impaired Renal HCO3- Excretion in Cystic FibrosisBerg, PederSvendsen, Samuel L.Sorensen, Mads V.Larsen, Casper K.Andersen, Jesper FrankJensen-Fangel, SørenJeppesen, MajbrittSchreiber, RainerCabrita, InesKunzelmann, KarlLeipziger, Jens2020-07-23T12:29:43-07:00doi:10.1681/ASN.2020010053hwp:resource-id:jnephrol;31/8/1711American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycystic fibrosis, ion transport, kidney tubule, renal tubular acidosisBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20200100531046-66731533-34502020-07-23T12:29:43-07:002020-08Journal of the American Society of NephrologyBasic Research31881711165517271657
- Mortality in US Hemodialysis Patients Following Exposure to Wildfire Smoke10.1681/ASN.2019101066Thu, 16 Jul 2020 09:45:48 GMT-07:00Mortality in US Hemodialysis Patients Following Exposure to Wildfire SmokeXi, YuzhiKshirsagar, Abhijit V.Wade, Timothy J.Richardson, David B.Brookhart, M. AlanWyatt, LaurenRappold, Ana G.2020-07-16T09:45:48-07:00doi:10.1681/ASN.2019101066hwp:resource-id:jnephrol;31/8/1824American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyenvironmental exposure, wildfire, hemodialysis patients, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20202020-08-01August 202010.1681/ASN.20191010661046-66731533-34502020-07-16T09:45:48-07:002020-08Journal of the American Society of NephrologyClinical Epidemiology31818241835
- Epithelial Vasopressin Type-2 Receptors Regulate Myofibroblasts by a YAP-CCN2–Dependent Mechanism in Polycystic Kidney Disease10.1681/ASN.2020020190Wed, 17 Jun 2020 06:33:10 GMT-07:00Epithelial Vasopressin Type-2 Receptors Regulate Myofibroblasts by a YAP-CCN2–Dependent Mechanism in Polycystic Kidney DiseaseDwivedi, NidhiTao, ShixinJamadar, AbedaSinha, SonaliHoward, ChristiannaWallace, Darren P.Fields, Timothy A.Leask, AndrewCalvet, James P.Rao, Reena2020-06-17T06:33:10-07:00doi:10.1681/ASN.2020020190hwp:resource-id:jnephrol;31/8/1697American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, renal fibrosis, vasopressin receptorBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20200201901046-66731533-34502020-06-17T06:33:10-07:002020-08Journal of the American Society of NephrologyBasic Research31816971710
- Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in Humans10.1681/ASN.2019121272Tue, 16 Jun 2020 05:23:36 GMT-07:00Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in HumansCollard, Didiervan Brussel, Peter M.van de Velde, LennartWijntjens, Gilbert W.M.Westerhof, Berend E.Karemaker, John M.Piek, Jan J.Reekers, Jim A.Vogt, Liffertde Winter, Robbert J.van den Born, Bert-Jan H.2020-06-16T05:23:36-07:00doi:10.1681/ASN.2019121272hwp:resource-id:jnephrol;31/8/1905American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal hemodynamics, glomerular hyperfiltration, renal hypertensionClinical ResearchClinical Researchresearch-article20202020-08-01August 202010.1681/ASN.20191212721046-66731533-34502020-06-16T05:23:36-07:002020-08Journal of the American Society of NephrologyClinical Research3181119052562571914257258
- Long-Term Functional Patency and Cost-Effectiveness of Arteriovenous Fistula Creation under Regional Anesthesia: a Randomized Controlled Trial10.1681/ASN.2019111209Fri, 24 Jul 2020 07:43:52 GMT-07:00Long-Term Functional Patency and Cost-Effectiveness of Arteriovenous Fistula Creation under Regional Anesthesia: a Randomized Controlled TrialAitken, EmmaKearns, RachelGaianu, LucianJackson, AndrewSteven, MarkKinsella, JohnClancy, MarcMacfarlane, Alan2020-07-24T07:43:52-07:00doi:10.1681/ASN.2019111209hwp:resource-id:jnephrol;31/8/1871American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous access, arteriovenous fistula, chronic dialysis, chronic kidney diseaseClinical ResearchClinical Researchresearch-article20202020-08-01August 202010.1681/ASN.20191112091046-66731533-34502020-07-24T07:43:52-07:002020-08Journal of the American Society of NephrologyClinical Research31818711882
- Distinct Modes of Balancing Glomerular Cell Proteostasis in Mucolipidosis Type II and III Prevent Proteinuria10.1681/ASN.2019090960Wed, 08 Jul 2020 09:11:03 GMT-07:00Distinct Modes of Balancing Glomerular Cell Proteostasis in Mucolipidosis Type II and III Prevent ProteinuriaSachs, WiebkeSachs, MarliesKrüger, ElkeZielinski, StephanieKretz, OliverHuber, Tobias B.Baranowsky, AnkeWestermann, Lena MarieVoltolini Velho, RenataLudwig, Nataniel FlorianoYorgan, Timur AlexanderDi Lorenzo, GiorgiaKollmann, KatrinBraulke, ThomasSchwartz, Ida VanessaSchinke, ThorstenDanyukova, TatyanaPohl, SandraMeyer-Schwesinger, Catherine2020-07-08T09:11:03-07:00doi:10.1681/ASN.2019090960hwp:resource-id:jnephrol;31/8/1796American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologymucolipidosis, osteopenia, proteotoxic stress, integrated stress response, glomerular disease, lysosomal storage disorderBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20190909601046-66731533-34502020-07-08T09:11:03-07:002020-08Journal of the American Society of NephrologyBasic Research31817961814
- Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy10.1681/ASN.2019101070Thu, 25 Jun 2020 08:23:13 GMT-07:00Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic CardiomyopathySodhi, KomalWang, XiaoliangChaudhry, Muhammad AslamLakhani, Hari VishalZehra, MishghanPratt, RebeccaNawab, AtharCottrill, Cameron L.Snoad, BrianBai, FangDenvir, JamesLiu, JiangSanabria, Juan R.Xie, ZijianAbraham, Nader G.Shapiro, Joseph I.2020-06-25T08:23:13-07:00doi:10.1681/ASN.2019101070hwp:resource-id:jnephrol;31/8/1746American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, obesity, oxidative stress, uremia, adipocyteBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20191010701046-66731533-34502020-06-25T08:23:13-07:002020-08Journal of the American Society of NephrologyBasic Research31338101746195717601957
- Obstructive Sleep Apnea, Other Sleep Characteristics, and Risk of CKD in the Atherosclerosis Risk in Communities Sleep Heart Health Study10.1681/ASN.2020010024Fri, 26 Jun 2020 07:17:32 GMT-07:00Obstructive Sleep Apnea, Other Sleep Characteristics, and Risk of CKD in the Atherosclerosis Risk in Communities Sleep Heart Health StudyFull, Kelsie M.Jackson, Chandra L.Rebholz, Casey M.Matsushita, KunihiroLutsey, Pamela L.2020-06-26T07:17:32-07:00doi:10.1681/ASN.2020010024hwp:resource-id:jnephrol;31/8/1859American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologysleep, aging, nocturnal hypoxemia, obstructive sleep apneaClinical EpidemiologyClinical Epidemiologyresearch-article20202020-08-01August 202010.1681/ASN.20200100241046-66731533-34502020-06-26T07:17:32-07:002020-08Journal of the American Society of NephrologyClinical Epidemiology31818591869
- The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD10.1681/ASN.2019101119Mon, 13 Jul 2020 11:02:22 GMT-07:00The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKDShin, Jung-ImSang, YingyingChang, Alex R.Dunning, Stephan C.Coresh, JosefInker, Lesley A.Selvin, ElizabethBallew, Shoshana H.Grams, Morgan E.2020-07-13T11:02:22-07:00doi:10.1681/ASN.2019101119hwp:resource-id:jnephrol;31/8/1847American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydisparities, metformin, chronic kidney disease, FDA drug label, creatinine, estimated glomerular filtration rate, chronic kidney disease, clinical epidemiology, creatinine, glomerular filtration rateClinical EpidemiologyClinical Epidemiologyresearch-article20202020-08-01August 202010.1681/ASN.20191011191046-66731533-34502020-07-13T11:02:22-07:002020-08Journal of the American Society of NephrologyClinical Epidemiology31881847165718581658
- Authors’ Reply10.1681/ASN.2020050707Wed, 08 Jul 2020 09:11:02 GMT-07:00Authors’ ReplyWeaver, Robert G.Tonelli, MarcelloLamb, Edmund J.Hemmelgarn, Brenda R.2020-07-08T09:11:02-07:00doi:10.1681/ASN.2020050707hwp:resource-id:jnephrol;31/8/1916American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, albuminuria, proteinuriaLetters to the EditorLetters to the Editorletter20202020-08-01August 202010.1681/ASN.20200507071046-66731533-34502020-07-08T09:11:02-07:002020-08Journal of the American Society of NephrologyLetters to the Editor31881916191519171916
- The Effects of High-Protein Diets on Kidney Health and LongevityAlthough high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with—and perhaps without—impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.10.1681/ASN.2020010028Wed, 15 Jul 2020 12:55:09 GMT-07:00The Effects of High-Protein Diets on Kidney Health and LongevityAlthough high-protein diets continue to be popular for weight loss and type 2 diabetes, evidence suggests that worsening renal function may occur in individuals with—and perhaps without—impaired kidney function. High dietary protein intake can cause intraglomerular hypertension, which may result in kidney hyperfiltration, glomerular injury, and proteinuria. It is possible that long-term high protein intake may lead to de novo CKD. The quality of dietary protein may also play a role in kidney health. Compared with protein from plant sources, animal protein has been associated with an increased risk of ESKD in several observational studies, including the Singapore Chinese Health Study. Potential mediators of kidney damage from animal protein include dietary acid load, phosphate content, gut microbiome dysbiosis, and resultant inflammation. In light of such findings, adopting current dietary approaches that include a high proportion of protein for weight reduction or glycemic control should be considered with care in those at high risk for kidney disease. Given the possibility of residual confounding within some observational studies and the conflicting evidence from previous trials, long-term studies including those with large sample sizes are warranted to better ascertain the effects of high protein intake on kidney health.Ko, Gang-JeeRhee, Connie M.Kalantar-Zadeh, KamyarJoshi, Shivam2020-07-15T12:55:09-07:00doi:10.1681/ASN.2020010028hwp:resource-id:jnephrol;31/8/1667American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologynutrition, chronic kidney disease, high protein diet, glomerular hyperfiltration, proteinuriaUp Front MattersReviewUp Front MattersReviewreview-article20202020-08-01August 202010.1681/ASN.20200100281046-66731533-34502020-07-15T12:55:09-07:002020-08Journal of the American Society of NephrologyUp Front Matters31816671679
- Proteomic Analysis Identifies Distinct Glomerular Extracellular Matrix in Collapsing Focal Segmental Glomerulosclerosis10.1681/ASN.2019070696Fri, 19 Jun 2020 10:06:05 GMT-07:00Proteomic Analysis Identifies Distinct Glomerular Extracellular Matrix in Collapsing Focal Segmental GlomerulosclerosisMerchant, Michael L.Barati, Michelle T.Caster, Dawn J.Hata, Jessica L.Hobeika, LilianeCoventry, SusanBrier, Michael E.Wilkey, Daniel W.Li, MingRood, Ilse M.Deegens, Jeroen K.Wetzels, Jack F.Larsen, Christopher P.Troost, Jonathan P.Hodgin, Jeffrey B.Mariani, Laura H.Kretzler, MatthiasKlein, Jon B.McLeish, Kenneth R.2020-06-19T10:06:05-07:00doi:10.1681/ASN.2019070696hwp:resource-id:jnephrol;31/8/1883American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, extracellular matrix, collapsing FSGS, glomerular epithelial cells, cathepsinClinical ResearchClinical Researchresearch-article20202020-08-01August 202010.1681/ASN.20190706961046-66731533-34502020-06-19T10:06:05-07:002020-08Journal of the American Society of NephrologyClinical Research31818831904
- A Modest Proposal to Spur Innovation in Chronic Dialysis Care10.1681/ASN.2020020138Tue, 16 Jun 2020 05:23:36 GMT-07:00A Modest Proposal to Spur Innovation in Chronic Dialysis CareHostetter, Thomas H.2020-06-16T05:23:36-07:00doi:10.1681/ASN.2020020138hwp:resource-id:jnephrol;31/8/1664American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyESKD, Research Support, chronic dialysisUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20202020-08-01August 202010.1681/ASN.20200201381046-66731533-34502020-06-16T05:23:36-07:002020-08Journal of the American Society of NephrologyUp Front Matters31816641666
- The Estimation Formula for the Urinary Albumin-Creatinine Ratio Based on the Protein-Creatinine Ratio Are Not Valid for a Kidney Transplant and a Living Donor Cohort10.1681/ASN.2020050545Wed, 08 Jul 2020 09:11:04 GMT-07:00The Estimation Formula for the Urinary Albumin-Creatinine Ratio Based on the Protein-Creatinine Ratio Are Not Valid for a Kidney Transplant and a Living Donor CohortJehn, UlrichGörlich, DennisReuter, Stefan2020-07-08T09:11:04-07:00doi:10.1681/ASN.2020050545hwp:resource-id:jnephrol;31/8/1915American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, kidney donation, albuminuriaLetters to the EditorLetters to the Editorletter20202020-08-01August 202010.1681/ASN.20200505451046-66731533-34502020-07-08T09:11:04-07:002020-08Journal of the American Society of NephrologyLetters to the Editor31881915191619161917
- Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty Model10.1681/ASN.2019101042Thu, 25 Jun 2020 08:23:13 GMT-07:00Therapeutic Effect of Adipose Derived Mesenchymal Stem Cell Transplantation in Reducing Restenosis in a Murine Angioplasty ModelCai, ChuanqiKilari, SreenivasuluZhao, ChengleiSimeon, Michael L.Misra, AvanishLi, Yiqingvan Wijnen, Andre J.Mukhopadhyay, DebabrataMisra, Sanjay2020-06-25T08:23:13-07:00doi:10.1681/ASN.2019101042hwp:resource-id:jnephrol;31/8/1781American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, stem cell, vascular accessBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20191010421046-66731533-34502020-06-25T08:23:13-07:002020-08Journal of the American Society of NephrologyBasic Research31817811795
- Striking a Balance in Simultaneous Heart Kidney Transplant: Optimizing Outcomes for All Wait-Listed Patients10.1681/ASN.2020030336Thu, 04 Jun 2020 05:58:30 GMT-07:00Striking a Balance in Simultaneous Heart Kidney Transplant: Optimizing Outcomes for All Wait-Listed PatientsShaw, Brian I.Sudan, Debra L.Boulware, L. EbonyMcElroy, Lisa M.2020-06-04T05:58:30-07:00doi:10.1681/ASN.2020030336hwp:resource-id:jnephrol;31/8/1661American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant outcomes, heart failureUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20202020-08-01August 202010.1681/ASN.20200303361046-66731533-34502020-06-04T05:58:30-07:002020-08Journal of the American Society of NephrologyUp Front Matters31816611664
- Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-210.1681/ASN.2020040432Tue, 05 May 2020 05:45:03 GMT-07:00Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2Farkash, Evan A.Wilson, Allecia M.Jentzen, Jeffrey M.2020-05-05T05:45:03-07:00doi:10.1681/ASN.2020040432hwp:resource-id:jnephrol;31/8/1683American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, SARS-CoV-2, acute kidney failure, autopsy, renal pathology, electron microscopyRapid CommunicationRapid Communicationresearch-article20202020-08-01August 202010.1681/ASN.20200404321046-66731533-34502020-05-05T05:45:03-07:002020-08Journal of the American Society of NephrologyRapid Communication31318101683249416872494
- AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL1 High-Risk Genotype10.1681/ASN.2020050558Fri, 19 Jun 2020 10:06:04 GMT-07:00AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL1 High-Risk GenotypeWu, HuijuanLarsen, Christopher P.Hernandez-Arroyo, Cesar F.Mohamed, Muner M.B.Caza, TiffanySharshir, Moh’dChughtai, AsimXie, LipingGimenez, Juan M.Sandow, Tyler A.Lusco, Mark A.Yang, HaichunAcheampong, EllenRosales, Ivy A.Colvin, Robert B.Fogo, Agnes B.Velez, Juan Carlos Q.2020-06-19T10:06:04-07:00doi:10.1681/ASN.2020050558hwp:resource-id:jnephrol;31/8/1688American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycollapsing glomerulopathy, APOL1, kidney biopsy, SARS-CoV-2, nephrotic, COVID-19Rapid CommunicationRapid Communicationresearch-article20202020-08-01August 202010.1681/ASN.20200505581046-66731533-34502020-06-19T10:06:04-07:002020-08Journal of the American Society of NephrologyRapid Communication31816881695
- Possible Protective Effect of Renin-Angiotensin System Inhibitors in COVID-19 Induced Acute Kidney Injury10.1681/ASN.2020050640Wed, 01 Jul 2020 08:29:06 GMT-07:00Possible Protective Effect of Renin-Angiotensin System Inhibitors in COVID-19 Induced Acute Kidney InjuryKow, Chia SiangHasan, Syed Shahzad2020-07-01T08:29:06-07:00doi:10.1681/ASN.2020050640hwp:resource-id:jnephrol;31/8/1917American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, COVID-19, renin-angiotensin system inhibitorLetters to the EditorLetters to the Editorletter20202020-08-01August 202010.1681/ASN.20200506401046-66731533-34502020-07-01T08:29:06-07:002020-08Journal of the American Society of NephrologyLetters to the Editor31881917191819181919
- Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and Experiences10.1681/ASN.2020050599Tue, 16 Jun 2020 07:39:41 GMT-07:00Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and ExperiencesEl Shamy, OsamaPatel, NiraleeAbdelbaset, Mohamed HalimChenet, LindaTokita, JojiLookstein, RobertLee, David S.Cohen, Noah A.Sharma, ShuchitaUribarri, Jaime2020-06-16T07:39:41-07:00doi:10.1681/ASN.2020050599hwp:resource-id:jnephrol;31/8/1680American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, peritoneal dialysis, acute renal failure, COVID-19Research LetterResearch Letterresearch-article20202020-08-01August 202010.1681/ASN.20200505991046-66731533-34502020-06-16T07:39:41-07:002020-08Journal of the American Society of NephrologyResearch Letter31816801682
- Epidemiology of COVID-19 in an Urban Dialysis Center10.1681/ASN.2020040534Fri, 19 Jun 2020 10:06:04 GMT-07:00Epidemiology of COVID-19 in an Urban Dialysis CenterCorbett, Richard W.Blakey, SarahNitsch, DorotheaLoucaidou, MarinaMcLean, AdamDuncan, NeillAshby, Damien R.,2020-06-19T10:06:04-07:00doi:10.1681/ASN.2020040534hwp:resource-id:jnephrol;31/8/1815American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical epidemiology, haemodialysis, COVID-19Clinical EpidemiologyClinical Epidemiologyresearch-article20202020-08-01August 202010.1681/ASN.20200405341046-66731533-34502020-06-19T10:06:04-07:002020-08Journal of the American Society of NephrologyClinical Epidemiology31818151823
- COVID-19, Racism, and Racial Disparities in Kidney Disease: Galvanizing the Kidney Community ResponseThis article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2020_07_21_JASN2020060809.mp310.1681/ASN.2020060809Mon, 13 Jul 2020 11:02:22 GMT-07:00COVID-19, Racism, and Racial Disparities in Kidney Disease: Galvanizing the Kidney Community ResponseThis article contains a podcast athttps://www.asn-online.org/media/podcast/JASN/2020_07_21_JASN2020060809.mp3Crews, Deidra C.Purnell, Tanjala S.2020-07-13T11:02:22-07:00doi:10.1681/ASN.2020060809hwp:resource-id:jnephrol;31/8/1American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyEthnic minority, health disparity, COVID-19, chronic kidney disease, structural racismUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20202020-08-01August 202010.1681/ASN.20200608091046-66731533-34502020-07-13T11:02:22-07:002020-08Journal of the American Society of NephrologyUp Front Matters31813
- Authors’ Reply10.1681/ASN.2020060799Wed, 01 Jul 2020 08:29:06 GMT-07:00Authors’ ReplyBatlle, DanielSoler, Maria JoseWelling, Paul A.Swaminathan, Sundararaman,2020-07-01T08:29:06-07:00doi:10.1681/ASN.2020060799hwp:resource-id:jnephrol;31/8/1918American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycovid-19, acute renal failure, ace2, soluble ACE2, AKI, ACE inhibitors, Angiotensin II receptor blockersLetters to the EditorLetters to the Editorletter20202020-08-01August 202010.1681/ASN.20200607991046-66731533-34502020-07-01T08:29:06-07:002020-08Journal of the American Society of NephrologyLetters to the Editor31881918191719191918
- Podocyte Integrin-β3 and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic Nephropathy10.1681/ASN.2019111163Fri, 24 Jul 2020 07:43:53 GMT-07:00Podocyte Integrin-β3 and Activated Protein C Coordinately Restrict RhoA Signaling and Ameliorate Diabetic NephropathyMadhusudhan, ThatiGhosh, SanchitaWang, HongjieDong, WeiGupta, DheerendraElwakiel, AhmedStoyanov, StoyanAl-Dabet, Moh’d MohanadKrishnan, ShruthiBiemann, RonaldNazir, SumraZimmermann, SilkeMathew, AkashGadi, IhsanRana, RajivZeng-Brouwers, JinyangMoeller, Marcus J.Schaefer, LilianaEsmon, Charles T.Kohli, ShreyReiser, JochenRezaie, Alireza R.Ruf, WolframIsermann, Berend2020-07-24T07:43:53-07:00doi:10.1681/ASN.2019111163hwp:resource-id:jnephrol;31/8/1762American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, integrin αvβ3, RhoA signaling, activated protein C, coagulation proteasesBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20191111631046-66731533-34502020-07-24T07:43:53-07:002020-08Journal of the American Society of NephrologyBasic Research31817621780
- Drug Testing for Residual Progression of Diabetic Kidney Disease in Mice Beyond Therapy with Metformin, Ramipril, and Empagliflozin10.1681/ASN.2019070703Tue, 23 Jun 2020 08:10:24 GMT-07:00Drug Testing for Residual Progression of Diabetic Kidney Disease in Mice Beyond Therapy with Metformin, Ramipril, and EmpagliflozinMotrapu, MangaŚwiderska, Monika KatarzynaMesas, IreneMarschner, Julian AurelioLei, YutianMartinez Valenzuela, LauraFu, JiaLee, KyungAngelotti, Maria LuciaAntonelli, GiuliaRomagnani, PaolaAnders, Hans-JoachimAnguiano, Lidia2020-06-23T08:10:24-07:00doi:10.1681/ASN.2019070703hwp:resource-id:jnephrol;31/8/1729American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulosclerosis, diabetic nephropathy, translational research, diabetic kidney disease, regenerationBasic ResearchBasic Researchresearch-article20202020-08-01August 202010.1681/ASN.20190707031046-66731533-34502020-06-23T08:10:24-07:002020-08Journal of the American Society of NephrologyBasic Research31817291745
- Anemia and Incident End-Stage Kidney Disease10.34067/KID.0000852020Wed, 20 May 2020 09:38:56 GMT-07:00Anemia and Incident End-Stage Kidney DiseaseSaraf, Santosh L.Hsu, Jesse Y.Ricardo, Ana C.Mehta, RupalChen, JingChen, Teresa K.Fischer, Michael J.Hamm, LeeSondheimer, JamesWeir, Matthew R.Zhang, XiaomingWolf, MylesLash, James P.2020-05-20T09:38:56-07:00doi:10.34067/KID.0000852020hwp:resource-id:kidney360;1/7/623American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, anemia, CKD progression, cohort studies, ESKD, ethnic groups, follow-up studies, hemoglobin, kidney failure, chronic, renal insufficiency, chronicOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-07-3010.34067/KID.00008520202641-76502020-05-20T09:38:56-07:002020-07-30Kidney360Original Investigations17623630
- Global Dialysis Perspective: Argentina10.34067/KID.0001222019Tue, 28 Apr 2020 09:39:51 GMT-07:00Global Dialysis Perspective: ArgentinaOrias, MarceloRosa Diez, Guillermo Javier2020-04-28T09:39:51-07:00doi:10.34067/KID.0001222019hwp:resource-id:kidney360;1/7/676American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, Argentina, cardiovascular diseases, delivery of health care, gross domestic product, hospitals, public, insurance, health, kidney failure, chronic life expectancy, local government, peritoneal dialysis, renal dialysis, renal insufficiency, chronicGlobal PerspectivesGlobal Perspectivesresearch-article20202020-07-3010.34067/KID.00012220192641-76502020-04-28T09:39:51-07:002020-07-30Kidney360Global Perspectives17676679
- Global Dialysis Perspective: Thailand10.34067/KID.0000762020Fri, 24 Apr 2020 07:54:10 GMT-07:00Global Dialysis Perspective: ThailandKanjanabuch, TalerngsakTakkavatakarn, Kullaya2020-04-24T07:54:10-07:00doi:10.34067/KID.0000762020hwp:resource-id:kidney360;1/7/671American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, government, gross domestic product, health expenditures, insurance, health, kidney failure, chronic, peritoneal dialysis, renal dialysis, renal insufficiency, chronic, renal replacement therapy, social security, Thailand, universal health insuranceGlobal PerspectivesGlobal Perspectivesresearch-article20202020-07-3010.34067/KID.00007620202641-76502020-04-24T07:54:10-07:002020-07-30Kidney360Global Perspectives17671675
- Effect of Renin-Angiotensin System Inhibitors on the Comparative Nephrotoxicity of NSAIDs and Opioids during Hospitalization10.34067/KID.0001432020Mon, 27 Apr 2020 01:35:29 GMT-07:00Effect of Renin-Angiotensin System Inhibitors on the Comparative Nephrotoxicity of NSAIDs and Opioids during HospitalizationMiano, Todd A.Shashaty, Michael G. S.Yang, WeiBrown, Jeremiah R.Zuppa, AthenaHennessy, Sean2020-04-27T13:35:29-07:00doi:10.34067/KID.0001432020hwp:resource-id:kidney360;1/7/604American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, ACE inhibitors, acute renal failure, angiotensin, chronic kidney disease, diuretics, drug interactions, drug nephrotoxicity, glomerular filtration rate, hospitalization, nephrotoxicityOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-07-3010.34067/KID.00014320202641-76502020-04-27T13:35:29-07:002020-07-30Kidney360Original Investigations17604613
- Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series10.34067/KID.0000182019Mon, 27 Apr 2020 09:33:02 GMT-07:00Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case SeriesKumar, DhirenYakubu, IdrisSafavi, FroughLevy, MarlonMoinuddin, IrfanKimball, PamelaKamal, LaylaKing, AnneMassey, DavisHalloran, PhilipGupta, Gaurav2020-04-27T09:33:02-07:00doi:10.34067/KID.0000182019hwp:resource-id:kidney360;1/7/663American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, antibody mediated rejection, chronic rejection, IL6 inhibition, immunosuppression, kidney transplant, rejection, tocilizumabOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-07-3010.34067/KID.00001820192641-76502020-04-27T09:33:02-07:002020-07-30Kidney360Original Investigations17663670
- Strategies to Expand the Deceased Donor Pool for Pediatric Kidney Transplant Recipients10.34067/KID.0001772020Fri, 15 May 2020 01:36:40 GMT-07:00Strategies to Expand the Deceased Donor Pool for Pediatric Kidney Transplant RecipientsKizilbash, Sarah J.Chavers, Blanche M.2020-05-15T13:36:40-07:00doi:10.34067/KID.0001772020hwp:resource-id:kidney360;1/7/691American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, child, death, growth and development, kidney failure, chronic, kidney transplantation, registries, tissue donors, transplant recipients, waiting listsPerspectivesPerspectivesresearch-article20202020-07-3010.34067/KID.00017720202641-76502020-05-15T13:36:40-07:002020-07-30Kidney360Perspectives17691693
- Fever and Gross Hematuria in a Kidney Transplant Recipient10.34067/KID.0000732020Thu, 30 Jul 2020 05:30:20 GMT-07:00Fever and Gross Hematuria in a Kidney Transplant RecipientThorne, PeterArroyo, Juan PabloConcepcion, Beatrice P.2020-07-30T05:30:20-07:00doi:10.34067/KID.0000732020hwp:resource-id:kidney360;1/7/712American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, adenovirus, fever, hematuria, transplantClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-07-3010.34067/KID.00007320202641-76502020-07-30T05:30:20-07:002020-07-30Kidney360Clinical Images in Nephrology and Dialysis17712713
- Frailty and the Potential Kidney Transplant Recipient: Time for a More Holistic Assessment?10.34067/KID.0001822020Fri, 22 May 2020 09:26:36 GMT-07:00Frailty and the Potential Kidney Transplant Recipient: Time for a More Holistic Assessment?Wu, Henry H.L.Woywodt, AlexanderNixon, Andrew C.2020-05-22T09:26:36-07:00doi:10.34067/KID.0001822020hwp:resource-id:kidney360;1/7/685American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360geriatric nephrology, assessment, decision making, shared, frailty, quality of life, renal insufficiency, chronic, renal replacement therapy, renal transplantationPerspectivesPerspectivesresearch-article20202020-07-3010.34067/KID.00018220202641-76502020-05-22T09:26:36-07:002020-07-30Kidney360Perspectives17685690
- Kidney Transplantation in Patients with HIVIndividuals with HIV are at increased risk for ESKD. Kidney transplantation is the best treatment for ESKD in the HIV+ population. Despite reduced access to transplantation, patients who are HIV+ have excellent outcomes and clearly benefit from receiving one. Common post-transplant complications and management concerns, including the optimal antiretroviral regimen, immunosuppression protocols, infectious prophylaxis, hepatitis C coinfection, metabolic complications, and malignancy are all discussed.10.34067/KID.0002112020Wed, 06 May 2020 01:43:10 GMT-07:00Kidney Transplantation in Patients with HIVIndividuals with HIV are at increased risk for ESKD. Kidney transplantation is the best treatment for ESKD in the HIV+ population. Despite reduced access to transplantation, patients who are HIV+ have excellent outcomes and clearly benefit from receiving one. Common post-transplant complications and management concerns, including the optimal antiretroviral regimen, immunosuppression protocols, infectious prophylaxis, hepatitis C coinfection, metabolic complications, and malignancy are all discussed.Sawinski, Deirdre2020-05-06T13:43:10-07:00doi:10.34067/KID.0002112020hwp:resource-id:kidney360;1/7/705American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, anti-retroviral agents, coinfection, hepatitis C, HIV infections, immunosuppression, kidney failure, chronic, kidney transplantationReview ArticlesReview Articlesreview-article20202020-07-3010.34067/KID.00021120202641-76502020-05-06T13:43:10-07:002020-07-30Kidney360Review Articles17705711
- Foreign Perspective on Achieving a Successful Peritoneal Dialysis-First Program10.34067/KID.0000712019Wed, 13 May 2020 01:27:03 GMT-07:00Foreign Perspective on Achieving a Successful Peritoneal Dialysis-First ProgramLi, Philip Kam-TaoRosenberg, Mark E.2020-05-13T13:27:03-07:00doi:10.34067/KID.0000712019hwp:resource-id:kidney360;1/7/680American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, cost-benefit analysis, hemodialysis, home, Hong Kong, kidney failure, chronic, PD-first policy, peritoneal dialysis, peritoneal dialysis, continuous ambulatory, renal insufficiency, chronic, renal replacement therapy, United StatesGlobal PerspectivesGlobal Perspectivesresearch-article20202020-07-3010.34067/KID.00007120192641-76502020-05-13T13:27:03-07:002020-07-30Kidney360Global Perspectives17680684
- CKRT Clotting and Cerebrovascular Accident in a Critically Ill Patient10.34067/KID.0003112020Thu, 30 Jul 2020 05:30:20 GMT-07:00CKRT Clotting and Cerebrovascular Accident in a Critically Ill PatientCervantes, Carmen ElenaMenez, StevenHanouneh, Mohamad2020-07-30T05:30:20-07:00doi:10.34067/KID.0003112020hwp:resource-id:kidney360;1/7/718American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, blood coagulation, citrates, continuous kidney replacement therapy, COVID-19, heparin, hypercoagulability, thromboembolism, thrombophiliaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-07-3010.34067/KID.00031120202641-76502020-07-30T05:30:20-07:002020-07-30Kidney360Clinical Images in Nephrology and Dialysis17718719
- COVID-19: A Home Dialysis Nurse Perspective10.34067/KID.0002672020Thu, 04 Jun 2020 01:34:49 GMT-07:00COVID-19: A Home Dialysis Nurse PerspectiveBushey, MargaretSpaeth, DonaLaCroix, Cynthia2020-06-04T13:34:49-07:00doi:10.34067/KID.0002672020hwp:resource-id:kidney360;1/7/694American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, ambulatory care facilities, COVID-19, emergency planning, hemodialysis, home, pandemic, renal dialysis, severe acute respiratory syndrome coronavirus 2, workflowPerspectivesPerspectivesresearch-article20202020-07-3010.34067/KID.00026720202641-76502020-06-04T13:34:49-07:002020-07-30Kidney360Perspectives17694696
- Acute Kidney Injury in the Time of COVID-1910.34067/KID.0003722020Thu, 11 Jun 2020 09:42:44 GMT-07:00Acute Kidney Injury in the Time of COVID-19Chan, LiliCoca, Steven G.2020-06-11T09:42:44-07:00doi:10.34067/KID.0003722020hwp:resource-id:kidney360;1/7/588American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney failure, chronic kidney disease, coronavirus, COVID-19, dialysis, SARS-CoV-2EditorialsEditorialseditorial20202020-07-3010.34067/KID.00037220202641-76502020-06-11T09:42:44-07:002020-07-30Kidney360Editorials17588590
- Acute Kidney Injury Associated with Coronavirus Disease 2019 in Urban New Orleans10.34067/KID.0002652020Wed, 13 May 2020 10:16:30 GMT-07:00Acute Kidney Injury Associated with Coronavirus Disease 2019 in Urban New OrleansMohamed, Muner M.B.Lukitsch, IvoTorres-Ortiz, Aldo E.Walker, Joseph B.Varghese, VipinHernandez-Arroyo, Cesar F.Alqudsi, MuhannadLeDoux, Jason R.Velez, Juan Carlos Q.2020-05-13T10:16:30-07:00doi:10.34067/KID.0002652020hwp:resource-id:kidney360;1/7/614American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, black, COVID-19, dialysis, hospital mortality, ICU, New Orleans, obesity, phenotype, proteinuria, renal replacement therapy, SARS, SARS-CoV-2, United StatesOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-07-3010.34067/KID.00026520202641-76502020-05-13T10:16:30-07:002020-07-30Kidney360Original Investigations17614622
- End Points for Clinical Trials in Primary HyperoxaluriaPatients with primary hyperoxaluria experience kidney stones from a young age and can develop progressive oxalate nephropathy. Progression to kidney failure often develops over a number of years, and is associated with systemic oxalosis, intensive dialysis, and often combined kidney and liver transplantation. There are no therapies approved by the Food and Drug Association. Thus, the Kidney Health Initiative, in partnership with the Oxalosis and Hyperoxaluria Foundation, initiated a project to identify end points for clinical trials. A workgroup of physicians, scientists, patients with primary hyperoxaluria, industry, and United States regulators critically examined the published literature for clinical outcomes and potential surrogate end points that could be used to evaluate new treatments. Kidney stones, change in eGFR, urine oxalate, and plasma oxalate were the strongest candidate end points. Kidney stones affect how patients with primary hyperoxaluria feel and function, but standards for measurement and monitoring are lacking. Primary hyperoxaluria registry data suggest that eGFR decline in most patients is gradual, but can be unpredictable. Epidemiologic data show a strong relationship between urine oxalate and long-term kidney function loss. Urine oxalate is reasonably likely to predict clinical benefit, due to its causal role in stone formation and kidney damage in CKD stages 1–3a, and plasma oxalate is likely associated with risk of systemic oxalosis in CKD 3b–5. Change in slope of eGFR could be considered the equivalent of a clinically meaningful end point in support of traditional approval. A substantial change in urine oxalate as a surrogate end point could support traditional approval in patients with primary hyperoxaluria type 1 and CKD stages 1–3a. A substantial change in markedly elevated plasma oxalate could support accelerated approval in patients with primary hyperoxaluria and CKD stages 3b–5. Primary hyperoxaluria type 1 accounts for the preponderance of available data, thus heavily influences the conclusions. Addressing gaps in data will further facilitate testing of promising new treatments, accelerating improved outcomes for patients with primary hyperoxaluria.10.2215/CJN.13821119Thu, 12 Mar 2020 07:57:36 GMT-07:00End Points for Clinical Trials in Primary HyperoxaluriaPatients with primary hyperoxaluria experience kidney stones from a young age and can develop progressive oxalate nephropathy. Progression to kidney failure often develops over a number of years, and is associated with systemic oxalosis, intensive dialysis, and often combined kidney and liver transplantation. There are no therapies approved by the Food and Drug Association. Thus, the Kidney Health Initiative, in partnership with the Oxalosis and Hyperoxaluria Foundation, initiated a project to identify end points for clinical trials. A workgroup of physicians, scientists, patients with primary hyperoxaluria, industry, and United States regulators critically examined the published literature for clinical outcomes and potential surrogate end points that could be used to evaluate new treatments. Kidney stones, change in eGFR, urine oxalate, and plasma oxalate were the strongest candidate end points. Kidney stones affect how patients with primary hyperoxaluria feel and function, but standards for measurement and monitoring are lacking. Primary hyperoxaluria registry data suggest that eGFR decline in most patients is gradual, but can be unpredictable. Epidemiologic data show a strong relationship between urine oxalate and long-term kidney function loss. Urine oxalate is reasonably likely to predict clinical benefit, due to its causal role in stone formation and kidney damage in CKD stages 1–3a, and plasma oxalate is likely associated with risk of systemic oxalosis in CKD 3b–5. Change in slope of eGFR could be considered the equivalent of a clinically meaningful end point in support of traditional approval. A substantial change in urine oxalate as a surrogate end point could support traditional approval in patients with primary hyperoxaluria type 1 and CKD stages 1–3a. A substantial change in markedly elevated plasma oxalate could support accelerated approval in patients with primary hyperoxaluria and CKD stages 3b–5. Primary hyperoxaluria type 1 accounts for the preponderance of available data, thus heavily influences the conclusions. Addressing gaps in data will further facilitate testing of promising new treatments, accelerating improved outcomes for patients with primary hyperoxaluria.Milliner, Dawn S.McGregor, Tracy L.Thompson, AlizaDehmel, BastianKnight, JohnRosskamp, RalfBlank, MelanieYang, SixunFargue, SoniaRumsby, GillGroothoff, JaapAllain, MeaghanWest, MelissaHollander, KimLowther, W. ToddLieske, John C.2020-03-12T07:57:36-07:00doi:10.2215/CJN.13821119hwp:resource-id:clinjasn;15/7/1056American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyoxalate, kidney stones, clinical trial end points, rare kidney disease, primary hyperoxaluria type 1, hyperoxaluria, primary, liver transplantation, renal dialysis, hyperoxaluria, kidney calculi, kidney, renal insufficiency, registries, biomarkers, renal insufficiency, chronicFeatureFeatureresearch-article20202020-07-01July 01, 202010.2215/CJN.138211191555-90411555-905X2020-03-12T07:57:36-07:002020-07-01Clinical Journal of the American Society of NephrologyFeature15710561065
- Secondary Hyperparathyroidism in a Patient with CKD10.2215/CJN.13411119Wed, 27 May 2020 07:35:57 GMT-07:00Secondary Hyperparathyroidism in a Patient with CKDHyder, RyyanSprague, Stuart M.2020-05-27T07:35:57-07:00doi:10.2215/CJN.13411119hwp:resource-id:clinjasn;15/7/1041American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, Hyperparathyroidism, Secondary, Renal Insufficiency, Chronic, parathyroid hormoneKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20202020-07-01July 01, 202010.2215/CJN.134111191555-90411555-905X2020-05-27T07:35:57-07:002020-07-01Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat15710411043
- Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis10.2215/CJN.00590120Fri, 22 May 2020 05:48:44 GMT-07:00Malaria, Collapsing Glomerulopathy, and Focal and Segmental GlomerulosclerosisAmoura, ArianeMoktefi, AnissaHalfon, MatthieuKarras, AlexandreRafat, CédricGibier, Jean-BaptisteGleeson, Patrick J.Servais, AudeArgy, NicolasMaillé, PascaleBelenfant, XavierGueutin, VictorDelpierre, AlexiaTricot, LeilaEl Karoui, KhalilJourde-Chiche, NoémieHouze, SandrineSahali, DilAudard, Vincent2020-05-22T05:48:44-07:00doi:10.2215/CJN.00590120hwp:resource-id:clinjasn;15/7/964American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFSGS, collapsing glomerulopathy, minimal change nephrotic syndrome, kidney biopsy, malaria infection, APOL1 protein, human, HIV-Associated Nephropathy, nephrotic syndrome, HIV Infections, immunohistochemistry, Follow-Up StudiesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-07-01July 01, 202010.2215/CJN.005901201555-90411555-905X2020-05-22T05:48:44-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles157964972
- The Importance of Kidney Medullary Tissue for the Accurate Diagnosis of BK Virus Allograft Nephropathy10.2215/CJN.13611119Mon, 29 Jun 2020 04:21:53 GMT-07:00The Importance of Kidney Medullary Tissue for the Accurate Diagnosis of BK Virus Allograft NephropathyNankivell, Brian J.Renthawa, JasveenShingde, MeenaKhan, Asrar2020-06-29T04:21:53-07:00doi:10.2215/CJN.13611119hwp:resource-id:clinjasn;15/7/1015American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBK Virus, kidney transplantation, Polyomavirus, immunohistochemistry, Polyomavirus Infections, kidney disease, Transplantation, Biopsy, Virus Replication, Banff schemaOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-07-01July 01, 202010.2215/CJN.136111191555-90411555-905X2020-06-29T04:21:53-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles15710151023
- Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan10.2215/CJN.13861119Thu, 11 Jun 2020 07:10:24 GMT-07:00Urinary Lithogenic Risk Profile in ADPKD Patients Treated with TolvaptanBargagli, MatteoDhayat, Nasser A.Anderegg, ManuelSemmo, MariamHuynh-Do, UyenVogt, BrunoFerraro, Pietro ManuelFuster, Daniel G.2020-06-11T07:10:24-07:00doi:10.2215/CJN.13861119hwp:resource-id:clinjasn;15/7/1007American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, kidney stones, tolvaptan, calcium oxalate, polycystic kidney, autosomal dominant, creatinine, glomerular filtration rate, uric acid, calcium phosphate, dibasic, dihydrate, linear models, citric acid, body mass index, alkalies, prospective studies, cohort studies, follow-up studies, kidney calculiOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20202020-07-01July 01, 202010.2215/CJN.138611191555-90411555-905X2020-06-11T07:10:24-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles157710079231014925
- Dialysis Regret10.2215/CJN.13781119Thu, 04 Jun 2020 05:59:34 GMT-07:00Dialysis RegretSaeed, FahadLadwig, Susan A.Epstein, Ronald M.Monk, Rebeca D.Duberstein, Paul R.2020-06-04T05:59:34-07:00doi:10.2215/CJN.13781119hwp:resource-id:clinjasn;15/7/957American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyregret, shared dialysis decision-making, decisional regret, aged, living wills, logistic models, life expectancy, renal dialysis, prognosis, terminal care, odds ratio, surveys and questionnaires, decision making, renal insufficiency, chronic, emotions, marital status, attitudeOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20202020-07-01July 01, 202010.2215/CJN.137811191555-90411555-905X2020-06-04T05:59:34-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles157957963
- The Electronic Medical Record and Nephrology Fellowship Education in the United States10.2215/CJN.14191119Tue, 23 Jun 2020 08:08:43 GMT-07:00The Electronic Medical Record and Nephrology Fellowship Education in the United StatesYuan, Christina M.Little, Dustin J.Marks, Eric S.Watson, Maura A.Raghavan, RajeevNee, Robert,2020-06-23T08:08:43-07:00doi:10.2215/CJN.14191119hwp:resource-id:clinjasn;15/7/949American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMedical Record, Nephrology Fellowship, Clinical Education, Burnout, Work Hours, Work Compression, Electronic Health Records, Fellowships and Scholarships, Reading, Social Desirability, Records, Physicians, Radiology, Surveys and Questionnaires, Documentation, FacultyOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20202020-07-01July 01, 202010.2215/CJN.141911191555-90411555-905X2020-06-23T08:08:43-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles1577949917956919
- ADPKD, Tolvaptan, and Nephrolithiasis Risk10.2215/CJN.07610520Thu, 11 Jun 2020 07:10:25 GMT-07:00ADPKD, Tolvaptan, and Nephrolithiasis RiskHoorn, Ewout J.Zietse, Robert2020-06-11T07:10:25-07:00doi:10.2215/CJN.07610520hwp:resource-id:clinjasn;15/7/923American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycalcium, cyclic AMP, cystic kidney, hypercalciuria, kidney stones, kidney tubule, polycystic kidney disease, risk factors, Polycystic Kidney, Autosomal Dominant, Tolvaptan, Kidney CalculiEditorialsEditorialseditorial20202020-07-01July 01, 202010.2215/CJN.076105201555-90411555-905X2020-06-11T07:10:25-07:002020-07-01Clinical Journal of the American Society of NephrologyEditorials157792310079251014
- Role of Skeletal Muscle Mitochondrial Dysfunction in CKD10.2215/CJN.08050520Fri, 26 Jun 2020 07:25:19 GMT-07:00Role of Skeletal Muscle Mitochondrial Dysfunction in CKDRyan, Alice S.2020-06-26T07:25:19-07:00doi:10.2215/CJN.08050520hwp:resource-id:clinjasn;15/7/912American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal Insufficiency, Chronic, Muscle, Skeletal, mitochondria, chronic kidney diseaseEditorialsEditorialseditorial20202020-07-01July 01, 202010.2215/CJN.080505201555-90411555-905X2020-06-26T07:25:19-07:002020-07-01Clinical Journal of the American Society of NephrologyEditorials1577912926913936
- JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA Nephropathy10.2215/CJN.11010919Thu, 30 Apr 2020 07:33:44 GMT-07:00JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA NephropathyTao, JianlingMariani, LauraEddy, SeanMaecker, HoldenKambham, NeerajaMehta, KshamaHartman, JohnWang, WeiqiKretzler, MatthiasLafayette, Richard A.2020-04-30T07:33:44-07:00doi:10.2215/CJN.11010919hwp:resource-id:clinjasn;15/7/973American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, Cell Signaling, gene transcription, pathology, Glomerulonephritis, IGA, Glomerular Mesangium, Diabetic, Nephropathies, Glomerulosclerosis, Focal Segmental, Phosphorylation, Monocytes, Leukocytes, Mononuclear, Transcriptome, Kidney, Glomerulus, JAK2 protein, human, Janus Kinase 2, kidney, proteinuria, BiopsyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-07-01July 01, 202010.2215/CJN.110109191555-90411555-905X2020-04-30T07:33:44-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles157973982
- Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic Syndrome10.2215/CJN.13371019Tue, 21 Apr 2020 04:51:20 GMT-07:00Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic SyndromeMason, Anna E.Sen, Ethan S.Bierzynska, AgnieszkaColby, ElizabethAfzal, MaryamDorval, GuillaumeKoziell, Ania B.Williams, MaggieBoyer, OliviaWelsh, Gavin I.Saleem, Moin A.,2020-04-21T04:51:20-07:00doi:10.2215/CJN.13371019hwp:resource-id:clinjasn;15/7/983American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, pediatric nephrology, progression of renal failure, transplant outcomes, Rituximab, Exome, Radar, immunosuppression, Base Sequence, Genetic Testing, Renal Insufficiency, Biopsy, Disease Progression, Registries, Cohort StudiesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20202020-07-01July 01, 202010.2215/CJN.133710191555-90411555-905X2020-04-21T04:51:20-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles1577983920994922
- Mortality and Recovery Associated with Kidney Failure due to Acute Kidney Injury10.2215/CJN.11200919Wed, 17 Jun 2020 06:44:42 GMT-07:00Mortality and Recovery Associated with Kidney Failure due to Acute Kidney InjuryShah, SilviLeonard, Anthony C.Harrison, KathleenMeganathan, KarthikeyanChristianson, Annette L.Thakar, Charuhas V.2020-06-17T06:44:42-07:00doi:10.2215/CJN.11200919hwp:resource-id:clinjasn;15/7/995American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, renal recovery, ESKD, mortality, race, sex, dialysis, Acute Kidney Injury, kidney, Hispanic Americans, Asian Continental Ancestry Group, diabetes mellitusOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-07-01July 01, 202010.2215/CJN.112009191555-90411555-905X2020-06-17T06:44:42-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles1579951006
- Primary Hyperoxaluria10.2215/CJN.13831119Thu, 12 Mar 2020 07:57:36 GMT-07:00Primary HyperoxaluriaLawrence, Jennifer E.Wattenberg, Debra J.2020-03-12T07:57:36-07:00doi:10.2215/CJN.13831119hwp:resource-id:clinjasn;15/7/909American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyprimary hyperoxaluria, patient perspective, hyperoxaluria, kidney stones, genetic disease, child, adult, humans, preschool child, adolescent, primary hyperoxaluria type 1, caregivers, gastrostomy, water, renal dialysis, oxalates, kidney calculi, kidney, parents, surveys and questionnaires, internet, type 2 diabetes mellitusPatient VoicePatient Voiceeditorial20202020-07-01July 01, 202010.2215/CJN.138311191555-90411555-905X2020-03-12T07:57:36-07:002020-07-01Clinical Journal of the American Society of NephrologyPatient Voice157909911
- Individualizing Treatment of Steroid-Resistant Nephrotic Syndrome10.2215/CJN.08080520Mon, 29 Jun 2020 04:21:53 GMT-07:00Individualizing Treatment of Steroid-Resistant Nephrotic SyndromeBagga, ArvindSinha, Aditi2020-06-29T04:21:53-07:00doi:10.2215/CJN.08080520hwp:resource-id:clinjasn;15/7/920American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, focal segmental glomerulosclerosis, idiopathic nephrotic syndrome, proteinuria, nephrotic syndromeEditorialsEditorialseditorial20202020-07-01July 01, 202010.2215/CJN.080805201555-90411555-905X2020-06-29T04:21:53-07:002020-07-01Clinical Journal of the American Society of NephrologyEditorials1577920983922994
- From Nihilism to Opportunity10.2215/CJN.07260520Tue, 23 Jun 2020 08:08:42 GMT-07:00From Nihilism to OpportunityOlson, Andrew P.J.Rosenberg, Mark E.2020-06-23T08:08:42-07:00doi:10.2215/CJN.07260520hwp:resource-id:clinjasn;15/7/917American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, outcomes, electronic health record, educationEditorialsEditorialseditorial20202020-07-01July 01, 202010.2215/CJN.072605201555-90411555-905X2020-06-23T08:08:42-07:002020-07-01Clinical Journal of the American Society of NephrologyEditorials1577917949919956
- Considering Our Patients and Tempering Terminology10.2215/CJN.07960520Thu, 25 Jun 2020 10:36:32 GMT-07:00Considering Our Patients and Tempering TerminologyIngelfinger, Julie R.2020-06-25T10:36:32-07:00doi:10.2215/CJN.07960520hwp:resource-id:clinjasn;15/7/914American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynomenclature, patient, language, terminologyEditorialsEditorialseditorial20202020-07-01July 01, 202010.2215/CJN.079605201555-90411555-905X2020-06-25T10:36:32-07:002020-07-01Clinical Journal of the American Society of NephrologyEditorials15777914937907916948908
- Correction10.2215/CJN.06290420Tue, 09 Jun 2020 06:29:26 GMT-07:00CorrectionAmerican Society of Nephrology2020-06-09T06:29:26-07:00doi:10.2215/CJN.06290420hwp:resource-id:clinjasn;15/7/1027American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20202020-07-01July 01, 202010.2215/CJN.062904201555-90411555-905X2020-06-09T06:29:26-07:002020-07-01Clinical Journal of the American Society of NephrologyErratum15157210272091027218
- Short-Term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated Rejection10.34067/KID.0001082019Thu, 19 Mar 2020 09:36:56 GMT-07:00Short-Term Immunopathological Changes Associated with Pulse Steroids/IVIG/Rituximab Therapy in Late Kidney Allograft Antibody Mediated RejectionDegner, Kenna R.Wilson, Nancy A.Reese, Shannon R.Parajuli, SandeshAziz, FahadGarg, NeetikaMohamed, MahaSingh, TriptiMandelbrot, Didier A.Panzer, Sarah E.Redfield, Robert R.Van Hyfte, KristinZhong, WeixiongHidalgo, Luis G.Djamali, Arjang2020-03-19T09:36:56-07:00doi:10.34067/KID.0001082019hwp:resource-id:kidney360;1/5/389American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, antibody mediated rejection, B-lymphocytes, regulatory BAFF, CD8-positive T-lymphocytes, DSA, immunoglobulins, intravenous, kidney transplantation, prospective studies, rituximab, T-lymphocytes, regulatory, Basic Science, Basic ScienceOriginal InvestigationsTransplantationOriginal InvestigationsTransplantationresearch-article20202020-05-2810.34067/KID.00010820192641-76502020-03-19T09:36:56-07:002020-05-28Kidney360Original Investigations15389398
- Green Effluent in a Patient on Continuous Veno-venous Hemodiafiltration10.34067/KID.0000242020Thu, 28 May 2020 10:00:25 GMT-07:00Green Effluent in a Patient on Continuous Veno-venous HemodiafiltrationDias Gonçalves, PriscilaRamos de Freitas, Geraldo RubensReis, Thiago de Azevedo2020-05-28T10:00:25-07:00doi:10.34067/KID.0000242020hwp:resource-id:kidney360;1/5/428American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Acute Kidney Injury and ICU Nephrology, Akute Kidney Injure, effluent, hemodiafiltration, methylene blueClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-05-2810.34067/KID.00002420202641-76502020-05-28T10:00:25-07:002020-05-28Kidney360Clinical Images in Nephrology and Dialysis15428429
- Facial Deformity in a Patient with Chronic Secondary Hyperparathyroidism10.34067/KID.0000352020Thu, 28 May 2020 10:00:25 GMT-07:00Facial Deformity in a Patient with Chronic Secondary HyperparathyroidismDhont, SebastiaanViaene, LiesbethEvenepoel, Pieter2020-05-28T10:00:25-07:00doi:10.34067/KID.0000352020hwp:resource-id:kidney360;1/5/430American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, Chronic Kidney Disease, dialysis, hyperparathyroidism, Leontiatis osseaClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-05-2810.34067/KID.00003520202641-76502020-05-28T10:00:25-07:002020-05-28Kidney360Clinical Images in Nephrology and Dialysis15430431
- Influence of Medications Containing Acid Salts on Serum Bicarbonate in CKD10.34067/KID.0000532019Tue, 31 Mar 2020 01:29:42 GMT-07:00Influence of Medications Containing Acid Salts on Serum Bicarbonate in CKDGardner, JohnTuttle, KunaniRaphael, Kalani L.2020-03-31T13:29:42-07:00doi:10.34067/KID.0000532019hwp:resource-id:kidney360;1/5/330American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acid/base and electrolyte disorders, acid-base equilibrium, acidosis, anion gap, bicarbonate, carbon dioxide, cross-sectional studies, diabetes mellitus, gabapentin, hydrochloric acid, metformin, polypharmacy, renal insufficiency, chronicOriginal InvestigationsAcid/Base and Electrolyte DisordersOriginal InvestigationsAcid/Base and Electrolyte Disordersresearch-article20202020-05-2810.34067/KID.00005320192641-76502020-03-31T13:29:42-07:002020-05-28Kidney360Original Investigations15330336
- Utility of Peritoneal Scintigraphy in Peritoneal Dialysis Patients: One Center Experience10.34067/KID.0000302020Tue, 24 Mar 2020 02:22:15 GMT-07:00Utility of Peritoneal Scintigraphy in Peritoneal Dialysis Patients: One Center ExperienceSosa Barrios, R. HaridianRioja Martín, María EugeniaBurguera Vion, VíctorSantos Carreño, Astrid LucíaFernández Lucas, MilagrosRivera Gorrín, Maite E.2020-03-24T14:22:15-07:00doi:10.34067/KID.0000302020hwp:resource-id:kidney360;1/5/354American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, dialysate leak, imaging test, peritoneal dialysis, renal replacement therapy, scintigraphyOriginal InvestigationsDialysisOriginal InvestigationsDialysisresearch-article20202020-05-2810.34067/KID.00003020202641-76502020-03-24T14:22:15-07:002020-05-28Kidney360Original Investigations15354358
- Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in Nephrology10.34067/KID.0000072020Thu, 02 Apr 2020 10:11:53 GMT-07:00Clinical Response and Pattern of B cell Suppression with Single Low Dose Rituximab in NephrologyGeorge, JacobAlex, SunuThomas, E.T. ArunGracious, NobleVineetha, Nalanda S.Kumar, Sajeev2020-04-02T10:11:53-07:00doi:10.34067/KID.0000072020hwp:resource-id:kidney360;1/5/359American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, antibody-mediated rejection, frequently relapsing nephrotic syndrome, idiopathic membranous nephropathy, immunosuppression, kidney transplantation, nephrotic syndrome, steroid-dependent nephrotic syndromeOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-05-2810.34067/KID.00000720202641-76502020-04-02T10:11:53-07:002020-05-28Kidney360Original Investigations15359367
- Use of Immune Checkpoint Inhibitors in End Stage Kidney Disease Patients, Single Center Experience and Review of the Literature10.34067/KID.0000422020Wed, 18 Mar 2020 08:02:50 GMT-07:00Use of Immune Checkpoint Inhibitors in End Stage Kidney Disease Patients, Single Center Experience and Review of the LiteratureHirsch, Jamie S.Wanchoo, RimdaNg, Jia H.Khanin, YuriyJhaveri, Kenar D.2020-03-18T08:02:50-07:00doi:10.34067/KID.0000422020hwp:resource-id:kidney360;1/5/399American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, checkpoint inhibitors, dialysis, immunotherapy, nivolumab, onconephrology, pembrolizumabBrief CommunicationBrief Communicationbrief-report20202020-05-2810.34067/KID.00004220202641-76502020-03-18T08:02:50-07:002020-05-28Kidney360Brief Communication15399402
- Anti-Cancer Activity of PAK4/NAMPT Inhibitor and Programmed Cell Death Protein-1 Antibody in Kidney Cancer10.34067/KID.0000282019Fri, 27 Mar 2020 02:22:52 GMT-07:00Anti-Cancer Activity of PAK4/NAMPT Inhibitor and Programmed Cell Death Protein-1 Antibody in Kidney CancerTrott, Josephine F.Abu Aboud, OmranMcLaughlin, BridgetAnderson, Katie L.Modiano, Jaime F.Kim, KyoungmiJen, Kuang-YuSenapedis, WilliamChang, HuaLandesman, YosefBaloglu, ErkanPili, RobertoWeiss, Robert H.2020-03-27T14:22:52-07:00doi:10.34067/KID.0000282019hwp:resource-id:kidney360;1/5/376American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360nephro-pharmacology, immunology, lymphocytes, metabolism, pathology, renal carcinoma, Basic ScienceOriginal InvestigationsNephropharmacologyOriginal InvestigationsNephropharmacologyresearch-article20202020-05-2810.34067/KID.00002820192641-76502020-03-27T14:22:52-07:002020-05-28Kidney360Original Investigations15376388
- Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney Disease10.34067/KID.0000982019Tue, 31 Mar 2020 06:00:11 GMT-07:00Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney DiseaseChang, Tara I.Wei, GuoBoucher, RobertKramer, HollyChertow, Glenn M.Cheung, Alfred K.Greene, TomWhelton, Paul K.Beddhu, Srinivasan2020-03-31T06:00:11-07:00doi:10.34067/KID.0000982019hwp:resource-id:kidney360;1/5/368American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Hypertension, Blood Pressure, Cause of Death, Hypertension, Randomized Controlled Trials, Renal Insufficiency, Chronic, SPRINTOriginal InvestigationsHypertensionOriginal InvestigationsHypertensionresearch-article20202020-05-2810.34067/KID.00009820192641-76502020-03-31T06:00:11-07:002020-05-28Kidney360Original Investigations15368375
- Gadolinium-Based Contrast Agent Use, Their Safety, and Practice EvolutionGadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.10.34067/KID.0000272019Wed, 15 Apr 2020 01:24:45 GMT-07:00Gadolinium-Based Contrast Agent Use, Their Safety, and Practice EvolutionGadolinium-based contrast agents (GBCAs) have provided much needed image enhancement in magnetic resonance imaging (MRI) important in the advancement of disease diagnosis and treatment. The paramagnetic properties of ionized gadolinium have facilitated these advancements, but ionized gadolinium carries toxicity risk. GBCAs were formulated with organic chelates designed to reduce these toxicity risks from unbound gadolinium ions. They were preferred over iodinated contrast used in computed tomography and considered safe for use. As their use expanded, the development of new diseases associated with their use (including nephrogenic systemic fibrosis) has drawn more attention and ultimately caution with their clinical administration in those with impaired renal function. Use of GBCAs in those with preserved renal function was considered to be safe. However, in this new era with emerging clinical and experimental evidence of brain gadolinium deposition in those with repeated exposure, these safety assumptions are once again brought into question. This review article aims to add new perspectives in thinking about the role of GBCA in current clinical use. The new information begs for further discussion and consideration of the risk-benefit ratio of use of GBCAs.Do, CatherineDeAguero, JoshuaBrearley, AdrianTrejo, XochitlHoward, TamaraEscobar, G. PatriciaWagner, Brent2020-04-15T13:24:45-07:00doi:10.34067/KID.0000272019hwp:resource-id:kidney360;1/6/561American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Chronic Kidney Disease, Contrast Media, Fibrosis, Gadolinium, Image Enhancement, Magnetic Resonance Imaging, Nephrogenic Fibrosing Dermopathy, Risk Assessment, Tomography, X-Ray Computed, Basic ScienceBasic Science for CliniciansBasic Science for Cliniciansresearch-article20202020-06-2510.34067/KID.00002720192641-76502020-04-15T13:24:45-07:002020-06-25Kidney360Basic Science for Clinicians16561568
- Use of Gadolinium-Based Contrast Agents in Patients with Severe Renal Impairment. Absence of Risk Versus Caution: A Nephrologist’s Perspective10.34067/KID.0003022020Thu, 25 Jun 2020 05:30:20 GMT-07:00Use of Gadolinium-Based Contrast Agents in Patients with Severe Renal Impairment. Absence of Risk Versus Caution: A Nephrologist’s PerspectiveRudnick, Michael R.Wahba, Ihab M.Leonberg-Yoo, Amanda K.2020-06-25T05:30:20-07:00doi:10.34067/KID.0003022020hwp:resource-id:kidney360;1/6/433American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, chronic kidney disease, gadolinium-based contrast agents, magnetic resonance imaging, nephrogenic systemic fibrosisEditorialEditorialeditorial20202020-06-2510.34067/KID.00030220202641-76502020-06-25T05:30:20-07:002020-06-25Kidney360Editorial16433435
- Sildenafil Citrate Does Not Reprogram Risk of Hypertension and Chronic Kidney Disease in Offspring of Preeclamptic Pregnancies in the Dahl SS/Jr Rat10.34067/KID.0001062020Fri, 17 Apr 2020 08:35:12 GMT-07:00Sildenafil Citrate Does Not Reprogram Risk of Hypertension and Chronic Kidney Disease in Offspring of Preeclamptic Pregnancies in the Dahl SS/Jr RatTurbeville, Hannah R.Johnson, Ashley C.Garrett, Michael R.Sasser, Jennifer M.2020-04-17T08:35:12-07:00doi:10.34067/KID.0001062020hwp:resource-id:kidney360;1/6/510American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Hypertension, Angiotensin II, Developmental Programming, Diet, Hypertension, Kidney Diseases, Phosphodiesterase 5 Inhibitors, Pre-Eclampsia, Pregnancy, Rats, Inbred Dahl, Sildenafil Citrate, Sodium Chloride, Basic ScienceOriginal InvestigationsHypertensionOriginal InvestigationsHypertensionresearch-article20202020-06-2510.34067/KID.00010620202641-76502020-04-17T08:35:12-07:002020-06-25Kidney360Original Investigations16510520
- Identification of Podocyte Cargo Proteins by Proteomic Analysis of Clathrin-Coated Vesicles10.34067/KID.0000212020Thu, 16 Apr 2020 01:40:02 GMT-07:00Identification of Podocyte Cargo Proteins by Proteomic Analysis of Clathrin-Coated VesiclesGroener, MarwinWang, YingCross, ElizabethTian, XuefeiEbenezer, KarenBaik, EunicePedigo, ChristopherSchiffer, MarioInoue, KazunoriIshibe, Shuta2020-04-16T13:40:02-07:00doi:10.34067/KID.0000212020hwp:resource-id:kidney360;1/6/480American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360glomerular and tubulointerstitial diseases, clathrin-coated vesicles, clathrin-mediated endocytosis, glomerular diseases, immunoblotting, kidney glomerulus, mice, podocytes, proteomics, Basic ScienceOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-06-2510.34067/KID.00002120202641-76502020-04-16T13:40:02-07:002020-06-25Kidney360Original Investigations16480490
- Dexamethasone for Preventing Major Adverse Kidney Events following Cardiac Surgery: Post-Hoc Analysis to Identify Subgroups10.34067/KID.0000812019Thu, 30 Apr 2020 06:13:33 GMT-07:00Dexamethasone for Preventing Major Adverse Kidney Events following Cardiac Surgery: Post-Hoc Analysis to Identify SubgroupsVenugopal, HemaJacob, Kirolos A.Dieleman, Jan M.Leaf, David E.2020-04-30T06:13:33-07:00doi:10.34067/KID.0000812019hwp:resource-id:kidney360;1/6/530American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, cardiac surgical procedures, cardiopulmonary bypass, dexamethasone, glucocorticoids, inflammation, steroidsBrief CommunicationsBrief Communicationsin-brief20202020-06-2510.34067/KID.00008120192641-76502020-04-30T06:13:33-07:002020-06-25Kidney360Brief Communications16530533
- Renal Manifestations of Common Variable Immunodeficiency10.34067/KID.0000432020Tue, 21 Apr 2020 01:45:16 GMT-07:00Renal Manifestations of Common Variable ImmunodeficiencyCaza, Tiffany N.Hassen, Samar I.Larsen, Christopher P.2020-04-21T13:45:16-07:00doi:10.34067/KID.0000432020hwp:resource-id:kidney360;1/6/491American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Glomerular and Tubulointerstitial Diseases, Glomerular disease, Immunodeficiency, Membranous nephropathy, Renal biopsy, Tubulointerstitial nephritisOriginal InvestigationsGlomerular and Tubulointerstitial DiseasesOriginal InvestigationsGlomerular and Tubulointerstitial Diseasesresearch-article20202020-06-2510.34067/KID.00004320202641-76502020-04-21T13:45:16-07:002020-06-25Kidney360Original Investigations16491500
- Refractory Proteinuria in a Patient with Lupus Nephritis10.34067/KID.0000652020Thu, 25 Jun 2020 05:30:20 GMT-07:00Refractory Proteinuria in a Patient with Lupus NephritisOda, YasuhiroHoshino, JunichiUbara, Yoshifumi2020-06-25T05:30:20-07:00doi:10.34067/KID.0000652020hwp:resource-id:kidney360;1/6/580American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360diabetes and the kidney, diabetic nephropathy, glomerulonephritis, lupus erythematosus, systemic, lupus nephritisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-06-2510.34067/KID.00006520202641-76502020-06-25T05:30:20-07:002020-06-25Kidney360Clinical Images in Nephrology and Dialysis16580581
- CT Scan Surprise in a Potential Kidney Donor10.34067/KID.0000662020Thu, 25 Jun 2020 05:30:20 GMT-07:00CT Scan Surprise in a Potential Kidney DonorSingh, PrinceBentall, AndrewErickson, Stephen B.2020-06-25T05:30:20-07:00doi:10.34067/KID.0000662020hwp:resource-id:kidney360;1/6/582American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Transplantation, ectopia, evaluation, fused Kidney, Living DonorsClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-06-2510.34067/KID.00006620202641-76502020-06-25T05:30:20-07:002020-06-25Kidney360Clinical Images in Nephrology and Dialysis16582583
- Association between NSAID Exposure and Kidney Function Decline in Primary Care Patients10.34067/KID.0001102019Tue, 07 Apr 2020 01:33:52 GMT-07:00Association between NSAID Exposure and Kidney Function Decline in Primary Care PatientsPai, Amy BartonVassalotti, Joseph A.Fox, Chester H.Carroll, Jennifer K.Pulver, Gerald E.Dickinson, L. MiriamPace, Wilson D.2020-04-07T13:33:52-07:00doi:10.34067/KID.0001102019hwp:resource-id:kidney360;1/6/521American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360nephro-pharmacology, acute kidney injury, adverse effects, anti-inflammatory agents, non-steroidal, chronic kidney disease, nonprescription drugs, NSAID, primary health care, renal insufficiency, chronic, United States Food and Drug AdministrationBrief CommunicationsBrief Communicationsbrief-report20202020-06-2510.34067/KID.00011020192641-76502020-04-07T13:33:52-07:002020-06-25Kidney360Brief Communications16521523
- Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney Disease10.34067/KID.0000962019Tue, 28 Apr 2020 09:39:51 GMT-07:00Vascular Dysfunction, Oxidative Stress, and Inflammation in Chronic Kidney DiseaseNowak, Kristen L.Jovanovich, AnnaFarmer-Bailey, HeatherBispham, NinaStruemph, TaylorMalaczewski, MikaelaWang, WeiChonchol, Michel2020-04-28T09:39:51-07:00doi:10.34067/KID.0000962019hwp:resource-id:kidney360;1/6/501American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360hemodynamics and vascular regulation, brachial artery, cardiovascular diseases, dilatation, endothelium, human umbilical vein endothelial cells, inflammation, NADP, oxidative stress, pulse wave analysis, renal insufficiency, chronic, vascular, vascular stiffnessOriginal InvestigationsHemodynamics and Vascular RegulationOriginal InvestigationsHemodynamics and Vascular Regulationresearch-article20202020-06-2510.34067/KID.00009620192641-76502020-04-28T09:39:51-07:002020-06-25Kidney360Original Investigations16501509
- Point-of-Care Ultrasound for Native Kidney Biopsies10.34067/KID.0001962020Mon, 27 Apr 2020 01:35:29 GMT-07:00Point-of-Care Ultrasound for Native Kidney BiopsiesPalacherla, JithendranathO’Neill, W. Charles2020-04-27T13:35:29-07:00doi:10.34067/KID.0001962020hwp:resource-id:kidney360;1/6/527American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Clinical Nephrology, Biopsy, Faculty, Internship and Residency, Kidney Diseases, Nephrology, Point-of-Care Systems, Radiation Exposure, Radiologists, Schools, Medical, Tomography, X-Ray Computed, Ultrasonography, WorkforceBrief CommunicationsBrief Communicationsin-brief20202020-06-2510.34067/KID.00019620202641-76502020-04-27T13:35:29-07:002020-06-25Kidney360Brief Communications16527529
- Prevalence and Risk Factors for CKD in the General Population of Southwestern Nicaragua10.1681/ASN.2019050521Fri, 29 May 2020 08:26:18 GMT-07:00Prevalence and Risk Factors for CKD in the General Population of Southwestern NicaraguaFerguson, RyanLeatherman, SarahFiore, MadelineMinnings, KaileyMosco, MarthaKaufman, JamesKerns, EricAmador, Juan JoseBrooks, Daniel R.Fiore, MelissaParekh, Rulan S.Fiore, Louis2020-05-29T08:26:18-07:00doi:10.1681/ASN.2019050521hwp:resource-id:jnephrol;31/7/1585American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyMesoamerican nephropathy, Nicaragua, chronic kidney disease, renal insufficiency, public health, epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20202020-07-01July 202010.1681/ASN.20190505211046-66731533-34502020-05-29T08:26:18-07:002020-07Journal of the American Society of NephrologyClinical Epidemiology31715851593
- Gut Microbial Metabolites Induce Donor-Specific Tolerance of Kidney Allografts through Induction of T Regulatory Cells by Short-Chain Fatty Acids10.1681/ASN.2019080852Mon, 01 Jun 2020 02:02:41 GMT-07:00Gut Microbial Metabolites Induce Donor-Specific Tolerance of Kidney Allografts through Induction of T Regulatory Cells by Short-Chain Fatty AcidsWu, HuilingSinger, JulianKwan, Tony K.Loh, Yik WenWang, ChuanminTan, JianLi, Yan J.Lai, Sum Wing ChristinaMacia, LaurenceAlexander, Stephen I.Chadban, Steven J.2020-06-01T14:02:41-07:00doi:10.1681/ASN.2019080852hwp:resource-id:jnephrol;31/7/1445American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, acute allograft rejection, tolerance, chronic allograft rejection, immunologyBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20190808521046-66731533-34502020-06-01T14:02:41-07:002020-07Journal of the American Society of NephrologyBasic Research31771445141714611418
- Cell-Based Phenotypic Drug Screening Identifies Luteolin as Candidate Therapeutic for Nephropathic Cystinosis10.1681/ASN.2019090956Fri, 05 Jun 2020 09:32:14 GMT-07:00Cell-Based Phenotypic Drug Screening Identifies Luteolin as Candidate Therapeutic for Nephropathic CystinosisDe Leo, EsterElmonem, Mohamed A.Berlingerio, Sante PrincieroBerquez, MarineFesta, Beatrice PaolaRaso, RobertoBellomo, FrancescoStarborg, TobiasJanssen, Manoe JacobaAbbaszadeh, ZeinabCairoli, SaraGoffredo, Bianca MariaMasereeuw, RosalindeDevuyst, OlivierLowe, MartinLevtchenko, ElenaLuciani, AlessandroEmma, FrancescoRega, Laura Rita2020-06-05T09:32:14-07:00doi:10.1681/ASN.2019090956hwp:resource-id:jnephrol;31/7/1522American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologylysosomal storage disease, autophagy, endocytosis, apoptosis, reactiveBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20190909561046-66731533-34502020-06-05T09:32:14-07:002020-07Journal of the American Society of NephrologyBasic Research31715221537
- In Memorium: Burton Rose, 1942–202010.1681/ASN.2020050702Thu, 11 Jun 2020 07:13:30 GMT-07:00In Memorium: Burton Rose, 1942–2020Hoenig, Melanie P.Steinman, Theodore I.Pollak, Martin R.Zeidel, Mark L.2020-06-11T07:13:30-07:00doi:10.1681/ASN.2020050702hwp:resource-id:jnephrol;31/7/1421American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyObituary, JASN, RoseUp Front MattersObituariesUp Front MattersObituariesother20202020-07-01July 202010.1681/ASN.20200507021046-66731533-34502020-06-11T07:13:30-07:002020-07Journal of the American Society of NephrologyUp Front Matters31714211422
- Inhibition of Estrogen Sulfotransferase (SULT1E1/EST) Ameliorates Ischemic Acute Kidney Injury in Mice10.1681/ASN.2019080767Mon, 18 May 2020 01:11:01 GMT-07:00Inhibition of Estrogen Sulfotransferase (SULT1E1/EST) Ameliorates Ischemic Acute Kidney Injury in MiceSilva Barbosa, Anne C.Zhou, DongXie, YangChoi, You-JinTung, Hung-ChunChen, XinyunXu, MeishuGibbs, Robert B.Poloyac, Samuel M.Liu, SilviaYu, YanpingLuo, JianhuaLiu, YouhuaXie, Wen2020-05-18T13:11:01-07:00doi:10.1681/ASN.2019080767hwp:resource-id:jnephrol;31/7/1496American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, renal ischemia-reperfusion, estrogen sulfotransferase, kidney-liver crosstalk, calcitriolBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20190807671046-66731533-34502020-05-18T13:11:01-07:002020-07Journal of the American Society of NephrologyBasic Research31714961508
- Early Predictors of Arteriovenous Fistula Maturation: A Novel Perspective on an Enduring Problem10.1681/ASN.2019080848Mon, 18 May 2020 01:11:01 GMT-07:00Early Predictors of Arteriovenous Fistula Maturation: A Novel Perspective on an Enduring ProblemFarrington, Crystal A.Robbin, Michelle L.Lee, TimmyBarker-Finkel, JillAllon, Michael2020-05-18T13:11:01-07:00doi:10.1681/ASN.2019080848hwp:resource-id:jnephrol;31/7/1617American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, vascular mapping, ultrasound, maturation, arterial diameterClinical ResearchClinical Researchresearch-article20202020-07-01July 202010.1681/ASN.20190808481046-66731533-34502020-05-18T13:11:01-07:002020-07Journal of the American Society of NephrologyClinical Research31716171627
- Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan10.1681/ASN.2019060623Wed, 03 Jun 2020 06:22:57 GMT-07:00Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in JapanAkizawa, TadaoIwasaki, ManabuYamaguchi, YusukeMajikawa, YoshikatsuReusch, Michael2020-06-03T06:22:57-07:00doi:10.1681/ASN.2019060623hwp:resource-id:jnephrol;31/7/1628American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, roxadustat, anemia, darbepoetin alfa, hemodialysis, clinical trialClinical ResearchClinical Researchresearch-article20202020-07-01July 202010.1681/ASN.20190606231046-66731533-34502020-06-03T06:22:57-07:002020-07Journal of the American Society of NephrologyClinical Research31744162810051005163910051007
- Neutrophil Gelatinase–Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting TH17 Immunity10.1681/ASN.2019090879Tue, 02 Jun 2020 09:18:14 GMT-07:00Neutrophil Gelatinase–Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting TH17 ImmunitySchreiber, AdrianRousselle, AnthonyKlocke, JanBachmann, SebastianPopovic, SuncicaBontscho, JuliaSchmidt-Ott, Kai M.Siffrin, VolkerJerke, UweAshraf, Muhammad ImtiazPanzer, UlfKettritz, Ralph2020-06-02T09:18:14-07:00doi:10.1681/ASN.2019090879hwp:resource-id:jnephrol;31/7/1569American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyANCA glomerulonephritis, ngal, TH17, neutrophilBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20190908791046-66731533-34502020-06-02T09:18:14-07:002020-07Journal of the American Society of NephrologyBasic Research31715691584
- Authors' Reply10.1681/ASN.2020050624Mon, 01 Jun 2020 02:02:41 GMT-07:00Authors' ReplyMacdougall, Iain C.Ford, Ian2020-06-01T14:02:41-07:00doi:10.1681/ASN.2020050624hwp:resource-id:jnephrol;31/7/1654American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyLetters to the EditorLetters to the Editorletter20202020-07-01July 202010.1681/ASN.20200506241046-66731533-34502020-06-01T14:02:41-07:002020-07Journal of the American Society of NephrologyLetters to the Editor31771654165316541654
- Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2019101121Tue, 02 Jun 2020 09:18:11 GMT-07:00Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney DiseaseBae, Kyongtae T.Shi, TiangeTao, ChengYu, Alan S. L.Torres, Vicente E.Perrone, Ronald D.Chapman, Arlene B.Brosnahan, GodelaSteinman, Theodore I.Braun, William E.Srivastava, AvantikaIrazabal, Maria V.Abebe, Kaleab Z.Harris, Peter C.Landsittel, Douglas P.,2020-06-02T09:18:11-07:00doi:10.1681/ASN.2019101121hwp:resource-id:jnephrol;31/7/1640American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, clinical trial, kidney volume, risk factorsClinical ResearchClinical Researchresearch-article20202020-07-01July 202010.1681/ASN.20191011211046-66731533-34502020-06-02T09:18:11-07:002020-07Journal of the American Society of NephrologyClinical Research31716401651
- Gerhard Giebisch (1927–2020): A Leader in Kidney Physiology10.1681/ASN.2020050669Fri, 05 Jun 2020 09:32:14 GMT-07:00Gerhard Giebisch (1927–2020): A Leader in Kidney PhysiologyMurer, HeiniWagner, Carsten A.2020-06-05T09:32:14-07:00doi:10.1681/ASN.2020050669hwp:resource-id:jnephrol;31/7/1419American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyObituary, Giebisch, Cell & Transport PhysiologyUp Front MattersObituariesUp Front MattersObituariesother20202020-07-01July 202010.1681/ASN.20200506691046-66731533-34502020-06-05T09:32:14-07:002020-07Journal of the American Society of NephrologyUp Front Matters31714191420
- At the Crossroads for Intravenous Iron Dosing10.1681/ASN.2020040540Mon, 01 Jun 2020 02:02:41 GMT-07:00At the Crossroads for Intravenous Iron DosingKshirsagar, Abhijit V.Li, XiaojuanRobinson, Bruce M.Brookhart, M. Alan2020-06-01T14:02:41-07:00doi:10.1681/ASN.2020040540hwp:resource-id:jnephrol;31/7/1653American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, dialysis, anemiaLetters to the EditorLetters to the Editorletter20202020-07-01July 202010.1681/ASN.20200405401046-66731533-34502020-06-01T14:02:41-07:002020-07Journal of the American Society of NephrologyLetters to the Editor31771653165416541654
- Phosphorylation of ACTN4 Leads to Podocyte Vulnerability and Proteinuric Glomerulosclerosis10.1681/ASN.2019101032Mon, 15 Jun 2020 09:37:08 GMT-07:00Phosphorylation of ACTN4 Leads to Podocyte Vulnerability and Proteinuric GlomerulosclerosisFeng, DiKumar, MukeshMuntel, JanGurley, Susan B.Birrane, GabrielStillman, Isaac E.Ding, LaiWang, MinxianAhmed, SaimaSchlondorff, JohannesAlper, Seth L.Ferrante, TomMarquez, Susan L.Ng, Carlos F.Novak, RichardIngber, Donald E.Steen, HannoPollak, Martin R.2020-06-15T09:37:08-07:00doi:10.1681/ASN.2019101032hwp:resource-id:jnephrol;31/7/1479American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, focal segmental glomerulosclerosis, glomerular disease, cytoskeleton, podocyte, proteinuriaBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20191010321046-66731533-34502020-06-15T09:37:08-07:002020-07Journal of the American Society of NephrologyBasic Research31714791495
- GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts10.1681/ASN.2020020151Thu, 04 Jun 2020 05:58:30 GMT-07:00GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based CohortsEriksen, Bjørn O.Palsson, RunolfurEbert, NatalieMelsom, Toralfvan der Giet, MarkusGudnason, VilmundurIndridason, Olafur S.Inker, Lesley A.Jenssen, Trond G.Levey, Andrew S.Solbu, Marit D.Tighiouart, HocineSchaeffner, Elke2020-06-04T05:58:30-07:00doi:10.1681/ASN.2020020151hwp:resource-id:jnephrol;31/7/1602American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyepidemiology and outcomes, geriatric nephrology, glomerular filtration rate, glomerular hyperfiltration, renal dysfunction, renal function declineClinical EpidemiologyClinical Epidemiologyresearch-article20202020-07-01July 202010.1681/ASN.20200201511046-66731533-34502020-06-04T05:58:30-07:002020-07Journal of the American Society of NephrologyClinical Epidemiology31716021615
- CKD Increases Carbonylation of HDL and Is Associated with Impaired Antiaggregant Properties10.1681/ASN.2019111205Tue, 09 Jun 2020 06:33:09 GMT-07:00CKD Increases Carbonylation of HDL and Is Associated with Impaired Antiaggregant PropertiesFlorens, NansCalzada, CatherineLemoine, SandrineBoulet, Marie MichèleGuillot, NicolasBarba, ChristopheRoux, JulieDelolme, FrédericPage, AdelinePoux, Jean MichelLaville, MauriceMoulin, PhilippeSoulère, LaurentGuebre-Egziabher, FitsumJuillard, LaurentSoulage, Christophe O.2020-06-09T06:33:09-07:00doi:10.1681/ASN.2019111205hwp:resource-id:jnephrol;31/7/1462American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, platelets, cardiovascular disease, dyslipidemia, thrombosis, dialysisBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20191112051046-66731533-34502020-06-09T06:33:09-07:002020-07Journal of the American Society of NephrologyBasic Research31714621477
- Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction10.1681/ASN.2019070728Thu, 11 Jun 2020 07:13:30 GMT-07:00Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal DysfunctionBobot, MickaëlThomas, LaurentMoyon, AnaïsFernandez, SamanthaMcKay, NathalieBalasse, LaureGarrigue, PhilippeBrige, PaulineChopinet, SophiePoitevin, StéphaneCérini, ClaireBrunet, PhilippeDignat-George, FrançoiseBurtey, StéphaneGuillet, BenjaminHache, Guillaume2020-06-11T07:13:30-07:00doi:10.1681/ASN.2019070728hwp:resource-id:jnephrol;31/7/1509American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, uremia, dementiaBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20190707281046-66731533-34502020-06-11T07:13:30-07:002020-07Journal of the American Society of NephrologyBasic Research31715091521
- This Month's Highlights10.1681/ASN.2020050733Tue, 30 Jun 2020 10:00:32 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2020-06-30T10:00:32-07:00doi:10.1681/ASN.2020050733hwp:resource-id:jnephrol;31/7/iAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20202020-07-01July 202010.1681/ASN.20200507331046-66731533-34502020-06-30T10:00:32-07:002020-07Journal of the American Society of NephrologyThis Month’s Highlights317ii
- Renomedullary Interstitial Cell Endothelin A Receptors Regulate BP and Renal Function10.1681/ASN.2020020232Tue, 02 Jun 2020 09:18:13 GMT-07:00Renomedullary Interstitial Cell Endothelin A Receptors Regulate BP and Renal FunctionHu, ChunyanLakshmipathi, JayalakshmiStuart, DeborahPeti-Peterdi, JanosGyarmati, GeorginaHao, Chuan-MingHansell, PeterKohan, Donald E.2020-06-02T09:18:13-07:00doi:10.1681/ASN.2020020232hwp:resource-id:jnephrol;31/7/1555American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyrenomedullary, interstitial cell, blood pressure, endothelin receptorBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20200202321046-66731533-34502020-06-02T09:18:13-07:002020-07Journal of the American Society of NephrologyBasic Research31715551568
- Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance Hemodialysis10.2215/CJN.10320819Fri, 26 Jun 2020 07:25:19 GMT-07:00Skeletal Muscle Mitochondrial Dysfunction Is Present in Patients with CKD before Initiation of Maintenance HemodialysisGamboa, Jorge L.Roshanravan, BabackTowse, TheodoreKeller, Chad A.Falck, Aaron M.Yu, ChangFrontera, Walter R.Brown, Nancy J.Ikizler, T. Alp2020-06-26T07:25:19-07:00doi:10.2215/CJN.10320819hwp:resource-id:clinjasn;15/7/926American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymitochondria, hemodialysis, Skeletal muscle, chronic kidney disease, Chronic inflammation, oxidative stress, Sarcopenia, Frailty, Mitochondrial Dynamics, Phosphocreatine, Phosphorus, Walk Test, Mitochondria, Muscle, DNM1L protein, human, Mitochondrial Proteins, Microtubule-Associated Proteins, Magnetic Resonance Spectroscopy, Muscle, Skeletal, Renal Insufficiency, Chronic, InflammationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-07-01July 01, 202010.2215/CJN.103208191555-90411555-905X2020-06-26T07:25:19-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles1577926912936913
- Patient and Caregiver Perspectives on Terms Used to Describe Kidney Health10.2215/CJN.00900120Thu, 25 Jun 2020 10:36:31 GMT-07:00Patient and Caregiver Perspectives on Terms Used to Describe Kidney HealthTong, AllisonLevey, Andrew S.Eckardt, Kai-UweAnumudu, SamayaArce, Cristina M.Baumgart, AmandaDunn, LoueseGutman, TaliaHarris, TessLightstone, LizScholes-Robertson, NicoleShen, Jenny I.Wheeler, David C.White, David M.Wilkie, MartinCraig, Jonathan C.Jadoul, MichelWinkelmayer, Wolfgang C.2020-06-25T10:36:31-07:00doi:10.2215/CJN.00900120hwp:resource-id:clinjasn;15/7/937American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycommunication, education, nomenclature, patient-centered care, chronic kidney disease, caregivers, focus groups, judgment, self-management, ownership, language, prognosis, personal satisfaction, renal insufficiency, chronic, kidney failure, decision making, patient participation, fear, patient-centered care, AustraliaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-07-01July 01, 202010.2215/CJN.009001201555-90411555-905X2020-06-25T10:36:31-07:002020-07-01Clinical Journal of the American Society of NephrologyOriginal Articles15777937907914948908916
- The Evolving Role of Calcineurin Inhibitors in Treating Lupus NephritisThe overall kidney survival among lupus nephritis patients has improved with currently used induction immunosuppression regimens of corticosteroids and either cyclophosphamide or mycophenolate mofetil; however, there still remains a significant number of lupus nephritis patients who do not achieve remission with these regimens. Investigators have looked at other immunosuppressive regimens for lupus nephritis, and there has been interest in the use of calcineurin inhibitors in this regard. Calcineurin inhibitors are potentially an attractive option because of their established ability to inhibit T cell function, attenuate proteinuria through non-immunologic means, and their safety in pregnancy and lactation. In this review, we discuss the findings and limitations of selected trials that evaluated the use of calcineurin inhibitors in the treatment of lupus nephritis, either with corticosteroids alone or as a component of multitarget therapy when combined with mycophenolate mofetil. There may be a role for calcineurin inhibitors among patients with heavy proteinuria, as well as younger patients with refractory lupus nephritis. The multitarget therapy trials reveal higher rates of remission compared with mycophenolate mofetil alone and cyclophosphamide; however, some trials highlight the possibility of more infectious adverse events. We discuss the need for further study of calcineurin inhibitors in more diverse patient populations and the need for trials with longer follow-up with “hard” endpoints beyond proteinuria reduction, such as worsening CKD or repeat protocol biopsies, given the calcineurin inhibitors ability to reduce proteinuria non-immunologically and thus increased rate of relapse when the drug is tapered. While there may indeed be a space for calcineurin inhibitors to help increase remission rates in lupus nephritis patients, more work is needed to help address the questions the studies available to date have yet to answer.10.2215/CJN.13761119Mon, 09 Mar 2020 06:34:41 GMT-07:00The Evolving Role of Calcineurin Inhibitors in Treating Lupus NephritisThe overall kidney survival among lupus nephritis patients has improved with currently used induction immunosuppression regimens of corticosteroids and either cyclophosphamide or mycophenolate mofetil; however, there still remains a significant number of lupus nephritis patients who do not achieve remission with these regimens. Investigators have looked at other immunosuppressive regimens for lupus nephritis, and there has been interest in the use of calcineurin inhibitors in this regard. Calcineurin inhibitors are potentially an attractive option because of their established ability to inhibit T cell function, attenuate proteinuria through non-immunologic means, and their safety in pregnancy and lactation. In this review, we discuss the findings and limitations of selected trials that evaluated the use of calcineurin inhibitors in the treatment of lupus nephritis, either with corticosteroids alone or as a component of multitarget therapy when combined with mycophenolate mofetil. There may be a role for calcineurin inhibitors among patients with heavy proteinuria, as well as younger patients with refractory lupus nephritis. The multitarget therapy trials reveal higher rates of remission compared with mycophenolate mofetil alone and cyclophosphamide; however, some trials highlight the possibility of more infectious adverse events. We discuss the need for further study of calcineurin inhibitors in more diverse patient populations and the need for trials with longer follow-up with “hard” endpoints beyond proteinuria reduction, such as worsening CKD or repeat protocol biopsies, given the calcineurin inhibitors ability to reduce proteinuria non-immunologically and thus increased rate of relapse when the drug is tapered. While there may indeed be a space for calcineurin inhibitors to help increase remission rates in lupus nephritis patients, more work is needed to help address the questions the studies available to date have yet to answer.Peleg, YonatanBomback, Andrew S.Radhakrishnan, Jai2020-03-09T06:34:41-07:00doi:10.2215/CJN.13761119hwp:resource-id:clinjasn;15/7/1066American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPregnancy, lupus nephritis, Calcineurin Inhibitors, Mycophenolic Acid, Follow-Up Studies, T-Lymphocytes, Cyclophosphamide, Immunosuppressive Agents, immunosuppression, proteinuria, Lactation, Adrenal Cortex Hormones, Recurrence, Biopsy, Infections, Renal Insufficiency, ChronicReviewReviewreview-article20202020-07-01July 01, 202010.2215/CJN.137611191555-90411555-905X2020-03-09T06:34:41-07:002020-07-01Clinical Journal of the American Society of NephrologyReview15710661072
- The Feasibility and Safety of Obtaining Research Kidney Biopsy Cores in Patients with Diabetes10.2215/CJN.13061019Mon, 27 Apr 2020 08:36:27 GMT-07:00The Feasibility and Safety of Obtaining Research Kidney Biopsy Cores in Patients with DiabetesHogan, Jonathan J.Owen, Jonathan G.Blady, Shira J.Almaani, SalemAvasare, Rupali S.Bansal, ShwetaLenz, OliverLuciano, Randy L.Parikh, Samir V.Ross, Michael J.Sharma, DeepSzerlip, HaroldWadhwani, ShikhaTownsend, Raymond R.Palmer, Matthew B.Susztak, KatalinMottl, Amy K.,2020-04-27T08:36:27-07:00doi:10.2215/CJN.13061019hwp:resource-id:clinjasn;15/7/1024American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, diabetic nephropathy, Feasibility Studies, Biopsy, diabetes mellitusResearch LetterResearch Letterresearch-article20202020-07-01July 01, 202010.2215/CJN.130610191555-90411555-905X2020-04-27T08:36:27-07:002020-07-01Clinical Journal of the American Society of NephrologyResearch Letter15710241026
- Genetic Roadmap for Kidney Involvement of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection10.2215/CJN.04370420Thu, 23 Apr 2020 06:00:39 GMT-07:00Genetic Roadmap for Kidney Involvement of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) InfectionZhang, Yue-miaoZhang, Hong2020-04-23T06:00:39-07:00doi:10.2215/CJN.04370420hwp:resource-id:clinjasn;15/7/1044American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, kidney involvement, severe acute respiratory syndrome coronavirus 2, human ACE2, genetic perspectivePerspectivesPerspectivesresearch-article20202020-07-01July 01, 202010.2215/CJN.043704201555-90411555-905X2020-04-23T06:00:39-07:002020-07-01Clinical Journal of the American Society of NephrologyPerspectives15710441046
- EHR-Based Clinical Trials10.2215/CJN.11860919Mon, 24 Feb 2020 09:10:56 GMT-08:00EHR-Based Clinical TrialsAbdel-Kader, KhaledJhamb, Manisha2020-02-24T09:10:56-08:00doi:10.2215/CJN.11860919hwp:resource-id:clinjasn;15/7/1050American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyelectronic health record, pragmatic, chronic kidney disease, acute kidney injury, humans, creatinine, kidney transplantation, nephrology, albuminuria, electronic health records, explosions, prevalence, blood pressure, translational medical research, patient selection, risk factors, developed countries, renal dialysis, chronic renal insufficiency, kidney, registries, biomarkers, phenotype, randomized controlled trialsPerspectivesPerspectivesresearch-article20202020-07-01July 01, 202010.2215/CJN.118609191555-90411555-905X2020-02-24T09:10:56-08:002020-07-01Clinical Journal of the American Society of NephrologyPerspectives15710501052
- Mineralocorticoid Receptor Antagonists in ESKD10.2215/CJN.13221019Wed, 08 Apr 2020 11:34:34 GMT-07:00Mineralocorticoid Receptor Antagonists in ESKDAgarwal, AdhishCheung, Alfred K.2020-04-08T11:34:34-07:00doi:10.2215/CJN.13221019hwp:resource-id:clinjasn;15/7/1047American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, mineralocorticoid receptor antagonists, renal dialysis, aldosterone, mineralocorticoids, cardiovascular diseases, risk factors, chronic kidney failure, chronic renal insufficiency, hyperaldosteronism, heart failure, diabetes mellitus, hospitalization, Kidney Failure, ChronicPerspectivesPerspectivesresearch-article20202020-07-01July 01, 202010.2215/CJN.132210191555-90411555-905X2020-04-08T11:34:34-07:002020-07-01Clinical Journal of the American Society of NephrologyPerspectives15710471049
- Complexities of Understanding Function from CKD-Associated DNA VariantsGenome-wide association studies (GWASs) have facilitated the unbiased discovery of hundreds of genomic loci associated with CKD and kidney function. The vast majority of disease-associated DNA variants are noncoding. Those that are causal in CKD pathogenesis likely modulate transcription of target genes in a cell type–specific manner. To gain novel biological insights into mechanisms driving the development of CKD, the causal variants (which are usually not the most significant variant reported in a GWAS), their target genes, and causal cell types need to be identified. This functional validation requires a large number of new data sets, complex bioinformatics analyses, and experimental cellular and in vivo studies. Here, we review the basic principles and some of the current approaches being leveraged to assign functional significance to a genotype–phenotype association.10.2215/CJN.15771219Mon, 08 Jun 2020 05:28:45 GMT-07:00Complexities of Understanding Function from CKD-Associated DNA VariantsGenome-wide association studies (GWASs) have facilitated the unbiased discovery of hundreds of genomic loci associated with CKD and kidney function. The vast majority of disease-associated DNA variants are noncoding. Those that are causal in CKD pathogenesis likely modulate transcription of target genes in a cell type–specific manner. To gain novel biological insights into mechanisms driving the development of CKD, the causal variants (which are usually not the most significant variant reported in a GWAS), their target genes, and causal cell types need to be identified. This functional validation requires a large number of new data sets, complex bioinformatics analyses, and experimental cellular and in vivo studies. Here, we review the basic principles and some of the current approaches being leveraged to assign functional significance to a genotype–phenotype association.Lin, JennieSusztak, Katalin2020-06-08T05:28:45-07:00doi:10.2215/CJN.15771219hwp:resource-id:clinjasn;15/7/1028American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyKidney Genomics Series, Genome-Wide Association Study, Computational Biology, Genomics, Genetic Association Studies, Renal Insufficiency, Chronic, DNAGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-07-01July 01, 202010.2215/CJN.157712191555-90411555-905X2020-06-08T05:28:45-07:002020-07-01Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease15710281040
- Nephrology Nomenclature: How to Accelerate Patient Anxiety, Suppress Engagement, and Mire the Advance of Medical Innovation10.2215/CJN.08730620Thu, 25 Jun 2020 10:36:32 GMT-07:00Nephrology Nomenclature: How to Accelerate Patient Anxiety, Suppress Engagement, and Mire the Advance of Medical InnovationConway, Paul T.2020-06-25T10:36:32-07:00doi:10.2215/CJN.08730620hwp:resource-id:clinjasn;15/7/907American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnxiety, Kidney Precision Medicine Project, KidneyX, Kidney Health Initiative, Patient Engagement, Advancing American Kidney Health, Pre-Dialysis, CKD stages, End Stage Renal Disease, Communication, Education, Nomenclature, Patient-Centered Care, Chronic Kidney Disease, Caregivers, Focus Groups, Judgment, Self-Management, Ownership, Language, Prognosis, Personal Satisfaction, Renal Insufficiency, Chronic, Kidney Failure, Chronic, Decision Making, Patient Participation, Fear, Patient-Centered CarePatient VoicePatient Voiceeditorial20202020-07-01July 01, 202010.2215/CJN.087306201555-90411555-905X2020-06-25T10:36:32-07:002020-07-01Clinical Journal of the American Society of NephrologyPatient Voice15777907937914908948916
- Understanding Work10.2215/CJN.12661019Mon, 24 Feb 2020 09:10:56 GMT-08:00Understanding WorkRosner, Mitchell HowardFalk, Ronald J.2020-02-24T09:10:56-08:00doi:10.2215/CJN.12661019hwp:resource-id:clinjasn;15/7/1053American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproductivity, relative value unit, benchmark, aged, humans, United States, relative value scales, current procedural terminology, U.S. Centers for Medicare and Medicaid Services, American Medical Association, nephrology, Medicaid, Medicare, efficiency, physicians, office visits, malpractice, renal dialysis, fibrinogenPerspectivesPerspectivesresearch-article20202020-07-01July 01, 202010.2215/CJN.126610191555-90411555-905X2020-02-24T09:10:56-08:002020-07-01Clinical Journal of the American Society of NephrologyPerspectives157121053183210551834
- Measuring Patient Activation as Part of Kidney Disease Policy: Are We There Yet?Optimal care occurs when patients possess the skills, knowledge, and confidence needed to effectively manage their health. Promoting such patient activation in kidney disease care is increasingly being prioritized, and patient activation has recently emerged as central to kidney disease legislative policy in the United States. Two options of the Centers for Medicare and Medicaid Services Kidney Care Choices model—the Kidney Care First option and the Comprehensive Kidney Care Contracting option—now include patient activation as a quality metric; both models specifically name the patient activation measure (PAM) as the patient-reported outcome to use when assessing activation in kidney disease. Because nephrology practices participating in these models will receive capitated payments according to changes in patients’ PAM scores, it is time to more critically evaluate this measure as it applies to patients with kidney disease. In this review, we raise important issues related to the PAM’s applicability to kidney health, review and summarize existing literature that applies this measure to patients with kidney disease, and outline key elements to consider when implementing the PAM into practice and policy. Our aim is to spur further dialogue regarding how to assess and address patient activation in kidney disease to facilitate best practices for supporting patients in the successful management of their kidney health.10.1681/ASN.2019121331Thu, 11 Jun 2020 07:13:31 GMT-07:00Measuring Patient Activation as Part of Kidney Disease Policy: Are We There Yet?Optimal care occurs when patients possess the skills, knowledge, and confidence needed to effectively manage their health. Promoting such patient activation in kidney disease care is increasingly being prioritized, and patient activation has recently emerged as central to kidney disease legislative policy in the United States. Two options of the Centers for Medicare and Medicaid Services Kidney Care Choices model—the Kidney Care First option and the Comprehensive Kidney Care Contracting option—now include patient activation as a quality metric; both models specifically name the patient activation measure (PAM) as the patient-reported outcome to use when assessing activation in kidney disease. Because nephrology practices participating in these models will receive capitated payments according to changes in patients’ PAM scores, it is time to more critically evaluate this measure as it applies to patients with kidney disease. In this review, we raise important issues related to the PAM’s applicability to kidney health, review and summarize existing literature that applies this measure to patients with kidney disease, and outline key elements to consider when implementing the PAM into practice and policy. Our aim is to spur further dialogue regarding how to assess and address patient activation in kidney disease to facilitate best practices for supporting patients in the successful management of their kidney health.Nair, DevikaCavanaugh, Kerri L.2020-06-11T07:13:31-07:00doi:10.1681/ASN.2019121331hwp:resource-id:jnephrol;31/7/1435American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyPatient self-assessment, kidney disease, outcomesUp Front MattersReviewsUp Front MattersReviewsresearch-article20202020-07-01July 202010.1681/ASN.20191213311046-66731533-34502020-06-11T07:13:31-07:002020-07Journal of the American Society of NephrologyUp Front Matters31714351443
- A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac HypertrophyCardiac hypertrophy is a common feature in patients with CKD. Recent studies revealed that two phosphate regulators, fibroblast growth factor-23 and α-Klotho, are highly involved in the pathophysiologic process of CKD-induced cardiac hypertrophy. With decreasing renal function, elevated fibroblast growth factor-23 and decreased α-Klotho may contribute to cardiac hypertrophy by targeting the heart directly or by inducing systemic changes, such as vascular injury, hemodynamic disorders, and inflammation. However, several studies have demonstrated that disturbances in the fibroblast growth factor-23/α-Klotho axis do not lead to cardiac hypertrophy. In this review, we describe the cardiac effects of the fibroblast growth factor-23/α-Klotho axis and summarize recent progress in this field. In addition, we present not only the main controversies in this field but also provide possible directions to resolve these disputes.10.1681/ASN.2020010081Thu, 11 Jun 2020 07:13:31 GMT-07:00A Land of Controversy: Fibroblast Growth Factor-23 and Uremic Cardiac HypertrophyCardiac hypertrophy is a common feature in patients with CKD. Recent studies revealed that two phosphate regulators, fibroblast growth factor-23 and α-Klotho, are highly involved in the pathophysiologic process of CKD-induced cardiac hypertrophy. With decreasing renal function, elevated fibroblast growth factor-23 and decreased α-Klotho may contribute to cardiac hypertrophy by targeting the heart directly or by inducing systemic changes, such as vascular injury, hemodynamic disorders, and inflammation. However, several studies have demonstrated that disturbances in the fibroblast growth factor-23/α-Klotho axis do not lead to cardiac hypertrophy. In this review, we describe the cardiac effects of the fibroblast growth factor-23/α-Klotho axis and summarize recent progress in this field. In addition, we present not only the main controversies in this field but also provide possible directions to resolve these disputes.Bao, Jing-FuHu, Pan-PanShe, Qin-YingLi, Aiqing2020-06-11T07:13:31-07:00doi:10.1681/ASN.2020010081hwp:resource-id:jnephrol;31/7/1423American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyfibroblast growth factor-23, α-Klotho, uremic cardiac hypertrophyUp Front MattersReviewsUp Front MattersReviewsresearch-article20202020-07-01July 202010.1681/ASN.20200100811046-66731533-34502020-06-11T07:13:31-07:002020-07Journal of the American Society of NephrologyUp Front Matters31714231434
- Hemodialysis with Cohort Isolation to Prevent Secondary Transmission during a COVID-19 Outbreak in Korea10.1681/ASN.2020040461Mon, 01 Jun 2020 02:02:41 GMT-07:00Hemodialysis with Cohort Isolation to Prevent Secondary Transmission during a COVID-19 Outbreak in KoreaCho, Jang-HeeKang, Seok HuiPark, Hayne ChoKim, Dong KiLee, Sang-HoDo, Jun YoungPark, Jong WonKim, Seong NamKim, Myeong SeongJin, KyubokKang, Gun WooPark, Sun-HeeKim, Yong-LimLee, Young-Ki,2020-06-01T14:02:41-07:00doi:10.1681/ASN.2020040461hwp:resource-id:jnephrol;31/7/1398American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycoronavirus, hemodialysis units, end-stage renal disease, quarantine, cohort isolation, COVID-19Clinical ResearchClinical Researchresearch-article20202020-07-01July 202010.1681/ASN.20200404611046-66731533-34502020-06-01T14:02:41-07:002020-07Journal of the American Society of NephrologyClinical Research31713981408
- Presentation and Outcomes of Patients with ESKD and COVID-1910.1681/ASN.2020040470Thu, 28 May 2020 12:40:01 GMT-07:00Presentation and Outcomes of Patients with ESKD and COVID-19Valeri, Anthony M.Robbins-Juarez, Shelief Y.Stevens, Jacob S.Ahn, WooinRao, Maya K.Radhakrishnan, JaiGharavi, Ali G.Mohan, SumitHusain, S. Ali2020-05-28T12:40:01-07:00doi:10.1681/ASN.2020040470hwp:resource-id:jnephrol;31/7/1409American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycoronavirus, dialysis, Epidemiology and outcomes, ESRD, COVID-19Rapid CommunicationRapid Communicationresearch-article20202020-07-01July 202010.1681/ASN.20200404701046-66731533-34502020-05-28T12:40:01-07:002020-07Journal of the American Society of NephrologyRapid Communication31714091415
- Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan, China10.1681/ASN.2020030354Fri, 08 May 2020 01:21:53 GMT-07:00Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan, ChinaXiong, FeiTang, HuiLiu, LiTu, CanTian, Jian-BoLei, Chun-TaoLiu, JingDong, Jun-WuChen, Wen-LiWang, Xiao-HuiLuo, DanShi, MingMiao, Xiao-PingZhang, Chun2020-05-08T13:21:53-07:00doi:10.1681/ASN.2020030354hwp:resource-id:jnephrol;31/7/1387American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, Clinical characteristics, Interventions, hemodialysisClinical EpidemiologyClinical Epidemiologyresearch-article20202020-07-01July 202010.1681/ASN.20200303541046-66731533-34502020-05-08T13:21:53-07:002020-07Journal of the American Society of NephrologyClinical Epidemiology31713871397
- Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology10.1681/ASN.2020040419Mon, 04 May 2020 10:56:16 GMT-07:00Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct PathophysiologyBatlle, DanielSoler, Maria JoseSparks, Matthew A.Hiremath, SwapnilSouth, Andrew M.Welling, Paul A.Swaminathan, Sundararaman,Sparks, Matthew A.Hiremath, SwapnilBatlle, DanielSouth, AndrewWelling, PaulLuther, J. MattCohen, JordanaByrd, James BrianBurrell, Louise M.Tomlinson, LaurieBhalla, VivekJosé Soler, MaríaSwaminathan, SundarRheault, Michelle N.Swaminathan, Sundar2020-05-04T10:56:16-07:00doi:10.1681/ASN.2020040419hwp:resource-id:jnephrol;31/7/1380American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyAcute kidney Injury, COVID-19, ACE2, Macrophage, ThromboticPerspectivePerspectiveresearch-article20202020-07-01July 202010.1681/ASN.20200404191046-66731533-34502020-05-04T10:56:16-07:002020-07Journal of the American Society of NephrologyPerspective31713801383
- Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-1910.1681/ASN.2020050589Mon, 08 Jun 2020 05:30:27 GMT-07:00Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19Adamsick, Meagan L.Gandhi, Ronak G.Bidell, Monique R.Elshaboury, Ramy H.Bhattacharyya, Roby P.Kim, Arthur Y.Nigwekar, SagarRhee, Eugene P.Sise, Meghan E.2020-06-08T05:30:27-07:00doi:10.1681/ASN.2020050589hwp:resource-id:jnephrol;31/7/1384American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, end-stage renal disease, antiviral, COVID-19PerspectivesPerspectivesresearch-article20202020-07-01July 202010.1681/ASN.20200505891046-66731533-34502020-06-08T05:30:27-07:002020-07Journal of the American Society of NephrologyPerspectives3172213845185191386519520
- Disaster Response to the COVID-19 Pandemic for Patients with Kidney Disease in New York City10.1681/ASN.2020040520Thu, 04 Jun 2020 05:58:30 GMT-07:00Disaster Response to the COVID-19 Pandemic for Patients with Kidney Disease in New York CityThe Division of Nephrology, Columbia University Vagelos College of Physicians Working GroupAhmad, Syeda B.Ahn, WooinAkomeah, JaneAl-Awqati, QaisAponte, Maria AlejandraAppel, Gerald B.Barasch, JonathanBaramidze, Irina Y.Beenken, AndrewBomback, Andrew S.Canetta, PietroChang, Jae-HyungClement, NishaCohen, David J.Craig, Bessie N.Daniel, EmilyCrew, Russell J.Douglas, DenzilDube, GeoffreyFernandez, HildaFerrer, RobinGharavi, Ali G.Ghavami, Iman AzamHusain, Syed AliKalloo, SeanKhairallah, PascaleKim, Jung SooKiryluk, KrzysztofLandry, DonaldLewis, JordannLee, MeeranLovisi, BrunoMedina, Allyson R.Marasa, MaddalenaMathew, DaisyPeleg, YonatanMehl, KarlaMorban, Maria M.Moses, AndrewMohan, SumitMorris, HeatherNelson, BradleyNestor, Jordan GabrielaNicasio, Vanna M.Nickolas, TomPaget, KathrynPiva, StaceyRadhakrishnan, JaiRao, Maya K.Sanna-Cherchi, SimoneShah, VaqarSampogna, Rosemary V.Shirazian, ShayanSiddall, EricStarakiewicz, PiotrStevens, Jacob S.Toma, KatherineValeri, AnthonyVerduzco, Hector AlvaradoWilliams, GailZheng, JasonMohan, SumitRao, Maya K.Stevens, Jacob S.Radhakrishnan, JaiGharavi, Ali G.2020-06-04T05:58:30-07:00doi:10.1681/ASN.2020040520hwp:resource-id:jnephrol;31/7/1371American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologypublic health, COVID-19, disaster planning, pandemic, organizational preparednessPerspectivePerspectiveresearch-article20202020-07-01July 202010.1681/ASN.20200405201046-66731533-34502020-06-04T05:58:30-07:002020-07Journal of the American Society of NephrologyPerspective31713711379
- Can Diet Induce Transplantation Tolerance?10.1681/ASN.2020050661Mon, 01 Jun 2020 02:02:41 GMT-07:00Can Diet Induce Transplantation Tolerance?Alegre, Maria-Luisa2020-06-01T14:02:41-07:00doi:10.1681/ASN.2020050661hwp:resource-id:jnephrol;31/7/1417American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologymicrobiota; short chain fatty acids, acetate, kidney transplantation, rejectionUp Front MattersEditorialUp Front MattersEditorialeditorial20202020-07-01July 202010.1681/ASN.20200506611046-66731533-34502020-06-01T14:02:41-07:002020-07Journal of the American Society of NephrologyUp Front Matters31771417144514181461
- Endogenous miR-204 Protects the Kidney against Chronic Injury in Hypertension and Diabetes10.1681/ASN.2019101100Tue, 02 Jun 2020 09:18:12 GMT-07:00Endogenous miR-204 Protects the Kidney against Chronic Injury in Hypertension and DiabetesCheng, YuanWang, DandanWang, FengLiu, JingHuang, BaoruiBaker, Maria AngelesYin, JianyongWu, RuiLiu, XuanchenRegner, Kevin R.Usa, KristieLiu, YongZhang, CongxiaoDong, LijinGeurts, Aron M.Wang, NiansongMiller, Sheldon S.He, YongchengLiang, Mingyu2020-06-02T09:18:12-07:00doi:10.1681/ASN.2019101100hwp:resource-id:jnephrol;31/7/1539American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, albuminuria, microRNA, hypertension, diabetesBasic ResearchBasic Researchresearch-article20202020-07-01July 202010.1681/ASN.20191011001046-66731533-34502020-06-02T09:18:12-07:002020-07Journal of the American Society of NephrologyBasic Research31715391554
- Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure10.1681/ASN.2019121308Tue, 02 Jun 2020 09:18:14 GMT-07:00Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart FailureNichols, Gregory A.Ustyugova, AnastasiaDéruaz-Luyet, AnoukO’Keeffe-Rosetti, MaureenBrodovicz, Kimberly G.2020-06-02T09:18:14-07:00doi:10.1681/ASN.2019121308hwp:resource-id:jnephrol;31/7/1594American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Economic Impact, Epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20202020-07-01July 202010.1681/ASN.20191213081046-66731533-34502020-06-02T09:18:14-07:002020-07Journal of the American Society of NephrologyClinical Epidemiology31715941601
- Mannose Binding Lectin Is Hydroxylated by Collagen Prolyl-4-hydroxylase and Inhibited by Some PHD Inhibitors10.34067/KID.0000092020Fri, 03 Apr 2020 01:25:57 GMT-07:00Mannose Binding Lectin Is Hydroxylated by Collagen Prolyl-4-hydroxylase and Inhibited by Some PHD InhibitorsBhute, Vijesh J.Harte, JamesHoughton, Jack W.Maxwell, Patrick H.2020-04-03T13:25:57-07:00doi:10.34067/KID.0000092020hwp:resource-id:kidney360;1/6/447American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, collagen prolyl-4-hydroxylase, FG-4592, HEK293 cells, hypoxia inducible factor, mannose binding lectin, PHD inhibitors, protein processing, post-translational, renal anemia, vadadustat; molidustat, Basic ScienceOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-06-2510.34067/KID.00000920202641-76502020-04-03T13:25:57-07:002020-06-25Kidney360Original Investigations16447457
- US Trends in Prevalence of Sleep Problems and Associations with Chronic Kidney Disease and Mortality10.34067/KID.0000862019Fri, 01 May 2020 09:42:46 GMT-07:00US Trends in Prevalence of Sleep Problems and Associations with Chronic Kidney Disease and MortalityShieu, MonicaMorgenstern, HalBragg-Gresham, JenniferGillespie, Brenda W.Shamim-Uzzaman, Q. AfifaTuot, DelphineSaydah, SharonRolka, DeborahBurrows, Nilka RiosPowe, Neil R.Saran, Rajiv,2020-05-01T09:42:46-07:00doi:10.34067/KID.0000862019hwp:resource-id:kidney360;1/6/458American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360chronic kidney disease, cross-sectional studies, logistic models, mortality, nocturia, prevalence, renal insufficiency, chronic, self report, sleep wake disorders, survival analysisOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-06-2510.34067/KID.00008620192641-76502020-05-01T09:42:46-07:002020-06-25Kidney360Original Investigations16458468
- Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD10.34067/KID.0000062020Mon, 13 Apr 2020 07:38:45 GMT-07:00Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKDGregg, L. ParkerCarmody, ThomasLe, DustinBharadwaj, NinaTrivedi, Madhukar H.Hedayati, S. Susan2020-04-13T07:38:45-07:00doi:10.34067/KID.0000062020hwp:resource-id:kidney360;1/6/436American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Chronic Kidney Disease, biomarkers, C-reactive protein, chronic kidney disease, depression, major depressive disorder, fatigue, high-sensitivity C-reactive protein, inflammation, interleukin-6, medically unexplained symptoms, quality of life, SertralineOriginal InvestigationsChronic Kidney DiseaseOriginal InvestigationsChronic Kidney Diseaseresearch-article20202020-06-2510.34067/KID.00000620202641-76502020-04-13T07:38:45-07:002020-06-25Kidney360Original Investigations16436446
- Acute Abdominal Pain in a COVID-19 Patient10.34067/KID.0002362020Thu, 25 Jun 2020 05:30:20 GMT-07:00Acute Abdominal Pain in a COVID-19 PatientMocerino, RyanKumar, Neelja2020-06-25T05:30:20-07:00doi:10.34067/KID.0002362020hwp:resource-id:kidney360;1/6/584American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, COVID-19, renal artery thrombosis, renal infarction, severe acute respiratory syndrome coronavirus 2, thrombosisClinical Images in Nephrology and DialysisClinical Images in Nephrology and Dialysisresearch-article20202020-06-2510.34067/KID.00023620202641-76502020-06-25T05:30:20-07:002020-06-25Kidney360Clinical Images in Nephrology and Dialysis16584585
- Early Use of Telehealth in Home Dialysis during the COVID-19 Pandemic in New York City10.34067/KID.0001662020Tue, 28 Apr 2020 09:39:51 GMT-07:00Early Use of Telehealth in Home Dialysis during the COVID-19 Pandemic in New York CitySrivatana, VeshLiu, FrankLevine, Daniel M.Kalloo, Sean D.2020-04-28T09:39:51-07:00doi:10.34067/KID.0001662020hwp:resource-id:kidney360;1/6/524American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, COVID-19, Hemodialysis, Home, New York City, Patient Care, Renal Dialysis, Telehealth, TelemedicineBrief CommunicationsBrief Communicationsin-brief20202020-06-2510.34067/KID.00016620202641-76502020-04-28T09:39:51-07:002020-06-25Kidney360Brief Communications16524526
- Automated Image Analyses of Glomerular Hypertrophy in a Mouse Model of Diabetic Nephropathy10.34067/KID.0001272019Fri, 01 May 2020 09:42:46 GMT-07:00Automated Image Analyses of Glomerular Hypertrophy in a Mouse Model of Diabetic NephropathyØstergaard, Mette V.Sembach, Frederikke E.Skytte, Jacob L.Roostalu, UrmasSecher, ThomasOvergaard, AgneteFink, Lisbeth N.Vrang, NielsJelsing, JacobHecksher-Sørensen, Jacob2020-05-01T09:42:46-07:00doi:10.34067/KID.0001272019hwp:resource-id:kidney360;1/6/469American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360diabetes and the kidney, 3D, CKD, diabetes mellitus, diabetic nephropathies, glomeruli, hypertrophy, kidney glomerulus, lightsheet, LSFM, microscopy, obesity, plant lectins, uninephrectomy, Basic ScienceOriginal InvestigationsDiabetes and the KidneyOriginal InvestigationsDiabetes and the Kidneyresearch-article20202020-06-2510.34067/KID.00012720192641-76502020-05-01T09:42:46-07:002020-06-25Kidney360Original Investigations16469479
- Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective of Two Nephrologists in Brazil10.34067/KID.0001672020Wed, 29 Apr 2020 09:47:10 GMT-07:00Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective of Two Nephrologists in BrazilSesso, RicardoDurão, Marcelino de Souza2020-04-29T09:47:10-07:00doi:10.34067/KID.0001672020hwp:resource-id:kidney360;1/6/541American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, Acute Kidney Disease, Brazil, Chronic Kidney Disease, COVID-19, Dialysis, PandemicGlobal PerspectivesGlobal Perspectivesresearch-article20202020-06-2510.34067/KID.00016720202641-76502020-04-29T09:47:10-07:002020-06-25Kidney360Global Perspectives16541543
- Providing Care to Patients with AKI and COVID-19 Infection: Experience of Front Line Nephrologists in New York10.34067/KID.0002002020Wed, 06 May 2020 01:43:10 GMT-07:00Providing Care to Patients with AKI and COVID-19 Infection: Experience of Front Line Nephrologists in New YorkFisher, MollyPrudhvi, KalyanBrogan, MaureenGolestaneh, Ladan2020-05-06T13:43:10-07:00doi:10.34067/KID.0002002020hwp:resource-id:kidney360;1/6/544American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, COVID-19, health resources, hospitalization, infections, nephrologists, New York City, pandemics, renal dialysis, severe acute respiratory syndrome coronavirus 2, workforceGlobal PerspectivesGlobal Perspectivesresearch-article20202020-06-2510.34067/KID.00020020202641-76502020-05-06T13:43:10-07:002020-06-25Kidney360Global Perspectives16544548
- Dialysis for Undocumented Immigrants: Challenges and Solutions10.34067/KID.0000682020Tue, 07 Apr 2020 01:33:52 GMT-07:00Dialysis for Undocumented Immigrants: Challenges and SolutionsBerger, Joseph R.Quinones, HenryVazquez, Miguel A.2020-04-07T13:33:52-07:00doi:10.34067/KID.0000682020hwp:resource-id:kidney360;1/6/549American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, catheter infections, delivery of health care, emergency service, hospital, kidney failure, chronic, patient care, quality of life, renal dialysis, resource allocation, safety-net providers, Texas, undocumented immigrantsPerspectivesPerspectivesresearch-article20202020-06-2510.34067/KID.00006820202641-76502020-04-07T13:33:52-07:002020-06-25Kidney360Perspectives16549552
- The Role of Telemedicine in Providing Nephrology Care in Rural Hospitals10.34067/KID.0001122019Wed, 22 Apr 2020 01:45:16 GMT-07:00The Role of Telemedicine in Providing Nephrology Care in Rural HospitalsLea, Janice P.Tannenbaum, Jerome2020-04-22T13:45:16-07:00doi:10.34067/KID.0001122019hwp:resource-id:kidney360;1/6/553American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360clinical nephrology, hemodialysis, home, hospitals, rural, renal dialysis, telemedicine, telenephrology, videoconferencingPerspectivesPerspectivesresearch-article20202020-06-2510.34067/KID.00011220192641-76502020-04-22T13:45:16-07:002020-06-25Kidney360Perspectives16553556
- COVID-19 Perspective from a Hemodialysis Patient10.34067/KID.0002842020Thu, 07 May 2020 01:26:35 GMT-07:00COVID-19 Perspective from a Hemodialysis PatientAllon, Michael2020-05-07T13:26:35-07:00doi:10.34067/KID.0002842020hwp:resource-id:kidney360;1/6/432American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, COVID-19, hemodialysis, patientPatient PerspectivePatient Perspectiveresearch-article20202020-06-2510.34067/KID.00028420202641-76502020-05-07T13:26:35-07:002020-06-25Kidney360Patient Perspective16432432
- Global Dialysis Perspective: Mexico10.34067/KID.0000912020Mon, 20 Apr 2020 08:06:50 GMT-07:00Global Dialysis Perspective: MexicoVasquez-Jimenez, EnzoMadero, Magdalena2020-04-20T08:06:50-07:00doi:10.34067/KID.0000912020hwp:resource-id:kidney360;1/6/534American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, delayed diagnosis, Diabetes Mellitus, dialysis, hypertension, kidney failure, chronic, Latin America, Mexico, obesity, prevalence, renal insufficiency, Chronic, risk factorsGlobal PerspectivesGlobal Perspectivesresearch-article20202020-06-2510.34067/KID.00009120202641-76502020-04-20T08:06:50-07:002020-06-25Kidney360Global Perspectives16534537
- Global Dialysis Perspective: Senegal10.34067/KID.0000882020Tue, 21 Apr 2020 01:45:16 GMT-07:00Global Dialysis Perspective: SenegalNiang, AbdouLemrabott, Ahmed Tall2020-04-21T13:45:16-07:00doi:10.34067/KID.0000882020hwp:resource-id:kidney360;1/6/538American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, diabetic nephropathies, hypertension, hypertensive nephropathy, kidney failure, nephritis, renal dialysis, renal replacement therapy, senegal, sub-Saharan AfricaGlobal PerspectivesGlobal Perspectivesresearch-article20202020-06-2510.34067/KID.00008820202641-76502020-04-21T13:45:16-07:002020-06-25Kidney360Global Perspectives16538540
- The Advancing American Kidney Health (AAKH) Executive Order: Promise and Caveats for Expanding Access to Kidney Transplantation10.34067/KID.0001172020Wed, 22 Apr 2020 01:45:16 GMT-07:00The Advancing American Kidney Health (AAKH) Executive Order: Promise and Caveats for Expanding Access to Kidney TransplantationLentine, Krista L.Mannon, Roslyn B.2020-04-22T13:45:16-07:00doi:10.34067/KID.0001172020hwp:resource-id:kidney360;1/6/557American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, access, advocacy, compensation, donor, organs, transplantPerspectivesPerspectivesresearch-article20202020-06-2510.34067/KID.00011720202641-76502020-04-22T13:45:16-07:002020-06-25Kidney360Perspectives16557560
- Setting Up and Expanding a Home Dialysis Program: Is There a Recipe for Success?Home dialysis modalities remain significantly underused in the United States despite similar overall survival in the modalities, and recent incentives to expand these modalities. Although the absolute number of patients using home modalities has grown, the proportion compared to in-center hemodialysis (ICHD) continues to remain quite low. Well known barriers to home dialysis utilization exist, and an organized and team-based approach is required to overcome these barriers. Herein, we describe our efforts at growing our home dialysis program at a large academic medical center, with the proportion of home dialysis patients growing from 12% to 21% over the past 9 years. We prioritized individualized education for patients and better training for physicians, with the help of existing resources, aimed at better utilization of home modalities; an example includes dedicated dialysis education classes taught twice monthly by an experienced nurse practitioner, as well as the utilization of the dialysis educator from a dialysis provider for inpatient education of patients with CKD. The nephrology fellowship curriculum was restructured with emphasis on home modalities, and participation in annual home dialysis conferences has been encouraged. For timely placement and troubleshooting of access for dialysis, we followed a complementary team approach using surgeons and interventional radiologists and nephrologists, driven by a standardized protocol developed at UAB, and comanaged by our access coordinators. A team-based approach, with emphasis on staff engagement and leadership opportunities for dialysis nurses as well as collaborative efforts from a team of clinical nephrologists and the dialysis provider helped maintain efficiency, kindle growth, and provide consistently high-quality clinical care in the home program. Lastly, efforts at reducing burden of disease such as decreased number of monthly visits as well as using innovative strategies, such as telenephrology and assisted PD and HHD, were instrumental in reducing attrition.10.34067/KID.0000662019Fri, 01 May 2020 01:31:00 GMT-07:00Setting Up and Expanding a Home Dialysis Program: Is There a Recipe for Success?Home dialysis modalities remain significantly underused in the United States despite similar overall survival in the modalities, and recent incentives to expand these modalities. Although the absolute number of patients using home modalities has grown, the proportion compared to in-center hemodialysis (ICHD) continues to remain quite low. Well known barriers to home dialysis utilization exist, and an organized and team-based approach is required to overcome these barriers. Herein, we describe our efforts at growing our home dialysis program at a large academic medical center, with the proportion of home dialysis patients growing from 12% to 21% over the past 9 years. We prioritized individualized education for patients and better training for physicians, with the help of existing resources, aimed at better utilization of home modalities; an example includes dedicated dialysis education classes taught twice monthly by an experienced nurse practitioner, as well as the utilization of the dialysis educator from a dialysis provider for inpatient education of patients with CKD. The nephrology fellowship curriculum was restructured with emphasis on home modalities, and participation in annual home dialysis conferences has been encouraged. For timely placement and troubleshooting of access for dialysis, we followed a complementary team approach using surgeons and interventional radiologists and nephrologists, driven by a standardized protocol developed at UAB, and comanaged by our access coordinators. A team-based approach, with emphasis on staff engagement and leadership opportunities for dialysis nurses as well as collaborative efforts from a team of clinical nephrologists and the dialysis provider helped maintain efficiency, kindle growth, and provide consistently high-quality clinical care in the home program. Lastly, efforts at reducing burden of disease such as decreased number of monthly visits as well as using innovative strategies, such as telenephrology and assisted PD and HHD, were instrumental in reducing attrition.Ahmad, MasoodWallace, Eric L.Jain, Gaurav2020-05-01T13:31:00-07:00doi:10.34067/KID.0000662019hwp:resource-id:kidney360;1/6/569American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, barriers to home dialysis, home dialysis, home dialysis academy, home hemodialysis, modality education, peritoneal dialysis, telenephrology, urgent peritoneal dialysisReview ArticleReview Articlereview-article20202020-06-2510.34067/KID.00006620192641-76502020-05-01T13:31:00-07:002020-06-25Kidney360Review Article16569579
- ARHGEF7 (β-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function10.1681/ASN.2019090982Wed, 18 Mar 2020 10:07:58 GMT-07:00ARHGEF7 (β-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular FunctionMatsuda, JunMaier, MirelaAoudjit, LamineBaldwin, CindyTakano, Tomoko2020-03-18T10:07:58-07:00doi:10.1681/ASN.2019090982hwp:resource-id:jnephrol;31/5/996American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyapoptosis, ARHGEF7 (β-PIX), Cdc42, podocyte, small Rho GTPase, yes-associated protein (YAP)Basic ResearchBasic Researchresearch-article20202020-05-01May 202010.1681/ASN.20190909821046-66731533-34502020-03-18T10:07:58-07:002020-05Journal of the American Society of NephrologyBasic Research3159961008
- The Value of Intravenous Iron: Beyond the Cave of Speculation10.1681/ASN.2019121340Mon, 06 Apr 2020 08:53:55 GMT-07:00The Value of Intravenous Iron: Beyond the Cave of SpeculationCoyne, Daniel W.Fishbane, Steven2020-04-06T08:53:55-07:00doi:10.1681/ASN.2019121340hwp:resource-id:jnephrol;31/5/896American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, Hemodialysis hazards, infection, cardiovascular eventsUp Front MattersEditorialsUp Front MattersEditorialseditorial20202020-05-01May 202010.1681/ASN.20191213401046-66731533-34502020-04-06T08:53:55-07:002020-05Journal of the American Society of NephrologyUp Front Matters315589611188971127
- Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis10.1681/ASN.2019070712Fri, 20 Mar 2020 07:40:36 GMT-07:00Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for CystinosisHollywood, Jennifer A.Przepiorski, AnetaD’Souza, Randall F.Sreebhavan, SreevalsanWolvetang, Ernst J.Harrison, Patrick T.Davidson, Alan J.Holm, Teresa M.2020-03-20T07:40:36-07:00doi:10.1681/ASN.2019070712hwp:resource-id:jnephrol;31/5/962American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyinduced pluripotent stem cells, kidney organoids, new treatments, kidney disease, cystinosisBasic ResearchBasic Researchresearch-article20202020-05-01May 202010.1681/ASN.20190707121046-66731533-34502020-03-20T07:40:36-07:002020-05Journal of the American Society of NephrologyBasic Research315962982
- Biomarkers of CKD in Children10.1681/ASN.2020020212Tue, 31 Mar 2020 09:03:01 GMT-07:00Biomarkers of CKD in ChildrenAl-Aly, ZiyadBowe, Benjamin2020-03-31T09:03:01-07:00doi:10.1681/ASN.2020020212hwp:resource-id:jnephrol;31/5/894American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, children, biomarkers, TNF receptor-1, soluble urokinase-type plasminogen activator receptor, kidney injury molecule 1Up Front MattersEditorialsUp Front MattersEditorialseditorial20202020-05-01May 202010.1681/ASN.20200202121046-66731533-34502020-03-31T09:03:01-07:002020-05Journal of the American Society of NephrologyUp Front Matters315589410678961077
- Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial10.1681/ASN.2019111168Thu, 30 Apr 2020 10:00:30 GMT-07:00Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized TrialJardine, Meg J.Zhou, ZienMahaffey, Kenneth W.Oshima, MegumiAgarwal, RajivBakris, GeorgeBajaj, Harpreet S.Bull, ScottCannon, Christopher P.Charytan, David M.de Zeeuw, DickDi Tanna, Gian LucaGreene, TomHeerspink, Hiddo J.L.Levin, AdeeraNeal, BrucePollock, CarolQiu, RoseSun, TaoWheeler, David C.Zhang, HongZinman, BernardRosenthal, NormanPerkovic, Vlado,Guerrero, Rodolfo Andres AhuadAizenberg, DiegoAlbisu, Juan PabloAlvarisqueta, AndresBartolacci, InesBerli, Mario AlbertoBordonava, AnselmoCalella, PedroCantero, Maria CeciliaCartasegna, Luis RodolfoCercos, EstebanColoma, Gabriela CeciliaColombo, HugoCommendatore, VictorCuadrado, JesusCuneo, Carlos AlbertoCusumano, Ana MariaDouthat, Walter GuillermoDran, Ricardo DarioFarias, EduardoFernandez, Maria FlorenciaFinkelstein, HernanFragale, GuillermoFretes, Jose OsvaldoGarcia, Nestor HoracioGastaldi, AnibalGelersztein, ElizabethGlenny, Jorge ArchibaldoGonzalez, Joaquin PabloColaso, Patricia del Carmen GonzalezGoycoa, ClaudiaGreloni, Gustavo CristianGuinsburg, AdrianHermida, SoniaJuncos, Luis IsaiasValdez, MariaKraft, FlorenciaKrynski, FernandoLanchiotti, Paulina VirginiaLeon de la Fuente, Ricardo AlfonsoMarchetta, NoraMele, PabloNicolai, SilviaNovoa, Pablo AntonioOrio, Silvia InesOtreras, FabianOviedo, AlejandraRaffaele, PabloResk, Jorge HectorRista, LucasPapini, Nelson RodriguezSala, JorgelinaSantos, Juan CarlosSchiavi, Lilia BeatrizSessa, HoracioCasabella, Tomas SmithUlla, Maria RosaVallejos, AugustoVillarino, AdrianaVisco, Virginia EstherWassermann, AlfredoZaidman, Cesar JavierCheung, Ngai WahDroste, CarolynFraser, IanJohnson, DavidMah, Peak MannNicholls, KathyPackham, DavidProietto, JosephRoberts, AnthonyRoger, SimonTsang, VenessaRaduan, Roberto AbrãoAlves da Costa, Fernando AugustoAmodeo, CelsoTuratti, Luiz Alberto AndreottiBregman, RachelCamelo Sanches, Fernanda CristinaCanani, Luis HenriqueChacra, Antônio RobertoCunha Borges, João LindolfoVêncio, Sérgio Alberto Cunhada Silva Franco, Roberto Jorged’Avila, Domingosde Souza Portes, Evandrode Souza, PedroDeboni, Luciane MônicaFilho, Fadlo FraigeNeto, Bruno GelonezeGomes, MarcusKohara, Suely KeikoKeitel, ElizeteSaraiva, Jose Francisco KerrKurtz Lisboa, Hugo Robertode Carvalho Contieri, Fabiana LossMilagres, RosângelaJunior, Renan MontenegroMoreira de Brito, ClaudiaHissa, Miguel NasserSabbag, Ângela Regina NazarioNoronha, IrenePanarotto, DanielFilho, Roberto PecoitsPereira, Márcio AntônioSaporito, WladmirScotton, Antonio ScafutoSchuch, TiagoSimões de Almeida, RobertoRamos, Cássio SlompoFelício, João SoaresThomé, FernandoTibes Hachmann, Jean CarloYamada, SérgioHayashida, Cesar YoitiPetry, Tarissa 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HermannJerwan-Keim, ReinholdMaxeiner, StephanPaschen, BjörnPlassmann, GeorgRose, LudgerGonzalez Orellana, Ronaldo ArturoHaase, Franklin PaulMoreira Diaz, Juan PabloRamirez Roca, Luis AlbertoSánchez Arenales, Jose AntonioSanchez Polo, José VicenteJuarez, Erick TurciosCsecsei, GyongyiCsiky, BotondDanos, PeterDeak, LaszloDudas, MihalyHarcsa, EleonoraKeltai, KatalinKeresztesi, SandorKiss, KrisztianKonyves, LaszloMajor, LajosMileder, MargitMolnar, MartaMucsi, JanosOroszlan, TamasOry, IvanParagh, GyorgyPeterfai, EvaPetro, GizellaRevesz, KatalinTakacs, RobertVangel, SandorVasas, SzilardZsom, MariannaAbraham, OommanBhushan, Raju SreeDeepak, DewanEdwin, Fernando M.Gopalakrishnan, NatarajanGracious, NobleHansraj, AlvaJain, DineshKeshavamurthy, C. 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Dovie LallaineBijata-Bronisz, RenataHotlos, LucynaJanuszewicz, AndrzejKaczmarek, BarbaraKaminska, AnnaLazuka, LechMadej, AndrzejMazur, StanislawMlodawska-Choluj, DorotaNowicki, MichalOrlowska-Kowalik, GrazynaPopenda, GrazynaRewerska, BarbaraSowinski, DariuszAngelescu, Liliana MonicaAnghel, VeronicaAvram, Rodica-IoanaBusegeanu, Mihaela-MagdalenaCif, AdrianaCosma, DanaCrisan, CarmenDemian, Luiza DespinaFerariu, Ioana EmiliaHalmagyi, IldikoHancu, NicolaeMunteanu, MirceaNegru, DoruOnaca, Adriana GabrielaPetrica, LigiaPopa, Amorin RemusRanetti, Aurelian-EmilSerafinceanu, CristianToarba, CristinaAgafyina, AlinaBarbarash, OlgaBarysheva, OlgaChizhov, DaniilDobronravov, VladimirDreval, AlexanderGlinkina, IrinaGrineva, ElenaKhirmanov, VladimirKolmakova, ElenaKoroleva, TatianaKvitkova, LiudmilaMarasaev, ViacheslavMkrtumyan, AshotMorugova, TatianaNagibovich, GalinaNagibovich, OlegNedogoda, SergeiOsipova, IrinaRaskina, TatianaSamoylova, YuliaSazonova, OlgaShamkhalova, MinaraShutemova, ElenaShwartz, 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- A Patient’s Perspective on Benzodiazepines, Co-Dispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center Hemodialysis10.2215/CJN.05150420Tue, 26 May 2020 02:18:37 GMT-07:00A Patient’s Perspective on Benzodiazepines, Co-Dispensed Opioids, and Mortality among Patients Initiating Long-Term In-Center HemodialysisThomas, Cher2020-05-26T14:18:37-07:00doi:10.2215/CJN.05150420hwp:resource-id:clinjasn;15/6/743American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybenzodiazepines, opioids, hemodialysis, analgesics, opioid, renal dialysis, drug prescriptionsPatient VoicePatient Voiceresearch-article20202020-06-08June 08, 202010.2215/CJN.051504201555-90411555-905X2020-05-26T14:18:37-07:002020-06-08Clinical Journal of the American Society of NephrologyPatient Voice1566743794744804
- Donor Characteristics and Short-Term Kidney Allograft Outcomes10.2215/CJN.05850420Wed, 13 May 2020 07:48:47 GMT-07:00Donor Characteristics and Short-Term Kidney Allograft OutcomesFriedewald, John J.Ho, Bing2020-05-13T07:48:47-07:00doi:10.2215/CJN.05850420hwp:resource-id:clinjasn;15/6/750American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydelayed graft function, ischemia, transplant outcomes, Tissue Donors, AllograftsEditorialsEditorialseditorial20202020-06-08June 08, 202010.2215/CJN.058504201555-90411555-905X2020-05-13T07:48:47-07:002020-06-08Clinical Journal of the American Society of NephrologyEditorials1566750813751821
- Can COMBINED Magnetic Resonance Imaging Measure the Progression of Kidney Disease?10.2215/CJN.04430420Tue, 28 Apr 2020 06:21:15 GMT-07:00Can COMBINED Magnetic Resonance Imaging Measure the Progression of Kidney Disease?Pruijm, Menno2020-04-28T06:21:15-07:00doi:10.2215/CJN.04430420hwp:resource-id:clinjasn;15/6/747American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, outcomes, magnetic resonance imaging, biomarker, Renin, Angiotensins, Sodium-Glucose Transporter 2 Inhibitors, Renal Insufficiency, Chronic, Renal Insufficiency, Disease Progression, Magnetic Resonance ImagingEditorialsEditorialseditorial20202020-06-08June 08, 202010.2215/CJN.044304201555-90411555-905X2020-04-28T06:21:15-07:002020-06-08Clinical Journal of the American Society of NephrologyEditorials1566747776749783
- Intradialytic Hypotension and Cardiac Arrhythmias in Patients Undergoing Maintenance Hemodialysis10.2215/CJN.06810619Thu, 07 May 2020 05:34:27 GMT-07:00Intradialytic Hypotension and Cardiac Arrhythmias in Patients Undergoing Maintenance HemodialysisMc Causland, Finnian R.Tumlin, Jim A.Roy-Chaudhury, PrabirKoplan, Bruce A.Costea, Alexandru I.Kher, VijayWilliamson, DonPokhariyal, SaurabhCharytan, David M.,2020-05-07T05:34:27-07:00doi:10.2215/CJN.06810619hwp:resource-id:clinjasn;15/6/805American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, cardiovascular disease, Bradycardia, Incidence, Arrhythmias, , Cardiac Conduction System Disease, hypotension, Tachycardia, VentricularOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20202020-06-08June 08, 202010.2215/CJN.068106191555-90411555-905X2020-05-07T05:34:27-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles156805812
- Management of Active Surveillance-Eligible Prostate Cancer during Pretransplantation Workup of Patients with Kidney Failure: A Simulation Study10.2215/CJN.14041119Thu, 07 May 2020 05:34:27 GMT-07:00Management of Active Surveillance-Eligible Prostate Cancer during Pretransplantation Workup of Patients with Kidney Failure: A Simulation StudyBieri, UweHübel, KerstinSeeger, HaraldKulkarni, Girish S.Sulser, TullioHermanns, ThomasWettstein, Marian S.2020-05-07T05:34:27-07:00doi:10.2215/CJN.14041119hwp:resource-id:clinjasn;15/6/822American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, quality-adjusted life years, life expectancy, quality of life, kidney transplantation, watchful waiting, calibration, expert testimony, renal insufficiency, prostatic neoplasms, cohort studies, dialysis, contraindicationsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-06-08June 08, 202010.2215/CJN.140411191555-90411555-905X2020-05-07T05:34:27-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles156822829
- Environmental Risks to Kidney Health10.2215/CJN.05290420Fri, 22 May 2020 05:48:44 GMT-07:00Environmental Risks to Kidney HealthKaufman, James S.2020-05-22T05:48:44-07:00doi:10.2215/CJN.05290420hwp:resource-id:clinjasn;15/6/745American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney, risk assessmentEditorialsEditorialseditorial20202020-06-08June 08, 202010.2215/CJN.052904201555-90411555-905X2020-05-22T05:48:44-07:002020-06-08Clinical Journal of the American Society of NephrologyEditorials1566745766746775
- Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical PracticeThe Kidney Disease: Improving Global Outcomes (KDIGO) 2017 “Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors” was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a “proof-of-concept” risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate’s profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.10.2215/CJN.12141019Fri, 10 Apr 2020 09:20:11 GMT-07:00Application of the 2017 KDIGO Guideline for the Evaluation and Care of Living Kidney Donors to Clinical PracticeThe Kidney Disease: Improving Global Outcomes (KDIGO) 2017 “Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors” was developed to assist medical professionals who evaluate living kidney donor candidates and provide care before, during, and after donation. This guideline Work Group concluded that a comprehensive approach to donor candidate risk assessment should replace eligibility decisions on the basis of assessments of single risk factors in isolation. To address all issues important to living donors in a pragmatic and comprehensive guideline, many of the guideline recommendations were on the basis of expert consensus opinion even when no direct evidence was available. To advance available evidence, original data analyses were also undertaken to produce a “proof-of-concept” risk projection model for kidney failure. This was done to illustrate how the community can advance a new quantitative framework of risk that considers each candidate’s profile of demographic and health characteristics. A public review by stakeholders and subject matter experts as well as industry and professional organizations informed the final formulation of the guideline. This review highlights the guideline framework, key concepts, and recommendations, and uses five patient scenarios and 12 guideline statements to illustrate how the guideline can be applied to support living donor evaluation and care in clinical practice.Garg, Amit X.Levey, Andrew S.Kasiske, Bertram L.Cheung, MichaelLentine, Krista L.,2020-04-10T09:20:11-07:00doi:10.2215/CJN.12141019hwp:resource-id:clinjasn;15/6/896American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDonor nephrectomy, Living donation, Patient-centered care, Risks, Guideline, risk factors, Living Donors, kidney transplantation, Consensus, Data Analysis, Kidney Diseases, Risk Assessment, Renal Insufficiency, kidney, DemographyFeaturesFeaturesresearch-article20202020-06-08June 08, 202010.2215/CJN.121410191555-90411555-905X2020-04-10T09:20:11-07:002020-06-08Clinical Journal of the American Society of NephrologyFeatures156896905
- The Effects of Intensive Blood Pressure Lowering on Markers of Mineral Metabolism in Persons with CKD in SPRINT10.2215/CJN.01400220Wed, 06 May 2020 04:57:17 GMT-07:00The Effects of Intensive Blood Pressure Lowering on Markers of Mineral Metabolism in Persons with CKD in SPRINTGinsberg, CharlesKatz, RonitChonchol, Michel B.Bullen, Alexander L.Raphael, Kalani L.Zhang, William R.Ambrosius, Walter T.Bates, Jeffrey T.Neyra, Javier A.Killeen, Anthony A.Punzi, HenryShlipak, Michael G.Ix, Joachim H.2020-05-06T04:57:17-07:00doi:10.2215/CJN.01400220hwp:resource-id:clinjasn;15/6/852American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hypertension, mineral metabolism, calcium, blood pressure, Biomarkers, Renal Insufficiency, Chronic, Minerals, Antihypertensive AgentsResearch LetterResearch Letterresearch-article20202020-06-08June 08, 202010.2215/CJN.014002201555-90411555-905X2020-05-06T04:57:17-07:002020-06-08Clinical Journal of the American Society of NephrologyResearch Letter156852854
- Environment-Wide Association Study of CKD10.2215/CJN.06780619Fri, 22 May 2020 09:48:27 GMT-07:00Environment-Wide Association Study of CKDLee, JeonghwanOh, SoheeKang, HabyeongKim, SunmiLee, GowoonLi, LilinKim, Clara TammyAn, Jung NamOh, Yun KyuLim, Chun SooKim, Dong KiKim, Yon SuChoi, KyunghoLee, Jung Pyo2020-05-22T09:48:27-07:00doi:10.2215/CJN.06780619hwp:resource-id:clinjasn;15/6/766American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyenvironmental chemicals, chronic kidney disease, glomerular filtration rate, lead, cadmium, volatile organic compounds, perfluorooctanoic acid, albuminuria, phenylglyoxylic acid, Cotinine, Thiocyanates, Volatile Organic Compounds, creatinine, Polycyclic Aromatic Hydrocarbons, risk factors, Caprylates, Fluorocarbons, Renal Insufficiency, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-06-08June 08, 202010.2215/CJN.067806191555-90411555-905X2020-05-22T09:48:27-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles1566766745775746
- Low Serum Bicarbonate and CKD Progression in Children10.2215/CJN.07060619Thu, 28 May 2020 03:00:08 GMT-07:00Low Serum Bicarbonate and CKD Progression in ChildrenBrown, Denver D.Roem, JenniferNg, Derek K.Reidy, Kimberly J.Kumar, JuhiAbramowitz, Matthew K.Mak, Robert H.Furth, Susan L.Schwartz, George J.Warady, Bradley A.Kaskel, Frederick J.Melamed, Michal L.2020-05-28T15:00:08-07:00doi:10.2215/CJN.07060619hwp:resource-id:clinjasn;15/6/755American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic metabolic acidosis, pediatrics, renal progression, bicarbonates, phosphates, alkalis, renal insufficiency, chronic, longitudinal studies, proteinuria, glomerular filtration rate, renal replacement therapy, anemia, acidosis, hypertension, demographyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-06-08June 08, 202010.2215/CJN.070606191555-90411555-905X2020-05-28T15:00:08-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles156755765
- Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD10.2215/CJN.13201019Tue, 28 Apr 2020 06:21:14 GMT-07:00Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKDSrivastava, AnandCai, XuanLee, JungwhaLi, WeiLarive, BrettKendrick, CynthiaGassman, Jennifer J.Middleton, John P.Carr, JamesRaphael, Kalani L.Cheung, Alfred K.Raj, Dominic S.Chonchol, Michel B.Fried, Linda F.Block, Geoffrey A.Sprague, Stuart M.Wolf, MylesIx, Joachim H.Prasad, Pottumarthi V.Isakova, Tamara2020-04-28T06:21:14-07:00doi:10.2215/CJN.13201019hwp:resource-id:clinjasn;15/6/776American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMRI, hypoxia, fibrosis, chronic kidney disease, ESRD, glomerular filtration rate, lanthanum carbonate, albuminuria, Niacinamide, Follow-Up Studies, Diffusion Magnetic Resonance Imaging, Renal Insufficiency, Chronic, Magnetic Resonance Imaging, Lanthanum, Biomarkers, OxygenOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-06-08June 08, 202010.2215/CJN.132010191555-90411555-905X2020-04-28T06:21:14-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles1566776747783749
- Disease Modeling To Understand the Pathomechanisms of Human Genetic Kidney DisordersThe class of human genetic kidney diseases is extremely broad and heterogeneous. Accordingly, the range of associated disease phenotypes is highly variable. Many children and adults affected by inherited kidney disease will progress to ESKD at some point in life. Extensive research has been performed on various different disease models to investigate the underlying causes of genetic kidney disease and to identify disease mechanisms that are amenable to therapy. We review some of the research highlights that, by modeling inherited kidney disease, contributed to a better understanding of the underlying pathomechanisms, leading to the identification of novel genetic causes, new therapeutic targets, and to the development of new treatments. We also discuss how the implementation of more efficient genome-editing techniques and tissue-culture methods for kidney research is providing us with personalized models for a precision-medicine approach that takes into account the specificities of the patient and the underlying disease. We focus on the most common model systems used in kidney research and discuss how, according to their specific features, they can differentially contribute to biomedical research. Unfortunately, no definitive treatment exists for most inherited kidney disorders, warranting further exploitation of the existing disease models, as well as the implementation of novel, complex, human patient–specific models to deliver research breakthroughs.10.2215/CJN.08890719Thu, 05 Mar 2020 06:30:37 GMT-08:00Disease Modeling To Understand the Pathomechanisms of Human Genetic Kidney DisordersThe class of human genetic kidney diseases is extremely broad and heterogeneous. Accordingly, the range of associated disease phenotypes is highly variable. Many children and adults affected by inherited kidney disease will progress to ESKD at some point in life. Extensive research has been performed on various different disease models to investigate the underlying causes of genetic kidney disease and to identify disease mechanisms that are amenable to therapy. We review some of the research highlights that, by modeling inherited kidney disease, contributed to a better understanding of the underlying pathomechanisms, leading to the identification of novel genetic causes, new therapeutic targets, and to the development of new treatments. We also discuss how the implementation of more efficient genome-editing techniques and tissue-culture methods for kidney research is providing us with personalized models for a precision-medicine approach that takes into account the specificities of the patient and the underlying disease. We focus on the most common model systems used in kidney research and discuss how, according to their specific features, they can differentially contribute to biomedical research. Unfortunately, no definitive treatment exists for most inherited kidney disorders, warranting further exploitation of the existing disease models, as well as the implementation of novel, complex, human patient–specific models to deliver research breakthroughs.Molinari, ElisaSayer, John A.2020-03-05T06:30:37-08:00doi:10.2215/CJN.08890719hwp:resource-id:clinjasn;15/6/855American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, transgenic mouse, zebrafish, molecular geneticsGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-06-08June 08, 202010.2215/CJN.088907191555-90411555-905X2020-03-05T06:30:37-08:002020-06-08Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease156855872
- SONAR10.2215/CJN.08540719Tue, 04 Feb 2020 09:06:07 GMT-08:00SONARWalsh, Michael2020-02-04T09:06:07-08:00doi:10.2215/CJN.08540719hwp:resource-id:clinjasn;15/6/889American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyatrasentan, randomized controlled trials, diabetic nephropathy, humans, albuminuria, diabetic nephropathies, endothelin A receptor antagonists, type 2 diabetes mellitus, creatinine, nephrology, incidence, confidence intervals, endothelin A receptor, sample size, reproducibility of results, pyrrolidines, chronic renal insufficiency, chronic kidney failure, kidneyPerspectivesPerspectivesresearch-article20202020-06-08June 08, 202010.2215/CJN.085407191555-90411555-905X2020-02-04T09:06:07-08:002020-06-08Clinical Journal of the American Society of NephrologyPerspectives156889891
- Impending Shortages of Kidney Replacement Therapy for COVID-19 Patients10.2215/CJN.05180420Tue, 28 Apr 2020 06:21:15 GMT-07:00Impending Shortages of Kidney Replacement Therapy for COVID-19 PatientsGoldfarb, David S.Benstein, Judith A.Zhdanova, OlgaHammer, ElizabethBlock, Clay A.Caplin, Nina J.Thompson, NathanCharytan, David M.2020-04-28T06:21:15-07:00doi:10.2215/CJN.05180420hwp:resource-id:clinjasn;15/6/880American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, kidney replacement, hemodialysis, peritoneal dialysis, intensive care medicine, COVID-19, severe acute respiratory syndrome coronavirus 2, Renal Replacement TherapyPerspectivesPerspectivesresearch-article20202020-06-08June 08, 202010.2215/CJN.051804201555-90411555-905X2020-04-28T06:21:15-07:002020-06-08Clinical Journal of the American Society of NephrologyPerspectives156880882
- Screening for Cancer in Patients with Glomerular Diseases10.2215/CJN.09000819Tue, 04 Feb 2020 09:06:07 GMT-08:00Screening for Cancer in Patients with Glomerular DiseasesPlaisier, EmmanuelleRonco, Pierre2020-02-04T09:06:07-08:00doi:10.2215/CJN.09000819hwp:resource-id:clinjasn;15/6/886American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCancer, nephrotic syndrome, membranous nephropathy, humans, human PLA2R1 protein, phospholipase A2 receptors, membranoproliferative glomerulonephritis, nephrologists, immunosuppressive agents, risk factors, nephrology, cost-benefit analysis, early detection of cancer, follow-up studies, kidney, recurrence, phospholipases A2, cytosolic phospholipases A2, treatment failure, thrombospondins, neoplasmsPerspectivesPerspectivesresearch-article20202020-06-08June 08, 202010.2215/CJN.090008191555-90411555-905X2020-02-04T09:06:07-08:002020-06-08Clinical Journal of the American Society of NephrologyPerspectives156886888
- How COVID-19 Has Changed the Management of Glomerular Diseases10.2215/CJN.04530420Fri, 24 Apr 2020 04:43:33 GMT-07:00How COVID-19 Has Changed the Management of Glomerular DiseasesBomback, Andrew S.Canetta, Pietro A.Ahn, WooinAhmad, Syeda B.Radhakrishnan, JaiAppel, Gerald B.2020-04-24T04:43:33-07:00doi:10.2215/CJN.04530420hwp:resource-id:clinjasn;15/6/876American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, immunosuppression, COVID-19, severe acute respiratory syndrome coronavirus 2, kidney diseasesPerspectivesPerspectivesresearch-article20202020-06-08June 08, 202010.2215/CJN.045304201555-90411555-905X2020-04-24T04:43:33-07:002020-06-08Clinical Journal of the American Society of NephrologyPerspectives156876879
- Chronicle of a Death Foretold10.2215/CJN.09390819Fri, 21 Feb 2020 07:05:01 GMT-08:00Chronicle of a Death ForetoldRifkin, Dena E.2020-02-21T07:05:01-08:00doi:10.2215/CJN.09390819hwp:resource-id:clinjasn;15/6/883American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymortality risk, study design, male, humans, conservative treatment, epidemiologists, hospice care, terminal care, kidney, chronic kidney failure, bias, neoplasmsPerspectivesPerspectivesresearch-article20202020-06-08June 08, 202010.2215/CJN.093908191555-90411555-905X2020-02-21T07:05:01-08:002020-06-08Clinical Journal of the American Society of NephrologyPerspectives156883885
- Association of Socioeconomic Status and Comorbidities with Racial Disparities during Kidney Transplant Evaluation10.2215/CJN.12541019Thu, 07 May 2020 05:34:26 GMT-07:00Association of Socioeconomic Status and Comorbidities with Racial Disparities during Kidney Transplant EvaluationMurphy, Karly A.Jackson, John W.Purnell, Tanjala S.Shaffer, Ashton A.Haugen, Christine E.Chu, Nadia M.Crews, Deidra C.Norman, Silas P.Segev, Dorry L.McAdams-DeMarco, Mara A.2020-05-07T05:34:26-07:00doi:10.2215/CJN.12541019hwp:resource-id:clinjasn;15/6/843American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, end stage kidney disease, kidney transplantation, risk factors, Incidence, Prospective Studies, African Americans, Social Class, Continental Population Groups, Renal Insufficiency, Employment, Comorbidity, Cohort StudiesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-06-08June 08, 202010.2215/CJN.125410191555-90411555-905X2020-05-07T05:34:26-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles156843851
- Inequity in Access to Transplantation in the United Kingdom10.2215/CJN.11460919Thu, 28 May 2020 03:00:07 GMT-07:00Inequity in Access to Transplantation in the United KingdomPruthi, RishiRobb, Matthew L.Oniscu, Gabriel C.Tomson, CharlesBradley, AndrewForsythe, John L.Metcalfe, WendyBradley, ClareDudley, ChristopherJohnson, Rachel J.Watson, ChristopherDraper, HeatherFogarty, DamianRavanan, RommelRoderick, Paul J.,2020-05-28T15:00:07-07:00doi:10.2215/CJN.11460919hwp:resource-id:clinjasn;15/6/830American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, Epidemiology and outcomes, ethnicity, kidney transplantation, inequity, socio-economic deprivation, transplant waiting list, renal dialysis, Ethnic Groups, Minority Groups, Universal Health Care, Cohort Studies, Body Mass Index, Prospective Studies, Social Class, Renal Replacement Therapy, African Americans, Diagnosis-Related Groups, Outcome Assessment, Health CareOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20202020-06-08June 08, 202010.2215/CJN.114609191555-90411555-905X2020-05-28T15:00:07-07:002020-06-08Clinical Journal of the American Society of NephrologyOriginal Articles1566830752842754
- A Case of Nephrotic Syndrome after Allogeneic Stem Cell Transplantation10.2215/CJN.00100120Fri, 06 Mar 2020 07:58:10 GMT-08:00A Case of Nephrotic Syndrome after Allogeneic Stem Cell TransplantationHogan, Jonathan J.2020-03-06T07:58:10-08:00doi:10.2215/CJN.00100120hwp:resource-id:clinjasn;15/6/873American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyidiopathic nephrotic syndrome, onconephrology, minimal change disease, glomerular disease, nephrotic syndrome, Hematopoietic Stem Cell, TransplantationKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20202020-06-08June 08, 202010.2215/CJN.001001201555-90411555-905X2020-03-06T07:58:10-08:002020-06-08Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire156873875
- Outpatient Management of the Kidney Transplant Recipient during the SARS-CoV-2 Virus Pandemic10.2215/CJN.04510420Tue, 28 Apr 2020 06:21:15 GMT-07:00Outpatient Management of the Kidney Transplant Recipient during the SARS-CoV-2 Virus PandemicGleeson, Shana E.Formica, Richard N.Marin, Ethan P.2020-04-28T06:21:15-07:00doi:10.2215/CJN.04510420hwp:resource-id:clinjasn;15/6/892American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunosuppression, virology, COVID-19, SARS Virus, Cough, Pandemics, Public Health, Outpatients, Oxygen, kidney transplantation, Physical Exertion, severe acute respiratory syndrome coronavirus 2, Severe Acute Respiratory Syndrome, Fever, Patient Care, Dyspnea, Cytomegalovirus InfectionsFeaturesFeaturesother20202020-06-08June 08, 202010.2215/CJN.045104201555-90411555-905X2020-04-28T06:21:15-07:002020-06-08Clinical Journal of the American Society of NephrologyFeatures156892895
- Will Universal Access to Health Care Mean Equitable Access to Kidney Transplantation?10.2215/CJN.03000320Thu, 28 May 2020 03:00:08 GMT-07:00Will Universal Access to Health Care Mean Equitable Access to Kidney Transplantation?Harhay, Meera N.Mark, Patrick B.2020-05-28T15:00:08-07:00doi:10.2215/CJN.03000320hwp:resource-id:clinjasn;15/6/752American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, healthcare, disparities, Health Services, Accessibility, Healthcare DisparitiesEditorialsEditorialseditorial20202020-06-08June 08, 202010.2215/CJN.030003201555-90411555-905X2020-05-28T15:00:08-07:002020-06-08Clinical Journal of the American Society of NephrologyEditorials1566752830754842
- ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment10.1681/ASN.2019070756Thu, 07 May 2020 10:08:18 GMT-07:00ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid TreatmentWidmeier, EugenYu, SeyoungNag, AnishChung, Youn WookNakayama, MakikoFernández-del-Río, LucíaHugo, HannahSchapiro, DavidBuerger, FlorianChoi, Won-IlHelmstädter, MartinKim, Jae-wooRyu, Ji-HwanLee, Min GooClarke, Catherine F.Hildebrandt, FriedhelmGee, Heon Yung2020-05-07T10:08:18-07:00doi:10.1681/ASN.2019070756hwp:resource-id:jnephrol;31/6/1191American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyADCK4, steroid-resistant nephrotic syndrome, coenzyme Q10, Q complex, 2,4-dihydroxybenzoic acidBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20190707561046-66731533-34502020-05-07T10:08:18-07:002020-06Journal of the American Society of NephrologyBasic Research31661191116712111169
- Incident Chronic Kidney Disease Risk among Hispanics/Latinos in the United States: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)10.1681/ASN.2019101008Thu, 16 Apr 2020 06:18:00 GMT-07:00Incident Chronic Kidney Disease Risk among Hispanics/Latinos in the United States: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)Ricardo, Ana C.Loop, Matthew ShaneGonzalez, FranklynLora, Claudia M.Chen, JinsongFranceschini, NoraKramer, Holly J.Toth-Manikowski, Stephanie M.Talavera, Gregory A.Daviglus, MarthaLash, James P.2020-04-16T06:18:00-07:00doi:10.1681/ASN.2019101008hwp:resource-id:jnephrol;31/6/1315American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, clinical epidemiology, risk factorsClinical EpidemiologyClinical Epidemiologyresearch-article20202020-06-01June 202010.1681/ASN.20191010081046-66731533-34502020-04-16T06:18:00-07:002020-06Journal of the American Society of NephrologyClinical Epidemiology31613151324
- Quantitative Proteomics of All 14 Renal Tubule Segments in Rat10.1681/ASN.2020010071Fri, 01 May 2020 07:53:50 GMT-07:00Quantitative Proteomics of All 14 Renal Tubule Segments in RatLimbutara, KaveeChou, Chung-LinKnepper, Mark A.2020-05-01T07:53:50-07:00doi:10.1681/ASN.2020010071hwp:resource-id:jnephrol;31/6/1255American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney tubule, Mass spectrometry, Database, Systems BiologyBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20200100711046-66731533-34502020-05-01T07:53:50-07:002020-06Journal of the American Society of NephrologyBasic Research31612551266
- Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids10.1681/ASN.2019090904Tue, 05 May 2020 05:45:03 GMT-07:00Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and GabapentinoidsVangala, ChandanNiu, JingboMontez-Rath, Maria E.Yan, JingyinNavaneethan, Sankar D.Naik, Aanand D.Winkelmayer, Wolfgang C.2020-05-05T05:45:03-07:00doi:10.1681/ASN.2019090904hwp:resource-id:jnephrol;31/6/1325American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyUnited States Renal Data System, clinical epidemiology, mineral metabolismClinical EpidemiologyClinical Epidemiologyresearch-article20202020-06-01June 202010.1681/ASN.20190909041046-66731533-34502020-05-05T05:45:03-07:002020-06Journal of the American Society of NephrologyClinical Epidemiology31613251334
- Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney10.1681/ASN.2019090962Thu, 07 May 2020 10:08:17 GMT-07:00Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult KidneyLaszczyk, Ann M.Higashi, Atsuko Y.Patel, Sanjeevkumar R.Johnson, Craig N.Soofi, AbdulAbraham, SajiDressler, Gregory R.2020-05-07T10:08:17-07:00doi:10.1681/ASN.2019090962hwp:resource-id:jnephrol;31/6/1212American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCell & Transport Physiology, diabetes insipidus, genetics and development, osmolality, renal epithelial cell, water channelsBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20190909621046-66731533-34502020-05-07T10:08:17-07:002020-06Journal of the American Society of NephrologyBasic Research31612121225
- Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted Tubule10.1681/ASN.2019090923Wed, 15 Apr 2020 09:19:02 GMT-07:00Renal Tubule Nedd4-2 Deficiency Stimulates Kir4.1/Kir5.1 and Thiazide-Sensitive NaCl Cotransporter in Distal Convoluted TubuleWu, PengSu, Xiao-TongGao, Zhong-XiuziZhang, Dan-DanDuan, Xin-PengXiao, YuStaub, OlivierWang, Wen-HuiLin, Dao-Hong2020-04-15T09:19:02-07:00doi:10.1681/ASN.2019090923hwp:resource-id:jnephrol;31/6/1226American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologypotassium channels, renal tubular epithelial cells, Cell Signaling, Cell and Transport Physiology, hypokalemiaBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20190909231046-66731533-34502020-04-15T09:19:02-07:002020-06Journal of the American Society of NephrologyBasic Research31612261242
- Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis10.1681/ASN.2019121285Thu, 16 Apr 2020 06:18:00 GMT-07:00Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus NephritisMejia-Vilet, Juan M.Zhang, Xiaolan L.Cruz, CristinoCano-Verduzco, Mayra L.Shapiro, John P.Nagaraja, Haikady N.Morales-Buenrostro, Luis E.Rovin, Brad H.2020-04-16T06:18:00-07:00doi:10.1681/ASN.2019121285hwp:resource-id:jnephrol;31/6/1335American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologysoluble CD163, CD163 receptor, lupus nephritis, biomarkers, systemic lupus erythematosus, macrophagesClinical ResearchClinical Researchresearch-article20202020-06-01June 202010.1681/ASN.20191212851046-66731533-34502020-04-16T06:18:00-07:002020-06Journal of the American Society of NephrologyClinical Research31613351347
- A Time-Updated, Parsimonious Model to Predict AKI in Hospitalized Children10.1681/ASN.2019070745Thu, 07 May 2020 10:08:17 GMT-07:00A Time-Updated, Parsimonious Model to Predict AKI in Hospitalized ChildrenSandokji, IbrahimYamamoto, YuBiswas, AdityaArora, TanimaUgwuowo, UgochukwuSimonov, MichaelSaran, IshanMartin, MelissaTestani, Jeffrey M.Mansour, SherryMoledina, Dennis G.Greenberg, Jason H.Wilson, F. Perry2020-05-07T10:08:17-07:00doi:10.1681/ASN.2019070745hwp:resource-id:jnephrol;31/6/1348American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, pediatrics, electronic health records, risk, feature selectionClinical ResearchClinical Researchresearch-article20202020-06-01June 202010.1681/ASN.20190707451046-66731533-34502020-05-07T10:08:17-07:002020-06Journal of the American Society of NephrologyClinical Research31613481357
- A Deregulated Stress Response Underlies Distinct INF2-Associated Disease Profiles10.1681/ASN.2019111174Fri, 22 May 2020 05:50:33 GMT-07:00A Deregulated Stress Response Underlies Distinct INF2-Associated Disease ProfilesBayraktar, SametNehrig, JulianMenis, EkaterinaKarli, KevserJanning, AnnetteStruk, ThaddäusHalbritter, JanMichgehl, UlfKrahn, Michael P.Schuberth, Christian E.Pavenstädt, HermannWedlich-Söldner, Roland2020-05-22T05:50:33-07:00doi:10.1681/ASN.2019111174hwp:resource-id:jnephrol;31/6/1296American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyactin, INF2, CaAR, focal segmental glomerulosclerosis, imagingBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20191111741046-66731533-34502020-05-22T05:50:33-07:002020-06Journal of the American Society of NephrologyBasic Research31612961313
- Mitochondria Matter: A Critical Role of ADCK4 in Stabilizing the CoQ Complex in Podocytes in Steroid-Resistant Nephrotic Syndrome10.1681/ASN.2020040467Thu, 07 May 2020 10:08:19 GMT-07:00Mitochondria Matter: A Critical Role of ADCK4 in Stabilizing the CoQ Complex in Podocytes in Steroid-Resistant Nephrotic SyndromeDaehn, Ilse S.2020-05-07T10:08:19-07:00doi:10.1681/ASN.2020040467hwp:resource-id:jnephrol;31/6/1167American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycoenzyme Q10, mitochondria, nephrotic syndrome, molecular geneticsEditorialEditorialresearch-article20202020-06-01June 202010.1681/ASN.20200404671046-66731533-34502020-05-07T10:08:19-07:002020-06Journal of the American Society of NephrologyEditorial31661167119111691211
- Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease10.1681/ASN.2019101131Thu, 07 May 2020 10:08:18 GMT-07:00Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone DiseaseDenburg, Michelle R.Koepsell, KristenLee, Jung-JinGerber, JeffreyBittinger, KyleTasian, Gregory E.2020-05-07T10:08:18-07:00doi:10.1681/ASN.2019101131hwp:resource-id:jnephrol;31/6/1358American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney stones, metabolism, intestine, pediatric nephrologyClinical ResearchClinical Researchresearch-article20202020-06-01June 202010.1681/ASN.20191011311046-66731533-34502020-05-07T10:08:18-07:002020-06Journal of the American Society of NephrologyClinical Research31613581369
- Experimental Antiglomerular Basement Membrane GN Induced by a Peptide from Actinomyces10.1681/ASN.2019060619Fri, 22 May 2020 05:50:33 GMT-07:00Experimental Antiglomerular Basement Membrane GN Induced by a Peptide from ActinomycesGu, Qiu-huaHuynh, MeganShi, YueJia, Xiao-yuLuo, Jie-jianJiang, Tai-jiaoCui, ZhaoOoi, Joshua D.Kitching, A. RichardZhao, Ming-hui2020-05-22T05:50:33-07:00doi:10.1681/ASN.2019060619hwp:resource-id:jnephrol;31/6/1282American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, pathology, renal injuryBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20190606191046-66731533-34502020-05-22T05:50:33-07:002020-06Journal of the American Society of NephrologyBasic Research31612821295
- This Month’s Highlights10.1681/ASN.2020040494Fri, 29 May 2020 09:59:49 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2020-05-29T09:59:49-07:00doi:10.1681/ASN.2020040494hwp:resource-id:jnephrol;31/6/iAmerican Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20202020-06-01June 202010.1681/ASN.20200404941046-66731533-34502020-05-29T09:59:49-07:002020-06Journal of the American Society of NephrologyThis Month’s Highlights316ii
- Nephron-Specific Disruption of Polycystin-1 Induces Cyclooxygenase-2–Mediated Blood Pressure Reduction Independent of Cystogenesis10.1681/ASN.2019090934Thu, 16 Apr 2020 06:17:59 GMT-07:00Nephron-Specific Disruption of Polycystin-1 Induces Cyclooxygenase-2–Mediated Blood Pressure Reduction Independent of CystogenesisLakshmipathi, JayalakshmiGao, YangHu, ChunyanStuart, DeborahGenzen, JonathanRamkumar, NirupamaKohan, Donald E.2020-04-16T06:17:59-07:00doi:10.1681/ASN.2019090934hwp:resource-id:jnephrol;31/6/1243American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologynephron, polycystic kidney disease, blood pressure, epithelial sodium transportBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20190909341046-66731533-34502020-04-16T06:17:59-07:002020-06Journal of the American Society of NephrologyBasic Research31612431254
- Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney DiseasesThe kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease.10.1681/ASN.2019121320Wed, 15 Apr 2020 09:19:01 GMT-07:00Beyond a Passive Conduit: Implications of Lymphatic Biology for Kidney DiseasesThe kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease.Jafree, Daniyal J.Long, David A.2020-04-15T09:19:01-07:00doi:10.1681/ASN.2019121320hwp:resource-id:jnephrol;31/6/1178American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologycell signaling, endothelial cells, kidney development, pathophysiology of renal disease and progression, renal cell biology, kidney diseaseReviewReviewreview-article20202020-06-01June 202010.1681/ASN.20191213201046-66731533-34502020-04-15T09:19:01-07:002020-06Journal of the American Society of NephrologyReview31611781190
- Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid–Mediated Activation of G Protein–Coupled Receptors GPR43 and GPR109A10.1681/ASN.2019101029Fri, 01 May 2020 07:53:51 GMT-07:00Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid–Mediated Activation of G Protein–Coupled Receptors GPR43 and GPR109ALi, Yan JunChen, XiaochenKwan, Tony K.Loh, Yik WenSinger, JulianLiu, YunziMa, JinTan, JianMacia, LaurenceMackay, Charles R.Chadban, Steven J.Wu, Huiling2020-05-01T07:53:51-07:00doi:10.1681/ASN.2019101029hwp:resource-id:jnephrol;31/6/1267American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, metabolism, chronic inflammationBasic ResearchBasic Researchresearch-article20202020-06-01June 202010.1681/ASN.20191010291046-66731533-34502020-05-01T07:53:51-07:002020-06Journal of the American Society of NephrologyBasic Research31612671281
- The Immunocompromised Transplant Recipient and SARS-CoV-2 Infection10.1681/ASN.2020040416Tue, 28 Apr 2020 02:53:06 GMT-07:00The Immunocompromised Transplant Recipient and SARS-CoV-2 InfectionFishman, Jay A.2020-04-28T14:53:06-07:00doi:10.1681/ASN.2020040416hwp:resource-id:jnephrol;31/6/1147American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, transplantation, immunosuppressionEditorialEditorialeditorial20202020-06-01June 201910.1681/ASN.20200404161046-66731533-34502020-04-28T14:53:06-07:002020-06Journal of the American Society of NephrologyEditorial31661147115011491156
- Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia10.1681/ASN.2020030276Tue, 28 Apr 2020 02:53:06 GMT-07:00Renal Involvement and Early Prognosis in Patients with COVID-19 PneumoniaPei, GuangchangZhang, ZhiguoPeng, JingLiu, LiuZhang, ChunxiuYu, ChongMa, ZufuHuang, YiLiu, WeiYao, YingZeng, RuiXu, Gang2020-04-28T14:53:06-07:00doi:10.1681/ASN.2020030276hwp:resource-id:jnephrol;31/6/1157American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyPneumonia, proteinuria, Hematuria, Acute Kidney Failure, COVID-19Rapid CommunicationRapid Communicationresearch-article20202020-06-01June 202010.1681/ASN.20200302761046-66731533-34502020-04-28T14:53:06-07:002020-06Journal of the American Society of NephrologyRapid Communication31611571165
- Counterpoint: Twice-Weekly Hemodialysis Should Be an Approach of Last Resort Even in Times of Dialysis Unit Stress10.1681/ASN.2020040412Thu, 16 Apr 2020 06:17:58 GMT-07:00Counterpoint: Twice-Weekly Hemodialysis Should Be an Approach of Last Resort Even in Times of Dialysis Unit StressMehrotra, Rajnish2020-04-16T06:17:58-07:00doi:10.1681/ASN.2020040412hwp:resource-id:jnephrol;31/6/1143American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, kidney failure, congestive heart failure, COVID-19EditorialEditorialresearch-article20202020-06-01June 202010.1681/ASN.20200404121046-66731533-34502020-04-16T06:17:58-07:002020-06Journal of the American Society of NephrologyEditorial31661143114111441142
- Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York10.1681/ASN.2020030375Tue, 21 Apr 2020 04:45:09 GMT-07:00Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New YorkThe Columbia University Kidney Transplant ProgramHusain, S. AliChang, Jae H.Cohen, David J.Crew, R. JohnDube, Geoffrey K.Fernandez, Hilda E.Morris, Heather K.Aaron, Justin G.Miko, Benjamin A.Pereira, Marcus R.Hardy, Mark A.McCune, Kasi R.Ratner, Lloyd E.Sandoval, P. RodrigoWeiner, JoshuaTsapepas, DemetraMohan, Sumit2020-04-21T16:45:09-07:00doi:10.1681/ASN.2020030375hwp:resource-id:jnephrol;31/6/1150American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant outcomes, kidney transplantation, Epidemiology and outcomes, COVID-19Rapid CommunicationRapid Communicationresearch-article20202020-06-01June 202010.1681/ASN.20200303751046-66731533-34502020-04-21T16:45:09-07:002020-06Journal of the American Society of NephrologyRapid Communication31661150114711561149
- COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?10.1681/ASN.2020030348Mon, 20 Apr 2020 12:06:55 GMT-07:00COVID-19 and Calcineurin Inhibitors: Should They Get Left Out in the Storm?Willicombe, MichelleThomas, DavidMcAdoo, Stephen2020-04-20T12:06:55-07:00doi:10.1681/ASN.2020030348hwp:resource-id:jnephrol;31/6/1145American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunosuppression, tacrolimus, transplantation, COVID-19PerspectivePerspectiveresearch-article20202020-06-01June 202010.1681/ASN.20200303481046-66731533-34502020-04-20T12:06:55-07:002020-06Journal of the American Society of NephrologyPerspective31611451146
- On the Etymology of Nephritis: A Historical Appraisal of its Origins10.1681/ASN.2019050510Thu, 16 Apr 2020 06:18:00 GMT-07:00On the Etymology of Nephritis: A Historical Appraisal of its OriginsEknoyan, Garabed2020-04-16T06:18:00-07:00doi:10.1681/ASN.2019050510hwp:resource-id:jnephrol;31/6/1170American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyBright’s disease, glomerulus, GN, nephritis, nephrosis, glomerulosclerosisUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20202020-06-01June 202010.1681/ASN.20190505101046-66731533-34502020-04-16T06:18:00-07:002020-06Journal of the American Society of NephrologyUp Front Matters31611701173
- Twice-Weekly Hemodialysis Is an Option for Many Patients in Times of Dialysis Unit Stress10.1681/ASN.2020030361Thu, 16 Apr 2020 06:17:58 GMT-07:00Twice-Weekly Hemodialysis Is an Option for Many Patients in Times of Dialysis Unit StressMeyer, Timothy W.Hostetter, Thomas H.Watnick, Suzanne2020-04-16T06:17:58-07:00doi:10.1681/ASN.2020030361hwp:resource-id:jnephrol;31/6/1141American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of NephrologyCOVID-19, hemodialysis, dialysisPerspectivePerspectiveeditorial20202020-06-01June 202010.1681/ASN.20200303611046-66731533-34502020-04-16T06:17:58-07:002020-06Journal of the American Society of NephrologyPerspective31661141114311421144
- The Broader Sharing of Deceased Donor Kidneys Is an Ethical and Legal Imperative10.1681/ASN.2020020121Mon, 20 Apr 2020 04:55:27 GMT-07:00The Broader Sharing of Deceased Donor Kidneys Is an Ethical and Legal ImperativeKlarman, Sharon E.Formica, Richard N.2020-04-20T04:55:27-07:00doi:10.1681/ASN.2020020121hwp:resource-id:jnephrol;31/6/1174American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, cadaver organ transplantation, clinical nephrologyPerspectivesPerspectivesresearch-article20202020-06-01June 202010.1681/ASN.20200201211046-66731533-34502020-04-20T04:55:27-07:002020-06Journal of the American Society of NephrologyPerspectives31611741176
- ESKD Treatment Choices Model: Responsible Home Dialysis Growth Requires Systems Changes10.34067/KID.0000672019Fri, 27 Mar 2020 11:05:26 GMT-07:00ESKD Treatment Choices Model: Responsible Home Dialysis Growth Requires Systems ChangesWallace, Eric L.Allon, Michael2020-03-27T11:05:26-07:00doi:10.34067/KID.0000672019hwp:resource-id:kidney360;1/5/424American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, Feasibility Studies, Hemodialysis, Home, Patient Preference, Peritoneal Dialysis, Renal Insufficiency, Chronic, Sustainable GrowthPerspectivePerspectiveresearch-article20202020-05-2810.34067/KID.00006720192641-76502020-03-27T11:05:26-07:002020-05-28Kidney360Perspective15424427
- Should Buttonhole Cannulation of Arteriovenous Fistulas be Used? PRO10.34067/KID.0000702020Tue, 14 Apr 2020 05:30:10 GMT-07:00Should Buttonhole Cannulation of Arteriovenous Fistulas be Used? PROLabriola, Laura2020-04-14T05:30:10-07:00doi:10.34067/KID.0000702020hwp:resource-id:kidney360;1/5/318American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, arteriovenous fistulas, buttonhole cannulation, catheterization, disinfection, needles, punctures, renal dialysisDebates in NephrologyDebates in Nephrologyresearch-article20202020-05-2810.34067/KID.00007020202641-76502020-04-14T05:30:10-07:002020-05-28Kidney360Debates in Nephrology15318321
- Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? Moderator Commentary10.34067/KID.0001682020Tue, 14 Apr 2020 05:30:10 GMT-07:00Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? Moderator CommentaryAgarwal, Anil K.2020-04-14T05:30:10-07:00doi:10.34067/KID.0001682020hwp:resource-id:kidney360;1/5/326American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, Buttonhole, Cannulation, Hemodialysis vascular access, Home hemodialysis, Infections, Rope LadderModerator CommentaryModerator Commentaryarticle-commentary20202020-05-2810.34067/KID.00016820202641-76502020-04-14T05:30:10-07:002020-05-28Kidney360Moderator Commentary15326329
- Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? CON10.34067/KID.0000602019Tue, 14 Apr 2020 05:30:10 GMT-07:00Should Buttonhole Cannulation of Arteriovenous Fistulas Be Used? CONMacRae, Jennifer M.2020-04-14T05:30:10-07:00doi:10.34067/KID.0000602019hwp:resource-id:kidney360;1/5/322American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, arteriovenous fistula, buttonhole, constant site cannulation, fistula, hemodialysis, rope ladder cannulation, vascular accessDebates in NephrologyDebates in Nephrologyresearch-article20202020-05-2810.34067/KID.00006020192641-76502020-04-14T05:30:10-07:002020-05-28Kidney360Debates in Nephrology15322325
- Global Dialysis Perspective: Japan10.34067/KID.0000162020Thu, 16 Apr 2020 06:16:51 GMT-07:00Global Dialysis Perspective: JapanHanafusa, NorioFukagawa, Masafumi2020-04-16T06:16:51-07:00doi:10.34067/KID.0000162020hwp:resource-id:kidney360;1/5/416American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360Dialysis, anemia, hemodiafiltration, hemodialysis, Japan, peritoneal dialysis, PTH, reimbursement, survival, transplantation, vascular accessGlobal PerspectivesGlobal Perspectivesresearch-article20202020-05-2810.34067/KID.00001620202641-76502020-04-16T06:16:51-07:002020-05-28Kidney360Global Perspectives15416419
- Peritoneal Dialysis for Acute Kidney Injury Treatment in the United States: Brought to You by the COVID-19 Pandemic10.34067/KID.0002152020Fri, 24 Apr 2020 02:30:46 GMT-07:00Peritoneal Dialysis for Acute Kidney Injury Treatment in the United States: Brought to You by the COVID-19 PandemicSrivatana, VeshAggarwal, VikramFinkelstein, Fredric O.Naljayan, MihranCrabtree, John H.Perl, Jeffrey2020-04-24T14:30:46-07:00doi:10.34067/KID.0002152020hwp:resource-id:kidney360;1/5/410American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, acute kidney injury, acute peritoneal dialysis, automated peritoneal dialysis, continuous ambulatory peritoneal dialysis, COVID-19, peritoneal dialysis, peritoneal dialysis catheterGlobal PerspectivesGlobal Perspectivesresearch-article20202020-05-2810.34067/KID.00021520202641-76502020-04-24T14:30:46-07:002020-05-28Kidney360Global Perspectives15410415
- Delivering Safe and Effective Hemodialysis in Patients with Suspected or Confirmed COVID-19 Infection: A Single-Center Perspective from Italy10.34067/KID.0001782020Fri, 17 Apr 2020 10:39:57 GMT-07:00Delivering Safe and Effective Hemodialysis in Patients with Suspected or Confirmed COVID-19 Infection: A Single-Center Perspective from ItalyGallieni, MaurizioSabiu, GianmarcoScorza, Daniele2020-04-17T10:39:57-07:00doi:10.34067/KID.0001782020hwp:resource-id:kidney360;1/5/403American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360dialysis, coronavirus, COVID-19, hemodialysis, infection, Italy, management, protocolGlobal PerspectivesGlobal Perspectivesresearch-article20202020-05-2810.34067/KID.00017820202641-76502020-04-17T10:39:57-07:002020-05-28Kidney360Global Perspectives15403409
- α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage Induction10.34067/KID.0000782019Tue, 24 Mar 2020 02:22:15 GMT-07:00α1-Acid Glycoprotein Attenuates Adriamycin-Induced Nephropathy via CD163 Expressing Macrophage InductionFujimura, RuiWatanabe, HiroshiNishida, KentoFujiwara, YukioKoga, TomoakiBi, JingImafuku, TadashiKobayashi, KazukiKomori, HisakazuMiyahisa, MasakoMaeda, HitoshiTanaka, MotokoMatsushita, KazutakaWada, TakashiFukagawa, MasafumiMaruyama, Toru2020-03-24T14:22:15-07:00doi:10.34067/KID.0000782019hwp:resource-id:kidney360;1/5/343American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360CKD, α1-acid glycoprotein, macrophage polarization, proteinuria, Basic ScienceOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-05-2810.34067/KID.00007820192641-76502020-03-24T14:22:15-07:002020-05-28Kidney360Original Investigations15343353
- Serum Transaminases at Presentation and Association with Acute Dialysis in Children with Hemolytic Uremic Syndrome10.34067/KID.0000222020Thu, 19 Mar 2020 09:36:56 GMT-07:00Serum Transaminases at Presentation and Association with Acute Dialysis in Children with Hemolytic Uremic SyndromeTalathi, SaurabhBarnes, MargauxAban, InmaculadaDimmitt, ReedAskenazi, David J.2020-03-19T09:36:56-07:00doi:10.34067/KID.0000222020hwp:resource-id:kidney360;1/5/337American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360acute kidney injury and ICU nephrology, acute kidney injury, dialysis, GI manifestations, hemolytic uremic syndrome, HUS, liver enzymes, renal insufficiency, severity, STECOriginal InvestigationsAcute Kidney Injury and ICU NephrologyOriginal InvestigationsAcute Kidney Injury and ICU Nephrologyresearch-article20202020-05-2810.34067/KID.00002220202641-76502020-03-19T09:36:56-07:002020-05-28Kidney360Original Investigations15337342
- The Role of Telemedicine in Kidney Transplantation: Opportunities and Challenges10.34067/KID.0000332020Fri, 03 Apr 2020 07:30:50 GMT-07:00The Role of Telemedicine in Kidney Transplantation: Opportunities and ChallengesConcepcion, Beatrice P.Forbes, Rachel C.2020-04-03T07:30:50-07:00doi:10.34067/KID.0000332020hwp:resource-id:kidney360;1/5/420American Society of NephrologyCopyright © 2020 by the American Society of NephrologyKidney360transplantation, access to health care, health services, kidney transplant, mobile health, telehealth, telemedicine, videoconferencingGlobal PerspectivesGlobal Perspectivesresearch-article20202020-05-2810.34067/KID.00003320202641-76502020-04-03T07:30:50-07:002020-05-28Kidney360Global Perspectives15420423
- Providing Continuous Renal Replacement Therapy in Patients on Extracorporeal Membrane Oxygenation10.2215/CJN.11220919Fri, 21 Feb 2020 07:05:02 GMT-08:00Providing Continuous Renal Replacement Therapy in Patients on Extracorporeal Membrane OxygenationKarakala, NithinJuncos, Luis A.2020-02-21T07:05:02-08:00doi:10.2215/CJN.11220919hwp:resource-id:clinjasn;15/5/704American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAKI, volume overload, acute renal failure, ischemic renal failure, kidney dysfunction, extracorporeal membrane oxygenation, continuous renal replacement therapyKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20202020-05-07May 07, 202010.2215/CJN.112209191555-90411555-905X2020-02-21T07:05:02-08:002020-05-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat155704706
- Kidney Health Initiative Roadmap for Kidney Replacement Therapy10.2215/CJN.15031219Tue, 14 Apr 2020 10:16:18 GMT-07:00Kidney Health Initiative Roadmap for Kidney Replacement TherapyGee, Patrick O.2020-04-14T10:16:18-07:00doi:10.2215/CJN.15031219hwp:resource-id:clinjasn;15/5/585American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal Replacement Therapy, Acute Kidney InjuryPatient VoicePatient Voiceresearch-article20202020-05-07May 07, 202010.2215/CJN.150312191555-90411555-905X2020-04-14T10:16:18-07:002020-05-07Clinical Journal of the American Society of NephrologyPatient Voice155585586
- Association of Serum Uromodulin with Death, Cardiovascular Events, and Kidney Failure in CKD10.2215/CJN.11780919Tue, 14 Apr 2020 10:16:18 GMT-07:00Association of Serum Uromodulin with Death, Cardiovascular Events, and Kidney Failure in CKDSteubl, DominikSchneider, Markus P.Meiselbach, HeikeNadal, JenniferSchmid, Matthias C.Saritas, TurgayKrane, VeraSommerer, ClaudiaBaid-Agrawal, SeemaVoelkl, JakobKotsis, FruzsinaKöttgen, AnnaEckardt, Kai-UweScherberich, Jürgen E.,2020-04-14T10:16:18-07:00doi:10.2215/CJN.11780919hwp:resource-id:clinjasn;15/5/616American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuromodulin, Tamm–Horsfall protein, chronic kidney disease, tubular function, end-stage renal disease, coronary artery disease, coronary angiography, glomerular filtration rate, albuminuria, confidence intervals, cardiovascular diseases, risk factors, renal insufficiency, chronic, myocardial infarction, stroke, hypertension, diabetes mellitus, regression analysis, peripheral vascular diseases, epithelial cellsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-05-07May 07, 202010.2215/CJN.117809191555-90411555-905X2020-04-14T10:16:18-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1555616589624591
- A Pharmacologic “Stress Test” for Assessing Select Antioxidant Defenses in Patients with CKD10.2215/CJN.15951219Tue, 14 Apr 2020 10:16:18 GMT-07:00A Pharmacologic “Stress Test” for Assessing Select Antioxidant Defenses in Patients with CKDZager, Richard A.Johnson, Ali C.M.Guillem, AlvaroKeyser, JeffSingh, Bhupinder2020-04-14T10:16:18-07:00doi:10.2215/CJN.15951219hwp:resource-id:clinjasn;15/5/633American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymice, creatinine, CST3 protein, human, cystatin C, albuminuria, antioxidants, lipocalin-2, tin, ferritins, tin protoporphyrin IX, protoporphyrins, hexosaminidases, healthy volunteers, exercise test, blood urea nitrogen, HAVCR1 protein, humanOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-05-07May 07, 202010.2215/CJN.159512191555-90411555-905X2020-04-14T10:16:18-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles155633642
- Discontinuation of RAAS Inhibition in Children with Advanced CKD10.2215/CJN.09750819Mon, 06 Apr 2020 08:22:57 GMT-07:00Discontinuation of RAAS Inhibition in Children with Advanced CKDvan den Belt, Sophie M.Heerspink, Hiddo J.L.Kirchner, MariettaGracchi, ValentinaThurn-Valsassina, DanielaBayazit, Aysun K.Niemirska, AnnaCanpolat, NurKaplan Bulut, IpekAzukaitis, KarolisDuzova, AliBacchetta, JustineShroff, RukshanaParipovic, DusanÖzçakar, Zeynep BirsinFidan, KibriyaErdogan, HakanGellermann, JuttaWühl, Elkede Zeeuw, DickMelk, AnetteQuerfeld, UweSchaefer, Franz2020-04-06T08:22:57-07:00doi:10.2215/CJN.09750819hwp:resource-id:clinjasn;15/5/625American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRAAS inhibition, pediatric nephrology, chronic renal disease, Hyperkalemia, albuminuria, Renin-Angiotensin System, creatinine, blood pressure, Potassium, Prospective Studies, Follow-Up Studies, glomerular filtration rate, Renal Insufficiency, Chronic, Cohort Studies, Blood Pressure Determination, hypotension, Comorbidity, AccelerationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-05-07May 07, 202010.2215/CJN.097508191555-90411555-905X2020-04-06T08:22:57-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1555625592632593
- A Primer on Congenital Anomalies of the Kidneys and Urinary Tracts (CAKUT)Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed.10.2215/CJN.12581019Wed, 18 Mar 2020 08:55:09 GMT-07:00A Primer on Congenital Anomalies of the Kidneys and Urinary Tracts (CAKUT)Congenital anomalies of the kidneys and urinary tracts (CAKUT) are disorders caused by defects in the development of the kidneys and their outflow tracts. The formation of the kidneys begins at week 3 and nephrogenesis continues until week 36, therefore, the kidneys and outflow tracts are susceptible to environmental risk factors that perturb development throughout gestation. Many genes have been implicated in kidney and outflow tract development, and mutations have been identified in patients with CAKUT. In severe cases of CAKUT, when the kidneys do not form, the fetus will not survive. However, in less severe cases, the baby can survive with combined kidney and outflow tract defects or they may only be identified in adulthood. In this review, we will cover the clinical presentation of CAKUT, its epidemiology, and its long-term outcomes. We will then discuss risk factors for CAKUT, including genetic and environmental contributions. Although severe CAKUT is rare, low nephron number is a much more common disorder with its effect on kidney function increasingly apparent as a person ages. Low nephron number appears to arise by the same mechanisms as CAKUT, but it differs in terms of the magnitude of the insult and the timing of when it occurs during gestation. By understanding the causes of CAKUT and low nephron number, we can begin to identify preventive treatments and establish clinical guidelines for how these patients should be followed.Murugapoopathy, VasikarGupta, Indra R.2020-03-18T08:55:09-07:00doi:10.2215/CJN.12581019hwp:resource-id:clinjasn;15/5/723American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycongenital anomalies of the kidney and urinary tract, genetics, development, kidney malformations, environment, epigenetics, pediatric nephrology, infant, CAKUT, risk factors, urogenital abnormalities, vesicoureteral reflux, nephrons, mutation, fetus, longitudinal studiesReviewsReviewsreview-article20202020-05-07May 07, 202010.2215/CJN.125810191555-90411555-905X2020-03-18T08:55:09-07:002020-05-07Clinical Journal of the American Society of NephrologyReviews155723731
- Systems Biology and Kidney DiseaseThe kidney is a complex organ responsible for maintaining multiple aspects of homeostasis in the human body. The combination of distinct, yet interrelated, molecular functions across different cell types make the delineation of factors associated with loss or decline in kidney function challenging. Consequently, there has been a paucity of new diagnostic markers and treatment options becoming available to clinicians and patients in managing kidney diseases. A systems biology approach to understanding the kidney leverages recent advances in computational technology and methods to integrate diverse sets of data. It has the potential to unravel the interplay of multiple genes, proteins, and molecular mechanisms that drive key functions in kidney health and disease. The emergence of large, detailed, multilevel biologic and clinical data from national databases, cohort studies, and trials now provide the critical pieces needed for meaningful application of systems biology approaches in nephrology. The purpose of this review is to provide an overview of the current state in the evolution of the field. Recent successes of systems biology to identify targeted therapies linked to mechanistic biomarkers in the kidney are described to emphasize the relevance to clinical care and the outlook for improving outcomes for patients with kidney diseases.10.2215/CJN.09990819Tue, 28 Jan 2020 11:10:19 GMT-08:00Systems Biology and Kidney DiseaseThe kidney is a complex organ responsible for maintaining multiple aspects of homeostasis in the human body. The combination of distinct, yet interrelated, molecular functions across different cell types make the delineation of factors associated with loss or decline in kidney function challenging. Consequently, there has been a paucity of new diagnostic markers and treatment options becoming available to clinicians and patients in managing kidney diseases. A systems biology approach to understanding the kidney leverages recent advances in computational technology and methods to integrate diverse sets of data. It has the potential to unravel the interplay of multiple genes, proteins, and molecular mechanisms that drive key functions in kidney health and disease. The emergence of large, detailed, multilevel biologic and clinical data from national databases, cohort studies, and trials now provide the critical pieces needed for meaningful application of systems biology approaches in nephrology. The purpose of this review is to provide an overview of the current state in the evolution of the field. Recent successes of systems biology to identify targeted therapies linked to mechanistic biomarkers in the kidney are described to emphasize the relevance to clinical care and the outlook for improving outcomes for patients with kidney diseases.Schaub, Jennifer A.Hamidi, HabibSubramanian, LalitaKretzler, Matthias2020-01-28T11:10:19-08:00doi:10.2215/CJN.09990819hwp:resource-id:clinjasn;15/5/695American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, transcriptional profiling, gene expression, kidney biopsy, Genomics, systems biology, bioinformatics, proteomics, precision medicine, humans, nephrology, human body, kidney diseases, kidney, urinary tract physiological phenomena, biomarkers, homeostasis, cohort studies, Kidney Genomics SeriesGenomics of Kidney DiseaseGenomics of Kidney Diseaseresearch-article20202020-05-07May 07, 202010.2215/CJN.099908191555-90411555-905X2020-01-28T11:10:19-08:002020-05-07Clinical Journal of the American Society of NephrologyGenomics of Kidney Disease155695703
- Metabolic Disorders with Kidney TransplantMetabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient’s ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%–30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.10.2215/CJN.09310819Mon, 13 Apr 2020 10:57:30 GMT-07:00Metabolic Disorders with Kidney TransplantMetabolic disorders are highly prevalent in kidney transplant candidates and recipients and can adversely affect post-transplant graft outcomes. Management of diabetes, hyperparathyroidism, and obesity presents distinct opportunities to optimize patients both before and after transplant as well as the ability to track objective data over time to assess a patient’s ability to partner effectively with the health care team and adhere to complex treatment regimens. Optimization of these particular disorders can most dramatically decrease the risk of surgical and cardiovascular complications post-transplant. Approximately 60% of nondiabetic patients experience hyperglycemia in the immediate post-transplant phase. Multiple risk factors have been identified related to development of new onset diabetes after transplant, and it is estimated that upward of 7%–30% of patients will develop new onset diabetes within the first year post-transplant. There are a number of medications studied in the kidney transplant population for diabetes management, and recent data and the risks and benefits of each regimen should be optimized. Secondary hyperparathyroidism occurs in most patients with CKD and can persist after kidney transplant in up to 66% of patients, despite an initial decrease in parathyroid hormone levels. Parathyroidectomy and medical management are the options for treatment of secondary hyperparathyroidism, but there is no randomized, controlled trial providing clear recommendations for optimal management, and patient-specific factors should be considered. Obesity is the most common metabolic disorder affecting the transplant population in both the pre- and post-transplant phases of care. Not only does obesity have associations and interactions with comorbid illnesses, such as diabetes, dyslipidemia, and cardiovascular disease, all of which increase morbidity and mortality post-transplant, but it also is intimately inter-related with access to transplantation for patients with kidney failure. We review these metabolic disorders and their management, including data in patients with kidney transplants.Cohen, ElizabethKorah, MariaCallender, GlendaBelfort de Aguiar, RenataHaakinson, Danielle2020-04-13T10:57:30-07:00doi:10.2215/CJN.09310819hwp:resource-id:clinjasn;15/5/732American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, diabetes, diabetic nephropathy, end stage kidney disease, hyperparathyroidism, kidney transplantation, metabolism, organ transplant, transplantation, cadaver organ transplantation, obesity, pediatric nephrology, phosphate binders, Parathyroidectomy, Cardiovascular Diseases, diabetes mellitus, Hyperglycemia, Renal Insufficiency, Chronic, Dyslipidemias, Hyperparathyroidism, Secondary, parathyroid hormone, Risk AssessmentReviewsReviewsreview-article20202020-05-07May 07, 202010.2215/CJN.093108191555-90411555-905X2020-04-13T10:57:30-07:002020-05-07Clinical Journal of the American Society of NephrologyReviews155732742
- On the Frontline of the COVID-19 Outbreak10.2215/CJN.03540320Sat, 28 Mar 2020 07:24:34 GMT-07:00On the Frontline of the COVID-19 OutbreakWatnick, SuzanneMcNamara, Elizabeth2020-03-28T07:24:34-07:00doi:10.2215/CJN.03540320hwp:resource-id:clinjasn;15/5/710American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, chronic dialysis, severe acute respiratory syndrome coronavirus 2, Disease Outbreaks, RecordsPerspectivesPerspectivesresearch-article20202020-05-07May 07, 202010.2215/CJN.035403201555-90411555-905X2020-03-28T07:24:34-07:002020-05-07Clinical Journal of the American Society of NephrologyPerspectives155710713
- Sound Science before Quick Judgement Regarding RAS Blockade in COVID-1910.2215/CJN.03530320Fri, 27 Mar 2020 02:03:21 GMT-07:00Sound Science before Quick Judgement Regarding RAS Blockade in COVID-19Sparks, Matthew A.South, AndrewWelling, PaulLuther, J. MattCohen, JordanaByrd, James BrianBurrell, Louise M.Batlle, DanielTomlinson, LaurieBhalla, VivekRheault, Michelle N.Soler, María JoséSwaminathan, SundarHiremath, Swapnil2020-03-27T14:03:21-07:00doi:10.2215/CJN.03530320hwp:resource-id:clinjasn;15/5/714American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyangiotensin, renin angiotensin system, virology, hypertension, ACE inhibitors, COVID-19, severe acute respiratory syndrome coronavirus 2, Renin-Angiotensin System, Angiotensin-Converting Enzyme InhibitorsPerspectivesPerspectivesresearch-article20202020-05-07May 07, 202010.2215/CJN.035303201555-90411555-905X2020-03-27T14:03:21-07:002020-05-07Clinical Journal of the American Society of NephrologyPerspectives155714716
- Lessons from the Experience in Wuhan to Reduce Risk of COVID-19 Infection in Patients Undergoing Long-Term Hemodialysis10.2215/CJN.03420320Thu, 02 Apr 2020 01:32:19 GMT-07:00Lessons from the Experience in Wuhan to Reduce Risk of COVID-19 Infection in Patients Undergoing Long-Term HemodialysisLi, JunhuaXu, Gang2020-04-02T13:32:19-07:00doi:10.2215/CJN.03420320hwp:resource-id:clinjasn;15/5/717American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, severe acute respiratory syndrome coronavirus 2, renal dialysis, Infections, Kidney Failure, Chronic, dialysis, hemodialysisPerspectivesPerspectivesresearch-article20202020-05-07May 07, 202010.2215/CJN.034203201555-90411555-905X2020-04-02T13:32:19-07:002020-05-07Clinical Journal of the American Society of NephrologyPerspectives155717719
- COVID-19 and the Inpatient Dialysis Unit10.2215/CJN.03750320Fri, 03 Apr 2020 02:54:11 GMT-07:00COVID-19 and the Inpatient Dialysis UnitBurgner, AnnaIkizler, T. AlpDwyer, Jamie P.2020-04-03T14:54:11-07:00doi:10.2215/CJN.03750320hwp:resource-id:clinjasn;15/5/720American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, infection control, COVID-19, severe acute respiratory syndrome coronavirus 2, inpatients, hospital departments, kidney failure, chronicPerspectivesPerspectivesresearch-article20202020-05-07May 07, 202010.2215/CJN.037503201555-90411555-905X2020-04-03T14:54:11-07:002020-05-07Clinical Journal of the American Society of NephrologyPerspectives155720722
- Mitigating Risk of COVID-19 in Dialysis Facilities10.2215/CJN.03340320Fri, 20 Mar 2020 01:20:05 GMT-07:00Mitigating Risk of COVID-19 in Dialysis FacilitiesKliger, Alan S.Silberzweig, Jeffrey2020-03-20T13:20:05-07:00doi:10.2215/CJN.03340320hwp:resource-id:clinjasn;15/5/707American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCOVID-19, severe acute respiratory syndrome coronavirus 2, renal dialysis, kidney failure, chronic, ambulatory care facilities, dialysisPerspectivesPerspectivesresearch-article20202020-05-07May 07, 202010.2215/CJN.033403201555-90411555-905X2020-03-20T13:20:05-07:002020-05-07Clinical Journal of the American Society of NephrologyPerspectives155707709
- Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial10.2215/CJN.08900719Fri, 03 Apr 2020 06:00:08 GMT-07:00Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled TrialHayashi, TerumasaMaruyama, ShoichiNangaku, MasaomiNarita, IchieiHirakata, HidekiTanabe, KenichiroMorita, SatoshiTsubakihara, YoshiharuImai, EnyuAkizawa, Tadao,2020-04-03T06:00:08-07:00doi:10.2215/CJN.08900719hwp:resource-id:clinjasn;15/5/608American Society of NephrologyCopyright © 2020 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hemoglobin, renal outcome, non-diabetic, Darbepoetin alfa, Hematinics, renal dialysis, glomerular filtration rate, kidney transplantation, Proportional Hazards Models, Renal Insufficiency, Chronic, diabetes mellitus, Hemoglobins, Cardiovascular DiseasesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20202020-05-07May 07, 202010.2215/CJN.089007191555-90411555-905X2020-04-03T06:00:08-07:002020-05-07Clinical Journal of the American Society of NephrologyOriginal Articles155608615
- Fructose Production and Metabolism in the KidneyUnderstanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.10.1681/ASN.2019101015Mon, 06 Apr 2020 08:53:56 GMT-07:00Fructose Production and Metabolism in the KidneyUnderstanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.Nakagawa, TakahikoJohnson, Richard J.Andres-Hernando, AnaRoncal-Jimenez, CarlosSanchez-Lozada, Laura G.Tolan, Dean R.Lanaspa, Miguel A.2020-04-06T08:53:56-07:00doi:10.1681/ASN.2019101015hwp:resource-id:jnephrol;31/5/898American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologyfructose, fructolysis, fructoneogenesis, gluconeogenesis, glycolysisReviewsReviewsreview-article20202020-05-01May 202010.1681/ASN.20191010151046-66731533-34502020-04-06T08:53:56-07:002020-05Journal of the American Society of NephrologyReviews315898906
- Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-InhibitorsGrowing evidence indicates that oxidative and endoplasmic reticular stress, which trigger changes in ion channels and inflammatory pathways that may undermine cellular homeostasis and survival, are critical determinants of injury in the diabetic kidney. Cells are normally able to mitigate these cellular stresses by maintaining high levels of autophagy, an intracellular lysosome-dependent degradative pathway that clears the cytoplasm of dysfunctional organelles. However, the capacity for autophagy in both podocytes and renal tubular cells is markedly impaired in type 2 diabetes, and this deficiency contributes importantly to the intensity of renal injury. The primary drivers of autophagy in states of nutrient and oxygen deprivation—sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and hypoxia-inducible factors (HIF-1α and HIF-2α)—can exert renoprotective effects by promoting autophagic flux and by exerting direct effects on sodium transport and inflammasome activation. Type 2 diabetes is characterized by marked suppression of SIRT1 and AMPK, leading to a diminution in autophagic flux in glomerular podocytes and renal tubules and markedly increasing their susceptibility to renal injury. Importantly, because insulin acts to depress autophagic flux, these derangements in nutrient deprivation signaling are not ameliorated by antihyperglycemic drugs that enhance insulin secretion or signaling. Metformin is an established AMPK agonist that can promote autophagy, but its effects on the course of CKD have been demonstrated only in the experimental setting. In contrast, the effects of sodium-glucose cotransporter–2 (SGLT2) inhibitors may be related primarily to enhanced SIRT1 and HIF-2α signaling; this can explain the effects of SGLT2 inhibitors to promote ketonemia and erythrocytosis and potentially underlies their actions to increase autophagy and mute inflammation in the diabetic kidney. These distinctions may contribute importantly to the consistent benefit of SGLT2 inhibitors to slow the deterioration in glomerular function and reduce the risk of ESKD in large-scale randomized clinical trials of patients with type 2 diabetes.10.1681/ASN.2020010010Fri, 10 Apr 2020 07:16:41 GMT-07:00Role of Impaired Nutrient and Oxygen Deprivation Signaling and Deficient Autophagic Flux in Diabetic CKD Development: Implications for Understanding the Effects of Sodium-Glucose Cotransporter 2-InhibitorsGrowing evidence indicates that oxidative and endoplasmic reticular stress, which trigger changes in ion channels and inflammatory pathways that may undermine cellular homeostasis and survival, are critical determinants of injury in the diabetic kidney. Cells are normally able to mitigate these cellular stresses by maintaining high levels of autophagy, an intracellular lysosome-dependent degradative pathway that clears the cytoplasm of dysfunctional organelles. However, the capacity for autophagy in both podocytes and renal tubular cells is markedly impaired in type 2 diabetes, and this deficiency contributes importantly to the intensity of renal injury. The primary drivers of autophagy in states of nutrient and oxygen deprivation—sirtuin-1 (SIRT1), AMP-activated protein kinase (AMPK), and hypoxia-inducible factors (HIF-1α and HIF-2α)—can exert renoprotective effects by promoting autophagic flux and by exerting direct effects on sodium transport and inflammasome activation. Type 2 diabetes is characterized by marked suppression of SIRT1 and AMPK, leading to a diminution in autophagic flux in glomerular podocytes and renal tubules and markedly increasing their susceptibility to renal injury. Importantly, because insulin acts to depress autophagic flux, these derangements in nutrient deprivation signaling are not ameliorated by antihyperglycemic drugs that enhance insulin secretion or signaling. Metformin is an established AMPK agonist that can promote autophagy, but its effects on the course of CKD have been demonstrated only in the experimental setting. In contrast, the effects of sodium-glucose cotransporter–2 (SGLT2) inhibitors may be related primarily to enhanced SIRT1 and HIF-2α signaling; this can explain the effects of SGLT2 inhibitors to promote ketonemia and erythrocytosis and potentially underlies their actions to increase autophagy and mute inflammation in the diabetic kidney. These distinctions may contribute importantly to the consistent benefit of SGLT2 inhibitors to slow the deterioration in glomerular function and reduce the risk of ESKD in large-scale randomized clinical trials of patients with type 2 diabetes.Packer, Milton2020-04-10T07:16:41-07:00doi:10.1681/ASN.2020010010hwp:resource-id:jnephrol;31/5/907American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, antihyperglycemic drugs, autophagyReviewsReviewsreview-article20202020-05-01May 202010.1681/ASN.20200100101046-66731533-34502020-04-10T07:16:41-07:002020-05Journal of the American Society of NephrologyReviews315907919
- Protein Kinase C-δ Mediates Kidney Tubular Injury in Cold Storage–Associated Kidney Transplantation10.1681/ASN.2019101060Tue, 14 Apr 2020 10:16:32 GMT-07:00Protein Kinase C-δ Mediates Kidney Tubular Injury in Cold Storage–Associated Kidney TransplantationZhu, JiefuZhang, GangSong, ZhixiaXiang, XiaohongShu, ShaoqunLiu, ZhiwenYang, DanyiWei, QingqingDong, Zheng2020-04-14T10:16:32-07:00doi:10.1681/ASN.2019101060hwp:resource-id:jnephrol;31/5/1050American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, mitochondria, PKCδ; kidney, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20202020-05-01May 202010.1681/ASN.20191010601046-66731533-34502020-04-14T10:16:32-07:002020-05Journal of the American Society of NephrologyBasic Research31510501065
- In Vivo Assessment of Size-Selective Glomerular Sieving in Transplanted Human Induced Pluripotent Stem Cell–Derived Kidney Organoids10.1681/ASN.2019060573Thu, 30 Apr 2020 10:00:29 GMT-07:00In Vivo Assessment of Size-Selective Glomerular Sieving in Transplanted Human Induced Pluripotent Stem Cell–Derived Kidney Organoidsvan den Berg, Cathelijne W.Koudijs, AngelaRitsma, LailaRabelink, Ton J.2020-04-30T10:00:29-07:00doi:10.1681/ASN.2019060573hwp:resource-id:jnephrol;31/5/921American Society of NephrologyCopyright © 2020 by the American Society of NephrologyJournal of the American Society of Nephrologypluripotent stem cells, kidney organoids, kidney transplantation, intravital microscopy, glomerular filtrationRapid CommunicationRapid Communicationresearch-article20202020-05-01May 202010.1681/ASN.20190605731046-66731533-34502020-04-30T10:00:29-07:002020-05Journal of the American Society of NephrologyRapid Communication315921929
- Managing Fluid Control in the Peritoneal Dialysis Population10.2215/CJN.04660419Thu, 23 May 2019 08:24:32 GMT-07:00Managing Fluid Control in the Peritoneal Dialysis PopulationGilford, Shari2019-05-23T08:24:32-07:00doi:10.2215/CJN.04660419hwp:resource-id:clinjasn;14/6/783American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, Fluid Therapy, Dialysis SolutionsPatient VoicePatient Voiceeditorial20192019-06-07June 07, 201910.2215/CJN.046604191555-90411555-905X2019-05-23T08:24:32-07:002019-06-07Clinical Journal of the American Society of NephrologyPatient Voice1466783882784893
- Growth Pattern of Kidney Cyst Number and Volume in Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.10360818Tue, 14 May 2019 05:21:59 GMT-07:00Growth Pattern of Kidney Cyst Number and Volume in Autosomal Dominant Polycystic Kidney DiseaseBae, Kyongtae T.Zhou, WenShen, ChengliLandsittel, Douglas P.Wu, ZhiyuanTao, ChengChapman, Arlene B.Torres, Vicente E.Yu, Alan S.L.Mrug, MichalBennett, William M.Harris, Peter C.,2019-05-14T05:21:59-07:00doi:10.2215/CJN.10360818hwp:resource-id:clinjasn;14/6/823American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, cystic kidney, kidney volume, Polycystic Kidney, Autosomal Dominant, Follow-Up Studies, Cysts, kidney, Genotype, Mutation, Demography, Ambulatory CareOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20192019-06-07June 07, 201910.2215/CJN.103608181555-90411555-905X2019-05-14T05:21:59-07:002019-06-07Clinical Journal of the American Society of NephrologyOriginal Articles146823833
- IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD10.2215/CJN.04360418Tue, 23 Apr 2019 08:39:19 GMT-07:00IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKDHung, Adriana M.Tsuchida, YoheiNowak, Kristen L.Sarkar, SudipaChonchol, MichelWhitfield, VictoriaSalas, NatjalieDikalova, AnnaYancey, Patricia G.Huang, JianshengLinton, MacRae F.Ikizler, T. AlpKon, Valentina2019-04-23T08:39:19-07:00doi:10.2215/CJN.04360418hwp:resource-id:clinjasn;14/5/702American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChronic inflammation, HDL, IL-1 inhibition, CKD, IL6 protein, human, IL1RN protein, human, Interleukin 1 Receptor Antagonist Protein, Superoxides, Macrophages, Peritoneal, Tumor Necrosis Factor-alpha, macrophages, Lipoproteins, HDL, Anti-Inflammatory Agents, Inflammation, Renal Insufficiency, Chronic, dialysis, Oxidants, Cholesterol, Cardiovascular Diseases, NLR Proteins, Receptors, Interleukin-1, oxidative stressOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20192019-05-07May 07, 201910.2215/CJN.043604181555-90411555-905X2019-04-23T08:39:19-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles145702711
- A Nutritional Lie or Lifestyle?10.2215/CJN.03450319Thu, 25 Apr 2019 08:06:53 GMT-07:00A Nutritional Lie or Lifestyle?Gee, Patrick O.2019-04-25T08:06:53-07:00doi:10.2215/CJN.03450319hwp:resource-id:clinjasn;14/5/643American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNutritional, Keto, Plant-based, nutritionPatient VoicePatient Voiceeditorial20192019-05-07May 07, 201910.2215/CJN.034503191555-90411555-905X2019-04-25T08:06:53-07:002019-05-07Clinical Journal of the American Society of NephrologyPatient Voice1455643682644691
- Serum Metabolites and Cardiac Death in Patients on Hemodialysis10.2215/CJN.12691018Mon, 08 Apr 2019 05:21:09 GMT-07:00Serum Metabolites and Cardiac Death in Patients on HemodialysisHu, Jiun-RueyGrams, Morgan E.Coresh, JosefHwang, SeungyoungKovesdy, Csaba P.Guallar, EliseoRhee, Eugene P.Shafi, Tariq2019-04-08T05:21:09-07:00doi:10.2215/CJN.12691018hwp:resource-id:clinjasn;14/5/747American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, hemodialysis, cardiovascular disease, mortality, metabolism, dialysis, Kidney Failure, ChronicResearch LetterResearch Letterletter20192019-05-07May 07, 201910.2215/CJN.126910181555-90411555-905X2019-04-08T05:21:09-07:002019-05-07Clinical Journal of the American Society of NephrologyResearch Letter145747749
- Correction10.2215/CJN.02630319Fri, 22 Mar 2019 06:46:37 GMT-07:00CorrectionAmerican Society of Nephrology2019-03-22T06:46:37-07:00doi:10.2215/CJN.02630319hwp:resource-id:clinjasn;14/5/750American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCorrection, erratum, pharmacology, anticoagulantsErratumErratumcorrection20192019-05-07May 07, 201910.2215/CJN.026303191555-90411555-905X2019-03-22T06:46:37-07:002019-05-07Clinical Journal of the American Society of NephrologyErratum141452750278750287
- Blood Microbiome in CKD10.2215/CJN.03420319Mon, 08 Apr 2019 05:21:09 GMT-07:00Blood Microbiome in CKDMair, Robert D.Sirich, Tammy L.2019-04-08T05:21:09-07:00doi:10.2215/CJN.03420319hwp:resource-id:clinjasn;14/5/648American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Blood MicrobiomeEditorialsEditorialseditorial20192019-05-07May 07, 201910.2215/CJN.034203191555-90411555-905X2019-04-08T05:21:09-07:002019-05-07Clinical Journal of the American Society of NephrologyEditorials1455648692649701
- Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure10.2215/CJN.11600918Mon, 22 Apr 2019 04:37:36 GMT-07:00Serum and Urine Albumin and Response to Loop Diuretics in Heart FailureCharokopos, AntoniosGriffin, MatthewRao, Veena S.Inker, LesleySury, KrishnaAsher, JenniferTurner, JeffreyMahoney, DevinCox, Zachary L.Wilson, F. PerryTestani, Jeffrey M.2019-04-22T04:37:36-07:00doi:10.2215/CJN.11600918hwp:resource-id:clinjasn;14/5/712American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiuretics, hypoalbuminemia, IL6 protein, human, Interleukin-6, albuminuria, Serum Albumin, creatinine, Sodium, Transitional Care, Sodium Potassium Chloride Symporter Inhibitors, Inpatients, Urinalysis, heart failure, Plasma, Inflammation, Cohort StudiesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20192019-05-07May 07, 201910.2215/CJN.116009181555-90411555-905X2019-04-22T04:37:36-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1455712650718652
- Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients10.2215/CJN.10640918Thu, 04 Apr 2019 08:01:02 GMT-07:00Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill PatientsChauhan, KinsukPattharanitima, PattharawinPatel, NiraleeDuffy, AineSaha, AparnaChaudhary, KumardeepDebnath, NehaVan Vleck, TielmanChan, LiliNadkarni, Girish N.Coca, Steven G.2019-04-04T08:01:02-07:00doi:10.2215/CJN.10640918hwp:resource-id:clinjasn;14/5/656American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypernatremia, mortality, mortality risk, Critical Illness, Sodium, Brain Edema, Hospital Mortality, Patient Admission, hospitalization, Hospitals, Critical CareOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20192019-05-07May 07, 201910.2215/CJN.106409181555-90411555-905X2019-04-04T08:01:02-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1455656645663647
- Diagnostic Performance of Blood Pressure Measurement Modalities in Living Kidney Donor Candidates10.2215/CJN.02780218Thu, 04 Apr 2019 08:01:01 GMT-07:00Diagnostic Performance of Blood Pressure Measurement Modalities in Living Kidney Donor CandidatesArmanyous, SherifOhashi, YasushiLioudis, MichaelSchold, Jesse D.Thomas, GeorgePoggio, Emilio D.Augustine, Joshua J.2019-04-04T08:01:01-07:00doi:10.2215/CJN.02780218hwp:resource-id:clinjasn;14/5/738American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, blood pressure, Masked Hypertension, Living Donors, American Heart Association, Prospective Studies, Blood Pressure Monitoring, Ambulatory, Blood Pressure Determination, hypertension, hypotensionOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20192019-05-07May 07, 201910.2215/CJN.027802181555-90411555-905X2019-04-04T08:01:01-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles145738746
- Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis Patients10.2215/CJN.03970318Mon, 15 Apr 2019 07:52:05 GMT-07:00Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis PatientsLi, XiaojuanCole, Stephen R.Kshirsagar, Abhijit V.Fine, Jason P.Stürmer, TilBrookhart, M. Alan2019-04-15T07:52:05-07:00doi:10.2215/CJN.03970318hwp:resource-id:clinjasn;14/5/728American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyintravenous iron administration strategies, comparative safety, infections, mortality, hemodialysis patients, anemia management, endstage kidney disease, dialysis, Iron, Confidence Intervals, Kidney Failure, Chronic, Proportional Hazards Models, Administration, Intravenous, anemia, MedicareOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-05-07May 07, 201910.2215/CJN.039703181555-90411555-905X2019-04-15T07:52:05-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles145728737
- Treatment Options for Refractory Lupus Nephritis10.2215/CJN.03230319Fri, 12 Apr 2019 05:26:18 GMT-07:00Treatment Options for Refractory Lupus NephritisAnders, Hans-JoachimHiepe, Falk2019-04-12T05:26:18-07:00doi:10.2215/CJN.03230319hwp:resource-id:clinjasn;14/5/653American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysystemic lupus erythematosus, lupus nephritis, transplantation, Immunosuppressive Agents, RituximabEditorialsEditorialseditorial20192019-05-07May 07, 201910.2215/CJN.032303191555-90411555-905X2019-04-12T05:26:18-07:002019-05-07Clinical Journal of the American Society of NephrologyEditorials1455653719655727
- Clinical Pharmacology of Antihypertensive Therapy for the Treatment of Hypertension in CKDCKD is common and frequently complicated with hypertension both predialysis and in ESKD. As a major modifiable risk factor for cardiovascular disease in this high-risk population, treatment of hypertension in CKD is important. We review the mechanisms and indications for the major classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-adrenergic blocking agents, dihydropyridine calcium channel blockers, thiazide diuretics, loop diuretics, mineralocorticoid receptor blockers, direct vasodilators, and centrally acting α-agonists. Recent evidence suggests that β-adrenergic blocking agents may have a greater role in patients on dialysis and that thiazide diuretics may have a greater role in patients with advanced CKD. We conclude with sharing our general prescribing algorithm for both patients with predialysis CKD and patients with ESKD on dialysis.10.2215/CJN.04330418Tue, 13 Nov 2018 05:46:38 GMT-08:00Clinical Pharmacology of Antihypertensive Therapy for the Treatment of Hypertension in CKDCKD is common and frequently complicated with hypertension both predialysis and in ESKD. As a major modifiable risk factor for cardiovascular disease in this high-risk population, treatment of hypertension in CKD is important. We review the mechanisms and indications for the major classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β-adrenergic blocking agents, dihydropyridine calcium channel blockers, thiazide diuretics, loop diuretics, mineralocorticoid receptor blockers, direct vasodilators, and centrally acting α-agonists. Recent evidence suggests that β-adrenergic blocking agents may have a greater role in patients on dialysis and that thiazide diuretics may have a greater role in patients with advanced CKD. We conclude with sharing our general prescribing algorithm for both patients with predialysis CKD and patients with ESKD on dialysis.Sinha, Arjun D.Agarwal, Rajiv2018-11-13T05:46:38-08:00doi:10.2215/CJN.04330418hwp:resource-id:clinjasn;14/5/757American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAntihypertensive Agents, Sodium Chloride Symporter Inhibitors, Angiotensin-Converting Enzyme Inhibitors, Sodium Potassium Chloride Symporter Inhibitors, Calcium Channel Blockers, NR3C2 protein, human, Receptors, Mineralocorticoid, Vasodilator Agents, risk factors, Pharmacology, Clinical, renal dialysis, Adrenergic beta-Antagonists, Kidney Failure, Chronic, hypertension, Angiotensin Receptor Antagonists, Algorithms, DihydropyridinesNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20192019-05-07May 07, 201910.2215/CJN.043304181555-90411555-905X2018-11-13T05:46:38-08:002019-05-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician145757764
- Mechanistic Insights into Loop Diuretic Responsiveness in Heart Failure10.2215/CJN.03590319Mon, 22 Apr 2019 04:37:35 GMT-07:00Mechanistic Insights into Loop Diuretic Responsiveness in Heart FailureEllison, David H.2019-04-22T04:37:35-07:00doi:10.2215/CJN.03590319hwp:resource-id:clinjasn;14/5/650American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfurosemide, diuretics, diuretic resistance, heart failure, Sodium Potassium Chloride Symporter InhibitorsEditorialsEditorialseditorial20192019-05-07May 07, 201910.2215/CJN.035903191555-90411555-905X2019-04-22T04:37:35-07:002019-05-07Clinical Journal of the American Society of NephrologyEditorials1455650712652718
- Evidence for Managing Hypernatremia10.2215/CJN.02950319Thu, 04 Apr 2019 08:01:01 GMT-07:00Evidence for Managing HypernatremiaSterns, Richard H.2019-04-04T08:01:01-07:00doi:10.2215/CJN.02950319hwp:resource-id:clinjasn;14/5/645American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypernatremia, hyponatremia, osmolality, cell volume regulation, clinical nephrology, diabetes insipidus, electrolytes, outcomes, pediatrics, water-electrolyte balance, sodiumEditorialsEditorialseditorial20192019-05-07May 07, 201910.2215/CJN.029503191555-90411555-905X2019-04-04T08:01:01-07:002019-05-07Clinical Journal of the American Society of NephrologyEditorials1455645656647663
- Nephrin Signaling Results in Integrin β1 Activation10.1681/ASN.2018040362Thu, 16 May 2019 08:48:43 GMT-07:00Nephrin Signaling Results in Integrin β1 ActivationDlugos, Christopher PhilippPicciotto, CaraLepa, CarolinKrakow, MalteStöber, AntjeEddy, Mee-LingWeide, ThomasJeibmann, AstridP. Krahn, MichaelVan Marck, VeerleKlingauf, JürgenRicker, AndreaWedlich-Söldner, RolandPavenstädt, HermannKlämbt, ChristianGeorge, Britta2019-05-16T08:48:43-07:00doi:10.1681/ASN.2018040362hwp:resource-id:jnephrol;30/6/1006American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologycytoskeleton, nephrin, renal cell biology, signalingBasic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20180403621046-66731533-34502019-05-16T08:48:43-07:002019-06Journal of the American Society of NephrologyBasic Research30610061019
- Exostosin 1/Exostosin 2–Associated Membranous Nephropathy10.1681/ASN.2018080852Mon, 06 May 2019 05:56:59 GMT-07:00Exostosin 1/Exostosin 2–Associated Membranous NephropathySethi, SanjeevMadden, Benjamin J.Debiec, HannaCharlesworth, M. CristineGross, LouAnnRavindran, AishwaryaHummel, Amber M.Specks, UlrichFervenza, Fernando C.Ronco, Pierre2019-05-06T05:56:59-07:00doi:10.1681/ASN.2018080852hwp:resource-id:jnephrol;30/6/1123American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyImmunology and pathology, membranous nephropathy, nephrotic syndromeClinical ResearchClinical Researchresearch-article20192019-06-01June 201910.1681/ASN.20180808521046-66731533-34502019-05-06T05:56:59-07:002019-06Journal of the American Society of NephrologyClinical Research30611231136
- A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKD10.1681/ASN.2018111150Mon, 29 Apr 2019 09:08:26 GMT-07:00A Randomized Trial of Magnesium Oxide and Oral Carbon Adsorbent for Coronary Artery Calcification in Predialysis CKDSakaguchi, YusukeHamano, TakayukiObi, YoshitsuguMonden, ChikakoOka, TatsufumiYamaguchi, SatoshiMatsui, IsaoHashimoto, NobuhiroMatsumoto, AyumiShimada, KarinTakabatake, YoshitsuguTakahashi, AtsushiKaimori, Jun-YaMoriyama, ToshikiYamamoto, RyoheiHorio, MasaruYamamoto, KoichiSugimoto, KenRakugi, HiromiIsaka, Yoshitaka2019-04-29T09:08:26-07:00doi:10.1681/ASN.2018111150hwp:resource-id:jnephrol;30/6/1073American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologymagnesium oxide, coronary artery calcification, chronic kidney disease, randomized controlled trial, oral carbon adsorbentClinical ResearchClinical Researchresearch-article20192019-06-01June 201910.1681/ASN.20181111501046-66731533-34502019-04-29T09:08:26-07:002019-06Journal of the American Society of NephrologyClinical Research30610731085
- Erythropoiesis-Stimulating Agents and Mortality10.1681/ASN.2019030266Tue, 23 Apr 2019 08:44:18 GMT-07:00Erythropoiesis-Stimulating Agents and MortalityDrüeke, Tilman B.Massy, Ziad A.2019-04-23T08:44:18-07:00doi:10.1681/ASN.2019030266hwp:resource-id:jnephrol;30/6/907American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic renal disease, erythropoietin, mortality risk, outcomesUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-06-01June 201910.1681/ASN.20190302661046-66731533-34502019-04-23T08:44:18-07:002019-06Journal of the American Society of NephrologyUp Front Matters306690710379081048
- Authors’ Reply10.1681/ASN.2019040353Mon, 06 May 2019 05:56:59 GMT-07:00Authors’ ReplyPun, Patrick H.Dupre, Matthew E.Tyson, ClarkAl-Khatib, Sana M.Granger, Christopher B.2019-05-06T05:56:59-07:00doi:10.1681/ASN.2019040353hwp:resource-id:jnephrol;30/6/1137-aAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, cardiovascular events, Hemodialysis hazards, cardiovascular diseaseLetter to the EditorLetter to the Editorletter20192019-06-01June 201910.1681/ASN.20190403531046-66731533-34502019-05-06T05:56:59-07:002019-06Journal of the American Society of NephrologyLetter to the Editor30661137113711381137
- CPR for OHCA Is Rarely Successful, and What Is “Success” Anyway?10.1681/ASN.2019020149Mon, 06 May 2019 05:56:59 GMT-07:00CPR for OHCA Is Rarely Successful, and What Is “Success” Anyway?Gelfand, Samantha L.Eneanya, Nwamaka D.Leonberg-Yoo, Amanda K.Berns, Jeffrey S.2019-05-06T05:56:59-07:00doi:10.1681/ASN.2019020149hwp:resource-id:jnephrol;30/6/1137American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyHemodialysis hazards, mortality risk, ESRD, quality of lifeLetter to the EditorLetter to the Editorletter20192019-06-01June 201910.1681/ASN.20190201491046-66731533-34502019-05-06T05:56:59-07:002019-06Journal of the American Society of NephrologyLetter to the Editor30661137113711371138
- Podocyte-Specific Sialylation-Deficient Mice Serve as a Model for Human FSGS10.1681/ASN.2018090951Tue, 30 Apr 2019 09:11:00 GMT-07:00Podocyte-Specific Sialylation-Deficient Mice Serve as a Model for Human FSGSNiculovic, Kristina M.Blume, LindaWedekind, HenriKats, ElinaAlbers, IrisGroos, StephanieAbeln, MarkusSchmitz, JessicaBeuke, EstherBräsen, Jan H.Melk, AnetteSchiffer, MarioWeinhold, BirgitMünster-Kühnel, Anja K.2019-04-30T09:11:00-07:00doi:10.1681/ASN.2018090951hwp:resource-id:jnephrol;30/6/1021American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, glomerular disease, podocyte, chronic kidney disease, cell adhesion, glycosylationBasic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20180909511046-66731533-34502019-04-30T09:11:00-07:002019-06Journal of the American Society of NephrologyBasic Research30610211035
- Exome-Based Rare-Variant Analyses in CKD10.1681/ASN.2018090909Mon, 13 May 2019 07:09:19 GMT-07:00Exome-Based Rare-Variant Analyses in CKDCameron-Christie, SophiaWolock, Charles J.Groopman, EmilyPetrovski, SlavéKamalakaran, SitharthanPovysil, GundulaVitsios, DimitriosZhang, MengqiFleckner, JanMarch, Ruth E.Gelfman, SaharMarasa, MaddalenaLi, YifuSanna-Cherchi, SimoneKiryluk, KrzysztofAllen, Andrew S.Fellström, Bengt C.Haefliger, CarolinaPlatt, AdamGoldstein, David B.Gharavi, Ali G.2019-05-13T07:09:19-07:00doi:10.1681/ASN.2018090909hwp:resource-id:jnephrol;30/6/1109American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, human genetics, molecular geneticsClinical ResearchClinical Researchresearch-article20192019-06-01June 201910.1681/ASN.20180909091046-66731533-34502019-05-13T07:09:19-07:002019-06Journal of the American Society of NephrologyClinical Research30611091122
- Dual Inhibition of Gastrointestinal Phosphate Absorption: More Questions Than Answers10.1681/ASN.2019040333Mon, 13 May 2019 07:09:20 GMT-07:00Dual Inhibition of Gastrointestinal Phosphate Absorption: More Questions Than AnswersYeung, Wing-Chi G.Toussaint, Nigel D.Badve, Sunil V.2019-05-13T07:09:20-07:00doi:10.1681/ASN.2019040333hwp:resource-id:jnephrol;30/6/909American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate binders, chronic kidney disease, randomized controlled trialsUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-06-01June 201910.1681/ASN.20190403331046-66731533-34502019-05-13T07:09:20-07:002019-06Journal of the American Society of NephrologyUp Front Matters306690910969101108
- This Month's Highlights10.1681/ASN.2019040422Fri, 31 May 2019 10:00:29 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2019-05-31T10:00:29-07:00doi:10.1681/ASN.2019040422hwp:resource-id:jnephrol;30/6/iAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20192019-06-01June 201910.1681/ASN.20190404221046-66731533-34502019-05-31T10:00:29-07:002019-06Journal of the American Society of NephrologyThis Month's Highlights306ii
- One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study)10.1681/ASN.2018121232Tue, 30 Apr 2019 09:11:01 GMT-07:00One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study)Wong, GermaineHope, Richard L.Howard, KirstenChapman, Jeremy R.Castells, AntoniRoger, Simon D.Bourke, Michael J.Macaskill, PetraTurner, RobinWilliams, GabrielleLim, Wai HonLok, Charmaine E.Diekmann, FritzCross, Nicholas B.Sen, ShaundeepAllen, Richard D.M.Chadban, Steven J.Pollock, Carol A.Tong, AllisonTeixeira-Pinto, ArmandoYang, Jean Y.H.Williams, NarelleAu, Eric Hoi KitKieu, AnhJames, LauraCraig, Jonathan C.2019-04-30T09:11:01-07:00doi:10.1681/ASN.2018121232hwp:resource-id:jnephrol;30/6/1061American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologycancer, chronic kidney disease, screening, test performanceClinical ResearchClinical Researchresearch-article20192019-06-01June 201910.1681/ASN.20181212321046-66731533-34502019-04-30T09:11:01-07:002019-06Journal of the American Society of NephrologyClinical Research30610611072
- Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells10.1681/ASN.2018080816Thu, 16 May 2019 08:48:44 GMT-07:00Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated CellsGiesecke, TorstenHimmerkus, NinaLeipziger, JensBleich, MarkusKoshimizu, Taka-akiFähling, MichaelSmorodchenko, AlinaShpak, JuliaKnappe, CarolinIsermann, JulianAyasse, NiklasKawahara, KatsumasaSchmoranzer, JanGimber, NiclasPaliege, AlexanderBachmann, SebastianMutig, Kerim2019-05-16T08:48:44-07:00doi:10.1681/ASN.2018080816hwp:resource-id:jnephrol;30/6/946American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacid-base homeostasis, antidiuretic hormone, distal renal tubular acidosis, intercalated cells, vasopressin V1a receptor, V-ATPaseBasic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20180808161046-66731533-34502019-05-16T08:48:44-07:002019-06Journal of the American Society of NephrologyBasic Research306946961
- Matching Human Unilateral AKI, a Reverse Translational Approach to Investigate Kidney Recovery after Ischemia10.1681/ASN.2018080808Thu, 09 May 2019 07:00:23 GMT-07:00Matching Human Unilateral AKI, a Reverse Translational Approach to Investigate Kidney Recovery after IschemiaSoranno, Danielle E.Gil, Hyo-WookKirkbride-Romeo, LaraAltmann, ChristopherMontford, John R.Yang, HaichunLevine, AniBuchanan, JaneFaubel, Sarah2019-05-09T07:00:23-07:00doi:10.1681/ASN.2018080808hwp:resource-id:jnephrol;30/6/990American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, animal models of disease, reverse translational research approach, chronic kidney disease, unilateral ischemia reperfusion injuryBasic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20180808081046-66731533-34502019-05-09T07:00:23-07:002019-06Journal of the American Society of NephrologyBasic Research3069901005
- Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial10.1681/ASN.2018101058Mon, 13 May 2019 07:09:20 GMT-07:00Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE TrialIx, Joachim H.Isakova, TamaraLarive, BrettRaphael, Kalani L.Raj, Dominic S.Cheung, Alfred K.Sprague, Stuart M.Fried, Linda F.Gassman, Jennifer J.Middleton, John P.Flessner, Michael F.Block, Geoffrey A.Wolf, Myles2019-05-13T07:09:20-07:00doi:10.1681/ASN.2018101058hwp:resource-id:jnephrol;30/6/1096American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, mineral metabolism, fibroblast growth factor, phosphate, clinical trial, pilot studyClinical ResearchClinical Researchresearch-article20192019-06-01June 201910.1681/ASN.20181010581046-66731533-34502019-05-13T07:09:20-07:002019-06Journal of the American Society of NephrologyClinical Research306610969091108910
- Extrarenal Signs of Proximal Renal Tubular Acidosis Persist in Nonacidemic Nbce1b/c-Null Mice10.1681/ASN.2018050545Tue, 30 Apr 2019 09:10:59 GMT-07:00Extrarenal Signs of Proximal Renal Tubular Acidosis Persist in Nonacidemic Nbce1b/c-Null MiceSalerno, Emily E.Patel, Sangita P.Marshall, AnikoMarshall, JordanAlsufayan, ThamerMballo, Cheikh S. AlassaneQuade, Bianca N.Parker, Mark D.2019-04-30T09:10:59-07:00doi:10.1681/ASN.2018050545hwp:resource-id:jnephrol;30/6/979American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic metabolic acidosis, genetic renal disease, Intracellular pH, renal proximal tubule cell, bicarbonate, NBCe1Basic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20180505451046-66731533-34502019-04-30T09:10:59-07:002019-06Journal of the American Society of NephrologyBasic Research306979989
- Renal Perfusion during Hemodialysis: Intradialytic Blood Flow Decline and Effects of Dialysate Cooling10.1681/ASN.2018121194Fri, 03 May 2019 06:45:00 GMT-07:00Renal Perfusion during Hemodialysis: Intradialytic Blood Flow Decline and Effects of Dialysate CoolingMarants, RaananQirjazi, ElenaGrant, Claire J.Lee, Ting-YimMcIntyre, Christopher W.2019-05-03T06:45:00-07:00doi:10.1681/ASN.2018121194hwp:resource-id:jnephrol;30/6/1086American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, renal hemodynamics, renal ischemia, renal function declineClinical ResearchClinical Researchresearch-article20192019-06-01June 201910.1681/ASN.20181211941046-66731533-34502019-05-03T06:45:00-07:002019-06Journal of the American Society of NephrologyClinical Research30610861095
- Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing Hemodialysis10.1681/ASN.2018101007Tue, 23 Apr 2019 08:44:17 GMT-07:00Types of Erythropoietin-Stimulating Agents and Mortality among Patients Undergoing HemodialysisSakaguchi, YusukeHamano, TakayukiWada, AtsushiMasakane, Ikuto2019-04-23T08:44:17-07:00doi:10.1681/ASN.2018101007hwp:resource-id:jnephrol;30/6/1037American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyerythropoietin-stimulating agents, mortality, hemodialysisClinical EpidemiologyClinical Epidemiologyresearch-article20192019-06-01June 201910.1681/ASN.20181010071046-66731533-34502019-04-23T08:44:17-07:002019-06Journal of the American Society of NephrologyClinical Epidemiology306610379071048908
- Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes10.1681/ASN.2018100983Tue, 30 Apr 2019 09:11:01 GMT-07:00Proximal Tubule Autophagy Differs in Type 1 and 2 DiabetesSakai, ShinsukeYamamoto, TakeshiTakabatake, YoshitsuguTakahashi, AtsushiNamba-Hamano, TomokoMinami, SatoshiFujimura, RyutaYonishi, HiroakiMatsuda, JunHesaka, AtsushiMatsui, IsaoMatsusaka, TaijiNiimura, FumioYanagita, MotokoIsaka, Yoshitaka2019-04-30T09:11:01-07:00doi:10.1681/ASN.2018100983hwp:resource-id:jnephrol;30/6/929American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, autophagy, autophagic flux, insulin, lysosomeBasic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20181009831046-66731533-34502019-04-30T09:11:01-07:002019-06Journal of the American Society of NephrologyBasic Research306929945
- Changes in Albuminuria But Not GFR are Associated with Early Changes in Kidney Structure in Type 2 Diabetes10.1681/ASN.2018111166Fri, 31 May 2019 10:00:30 GMT-07:00Changes in Albuminuria But Not GFR are Associated with Early Changes in Kidney Structure in Type 2 DiabetesLooker, Helen C.Mauer, MichaelSaulnier, Pierre-JeanHarder, Jennifer L.Nair, VijiBoustany-Kari, Carine M.Guarnieri, PaoloHill, JonEsplin, Cordell A.Kretzler, MatthiasNelson, Robert G.Najafian, Behzad2019-05-31T10:00:30-07:00doi:10.1681/ASN.2018111166hwp:resource-id:jnephrol;30/6/1049American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, renal morphology., type 2 diabetesClinical EpidemiologyClinical Epidemiologyresearch-article20192019-06-01June 201910.1681/ASN.20181111661046-66731533-34502019-05-31T10:00:30-07:002019-06Journal of the American Society of NephrologyClinical Epidemiology30610491059
- Protein O-GlcNAcylation Is Essential for the Maintenance of Renal Energy Homeostasis and Function via Lipolysis during Fasting and Diabetes10.1681/ASN.2018090950Wed, 01 May 2019 12:15:13 GMT-07:00Protein O-GlcNAcylation Is Essential for the Maintenance of Renal Energy Homeostasis and Function via Lipolysis during Fasting and DiabetesSugahara, ShoKume, ShinjiChin-Kanasaki, MasamiTomita, IsseiYasuda-Yamahara, MakoYamahara, KosukeTakeda, NaokoOsawa, NorihisaYanagita, MotokoAraki, Shin-ichiMaegawa, Hiroshi2019-05-01T12:15:13-07:00doi:10.1681/ASN.2018090950hwp:resource-id:jnephrol;30/6/962American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes mellitus, lipids, obesity, renal proximal tubule cellBasic ResearchBasic Researchresearch-article20192019-06-01June 201910.1681/ASN.20180909501046-66731533-34502019-05-01T12:15:13-07:002019-06Journal of the American Society of NephrologyBasic Research306962978
- Arterial Stiffness in the Heart Disease of CKDCKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.10.1681/ASN.2019020117Tue, 30 Apr 2019 09:11:00 GMT-07:00Arterial Stiffness in the Heart Disease of CKDCKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.Zanoli, LucaLentini, PaoloBriet, MarieCastellino, PietroHouse, Andrew A.London, Gerard M.Malatino, LorenzoMcCullough, Peter A.Mikhailidis, Dimitri P.Boutouyrie, Pierre2019-04-30T09:11:00-07:00doi:10.1681/ASN.2019020117hwp:resource-id:jnephrol;30/6/918American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyarteries, cardiovascular disease, chronic kidney disease, Chronic inflammation, arteriosclerosis, pulse wave velocityUp Front MattersReviewUp Front MattersReviewresearch-article20192019-06-01June 201910.1681/ASN.20190201171046-66731533-34502019-04-30T09:11:00-07:002019-06Journal of the American Society of NephrologyUp Front Matters306918928
- Pyelonephritis: A Historical Reappraisal10.1681/ASN.2019010017Fri, 26 Apr 2019 06:42:40 GMT-07:00Pyelonephritis: A Historical ReappraisalAnumudu, SamayaEknoyan, Garabed2019-04-26T06:42:40-07:00doi:10.1681/ASN.2019010017hwp:resource-id:jnephrol;30/6/914American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologybacteriuria, pyelonephritis, interstitial nephritis, contracted kidney, nephritisUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20192019-06-01June 201910.1681/ASN.20190100171046-66731533-34502019-04-26T06:42:40-07:002019-06Journal of the American Society of NephrologyUp Front Matters306914917
- Solving Baroreceptor Mystery: Role of PIEZO Ion Channels10.1681/ASN.2019020160Wed, 01 May 2019 12:15:12 GMT-07:00Solving Baroreceptor Mystery: Role of PIEZO Ion ChannelsBurke, Suzanne D.Jordan, JensHarrison, David G.Karumanchi, S. Ananth2019-05-01T12:15:12-07:00doi:10.1681/ASN.2019020160hwp:resource-id:jnephrol;30/6/911American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20192019-06-01June 201910.1681/ASN.20190201601046-66731533-34502019-05-01T12:15:12-07:002019-06Journal of the American Society of NephrologyUp Front Matters306911913
- Blood Microbiome Profile in CKD10.2215/CJN.12161018Mon, 08 Apr 2019 05:21:09 GMT-07:00Blood Microbiome Profile in CKDShah, Neal B.Allegretti, Andrew S.Nigwekar, Sagar U.Kalim, SahirZhao, SophiaLelouvier, BenjaminServant, FlorenceSerena, GloriaThadhani, Ravi IshwarRaj, Dominic S.Fasano, Alessio2019-04-08T05:21:09-07:00doi:10.2215/CJN.12161018hwp:resource-id:clinjasn;14/5/692American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBlood microbiome, chronic kidney disease, Proteobacteria, DNA, Bacterial, DNA, Ribosomal, glomerular filtration rate, Enterobacteriaceae, Endotoxemia, Cross-Sectional Studies, Pilot Projects, Dysbiosis, Metagenomics, Microbiota, Pseudomonadaceae, Sequence Analysis, DNA, Polymerase Chain Reaction, Renal Insufficiency, Chronic, PermeabilityOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-05-07May 07, 201910.2215/CJN.121610181555-90411555-905X2019-04-08T05:21:09-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1455692648701649
- Pruritus and Patient Reported Outcomes in Non-Dialysis CKD10.2215/CJN.09600818Thu, 11 Apr 2019 05:03:23 GMT-07:00Pruritus and Patient Reported Outcomes in Non-Dialysis CKDSukul, NidhiSpeyer, ElodieTu, CharlotteBieber, Brian A.Li, YunLopes, Antonio A.Asahi, KoichiMariani, LauraLaville, MauriceRayner, Hugh C.Stengel, BénédicteRobinson, Bruce M.Pisoni, Ronald L.,2019-04-11T05:03:23-07:00doi:10.2215/CJN.09600818hwp:resource-id:clinjasn;14/5/673American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUremic pruritus, chronic kidney disease, depression, quality of life, Patient Reported Outcome Measures, Cross-Sectional Studies, Prevalence, Linear Models, Surveys and Questionnaires, dialysis, Renal Insufficiency, Chronic, Pruritus, diabetes mellitus, Lung DiseasesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-05-07May 07, 201910.2215/CJN.096008181555-90411555-905X2019-04-11T05:03:23-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles145673681
- Plant-Based Diets and Incident CKD and Kidney Function10.2215/CJN.12391018Thu, 25 Apr 2019 08:06:53 GMT-07:00Plant-Based Diets and Incident CKD and Kidney FunctionKim, HyunjuCaulfield, Laura E.Garcia-Larsen, VanessaSteffen, Lyn M.Grams, Morgan E.Coresh, JosefRebholz, Casey M.2019-04-25T08:06:53-07:00doi:10.2215/CJN.12391018hwp:resource-id:clinjasn;14/5/682American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPlant-based diet indices, vegetarian diet index, chronic kidney disease, kidney function, glomerular filtration rate, Proportional Hazards Models, Follow-Up Studies, Diet, Vegetarian, Diet, Renal Insufficiency, Chronic, kidney, AtherosclerosisOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-05-07May 07, 201910.2215/CJN.123910181555-90411555-905X2019-04-25T08:06:53-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1455682643691644
- Hepatorenal SyndromeHepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified. Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage. Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option. Several controlled studies proved that terlipressin is effective at reversing hepatorenal syndrome and may improve short-term survival. Not all patients are responders, and even in responders, early mortality rates are very high in the absence of liver transplantation. Liver transplantation is the only curative treatment of hepatorenal syndrome. In the long term, patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome. Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN. Hepatorenal syndrome and ATN may be considered as a continuum rather than distinct entities. Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver–kidney transplantation.10.2215/CJN.12451018Wed, 17 Apr 2019 05:03:07 GMT-07:00Hepatorenal SyndromeHepatorenal syndrome is a severe complication of end-stage cirrhosis characterized by increased splanchnic blood flow, hyperdynamic state, a state of decreased central volume, activation of vasoconstrictor systems, and extreme kidney vasoconstriction leading to decreased GFR. The contribution of systemic inflammation, a key feature of cirrhosis, in the development of hepatorenal syndrome has been highlighted in recent years. The mechanisms by which systemic inflammation precipitates kidney circulatory changes during hepatorenal syndrome need to be clarified. Early diagnosis is central in the management and recent changes in the definition of hepatorenal syndrome help identify patients at an earlier stage. Vasoconstrictive agents (terlipressin in particular) and albumin are the first-line treatment option. Several controlled studies proved that terlipressin is effective at reversing hepatorenal syndrome and may improve short-term survival. Not all patients are responders, and even in responders, early mortality rates are very high in the absence of liver transplantation. Liver transplantation is the only curative treatment of hepatorenal syndrome. In the long term, patients transplanted with hepatorenal syndrome tend to have lower GFR compared with patients without hepatorenal syndrome. Differentiating hepatorenal syndrome from acute tubular necrosis (ATN) is often a challenging yet important step because vasoconstrictors are not justified for the treatment of ATN. Hepatorenal syndrome and ATN may be considered as a continuum rather than distinct entities. Emerging biomarkers may help differentiate these two conditions and provide prognostic information on kidney recovery after liver transplantation, and potentially affect the decision for simultaneous liver–kidney transplantation.Francoz, ClaireDurand, FrançoisKahn, Jeffrey A.Genyk, Yuri S.Nadim, Mitra K.2019-04-17T05:03:07-07:00doi:10.2215/CJN.12451018hwp:resource-id:clinjasn;14/5/774American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhepatorenal, acute kidney injury, liver transplantation, Hepatorenal Syndrome, terlipressin, Vasoconstrictor Agents, Liver Transplantation, Vasoconstriction, kidney transplantation, Prognosis, glomerular filtration rate, Lypressin, Renal Circulation, Liver Cirrhosis, Kidney Tubular Necrosis, Acute, Albumins, Inflammation, Biomarkers, Early DiagnosisReviewReviewresearch-article20192019-05-07May 07, 201910.2215/CJN.124510181555-90411555-905X2019-04-17T05:03:07-07:002019-05-07Clinical Journal of the American Society of NephrologyReview145774781
- Major Adverse Kidney Events in Pediatric Sepsis10.2215/CJN.12201018Thu, 18 Apr 2019 06:41:38 GMT-07:00Major Adverse Kidney Events in Pediatric SepsisWeiss, Scott L.Balamuth, FranThurm, Cary W.Downes, Kevin J.Fitzgerald, Julie C.Laskin, Benjamin L.2019-04-18T06:41:38-07:00doi:10.2215/CJN.12201018hwp:resource-id:clinjasn;14/5/664American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypediatrics, outcomes, clinical trial, acute kidney failure, Length of Stay, Blood Culture, Incidence, Retrospective Studies, Hospital Costs, Patient Readmission, glomerular filtration rate, Inpatients, Logistic Models, Health Information Systems, Anti-Bacterial Agents, Confidence Intervals, Shock, Septic, Sepsis, Patient Discharge, Kidney Replacement TherapyOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20192019-05-07May 07, 201910.2215/CJN.122010181555-90411555-905X2019-04-18T06:41:38-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles145664672
- How Community Engagement Is Enhancing NIDDK Research10.2215/CJN.14591218Wed, 27 Mar 2019 07:03:06 GMT-07:00How Community Engagement Is Enhancing NIDDK ResearchKimmel, Paul L.Jefferson, NicholeNorton, Jenna M.Star, Robert A.2019-03-27T07:03:06-07:00doi:10.2215/CJN.14591218hwp:resource-id:clinjasn;14/5/768American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient engagement, community engagement, kidney disease, chronic kidney disease, chronic kidney failure, National Institute of Diabetes and Digestive and Kidney Diseases (U.S.), Research, CommunityPerspectivesPerspectivesresearch-article20192019-05-07May 07, 201910.2215/CJN.145912181555-90411555-905X2019-03-27T07:03:06-07:002019-05-07Clinical Journal of the American Society of NephrologyPerspectives145768770
- Transitional Care Units: Greater Than the Sum of Their Parts10.2215/CJN.12301018Wed, 27 Mar 2019 07:03:06 GMT-07:00Transitional Care Units: Greater Than the Sum of Their PartsBowman, Brendan T.2019-03-27T07:03:06-07:00doi:10.2215/CJN.12301018hwp:resource-id:clinjasn;14/5/765American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, transitional care unit, transitional dialysis, incident dialysis, peritoneal dialysis, Hemodialysis, Home, Transitional Care, Orientation, Spatial, Nutrition Therapy, kidney, dietPerspectivesPerspectivesresearch-article20192019-05-07May 07, 201910.2215/CJN.123010181555-90411555-905X2019-03-27T07:03:06-07:002019-05-07Clinical Journal of the American Society of NephrologyPerspectives145765767
- Retooling Nephrology with Ultrasound10.2215/CJN.10430818Wed, 27 Mar 2019 07:03:06 GMT-07:00Retooling Nephrology with UltrasoundO’Neill, W. CharlesRoss, Daniel W.2019-03-27T07:03:06-07:00doi:10.2215/CJN.10430818hwp:resource-id:clinjasn;14/5/771American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, nephrology, ultrasonographyPerspectivesPerspectivesresearch-article20192019-05-07May 07, 201910.2215/CJN.104308181555-90411555-905X2019-03-27T07:03:06-07:002019-05-07Clinical Journal of the American Society of NephrologyPerspectives145771773
- Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis10.2215/CJN.10570918Fri, 12 Apr 2019 05:26:17 GMT-07:00Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus NephritisHuang, XianghuaChen, WencuiRen, GuishengZhao, LiangGuo, JinzhouGong, DehuaZeng, CaihongHu, WeixinLiu, Zhihong2019-04-12T05:26:17-07:00doi:10.2215/CJN.10570918hwp:resource-id:clinjasn;14/5/719American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrefractory, efficacy, Hematopoietic Stem Cell Mobilization, lupus nephritis, Antilymphocyte Serum, Peripheral Blood Stem Cells, Disease-Free Survival, Blood Platelets, Cyclophosphamide, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Transplantation, Transplantation, Autologous, Recurrence, Immunologic Tests, Granulocytes, proteinuria, Gastrointestinal Tract, peritoneal dialysisOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20192019-05-07May 07, 201910.2215/CJN.105709181555-90411555-905X2019-04-12T05:26:17-07:002019-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1455719653727655
- Post-Transplant Lymphoproliferative Disorder in a Kidney Transplant Recipient10.2215/CJN.00180119Mon, 25 Feb 2019 09:10:54 GMT-08:00Post-Transplant Lymphoproliferative Disorder in a Kidney Transplant RecipientAgarwal, GauravMannon, Roslyn B.2019-02-25T09:10:54-08:00doi:10.2215/CJN.00180119hwp:resource-id:clinjasn;14/5/751American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, PTLD, immunosuppression, EBVKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20192019-05-07May 07, 201910.2215/CJN.001801191555-90411555-905X2019-02-25T09:10:54-08:002019-05-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire145751753
- A Case of ANCA-Associated Vasculitis10.2215/CJN.14601218Fri, 05 Apr 2019 06:39:37 GMT-07:00A Case of ANCA-Associated VasculitisHogan, Jonathan J.2019-04-05T06:39:37-07:00doi:10.2215/CJN.14601218hwp:resource-id:clinjasn;14/5/754American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, glomerulonephritis, vasculitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil CytoplasmicKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20192019-05-07May 07, 201910.2215/CJN.146012181555-90411555-905X2019-04-05T06:39:37-07:002019-05-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire145754756
- Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital ImagingUrine output is widely used as a criterion for the diagnosis of AKI. Although several potential mechanisms of septic AKI have been identified, regulation of urine flow after glomerular filtration has not been evaluated. This study evaluated changes in urine flow in mice with septic AKI. The intratubular urine flow rate was monitored in real time by intravital imaging using two-photon laser microscopy. The tubular flow rate, as measured by freely filtered dye (FITC-inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2 hours, the tubular flow rate was slower in mice injected with LPS than in mice injected with saline, whereas BP and GFR were similar in the two groups. Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal tubules that showed reduced tubular flow at 2 hours and luminal obstruction with cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor 4 in mice abolished these effects, whereas neutralization of TNF-α had little effect on LPS-induced tubular flow retention. Rapid intravenous fluid resuscitation within 6 hours improved the tubular flow rate only when accompanied by the dilation of obstructed proximal tubules with accumulated LPS. These findings suggest that LPS reduces the intratubular urine flow rate during early phases of endotoxemia through a Toll-like receptor 4–dependent mechanism, and that the efficacy of fluid resuscitation may depend on the response of tubules with LPS accumulation.10.1681/ASN.2014060577Wed, 08 Apr 2015 01:17:09 GMT-07:00Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital ImagingUrine output is widely used as a criterion for the diagnosis of AKI. Although several potential mechanisms of septic AKI have been identified, regulation of urine flow after glomerular filtration has not been evaluated. This study evaluated changes in urine flow in mice with septic AKI. The intratubular urine flow rate was monitored in real time by intravital imaging using two-photon laser microscopy. The tubular flow rate, as measured by freely filtered dye (FITC-inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2 hours, the tubular flow rate was slower in mice injected with LPS than in mice injected with saline, whereas BP and GFR were similar in the two groups. Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal tubules that showed reduced tubular flow at 2 hours and luminal obstruction with cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor 4 in mice abolished these effects, whereas neutralization of TNF-α had little effect on LPS-induced tubular flow retention. Rapid intravenous fluid resuscitation within 6 hours improved the tubular flow rate only when accompanied by the dilation of obstructed proximal tubules with accumulated LPS. These findings suggest that LPS reduces the intratubular urine flow rate during early phases of endotoxemia through a Toll-like receptor 4–dependent mechanism, and that the efficacy of fluid resuscitation may depend on the response of tubules with LPS accumulation.Nakano, DaisukeDoi, KentKitamura, HiroakiKuwabara, TakashigeMori, KiyoshiMukoyama, MasashiNishiyama, Akira2015-04-08T13:17:09-07:00doi:10.1681/ASN.2014060577hwp:resource-id:jnephrol;26/12/3035American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyARF, oliguria, renal tubular epithelial cells, LPSBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140605771046-66731533-34502015-04-08T13:17:09-07:002015-12Journal of the American Society of NephrologyBasic Research261230353044
- Cellular Senescence in the KidneySenescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury. Senescence has diverse physiologic roles and experimental studies support its importance in nephrogenesis, successful tissue repair, and in opposing malignant transformation. However, recent murine studies have shown that depletion of chronically senescent cells extends healthy lifespan and delays age-associated disease—implicating senescence and the senescence-associated secretory phenotype as drivers of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in kidney disease. In this review, we examine current knowledge and areas of ongoing uncertainty regarding senescence in the human kidney and experimental models. We summarize evidence supporting the role of senescence in normal kidney development and homeostasis but also senescence-induced maladaptive repair, renal fibrosis, and transplant failure. Recent studies using senescent cell manipulation and depletion as novel therapies to treat renal disease are discussed, and we explore unanswered questions for future research.10.1681/ASN.2018121251Thu, 18 Apr 2019 07:55:21 GMT-07:00Cellular Senescence in the KidneySenescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury. Senescence has diverse physiologic roles and experimental studies support its importance in nephrogenesis, successful tissue repair, and in opposing malignant transformation. However, recent murine studies have shown that depletion of chronically senescent cells extends healthy lifespan and delays age-associated disease—implicating senescence and the senescence-associated secretory phenotype as drivers of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in kidney disease. In this review, we examine current knowledge and areas of ongoing uncertainty regarding senescence in the human kidney and experimental models. We summarize evidence supporting the role of senescence in normal kidney development and homeostasis but also senescence-induced maladaptive repair, renal fibrosis, and transplant failure. Recent studies using senescent cell manipulation and depletion as novel therapies to treat renal disease are discussed, and we explore unanswered questions for future research.Docherty, Marie-HelenaO’Sullivan, Eoin D.Bonventre, Joseph V.Ferenbach, David A.2019-04-18T07:55:21-07:00doi:10.1681/ASN.2018121251hwp:resource-id:jnephrol;30/5/726American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, kidney development, acute renal failure, chronic kidney disease, progression of renal failureReviewReviewreview-article20192019-05-01May 201910.1681/ASN.20181212511046-66731533-34502019-04-18T07:55:21-07:002019-05Journal of the American Society of NephrologyReview305726736
- This Month's Highlights10.1681/ASN.2019030307Tue, 30 Apr 2019 10:00:25 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2019-04-30T10:00:25-07:00doi:10.1681/ASN.2019030307hwp:resource-id:jnephrol;30/5/iAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20192019-05-01May 201910.1681/ASN.20190303071046-66731533-34502019-04-30T10:00:25-07:002019-05Journal of the American Society of NephrologyThis Month’s Highlights305ii
- Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance10.1681/ASN.2018060609Tue, 02 Apr 2019 06:59:55 GMT-07:00Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose IntoleranceOpdebeeck, BrittMaudsley, StuartAzmi, AbdelkrimDe Maré, AnneliesDe Leger, WoutMeijers, BjornVerhulst, AnjaEvenepoel, PieterD’Haese, Patrick C.Neven, Ellen2019-04-02T06:59:55-07:00doi:10.1681/ASN.2018060609hwp:resource-id:jnephrol;30/5/751American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, vascular calcification, indoxyl sulfate, p-cresyl sulfate, hyperglycemiaBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180606091046-66731533-34502019-04-02T06:59:55-07:002019-05Journal of the American Society of NephrologyBasic Research305751766
- Protein Phosphatase 1 Inhibitor–1 Mediates the cAMP-Dependent Stimulation of the Renal NaCl Cotransporter10.1681/ASN.2018050540Fri, 22 Mar 2019 06:46:48 GMT-07:00Protein Phosphatase 1 Inhibitor–1 Mediates the cAMP-Dependent Stimulation of the Renal NaCl CotransporterPenton, DavidMoser, SandraWengi, AgnieszkaCzogalla, JanRosenbaek, Lena LindtoftRigendinger, FritzFaresse, NourdineMartins, Joana R.Fenton, Robert A.Loffing-Cueni, DominiqueLoffing, Johannes2019-03-22T06:46:48-07:00doi:10.1681/ASN.2018050540hwp:resource-id:jnephrol;30/5/737American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyCell & Transport Physiology, cyclic AMP, distal tubule, Na transport, NaCl cotransporter, signalingBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180505401046-66731533-34502019-03-22T06:46:48-07:002019-05Journal of the American Society of NephrologyBasic Research305737750
- Thrombospondin Type 1 Domain–Containing 7A Localizes to the Slit Diaphragm and Stabilizes Membrane Dynamics of Fully Differentiated Podocytes10.1681/ASN.2018090941Wed, 10 Apr 2019 08:09:50 GMT-07:00Thrombospondin Type 1 Domain–Containing 7A Localizes to the Slit Diaphragm and Stabilizes Membrane Dynamics of Fully Differentiated PodocytesHerwig, JohannaSkuza, SinahSachs, WiebkeSachs, MarliesFailla, Antonio VirgilioRune, GabrieleMeyer, Tobias N.Fester, LarsMeyer-Schwesinger, Catherine2019-04-10T08:09:50-07:00doi:10.1681/ASN.2018090941hwp:resource-id:jnephrol;30/5/824American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyTHSD7A, podocyte, membranous nephropathy, slit diaphragmBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180909411046-66731533-34502019-04-10T08:09:50-07:002019-05Journal of the American Society of NephrologyBasic Research305824839
- Mutations in NUP160 Are Implicated in Steroid-Resistant Nephrotic Syndrome10.1681/ASN.2018080786Mon, 25 Mar 2019 04:21:47 GMT-07:00Mutations in NUP160 Are Implicated in Steroid-Resistant Nephrotic SyndromeZhao, FengZhu, Jun-yiRichman, AdamFu, YulongHuang, WenChen, NanPan, XiaoxiaYi, CuiliDing, XiaohuaWang, SiWang, PingNie, XiaojingHuang, JunYang, YonghuiYu, ZihuaHan, Zhe2019-03-25T04:21:47-07:00doi:10.1681/ASN.2018080786hwp:resource-id:jnephrol;30/5/840American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologynephrocyte, Drosophila, nephrotic syndrome, NUP160, genetic renal disease, human geneticsBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180807861046-66731533-34502019-03-25T04:21:47-07:002019-05Journal of the American Society of NephrologyBasic Research3055840719853720
- Filling the Gap: Drosophila Nephrocytes as Model System in Kidney Research10.1681/ASN.2019020181Mon, 25 Mar 2019 04:21:46 GMT-07:00Filling the Gap: Drosophila Nephrocytes as Model System in Kidney ResearchMarelja, ZvonimirSimons, Matias2019-03-25T04:21:46-07:00doi:10.1681/ASN.2019020181hwp:resource-id:jnephrol;30/5/719American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyDrosophila, nephrotic syndrome, genetic renal diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-05-01May 201910.1681/ASN.20190201811046-66731533-34502019-03-25T04:21:46-07:002019-05Journal of the American Society of NephrologyUp Front Matters3055719840720853
- Severe Arterial Hypertension from Cullin 3 Mutations Is Caused by Both Renal and Vascular Effects10.1681/ASN.2017121307Tue, 09 Apr 2019 04:37:58 GMT-07:00Severe Arterial Hypertension from Cullin 3 Mutations Is Caused by Both Renal and Vascular EffectsAbdel Khalek, WaedRafael, ChloéLoisel-Ferreira, IrmineKouranti, IlektraClauser, EricHadchouel, JulietteJeunemaitre, Xavier2019-04-09T04:37:58-07:00doi:10.1681/ASN.2017121307hwp:resource-id:jnephrol;30/5/811American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, Ubiquitination, RhoA, WNK kinases, distal tubule, Hemodynamics and Vascular RegulationBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20171213071046-66731533-34502019-04-09T04:37:58-07:002019-05Journal of the American Society of NephrologyBasic Research305811823
- An Antifungal for Antidiuresis?10.1681/ASN.2019030285Fri, 12 Apr 2019 05:27:19 GMT-07:00An Antifungal for Antidiuresis?Verbalis, Joseph G.2019-04-12T05:27:19-07:00doi:10.1681/ASN.2019030285hwp:resource-id:jnephrol;30/5/717American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyantidiuresis, osmotic water transport, fluconozoleUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-05-01May 201910.1681/ASN.20190302851046-66731533-34502019-04-12T05:27:19-07:002019-05Journal of the American Society of NephrologyUp Front Matters3055717795718810
- Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study10.1681/ASN.2018101017Wed, 10 Apr 2019 08:09:50 GMT-07:00Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort StudyJarrick, SimonLundberg, SigridWelander, AdinaCarrero, Juan-JesusHöijer, JonasBottai, MatteoLudvigsson, Jonas F.2019-04-10T08:09:50-07:00doi:10.1681/ASN.2018101017hwp:resource-id:jnephrol;30/5/866American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologymortality risk, IgA nephropathy, end-stage renal disease, Epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20192019-05-01May 201910.1681/ASN.20181010171046-66731533-34502019-04-10T08:09:50-07:002019-05Journal of the American Society of NephrologyClinical Epidemiology3055866720876722
- Authors’ Reply10.1681/ASN.2019020124Mon, 25 Mar 2019 04:21:48 GMT-07:00Authors’ ReplyMarques, Igor Denizarde BacelarElias, Rosilene MottaMoysés, Rosa Maria AffonsoDavid-Neto, Elias2019-03-25T04:21:48-07:00doi:10.1681/ASN.2019020124hwp:resource-id:jnephrol;30/5/906American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, renal osteodystrophy, zoledronic acidLetter to the EditorLetter to the Editorletter20192019-05-01May 201910.1681/ASN.20190201241046-66731533-34502019-03-25T04:21:48-07:002019-05Journal of the American Society of NephrologyLetter to the Editor3055906905906905
- Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking10.1681/ASN.2018060668Mon, 15 Apr 2019 07:52:24 GMT-07:00Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 TraffickingVukićević, TanjaHinze, ChristianBaltzer, SandrineHimmerkus, NinaQuintanova, CatarinaZühlke, KerstinCompton, FriederikeAhlborn, RobertDema, AlessandroEichhorst, JennyWiesner, BurkhardBleich, MarkusSchmidt-Ott, Kai M.Klussmann, Enno2019-04-15T07:52:24-07:00doi:10.1681/ASN.2018060668hwp:resource-id:jnephrol;30/5/795American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologycyclic AMP, diabetes insipidus, intracellular signal, renal cell biology, vasopressin, water channelsBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180606681046-66731533-34502019-04-15T07:52:24-07:002019-05Journal of the American Society of NephrologyBasic Research3055795717810718
- Mortality Risk in IgA Nephropathy10.1681/ASN.2018121255Wed, 10 Apr 2019 08:09:50 GMT-07:00Mortality Risk in IgA NephropathyGlassock, Richard J.2019-04-10T08:09:50-07:00doi:10.1681/ASN.2018121255hwp:resource-id:jnephrol;30/5/720American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, mortality risk, End Stage Kidney Disease riskUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-05-01May 201910.1681/ASN.20181212551046-66731533-34502019-04-10T08:09:50-07:002019-05Journal of the American Society of NephrologyUp Front Matters3055720866722876
- Single-Cell RNA Sequencing Identifies Candidate Renal Resident Macrophage Gene Expression Signatures across Species10.1681/ASN.2018090931Thu, 04 Apr 2019 08:01:11 GMT-07:00Single-Cell RNA Sequencing Identifies Candidate Renal Resident Macrophage Gene Expression Signatures across SpeciesZimmerman, Kurt A.Bentley, Melissa R.Lever, Jeremie M.Li, ZhangCrossman, David K.Song, Cheng JackLiu, ShanrunCrowley, Michael R.George, James F.Mrug, MichalYoder, Bradley K.2019-04-04T08:01:11-07:00doi:10.1681/ASN.2018090931hwp:resource-id:jnephrol;30/5/767American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologymacrophages., transcriptional profiling, immunologyBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180909311046-66731533-34502019-04-04T08:01:11-07:002019-05Journal of the American Society of NephrologyBasic Research3055767715781716
- GNAS: A New Nephrogenic Cause of Inappropriate Antidiuresis10.1681/ASN.2019020143Mon, 08 Apr 2019 05:32:29 GMT-07:00GNAS: A New Nephrogenic Cause of Inappropriate AntidiuresisBichet, Daniel G.Granier, SébastienBockenhauer, Detlef2019-04-08T05:32:29-07:00doi:10.1681/ASN.2019020143hwp:resource-id:jnephrol;30/5/722American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyGNAS, hyponatremia, nephrogenic syndromeUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-05-01May 201910.1681/ASN.20190201431046-66731533-34502019-04-08T05:32:29-07:002019-05Journal of the American Society of NephrologyUp Front Matters3055722877725889
- Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population10.1681/ASN.2018090942Thu, 11 Apr 2019 05:08:13 GMT-07:00Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese PopulationTanikawa, ChizuKamatani, YoichiroTerao, ChikashiUsami, MasayukiTakahashi, AtsushiMomozawa, YukihideSuzuki, KichiyaOgishima, SoichiShimizu, AtsushiSatoh, MamoruMatsuo, KeitaroMikami, HaruoNaito, MarikoWakai, KenjiYamaji, TaikiSawada, NorieIwasaki, MotokiTsugane, ShoichiroKohri, KenjiroYu, Alan S.L.Yasui, TakahiroMurakami, YoshinoriKubo, MichiakiMatsuda, Koichi2019-04-11T05:08:13-07:00doi:10.1681/ASN.2018090942hwp:resource-id:jnephrol;30/5/855American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney stones, human genetics, genetics and developmentClinical EpidemiologyClinical Epidemiologyresearch-article20192019-05-01May 201910.1681/ASN.20180909421046-66731533-34502019-04-11T05:08:13-07:002019-05Journal of the American Society of NephrologyClinical Epidemiology305855864
- The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration10.1681/ASN.2018090945Thu, 18 Apr 2019 07:55:21 GMT-07:00The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session DurationDember, Laura M.Lacson, EduardoBrunelli, Steven M.Hsu, Jesse Y.Cheung, Alfred K.Daugirdas, John T.Greene, TomKovesdy, Csaba P.Miskulin, Dana C.Thadhani, Ravi I.Winkelmayer, Wolfgang C.Ellenberg, Susan S.Cifelli, DeniseMadigan, RosemaryYoung, AmyAngeletti, MichaelWingard, Rebecca L.Kahn, ChristinaNissenson, Allen R.Maddux, Franklin W.Abbott, Kevin C.Landis, J. Richard2019-04-18T07:55:21-07:00doi:10.1681/ASN.2018090945hwp:resource-id:jnephrol;30/5/890American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyTiME Trial, dialysis session duration, learning health system, NIH Health Care Systems Research Collaboratory, opt-out consent, consent waiverClinical ResearchClinical Researchresearch-article20192019-05-01May 201910.1681/ASN.20180909451046-66731533-34502019-04-18T07:55:21-07:002019-05Journal of the American Society of NephrologyClinical Research305890903
- Germline-Derived Gain-of-Function Variants of Gsα-Coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate Antidiuresis10.1681/ASN.2018121268Mon, 08 Apr 2019 05:32:29 GMT-07:00Germline-Derived Gain-of-Function Variants of Gsα-Coding GNAS Gene Identified in Nephrogenic Syndrome of Inappropriate AntidiuresisMiyado, MamiFukami, MakiTakada, ShujiTerao, MihoNakabayashi, KazuhikoHata, KenichiroMatsubara, YoichiTanaka, YokoSasaki, GoroNagasaki, KeisukeShiina, MasaakiOgata, KazuhiroMasunaga, YouheiSaitsu, HirotomoOgata, Tsutomu2019-04-08T05:32:29-07:00doi:10.1681/ASN.2018121268hwp:resource-id:jnephrol;30/5/877American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, molecular genetics, vasopressin, water-electrolyte balance, water transport, signalingClinical ResearchClinical Researchresearch-article20192019-05-01May 201910.1681/ASN.20181212681046-66731533-34502019-04-08T05:32:29-07:002019-05Journal of the American Society of NephrologyClinical Research3055877722889725
- Inhibition of Sodium Glucose Cotransporter 2 Attenuates the Dysregulation of Kelch-Like 3 and NaCl Cotransporter in Obese Diabetic Mice10.1681/ASN.2018070703Tue, 26 Mar 2019 06:34:53 GMT-07:00Inhibition of Sodium Glucose Cotransporter 2 Attenuates the Dysregulation of Kelch-Like 3 and NaCl Cotransporter in Obese Diabetic MiceIshizawa, KenichiWang, QinLi, JinpingXu, NingNemoto, YoshikazuMorimoto, ChikayukiFujii, WataruTamura, YoshifuruFujigaki, YoshihideTsukamoto, KazuhisaFujita, ToshiroUchida, ShunyaShibata, Shigeru2019-03-26T06:34:53-07:00doi:10.1681/ASN.2018070703hwp:resource-id:jnephrol;30/5/782American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperglycemia, Cell Signaling, diabetes mellitus, distal tubule, Na transportBasic ResearchBasic Researchresearch-article20192019-05-01May 201910.1681/ASN.20180707031046-66731533-34502019-03-26T06:34:53-07:002019-05Journal of the American Society of NephrologyBasic Research305782794
- How to Find a Resident Kidney Macrophage: the Single-Cell Sequencing Solution10.1681/ASN.2019030245Thu, 04 Apr 2019 08:01:11 GMT-07:00How to Find a Resident Kidney Macrophage: the Single-Cell Sequencing SolutionClatworthy, Menna R.2019-04-04T08:01:11-07:00doi:10.1681/ASN.2019030245hwp:resource-id:jnephrol;30/5/715American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologymacrophages., mRNA, immunologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-05-01May 201910.1681/ASN.20190302451046-66731533-34502019-04-04T08:01:11-07:002019-05Journal of the American Society of NephrologyUp Front Matters3055715767716781
- Biphosphonate Therapy, Risk of Fracture, and Sites of Bone Mineral Density Assessments in Kidney Transplantation10.1681/ASN.2019010079Mon, 25 Mar 2019 04:21:47 GMT-07:00Biphosphonate Therapy, Risk of Fracture, and Sites of Bone Mineral Density Assessments in Kidney TransplantationTabibzadeh, NahidChavarot, NathalieFlamant, MartinVidal-Petiot, Emmanuelle2019-03-25T04:21:47-07:00doi:10.1681/ASN.2019010079hwp:resource-id:jnephrol;30/5/905American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, mineral metabolism, renal osteodystrophyLetter to the EditorLetter to the Editorletter20192019-05-01May 201910.1681/ASN.20190100791046-66731533-34502019-03-25T04:21:47-07:002019-05Journal of the American Society of NephrologyLetter to the Editor3055905906905906
- T Cells Play a Causal Role in Diastolic Dysfunction during Uremic Cardiomyopathy10.1681/ASN.2017101138Wed, 06 Feb 2019 07:08:20 GMT-08:00T Cells Play a Causal Role in Diastolic Dysfunction during Uremic CardiomyopathyWinterberg, Pamela D.Robertson, Jennifer M.Kelleman, Michael S.George, Roshan P.Ford, Mandy L.2019-02-06T07:08:20-08:00doi:10.1681/ASN.2017101138hwp:resource-id:jnephrol;30/3/407American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, T-Lymphocyte Subsets, 129 Mice, Diastolic Heart Failure, Doppler EchocardiographyBasic ResearchBasic Researchresearch-article20192019-03-01March 201910.1681/ASN.20171011381046-66731533-34502019-02-06T07:08:20-08:002019-03Journal of the American Society of NephrologyBasic Research303407420
- Iron, Hepcidin, and Death in Human AKI10.1681/ASN.2018100979Fri, 08 Feb 2019 05:19:07 GMT-08:00Iron, Hepcidin, and Death in Human AKILeaf, David E.Rajapurkar, MohanLele, Suhas S.Mukhopadhyay, BanibrataBoerger, Emily A.S.Mc Causland, Finnian R.Eisenga, Michele F.Singh, KarandeepBabitt, Jodie L.Kellum, John A.Palevsky, Paul M.Christov, MartaWaikar, Sushrut S.2019-02-08T05:19:07-08:00doi:10.1681/ASN.2018100979hwp:resource-id:jnephrol;30/3/493American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, mortality risk, nephrotoxicity, outcomesClinical ResearchClinical Researchresearch-article20192019-03-01March 201910.1681/ASN.20181009791046-66731533-34502019-02-08T05:19:07-08:002019-03Journal of the American Society of NephrologyClinical Research303493504
- Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of Sec63 in Collecting Ducts10.1681/ASN.2018060614Mon, 11 Feb 2019 03:41:49 GMT-08:00Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of Sec63 in Collecting DuctsIshikawa, YasunobuFedeles, SorinMarlier, ArnaudZhang, ChaoGallagher, Anna-RachelLee, Ann-HweeSomlo, Stefan2019-02-11T03:41:49-08:00doi:10.1681/ASN.2018060614hwp:resource-id:jnephrol;30/3/443American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, chronic kidney disease, renal tubular epithelial cells, renal fibrosis, endoplasmic reticulumBasic ResearchBasic Researchresearch-article20192019-03-01March 201910.1681/ASN.20180606141046-66731533-34502019-02-11T03:41:49-08:002019-03Journal of the American Society of NephrologyBasic Research303443459
- Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Coq6 Knockout Mice10.1681/ASN.2018060625Fri, 08 Feb 2019 05:19:07 GMT-08:00Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Coq6 Knockout MiceWidmeier, EugenAirik, MerlinHugo, HannahSchapiro, DavidWedel, JohannesGhosh, Chandra C.Nakayama, MakikoSchneider, RonenAwad, Agape M.Nag, AnishCho, JangSchueler, MarkusClarke, Catherine F.Airik, RannarHildebrandt, Friedhelm2019-02-08T05:19:07-08:00doi:10.1681/ASN.2018060625hwp:resource-id:jnephrol;30/3/393American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, podocyte, focal segmental glomerulosclerosisBasic ResearchBasic Researchresearch-article20192019-03-01March 201910.1681/ASN.20180606251046-66731533-34502019-02-08T05:19:07-08:002019-03Journal of the American Society of NephrologyBasic Research303393405
- Long-Range Chromatin Interactions in the Kidney10.1681/ASN.2019010044Wed, 13 Feb 2019 06:28:49 GMT-08:00Long-Range Chromatin Interactions in the KidneyGuan, YutingLiu, HongboSusztak, Katalin2019-02-13T06:28:49-08:00doi:10.1681/ASN.2019010044hwp:resource-id:jnephrol;30/3/367American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyGWAS, DAB2, Hi-C, kidneyUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-03-01March 201910.1681/ASN.20190100441046-66731533-34502019-02-13T06:28:49-08:002019-03Journal of the American Society of NephrologyUp Front Matters3033367421369441
- Cardiopulmonary Resuscitation in Outpatient Dialysis Clinics: Perception of Futility?10.1681/ASN.2019010046Thu, 07 Feb 2019 06:03:22 GMT-08:00Cardiopulmonary Resuscitation in Outpatient Dialysis Clinics: Perception of Futility?Imbeault, BenoitChan, Christopher T.2019-02-07T06:03:22-08:00doi:10.1681/ASN.2019010046hwp:resource-id:jnephrol;30/3/369American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular, dialysis, sudden cardiac deathUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-03-01March 201910.1681/ASN.20190100461046-66731533-34502019-02-07T06:03:22-08:002019-03Journal of the American Society of NephrologyUp Front Matters3033369461370470
- Erratum10.1681/ASN.2019010051Thu, 28 Feb 2019 10:00:23 GMT-08:00ErratumAmerican Society of Nephrology2019-02-28T10:00:23-08:00doi:10.1681/ASN.2019010051hwp:resource-id:jnephrol;30/3/518American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20192019-03-01March 201910.1681/ASN.20190100511046-66731533-34502019-02-28T10:00:23-08:002019-03Journal of the American Society of NephrologyErrata302931151827455182754
- Erratum10.1681/ASN.2019010048Thu, 28 Feb 2019 10:00:23 GMT-08:00ErratumAmerican Society of Nephrology2019-02-28T10:00:23-08:00doi:10.1681/ASN.2019010048hwp:resource-id:jnephrol;30/3/517American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20192019-03-01March 201910.1681/ASN.20190100481046-66731533-34502019-02-28T10:00:23-08:002019-03Journal of the American Society of NephrologyErrata302931051725105172517
- Erratum10.1681/ASN.2018121245Thu, 28 Feb 2019 10:00:23 GMT-08:00ErratumAmerican Society of Nephrology2019-02-28T10:00:23-08:00doi:10.1681/ASN.2018121245hwp:resource-id:jnephrol;30/3/516American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20192019-03-01March 201910.1681/ASN.20181212451046-66731533-34502019-02-28T10:00:23-08:002019-03Journal of the American Society of NephrologyErrata302531516175516186
- An Organizational-Level Program of Intervention for AKI: A Pragmatic Stepped Wedge Cluster Randomized Trial10.1681/ASN.2018090886Thu, 21 Feb 2019 12:58:52 GMT-08:00An Organizational-Level Program of Intervention for AKI: A Pragmatic Stepped Wedge Cluster Randomized TrialSelby, Nicholas M.Casula, AnnaLamming, LauraStoves, JohnSamarasinghe, YohanLewington, Andrew J.Roberts, RussellShah, NikunjJohnson, MelanieJackson, NatalieJones, CarolLenguerrand, ErikMcDonach, EileenFluck, Richard J.Mohammed, Mohammed A.Caskey, Fergus J.Bosomworth, MikeDuncan, GeorgieGarner, AshleyAzad, RafaqBal, BethanyBatuista, ArleneHussain, RazyaHeppleston, EricaBenton, SallyMcKibben, CraigSlevin, Julie2019-02-21T12:58:52-08:00doi:10.1681/ASN.2018090886hwp:resource-id:jnephrol;30/3/505American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, e-alert, care bundle, education, AKIClinical ResearchClinical Researchresearch-article20192019-03-01March 201910.1681/ASN.20180908861046-66731533-34502019-02-21T12:58:52-08:002019-03Journal of the American Society of NephrologyClinical Research3033505371515372
- A Pragmatic Step Forward: AKI and Beyond10.1681/ASN.2019010076Thu, 21 Feb 2019 12:58:52 GMT-08:00A Pragmatic Step Forward: AKI and BeyondDember, Laura M.2019-02-21T12:58:52-08:00doi:10.1681/ASN.2019010076hwp:resource-id:jnephrol;30/3/371American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, hospitalization, clinical trialUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-03-01March 201910.1681/ASN.20190100761046-66731533-34502019-02-21T12:58:52-08:002019-03Journal of the American Society of NephrologyUp Front Matters3033371505372515
- Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci10.1681/ASN.2018030309Wed, 13 Feb 2019 06:28:49 GMT-08:00Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study LociSieber, Karsten B.Batorsky, AnnaSiebenthall, KyleHudkins, Kelly L.Vierstra, Jeff D.Sullivan, ShawnSur, AakashMcNulty, MichelleSandstrom, RichardReynolds, AlexBates, DanielDiegel, MorganDunn, DouglassNelson, JemmaBuckley, MichaelKaul, RajinderSampson, Matthew G.Himmelfarb, JonathanAlpers, Charles E.Waterworth, DawnAkilesh, Shreeram2019-02-13T06:28:49-08:00doi:10.1681/ASN.2018030309hwp:resource-id:jnephrol;30/3/421American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyEpigenetics, gene transcription, mesangial cells, podocyte, tubule cells, Human genomicsBasic ResearchBasic Researchresearch-article20192019-03-01March 201910.1681/ASN.20180303091046-66731533-34502019-02-13T06:28:49-08:002019-03Journal of the American Society of NephrologyBasic Research3033421367441369
- Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis10.1681/ASN.2018030277Wed, 06 Feb 2019 07:08:21 GMT-08:00Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate LithogenesisKhamaysi, AhlamAnbtawee-Jomaa, ShireenFremder, MoranEini-Rider, HadarShimshilashvili, LianaAharon, SaraAizenshtein, ElinaShlomi, TomerNoguchi, AudreySpringer, DanielleMoe, Orson W.Shcheynikov, NikolayMuallem, ShmuelOhana, Ehud2019-02-06T07:08:21-08:00doi:10.1681/ASN.2018030277hwp:resource-id:jnephrol;30/3/381American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologysuccinate, citrate, calcium-oxalate kidney stones, SUCNR1, signaling, ion transportBasic ResearchBasic Researchresearch-article20192019-03-01March 201910.1681/ASN.20180302771046-66731533-34502019-02-06T07:08:21-08:002019-03Journal of the American Society of NephrologyBasic Research303381392
- Lower Extremity Amputation and Health Care Utilization in the Last Year of Life among Medicare Beneficiaries with ESRD10.1681/ASN.2018101002Tue, 19 Feb 2019 06:47:10 GMT-08:00Lower Extremity Amputation and Health Care Utilization in the Last Year of Life among Medicare Beneficiaries with ESRDButler, Catherine R.Schwarze, Margaret L.Katz, RonitHailpern, Susan M.Kreuter, WilliamHall, Yoshio N.Montez Rath, Maria E.O'Hare, Ann M.2019-02-19T06:47:10-08:00doi:10.1681/ASN.2018101002hwp:resource-id:jnephrol;30/3/481American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, end-of-life, amputation, surgery, vascular disease, palliative careClinical EpidemiologyClinical Epidemiologyresearch-article20192019-03-01March 201910.1681/ASN.20181010021046-66731533-34502019-02-19T06:47:10-08:002019-03Journal of the American Society of NephrologyClinical Epidemiology3033481373491374
- Outcomes for Hemodialysis Patients Given Cardiopulmonary Resuscitation for Cardiac Arrest at Outpatient Dialysis Clinics10.1681/ASN.2018090911Thu, 07 Feb 2019 06:03:21 GMT-08:00Outcomes for Hemodialysis Patients Given Cardiopulmonary Resuscitation for Cardiac Arrest at Outpatient Dialysis ClinicsPun, Patrick H.Dupre, Matthew E.Starks, Monique A.Tyson, ClarkVellano, KimberlySvetkey, Laura P.Hansen, SteenFrizzelle, Brian G.McNally, BryanJollis, James G.Al-Khatib, Sana M.Granger, Christopher B.,2019-02-07T06:03:21-08:00doi:10.1681/ASN.2018090911hwp:resource-id:jnephrol;30/3/461American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular, hemodialysis, cardiovascular events, Life-threatening, dialysis complicationsClinical EpidemiologyClinical Epidemiologyresearch-article20192019-03-01March 201910.1681/ASN.20180909111046-66731533-34502019-02-07T06:03:21-08:002019-03Journal of the American Society of NephrologyClinical Epidemiology3033461369470370
- This Month's Highlights10.1681/ASN.2019010080Thu, 28 Feb 2019 10:00:23 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2019-02-28T10:00:23-08:00doi:10.1681/ASN.2019010080hwp:resource-id:jnephrol;30/3/iAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20192019-03-01March 201910.1681/ASN.20190100801046-66731533-34502019-02-28T10:00:23-08:002019-03Journal of the American Society of NephrologyThis Month’s Highlights303ii
- Traditional Urinary Biomarkers in the Assessment of Hospital-Acquired AKITraditional biomarkers, such as urine chemistries and urine microscopic elements, are used in the diagnosis and care of patients with AKI. Urine chemistries, such as fractional excretion of sodium and fractional excretion of urea, are useful for differentiating prerenal AKI from acute tubular necrosis only in select patients. Urine microscopy using a quantitative evaluation of the urine sediment for renal tubular epithelial cells, renal tubular epithelial cell casts, and granular casts has recently been shown to differentiate prerenal AKI from acute tubular necrosis and also provide prognostic information. Urine microscopy has also been noted to compare favorably with new urine biomarkers for diagnosis and prognosis of AKI. Thus, current information on urine diagnostics suggests that urine chemistries have a limited role in differential diagnosis of AKI, whereas urine microscopy and new urine biomarkers may be used together to differentiate prerenal AKI from acute tubular necrosis and predict such outcomes as worsened AKI, acute dialysis, and death.mark.perazella@yale.edu10.2215/CJN.09490911Thu, 17 Nov 2011 08:23:00 GMT-08:00Traditional Urinary Biomarkers in the Assessment of Hospital-Acquired AKITraditional biomarkers, such as urine chemistries and urine microscopic elements, are used in the diagnosis and care of patients with AKI. Urine chemistries, such as fractional excretion of sodium and fractional excretion of urea, are useful for differentiating prerenal AKI from acute tubular necrosis only in select patients. Urine microscopy using a quantitative evaluation of the urine sediment for renal tubular epithelial cells, renal tubular epithelial cell casts, and granular casts has recently been shown to differentiate prerenal AKI from acute tubular necrosis and also provide prognostic information. Urine microscopy has also been noted to compare favorably with new urine biomarkers for diagnosis and prognosis of AKI. Thus, current information on urine diagnostics suggests that urine chemistries have a limited role in differential diagnosis of AKI, whereas urine microscopy and new urine biomarkers may be used together to differentiate prerenal AKI from acute tubular necrosis and predict such outcomes as worsened AKI, acute dialysis, and death.Perazella, Mark A.G. Coca, Steven2011-11-17T08:23:00-08:00doi:10.2215/CJN.09490911hwp:resource-id:clinjasn;7/1/167American Society of NephrologyCopyright © 2012 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20122012-01-01January 13, 201210.2215/CJN.094909111555-90411555-905X2011-11-17T08:23:00-08:002012-01Clinical Journal of the American Society of NephrologyMini-Review71167174
- Recovery of Kidney Function in Children Treated with Maintenance Dialysis10.2215/CJN.01500218Thu, 20 Sep 2018 09:05:10 GMT-07:00Recovery of Kidney Function in Children Treated with Maintenance DialysisBonthuis, MarjoleinHarambat, JérômeBérard, EtienneCransberg, KarlienDuzova, AliGarneata, LilianaHerthelius, MariaLungu, Adrian C.Jahnukainen, TimoKaltenegger, LukasAriceta, GemaMaurer, ElisabethPalsson, RunolfurSinha, Manish D.Testa, SaraGroothoff, Jaap W.Jager, Kitty J.,2018-09-20T09:05:10-07:00doi:10.2215/CJN.01500218hwp:resource-id:clinjasn;13/10/1510American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal function recovery, chronic dialysis, pediatric nephrology, ESRD, renal dialysis, kidney transplantation, Edetic Acid, Incidence, Proportional Hazards Models, Kidney Failure, Chronic, peritoneal dialysis, kidney, Renal Insufficiency, Hemolytic-Uremic Syndrome, Registries, vasculitis, Cohort StudiesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-10-08October 08, 201810.2215/CJN.015002181555-90411555-905X2018-09-20T09:05:10-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles131015101516
- Vascular Dysfunction, Oxidative Stress, and Inflammation in Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.05850518Tue, 18 Sep 2018 08:09:52 GMT-07:00Vascular Dysfunction, Oxidative Stress, and Inflammation in Autosomal Dominant Polycystic Kidney DiseaseNowak, Kristen L.Wang, WeiFarmer-Bailey, HeatherGitomer, BereniceMalaczewski, MikaelaKlawitter, JelenaJovanovich, AnnaChonchol, Michel2018-09-18T08:09:52-07:00doi:10.2215/CJN.05850518hwp:resource-id:clinjasn;13/10/1493American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, endothelium, polycystic kidney disease, pulse wave velocity, vascular, inflammation, Pulse Wave Analysis, Brachial Artery, Vascular Stiffness, Polycystic Kidney, Autosomal Dominant, Ascorbic Acid, Complement Factor B, glomerular filtration rate, Confidence Intervals, Dilatation, Tandem Mass Spectrometry, endothelial cells, Dilatation, Pathologic, oxidative stress, Inflammation, Enzyme-Linked Immunosorbent Assay, Chromatography, Liquid, hypertension, lipidsOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20182018-10-08October 08, 201810.2215/CJN.058505181555-90411555-905X2018-09-18T08:09:52-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles131014931501
- The Relationship between Intradialytic Hypotension and Hospitalized Mesenteric Ischemia10.2215/CJN.13891217Thu, 20 Sep 2018 09:05:09 GMT-07:00The Relationship between Intradialytic Hypotension and Hospitalized Mesenteric IschemiaSeong, Eun YoungZheng, YuanchaoWinkelmayer, Wolfgang C.Montez-Rath, Maria E.Chang, Tara I.2018-09-20T09:05:09-07:00doi:10.2215/CJN.13891217hwp:resource-id:clinjasn;13/10/1517American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, vascular disease, end stage kidney disease, renal dialysis, coronary artery disease, blood pressure, Peripheral Arterial Disease, risk factors, Case-Control Studies, Mesenteric Ischemia, Prevalence, Kidney Failure, Chronic, hypotension, diabetes mellitusOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-10-08October 08, 201810.2215/CJN.138912171555-90411555-905X2018-09-20T09:05:09-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles1310101517145315251454
- Inching toward a Greater Understanding of Genetic Hypercalciuria10.2215/CJN.10030818Wed, 19 Sep 2018 07:31:57 GMT-07:00Inching toward a Greater Understanding of Genetic HypercalciuriaShah, Ronak JagdeepLieske, John C.2018-09-19T07:31:57-07:00doi:10.2215/CJN.10030818hwp:resource-id:clinjasn;13/10/1460American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypercalciuria, nephrolithiasis, human genetics, Claudins, Genetic TherapyEditorialsEditorialseditorial20182018-10-08October 08, 201810.2215/CJN.100308181555-90411555-905X2018-09-19T07:31:57-07:002018-10-08Clinical Journal of the American Society of NephrologyEditorials1310101460154214621549
- Proton Pump Inhibitors in Kidney Disease10.2215/CJN.10110818Thu, 27 Sep 2018 07:58:47 GMT-07:00Proton Pump Inhibitors in Kidney DiseaseLazarus, BenjaminGrams, Morgan E.2018-09-27T07:58:47-07:00doi:10.2215/CJN.10110818hwp:resource-id:clinjasn;13/10/1458American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyProton Pump Inhibitors, kidney diseaseEditorialsEditorialseditorial20182018-10-08October 08, 201810.2215/CJN.101108181555-90411555-905X2018-09-27T07:58:47-07:002018-10-08Clinical Journal of the American Society of NephrologyEditorials1310101458153414591541
- Uromodulin and Nephron Mass10.2215/CJN.03600318Fri, 27 Jul 2018 09:42:09 GMT-07:00Uromodulin and Nephron MassPivin, EdwardPonte, Belende Seigneux, SophieAckermann, DanielGuessous, IdrisEhret, GeorgPechère-Bertschi, AntoinetteOlinger, EricMohaupt, MarkusVogt, BrunoMartin, Pierre-YvesBurnier, MichelBochud, MurielleDevuyst, OlivierPruijm, Menno2018-07-27T09:42:09-07:00doi:10.2215/CJN.03600318hwp:resource-id:clinjasn;13/10/1556American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular filtration rate, birthweight, Tamm-Horsfall, biomarker, living kidney donation, tubule cells, Nephrons, Macrophage Activation Syndrome, Molecular Weight, NephrectomyResearch LetterResearch Letterletter20182018-10-08October 08, 201810.2215/CJN.036003181555-90411555-905X2018-07-27T09:42:09-07:002018-10-08Clinical Journal of the American Society of NephrologyResearch Letter131015561557
- Metabolic Acidosis and Cardiovascular Disease Risk in CKD10.2215/CJN.10120818Thu, 20 Sep 2018 09:05:11 GMT-07:00Metabolic Acidosis and Cardiovascular Disease Risk in CKDAbramowitz, Matthew K.2018-09-20T09:05:11-07:00doi:10.2215/CJN.10120818hwp:resource-id:clinjasn;13/10/1451American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic metabolic acidosis, cardiovascular disease, chronic kidney disease, acidosis, Renal Insufficiency, Chronic, Acid-Base EquilibriumEditorialsEditorialseditorial20182018-10-08October 08, 201810.2215/CJN.101208181555-90411555-905X2018-09-20T09:05:11-07:002018-10-08Clinical Journal of the American Society of NephrologyEditorials1310101451146314521470
- Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health10.2215/CJN.04670418Thu, 13 Sep 2018 10:03:40 GMT-07:00Perfluorinated Chemicals as Emerging Environmental Threats to Kidney HealthStanifer, John W.Stapleton, Heather M.Souma, TomokazuWittmer, AshleyZhao, XinluBoulware, L. Ebony2018-09-13T10:03:40-07:00doi:10.2215/CJN.04670418hwp:resource-id:clinjasn;13/10/1479American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyActin Cytoskeleton, Environment, Epidemiologic Studies, Epithelial-Mesenchymal Transition, Exposure, Global Health, Health Disparities, kidney, Kidney Diseases, Kidney Tubules, Proximal, oxidative stress, Permeability, Peroxisome Proliferators, Pollutants, Toxicology, NF-E2-Related Factor 2Original ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-10-08October 08, 201810.2215/CJN.046704181555-90411555-905X2018-09-13T10:03:40-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles131014791492
- Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis10.2215/CJN.02190218Thu, 27 Sep 2018 07:58:48 GMT-07:00Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on HemodialysisVangala, ChandanNiu, JingboLenihan, Colin R.Mitch, William E.Navaneethan, Sankar D.Winkelmayer, Wolfgang C.2018-09-27T07:58:48-07:00doi:10.2215/CJN.02190218hwp:resource-id:clinjasn;13/10/1534American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, Epidemiology and outcomes, drug safety, case-control, USRDS, Odds Ratio, Proton Pump Inhibitors, renal dialysis, Logistic Models, Histamine, Medicare Part D, Histamine H2 Antagonists, Kidney Failure, Chronic, Hip Fractures, obesityOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-10-08October 08, 201810.2215/CJN.021902181555-90411555-905X2018-09-27T07:58:48-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles1310101534145815411459
- Young Kidney Professionals’ Perspectives and Attitudes about Consuming Scientific InformationThe digital era has seen rapid changes in how information is consumed. Traditional dissemination of scholarly work through biomedical journals may not be optimally tailored to the preferences of younger clinicians and researchers. We aimed to describe the perspectives of young clinicians and researchers in kidney disease on consuming scientific information. Three focus groups were conducted during the 2017 American Society of Nephrology Kidney Week with a total of 29 nephrologists and researchers (ages 40 years old and younger) purposively sampled through our networks and the American Society of Nephrology registration database. Data were analyzed thematically. Of the 72 participants invited, 29 participated from 28 centers across 13 countries. Five themes were identified: capturing and retaining attention (with subthemes of triggering interest, optimizing readability, and navigation to sustain motivation); having discernible relevance (resonating with clinical and research interests, supporting professional development, action-oriented and readily applicable, able to disseminate, contextualizing the study, and filtering out informational noise); immediacy and efficiency in processing information (requiring instantaneous and easy access, enabling rapid understanding, and facilitating comprehension of complex concepts); trusting legitimate and credible sources (authoritative indicator of importance and quality, reputable experts broadening perspective, certainty and confidence with collegial input, accurate framing and translation of the message, ascertaining methodologic detail and nuances, and integrating the patient perspective); and social dialoguing and debate. Immediate and digitally optimized access motivated young kidney professionals to consume scientific information. Mechanisms that enable them to distil relevant and new evidence, appraise and apply information to clinical practice and research, disseminate studies to colleagues, and engage in discussion and debate may enhance their comprehension, confidence, interpretation, and use of scientific literature.10.2215/CJN.01760218Fri, 24 Aug 2018 05:38:16 GMT-07:00Young Kidney Professionals’ Perspectives and Attitudes about Consuming Scientific InformationThe digital era has seen rapid changes in how information is consumed. Traditional dissemination of scholarly work through biomedical journals may not be optimally tailored to the preferences of younger clinicians and researchers. We aimed to describe the perspectives of young clinicians and researchers in kidney disease on consuming scientific information. Three focus groups were conducted during the 2017 American Society of Nephrology Kidney Week with a total of 29 nephrologists and researchers (ages 40 years old and younger) purposively sampled through our networks and the American Society of Nephrology registration database. Data were analyzed thematically. Of the 72 participants invited, 29 participated from 28 centers across 13 countries. Five themes were identified: capturing and retaining attention (with subthemes of triggering interest, optimizing readability, and navigation to sustain motivation); having discernible relevance (resonating with clinical and research interests, supporting professional development, action-oriented and readily applicable, able to disseminate, contextualizing the study, and filtering out informational noise); immediacy and efficiency in processing information (requiring instantaneous and easy access, enabling rapid understanding, and facilitating comprehension of complex concepts); trusting legitimate and credible sources (authoritative indicator of importance and quality, reputable experts broadening perspective, certainty and confidence with collegial input, accurate framing and translation of the message, ascertaining methodologic detail and nuances, and integrating the patient perspective); and social dialoguing and debate. Immediate and digitally optimized access motivated young kidney professionals to consume scientific information. Mechanisms that enable them to distil relevant and new evidence, appraise and apply information to clinical practice and research, disseminate studies to colleagues, and engage in discussion and debate may enhance their comprehension, confidence, interpretation, and use of scientific literature.Tong, AllisonCrews, Deidra C.Schell, Jane O.de Boer, Ian H.Chonchol, MichelMehrotra, Rajnish2018-08-24T05:38:16-07:00doi:10.2215/CJN.01760218hwp:resource-id:clinjasn;13/10/1587American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, renal failure, Nephrologists, Comprehension, Motivation, Focus Groups, Research Personnel, Research, Kidney Diseases, Orientation, Spatial, Attitude, AttentionFeatureFeatureresearch-article20182018-10-08October 08, 201810.2215/CJN.017602181555-90411555-905X2018-08-24T05:38:16-07:002018-10-08Clinical Journal of the American Society of NephrologyFeature131015871597
- PD Solutions and Peritoneal Health10.2215/CJN.09590818Fri, 31 Aug 2018 06:55:10 GMT-07:00PD Solutions and Peritoneal HealthCho, YeoungjeeJohnson, David W.2018-08-31T06:55:10-07:00doi:10.2215/CJN.09590818hwp:resource-id:clinjasn;13/10/1455American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, peritoneal membrane, Epidemiology and outcomes, ultrafiltration, Chronic inflammation, Peritoneum, Dialysis SolutionsEditorialsEditorialseditorial20182018-10-08October 08, 201810.2215/CJN.095908181555-90411555-905X2018-08-31T06:55:10-07:002018-10-08Clinical Journal of the American Society of NephrologyEditorials1310101455152614571533
- Beware Intradialytic Hypotension10.2215/CJN.10150818Thu, 20 Sep 2018 09:05:10 GMT-07:00Beware Intradialytic HypotensionInrig, Jula K.2018-09-20T09:05:10-07:00doi:10.2215/CJN.10150818hwp:resource-id:clinjasn;13/10/1453American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyintradialytic hypotension, end stage kidney disease, mesenteric ischemia, hemodialysis, hypotension, dialysisEditorialsEditorialseditorial20182018-10-08October 08, 201810.2215/CJN.101508181555-90411555-905X2018-09-20T09:05:10-07:002018-10-08Clinical Journal of the American Society of NephrologyEditorials1310101453151714541525
- Biocompatible Solutions and Long-Term Changes in Peritoneal Solute Transport10.2215/CJN.02380218Fri, 31 Aug 2018 06:55:11 GMT-07:00Biocompatible Solutions and Long-Term Changes in Peritoneal Solute TransportElphick, Emma H.Teece, LucyChess, James A.Do, Jun-YoungKim, Yong-LimLee, H. BahlDavison, Sara N.Topley, NicholasDavies, Simon J.Lambie, Mark2018-08-31T06:55:11-07:00doi:10.2215/CJN.02380218hwp:resource-id:clinjasn;13/10/1526American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal membrane, Peritoneal Fibrosis, icodextrin, creatinine, IL6 protein, human, Interleukin-6, Dialysis Solutions, peritoneal dialysis, Peritoneum, Glucans, Glucose, Peritonitis, Inflammation, hospitalizationOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-10-08October 08, 201810.2215/CJN.023802181555-90411555-905X2018-08-31T06:55:11-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles13101061526145590915331457909
- Site of Care and Health Outcomes of Veterans Undergoing Maintenance Dialysis10.2215/CJN.06100518Thu, 14 Jun 2018 06:51:37 GMT-07:00Site of Care and Health Outcomes of Veterans Undergoing Maintenance DialysisKourany, WissamCrowley, Susan T.2018-06-14T06:51:37-07:00doi:10.2215/CJN.06100518hwp:resource-id:clinjasn;13/7/979American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyVeteran, dialysis, mortality, renal dialysis, Maintenance, Kidney Failure, Chronic, United States Department of Veterans AffairsEditorialsEditorialseditorial20182018-07-06July 06, 201810.2215/CJN.061005181555-90411555-905X2018-06-14T06:51:37-07:002018-07-06Clinical Journal of the American Society of NephrologyEditorials137797910559811062
- The Changing Spectrum of Heroin-Associated Kidney Disease10.2215/CJN.06080518Fri, 15 Jun 2018 07:25:42 GMT-07:00The Changing Spectrum of Heroin-Associated Kidney DiseaseSethi, Sanjeev2018-06-15T07:25:42-07:00doi:10.2215/CJN.06080518hwp:resource-id:clinjasn;13/7/975American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAmyloidosis, Heroin-use, drug abuse, Heroin, Kidney Diseases, Heroin DependenceEditorialsEditorialseditorial20182018-07-06July 06, 201810.2215/CJN.060805181555-90411555-905X2018-06-15T07:25:42-07:002018-07-06Clinical Journal of the American Society of NephrologyEditorials137797510309761036
- Correction10.2215/CJN.05270418Wed, 30 May 2018 07:37:14 GMT-07:00CorrectionAmerican Society of Nephrology2018-05-30T07:37:14-07:00doi:10.2215/CJN.05270418hwp:resource-id:clinjasn;13/7/1079American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correction, Eosinophils, Nephritis, Interstitial, OrganizationsErratumErratumcorrection20182018-07-06July 06, 201810.2215/CJN.052704181555-90411555-905X2018-05-30T07:37:14-07:002018-07-06Clinical Journal of the American Society of NephrologyErratum1387111079185710791862
- Clinical Pharmacokinetics in Kidney DiseaseKidney disease is an increasingly common comorbidity that alters the pharmacokinetics of many drugs. Prescribing to patients with kidney disease requires knowledge about the drug, the extent of the patient’s altered physiology, and pharmacokinetic principles that influence the design of dosing regimens. There are multiple physiologic effects of impaired kidney function, and the extent to which they occur in an individual at any given time can be difficult to define. Although some guidelines are available for dosing in kidney disease, they may be on the basis of limited data or not widely applicable, and therefore, an understanding of pharmacokinetic principles and how to apply them is important to the practicing clinician. Whether kidney disease is acute or chronic, drug clearance decreases, and the volume of distribution may remain the same or increase. Although in CKD, these changes progress relatively slowly, they are dynamic in AKI, and recovery is possible depending on the etiology and treatments. This, and the use of kidney replacement therapies further complicate attempts to quantify drug clearance at the time of prescribing and dosing in AKI. The required change in the dosing regimen can be estimated or even quantitated in certain instances through the application of pharmacokinetic principles to guide rational drug dosing. This offers an opportunity to provide personalized medical care and minimizes adverse drug events from either under- or overdosing. We discuss the principles of pharmacokinetics that are fundamental for the design of an appropriate dosing regimen in this review.10.2215/CJN.00340118Fri, 22 Jun 2018 06:19:46 GMT-07:00Clinical Pharmacokinetics in Kidney DiseaseKidney disease is an increasingly common comorbidity that alters the pharmacokinetics of many drugs. Prescribing to patients with kidney disease requires knowledge about the drug, the extent of the patient’s altered physiology, and pharmacokinetic principles that influence the design of dosing regimens. There are multiple physiologic effects of impaired kidney function, and the extent to which they occur in an individual at any given time can be difficult to define. Although some guidelines are available for dosing in kidney disease, they may be on the basis of limited data or not widely applicable, and therefore, an understanding of pharmacokinetic principles and how to apply them is important to the practicing clinician. Whether kidney disease is acute or chronic, drug clearance decreases, and the volume of distribution may remain the same or increase. Although in CKD, these changes progress relatively slowly, they are dynamic in AKI, and recovery is possible depending on the etiology and treatments. This, and the use of kidney replacement therapies further complicate attempts to quantify drug clearance at the time of prescribing and dosing in AKI. The required change in the dosing regimen can be estimated or even quantitated in certain instances through the application of pharmacokinetic principles to guide rational drug dosing. This offers an opportunity to provide personalized medical care and minimizes adverse drug events from either under- or overdosing. We discuss the principles of pharmacokinetics that are fundamental for the design of an appropriate dosing regimen in this review.Lea-Henry, Tom N.Carland, Jane E.Stocker, Sophie L.Sevastos, JacobRoberts, Darren M.2018-06-22T06:19:46-07:00doi:10.2215/CJN.00340118hwp:resource-id:clinjasn;13/7/1085American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypharmacokinetics, kidney disease, chronic kidney disease, acute kidney injury, dialysis, clearance, volume of distributionNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-07-06July 06, 201810.2215/CJN.003401181555-90411555-905X2018-06-22T06:19:46-07:002018-07-06Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician13771085108310951084
- Dialysis Provider and Outcomes among United States Veterans Who Transition to Dialysis10.2215/CJN.12951117Thu, 14 Jun 2018 06:51:36 GMT-07:00Dialysis Provider and Outcomes among United States Veterans Who Transition to DialysisStreja, ElaniKovesdy, Csaba PalSoohoo, MelissaObi, YoshitsuguRhee, Connie M.Park, ChristinaChen, Joline L.T.Nakata, TracyNguyen, Danh V.Amin, Alpesh N.Jacobsen, Steven J.Sim, John J.Kalantar-Zadeh, Kamyar2018-06-14T06:51:36-07:00doi:10.2215/CJN.12951117hwp:resource-id:clinjasn;13/7/1055American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyComorbidity, Dialysis Initiation, Dialysis Provider, Female, glomerular filtration rate, hospitalization, Humans, Incidence, Kidney Failure, Chronic, mortality, Odds Ratio, renal dialysis, Risk, VeteransOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-07-06July 06, 201810.2215/CJN.129511171555-90411555-905X2018-06-14T06:51:36-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137710559791062981
- 12 Tips to Nephrology Teams Supporting Patients with Advanced Kidney Disease10.2215/CJN.06400518Thu, 28 Jun 2018 06:16:43 GMT-07:0012 Tips to Nephrology Teams Supporting Patients with Advanced Kidney DiseaseHickey, Edward V.2018-06-28T06:16:43-07:00doi:10.2215/CJN.06400518hwp:resource-id:clinjasn;13/7/971American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology teams, patients, veterans, patient advocate, caregiver, American Association of Kidney Patients, AAKP, Veterans Health Initiative, qualitative research, quantitative research, family members, emotions, patient burdens, alienation, abandonment, fear, isolation, resilience, blame, Nephrologists, Kidney Diseases, kidneyPatient VoicePatient Voiceresearch-article20182018-07-06July 06, 201810.2215/CJN.064005181555-90411555-905X2018-06-28T06:16:43-07:002018-07-06Clinical Journal of the American Society of NephrologyPatient Voice137797110229721029
- Overcoming Translational Barriers in Acute Kidney InjuryAKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “AKI Outcomes: Overcoming Barriers in AKI” workshop on February 10–12, 2015. The workshop used a reverse translational medicine approach to identify steps necessary to achieve clinical success. During the workshop, breakout groups were charged first to design feasible, phase 2, proof-of-concept clinical trials for delayed transplant graft function, prevention of AKI (primary prevention), and treatment of AKI (secondary prevention and recovery). Breakout groups then were responsible for identification of preclinical animal models that would replicate the pathophysiology of the phase 2 proof-of-concept patient population, including primary and secondary end points. Breakout groups identified considerable gaps in knowledge regarding human AKI, our understanding of the pathophysiology of AKI in preclinical animal models, and the fidelity of cellular and molecular targets that have been evaluated preclinically to provide information regarding human AKI of various etiologies. The workshop concluded with attendees defining a new path forward to a better understanding of the etiology, pathology, and pathophysiology of human AKI.10.2215/CJN.06820617Fri, 09 Mar 2018 06:45:09 GMT-08:00Overcoming Translational Barriers in Acute Kidney InjuryAKI is a complex clinical condition associated with high mortality, morbidity, and health care costs. Despite improvements in methodology and design of clinical trials, and advances in understanding the underlying pathophysiology of rodent AKI, no pharmacologic agent exists for the prevention or treatment of AKI in humans. To address the barriers that affect successful clinical translation of drug targets identified and validated in preclinical animal models of AKI in this patient population, the National Institute of Diabetes and Digestive and Kidney Diseases convened the “AKI Outcomes: Overcoming Barriers in AKI” workshop on February 10–12, 2015. The workshop used a reverse translational medicine approach to identify steps necessary to achieve clinical success. During the workshop, breakout groups were charged first to design feasible, phase 2, proof-of-concept clinical trials for delayed transplant graft function, prevention of AKI (primary prevention), and treatment of AKI (secondary prevention and recovery). Breakout groups then were responsible for identification of preclinical animal models that would replicate the pathophysiology of the phase 2 proof-of-concept patient population, including primary and secondary end points. Breakout groups identified considerable gaps in knowledge regarding human AKI, our understanding of the pathophysiology of AKI in preclinical animal models, and the fidelity of cellular and molecular targets that have been evaluated preclinically to provide information regarding human AKI of various etiologies. The workshop concluded with attendees defining a new path forward to a better understanding of the etiology, pathology, and pathophysiology of human AKI.Zuk, AnnaPalevsky, Paul M.Fried, LindaHarrell, Frank E.Khan, SaminaMcKay, Dianne B.Devey, LukeChawla, Lakhmirde Caestecker, MarkKaufman, James S.Thompson, B. TaylorAgarwal, AnupamGreene, TomOkusa, Mark DouglasBonventre, Joseph V.Dember, Laura M.Liu, Kathleen D.Humphreys, Benjamin D.Gossett, DanielXie, YiningNorton, Jenna M.Kimmel, Paul L.Star, Robert A.2018-03-09T06:45:09-08:00doi:10.2215/CJN.06820617hwp:resource-id:clinjasn;13/7/1113American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, Acute kidney injury, animal models, Secondary Prevention, Translational Medical Research, Rodentia, National Institute of Diabetes and Digestive and Kidney Diseases (U.S.), Acute Kidney Injury, Primary Prevention, Health Care Costs, delayed graft function, Models, AnimalFeatureFeatureresearch-article20182018-07-06July 06, 201810.2215/CJN.068206171555-90411555-905X2018-03-09T06:45:09-08:002018-07-06Clinical Journal of the American Society of NephrologyFeature13711131123
- Urinary Phosphorus Excretion10.2215/CJN.06260518Tue, 19 Jun 2018 08:09:53 GMT-07:00Urinary Phosphorus ExcretionCupisti, AdamascoGallieni, Maurizio2018-06-19T08:09:53-07:00doi:10.2215/CJN.06260518hwp:resource-id:clinjasn;13/7/973American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal insufficiency, nutrition, phosphate uptake, chronic kidney disease, Phosphorus, Phosphorus, dietaryEditorialsEditorialseditorial20182018-07-06July 06, 201810.2215/CJN.062605181555-90411555-905X2018-06-19T08:09:53-07:002018-07-06Clinical Journal of the American Society of NephrologyEditorials137797310029741012
- Emotional Impact of Illness and Care on Patients with Advanced Kidney Disease10.2215/CJN.14261217Thu, 28 Jun 2018 06:16:44 GMT-07:00Emotional Impact of Illness and Care on Patients with Advanced Kidney DiseaseO’Hare, Ann M.Richards, ClaireSzarka, JackieMcFarland, Lynne V.Showalter, WhitneyVig, Elizabeth K.Sudore, Rebecca L.Crowley, Susan T.Trivedi, RanakTaylor, Janelle S.2018-06-28T06:16:44-07:00doi:10.2215/CJN.14261217hwp:resource-id:clinjasn;13/7/1022American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAbandonment, Advance Care Planning, Advanced Kidney Disease, dialysis, Emotions, Fragmentation, glomerular filtration rate, Grounded Theory, Humans, Isolation, kidney, Loneliness, Mistrust, Patient Experience, Patient-centered, peritoneal dialysis, renal dialysis, Self-blame, SpecializationOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20182018-07-06July 06, 201810.2215/CJN.142612171555-90411555-905X2018-06-28T06:16:44-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137710229711029972
- Evolving Epidemiology of Pediatric Glomerular Disease10.2215/CJN.06220518Mon, 18 Jun 2018 08:20:51 GMT-07:00Evolving Epidemiology of Pediatric Glomerular DiseaseRheault, Michelle N.Wenderfer, Scott E.2018-06-18T08:20:51-07:00doi:10.2215/CJN.06220518hwp:resource-id:clinjasn;13/7/977American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, pediatric nephrology, kidney biopsy, focal segmental glomerulosclerosis, membranous nephropathy, Kidney Glomerulus, Kidney DiseasesEditorialsEditorialseditorial20182018-07-06July 06, 201810.2215/CJN.062205181555-90411555-905X2018-06-18T08:20:51-07:002018-07-06Clinical Journal of the American Society of NephrologyEditorials137797710479781054
- Prevalence of Central Vein Stenosis in Patients Referred for Vein Mapping10.2215/CJN.14001217Tue, 08 May 2018 08:04:08 GMT-07:00Prevalence of Central Vein Stenosis in Patients Referred for Vein MappingTedla, Fasika M.Clerger, GuerrierDistant, DaleSalifu, Moro2018-05-08T08:04:08-07:00doi:10.2215/CJN.14001217hwp:resource-id:clinjasn;13/7/1063American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Body Mass Index, Central Vein Stenosis, Central Venous Catheters, chronic kidney disease, Confidence Intervals, Constriction, Pathologic, dialysis, ESRD, ESKD, Female, Fistula, Humans, kidney transplantation, Logistic Models, Odds Ratio, Phlebography, Prevalence, renal dialysis, Renal Insufficiency, Chronic, Retrospective Studies, Vein Mapping, VeinsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-07-06July 06, 201810.2215/CJN.140012171555-90411555-905X2018-05-08T08:04:08-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles13710631068
- Risk Factors and Outcomes of Rapid Correction of Severe Hyponatremia10.2215/CJN.13061117Tue, 05 Jun 2018 06:50:04 GMT-07:00Risk Factors and Outcomes of Rapid Correction of Severe HyponatremiaGeorge, Jason C.Zafar, WaleedBucaloiu, Ion DanChang, Alex R.2018-06-05T06:50:04-07:00doi:10.2215/CJN.13061117hwp:resource-id:clinjasn;13/7/984American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAged, Brain, Central Pontine Myelinolysis, Comorbidity, Demyelinating Diseases, Female, Humans, hypokalemia, hyponatremia, Incidence, Magnetic Resonance Imaging, Mineralocorticoid Receptor Antagonists, Osmotic Demyelination, Outpatients, Rapid Correction, Retrospective Studies, risk factors, Schizophrenia, SodiumOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20182018-07-06July 06, 201810.2215/CJN.130611171555-90411555-905X2018-06-05T06:50:04-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137984992
- Introduction to Nephropharmacology for the Clinician10.2215/CJN.03180318Mon, 16 Apr 2018 07:17:07 GMT-07:00Introduction to Nephropharmacology for the ClinicianNolin, Thomas D.Perazella, Mark A.2018-04-16T07:17:07-07:00doi:10.2215/CJN.03180318hwp:resource-id:clinjasn;13/7/1083American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Drug-related Side Effects and Adverse Reactions, Humans, kidney, kidney disease, nephrology, Pharmacodynamics, Pharmacogenetics, pharmacokinetics, Pharmacology, Renal Insufficiency, Chronic, United StatesNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-07-06July 06, 201810.2215/CJN.031803181555-90411555-905X2018-04-16T07:17:07-07:002018-07-06Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician13771083108510841095
- Commentary on “Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in CKD”10.2215/CJN.13431118Fri, 28 Dec 2018 08:27:50 GMT-08:00Commentary on “Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in CKD”Kestenbaum, Bryan R.Seliger, Stephen L.2018-12-28T08:27:50-08:00doi:10.2215/CJN.13431118hwp:resource-id:clinjasn;14/1/137American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, randomized controlled trials, chronic kidney disease, Atrial FibrillationCommentaryCommentaryarticle-commentary20192019-01-07January 07, 201910.2215/CJN.134311181555-90411555-905X2018-12-28T08:27:50-08:002019-01-07Clinical Journal of the American Society of NephrologyCommentary1411137125138136
- Correction10.2215/CJN.12621018Mon, 19 Nov 2018 07:17:42 GMT-08:00CorrectionAmerican Society of Nephrology2018-11-19T07:17:42-08:00doi:10.2215/CJN.12621018hwp:resource-id:clinjasn;14/1/111American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correctionErratumErratumcorrection20192019-01-07January 07, 201910.2215/CJN.126210181555-90411555-905X2018-11-19T07:17:42-08:002019-01-07Clinical Journal of the American Society of NephrologyErratum1411011115021111509
- The Millennial Physician and the Obesity Epidemic10.2215/CJN.13851118Thu, 27 Dec 2018 07:36:17 GMT-08:00The Millennial Physician and the Obesity EpidemicKramer, HollyShoham, David2018-12-27T07:36:17-08:00doi:10.2215/CJN.13851118hwp:resource-id:clinjasn;14/1/4American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyobesity, chronic kidney disease, public health, sugar-sweetened beverages, Sweetening Agents, Sugars, Beverages, CarbohydratesEditorialsEditorialseditorial20192019-01-07January 07, 201910.2215/CJN.138511181555-90411555-905X2018-12-27T07:36:17-08:002019-01-07Clinical Journal of the American Society of NephrologyEditorials1411141496256
- Good Guys, Bad Guys, Guesses, and Near Misses in Nephrology10.2215/CJN.13801118Mon, 17 Dec 2018 07:27:02 GMT-08:00Good Guys, Bad Guys, Guesses, and Near Misses in NephrologyEdmonston, DanielWolf, Myles2018-12-17T07:27:02-08:00doi:10.2215/CJN.13801118hwp:resource-id:clinjasn;14/1/7American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFGF23, phosphate, SGLT2 inhibitors, CKD, clinical trials, nephrology, diuretics, Research Personnel, SLC5A2 protein, human, Sodium-Glucose Transporter 2, Renal Insufficiency, Chronic, Kidney Tubules, Proximal, Hypoglycemic Agents, Biotechnology, GlucoseEditorialsEditorialseditorial20192019-01-07January 07, 201910.2215/CJN.138011181555-90411555-905X2018-12-17T07:27:02-08:002019-01-07Clinical Journal of the American Society of NephrologyEditorials1411766973
- Diet and Risk for Developing Kidney Disease10.2215/CJN.13601118Thu, 27 Dec 2018 07:36:18 GMT-08:00Diet and Risk for Developing Kidney DiseaseSunwold, Duane2018-12-27T07:36:18-08:00doi:10.2215/CJN.13601118hwp:resource-id:clinjasn;14/1/1American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, Sweetening Agents, beverages, Diet, Risk, kidney diseasePatient VoicePatient Voiceeditorial20192019-01-07January 07, 201910.2215/CJN.136011181555-90411555-905X2018-12-27T07:36:18-08:002019-01-07Clinical Journal of the American Society of NephrologyPatient Voice1411114492656
- Patient Priorities for Research Involving Peritoneal Dialysis10.2215/CJN.13621118Thu, 20 Dec 2018 08:52:59 GMT-08:00Patient Priorities for Research Involving Peritoneal DialysisHaydak, Jonathan2018-12-20T08:52:59-08:00doi:10.2215/CJN.13621118hwp:resource-id:clinjasn;14/1/3American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, Research, Peritoneal Dialysis, Continuous AmbulatoryPatient VoicePatient Voiceeditorial20192019-01-07January 07, 201910.2215/CJN.136211181555-90411555-905X2018-12-20T08:52:59-08:002019-01-07Clinical Journal of the American Society of NephrologyPatient Voice1411374383
- A Patient’s View on Exercise and ESKD10.2215/CJN.00150119Tue, 29 Jan 2019 08:36:56 GMT-08:00A Patient’s View on Exercise and ESKDJefferson, Nichole M.2019-01-29T08:36:56-08:00doi:10.2215/CJN.00150119hwp:resource-id:clinjasn;14/2/171American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPatient, Kidney Failure, Chronic, ExercisePatient VoicePatient Voiceeditorial20192019-02-07February 07, 201910.2215/CJN.001501191555-90411555-905X2019-01-29T08:36:56-08:002019-02-07Clinical Journal of the American Society of NephrologyPatient Voice1422171268171276
- Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis10.2215/CJN.08580718Thu, 31 Jan 2019 09:00:36 GMT-08:00Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance HemodialysisSaglimbene, Valeria M.Wong, GermaineRuospo, MarinellaPalmer, Suetonia C.Garcia-Larsen, VanessaNatale, PatriziaTeixeira-Pinto, ArmandoCampbell, Katrina L.Carrero, Juan-JesusStenvinkel, PeterGargano, LetiziaMurgo, Angelo M.Johnson, David W.Tonelli, MarcelloGelfman, RubénCelia, EduardoEcder, TevfikBernat, Amparo G.Del Castillo, DomingoTimofte, DeliaTörök, MariettaBednarek-Skublewska, AnnaDuława, JanStroumza, PaulHoischen, SusanneHansis, MartinFabricius, ElisabethFelaco, PaoloWollheim, CharlottaHegbrant, JörgenCraig, Jonathan C.Strippoli, Giovanni F.M.2019-01-31T09:00:36-08:00doi:10.2215/CJN.08580718hwp:resource-id:clinjasn;14/2/250American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, mortality, hemodialysis, clinical epidemiology, clinical nephrology, Epidemiology and outcomes, ESRD, mortality risk, risk factors, survival, Vegetables, Fruit, Asthma, Hyperkalemia, Diet, Risk, Hypersensitivity, Proportional Hazards Models, renal dialysis, Cardiovascular Diseases, Surveys and QuestionnairesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-02-07February 07, 201910.2215/CJN.085807181555-90411555-905X2019-01-31T09:00:36-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1422250180260181
- Benefits and Barriers to and Desired Outcomes with Exercise in Patients with ESKD10.2215/CJN.09700818Tue, 29 Jan 2019 08:36:57 GMT-08:00Benefits and Barriers to and Desired Outcomes with Exercise in Patients with ESKDMoorman, DanielleSuri, RitaHiremath, SwapnilJegatheswaran, JanuviKumar, TeerathBugeja, AnnZimmerman, Deborah2019-01-29T08:36:57-08:00doi:10.2215/CJN.09700818hwp:resource-id:clinjasn;14/2/268American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyExercise, dialysis, outcomes, renal dialysis, Resistance Training, Longevity, Tertiary Care Centers, Kidney Failure, Chronic, peritoneal dialysis, Fatigue, Surveys and QuestionnairesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-02-07February 07, 201910.2215/CJN.097008181555-90411555-905X2019-01-29T08:36:57-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1422268171276171
- Assessing Clinical Relevance of Uremic Toxins10.2215/CJN.14931218Mon, 21 Jan 2019 07:45:34 GMT-08:00Assessing Clinical Relevance of Uremic ToxinsFlythe, Jennifer E.Hostetter, Thomas H.2019-01-21T07:45:34-08:00doi:10.2215/CJN.14931218hwp:resource-id:clinjasn;14/2/182American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyToxins, Biological, uremiaEditorialsEditorialseditorial20192019-02-07February 07, 201910.2215/CJN.149312181555-90411555-905X2019-01-21T07:45:34-08:002019-02-07Clinical Journal of the American Society of NephrologyEditorials1422182261183267
- Correction10.2215/CJN.13671118Thu, 10 Jan 2019 12:47:20 GMT-08:00CorrectionAmerican Society of Nephrology2019-01-10T12:47:20-08:00doi:10.2215/CJN.13671118hwp:resource-id:clinjasn;14/2/277American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correctionErratumErratumcorrection20192019-02-07February 07, 201910.2215/CJN.136711181555-90411555-905X2019-01-10T12:47:20-08:002019-02-07Clinical Journal of the American Society of NephrologyErratum14212772627735
- Influence of Reimbursement Policies on Dialysis Modality Distribution around the World10.2215/CJN.13741118Thu, 13 Dec 2018 10:20:08 GMT-08:00Influence of Reimbursement Policies on Dialysis Modality Distribution around the WorldBrown, Edwina Anne2018-12-13T10:20:08-08:00doi:10.2215/CJN.13741118hwp:resource-id:clinjasn;14/1/10American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfinancial reimbursement, peritoneal dialysis, hemodialysis, global distribution, dialysis, Policy, Kidney Failure, ChronicEditorialsEditorialseditorial20192019-01-07January 07, 201910.2215/CJN.137411181555-90411555-905X2018-12-13T10:20:08-08:002019-01-07Clinical Journal of the American Society of NephrologyEditorials141110841293
- Fostering Innovation in Symptom Management among Hemodialysis PatientsIndividuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes. Moreover, patients on hemodialysis have identified symptom management as a key area for research and innovation, prioritizing symptom alleviation over other health outcomes such as mortality and biochemical indices. Despite the importance of symptoms to patients, there has been little research explicitly geared toward improving patient symptoms, and therefore minimal innovation in symptom management. In general, the physiologic underpinnings of symptoms are poorly understood, hampering the development of targeted therapies. In fact, there have been few drugs or devices approved by the US Food and Drug Administration for the indication of improving any patient-reported outcomes for patients on hemodialysis. Recognizing this gap in innovation, the Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to first prioritize symptoms for the development of therapeutic interventions, and then identify near-term actionable research goals for the prioritized physical symptoms of insomnia, muscle cramps, and fatigue. This paper summarizes the pathophysiology of the three prioritized symptoms, identifies key knowledge gaps, acknowledges factors that challenge development of new therapies, and offers the nephrology community actionable research goals for insomnia, muscle cramps, and fatigue.10.2215/CJN.07670618Mon, 05 Nov 2018 09:59:00 GMT-08:00Fostering Innovation in Symptom Management among Hemodialysis PatientsIndividuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes. Moreover, patients on hemodialysis have identified symptom management as a key area for research and innovation, prioritizing symptom alleviation over other health outcomes such as mortality and biochemical indices. Despite the importance of symptoms to patients, there has been little research explicitly geared toward improving patient symptoms, and therefore minimal innovation in symptom management. In general, the physiologic underpinnings of symptoms are poorly understood, hampering the development of targeted therapies. In fact, there have been few drugs or devices approved by the US Food and Drug Administration for the indication of improving any patient-reported outcomes for patients on hemodialysis. Recognizing this gap in innovation, the Kidney Health Initiative, a public–private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to first prioritize symptoms for the development of therapeutic interventions, and then identify near-term actionable research goals for the prioritized physical symptoms of insomnia, muscle cramps, and fatigue. This paper summarizes the pathophysiology of the three prioritized symptoms, identifies key knowledge gaps, acknowledges factors that challenge development of new therapies, and offers the nephrology community actionable research goals for insomnia, muscle cramps, and fatigue.Flythe, Jennifer E.Hilliard, TandreaLumby, ElenaCastillo, GracielaOrazi, JazmineAbdel-Rahman, Emaad M.Pai, Amy BartonRivara, Matthew BertrandSt. Peter, Wendy L.Weisbord, Steven DarrowWilkie, Caroline M.Mehrotra, Rajnish,2018-11-05T09:59:00-08:00doi:10.2215/CJN.07670618hwp:resource-id:clinjasn;14/1/150American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, dialysis, end stage kidney disease, ESRD, hemodialysis, ESKD, kidney diseaseFeatureFeatureresearch-article20192019-01-07January 07, 201910.2215/CJN.076706181555-90411555-905X2018-11-05T09:59:00-08:002019-01-07Clinical Journal of the American Society of NephrologyFeature141150160
- An International Analysis of Dialysis Services Reimbursement10.2215/CJN.08150718Thu, 13 Dec 2018 10:20:08 GMT-08:00An International Analysis of Dialysis Services Reimbursementvan der Tol, ArjanLameire, NorbertMorton, Rachael L.Van Biesen, WimVanholder, Raymond2018-12-13T10:20:08-08:00doi:10.2215/CJN.08150718hwp:resource-id:clinjasn;14/1/84American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygovernment reimbursement for dialysis services, hemodialysis, peritoneal dialysis, worldwide survey, dialysis health economic, chronic dialysis, prevention CKD, prevalence of dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-01-07January 07, 201910.2215/CJN.081507181555-90411555-905X2018-12-13T10:20:08-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles141184109312
- Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney DiseasePatients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25–30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.10.2215/CJN.06430518Fri, 28 Dec 2018 08:27:50 GMT-08:00Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney DiseasePatients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25–30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.Garlo, Katherine G.Steele, David J.R.Nigwekar, Sagar U.Chan, Kevin E.2018-12-28T08:27:50-08:00doi:10.2215/CJN.06430518hwp:resource-id:clinjasn;14/1/125American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnti-coagulation, chronic kidney disease, Warfarin, Direct acting oral anticoagulants, creatinine, Stroke, Accidental Falls, Vulnerable Populations, Brain Ischemia, dialysis, Hemorrhage, Renal Insufficiency, Chronic, Blood Coagulation, ScholarOne supportEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20192019-01-07January 07, 201910.2215/CJN.064305181555-90411555-905X2018-12-28T08:27:50-08:002019-01-07Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology1411125137136138
- Utility of Electronic Medical Record Alerts to Prevent Drug NephrotoxicityNephrotoxin-induced AKI is an iatrogenic form of AKI that can be potentially avoided or ameliorated by prompt recognition and appropriate prescriber actions. Drug-targeted alerts, either for patients at risk of AKI or patients with existing AKI, may lead to more appropriate drug dosing and management and improved clinical outcomes. However, alerts of this type are complicated to create, have a high potential for error and off-target effects, and may be difficult to evaluate. Although many studies have shown that these alerts can reduce the rate of inappropriate prescribing, few studies have examined the utility of such alerts in terms of patient benefit. In this review, we examine the current state of the literature in this area, identify key technical challenges, and suggest methods of evaluation for drug-targeted AKI alerts.10.2215/CJN.13841217Thu, 05 Apr 2018 06:42:12 GMT-07:00Utility of Electronic Medical Record Alerts to Prevent Drug NephrotoxicityNephrotoxin-induced AKI is an iatrogenic form of AKI that can be potentially avoided or ameliorated by prompt recognition and appropriate prescriber actions. Drug-targeted alerts, either for patients at risk of AKI or patients with existing AKI, may lead to more appropriate drug dosing and management and improved clinical outcomes. However, alerts of this type are complicated to create, have a high potential for error and off-target effects, and may be difficult to evaluate. Although many studies have shown that these alerts can reduce the rate of inappropriate prescribing, few studies have examined the utility of such alerts in terms of patient benefit. In this review, we examine the current state of the literature in this area, identify key technical challenges, and suggest methods of evaluation for drug-targeted AKI alerts.Martin, MelissaWilson, F. Perry2018-04-05T06:42:12-07:00doi:10.2215/CJN.13841217hwp:resource-id:clinjasn;14/1/115American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, acute renal failure, Alert, Clinical Decision Support, drug nephrotoxicity, Drug Prescriptions, Electronic Health Records, Humans, Iatrogenic Disease, Inappropriate Prescribing, nephrotoxicity, pharmacokineticsNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20192019-01-07January 07, 201910.2215/CJN.138412171555-90411555-905X2018-04-05T06:42:12-07:002019-01-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician141115123
- Bleeding Complications after Pediatric Kidney Biopsy10.2215/CJN.05890518Thu, 06 Dec 2018 07:04:03 GMT-08:00Bleeding Complications after Pediatric Kidney BiopsyVarnell, Charles D.Stone, Hillarey K.Welge, Jeffrey A.2018-12-06T07:04:03-08:00doi:10.2215/CJN.05890518hwp:resource-id:clinjasn;14/1/57American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, pediatric nephrology, kidney biopsy, renal biopsy, Retrospective Studies, Outpatients, Inpatients, MEDLINE, Prospective Studies, Kidney Diseases, Biopsy, kidney transplantation, Hematoma, Blood TransfusionOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20192019-01-07January 07, 201910.2215/CJN.058905181555-90411555-905X2018-12-06T07:04:03-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1415765
- The Use of Selected Urine Chemistries in the Diagnosis of Kidney DisordersUrinary chemistries vary widely in both health and disease and are affected by diet, volume status, medications, and disease states. When properly examined, these tests provide important insight into the mechanism and therapy of various clinical disorders that are first detected by abnormalities in plasma chemistries. These tests cannot be interpreted in isolation, but instead require knowledge of key clinical information, such as medications, physical examination, and plasma chemistries, to include kidney function. When used appropriately and with knowledge of limitations, urine chemistries can provide important insight into the pathophysiology and treatment of a wide variety of disorders.10.2215/CJN.10330818Wed, 09 Jan 2019 02:18:02 GMT-08:00The Use of Selected Urine Chemistries in the Diagnosis of Kidney DisordersUrinary chemistries vary widely in both health and disease and are affected by diet, volume status, medications, and disease states. When properly examined, these tests provide important insight into the mechanism and therapy of various clinical disorders that are first detected by abnormalities in plasma chemistries. These tests cannot be interpreted in isolation, but instead require knowledge of key clinical information, such as medications, physical examination, and plasma chemistries, to include kidney function. When used appropriately and with knowledge of limitations, urine chemistries can provide important insight into the pathophysiology and treatment of a wide variety of disorders.Palmer, Biff F.Clegg, Deborah Joy2019-01-09T14:18:02-08:00doi:10.2215/CJN.10330818hwp:resource-id:clinjasn;14/2/306American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUrologic Diseases, Physical Examination, Urinary Tract Physiological Phenomena, Diagnostic Tests, Routine, DietReviewsReviewsarticle-commentary20192019-02-07February 07, 201910.2215/CJN.103308181555-90411555-905X2019-01-09T14:18:02-08:002019-02-07Clinical Journal of the American Society of NephrologyReviews14142830612413161241
- Diuretic use in incident ESKD10.2215/CJN.13361118Wed, 19 Dec 2018 06:42:44 GMT-08:00Diuretic use in incident ESKDWang, KeBansal, Nisha2018-12-19T06:42:44-08:00doi:10.2215/CJN.13361118hwp:resource-id:clinjasn;14/1/13American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyKidney Failure, Chronic, diuretics, kidney transplantation, end stage kidney diseaseEditorialsEditorialseditorial20192019-01-07January 07, 201910.2215/CJN.133611181555-90411555-905X2018-12-19T06:42:44-08:002019-01-07Clinical Journal of the American Society of NephrologyEditorials1411139515102
- Patient and Caregiver Priorities for Outcomes in Peritoneal Dialysis10.2215/CJN.05380518Thu, 20 Dec 2018 08:52:59 GMT-08:00Patient and Caregiver Priorities for Outcomes in Peritoneal DialysisManera, Karine E.Johnson, David W.Craig, Jonathan C.Shen, Jenny I.Ruiz, LorenaWang, Angela Yee-MoonYip, TerenceFung, Samuel K.S.Tong, MatthewLee, AchillesCho, YeoungjeeViecelli, Andrea K.Sautenet, BenedicteTeixeira-Pinto, ArmandoBrown, Edwina AnneBrunier, GillianDong, JieDunning, TonyMehrotra, RajnishNaicker, SaraladeviPecoits-Filho, RobertoPerl, JeffreyWilkie, MartinTong, Allison2018-12-20T08:52:59-08:00doi:10.2215/CJN.05380518hwp:resource-id:clinjasn;14/1/74American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOutcomes, Caregivers, blood pressure, quality of life, Self-Management, Decision Making, Patient Participation, peritoneal dialysis, Wakefulness, Life StyleOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-01-07January 07, 201910.2215/CJN.053805181555-90411555-905X2018-12-20T08:52:59-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1411743833
- Association of Continuation of Loop Diuretics at Hemodialysis Initiation with Clinical Outcomes10.2215/CJN.05080418Wed, 19 Dec 2018 06:42:43 GMT-08:00Association of Continuation of Loop Diuretics at Hemodialysis Initiation with Clinical OutcomesSibbel, ScottWalker, Adam G.Colson, CareyTentori, FrancescaBrunelli, Steven M.Flythe, Jennifer2018-12-19T06:42:43-08:00doi:10.2215/CJN.05080418hwp:resource-id:clinjasn;14/1/95American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiuretics, hemodialysis, hospitalization, mortality, renal dialysis, Kidney Dialysis, Sodium Potassium Chloride Symporter Inhibitors, Weight Gain, blood pressure, Medicare Part A, ultrafiltration, Confidence Intervals, Incidence, Intention to Treat Analysis, Renal Insufficiency, Chronic, Body Weight, hypotension, Blood Pressure Determination, Diagnosis-Related Groups, PotassiumOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-01-07January 07, 201910.2215/CJN.050804181555-90411555-905X2018-12-19T06:42:43-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1411951310215
- Increasing Awareness of Early Risk of AKI in Neonates10.2215/CJN.13461118Thu, 31 Jan 2019 09:00:34 GMT-08:00Increasing Awareness of Early Risk of AKI in NeonatesKamath, NiveditaLuyckx, Valerie A.2019-01-31T09:00:34-08:00doi:10.2215/CJN.13461118hwp:resource-id:clinjasn;14/2/172American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyInfant, Newborn, Humans, Acute Kidney Injury, Risk, NeonatesEditorialsEditorialseditorial20192019-02-07February 07, 201910.2215/CJN.134611181555-90411555-905X2019-01-31T09:00:34-08:002019-02-07Clinical Journal of the American Society of NephrologyEditorials1422172184174195
- Blood Pressure Variability in CKD10.2215/CJN.14991218Fri, 18 Jan 2019 08:36:27 GMT-08:00Blood Pressure Variability in CKDMurphy, DanielDrawz, Paul E.2019-01-18T08:36:27-08:00doi:10.2215/CJN.14991218hwp:resource-id:clinjasn;14/2/175American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhomocysteine, Renal Insufficiency, Chronic, hypertension, Blood Pressure VariabilityEditorialsEditorialseditorial20192019-02-07February 07, 201910.2215/CJN.149912181555-90411555-905X2019-01-18T08:36:27-08:002019-02-07Clinical Journal of the American Society of NephrologyEditorials1422175233177240
- Integration of Genetic Testing and Pathology for the Diagnosis of Adults with FSGS10.2215/CJN.08750718Tue, 15 Jan 2019 05:33:02 GMT-08:00Integration of Genetic Testing and Pathology for the Diagnosis of Adults with FSGSYao, TonyUdwan, KhalilJohn, RohanRana, AkanchayaHaghighi, AmirrezaXu, LizhenHack, SaidahReich, Heather N.Hladunewich, Michelle AdrienneCattran, Daniel C.Paterson, Andrew D.Pei, YorkBarua, Moumita2019-01-15T05:33:02-08:00doi:10.2215/CJN.08750718hwp:resource-id:clinjasn;14/2/213American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFSGS, idiopathic nephrotic syndrome, human genetics, type 4A collagen, renal development, Glomerular Basement Membrane, Podocytes, nephrotic syndrome, Whole Exome Sequencing, Urogenital Abnormalities, vesico-ureteral reflux, kidney, glomerulonephritis, Kidney Failure, Chronic, Renal Insufficiency, Genetic Testing, Registries, Cohort StudiesOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20192019-02-07February 07, 201910.2215/CJN.087507181555-90411555-905X2019-01-15T05:33:02-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles142213223
- Clinical Pharmacology of Oral Anticoagulants in Patients with Kidney DiseaseOral anticoagulants are commonly used drugs in patients with CKD and patients with ESKD to treat atrial fibrillation to reduce stroke and systemic embolism. Some of these drugs are used to treat or prevent deep venous thrombosis and pulmonary embolism in patients with CKD who undergo knee and hip replacement surgeries. Warfarin is the only anticoagulant that is approved for use by the Food and Drug Administration in individuals with mechanical heart valves. Each oral anticoagulant affects the coagulation profile in the laboratory uniquely. Warfarin and apixaban are the only anticoagulants that are Food and Drug Administration approved for use in patients with CKD and patients with ESKD. However, other oral anticoagulants are commonly used off label in this patient population. Given the acquired risk of bleeding from uremia, these drugs are known to cause increased bleeding events, hospitalization, and overall morbidity. Each anticoagulant has unique pharmacologic properties of which nephrologists need to be aware to optimally manage patients. In addition, nephrologists are increasingly asked to aid in the management of adverse bleeding events related to oral anticoagulant use in patients with CKD and patients with ESKD. This article summarizes the clinical pharmacology of these drugs and identifies knowledge gaps in the literature related to their use.10.2215/CJN.02170218Fri, 25 May 2018 07:36:53 GMT-07:00Clinical Pharmacology of Oral Anticoagulants in Patients with Kidney DiseaseOral anticoagulants are commonly used drugs in patients with CKD and patients with ESKD to treat atrial fibrillation to reduce stroke and systemic embolism. Some of these drugs are used to treat or prevent deep venous thrombosis and pulmonary embolism in patients with CKD who undergo knee and hip replacement surgeries. Warfarin is the only anticoagulant that is approved for use by the Food and Drug Administration in individuals with mechanical heart valves. Each oral anticoagulant affects the coagulation profile in the laboratory uniquely. Warfarin and apixaban are the only anticoagulants that are Food and Drug Administration approved for use in patients with CKD and patients with ESKD. However, other oral anticoagulants are commonly used off label in this patient population. Given the acquired risk of bleeding from uremia, these drugs are known to cause increased bleeding events, hospitalization, and overall morbidity. Each anticoagulant has unique pharmacologic properties of which nephrologists need to be aware to optimally manage patients. In addition, nephrologists are increasingly asked to aid in the management of adverse bleeding events related to oral anticoagulant use in patients with CKD and patients with ESKD. This article summarizes the clinical pharmacology of these drugs and identifies knowledge gaps in the literature related to their use.Jain, NishankReilly, Robert F.2018-05-25T07:36:53-07:00doi:10.2215/CJN.02170218hwp:resource-id:clinjasn;14/2/278American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnticoagulants, Apixaban, Atrial Fibrillation, chronic kidney disease, Dabigatran, Edoroxaban, End-stage Kidney Disease, Heart Valves, hospitalization, Humans, Kidney Failure, Chronic, Nephrologists, Off-label Use, Oral Anticoagulants, Pharmaceutical Preparations, Pulmonary Embolism, Pyrazoles, Pyridones, Renal Insufficiency, Chronic, Rivaroxaban, Stroke, United States Food and Drug Administration, uremia, Venous Thrombosis, WarfarinNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20192019-02-07February 07, 201910.2215/CJN.021702181555-90411555-905X2018-05-25T07:36:53-07:002019-02-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician141425278750287750
- Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance Hemodialysis10.2215/CJN.06190518Mon, 21 Jan 2019 07:45:34 GMT-08:00Trimethylamine N-Oxide and Cardiovascular Outcomes in Patients with ESKD Receiving Maintenance HemodialysisStubbs, Jason R.Stedman, Margaret R.Liu, SaiLong, JinFranchetti, YokoWest, Raymond E.Prokopienko, Alexander J.Mahnken, Jonathan D.Chertow, Glenn M.Nolin, Thomas D.2019-01-21T07:45:34-08:00doi:10.2215/CJN.06190518hwp:resource-id:clinjasn;14/2/261American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, dialysis, end-stage renal disease, mortality, heart disease, renal dialysis, end-stage kidney disease, trimethylamine, trimethyloxamine, Rodentia, Kidney Failure, Chronic, Methylamines, Angina, Unstable, Hyperparathyroidism, Secondary, Myocardial Infarction, Stroke, Atherosclerosis, hospitalization, Bacteria, Oxides, Cohort StudiesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-02-07February 07, 201910.2215/CJN.061905181555-90411555-905X2019-01-21T07:45:34-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1422261182267183
- Variability in Cinacalcet Prescription across US Hemodialysis Facilities10.2215/CJN.09550818Mon, 21 Jan 2019 07:45:33 GMT-08:00Variability in Cinacalcet Prescription across US Hemodialysis FacilitiesFuller, Douglas S.Xing, ShanBelozeroff, VasilyYehoshua, AlonMorgenstern, HalRobinson, Bruce M.Rubin, Robert J.Bhatt, NishaPisoni, Ronald L.2019-01-21T07:45:33-08:00doi:10.2215/CJN.09550818hwp:resource-id:clinjasn;14/2/241American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCalcimimetics, DOPPS, public policy, Cinacalcet Hydrochloride, renal dialysis, Cross-Sectional Studies, Prevalence, Motivation, Hyperparathyroidism, Secondary, Kidney Failure, Chronic, Prospective Payment System, parathyroid hormone, Medicare, Diagnosis-Related GroupsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-02-07February 07, 201910.2215/CJN.095508181555-90411555-905X2019-01-21T07:45:33-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1422241178249179
- Blood Pressure Variability, Mortality, and Cardiovascular Outcomes in CKD Patients10.2215/CJN.04030318Wed, 02 Jan 2019 07:01:12 GMT-08:00Blood Pressure Variability, Mortality, and Cardiovascular Outcomes in CKD PatientsMallamaci, FrancescaTripepi, GiovanniD’Arrigo, GraziellaBorrelli, SilvioGarofalo, CarloStanzione, GiovannaProvenzano, MicheleDe Nicola, LucaConte, GiuseppeMinutolo, RobertoZoccali, Carmine2019-01-02T07:01:12-08:00doi:10.2215/CJN.04030318hwp:resource-id:clinjasn;14/2/233American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, cardiovascular, mortality risk, chronic kidney disease, Prognosis, blood pressure, Systole, Renal Insufficiency, Chronic, Ambulatory CareOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20192019-02-07February 07, 201910.2215/CJN.040303181555-90411555-905X2019-01-02T07:01:12-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1422233175240177
- Medication Prescription Patterns for Secondary Hyperparathyroidism10.2215/CJN.15081218Mon, 21 Jan 2019 07:45:32 GMT-08:00Medication Prescription Patterns for Secondary HyperparathyroidismSeethapathy, HarishNigwekar, Sagar U.2019-01-21T07:45:32-08:00doi:10.2215/CJN.15081218hwp:resource-id:clinjasn;14/2/178American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, cinacalcet, hyperparathyroidism, bundling, parathyroid hormone, Drug Prescriptions, Hyperparathyroidism, SecondaryEditorialsEditorialseditorial20192019-02-07February 07, 201910.2215/CJN.150812181555-90411555-905X2019-01-21T07:45:32-08:002019-02-07Clinical Journal of the American Society of NephrologyEditorials1422178241179249
- Does an Apple (or Many) Each Day, Keep Mortality Away?10.2215/CJN.15001218Thu, 31 Jan 2019 09:00:35 GMT-08:00Does an Apple (or Many) Each Day, Keep Mortality Away?Moorthi, Ranjani N.2019-01-31T09:00:35-08:00doi:10.2215/CJN.15001218hwp:resource-id:clinjasn;14/2/180American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyVegetables, Fruit, Cohort Studies, dialysis, Surveys and Questionnaires, Risk, cardiovascular diseaseEditorialsEditorialseditorial20192019-02-07February 07, 201910.2215/CJN.150012181555-90411555-905X2019-01-31T09:00:35-08:002019-02-07Clinical Journal of the American Society of NephrologyEditorials1422180250181260
- Inadequate Dietary Potassium and Progression of CKD10.2215/CJN.01020119Thu, 14 Feb 2019 05:53:10 GMT-08:00Inadequate Dietary Potassium and Progression of CKDDuBose, Thomas D.2019-02-14T05:53:10-08:00doi:10.2215/CJN.01020119hwp:resource-id:clinjasn;14/3/319American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypokalemia, nutrition, oxidative stress, chronic kidney disease, Potassium, Dietary, Disease Progression, Renal Insufficiency, ChronicEditorialEditorialeditorial20192019-03-07March 07, 201910.2215/CJN.010201191555-90411555-905X2019-02-14T05:53:10-08:002019-03-07Clinical Journal of the American Society of NephrologyEditorial1433319330320340
- Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid Nephrolithiasis10.2215/CJN.10420818Mon, 11 Feb 2019 03:40:22 GMT-08:00Net Acid Excretion and Urinary Organic Anions in Idiopathic Uric Acid NephrolithiasisBobulescu, I. AlexandruPark, Sun K.Xu, L.H. RichieBlanco, FranciscoPoindexter, JohnAdams-Huet, BeverleyDavidson, Taylor L.Sakhaee, KhashayarMaalouf, Naim M.Moe, Orson W.2019-02-11T03:40:22-08:00doi:10.2215/CJN.10420818hwp:resource-id:clinjasn;14/3/411American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuric acid, kidney stones, metabolic study, urine metabolomics, Body Mass Index, Metabolic Syndrome, Protons, Prevalence, Fasting, Buffers, Ammonium Compounds, Metabolomics, Citric Acid Cycle, Inpatients, obesity, Kidney Calculi, kidney, Anions, Amino Acids, lipidsOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20192019-03-07March 07, 201910.2215/CJN.104208181555-90411555-905X2019-02-11T03:40:22-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles143411420
- Correction10.2215/CJN.13901118Thu, 20 Dec 2018 08:52:58 GMT-08:00CorrectionAmerican Society of Nephrology2018-12-20T08:52:58-08:00doi:10.2215/CJN.13901118hwp:resource-id:clinjasn;14/3/431American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correctionErratumErratumcorrection20192019-03-07March 7, 201910.2215/CJN.139011181555-90411555-905X2018-12-20T08:52:58-08:002019-03-07Clinical Journal of the American Society of NephrologyErratum1431143116694311679
- Enhanced Removal of Protein-Bound Uremic Toxins Using Displacers10.2215/CJN.00500119Wed, 06 Feb 2019 07:08:09 GMT-08:00Enhanced Removal of Protein-Bound Uremic Toxins Using DisplacersVan Biesen, WimEloot, Sunny2019-02-06T07:08:09-08:00doi:10.2215/CJN.00500119hwp:resource-id:clinjasn;14/3/324American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIbuprofen, protein binding, protein bound uremic toxin (PBUT), dialysis, Toxins, Biological, Proteins, Biophysical Phenomena, uremiaEditorialEditorialeditorial20192019-03-07March 07, 201910.2215/CJN.005001191555-90411555-905X2019-02-06T07:08:09-08:002019-03-07Clinical Journal of the American Society of NephrologyEditorial1433324394326402
- Differences in Dialysis Center Practices in Determining Hemodialysis Patient Postdialysis Target Weight and Patient Survival and Hospitalizations10.2215/CJN.15181218Tue, 05 Feb 2019 06:51:23 GMT-08:00Differences in Dialysis Center Practices in Determining Hemodialysis Patient Postdialysis Target Weight and Patient Survival and HospitalizationsDavenport, Andrew2019-02-05T06:51:23-08:00doi:10.2215/CJN.15181218hwp:resource-id:clinjasn;14/3/321American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, survival, hypotension, dry weight, sodium modelling, center practice, dialysis, Body Weight, hospitalizationEditorialEditorialeditorial20192019-03-07March 07, 201910.2215/CJN.151812181555-90411555-905X2019-02-05T06:51:23-08:002019-03-07Clinical Journal of the American Society of NephrologyEditorial1433321385323393
- Central Venous Stenosis, Access Outcome and Survival in Patients undergoing Maintenance Hemodialysis10.2215/CJN.07010618Thu, 14 Feb 2019 05:53:10 GMT-08:00Central Venous Stenosis, Access Outcome and Survival in Patients undergoing Maintenance HemodialysisAdwaney, AnamikaLim, CharlotteBlakey, SarahDuncan, NeillAshby, Damien R.2019-02-14T05:53:10-08:00doi:10.2215/CJN.07010618hwp:resource-id:clinjasn;14/3/378American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCentral Venous Catheter, Central Venous Stenosis, Tunneled Dialysis Catheter, arteriovenous fistula, risk factors, hemodialysis, dialysis, Incidence, Proportional Hazards Models, Constriction, Pathologic, Retrospective Studies, Cohort Studies, Catheterization, Pacemaker, ArtificialOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-03-07March 7, 201910.2215/CJN.070106181555-90411555-905X2019-02-14T05:53:10-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles143378384
- Proteinuria Reduction as a Surrogate End Point in Trials of IgA NephropathyIgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment’s effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment’s effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment’s effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.10.2215/CJN.08600718Fri, 11 Jan 2019 09:16:22 GMT-08:00Proteinuria Reduction as a Surrogate End Point in Trials of IgA NephropathyIgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment’s effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment’s effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment’s effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.Thompson, AlizaCarroll, KevinA. Inker, LesleyFloege, JürgenPerkovic, VladoBoyer-Suavet, SoniaW. Major, RupertI. Schimpf, JudithBarratt, JonathanCattran, Daniel C.S. Gillespie, BarbaraKausz, AnnamariaW. Mercer, AlexReich, Heather N.H. Rovin, BradWest, MelissaNachman, Patrick H.2019-01-11T09:16:22-08:00doi:10.2215/CJN.08600718hwp:resource-id:clinjasn;14/3/469American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, surrogate endpoint, clinical trials, Glomerulonephritis, IGA, creatinine, risk factors, proteinuria, kidney, Kidney Failure, ChronicFeatureFeatureresearch-article20192019-03-07March 7, 201910.2215/CJN.086007181555-90411555-905X2019-01-11T09:16:22-08:002019-03-07Clinical Journal of the American Society of NephrologyFeature143469481
- Clinical Pharmacology in HIV TherapyThe success of combination antiretroviral therapy in the treatment of HIV-1–positive individuals has shifted clinical attention toward combination antiretroviral drug regimens that optimize tolerability, long-term safety, and durable efficacy. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non–HIV-associated comorbidities, which may be observed earlier than in age-matched controls and despite the best available combination antiretroviral therapy. Similarly, HIV-1–positive individuals are now diagnosed and treated earlier with anticipated lifelong therapy. The contribution of specific antiretroviral agents to long-term morbidity and mortality is dependent on the pharmacologic characteristics of these agents, and it is increasingly important in this context.10.2215/CJN.02240218Tue, 29 May 2018 07:21:32 GMT-07:00Clinical Pharmacology in HIV TherapyThe success of combination antiretroviral therapy in the treatment of HIV-1–positive individuals has shifted clinical attention toward combination antiretroviral drug regimens that optimize tolerability, long-term safety, and durable efficacy. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non–HIV-associated comorbidities, which may be observed earlier than in age-matched controls and despite the best available combination antiretroviral therapy. Similarly, HIV-1–positive individuals are now diagnosed and treated earlier with anticipated lifelong therapy. The contribution of specific antiretroviral agents to long-term morbidity and mortality is dependent on the pharmacologic characteristics of these agents, and it is increasingly important in this context.Atta, Mohamed G.De Seigneux, SophieLucas, Gregory M.2018-05-29T07:21:32-07:00doi:10.2215/CJN.02240218hwp:resource-id:clinjasn;14/3/435American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydrug interactions, drug nephrotoxicity, pharmacokinetics, antiretroviral therapy, HIV, Anti-Retroviral Agents, HIV-1, Pharmacology, Clinical, Comorbidity, Morbidity, HIV Infections, Attention, Health Services AccessibilityNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20192019-03-07March 07, 201910.2215/CJN.022402181555-90411555-905X2018-05-29T07:21:32-07:002019-03-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician143435444
- Associations between Hemodialysis Facility Practices to Manage Fluid Volume and Intradialytic Hypotension and Patient Outcomes10.2215/CJN.08240718Tue, 05 Feb 2019 06:51:23 GMT-08:00Associations between Hemodialysis Facility Practices to Manage Fluid Volume and Intradialytic Hypotension and Patient OutcomesDasgupta, IndranilThomas, G. NeilClarke, JoanneSitch, AliceMartin, JamesBieber, BrianHecking, ManfredKaraboyas, AngeloPisoni, RonaldPort, FriedrichRobinson, BruceRayner, Hugh2019-02-05T06:51:23-08:00doi:10.2215/CJN.08240718hwp:resource-id:clinjasn;14/3/385American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, dialysis volume, hemodialysis, hospitalization, mortality risk, renal dialysis, blood pressure, Body Mass Index, Sodium, Frailty, Temperature, Dialysis Solutions, hypotension, diabetes mellitus, Prediabetic State, Comorbidity, SmokingOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-03-07March 07, 201910.2215/CJN.082407181555-90411555-905X2019-02-05T06:51:23-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1433385321393323
- Buttonhole versus Stepladder Cannulation for Home Hemodialysis10.2215/CJN.08310718Fri, 18 Jan 2019 08:36:27 GMT-08:00Buttonhole versus Stepladder Cannulation for Home HemodialysisHuang, Shih-Han S.MacRae, JenniferRoss, DanaImtiaz, RameezHollingsworth, BrittanyNesrallah, Gihad E.Copland, Michael A.McFarlane, Philip A.Chan, Christopher T.Zimmerman, Deborah2019-01-18T08:36:27-08:00doi:10.2215/CJN.08310718hwp:resource-id:clinjasn;14/3/403American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis access, Cannulation, Buttonhole, Step-Ladder, randomized controlled trials, Hemodialysis, Home, Central Venous Catheters, Patient Selection, Pilot Projects, Kidney Failure, Chronic, Catheterization, arteriovenous fistula, diabetes mellitus, Demography, Pain, Information Storage and RetrievalOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-03-07March 07, 201910.2215/CJN.083107181555-90411555-905X2019-01-18T08:36:27-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles143403410
- Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor10.2215/CJN.05240418Tue, 12 Feb 2019 07:06:19 GMT-08:00Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding CompetitorMadero, MagdalenaCano, Karla B.Campos, IsraelTao, XiaMaheshwari, VaibhavBrown, JillianCornejo, BeatrizHandelman, GarryThijssen, StephanKotanko, Peter2019-02-12T07:06:19-08:00doi:10.2215/CJN.05240418hwp:resource-id:clinjasn;14/3/394American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIbuprofen, protein bound uremic toxins, albumin binding competitors, displacer infusion, toxin displacement, p-Cresyl sulfate, Indoxyl sulfate, dialytic removal, hemodialysis, Indican, dialysis, creatinine, Tryptophan, urea, Dialysis Solutions, Binding Sites, Albumins, Toxins, Biological, SulfatesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20192019-03-07March 07, 201910.2215/CJN.052404181555-90411555-905X2019-02-12T07:06:19-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1433394324402326
- Efficacy and Safety of Imarikiren in Patients with Type 2 Diabetes and Microalbuminuria10.2215/CJN.07720618Tue, 12 Feb 2019 07:06:19 GMT-08:00Efficacy and Safety of Imarikiren in Patients with Type 2 Diabetes and MicroalbuminuriaIto, SadayoshiKagawa, TomoyaSaiki, TakuyaShimizu, KoheiKuroda, ShingoSano, YuheiUmeda, Yuusuke2019-02-12T07:06:19-08:00doi:10.2215/CJN.07720618hwp:resource-id:clinjasn;14/3/354American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyImarikiren, diabetes, microalbuminuria, direct renin inhibitor, randomized, placebo-controlled, double-blind, candesartan cilexetil, albuminuria, Diabetic Nephropathies, Renin, creatinine, Diabetes Mellitus, Type 2, Double-Blind Method, glomerular filtration rate, Incidence, blood pressure, candesartan, Tetrazoles, Benzimidazoles, Biphenyl Compounds, AlbuminsOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20192019-03-07March 07, 201910.2215/CJN.077206181555-90411555-905X2019-02-12T07:06:19-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles143354363
- The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney Disease10.2215/CJN.13921217Tue, 21 Aug 2018 05:47:50 GMT-07:00The Effect of Increasing Dialysate Magnesium on Serum Calcification Propensity in Subjects with End Stage Kidney DiseaseBressendorff, IainHansen, DitteSchou, MortenPasch, AndreasBrandi, Lisbet2018-08-21T05:47:50-07:00doi:10.2215/CJN.13921217hwp:resource-id:clinjasn;13/9/1373American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymagnesium, chronic hemodialysis, end stage kidney disease, mineral metabolism, randomized controlled trials, cardiovascular disease, Bicarbonates, calcium, alpha-2-HS-Glycoprotein, Confidence Intervals, renal dialysis, Kidney Failure, Chronic, Dialysis Solutions, Calcification, Physiologic, parathyroid hormone, Humerus, PhosphatesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-09-07September 07, 201810.2215/CJN.139212171555-90411555-905X2018-08-21T05:47:50-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13991373130913801310
- Magnesium Concentration in Dialysate10.2215/CJN.08380718Tue, 21 Aug 2018 05:47:50 GMT-07:00Magnesium Concentration in DialysateFloege, Jürgen2018-08-21T05:47:50-07:00doi:10.2215/CJN.08380718hwp:resource-id:clinjasn;13/9/1309American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, magnesium, vascular calcification, hemodialysis, Dialysis Solutions, renal dialysisEditorialsEditorialseditorial20182018-09-07September 07, 201810.2215/CJN.083807181555-90411555-905X2018-08-21T05:47:50-07:002018-09-07Clinical Journal of the American Society of NephrologyEditorials13991309137313101380
- Dementia in Dialysis10.2215/CJN.08610718Thu, 09 Aug 2018 09:22:40 GMT-07:00Dementia in DialysisWeintraub, Judy2018-08-09T09:22:40-07:00doi:10.2215/CJN.08610718hwp:resource-id:clinjasn;13/9/1305American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydementia, dialysis, renal dialysis, Kidney Failure, ChronicPatient VoicePatient Voiceeditorial20182018-09-07September 07, 201810.2215/CJN.086107181555-90411555-905X2018-08-09T09:22:40-07:002018-09-07Clinical Journal of the American Society of NephrologyPatient Voice13991305133913061347
- Determinants of Arteriovenous Fistula Maturation10.2215/CJN.08860718Thu, 23 Aug 2018 06:23:54 GMT-07:00Determinants of Arteriovenous Fistula MaturationHentschel, Dirk M.2018-08-23T06:23:54-07:00doi:10.2215/CJN.08860718hwp:resource-id:clinjasn;13/9/1307American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, dialysis access, vascular accessEditorialsEditorialseditorial20182018-09-07September 07, 201810.2215/CJN.088607181555-90411555-905X2018-08-23T06:23:54-07:002018-09-07Clinical Journal of the American Society of NephrologyEditorials13999130713581364130813631372
- Dementia, Alzheimer’s Disease, and Mortality after Hemodialysis Initiation10.2215/CJN.10150917Thu, 09 Aug 2018 09:22:40 GMT-07:00Dementia, Alzheimer’s Disease, and Mortality after Hemodialysis InitiationMcAdams-DeMarco, Mara A.Daubresse, MatthewBae, SunjaeGross, Alden L.Carlson, Michelle C.Segev, Dorry L.2018-08-09T09:22:40-07:00doi:10.2215/CJN.10150917hwp:resource-id:clinjasn;13/9/1339American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, geriatric nephrology, risk factors, Incidence, Proportional Hazards Models, kidney transplantation, Executive Function, renal dialysis, Alzheimer’s Disease, Medicare, Institutionalization, RegistriesOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20182018-09-07September 07, 201810.2215/CJN.101509171555-90411555-905X2018-08-09T09:22:40-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13991339130513471306
- Regulatory Considerations for Hemodiafiltration in the United StatesOnline hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10−6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.10.2215/CJN.12641117Tue, 06 Mar 2018 06:04:23 GMT-08:00Regulatory Considerations for Hemodiafiltration in the United StatesOnline hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10−6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.Ward, Richard A.Vienken, JörgSilverstein, Douglas M.Ash, StephenCanaud, Bernard2018-03-06T06:04:23-08:00doi:10.2215/CJN.12641117hwp:resource-id:clinjasn;13/9/1444American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodiafiltration, regulatory approval, United States, United States Food and Drug Administration, Molecular Weight, renal dialysis, Maintenance, Online Systems, water-electrolyte balance, Endotoxins, InfertilityFeatureFeatureresearch-article20182018-09-07September 07, 201810.2215/CJN.126411171555-90411555-905X2018-03-06T06:04:23-08:002018-09-07Clinical Journal of the American Society of NephrologyFeature13914441449
- Clinical PharmacodynamicsPharmacokinetics and pharmacodynamics follow the logic of cause and consequence. Receptor-mediated and reversible effects can be distinguished from direct and irreversible effects. Reversible effects are capacity-limited and saturable whereas irreversible effects are limited only by the number of viable targets. In the case of receptor-mediated and reversible effects a threshold and a ceiling concentration can be defined. Antimicrobial drugs with concentration-dependent action are distinguished from drugs with time-dependent action. Concentration-dependent effects are associated with a high ceiling concentration and the target is the high peak. Time-dependent effects are associated with a high threshold concentration and the target is the high trough. During kidney dysfunction, alterations of drug response are usually attributed to pharmacokinetic but rarely to pharmacodynamic changes. Dose adjustment calculations, therefore, tacitly presume that pharmacodynamic parameters remain unchanged while only pharmacokinetic parameters are altered in kidney failure. Kidney dysfunction influences the pharmacokinetic parameters of at least 50% of all essential drugs. Clinicians usually consider pharmacokinetics when kidney disease is found, but pharmacodynamics is as important. Alterations of pharmacodynamic parameters are conceivable but only rarely reported in kidney failure. Sometimes surprising dosing adjustments are needed when pharmacodynamic concepts are brought into the decision process of which dose to choose. Pharmacokinetics and pharmacodynamics should both be considered when any dosing regimen is determined.10.2215/CJN.10960917Wed, 16 May 2018 08:01:30 GMT-07:00Clinical PharmacodynamicsPharmacokinetics and pharmacodynamics follow the logic of cause and consequence. Receptor-mediated and reversible effects can be distinguished from direct and irreversible effects. Reversible effects are capacity-limited and saturable whereas irreversible effects are limited only by the number of viable targets. In the case of receptor-mediated and reversible effects a threshold and a ceiling concentration can be defined. Antimicrobial drugs with concentration-dependent action are distinguished from drugs with time-dependent action. Concentration-dependent effects are associated with a high ceiling concentration and the target is the high peak. Time-dependent effects are associated with a high threshold concentration and the target is the high trough. During kidney dysfunction, alterations of drug response are usually attributed to pharmacokinetic but rarely to pharmacodynamic changes. Dose adjustment calculations, therefore, tacitly presume that pharmacodynamic parameters remain unchanged while only pharmacokinetic parameters are altered in kidney failure. Kidney dysfunction influences the pharmacokinetic parameters of at least 50% of all essential drugs. Clinicians usually consider pharmacokinetics when kidney disease is found, but pharmacodynamics is as important. Alterations of pharmacodynamic parameters are conceivable but only rarely reported in kidney failure. Sometimes surprising dosing adjustments are needed when pharmacodynamic concepts are brought into the decision process of which dose to choose. Pharmacokinetics and pharmacodynamics should both be considered when any dosing regimen is determined.Keller, FriederHann, Alexander2018-05-16T08:01:30-07:00doi:10.2215/CJN.10960917hwp:resource-id:clinjasn;13/9/1413American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTacrolimus, pharmacokinetics, kidney failure, chemotherapyNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-09-07September 07, 201810.2215/CJN.109609171555-90411555-905X2018-05-16T08:01:30-07:002018-09-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician13914131420
- Gut-Derived Metabolites and Chronic Kidney Disease10.2215/CJN.08200718Tue, 07 Aug 2018 08:07:05 GMT-07:00Gut-Derived Metabolites and Chronic Kidney DiseaseVanholder, RaymondGlorieux, Griet2018-08-07T08:07:05-07:00doi:10.2215/CJN.08200718hwp:resource-id:clinjasn;13/9/1311American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuremia, uremic toxins, intestine, colon, microbiome, gut, metabolome, indoxyl sulfate, p-cresyl sulfate, regenerative medicine, sorption, adsorption, prebiotics, probiotics, synbiotics, xenobiotics, antibiotics, metabolomicsEditorialsEditorialseditorial20182018-09-07September 07, 201810.2215/CJN.082007181555-90411555-905X2018-08-07T08:07:05-07:002018-09-07Clinical Journal of the American Society of NephrologyEditorials13991311139813131404
- Circumstances of Death among Undocumented Immigrants Who Rely on Emergency-Only Hemodialysis10.2215/CJN.03440318Fri, 13 Jul 2018 12:26:28 GMT-07:00Circumstances of Death among Undocumented Immigrants Who Rely on Emergency-Only HemodialysisCervantes, LiliaO’Hare, AnnChonchol, MichelHull, MadelyneVan Bockern, JaniceThompson, MandyZoucha, Jeff2018-07-13T12:26:28-07:00doi:10.2215/CJN.03440318hwp:resource-id:clinjasn;13/9/1405American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydisparities, hemodialysis, end stage kidney disease, hispanic, mortality, Undocumented Immigrants, renal dialysis, DeathResearch LetterResearch Letterletter20182018-09-07September 07, 201810.2215/CJN.034403181555-90411555-905X2018-07-13T12:26:28-07:002018-09-07Clinical Journal of the American Society of NephrologyResearch Letter13914051406
- IgA Nephropathy Susceptibility Loci and Disease Progression10.2215/CJN.13701217Tue, 24 Jul 2018 01:47:04 GMT-07:00IgA Nephropathy Susceptibility Loci and Disease ProgressionShi, ManmanOuyang, YanYang, MingxinYang, MengZhang, XiaoyanHuang, WeiWang, WeimingWang, ZhaohuiZhang, WenChen, XiaonongPan, XiaoxiaRen, HongChen, NanXie, Jingyuan2018-07-24T13:47:04-07:00doi:10.2215/CJN.13701217hwp:resource-id:clinjasn;13/9/1330American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, progression, genetic risk score, Glomerulonephritis, IGA, Genome-Wide Association Study, Polymorphism, Single Nucleotide, glomerular filtration rate, Follow-Up Studies, Regression Analysis, Kidney Failure, Chronic, Risk, Disease Progression, Quality Control, HLA-DQ AntigensOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20182018-09-07September 07, 201810.2215/CJN.137012171555-90411555-905X2018-07-24T13:47:04-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13913301338
- Characteristics of Colon-Derived Uremic Solutes10.2215/CJN.03150318Tue, 07 Aug 2018 08:07:06 GMT-07:00Characteristics of Colon-Derived Uremic SolutesMair, Robert D.Sirich, Tammy L.Plummer, Natalie S.Meyer, Timothy W.2018-08-07T08:07:06-07:00doi:10.2215/CJN.03150318hwp:resource-id:clinjasn;13/9/1398American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal dialysis, creatinine, urea, Kidney Failure, Chronic, kidney, Renal Insufficiency, Metabolomics, Colon, Colectomy, SulfatasesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-09-07September 07, 201810.2215/CJN.031503181555-90411555-905X2018-08-07T08:07:06-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13991398131114041313
- Variations in 24-Hour BP Profiles in Cohorts of Patients with Kidney Disease around the World10.2215/CJN.13181117Thu, 05 Jul 2018 05:09:31 GMT-07:00Variations in 24-Hour BP Profiles in Cohorts of Patients with Kidney Disease around the WorldDrawz, Paul E.Brown, RolandDe Nicola, LucaFujii, NaohikoGabbai, Francis B.Gassman, JenniferHe, JiangIimuro, SatoshiLash, JamesMinutolo, RobertoPhillips, Robert A.Rudser, KyleRuilope, LuisSteigerwalt, SusanTownsend, Raymond R.Xie, DaweiRahman, Mahboob,2018-07-05T05:09:31-07:00doi:10.2215/CJN.13181117hwp:resource-id:clinjasn;13/9/1348American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, chronic kidney disease, ethnicity, Masked Hypertension, Antihypertensive Agents, Prevalence, Blood Pressure Monitoring, Ambulatory, Cohort Studies, White Coat Hypertension, blood pressure, Renal Insufficiency, Chronic, kidney, proteinuria, Comorbidity, diabetes mellitusOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20182018-09-07September 07, 201810.2215/CJN.131811171555-90411555-905X2018-07-05T05:09:31-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13913481357
- Hemodiafiltration to Address Unmet Medical Needs ESKD PatientsHemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient’s blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.10.2215/CJN.12631117Tue, 06 Mar 2018 06:04:22 GMT-08:00Hemodiafiltration to Address Unmet Medical Needs ESKD PatientsHemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient’s blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.Canaud, BernardVienken, JörgAsh, StephenWard, Richard A.2018-03-06T06:04:22-08:00doi:10.2215/CJN.12631117hwp:resource-id:clinjasn;13/9/1435American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodiafiltration, Clinical outcomes, Technical requirements, Therapy prescription, Bacteria, Blood Volume, Convection, Dialysis Solutions, Endotoxins, Europe, Filtration, Humans, hypotension, Japan, Kidney Failure, Chronic, Kidneys, Artificial, Molecular Weight, renal dialysis, ultrafiltration, water-electrolyte balanceFeatureFeatureresearch-article20182018-09-07September 07, 201810.2215/CJN.126311171555-90411555-905X2018-03-06T06:04:22-08:002018-09-07Clinical Journal of the American Society of NephrologyFeature13914351443
- Association of Preexisting Arterial Intimal Hyperplasia with Arteriovenous Fistula Outcomes10.2215/CJN.13431217Thu, 23 Aug 2018 06:23:53 GMT-07:00Association of Preexisting Arterial Intimal Hyperplasia with Arteriovenous Fistula OutcomesAllon, MichaelLitovsky, Silvio H.Zhang, YingyingLe, HaCheung, Alfred K.Shiu, Yan-Ting2018-08-23T06:23:53-07:00doi:10.2215/CJN.13431217hwp:resource-id:clinjasn;13/9/1358American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, Hyperplasia, Constriction, Pathologic, Prospective Studies, Tunica Intima, Veins, arteries, Calcinosis, arteriovenous fistula, DemographyOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-09-07September 07, 201810.2215/CJN.134312171555-90411555-905X2018-08-23T06:23:53-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13999135813071364136313081372
- Association of Urinary Biomarkers of Kidney Injury with Estimated GFR Decline in HIV-Infected Individuals following Tenofovir Disoproxil Fumarate Initiation10.2215/CJN.01700218Tue, 28 Aug 2018 07:51:51 GMT-07:00Association of Urinary Biomarkers of Kidney Injury with Estimated GFR Decline in HIV-Infected Individuals following Tenofovir Disoproxil Fumarate InitiationAscher, Simon B.Scherzer, RebeccaEstrella, Michelle M.Zhang, William R.Muiru, Anthony N.Jotwani, VasanthaGrunfeld, CarlParikh, Chirag R.Gustafson, DeborahYoung, MarySharma, AnjaliCohen, Mardge H.Ng, Derek K.Palella, Frank J.Witt, Mallory D.Ho, KenShlipak, Michael G.2018-08-28T07:51:51-07:00doi:10.2215/CJN.01700218hwp:resource-id:clinjasn;13/9/1321American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHIV, Kidney injury, Tenofovir disoproxil fumarate, Tenofovir, LCN2 protein, human, Lipocalin-2, Cystatin C, Uromodulin, interleukin 18 protein, human, creatinine, risk factors, Chemokine CCL2, Cohort Studies, epidermal growth factor, Acquired Immunodeficiency Syndrome, Hepatitis A Virus Cellular Receptor 1, glomerular filtration rate, Biomarkers, Demography, AlbuminsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-09-07September 07, 201810.2215/CJN.017002181555-90411555-905X2018-08-28T07:51:51-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13913211329
- Postoperative Ultrasound, Unassisted Maturation, and Subsequent Primary Patency of Arteriovenous Fistulas10.2215/CJN.02230218Thu, 23 Aug 2018 06:23:55 GMT-07:00Postoperative Ultrasound, Unassisted Maturation, and Subsequent Primary Patency of Arteriovenous FistulasFarrington, Crystal A.Robbin, Michelle L.Lee, TimmyBarker-Finkel, JillAllon, Michael2018-08-23T06:23:55-07:00doi:10.2215/CJN.02230218hwp:resource-id:clinjasn;13/9/1364American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, arteriovenous fistula, hemodialysis access, Humans, ROC Curve, Forearm, Logistic Models, Constriction, Pathologic, Prospective Studies, renal dialysis, Survival AnalysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-09-07September 07, 201810.2215/CJN.022302181555-90411555-905X2018-08-23T06:23:55-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13999136413071358137213081363
- Clinical and Economic Benefits of Antimicrobial Stewardship Programs in Hemodialysis Facilities10.2215/CJN.12521117Thu, 23 Aug 2018 06:23:54 GMT-07:00Clinical and Economic Benefits of Antimicrobial Stewardship Programs in Hemodialysis FacilitiesD’Agata, Erika M.C.Tran, DianaBautista, JosefShemin, DouglasGrima, Daniel2018-08-23T06:23:54-07:00doi:10.2215/CJN.12521117hwp:resource-id:clinjasn;13/9/1389American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, maintenance hemodialysis, vancomycin, cefazolin, multidrug-resistant organisms, Clostridium difficile, infections, mortality, costs, Anti-Infective Agents, Cost Savings, Outpatients, Antimicrobial Stewardship, renal dialysis, Clostridium Infections, Anti-Bacterial Agents, Enterococcus, Health Care Costs, ProbabilityOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-09-07September 07, 201810.2215/CJN.125211171555-90411555-905X2018-08-23T06:23:54-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13913891397
- Two-Year Observational Study of Bloodstream Infection Rates in Hemodialysis Facility Patients with and without Catheters10.2215/CJN.13551217Fri, 07 Sep 2018 01:00:24 GMT-07:00Two-Year Observational Study of Bloodstream Infection Rates in Hemodialysis Facility Patients with and without CathetersBrown, Robert S.Brickel, KristinDavis, Roger B.2018-09-07T13:00:24-07:00doi:10.2215/CJN.13551217hwp:resource-id:clinjasn;13/9/1381American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis access, risk factors, Bloodstream infection, hemodialysis catheter, quality care, dialysis providers, Odds Ratio, renal dialysis, Risk, Outpatients, Censuses, Catheter-Related Infections, Bacteremia, Medicare, CathetersOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-09-07September 07, 201810.2215/CJN.135512171555-90411555-905X2018-09-07T13:00:24-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13913811388
- Association of Inpatient Palliative Care with Health Care Utilization and Postdischarge Outcomes among Medicare Beneficiaries with End Stage Kidney Disease10.2215/CJN.00180118Thu, 19 Jul 2018 05:51:09 GMT-07:00Association of Inpatient Palliative Care with Health Care Utilization and Postdischarge Outcomes among Medicare Beneficiaries with End Stage Kidney DiseaseChettiar, AlexisMontez-Rath, MariaLiu, SaiHall, Yoshio N.O’Hare, Ann M.Kurella Tamura, Manjula2018-07-19T05:51:09-07:00doi:10.2215/CJN.00180118hwp:resource-id:clinjasn;13/8/1180American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinpatient palliative care, healthcare resource utilization, post-discharge outcomes, ESRD, end-of-life care, Hospices, Patient Readmission, Length of Stay, Palliative Care, Inpatients, Propensity Score, quality of life, Hospice Care, Patient Discharge, hospitalization, Medicare, Kidney Failure, Chronic, Cohort StudiesOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20182018-08-07August 07, 201810.2215/CJN.001801181555-90411555-905X2018-07-19T05:51:09-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13881180113811871139
- Drug Coated Balloon Angioplasty in Failing AV Fistulas10.2215/CJN.14231217Tue, 24 Jul 2018 01:47:04 GMT-07:00Drug Coated Balloon Angioplasty in Failing AV FistulasTrerotola, Scott O.Lawson, JeffreyRoy-Chaudhury, PrabirSaad, Theodore F.2018-07-24T13:47:04-07:00doi:10.2215/CJN.14231217hwp:resource-id:clinjasn;13/8/1215American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis access, randomized controlled trials, restenosis, paclitaxel, Constriction, Pathologic, Angioplasty, Balloon, Angioplasty, Balloon, CoronaryOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-08-07August 07, 201810.2215/CJN.142312171555-90411555-905X2018-07-24T13:47:04-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles1314887121511401073122411411073
- Commentary on Complications of Immunosuppressive Treatments for Glomerulonephritis10.2215/CJN.07610618Tue, 24 Jul 2018 01:47:05 GMT-07:00Commentary on Complications of Immunosuppressive Treatments for GlomerulonephritisKestenbaum, Bryan R.Seliger, Stephen L.2018-07-24T13:47:05-07:00doi:10.2215/CJN.07610618hwp:resource-id:clinjasn;13/8/1276American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulonephritis, Immunosuppressive AgentsCommentaryCommentaryarticle-commentary20182018-08-07August 07, 201810.2215/CJN.076106181555-90411555-905X2018-07-24T13:47:05-07:002018-08-07Clinical Journal of the American Society of NephrologyCommentary13881276126412771275
- Metabolic Changes with Base-Loading in CKD10.2215/CJN.01830218Fri, 22 Jun 2018 06:19:45 GMT-07:00Metabolic Changes with Base-Loading in CKDScialla, Julia J.Brown, LandonGurley, SusanCorcoran, David L.Bain, James R.Muehlbauer, Michael J.O’Neal, Sara K.M. O’Connell, ThomasWolf, MylesMelamed, Michal L.Hostetter, Thomas H.Abramowitz, Matthew K.2018-06-22T06:19:45-07:00doi:10.2215/CJN.01830218hwp:resource-id:clinjasn;13/8/1244American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic metabolic acidosis, chronic kidney disease, metabolism, Renal Insufficiency, Chronic, kidneyResearch LetterResearch LetterResearch Letter20182018-08-07August 07, 201810.2215/CJN.018302181555-90411555-905X2018-06-22T06:19:45-07:002018-08-07Clinical Journal of the American Society of NephrologyResearch Letter13812441246
- Proximal Tubular Secretory ClearanceThe secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings. Major barriers to estimating tubular solute clearance include uncertainty regarding optimal endogenous secretory markers and a lack of standardized laboratory assays. The creation of new methods to measure tubular secretion could catalyze advances in kidney disease research and clinical care. Differences in secretory clearance relative to the GFR could help distinguish among the causes of CKD, particularly for disorders that primarily affect the tubulointerstitium. As the primary mechanism by which the kidneys excrete medications, tubular secretory clearance offers promise for improving kidney medication dosing, which is currently exclusively on the basis of filtration. The differing metabolic profiles of retained solutes eliminated by secretion versus glomerular filtration suggest that secretory clearance could uniquely inform uremic toxicity, refine existing measures of residual kidney function, and improve prediction of cardiovascular and kidney disease outcomes. Interdisciplinary research across clinical, translational, and laboratory medicine is needed to bring this often neglected kidney function into the limelight.10.2215/CJN.12001017Wed, 28 Feb 2018 07:15:55 GMT-08:00Proximal Tubular Secretory ClearanceThe secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings. Major barriers to estimating tubular solute clearance include uncertainty regarding optimal endogenous secretory markers and a lack of standardized laboratory assays. The creation of new methods to measure tubular secretion could catalyze advances in kidney disease research and clinical care. Differences in secretory clearance relative to the GFR could help distinguish among the causes of CKD, particularly for disorders that primarily affect the tubulointerstitium. As the primary mechanism by which the kidneys excrete medications, tubular secretory clearance offers promise for improving kidney medication dosing, which is currently exclusively on the basis of filtration. The differing metabolic profiles of retained solutes eliminated by secretion versus glomerular filtration suggest that secretory clearance could uniquely inform uremic toxicity, refine existing measures of residual kidney function, and improve prediction of cardiovascular and kidney disease outcomes. Interdisciplinary research across clinical, translational, and laboratory medicine is needed to bring this often neglected kidney function into the limelight.Wang, KeKestenbaum, Bryan2018-02-28T07:15:55-08:00doi:10.2215/CJN.12001017hwp:resource-id:clinjasn;13/8/1291American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproximal tubule, renal proximal tubule cell, tubule cells, uremia, chronic kidney disease, creatinine clearance, drug excretion, glomerular filtration rate, Glomerular Basement Membrane, Capillaries, Uncertainty, Interdisciplinary Research, Metabolome, Renal Circulation, kidney, Renal Insufficiency, ChronicReviewsReviewsreview-article20182018-08-07August 07, 201810.2215/CJN.120010171555-90411555-905X2018-02-28T07:15:55-08:002018-08-07Clinical Journal of the American Society of NephrologyReviews13812911296
- Complications of Immunosuppression in Glomerular DiseaseMost glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.10.2215/CJN.01920218Tue, 24 Jul 2018 01:47:03 GMT-07:00Complications of Immunosuppression in Glomerular DiseaseMost glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.Jefferson, J. Ashley2018-07-24T13:47:03-07:00doi:10.2215/CJN.01920218hwp:resource-id:clinjasn;13/8/1264American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, rituximab, glucocorticoids, mycophenolate mofetil, cyclophosphamide, tacrolimus, adverse events, lupus nephritis, ANCA, membranous nephropathy, IgA nephropathy, Immunosuppressive Agents, glomerulonephritis, immunosuppression, Kidney Failure, Chronic, kidneyEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20182018-08-07August 07, 201810.2215/CJN.019202181555-90411555-905X2018-07-24T13:47:03-07:002018-08-07Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology13881264127612751277
- Alteration of HDL Protein Composition with Hemodialysis Initiation10.2215/CJN.11321017Wed, 25 Jul 2018 10:04:32 GMT-07:00Alteration of HDL Protein Composition with Hemodialysis InitiationWang, KeZelnick, Leila R.Hoofnagle, Andrew N.Vaisar, TomasHenderson, Clark M.Imrey, Peter B.Robinson-Cohen, Cassiannede Boer, Ian H.Shiu, Yan-TingHimmelfarb, JonathanBeck, Gerald J.Kestenbaum, Bryan2018-07-25T10:04:32-07:00doi:10.2215/CJN.11321017hwp:resource-id:clinjasn;13/8/1225American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyApolipoproteins, Cardiovascular Diseases, Cholesterol, Comorbidity, Demography, Fistula, Haptoglobins, Hemodialysis Initiation, Hemoglobins, High-density Lipoprotein, Humans, Inflammation, Isotopes, Linear Models, Lipid Metabolism, Lipoproteins, HDL, Mass Spectrometry, Phospholipid Transfer Proteins, Proteomic Analysis, renal dialysis, Renal Insufficiency, Chronic, risk factorsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-08-07August 07, 201810.2215/CJN.113210171555-90411555-905X2018-07-25T10:04:32-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13812251233
- Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.01520218Thu, 19 Jul 2018 05:51:10 GMT-07:00Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney DiseaseEdwards, Marie E.Chebib, Fouad T.Irazabal, Maria V.Ofstie, Troy G.Bungum, Lisa A.Metzger, Andrew J.Senum, Sarah R.Hogan, Marie C.El-Zoghby, Ziad M.Kline, Timothy L.Harris, Peter C.Czerwiec, Frank S.Torres, Vicente E.2018-07-19T05:51:10-07:00doi:10.2215/CJN.01520218hwp:resource-id:clinjasn;13/8/1153American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, Benzazepines, chronic kidney disease, EGFR protein, human, Follow-Up Studies, glomerular filtration rate, Humans, polycystic kidney disease, Polycystic Kidney, Autosomal Dominant, Receptor, Epidermal Growth Factor, Renal Insufficiency, Chronic, Renal Replacement Therapy, TEMPO, Tolvaptan, vasopressin, Vasopressin Receptor AntagonistOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20182018-08-07August 07, 201810.2215/CJN.015202181555-90411555-905X2018-07-19T05:51:10-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles138611539101161910
- Cost of Dialysis Therapy by Modality in Manitoba10.2215/CJN.10180917Wed, 18 Jul 2018 06:16:05 GMT-07:00Cost of Dialysis Therapy by Modality in ManitobaBeaudry, AlainFerguson, Thomas W.Rigatto, ClaudioTangri, NavdeepDumanski, SandiKomenda, Paul2018-07-18T06:16:05-07:00doi:10.2215/CJN.10180917hwp:resource-id:clinjasn;13/8/1197American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, chronic hemodialysis, clinical epidemiology, dialysis, Economic Analysis, Economic Impact, Epidemiology and outcomes, hemodialysis, renal dialysis, Prevalence, Hospitals, General, Kidney Failure, Chronic, peritoneal dialysis, Kidneys, Artificial, Cost of IllnessOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-08-07August 07, 201810.2215/CJN.101809171555-90411555-905X2018-07-18T06:16:05-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13811971203
- End of Life, Withdrawal, and Palliative Care Utilization among Patients Receiving Maintenance Hemodialysis Therapy10.2215/CJN.00590118Thu, 19 Jul 2018 05:51:09 GMT-07:00End of Life, Withdrawal, and Palliative Care Utilization among Patients Receiving Maintenance Hemodialysis TherapyChen, Joy Chieh-YuThorsteinsdottir, BjorgVaughan, Lisa E.Feely, Molly A.Albright, Robert C.Onuigbo, MacaulayNorby, Suzanne M.Gossett, Christy L.D’Uscio, Margaret M.Williams, Amy W.Dillon, John J.Hickson, LaTonya J.2018-07-19T05:51:09-07:00doi:10.2215/CJN.00590118hwp:resource-id:clinjasn;13/8/1172American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypalliative care, hemodialysis withdrawal, end stage kidney disease, chronic hemodialysis, geriatric nephrology, hospice, intensive care unit, goals of care, diabetes, death notification form, geriatric medicine, mortality, healthcare power of attorney, palliative nephrology, risk factors, Logistic Models, Cohort Studies, Frailty, Hospital Mortality, hospitalization, Referral and Consultation, Terminal CareOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20182018-08-07August 07, 201810.2215/CJN.005901181555-90411555-905X2018-07-19T05:51:09-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13881172113811791139
- Meeting the Palliative Care Needs of Maintenance Hemodialysis Patients10.2215/CJN.07390618Thu, 19 Jul 2018 05:51:08 GMT-07:00Meeting the Palliative Care Needs of Maintenance Hemodialysis PatientsGrubbs, Vanessa2018-07-19T05:51:08-07:00doi:10.2215/CJN.07390618hwp:resource-id:clinjasn;13/8/1138American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypalliative care, maintenance hemodialysis, advance care planning, end of life care, hospice, end stage kidney disease, dialysis withdrawal, ESCO, renal dialysisEditorialsEditorialseditorial20182018-08-07August 07, 201810.2215/CJN.073906181555-90411555-905X2018-07-19T05:51:08-07:002018-08-07Clinical Journal of the American Society of NephrologyEditorials13888113811801172113911871179
- Characterizing Approaches to Dialysis Decision Making with Older Adults10.2215/CJN.01740218Thu, 26 Jul 2018 06:21:31 GMT-07:00Characterizing Approaches to Dialysis Decision Making with Older AdultsLadin, KerenPandya, RenukaPerrone, Ronald D.Meyer, Klemens B.Kannam, AllisonLoke, RohiniOskoui, TiraWeiner, Daniel E.Wong, John B.2018-07-26T06:21:31-07:00doi:10.2215/CJN.01740218hwp:resource-id:clinjasn;13/8/1188American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, dialysis, quality of life, end stage kidney disease, decision-making, conservative management, patient engagement, Patient Participation, renal dialysis, Physician's Role, Conservative Treatment, Choice Behavior, Renal Replacement Therapy, Comprehension, Kidney DiseasesOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20182018-08-07August 07, 201810.2215/CJN.017402181555-90411555-905X2018-07-26T06:21:31-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13881188113311961134
- Clinical Pharmacokinetics in Kidney DiseaseA change in pharmacokinetics can alter drug exposure and predispose the patient to either over- or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between individuals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drug’s properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.10.2215/CJN.05150418Tue, 24 Jul 2018 01:47:03 GMT-07:00Clinical Pharmacokinetics in Kidney DiseaseA change in pharmacokinetics can alter drug exposure and predispose the patient to either over- or underdosing, potentially resulting in adverse drug reactions or therapeutic failure. Kidney disease is characterized by multiple physiologic effects, which induce clinically significant changes in pharmacokinetics. These vary between individuals and may be quantitated in certain instances. An understanding of pharmacokinetic concepts is, therefore, important for a rational approach to the design of drug dosing regimens for the delivery of personalized medical care. Whether kidney disease is acute or chronic, drug clearance decreases and the volume of distribution may remain unchanged or increase. AKI is defined by dynamic changes in kidney function, which complicates attempts to accurately quantify drug clearance. In contrast, changes in drug clearance progress more slowly with CKD. In general, kidney replacement therapies increase drug clearance, but the extent to which this occurs depends on the modality used and its duration, the drug’s properties, and the timing of drug administration. However, the changes in drug handling associated with kidney disease are not isolated to reduced kidney clearance and an appreciation of the scale of potential derangements is important. In most instances, the first dose administered in patients with kidney disease is the same as in patients with normal kidney function. However, in some cases, a higher (loading) initial dose is given to rapidly achieve therapeutic concentrations, followed by a lower maintenance dose, as is well described when prescribing anti-infectives to patients with sepsis and AKI. This review provides an overview of how pharmacokinetic principles can be applied to patients with kidney disease to personalize dosage regimens. Patients with kidney disease are a vulnerable population and the increasing prevalence of kidney disease means that these considerations are important for all prescribers.Roberts, Darren M.Sevastos, JacobCarland, Jane E.Stocker, Sophie L.Lea-Henry, Tom N.2018-07-24T13:47:03-07:00doi:10.2215/CJN.05150418hwp:resource-id:clinjasn;13/8/1254American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPharmacokinetics, kidney disease, chronic kidney disease, acute kidney injury, dialysis, clearance, volume of distribution, personalized medicine, Prevalence, Vulnerable Populations, Renal Replacement Therapy, Acute Kidney Injury, Sepsis, Renal Insufficiency, Chronic, Drug-Related Side Effects and Adverse ReactionsNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-08-07August 07, 201810.2215/CJN.051504181555-90411555-905X2018-07-24T13:47:03-07:002018-08-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician13812541263
- Person-Centered Approach to Deciding on Long-Term Dialysis10.2215/CJN.07300618Thu, 26 Jul 2018 06:21:30 GMT-07:00Person-Centered Approach to Deciding on Long-Term DialysisEilers, Denise2018-07-26T06:21:30-07:00doi:10.2215/CJN.07300618hwp:resource-id:clinjasn;13/8/1133American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhome hemodialysis, conservative management, patient centered care, dialysis choice, shared decision makingPatient VoicePatient Voiceresearch-article20182018-08-07August 07, 201810.2215/CJN.073006181555-90411555-905X2018-07-26T06:21:30-07:002018-08-07Clinical Journal of the American Society of NephrologyPatient Voice13881133118811341196
- Correction10.2215/CJN.06120518Fri, 15 Jun 2018 07:25:44 GMT-07:00CorrectionAmerican Society of Nephrology2018-06-15T07:25:44-07:00doi:10.2215/CJN.06120518hwp:resource-id:clinjasn;13/8/1247American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correctionErratumErratumcorrection20182018-08-07August 07, 201810.2215/CJN.061205181555-90411555-905X2018-06-15T07:25:44-07:002018-08-07Clinical Journal of the American Society of NephrologyErratum138512477871247789
- Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney Disease10.2215/CJN.11631017Tue, 19 Jun 2018 08:09:52 GMT-07:00Intravenous Epoetin Alfa-epbx versus Epoetin Alfa for Treatment of Anemia in End-Stage Kidney DiseaseFishbane, StevenSingh, BhupinderKumbhat, SeemaWisemandle, Wayne A.Martin, Nancy E.2018-06-19T08:09:52-07:00doi:10.2215/CJN.11631017hwp:resource-id:clinjasn;13/8/1204American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Epoetin Alfa, Antibodies, Neutralizing, Biosimilar Pharmaceuticals, Double-Blind Method, Incidence, Confidence Intervals, Least-Squares Analysis, EPO protein, human, erythropoietin, renal dialysis, Kidney Failure, Chronic, anemia, Hemoglobins, Red-Cell Aplasia, Pure, Body WeightOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-08-07August 07, 201810.2215/CJN.116310171555-90411555-905X2018-06-19T08:09:52-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13812041214
- Drug-Coated Balloon Angioplasty for Hemodialysis Fistula Maintenance10.2215/CJN.07360618Tue, 24 Jul 2018 01:47:04 GMT-07:00Drug-Coated Balloon Angioplasty for Hemodialysis Fistula MaintenanceSachdeva, BharatAbreo, Kenneth2018-07-24T13:47:04-07:00doi:10.2215/CJN.07360618hwp:resource-id:clinjasn;13/8/1140American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAngioplasty, Balloon, Angioplasty, Balloon, Coronary, renal dialysis, FistulaEditorialsEditorialseditorial20182018-08-07August 07, 201810.2215/CJN.073606181555-90411555-905X2018-07-24T13:47:04-07:002018-08-07Clinical Journal of the American Society of NephrologyEditorials13881140121511411224
- COL4A3 Gene Variants and Diabetic Kidney Disease in MODY10.2215/CJN.09100817Mon, 16 Jul 2018 07:44:52 GMT-07:00COL4A3 Gene Variants and Diabetic Kidney Disease in MODYWang, YitingZhang, JunlinZhao, YingwangWang, ShanshanZhang, JieHan, QianqianZhang, RuiGuo, RuikunLi, HanyuLi, LiWang, TingliTang, XiHe, ChangzhengTeng, GeerGu, WeiyueLiu, Fang2018-07-16T07:44:52-07:00doi:10.2215/CJN.09100817hwp:resource-id:clinjasn;13/8/1162American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiopsy, COL4A3 gene, Diabetes Mellitus, Type 2, Diabetic Nephropathies, diabetic nephropathy, Fluorescent Antibody Technique, gene expression, Gene Frequency, Glomerular Basement Membrane, Humans, kidney, Kidney Failure, Chronic, Maturity-onset diabetes of the young, Parents, Phenotype, Protein Interaction Maps, proteinuria, Staining and Labeling, Susceptibility gene, Whole Exome SequencingOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20182018-08-07August 07, 201810.2215/CJN.091008171555-90411555-905X2018-07-16T07:44:52-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13881162113511711137
- Ptolemy and Copernicus Revisited10.2215/CJN.05090418Thu, 17 May 2018 06:08:05 GMT-07:00Ptolemy and Copernicus RevisitedCoca, Steven G.2018-05-17T06:08:05-07:00doi:10.2215/CJN.05090418hwp:resource-id:clinjasn;13/6/825American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyheart failure, kidney, Acute Kidney Injury, Atherosclerotic Events, AtherosclerosisEditorialsEditorialseditorial20182018-06-07June 07, 201810.2215/CJN.050904181555-90411555-905X2018-05-17T06:08:05-07:002018-06-07Clinical Journal of the American Society of NephrologyEditorials1366825833828841
- Donor Outcomes10.2215/CJN.05000418Thu, 31 May 2018 07:11:29 GMT-07:00Donor OutcomesSaunders, Milda R.Josephson, Michelle A.2018-05-31T07:11:29-07:00doi:10.2215/CJN.05000418hwp:resource-id:clinjasn;13/6/831American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyLiving donation, Donor outcomes, PerspectivesEditorialsEditorialseditorial20182018-06-07June 07, 201810.2215/CJN.050004181555-90411555-905X2018-05-31T07:11:29-07:002018-06-07Clinical Journal of the American Society of NephrologyEditorials13666831823916832824926
- Living Donation10.2215/CJN.05520518Thu, 31 May 2018 07:11:28 GMT-07:00Living DonationDíaz-González de Ferris, Maria E.Díaz-González, Lourdes M.Ferris, Michael Ted2018-05-31T07:11:28-07:00doi:10.2215/CJN.05520518hwp:resource-id:clinjasn;13/6/823American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, kidney donation, living donation, donor, transplantationPatient VoicePatient Voiceresearch-article20182018-06-07June 07, 201810.2215/CJN.055205181555-90411555-905X2018-05-31T07:11:28-07:002018-06-07Clinical Journal of the American Society of NephrologyPatient Voice13666823831916824832926
- Comparative Effects of Cholecalciferol and Calcitriol on Circulating Markers of CKD Mineral Bone Disorder10.2215/CJN.00480118Wed, 07 Mar 2018 05:44:58 GMT-08:00Comparative Effects of Cholecalciferol and Calcitriol on Circulating Markers of CKD Mineral Bone DisorderZelnick, Leila R.de Boer, Ian H.Kestenbaum, Bryan R.Chonchol, MichelKendrick, Jessica2018-03-07T05:44:58-08:00doi:10.2215/CJN.00480118hwp:resource-id:clinjasn;13/6/927American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrology25-hydroxyvitamin D, Calcifediol, Calcitriol, Cholecalciferol, chronic kidney disease, Chronic Kidney Disease-Mineral and Bone Disorder, clinical trial, Dihydroxycholecalciferols, Fibroblast Growth Factors, mineral metabolism, Minerals, obesity, parathyroid hormone, Renal Insufficiency, Chronic, Vitamin D, Vitamin D3 24-HydroxylaseResearch LetterResearch Letterresearch-article20182018-06-07June 07, 201810.2215/CJN.004801181555-90411555-905X2018-03-07T05:44:58-08:002018-06-07Clinical Journal of the American Society of NephrologyResearch Letter136927928
- Identifying Outcomes that Are Important to Living Kidney Donors10.2215/CJN.13441217Thu, 31 May 2018 07:11:29 GMT-07:00Identifying Outcomes that Are Important to Living Kidney DonorsHanson, Camilla S.Chapman, Jeremy R.Gill, John S.Kanellis, JohnWong, GermaineCraig, Jonathan C.Teixeira-Pinto, ArmandoChadban, Steve J.Garg, Amit X.Ralph, Angelique F.Pinter, JuleLewis, Joshua R.Tong, Allison2018-05-31T07:11:29-07:00doi:10.2215/CJN.13441217hwp:resource-id:clinjasn;13/6/916American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Pain, Australia, Canada, Decision Making, Focus Groups, Informed Consent, Kidney Donors, Life Style, Living Donors, Nephrectomy, Nominal Group Technique, outcomes, Personal Satisfaction, Qualitative Research, Renal Insufficiency, Risk AssessmentOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-06-07June 07, 201810.2215/CJN.134412171555-90411555-905X2018-05-31T07:11:29-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles13666916823831926824832
- Concentrations of Trace Elements and Clinical Outcomes in Hemodialysis Patients10.2215/CJN.11451017Thu, 29 Mar 2018 06:09:57 GMT-07:00Concentrations of Trace Elements and Clinical Outcomes in Hemodialysis PatientsTonelli, MarcelloWiebe, NatashaBello, AminuField, Catherine J.Gill, John S.Hemmelgarn, Brenda R.Holmes, Daniel T.Jindal, KailashKlarenbach, Scott W.Manns, Braden J.Thadhani, RaviKinniburgh, David,2018-03-29T06:09:57-07:00doi:10.2215/CJN.11451017hwp:resource-id:clinjasn;13/6/907American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyArsenic, Cadmium, Copper, Follow-up Studies, hemodialysis, hospitalization, Humans, Ions, Lead, Logistic Models, Longitudinal Studies, Manganese, Mercury, Prospective Studies, renal dialysis, Selenium, Trace Elements, ZincOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-06-07June 07, 201810.2215/CJN.114510171555-90411555-905X2018-03-29T06:09:57-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136907915
- Association between Duration of Predialysis Care and Mortality after Dialysis Start10.2215/CJN.11951017Mon, 05 Mar 2018 07:48:22 GMT-08:00Association between Duration of Predialysis Care and Mortality after Dialysis StartLiu, PingQuinn, Robert R.Oliver, Matthew J.Ronksley, Paul E.Hemmelgarn, Brenda R.Quan, HudeHiremath, SwapnilBello, Aminu K.Blake, Peter G.Garg, Amit X.Johnson, JohnVerrelli, MauroZacharias, James M.Abd ElHafeez, SamarTonelli, MarcelloRavani, Pietro2018-03-05T07:48:22-08:00doi:10.2215/CJN.11951017hwp:resource-id:clinjasn;13/6/893American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney failure, predialysis care, referral, mortality risk, nephrology, Inpatients, Proportional Hazards Models, Retrospective Studies, Outpatients, Canada, Renal Insufficiency, Chronic, peritoneal dialysis, Disease Progression, Fluid Therapy, Referral and Consultation, Demography, renal dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-06-07June 07, 201810.2215/CJN.119510171555-90411555-905X2018-03-05T07:48:22-08:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136893899
- Prevalence of Hypertension in Children with Early-Stage ADPKD10.2215/CJN.11401017Thu, 19 Apr 2018 07:58:40 GMT-07:00Prevalence of Hypertension in Children with Early-Stage ADPKDMassella, LauraMekahli, DjalilaParipović, DušanPrikhodina, LarisaGodefroid, NathalieNiemirska, AnnaAğbaş, AyşeKalicka, KarolinaJankauskiene, AugustinaMizerska-Wasiak, MalgorzataAfonso, Alberto CaldasSalomon, RémiDeschênes, GeorgesAriceta, GemaÖzçakar, Z. BirsinTeixeira, AnaDuzova, AliHarambat, JérômeSeeman, TomášHrčková, GabrielaLungu, Adrian CatalinPapizh, SvetlanaPeco-Antic, AmiraDe Rechter, StéphanieGiordano, UgoKirchner, MariettaLutz, TeresaSchaefer, FranzDevuyst, OlivierWühl, ElkeEmma, Francesco2018-04-19T07:58:40-07:00doi:10.2215/CJN.11401017hwp:resource-id:clinjasn;13/6/874American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyABPM, Ambulatory Blood Pressure Monitoring, Antihypertensive Agents, Autosomal Dominant Polycystic Kidney Disease, blood pressure, Blood Pressure Determination, Blood Pressure Monitoring, Ambulatory, Child, Cysts, Humans, hypertension, kidney, Logistic Models, pediatrics, Polycystic Kidney, Autosomal Dominant, Prevalence, Retrospective Studies, Rhythm AnalysisOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20182018-06-07June 07, 201810.2215/CJN.114010171555-90411555-905X2018-04-19T07:58:40-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136874883
- Teaching Pediatric Peritoneal Dialysis Globally through Virtual Simulation10.2215/CJN.10460917Wed, 02 May 2018 05:56:47 GMT-07:00Teaching Pediatric Peritoneal Dialysis Globally through Virtual SimulationOlszewski, Aleksandra E.Daniel, Dennis A.Stein, Deborah R.McCulloch, Mignon I.Su, Sharon W.Hames, Daniel L.Wolbrink, Traci A.2018-05-02T05:56:47-07:00doi:10.2215/CJN.10460917hwp:resource-id:clinjasn;13/6/900American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChild, Curriculum, Global Health, Health Personnel, Humans, Kidney Diseases, Knowledge, Learning, Linear Models, Medical Education, Nephrology Education, Nursing Education, pediatric nephrology, peritoneal dialysis, Personal Satisfaction, Prevalence, Prospective Studies, Serious Gaming, Surveys And Questionnaires, Virtual SimulationOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-06-07June 07, 201810.2215/CJN.104609171555-90411555-905X2018-05-02T05:56:47-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136900906
- Race in America10.2215/CJN.04890418Thu, 24 May 2018 06:17:07 GMT-07:00Race in AmericaTuttle, Katherine R.2018-05-24T06:17:07-07:00doi:10.2215/CJN.04890418hwp:resource-id:clinjasn;13/6/829American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic kidney disease, disparities, clinical trials, social determinants of health, healthcare access and quality, diabetes mellitus, Continental Population Groups, Renal Insufficiency, ChronicEditorialsEditorialseditorial20182018-06-07June 07, 201810.2215/CJN.048904181555-90411555-905X2018-05-24T06:17:07-07:002018-06-07Clinical Journal of the American Society of NephrologyEditorials1366829884830892
- Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 Diabetes10.2215/CJN.11871017Thu, 24 May 2018 06:17:08 GMT-07:00Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 DiabetesGerber, ClaireCai, XuanLee, JungwhaCraven, TimothyScialla, JuliaSouma, NaoSrivastava, AnandMehta, RupalPaluch, AmandaHodakowski, AlexanderFrazier, RebeccaCarnethon, Mercedes R.Wolf, Myles SeligIsakova, Tamara2018-05-24T06:17:08-07:00doi:10.2215/CJN.11871017hwp:resource-id:clinjasn;13/6/884American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiological Factors, Cardiovascular Diseases, chronic kidney disease, Confidence Intervals, creatinine, diabetes, Diabetes Mellitus, Type 2, Disease Progression, Follow-up Studies, glomerular filtration rate, Humans, Incidence, Renal Insufficiency, Renal Insufficiency, Chronic, risk factorsOriginal ArticlesDiabetes and The KidneyOriginal ArticlesDiabetes and The Kidneyresearch-article20182018-06-07June 07, 201810.2215/CJN.118710171555-90411555-905X2018-05-24T06:17:08-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles1366884829892830
- Clear the Fog around Parathyroid Hormone Assays10.2215/CJN.01730218Mon, 05 Mar 2018 07:48:22 GMT-08:00Clear the Fog around Parathyroid Hormone AssaysHocher, BertholdZeng, Shufei2018-03-05T07:48:22-08:00doi:10.2215/CJN.01730218hwp:resource-id:clinjasn;13/4/524American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAssays, Biological Assay, CKD, oxidative stress, PTHEditorialsEditorialseditorial20182018-04-06April 06, 201810.2215/CJN.017302181555-90411555-905X2018-03-05T07:48:22-08:002018-04-06Clinical Journal of the American Society of NephrologyEditorials1344524569526576
- Community-Based CKD Screening in Black Americans10.2215/CJN.02320218Thu, 15 Mar 2018 06:59:34 GMT-07:00Community-Based CKD Screening in Black AmericansNorris, Keith C.Nicholas, Susanne B.2018-03-15T06:59:34-07:00doi:10.2215/CJN.02320218hwp:resource-id:clinjasn;13/4/521American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyScreening, African American, Chronic Kidney Disease, African DescentEditorialsEditorialseditorial20182018-04-06April 06, 201810.2215/CJN.023202181555-90411555-905X2018-03-15T06:59:34-07:002018-04-06Clinical Journal of the American Society of NephrologyEditorials1344521551523559
- Metabolic and Hypertensive Complications of Pregnancy in Women with Nephrolithiasis10.2215/CJN.12171017Thu, 22 Feb 2018 07:39:25 GMT-08:00Metabolic and Hypertensive Complications of Pregnancy in Women with NephrolithiasisTangren, Jessica SheehanPowe, Camille E.Ecker, JeffreyBramham, KateAnkers, ElizabethKarumanchi, S. AnanthThadhani, Ravi2018-02-22T07:39:25-08:00doi:10.2215/CJN.12171017hwp:resource-id:clinjasn;13/4/612American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, preeclampsia, pregnancy, gestational diabetes, Humans, Female, Diabetes, Gestational, Body Mass Index, Pregnancy Outcome, Pre-Eclampsia, Metabolic Syndrome, Pregnancy Trimester, Third, Gestational Age, blood pressure, Linear Models, Intensive Care, Neonatal, Hospitals, General, Retrospective Studies, Kidney Calculi, hypertension, Renal Insufficiency, Chronic, Tomography, Massachusetts, Infant, NewbornOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20182018-04-06April 06, 201810.2215/CJN.121710171555-90411555-905X2018-02-22T07:39:25-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134612619
- β-Blocker Dialyzability in Maintenance Hemodialysis Patients10.2215/CJN.07470717Thu, 08 Mar 2018 10:12:42 GMT-08:00β-Blocker Dialyzability in Maintenance Hemodialysis PatientsTieu, AlvinVelenosi, Thomas J.Kucey, Andrew S.Weir, Matthew A.Urquhart, Bradley L.2018-03-08T10:12:42-08:00doi:10.2215/CJN.07470717hwp:resource-id:clinjasn;13/4/604American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybeta blocker, hemodialysis, dialyzability, pharmacokinetics, dialytic clearance, Humans, carvedilol, Bisoprolol, Metoprolol, Atenolol, Cross-Over Studies, renal dialysis, Propanolamines, Carbazoles, Adrenergic beta-Antagonists, Dialysis SolutionsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-04-06April 06, 201810.2215/CJN.074707171555-90411555-905X2018-03-08T10:12:42-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134604611
- Serum Bicarbonate Concentration and Cognitive Function in Hypertensive Adults10.2215/CJN.07050717Thu, 22 Mar 2018 05:49:23 GMT-07:00Serum Bicarbonate Concentration and Cognitive Function in Hypertensive AdultsDobre, MirelaGaussoin, Sarah A.Bates, Jeffrey T.Chonchol, Michel B.Cohen, Debbie L.Hostetter, Thomas H.Raphael, Kalani L.Taylor, Addison A.Lerner, Alan J.Wright, Jackson T.Rahman, Mahboob,2018-03-22T05:49:23-07:00doi:10.2215/CJN.07050717hwp:resource-id:clinjasn;13/4/596American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBicarbonate, chronic kidney disease, cognitive function, Adult, Cross-Sectional Studies, albuminuria, Executive Function, Bicarbonates, Linear Models, Language, blood pressure, White Matter, Renal Insufficiency, Chronic, Cohort Studies, Cognition, Memory, Attention, Cerebrovascular Circulation, acidosis, Comorbidity, Magnetic Resonance Imaging, Homeostasis, Demography, HumansOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20182018-04-06April 06, 201810.2215/CJN.070507171555-90411555-905X2018-03-22T05:49:23-07:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles1344596527603528
- Treatment of Severe HyponatremiaPatients with severe (serum sodium ≤120 mEq/L), symptomatic hyponatremia can develop life-threatening or fatal complications from cerebral edema if treatment is inadequate and permanent neurologic disability from osmotic demyelination if treatment is excessive. Unfortunately, as is true of all electrolyte disturbances, there are no randomized trials to guide the treatment of this challenging disorder. Rather, therapeutic decisions rest on physiologic principles, animal models, observational studies, and single-patient reports. European guidelines and recommendations of an American Expert panel have come to similar conclusions on how much correction of hyponatremia is enough and how much is too much, but there are important differences. We review the evidence supporting these recommendations, identifying areas that rest on relatively solid ground and highlighting areas in greatest need of additional data.10.2215/CJN.10440917Tue, 02 Jan 2018 10:59:16 GMT-08:00Treatment of Severe HyponatremiaPatients with severe (serum sodium ≤120 mEq/L), symptomatic hyponatremia can develop life-threatening or fatal complications from cerebral edema if treatment is inadequate and permanent neurologic disability from osmotic demyelination if treatment is excessive. Unfortunately, as is true of all electrolyte disturbances, there are no randomized trials to guide the treatment of this challenging disorder. Rather, therapeutic decisions rest on physiologic principles, animal models, observational studies, and single-patient reports. European guidelines and recommendations of an American Expert panel have come to similar conclusions on how much correction of hyponatremia is enough and how much is too much, but there are important differences. We review the evidence supporting these recommendations, identifying areas that rest on relatively solid ground and highlighting areas in greatest need of additional data.Sterns, Richard H.2018-01-02T10:59:16-08:00doi:10.2215/CJN.10440917hwp:resource-id:clinjasn;13/4/641American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyosmolality, hypokalemia, clinical nephrology, humans, Animals, United States, hyponatremia, Brain Edema, Sodium, Water-Electrolyte Imbalance, Demyelinating Diseases, Osmosis, Models, Animal, electrolytesEvidence-Based NephrologyEvidence-Based Nephrologyreview-article20182018-04-06April 06, 201810.2215/CJN.104409171555-90411555-905X2018-01-02T10:59:16-08:002018-04-06Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology1344641650649651
- Systems Thinking and LeadershipInfections are the second leading cause of death for patients with ESKD. Despite multiple efforts, nephrologists have been unable to prevent infections in dialysis facilities. The American Society of Nephrology and the Centers for Disease Control and Prevention have partnered to create Nephrologists Transforming Dialysis Safety to promote nephrologist leadership and engagement in efforts to “Target Zero” preventable dialysis infections. Because traditional approaches to infection control and prevention in dialysis facilities have had limited success, Nephrologists Transforming Dialysis Safety is reconceptualizing the problem in the context of the complexity of health care systems and organizational behavior. By identifying different parts of a problem and attempting to understand how these parts interact and produce a result, systems thinking has effectively tackled difficult problems in dynamic settings. The dialysis facility is composed of different physical and human elements that are interconnected and affect not only behavior but also, the existence of a culture of safety that promotes infection prevention. Because dialysis infections result from a complex system of interactions between caregivers, patients, dialysis organizations, and the environment, attempts to address infections by focusing on one element in isolation often fail. Creating a sense of urgency and commitment to eradicating dialysis infections requires leadership and motivational skills. These skills are not taught in the standard nephrology or medical director curriculum. Effective leadership by medical directors and engagement in infection prevention by nephrologists are required to create a culture of safety. It is imperative that nephrologists commit to leadership training and embrace their potential as change agents to prevent infections in dialysis facilities. This paper explores the systemic factors contributing to the ongoing dialysis infection crisis in the United States and the role of nephrologists in instilling a culture of safety in which infections can be anticipated and prevented.10.2215/CJN.09740917Thu, 22 Mar 2018 05:49:24 GMT-07:00Systems Thinking and LeadershipInfections are the second leading cause of death for patients with ESKD. Despite multiple efforts, nephrologists have been unable to prevent infections in dialysis facilities. The American Society of Nephrology and the Centers for Disease Control and Prevention have partnered to create Nephrologists Transforming Dialysis Safety to promote nephrologist leadership and engagement in efforts to “Target Zero” preventable dialysis infections. Because traditional approaches to infection control and prevention in dialysis facilities have had limited success, Nephrologists Transforming Dialysis Safety is reconceptualizing the problem in the context of the complexity of health care systems and organizational behavior. By identifying different parts of a problem and attempting to understand how these parts interact and produce a result, systems thinking has effectively tackled difficult problems in dynamic settings. The dialysis facility is composed of different physical and human elements that are interconnected and affect not only behavior but also, the existence of a culture of safety that promotes infection prevention. Because dialysis infections result from a complex system of interactions between caregivers, patients, dialysis organizations, and the environment, attempts to address infections by focusing on one element in isolation often fail. Creating a sense of urgency and commitment to eradicating dialysis infections requires leadership and motivational skills. These skills are not taught in the standard nephrology or medical director curriculum. Effective leadership by medical directors and engagement in infection prevention by nephrologists are required to create a culture of safety. It is imperative that nephrologists commit to leadership training and embrace their potential as change agents to prevent infections in dialysis facilities. This paper explores the systemic factors contributing to the ongoing dialysis infection crisis in the United States and the role of nephrologists in instilling a culture of safety in which infections can be anticipated and prevented.Wong, Leslie P.2018-03-22T05:49:24-07:00doi:10.2215/CJN.09740917hwp:resource-id:clinjasn;13/4/655American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, hemodialysis, ESRD, infections, patient safety, Humans, United States, Nephrologists, nephrology, Physician Executives, Leadership, Caregivers, Cause of Death, Kidney Failure, Chronic, Infection Control, Centers for Disease Control and Prevention (U.S.), Delivery of Health Care, Curriculum, Systems AnalysisFeatureFeatureresearch-article20182018-04-06April 06, 201810.2215/CJN.097409171555-90411555-905X2018-03-22T05:49:24-07:002018-04-06Clinical Journal of the American Society of NephrologyFeature1344444655663666669671662665668670673
- The Role of Bicarbonate in Cognition10.2215/CJN.02390218Thu, 22 Mar 2018 05:49:23 GMT-07:00The Role of Bicarbonate in CognitionSozio, Stephen M.McAdams-DeMarco, Mara2018-03-22T05:49:23-07:00doi:10.2215/CJN.02390218hwp:resource-id:clinjasn;13/4/527American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacidosis, Bicarbonates, chronic kidney disease, Cognition, dementiaEditorialsEditorialseditorial20182018-04-06April 06, 201810.2215/CJN.023902181555-90411555-905X2018-03-22T05:49:23-07:002018-04-06Clinical Journal of the American Society of NephrologyEditorials1344527596528603
- Commentary on Treatment of Severe Hyponatremia10.2215/CJN.13381217Tue, 02 Jan 2018 10:59:15 GMT-08:00Commentary on Treatment of Severe HyponatremiaSeliger, StephenKestenbaum, Bryan2018-01-02T10:59:15-08:00doi:10.2215/CJN.13381217hwp:resource-id:clinjasn;13/4/650American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyponatremia, Epidemiology and outcomes, Retrospective Studies, Consensus, Prospective Studies, Demyelinating Diseases, Osmosis, Syndrome, Models, TheoreticalCommentaryCommentaryarticle-commentary20182018-04-06April 06, 201810.2215/CJN.133812171555-90411555-905X2018-01-02T10:59:15-08:002018-04-06Clinical Journal of the American Society of NephrologyCommentary1344650641651649
- Central Blood Pressure and Cardiovascular Outcomes in Chronic Kidney Disease10.2215/CJN.08620817Fri, 23 Feb 2018 11:41:49 GMT-08:00Central Blood Pressure and Cardiovascular Outcomes in Chronic Kidney DiseaseRahman, MahboobHsu, Jesse YenchihDesai, NirajHsu, Chi-yuanAnderson, Amanda H.Appel, Lawrence J.Chen, JingCohen, Debbie L.Drawz, Paul E.He, JiangQiang, PanRicardo, Ana C.Steigerwalt, SusanWeir, Matthew R.Wright, Jackson T.Zhang, XiaomingTownsend, Raymond R.,2018-02-23T11:41:49-08:00doi:10.2215/CJN.08620817hwp:resource-id:clinjasn;13/4/585American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Middle Aged, blood pressure, Prospective Studies, Arterial Pressure, Proportional Hazards Models, Confidence Intervals, Cardiovascular Diseases, Follow-Up Studies, Longitudinal Studies, risk factors, Renal Insufficiency, Chronic, AortaOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20182018-04-06April 06, 201810.2215/CJN.086208171555-90411555-905X2018-02-23T11:41:49-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134585595
- Performance on the Nephrology In-Training Examination and ABIM Nephrology Certification Examination Outcomes10.2215/CJN.05580517Wed, 28 Feb 2018 07:15:54 GMT-08:00Performance on the Nephrology In-Training Examination and ABIM Nephrology Certification Examination OutcomesJurich, DanielDuhigg, Lauren M.Plumb, Troy J.Haist, Steven A.Hawley, Janine L.Lipner, Rebecca S.Smith, LaurelNorby, Suzanne M.2018-02-28T07:15:54-08:00doi:10.2215/CJN.05580517hwp:resource-id:clinjasn;13/5/710American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIn-Training Examination, Board Certification Examination, Fellowship Programs, American Board of Internal Medicine, Fellowships and Scholarships, nephrology, Schools, Medical, Confidence Intervals, Certification, Feedback, Regression Analysis, Cohort StudiesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-05-07May 07, 201810.2215/CJN.055805171555-90411555-905X2018-02-28T07:15:54-08:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles135710717
- The Effect of Learning Styles on Adverse Events in Home Hemodialysis Patients10.2215/CJN.12161017Mon, 16 Apr 2018 07:17:07 GMT-07:00The Effect of Learning Styles on Adverse Events in Home Hemodialysis PatientsAuguste, Bourne L.Al-Muhaiteeb, AbdullahChan, Christopher T.2018-04-16T07:17:07-07:00doi:10.2215/CJN.12161017hwp:resource-id:clinjasn;13/5/782American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhome hemodialysis, Learning styles, Adverse Events, Humans, Hemodialysis, Home, LearningResearch LetterResearch Letterletter20182018-05-07May 07, 201810.2215/CJN.121610171555-90411555-905X2018-04-16T07:17:07-07:002018-05-07Clinical Journal of the American Society of NephrologyResearch Letter135782783
- Survey of Kidney Biopsy Clinical Practice and Training in the United States10.2215/CJN.13471217Wed, 18 Apr 2018 07:10:55 GMT-07:00Survey of Kidney Biopsy Clinical Practice and Training in the United StatesYuan, Christina M.Nee, RobertLittle, Dustin J.Narayan, RajeevChilds, John M.Prince, Lisa K.Raghavan, RajeevOliver, James D.,2018-04-18T07:10:55-07:00doi:10.2215/CJN.13471217hwp:resource-id:clinjasn;13/5/718American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiopsy, Contraindications, Curriculum, Fellowships and Scholarships, Interventional Radiology, kidney biopsy, Military Personnel, Nephrologists, nephrology, Nephrology Education, Nephrology Fellowship, Program Directors, Surveys and Questionnaires, Thinking, Transplants, United StatesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-05-07May 07, 201810.2215/CJN.134712171555-90411555-905X2018-04-18T07:10:55-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1355718681725682
- Antimalarial Drugs for the Prevention of Chronic Kidney Disease in Patients with Rheumatoid Arthritis10.2215/CJN.03300318Mon, 16 Apr 2018 07:17:07 GMT-07:00Antimalarial Drugs for the Prevention of Chronic Kidney Disease in Patients with Rheumatoid ArthritisRodrigues, Jennifer C.Bargman, Joanne M.2018-04-16T07:17:07-07:00doi:10.2215/CJN.03300318hwp:resource-id:clinjasn;13/5/679American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAntimalarials, Arthritis, Rheumatoid, B-lymphocytes, Cell Differentiation, Chronic inflammation, chronic kidney disease, cytokines, Dendritic Cells, Fibroblasts, Gastrointestinal Microbiome, Homeostasis, Humans, Hydroxychloroquine, Renal Insufficiency, Chronic, Rheumatoid Arthritis, Rheumatoid Factor, Smoking, Synovial Membrane, Th17 CellsEditorialsEditorialseditorial20182018-05-07May 07, 201810.2215/CJN.033003181555-90411555-905X2018-04-16T07:17:07-07:002018-05-07Clinical Journal of the American Society of NephrologyEditorials1355679702680709
- Is There a Need for Additional DQ Matching?10.2215/CJN.03720318Mon, 23 Apr 2018 05:36:44 GMT-07:00Is There a Need for Additional DQ Matching?Süsal, CanerZeier, Martin2018-04-23T05:36:44-07:00doi:10.2215/CJN.03720318hwp:resource-id:clinjasn;13/5/683American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyABO Blood-Group System, Alleles, HLA Antigens, kidney transplantation, New Zealand, Registries, renal dialysis, Tissue Donors, Transplantation, HomologousEditorialsEditorialseditorial20182018-05-07May 07, 201810.2215/CJN.037203181555-90411555-905X2018-04-23T05:36:44-07:002018-05-07Clinical Journal of the American Society of NephrologyEditorials1355683763684771
- Symptom Prioritization among Adults Receiving In-Center Hemodialysis10.2215/CJN.10850917Tue, 20 Mar 2018 06:45:41 GMT-07:00Symptom Prioritization among Adults Receiving In-Center HemodialysisFlythe, Jennifer E.Hilliard, TandreaCastillo, GracielaIkeler, KourtneyOrazi, JazmineAbdel-Rahman, EmaadPai, Amy BartonRivara, Matthew B.St. Peter, Wendy L.Weisbord, Steven D.Wilkie, CarolineMehrotra, Rajnish2018-03-20T06:45:41-07:00doi:10.2215/CJN.10850917hwp:resource-id:clinjasn;13/5/735American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, dialysis, end-stage renal disease, ESRD, hemodialysis, Sleep Initiation and Maintenance Disorders, depression, Focus Groups, Frustration, quality of life, Anxiety, Emotions, Fatigue, Surveys and Questionnaires, Nausea, Vomiting, renal dialysis, PainOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-05-07May 07, 201810.2215/CJN.108509171555-90411555-905X2018-03-20T06:45:41-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles135735745
- Long-Term Consequences of Acute Kidney Injury in Children10.2215/CJN.03430318Fri, 20 Apr 2018 07:37:14 GMT-07:00Long-Term Consequences of Acute Kidney Injury in ChildrenSutherland, Scott M.2018-04-20T07:37:14-07:00doi:10.2215/CJN.03430318hwp:resource-id:clinjasn;13/5/677American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Adult, Attention, Cardiovascular Diseases, Child, Hospitalized, children, Hospital Mortality, Humans, hypertension, Intensive Care Units, proteinuria, Renal Insufficiency, Chronic, Respiration, ArtificialEditorialsEditorialseditorial20182018-05-07May 07, 201810.2215/CJN.034303181555-90411555-905X2018-04-20T07:37:14-07:002018-05-07Clinical Journal of the American Society of NephrologyEditorials1355677685678692
- Does the Kidney Biopsy Portend the Future of Nephrology?10.2215/CJN.03380318Wed, 18 Apr 2018 07:10:54 GMT-07:00Does the Kidney Biopsy Portend the Future of Nephrology?Gilbert, Scott J.2018-04-18T07:10:54-07:00doi:10.2215/CJN.03380318hwp:resource-id:clinjasn;13/5/681American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Biopsy, Fellowship, histopathology, kidney, kidney biopsy, nephrology, Precision Medicine, Prognosis, Renal Insufficiency, Chronic, TrainingEditorialsEditorialseditorial20182018-05-07May 07, 201810.2215/CJN.033803181555-90411555-905X2018-04-18T07:10:54-07:002018-05-07Clinical Journal of the American Society of NephrologyEditorials1355681718682725
- Opioid Analgesics and Adverse Outcomes among Hemodialysis Patients10.2215/CJN.09910917Thu, 19 Apr 2018 07:58:40 GMT-07:00Opioid Analgesics and Adverse Outcomes among Hemodialysis PatientsIshida, Julie H.McCulloch, Charles E.Steinman, Michael A.Grimes, Barbara A.Johansen, Kirsten L.2018-04-19T07:58:40-07:00doi:10.2215/CJN.09910917hwp:resource-id:clinjasn;13/5/746American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, clinical epidemiology, United States Renal Data System, opioid, Humans, United States, Middle Aged, Analgesics, Opioid, Cohort Studies, Opioid-Related Disorders, Pain, Morphine, Medicare, hospitalization, renal dialysis, Emergency Service, HospitalOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-05-07May 07, 201810.2215/CJN.099109171555-90411555-905X2018-04-19T07:58:40-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1355746675753676
- Appropriate Use of Opioids in Patients with Kidney Diseases10.2215/CJN.03540318Thu, 19 Apr 2018 07:58:40 GMT-07:00Appropriate Use of Opioids in Patients with Kidney DiseasesWhite, David M.2018-04-19T07:58:40-07:00doi:10.2215/CJN.03540318hwp:resource-id:clinjasn;13/5/675American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAccidental Falls, Analgesics, Analgesics, Opioid, Confounding Factors (Epidemiology), dialysis, Female, Fractures, Bone, Health Personnel, hemodialysis, Humans, Kidney Diseases, nephrology, Opioid-Related Disorders, Pain Management, Prescriptions, quality of life, renal dialysisPatient VoicePatient Voiceresearch-article20182018-05-07May 07, 201810.2215/CJN.035403181555-90411555-905X2018-04-19T07:58:40-07:002018-05-07Clinical Journal of the American Society of NephrologyPatient Voice1355675746676753
- Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes10.2215/CJN.09510817Fri, 23 Mar 2018 05:56:14 GMT-07:00Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in DiabetesSchroeder, Emily B.Chonchol, MichelShetterly, Susan M.Powers, J. DavidAdams, John L.Schmittdiel, Julie A.Nichols, Gregory A.O’Connor, Patrick J.Steiner, John F.2018-03-23T05:56:14-07:00doi:10.2215/CJN.09510817hwp:resource-id:clinjasn;13/5/727American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, cardiovascular disease, kidney disease, hypertension, Acute Coronary Syndrome, Adrenergic beta-Antagonists, aldosterone, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Angiotensins, Antihypertensive Agents, Calcium Channel Blockers, Cohort Studies, Coronary Artery Bypass, Dihydropyridines, heart failure, Myocardial Infarction, Peptidyl-Dipeptidase A, Percutaneous Coronary Intervention, Propensity Score, Proportional Hazards Models, Sodium Chloride Symporter Inhibitors, Sodium Potassium Chloride Symporter Inhibitors, StrokeOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20182018-05-07May 07, 201810.2215/CJN.095108171555-90411555-905X2018-03-23T05:56:14-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles135727734
- Pharmacology behind Common Drug NephrotoxicitiesPatients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. A combination of factors including the innate nephrotoxicity of drugs, underlying patient characteristics that increase their risk for kidney injury, and the metabolism and pathway of excretion by the kidneys of the various agents administered enhance risk for drug-induced nephrotoxicity. This paper will review these clinically relevant aspects of drug-induced nephrotoxicity for the clinical nephrologist.10.2215/CJN.00150118Thu, 05 Apr 2018 06:42:13 GMT-07:00Pharmacology behind Common Drug NephrotoxicitiesPatients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. A combination of factors including the innate nephrotoxicity of drugs, underlying patient characteristics that increase their risk for kidney injury, and the metabolism and pathway of excretion by the kidneys of the various agents administered enhance risk for drug-induced nephrotoxicity. This paper will review these clinically relevant aspects of drug-induced nephrotoxicity for the clinical nephrologist.Perazella, Mark A.2018-04-05T06:42:13-07:00doi:10.2215/CJN.00150118hwp:resource-id:clinjasn;13/12/1897American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, acute renal failure, drug nephrotoxicity, Drug Transporters, Humans, kidney, metabolism, Nephrologists, Nonprescription Drugs, Pharmacology, Proximal Tubulopathy, Renal Elimination, RiskNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-12-07December 07, 201810.2215/CJN.001501181555-90411555-905X2018-04-05T06:42:13-07:002018-12-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician131218971908
- Correction10.2215/CJN.12071018Fri, 09 Nov 2018 05:47:19 GMT-08:00CorrectionAmerican Society of Nephrology2018-11-09T05:47:19-08:00doi:10.2215/CJN.12071018hwp:resource-id:clinjasn;13/12/1889American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correctionErratumErratumcorrection20182018-12-07December 07, 201810.2215/CJN.120710181555-90411555-905X2018-11-09T05:47:19-08:002018-12-07Clinical Journal of the American Society of NephrologyErratum1312318895021889517
- Home-Based Care for CKD for High-Risk Populations10.2215/CJN.12411018Thu, 15 Nov 2018 07:48:00 GMT-08:00Home-Based Care for CKD for High-Risk PopulationsRodgers, Wendy2018-11-15T07:48:00-08:00doi:10.2215/CJN.12411018hwp:resource-id:clinjasn;13/12/1777American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD Zuni minority, Home Care Services, risk factors, Renal Insufficiency, ChronicPatient VoicePatient Voiceeditorial20182018-12-07December 07, 201810.2215/CJN.124110181555-90411555-905X2018-11-15T07:48:00-08:002018-12-07Clinical Journal of the American Society of NephrologyPatient Voice13121212177717791801177817801809
- Health Insurance in the First 3 Months of Hemodialysis and Early Vascular Access10.2215/CJN.06660518Thu, 01 Nov 2018 09:08:47 GMT-07:00Health Insurance in the First 3 Months of Hemodialysis and Early Vascular AccessLin, EugeneMell, Matthew W.Winkelmayer, Wolfgang C.Erickson, Kevin F.2018-11-01T09:08:47-07:00doi:10.2215/CJN.06660518hwp:resource-id:clinjasn;13/12/1866American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, Economic Impact, hemodialysis access, United States Renal Data System, renal dialysis, Medicaid, Central Venous Catheters, Odds Ratio, Medically Uninsured, Risk, Retrospective Studies, Kidney Failure, Chronic, Medicare, Insurance Coverage, Insurance, Health, arteriovenous fistula, hospitalization, RegistriesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-12-07December 07, 201810.2215/CJN.066605181555-90411555-905X2018-11-01T09:08:47-07:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles131218661875
- Procurement Biopsies in the Evaluation of Deceased Donor Kidneys10.2215/CJN.04150418Thu, 25 Oct 2018 02:00:13 GMT-07:00Procurement Biopsies in the Evaluation of Deceased Donor KidneysCarpenter, DustinHusain, S. AliBrennan, CoreyBatal, IbrahimHall, Isaac E.Santoriello, DominickRosen, RaphaelCrew, R. JohnCampenot, EricDube, Geoffrey K.Radhakrishnan, JaiStokes, M. BarrySandoval, P. RodrigoD’Agati, VivetteCohen, David J.Ratner, Lloyd E.Markowitz, GlenMohan, Sumit2018-10-25T14:00:13-07:00doi:10.2215/CJN.04150418hwp:resource-id:clinjasn;13/12/1876American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, transplant pathology, kidney biopsy, Graft Survival, Retrospective Studies, Frozen Sections, Pathologists, kidney transplantation, Prognosis, Follow-Up Studies, Allografts, Paraffin Embedding, Reproducibility of Results, Kidney Diseases, kidney, Tissue Donors, Biopsy, Vascular Diseases, AtrophyOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-12-07December 07, 201810.2215/CJN.041504181555-90411555-905X2018-10-25T14:00:13-07:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles131218761885
- Does What Goes Around Always Come Around?10.2215/CJN.12291018Thu, 15 Nov 2018 07:47:58 GMT-08:00Does What Goes Around Always Come Around?Trachtman, Howard2018-11-15T07:47:58-08:00doi:10.2215/CJN.12291018hwp:resource-id:clinjasn;13/12/1788American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMinimal change disease, children, Nephrosis, Lipoid, Adrenocorticotropic Hormone, Adrenal Cortex Hormones, Immunosuppressive Agents, Steroids, Anti-Infective AgentsEditorialsEditorialseditorial20182018-12-07December 07, 201810.2215/CJN.122910181555-90411555-905X2018-11-15T07:47:58-08:002018-12-07Clinical Journal of the American Society of NephrologyEditorials1312121788185917901865
- Persistent Hematuria in ANCA Vasculitis10.2215/CJN.14101217Thu, 25 Jan 2018 06:03:51 GMT-08:00Persistent Hematuria in ANCA VasculitisMahoney, Shannon L.Nachman, Patrick H.2018-01-25T06:03:51-08:00doi:10.2215/CJN.14101217hwp:resource-id:clinjasn;13/2/201American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA vasculitis, hematuria, relapse, Antibodies, Antineutrophil Cytoplasmic, Hematuria, Anti-Neutrophil Cytoplasmic Antibody-Associated VasculitisEditorialsEditorialseditorial20182018-02-07February 07, 201810.2215/CJN.141012171555-90411555-905X2018-01-25T06:03:51-08:002018-02-07Clinical Journal of the American Society of NephrologyEditorials1322201251202257
- Anion Gap as a Determinant of Ionized Fraction of Divalent Cations in Hemodialysis Patients10.2215/CJN.07930717Mon, 27 Nov 2017 06:42:21 GMT-08:00Anion Gap as a Determinant of Ionized Fraction of Divalent Cations in Hemodialysis PatientsSakaguchi, YusukeHamano, TakayukiKubota, KeiichiOka, TatsufumiYamaguchi, SatoshiMatsumoto, AyumiHashimoto, NobuhiroMori, DaisukeObi, YasueMatsui, IsaoIsaka, Yoshitaka2017-11-27T06:42:21-08:00doi:10.2215/CJN.07930717hwp:resource-id:clinjasn;13/2/274American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMagnesium, calcium, hemodialysis, chronic kidney disease, renal dialysis, Cations, Divalent, Prevalence, Acid-Base Equilibrium, Cross-Sectional Studies, Outpatients, Fluid Therapy, Anions, Metabolic Diseases, Kidney Failure, ChronicOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-02-07February 07, 201810.2215/CJN.079307171555-90411555-905X2017-11-27T06:42:21-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles132274281
- Why Nomenclature for Pharmacist-Led Interventions Matters10.2215/CJN.13601217Tue, 02 Jan 2018 10:59:16 GMT-08:00Why Nomenclature for Pharmacist-Led Interventions MattersPai, Amy Barton2018-01-02T10:59:16-08:00doi:10.2215/CJN.13601217hwp:resource-id:clinjasn;13/2/198American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypharmacist, medication management, hospitalizations, Humans, Pharmacists, Comorbidity, Polypharmacy, Chronic Disease, Medicare, hospitalization, Renal Insufficiency, ChronicEditorialsEditorialseditorial20182018-02-07February 07, 201810.2215/CJN.136012171555-90411555-905X2018-01-02T10:59:16-08:002018-02-07Clinical Journal of the American Society of NephrologyEditorials1322198231200241
- Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome10.2215/CJN.05670517Thu, 16 Nov 2017 06:49:11 GMT-08:00Prevalence of Novel MAGED2 Mutations in Antenatal Bartter SyndromeLegrand, AnneTreard, CyrielleRoncelin, IsabelleDreux, SophieBertholet-Thomas, AuréliaBroux, FrançoiseBruno, DanieleDecramer, StéphaneDeschenes, GeorgesDjeddi, DjamalGuigonis, VincentJay, NadineKhalifeh, TackwaLlanas, BrigitteMorin, DenisMorin, GillesNobili, FrançoisPietrement, ChristineRyckewaert, AmélieSalomon, RémiVrillon, IsabelleBlanchard, AnneVargas-Poussou, Rosa2017-11-16T06:49:11-08:00doi:10.2215/CJN.05670517hwp:resource-id:clinjasn;13/2/242American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, molecular genetics, pediatric nephrology, Humans, Male, Female, Pregnancy, Bartter Syndrome, Polyhydramnios, Prevalence, Mutation, Frameshift Mutation, RNA Splicing, Sequence Deletion, X Chromosome, Retrospective StudiesOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20182018-02-07February 07, 201810.2215/CJN.056705171555-90411555-905X2017-11-16T06:49:11-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles132242250
- Employment among Patients on Dialysis10.2215/CJN.13491217Thu, 18 Jan 2018 07:19:29 GMT-08:00Employment among Patients on DialysisHallab, AymanWish, Jay B.2018-01-18T07:19:29-08:00doi:10.2215/CJN.13491217hwp:resource-id:clinjasn;13/2/203American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, chronic dialysis, renal dialysis, Unemployment, Finland, Income Tax, Motivation, peritoneal dialysis, Renal Insufficiency, Chronic, Employment, Registries, Medicare, Kidney Failure, ChronicEditorialsEditorialseditorial20182018-02-07February 07, 201810.2215/CJN.134912171555-90411555-905X2018-01-18T07:19:29-08:002018-02-07Clinical Journal of the American Society of NephrologyEditorials1322203265204273
- Medicare’s New Prospective Payment System on Facility Provision of Peritoneal Dialysis10.2215/CJN.05680518Mon, 19 Nov 2018 07:17:42 GMT-08:00Medicare’s New Prospective Payment System on Facility Provision of Peritoneal DialysisWang, VirginiaCoffman, Cynthia J.Sanders, Linda L.Lee, Shoou-Yih D.Hirth, Richard A.Maciejewski, Matthew L.2018-11-19T07:17:42-08:00doi:10.2215/CJN.05680518hwp:resource-id:clinjasn;13/12/1833American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, Medicare, ESKD, policy, dialysis facilities, renal dialysis, Health Resources, Odds Ratio, Retrospective Studies, Incidence, quality of life, Kidney Failure, Chronic, Prospective Payment SystemOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-12-07December 07, 201810.2215/CJN.056805181555-90411555-905X2018-11-19T07:17:42-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles131218331841
- Novel Models for Health Care Delivery for CKD for Disadvantaged Populations10.2215/CJN.12591018Thu, 15 Nov 2018 07:47:59 GMT-08:00Novel Models for Health Care Delivery for CKD for Disadvantaged PopulationsLunyera, JosephDiamantidis, Clarissa Jonas2018-11-15T07:47:59-08:00doi:10.2215/CJN.12591018hwp:resource-id:clinjasn;13/12/1779American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical trial, Vulnerable Populations, Renal, Insufficiency, Chronic, PovertyEditorialsEditorialseditorial20182018-12-07December 07, 201810.2215/CJN.125910181555-90411555-905X2018-11-15T07:47:59-08:002018-12-07Clinical Journal of the American Society of NephrologyEditorials13121212177917771801178017781809
- Clinical and Regulatory Considerations for Central Venous Catheters for HemodialysisCentral venous catheters remain a vital option for access for patients receiving maintenance hemodialysis. There are many important and evolving clinical and regulatory considerations for all stakeholders for these devices. Innovation and transparent and comprehensive regulatory review of these devices is essential to stimulate innovation to help promote better outcomes for patients receiving maintenance hemodialysis. A workgroup that included representatives from academia, industry, and the US Food and Drug Administration was convened to identify the major design considerations and clinical and regulatory challenges of central venous catheters for hemodialysis. Our intent is to foster improved understanding of these devices and provide the foundation for strategies to foster innovation of these devices.10.2215/CJN.14251217Thu, 11 Oct 2018 05:36:10 GMT-07:00Clinical and Regulatory Considerations for Central Venous Catheters for HemodialysisCentral venous catheters remain a vital option for access for patients receiving maintenance hemodialysis. There are many important and evolving clinical and regulatory considerations for all stakeholders for these devices. Innovation and transparent and comprehensive regulatory review of these devices is essential to stimulate innovation to help promote better outcomes for patients receiving maintenance hemodialysis. A workgroup that included representatives from academia, industry, and the US Food and Drug Administration was convened to identify the major design considerations and clinical and regulatory challenges of central venous catheters for hemodialysis. Our intent is to foster improved understanding of these devices and provide the foundation for strategies to foster innovation of these devices.Silverstein, Douglas M.Trerotola, Scott O.Clark, TimothyJames, GarthNg, WingDwyer, AmyFlorescu, Marius C.Shingarev, RomanAsh, Stephen R.,2018-10-11T05:36:10-07:00doi:10.2215/CJN.14251217hwp:resource-id:clinjasn;13/12/1924American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, dialysis access, end stage kidney disease, hemodialysis, hemodialysis accessFeaturesFeaturesresearch-article20182018-12-07December 07, 201810.2215/CJN.142512171555-90411555-905X2018-10-11T05:36:10-07:002018-12-07Clinical Journal of the American Society of NephrologyFeatures131219241932
- Monoclonal Gammopathies and Kidney Disease10.2215/CJN.12401018Thu, 15 Nov 2018 07:47:58 GMT-08:00Monoclonal Gammopathies and Kidney DiseaseWang, Christina HaoHogan, Jonathan J.2018-11-15T07:47:58-08:00doi:10.2215/CJN.12401018hwp:resource-id:clinjasn;13/12/1781American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMonoclonal gammopathy, ESRD, Paraprotein, chronic kidney disease, Paraproteinemias, Kidney Diseases, ESKD, end stage kidney diseaseEditorialsEditorialseditorial20182018-12-07December 07, 201810.2215/CJN.124010181555-90411555-905X2018-11-15T07:47:58-08:002018-12-07Clinical Journal of the American Society of NephrologyEditorials1312121781181017821815
- Treatment of Drug-Induced Acute Tubulointerstitial Nephritis10.2215/CJN.12001018Mon, 05 Nov 2018 09:59:01 GMT-08:00Treatment of Drug-Induced Acute Tubulointerstitial NephritisMoledina, Dennis G.Perazella, Mark A.2018-11-05T09:59:01-08:00doi:10.2215/CJN.12001018hwp:resource-id:clinjasn;13/12/1785American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute tubulointerstitial nephritis, drugs, corticosteroids, acute kidney injury, acute kidney disease, Nephritis, , Interstitial, Kidney Tubular Necrosis, Acute, Drug-Related Side Effects and Adverse ReactionsEditorialsEditorialseditorial20182018-12-07December 07, 201810.2215/CJN.120010181555-90411555-905X2018-11-05T09:59:01-08:002018-12-07Clinical Journal of the American Society of NephrologyEditorials1312121785185117871858
- Prevalence of Opioid, Gabapentinoid, and NSAID Use in Patients with CKD10.2215/CJN.08530718Thu, 08 Nov 2018 06:21:10 GMT-08:00Prevalence of Opioid, Gabapentinoid, and NSAID Use in Patients with CKDNovick, Tessa K.Surapaneni, AdityaShin, Jung-ImBallew, Shoshana H.Alexander, G. CalebInker, Lesley A.Chang, Alex R.Grams, Morgan E.2018-11-08T06:21:10-08:00doi:10.2215/CJN.08530718hwp:resource-id:clinjasn;13/12/1886American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, pain medications, chronic pain, Prevalence, Analgesics, Opioid, Anti-Inflammatory Agents, Non-Steroidal, Renal Insufficiency, ChronicResearch LetterResearch Letterletter20182018-12-07December 07, 201810.2215/CJN.085307181555-90411555-905X2018-11-08T06:21:10-08:002018-12-07Clinical Journal of the American Society of NephrologyResearch Letter131218861888
- Still Asking “Which Rate Is Right?” Years Later10.2215/CJN.12371018Thu, 29 Nov 2018 07:49:44 GMT-08:00Still Asking “Which Rate Is Right?” Years LaterWoodell, Tyler B.Rifkin, Dena E.2018-11-29T07:49:44-08:00doi:10.2215/CJN.12371018hwp:resource-id:clinjasn;13/12/1783American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlbumins, Ambulatory Care, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Attitude, creatinine, Decision Making, Delivery of Health Care, diabetes mellitus, Evidence-Based Practice, Hemoglobins, Hyperkalemia, Patient-Centered Care, proteinuria, Quality of Health Care, Renal Insufficiency, Chronic, VeteransEditorialsEditorialseditorial20182018-12-07December 07, 201810.2215/CJN.123710181555-90411555-905X2018-11-29T07:49:44-08:002018-12-07Clinical Journal of the American Society of NephrologyEditorials1312121783184217841850
- Facility-Level Variations in Kidney Disease Care among Veterans with Diabetes and CKD10.2215/CJN.03830318Thu, 29 Nov 2018 07:49:44 GMT-08:00Facility-Level Variations in Kidney Disease Care among Veterans with Diabetes and CKDNavaneethan, Sankar D.Akeroyd, Julia M.Ramsey, DavidAhmed, Sarah T.Mishra, Shiva RajPetersen, Laura A.Muntner, PaulBallantyne, ChristieWinkelmayer, Wolfgang C.Ramanathan, VenkatVirani, Salim S.2018-11-29T07:49:44-08:00doi:10.2215/CJN.03830318hwp:resource-id:clinjasn;13/12/1842American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, practice patterns, nephrology visits, variations, albuminuria, glomerular filtration rate, Angiotensin-Converting Enzyme Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, creatinine, blood pressure, Veterans, Confidence Intervals, Kidney Function Tests, Renal Insufficiency, Chronic, diabetes mellitus, Hemoglobins, Angiotensin Receptor Antagonists, Albumins, Outcome Assessment (Health Care), Referral and ConsultationOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20182018-12-07December 07, 201810.2215/CJN.038303181555-90411555-905X2018-11-29T07:49:44-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1312121842178318501784
- Extended Duration Nocturnal Hemodialysis and Changes in Plasma Metabolite Profiles10.2215/CJN.08790817Wed, 14 Feb 2018 06:44:28 GMT-08:00Extended Duration Nocturnal Hemodialysis and Changes in Plasma Metabolite ProfilesKalim, SahirWald, RonYan, Andrew T.Goldstein, Marc B.Kiaii, MercedehXu, DihuaBerg, Anders H.Clish, ClaryThadhani, RaviRhee, Eugene P.Perl, Jeffrey2018-02-14T06:44:28-08:00doi:10.2215/CJN.08790817hwp:resource-id:clinjasn;13/3/436American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuremic toxins, nocturnal dialysis, metabolomics, hemodialysis, Humans, Indican, renal dialysis, Acetylcarnitine, trimethylamine, Carnitine, Prospective Studies, Amino Acids, Branched-Chain, Metabolome, Statistics, Nonparametric, Control Groups, 4-cresol sulfate, Sulfuric Acid Esters, Cresols, Methylamines, Mass Spectrometry, Chromatography, Liquid, Sulfates, OxidesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-03-07March 07, 201810.2215/CJN.087908171555-90411555-905X2018-02-14T06:44:28-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1333436361444362
- Twenty-Four–Hour Ambulatory Blood Pressure versus Clinic Blood Pressure Measurements and Risk of Adverse Outcomes in Children with CKD10.2215/CJN.09630917Tue, 13 Feb 2018 07:28:17 GMT-08:00Twenty-Four–Hour Ambulatory Blood Pressure versus Clinic Blood Pressure Measurements and Risk of Adverse Outcomes in Children with CKDKu, ElaineMcCulloch, Charles E.Warady, Bradley A.Furth, Susan L.Grimes, Barbara A.Mitsnefes, Mark M.2018-02-13T07:28:17-08:00doi:10.2215/CJN.09630917hwp:resource-id:clinjasn;13/3/422American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, pediatric nephrology, Child, Humans, blood pressure, Hypertrophy, Left Ventricular, Blood Pressure Monitoring, Ambulatory, Cross-Sectional Studies, Follow-Up Studies, Blood Pressure Determination, Systole, Renal Insufficiency, Chronic, Kidney Failure, ChronicOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20182018-03-07March 07, 201810.2215/CJN.096309171555-90411555-905X2018-02-13T07:28:17-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1333422359428360
- Efficacy and Long-Term Safety of C.E.R.A. Maintenance in Pediatric Hemodialysis Patients with Anemia of CKD10.2215/CJN.03570417Thu, 02 Nov 2017 07:40:19 GMT-07:00Efficacy and Long-Term Safety of C.E.R.A. Maintenance in Pediatric Hemodialysis Patients with Anemia of CKDFischbach, MichelWühl, ElkeReigner, Sylvie C. MeyerMorgan, ZoeSchaefer, Franz2017-11-02T07:40:19-07:00doi:10.2215/CJN.03570417hwp:resource-id:clinjasn;13/1/81American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, anemia, epoetin, C.E.R.A., Adult, Humans, continuous erythropoietin receptor activator, epoetin beta, Hematinics, Epoetin Alfa, kidney transplantation, erythropoietin, Polyethylene Glycols, Hemoglobins, Renal Insufficiency, Chronic, renal dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-01-06January 06, 201810.2215/CJN.035704171555-90411555-905X2017-11-02T07:40:19-07:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1314168190790907
- Trust Patient Insights at Both the Individual and National Level10.2215/CJN.13211117Thu, 21 Dec 2017 10:04:43 GMT-08:00Trust Patient Insights at Both the Individual and National LevelConway, Paul T.2017-12-21T10:04:43-08:00doi:10.2215/CJN.13211117hwp:resource-id:clinjasn;13/1/1American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient engagement, Center for Dialysis Innovation, Kidney Health Initiative, Center for Clinical Trial Transformation, Kidney Precision Medicine Project, Kidney Innovation Accelerator, Health and Human Services, Patient Engagement Advisory Committee, Home peritoneal dialysis, kidney transplantation, hemodialysis, Patient Advocacy, Caregivers, nephrology, Leadership, Biological Phenomena, Physiological Phenomena, Trust, SocietiesPatient VoicePatient Voiceeditorial20182018-01-06January 06, 201810.2215/CJN.132111171555-90411555-905X2017-12-21T10:04:43-08:002018-01-06Clinical Journal of the American Society of NephrologyPatient Voice131111113631001092372108117
- Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome10.2215/CJN.04120417Fri, 10 Nov 2017 06:21:40 GMT-08:00Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic SyndromeWarejko, Jillian K.Tan, WeizhenDaga, AnkanaSchapiro, DavidLawson, Jennifer A.Shril, ShirleeLovric, SvjetlanaAshraf, ShaziaRao, JiaHermle, TobiasJobst-Schwan, TilmanWidmeier, EugenMajmundar, Amar J.Schneider, RonenGee, Heon YungSchmidt, J. MagdalenaVivante, Asafvan der Ven, Amelie T.Ityel, HadasChen, JingSadowski, Carolin E.Kohl, StefanPabst, Werner L.Nakayama, MakikoSomers, Michael J.G.Rodig, Nancy M.Daouk, GhalebBaum, MichelleStein, Deborah R.Ferguson, Michael A.Traum, Avram Z.Soliman, Neveen A.Kari, Jameela A.El Desoky, SherifFathy, HananZenker, MartinBakkaloglu, Sevcan A.Müller, DominikNoyan, AytulOzaltin, FatihCadnapaphornchai, Melissa A.Hashmi, SeemaHopcian, JeffreyKopp, Jeffrey B.Benador, NadineBockenhauer, DetlefBogdanovic, RadovanStajić, NatašaChernin, GilEttenger, RobertFehrenbach, HenryKemper, MarkusMunarriz, Reyner LozaPodracka, LudmilaBüscher, RainerSerdaroglu, ErkinTasic, VeliborMane, ShrikantLifton, Richard P.Braun, Daniela A.Hildebrandt, Friedhelm2017-11-10T06:21:40-08:00doi:10.2215/CJN.04120417hwp:resource-id:clinjasn;13/1/53American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, pediatric, molecular genetics, Child, Humans, Nephrosis, congenital, nephrotic syndrome, Exome, kidney transplantation, Mutation, Kidney Failure, Chronic, Renal Insufficiency, Chronic, PhenotypeOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20182018-01-06January 06, 201810.2215/CJN.041204171555-90411555-905X2017-11-10T06:21:40-08:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1315362
- Consequences of Overinterpreting Serum Creatinine Increases when Achieving BP Reduction10.2215/CJN.11811017Fri, 03 Nov 2017 02:30:09 GMT-07:00Consequences of Overinterpreting Serum Creatinine Increases when Achieving BP ReductionYamout, HalaBakris, George L.2017-11-03T14:30:09-07:00doi:10.2215/CJN.11811017hwp:resource-id:clinjasn;13/1/9American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycreatinine, acute kidney injury, blood pressure, hypertension, Kidney Function Tests, hypotensionEditorialsEditorialseditorial20182018-01-06January 06, 201810.2215/CJN.118110171555-90411555-905X2017-11-03T14:30:09-07:002018-01-06Clinical Journal of the American Society of NephrologyEditorials13119731080
- New Frontiers in Treating Uremic Metabolic Acidosis10.2215/CJN.11771017Sat, 04 Nov 2017 02:30:09 GMT-07:00New Frontiers in Treating Uremic Metabolic AcidosisBrown, DenverMelamed, Michal L.2017-11-04T14:30:09-07:00doi:10.2215/CJN.11771017hwp:resource-id:clinjasn;13/1/4American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacidosis, chronic kidney disease, chronic metabolic acidosis, uremiaEditorialsEditorialseditorial20182018-01-06January 06, 201810.2215/CJN.117710171555-90411555-905X2017-11-04T14:30:09-07:002018-01-06Clinical Journal of the American Society of NephrologyEditorials1311426535
- The Making Dialysis Safer for Patients CoalitionThe Making Dialysis Safer for Patients Coalition is a partnership of organizations and individual stakeholders that share the common goal to prevent bloodstream infections among patients receiving hemodialysis. Led by the Centers for Disease Control and Prevention (CDC), in collaboration with the CDC Foundation, this public-private partnership strives to improve adherence to evidence-based recommendations, share information and experiences, and engage patients in infection prevention efforts.10.2215/CJN.02730317Wed, 09 Aug 2017 08:31:27 GMT-07:00The Making Dialysis Safer for Patients CoalitionThe Making Dialysis Safer for Patients Coalition is a partnership of organizations and individual stakeholders that share the common goal to prevent bloodstream infections among patients receiving hemodialysis. Led by the Centers for Disease Control and Prevention (CDC), in collaboration with the CDC Foundation, this public-private partnership strives to improve adherence to evidence-based recommendations, share information and experiences, and engage patients in infection prevention efforts.Patel, Priti R.Brinsley-Rainisch, Kristin2017-08-09T08:31:27-07:00doi:10.2215/CJN.02730317hwp:resource-id:clinjasn;13/1/175American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient safety, infection prevention, bloodstream infection, vascular access infection, patient engagement, dialysis, Bacteremia, Centers for Disease Control and Prevention (U.S.), Cooperative Behavior, Fluid Therapy, Goals, Humans, Organizations, Public-Private Sector Partnerships, renal dialysis, United StatesFeatureFeatureresearch-article20182018-01-06January 06, 201810.2215/CJN.027303171555-90411555-905X2017-08-09T08:31:27-07:002018-01-06Clinical Journal of the American Society of NephrologyFeature131175181
- Rest Easy with Intravenous Iron for Dialysis Patients?10.2215/CJN.00930118Tue, 20 Feb 2018 07:08:12 GMT-08:00Rest Easy with Intravenous Iron for Dialysis Patients?Li, XiaojuanKshirsagar, Abhijit V.2018-02-20T07:08:12-08:00doi:10.2215/CJN.00930118hwp:resource-id:clinjasn;13/3/363American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHepcidins, Hematinics, Iron, metal transporting protein 1, nephrology, renal dialysis, anemia, Cation Transport Proteins, Iron Metabolism Disorders, Intestinal AbsorptionEditorialsEditorialseditorial20182018-03-07March 07, 201810.2215/CJN.009301181555-90411555-905X2018-02-20T07:08:12-08:002018-03-07Clinical Journal of the American Society of NephrologyEditorials1333363457365467
- Serum Sodium and Cognition in Older Community-Dwelling Men10.2215/CJN.07400717Thu, 08 Feb 2018 05:51:07 GMT-08:00Serum Sodium and Cognition in Older Community-Dwelling MenNowak, Kristen L.Yaffe, KristineOrwoll, Eric S.Ix, Joachim H.You, ZhiyingBarrett-Connor, ElizabethHoffman, Andrew R.Chonchol, Michel2018-02-08T05:51:07-08:00doi:10.2215/CJN.07400717hwp:resource-id:clinjasn;13/3/366American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAging, cognitive, electrolytes, Cross-Sectional Studies, Trail Making Test, Cognitive Dysfunction, Sodium, hyponatremia, Fasting, Prospective Studies, Follow-Up Studies, Logistic Models, Independent Living, Osteoporotic Fractures, Prevalence, CognitionOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20182018-03-07March 07, 201810.2215/CJN.074007171555-90411555-905X2018-02-08T05:51:07-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133366374
- Neurocognitive and Educational Outcomes in Children and Adolescents with CKD10.2215/CJN.09650917Thu, 22 Feb 2018 07:39:26 GMT-08:00Neurocognitive and Educational Outcomes in Children and Adolescents with CKDChen, KerryDidsbury, Madeleinevan Zwieten, AnitaHowell, MartinKim, SiahTong, AllisonHoward, KirstenNassar, NatashaBarton, BelindaLah, SuncicaLorenzo, JenniferStrippoli, GiovanniPalmer, SuetoniaTeixeira-Pinto, ArmandoMackie, FionaMcTaggart, StevenWalker, AmandaKara, TonyaCraig, Jonathan C.Wong, Germaine2018-02-22T07:39:26-08:00doi:10.2215/CJN.09650917hwp:resource-id:clinjasn;13/3/387American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, pediatrics, Epidemiology and outcomes, transplant outcomes, dialysis, Neurocognition, Education, Child, Adolescent, Humans, Cross-Sectional Studies, Executive Function, Reading, Transplant Recipients, kidney transplantation, Confidence Intervals, Cohort Studies, Cognition, Renal Insufficiency, Chronic, Memory, Mathematics, Bias, IntelligenceOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-03-07March 07, 201810.2215/CJN.096509171555-90411555-905X2018-02-22T07:39:26-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1333387357397358
- Definitions and End Points for Interventional Studies for Arteriovenous Dialysis AccessThis paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access’ evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1—patent arteriovenous access, stage 2—physiologically mature arteriovenous access, and stage 3—clinically functional arteriovenous access. Once the requirements of a stage 3—clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.10.2215/CJN.11531116Thu, 20 Jul 2017 01:51:37 GMT-07:00Definitions and End Points for Interventional Studies for Arteriovenous Dialysis AccessThis paper is part of the Clinical Trial Endpoints for Dialysis Vascular Access Project of the American Society of Nephrology Kidney Health Initiative. The purpose of this project is to promote research in vascular access by clarifying trial end points which would be best suited to inform decisions in those situations in which supportive clinical data are required. The focus of a portion of the project is directed toward arteriovenous access. There is a potential for interventional studies to be directed toward any of the events that may be associated with an arteriovenous access’ evolution throughout its life cycle, which has been divided into five distinct phases. Each one of these has the potential for relatively unique problems. The first three of these correspond to three distinct stages of arteriovenous access development, each one of which has been characterized by objective direct and/or indirect criteria. These are characterized as: stage 1—patent arteriovenous access, stage 2—physiologically mature arteriovenous access, and stage 3—clinically functional arteriovenous access. Once the requirements of a stage 3—clinically functional arteriovenous access have been met, the fourth phase of its life cycle begins. This is the phase of sustained clinical use from which the arteriovenous access may move back and forth between it and the fifth phase, dysfunction. From this phase of its life cycle, the arteriovenous access requires a maintenance procedure to preserve or restore sustained clinical use. Using these definitions, clinical trial end points appropriate to the various phases that characterize the evolution of the arteriovenous access life cycle have been identified. It is anticipated that by using these definitions and potential end points, clinical trials can be designed that more closely correlate with the goals of the intervention and provide appropriate supportive data for clinical, regulatory, and coverage decisions.Beathard, Gerald A.Lok, Charmaine E.Glickman, Marc H.Al-Jaishi, Ahmed A.Bednarski, DonnaCull, David L.Lawson, Jeffery H.Lee, Timmy C.Niyyar, Vandana D.Syracuse, DonnaTrerotola, Scott O.Roy-Chaudhury, PrabirShenoy, SurendraUnderwood, MargoWasse, HaimanotWoo, KarenYuo, Theodore H.Huber, Thomas S.2017-07-20T13:51:37-07:00doi:10.2215/CJN.11531116hwp:resource-id:clinjasn;13/3/501American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, arteriovenous graft, hemodialysis access, vascular access, clinical trialMoving Points in NephrologyMoving Points in Nephrologyresearch-article20182018-03-07March 07, 201810.2215/CJN.115311161555-90411555-905X2017-07-20T13:51:37-07:002018-03-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology133333501490495513512494500518
- FDA Regulatory Perspectives for Studies on Hemodialysis Vascular AccessIn an effort to foster innovation and new product development, the American Society of Nephrology and the US Food and Drug Administration partnered to form the Kidney Health Initiative in 2012. Part of the Kidney Health Initiative’s mission is to foster development of therapies by creating a collaborative environment where the US Food and Drug Administration and the greater nephrology community can interact to optimize product evaluation. This particular Kidney Health Initiative project focused on products related to hemodialysis vascular access, with the goal of clarifying appropriate trial end points that could subsequently inform clinical, regulatory, and coverage decisions. Both the lack of common definitions and the lack of consensus on trial end points have been viewed as barriers to innovation in this area. Toward this end, the Kidney Health Initiative convened teams of expert stakeholders to address these issues for each major vascular access category (arteriovenous grafts, arteriovenous fistulas, and central venous catheters), and each team provided recommendations. This commentary provides an overview of the US Food and Drug Administration centers that regulate hemodialysis vascular access and certain laws and regulations that affect these products as well as our perspectives on some of the issues raised and end points proposed by the Kidney Health Initiative teams. The standardized definitions and clinical trial end points proposed by the teams represent an important step forward to improve innovation in this area.10.2215/CJN.02900317Mon, 24 Jul 2017 06:07:47 GMT-07:00FDA Regulatory Perspectives for Studies on Hemodialysis Vascular AccessIn an effort to foster innovation and new product development, the American Society of Nephrology and the US Food and Drug Administration partnered to form the Kidney Health Initiative in 2012. Part of the Kidney Health Initiative’s mission is to foster development of therapies by creating a collaborative environment where the US Food and Drug Administration and the greater nephrology community can interact to optimize product evaluation. This particular Kidney Health Initiative project focused on products related to hemodialysis vascular access, with the goal of clarifying appropriate trial end points that could subsequently inform clinical, regulatory, and coverage decisions. Both the lack of common definitions and the lack of consensus on trial end points have been viewed as barriers to innovation in this area. Toward this end, the Kidney Health Initiative convened teams of expert stakeholders to address these issues for each major vascular access category (arteriovenous grafts, arteriovenous fistulas, and central venous catheters), and each team provided recommendations. This commentary provides an overview of the US Food and Drug Administration centers that regulate hemodialysis vascular access and certain laws and regulations that affect these products as well as our perspectives on some of the issues raised and end points proposed by the Kidney Health Initiative teams. The standardized definitions and clinical trial end points proposed by the teams represent an important step forward to improve innovation in this area.Hurst, Frank P.Lee, Robert E.Thompson, Aliza M.Pullin, Brian D.Silverstein, Douglas M.2017-07-24T06:07:47-07:00doi:10.2215/CJN.02900317hwp:resource-id:clinjasn;13/3/513American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, hemodialysis, hemodialysis access, vascular access, arteriovenous access, arteriovenous graft, arteriovenous fistula, Central Venous Catheters, Consensus, Goals, nephrology, renal dialysis, United StatesMoving Points in NephrologyMoving Points in Nephrologyresearch-article20182018-03-07March 07, 201810.2215/CJN.029003171555-90411555-905X2017-07-24T06:07:47-07:002018-03-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology133333513490495501518494500512
- Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator Hemodialysis Catheter Locking Solution10.2215/CJN.08510817Mon, 15 Jan 2018 09:38:04 GMT-08:00Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator Hemodialysis Catheter Locking SolutionHemmelgarn, Brenda R.Manns, Braden J.Soroka, Steven D.Levin, AdeeraMacRae, JenniferTennankore, KarthikWilson, Jo-Anne S.Weaver, Robert G.Ravani, PietroQuinn, Robert R.Tonelli, MarcelloKiaii, MercedehMossop, PaulaScott-Douglas, Nairne2018-01-15T09:38:04-08:00doi:10.2215/CJN.08510817hwp:resource-id:clinjasn;13/3/429American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, catheter locking solution, catheter malfunction, Male, Humans, Aged, Tissue Plasminogen Activator, Heparin, Hemodialysis Solutions, Citric Acid, Prospective Studies, Incidence, Standard of Care, Citrates, renal dialysis, Catheterization, Bacteremia, Health Care CostsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-03-07March 07, 201810.2215/CJN.085108171555-90411555-905X2018-01-15T09:38:04-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133429435
- Responsive Designed Interventions Are Needed to Support Positive Outcomes of Children and Adolescents with CKD10.2215/CJN.00990118Thu, 22 Feb 2018 07:39:25 GMT-08:00Responsive Designed Interventions Are Needed to Support Positive Outcomes of Children and Adolescents with CKDHartwell, Lori M.2018-02-22T07:39:25-08:00doi:10.2215/CJN.00990118hwp:resource-id:clinjasn;13/3/357American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChild, Adolescent, Humans, Renal Insufficient, ChronicPatient VoicePatient Voiceresearch-article20182018-03-07March 07, 201810.2215/CJN.009901181555-90411555-905X2018-02-22T07:39:25-08:002018-03-07Clinical Journal of the American Society of NephrologyPatient Voice1333357387358397
- Safety of Intravenous Iron in Dialysis10.2215/CJN.05390517Tue, 20 Feb 2018 07:08:13 GMT-08:00Safety of Intravenous Iron in DialysisHougen, IngridCollister, DavidBourrier, MathieuFerguson, ThomasHochheim, LauraKomenda, PaulRigatto, ClaudioTangri, Navdeep2018-02-20T07:08:13-08:00doi:10.2215/CJN.05390517hwp:resource-id:clinjasn;13/3/457American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, intravenous, chronic kidney disease, dialysis, ferryl iron, Iron, Risk, Follow-Up Studies, Administration, Intravenous, Libraries, Uncertainty, Proportional Hazards Models, hospitalization, renal dialysis, Randomized Controlled Trials as TopicOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-03-07March 07, 201810.2215/CJN.053905171555-90411555-905X2018-02-20T07:08:13-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1333457363467365
- Recommended Clinical Trial End Points for Dialysis CathetersCentral venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.10.2215/CJN.12011116Thu, 20 Jul 2017 01:51:36 GMT-07:00Recommended Clinical Trial End Points for Dialysis CathetersCentral venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.Allon, MichaelBrouwer-Maier, Deborah J.Abreo, KennethBaskin, Kevin M.Bregel, KayChand, Deepa H.Easom, Andrea M.Mermel, LeonardMokrzycki, Michele H.Patel, Priti R.Roy-Chaudhury, PrabirShenoy, SurendraValentini, Rudolph P.Wasse, Haimanot2017-07-20T13:51:36-07:00doi:10.2215/CJN.12011116hwp:resource-id:clinjasn;13/3/495American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycentral vein, vascular access, dialysis access, Bacteremia, Blood Culture, Catheter-Related Infections, Central Venous Catheters, Chills, Constriction, Pathologic, Edema, Humans, hypotension, Phlebography, renal dialysis, Uncertainty, United States, United States Food and Drug Administration, Veins, Venous PressureMoving Points in NephrologyMoving Points in Nephrologyresearch-article20182018-03-07March 07, 201810.2215/CJN.120111161555-90411555-905X2017-07-20T13:51:36-07:002018-03-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology133333495490501513500494512518
- Clinical Trial End Points for Hemodialysis Vascular Access10.2215/CJN.13321216Tue, 27 Feb 2018 08:03:55 GMT-08:00Clinical Trial End Points for Hemodialysis Vascular AccessShenoy, SurendraAllon, MichaelBeathard, GeraldBrouwer-Maier, DeborahDember, Laura M.Glickman, MarkLee, CelesteLitchfield, TerryLok, CharmaineHuber, ThomasRoy-Chaudhury, PrabirWork, JackWest, MelissaWasse, Haimanot2018-02-27T08:03:55-08:00doi:10.2215/CJN.13321216hwp:resource-id:clinjasn;13/3/490American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, vascular, Humans, Consensus, Biological Products, renal dialysis, Polytetrafluoroethylene, arteriovenous fistulaMoving Points in NephrologyMoving Points in Nephrologyresearch-article20182018-03-07March 07, 201810.2215/CJN.133212161555-90411555-905X2018-02-27T08:03:55-08:002018-03-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology133333490495501513494500512518
- Weekly Standard Kt/Vurea and Clinical Outcomes in Home and In-Center Hemodialysis10.2215/CJN.05680517Thu, 11 Jan 2018 11:49:59 GMT-08:00Weekly Standard Kt/Vurea and Clinical Outcomes in Home and In-Center HemodialysisRivara, Matthew B.Ravel, VanessaStreja, ElaniObi, YoshitsuguSoohoo, MelissaCheung, Alfred K.Himmelfarb, JonathanKalantar-Zadeh, KamyarMehrotra, Rajnish2018-01-11T11:49:59-08:00doi:10.2215/CJN.05680517hwp:resource-id:clinjasn;13/3/445American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis adequacy, mortality risk, Epidemiology and outcomes, Hemodialysis, Home, renal dialysis, calcium bicarbonate, blood pressure, Phosphorus, Potassium, Confidence Intervals, Odds Ratio, Bicarbonates, Blood Pressure Determination, Risk, hospitalizationOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-03-07March 07, 201810.2215/CJN.056805171555-90411555-905X2018-01-11T11:49:59-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133445455
- Intensive Hemodialysis Fails to Reduce Plasma Levels of Uremic Solutes10.2215/CJN.00950118Wed, 14 Feb 2018 06:44:28 GMT-08:00Intensive Hemodialysis Fails to Reduce Plasma Levels of Uremic SolutesSirich, Tammy L.Meyer, Timothy W.2018-02-14T06:44:28-08:00doi:10.2215/CJN.00950118hwp:resource-id:clinjasn;13/3/361American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, uremia, renal dialysis, Renal Insufficiency, Plasma, Mass, SpectrometryEditorialsEditorialseditorial20182018-03-07March 07, 201810.2215/CJN.009501181555-90411555-905X2018-02-14T06:44:28-08:002018-03-07Clinical Journal of the American Society of NephrologyEditorials1333361436362444
- The Enigma of Blood Pressure Measurement in Children with CKD10.2215/CJN.00110118Tue, 13 Feb 2018 07:28:17 GMT-08:00The Enigma of Blood Pressure Measurement in Children with CKDFalkner, Bonita2018-02-13T07:28:17-08:00doi:10.2215/CJN.00110118hwp:resource-id:clinjasn;13/3/359American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, chronic kidney disease, blood pressure measurement, Child, Adult, Humans, Blood Pressure Monitoring, Ambulatory, blood pressure, White Coat Hypertension, Reference Values, Blood Pressure Determination, hypertension, Sleep, Wakefulness, Renal Insufficiency, ChronicEditorialsEditorialseditorial20182018-03-07March 07, 201810.2215/CJN.001101181555-90411555-905X2018-02-13T07:28:17-08:002018-03-07Clinical Journal of the American Society of NephrologyEditorials1333359422360428
- Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes10.2215/CJN.05280517Tue, 16 Jan 2018 06:07:31 GMT-08:00Kidney Biomarkers and Decline in eGFR in Patients with Type 2 DiabetesGarlo, Katherine G.White, William B.Bakris, George L.Zannad, FaiezWilson, Craig A.Kupfer, StuartVaduganathan, MuthiahMorrow, David A.Cannon, Christopher P.Charytan, David M.2018-01-16T06:07:31-08:00doi:10.2215/CJN.05280517hwp:resource-id:clinjasn;13/3/398American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, diabetes mellitus, progression of chronic renal failure, randomized controlled trials, Cystatin C, Lipocalin-2, Acute Coronary Syndrome, glomerular filtration rate, Diabetes Mellitus, Type 2, Factor IX, risk factors, kidney, proteinuria, Renal Insufficiency, Chronic, Cohort Studies, Biomarkers, renal dialysisOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20182018-03-07March 07, 201810.2215/CJN.052805171555-90411555-905X2018-01-16T06:07:31-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133398405
- ACCORDION: Ensuring That We Hear the Music Clearly10.2215/CJN.11370918Thu, 25 Oct 2018 02:00:11 GMT-07:00ACCORDION: Ensuring That We Hear the Music ClearlyWong, Muh GeotHeerspink, Hiddo J.L.Perkovic, Vlado2018-10-25T14:00:11-07:00doi:10.2215/CJN.11370918hwp:resource-id:clinjasn;13/11/1621American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBlood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, End Stage Kidney Disease, Lipids, Prevalence, Renal Insufficiency, Risk FactorsEditorialsEditorialseditorial20182018-11-07November 07, 201810.2215/CJN.113709181555-90411555-905X2018-10-25T14:00:11-07:002018-11-07Clinical Journal of the American Society of NephrologyEditorials1311111621169316231702
- Kidney Function Reserve Capacity in Early and Later Stage Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.03650318Tue, 25 Sep 2018 07:56:06 GMT-07:00Kidney Function Reserve Capacity in Early and Later Stage Autosomal Dominant Polycystic Kidney DiseaseMesschendorp, A. Liannevan Londen, MarcoTaylor, Jacob M.de Borst, Martin H.Navis, GerjanCasteleijn, Niek F.Gaillard, Carlo A.J.M.Bakker, Stephan J.L.Gansevoort, Ron T.,2018-09-25T07:56:06-07:00doi:10.2215/CJN.03650318hwp:resource-id:clinjasn;13/11/1680American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, hyperfiltration, filtration fraction, kidney function reserve capacity, Iothalamic Acid, Polycystic Kidney, Autosomal Dominant, glomerular filtration rate, Dopamine, Cross-Sectional Studies, Reference Values, Nephrons, tyrphostin A23, Tyrphostins, EGFR protein, human, Receptor, Epidermal Growth Factor, Renal Insufficiency, ChronicOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20182018-11-07November 07, 201810.2215/CJN.036503181555-90411555-905X2018-09-25T07:56:06-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131116801692
- MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular Access10.2215/CJN.02410218Fri, 21 Sep 2018 06:27:11 GMT-07:00MicroRNA-21 and Venous Neointimal Hyperplasia of Dialysis Vascular AccessWu, Chih-ChengChen, Li-JingHsieh, Mu-YangLo, Chien-MingLin, Ming-HsienTsai, Hsiao-EnSong, Hsiang-LinChiu, Jeng-Jiann2018-09-21T06:27:11-07:00doi:10.2215/CJN.02410218hwp:resource-id:clinjasn;13/11/1712American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMicroRNA, neointima, dialysis, hyperplasia, Neointima, Hyperplasia, renal dialysis, Down-Regulation, Up-Regulation, In Situ Hybridization, Angioplasty, arteriovenous fistulaOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-11-07November 07, 201810.2215/CJN.024102181555-90411555-905X2018-09-21T06:27:11-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131117121720
- High-Dose Seasonal Influenza Vaccine in Patients Undergoing Dialysis10.2215/CJN.03390318Tue, 23 Oct 2018 07:00:25 GMT-07:00High-Dose Seasonal Influenza Vaccine in Patients Undergoing DialysisMiskulin, Dana C.Weiner, Daniel E.Tighiouart, HocineLacson, Eduardo K.Meyer, Klemens B.Dad, TaimurManley, Harold J.2018-10-23T07:00:25-07:00doi:10.2215/CJN.03390318hwp:resource-id:clinjasn;13/11/1703American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinfection, dialysis, Aged, Humans, Influenza Vaccines, Influenza, Human, Seasons, renal dialysis, Vaccination, Immunization, hospitalizationOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-11-07November 07, 201810.2215/CJN.033903181555-90411555-905X2018-10-23T07:00:25-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1311111703162417111626
- Changes in Transfusion Coding Among Hospitalized Medicare Beneficiaries after Implementation of ICD-1010.2215/CJN.10180818Tue, 16 Oct 2018 07:57:47 GMT-07:00Changes in Transfusion Coding Among Hospitalized Medicare Beneficiaries after Implementation of ICD-10Weinhandl, Eric D.Kubisiak, Kristine M.2018-10-16T07:57:47-07:00doi:10.2215/CJN.10180818hwp:resource-id:clinjasn;13/11/1730American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclaims, dialysis, Medicare, quality, transfusion, International Classification of Diseases, Platelet Transfusion, Blood TransfusionResearch LetterResearch Letterresearch-article20182018-11-07November 07, 201810.2215/CJN.101808181555-90411555-905X2018-10-16T07:57:47-07:002018-11-07Clinical Journal of the American Society of NephrologyResearch Letter131117301731
- Kidney Biopsy in Hospitalized Patients with Acute Kidney Disease10.2215/CJN.11400918Mon, 22 Oct 2018 07:26:59 GMT-07:00Kidney Biopsy in Hospitalized Patients with Acute Kidney DiseaseWeisbord, Steven Darrow2018-10-22T07:26:59-07:00doi:10.2215/CJN.11400918hwp:resource-id:clinjasn;13/11/1617American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, Hospitalized Patients, Risk, kidney diseaseEditorialsEditorialseditorial20182018-11-07November 07, 201810.2215/CJN.114009181555-90411555-905X2018-10-22T07:26:59-07:002018-11-07Clinical Journal of the American Society of NephrologyEditorials1311111617163316181640
- Medication Safety Principles and Practice in CKDEnsuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated via the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use.10.2215/CJN.00580118Mon, 18 Jun 2018 08:20:52 GMT-07:00Medication Safety Principles and Practice in CKDEnsuring patient safety is a priority of medical care because iatrogenic injury has been a primary concern. Medications are an important source of medical errors, and kidney disease is a thoroughfare of factors threatening safe administration of medicines. Principal among these is reduced kidney function because almost half of all medications used are eliminated via the kidney. Additionally, kidney patients often suffer from multimorbidity, including diabetes, hypertension, and heart failure, with a range of prescribers who often do not coordinate treatments. Patients with kidney disease are also susceptible to further kidney injury and metabolic derangements from medications, which can worsen the disease. In this review, we will present the key issues and threats to safe medication use in kidney disease, with a focus on predialysis CKD, as the scope of medication safety in ESKD and transplantation are unique and deserve their own consideration. We discuss drugs that need to be avoided or dose modified, and review the complications of a range of medications routinely administered in CKD, as these also call for cautious use.Whittaker, Chanel F.Miklich, Margaret A.Patel, Roshni S.Fink, Jeffrey C.2018-06-18T08:20:52-07:00doi:10.2215/CJN.00580118hwp:resource-id:clinjasn;13/11/1738American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymedication safety, deprescribing, chronic kidney disease, renal drug dosing, Patient Safety, Pharmaceutical Preparations, Multimorbidity, Iatrogenic Disease, Renal Insufficiency, Chronic, Kidney Failure, Chronic, diabetes mellitus, hypertension, Medical Errors, heart failureNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-11-07November 07, 201810.2215/CJN.005801181555-90411555-905X2018-06-18T08:20:52-07:002018-11-07Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician131117381746
- Treatment Adherence in Young Adults Receiving Kidney Replacement Therapy10.2215/CJN.11200918Tue, 16 Oct 2018 07:57:46 GMT-07:00Treatment Adherence in Young Adults Receiving Kidney Replacement TherapyDuquette, PamHelm, Kelly2018-10-16T07:57:46-07:00doi:10.2215/CJN.11200918hwp:resource-id:clinjasn;13/11/1615American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyadherence, young adult, Kidney Replacement Therapy, Renal Replacement Therapy, Caregiver, KRT, RRTPatient VoicesPatient Voiceseditorial20182018-11-07November 07, 201810.2215/CJN.112009181555-90411555-905X2018-10-16T07:57:46-07:002018-11-07Clinical Journal of the American Society of NephrologyPatient Voices13111111161516131669161616141679
- Increasing Protection of Dialysis Patients against Influenza10.2215/CJN.11670918Tue, 23 Oct 2018 07:00:24 GMT-07:00Increasing Protection of Dialysis Patients against InfluenzaLindley, Megan C.Kim, David K.2018-10-23T07:00:24-07:00doi:10.2215/CJN.11670918hwp:resource-id:clinjasn;13/11/1624American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinfluenza, vaccination, dialysis patients, flu, kidneyEditorialsEditorialseditorial20182018-11-07November 07, 201810.2215/CJN.116709181555-90411555-905X2018-10-23T07:00:24-07:002018-11-07Clinical Journal of the American Society of NephrologyEditorials1311111624170316261711
- Urea for the Treatment of Hyponatremia10.2215/CJN.04020318Tue, 04 Sep 2018 06:32:18 GMT-07:00Urea for the Treatment of HyponatremiaRondon-Berrios, HelbertTandukar, SrijanMor, Maria K.Ray, Evan C.Bender, Filitsa H.Kleyman, Thomas R.Weisbord, Steven D.2018-09-04T06:32:18-07:00doi:10.2215/CJN.04020318hwp:resource-id:clinjasn;13/11/1627American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyponatremia, urea, inappropriate ADH syndromeOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20182018-11-07November 07, 201810.2215/CJN.040203181555-90411555-905X2018-09-04T06:32:18-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131116271632
- Associations with Wellbeing and Medication Adherence in Young Adults Receiving Kidney Replacement Therapy10.2215/CJN.02450218Tue, 16 Oct 2018 07:57:48 GMT-07:00Associations with Wellbeing and Medication Adherence in Young Adults Receiving Kidney Replacement TherapyHamilton, Alexander JamesCaskey, Fergus J.Casula, AnnaInward, Carol D.Ben-Shlomo, Yoav2018-10-16T07:57:48-07:00doi:10.2215/CJN.02450218hwp:resource-id:clinjasn;13/11/1669American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDepression, kidney transplantation, risk factors, dialysis, Medication Adherence, Cross-Sectional Studies, Patient Participation, Personal Satisfaction, Linear Models, Neuroticism, quality of life, Body Image, Extraversion (Psychology), renal dialysis, Patient Satisfaction, Surveys and Questionnaires, Social Support, Physician-Patient Relations, Comorbidity, Parents, Registries, BiasOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-11-07November 07, 201810.2215/CJN.024502181555-90411555-905X2018-10-16T07:57:48-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131111113166916131615431167916141616431
- Treatment Adherence in Young Adults Receiving Kidney Replacement Therapy10.2215/CJN.11230918Tue, 16 Oct 2018 07:57:48 GMT-07:00Treatment Adherence in Young Adults Receiving Kidney Replacement TherapyGrandinetti, Amanda2018-10-16T07:57:48-07:00doi:10.2215/CJN.11230918hwp:resource-id:clinjasn;13/11/1613American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyKidney Replacement Therapy, Renal Replacement Therapy, KRT, RRT, patient adherence, young adultsPatient VoicesPatient Voiceseditorial20182018-11-07November 07, 201810.2215/CJN.112309181555-90411555-905X2018-10-16T07:57:48-07:002018-11-07Clinical Journal of the American Society of NephrologyPatient Voices13111111161316151669161416161679
- Better Patient Ambulatory Care Experience10.2215/CJN.11260918Thu, 18 Oct 2018 07:16:24 GMT-07:00Better Patient Ambulatory Care ExperienceTuot, Delphine S.2018-10-18T07:16:24-07:00doi:10.2215/CJN.11260918hwp:resource-id:clinjasn;13/11/1619American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, patient experience, hospitalization, Ambulatory Care, Renal Insufficiency, ChronicEditorialsEditorialseditorial20182018-11-07November 07, 201810.2215/CJN.112609181555-90411555-905X2018-10-18T07:16:24-07:002018-11-07Clinical Journal of the American Society of NephrologyEditorials1311111619165916201667
- Long-Term Effects of Intensive Glycemic and Blood Pressure Control and Fenofibrate Use on Kidney Outcomes10.2215/CJN.06200518Thu, 25 Oct 2018 02:00:12 GMT-07:00Long-Term Effects of Intensive Glycemic and Blood Pressure Control and Fenofibrate Use on Kidney OutcomesMottl, Amy K.Buse, John B.Ismail-Beigi, FaramarzSigal, Ronald J.Pedley, Carolyn F.Papademetriou, VasiliosSimmons, Debra L.Katz, LoisMychaleckyj, Josyf C.Craven, Timothy E.2018-10-25T14:00:12-07:00doi:10.2215/CJN.06200518hwp:resource-id:clinjasn;13/11/1693American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, clinical trial, fibrates, glycemic control, blood pressure control, Fenofibrate, blood pressure, Diabetes Mellitus, Type 2, creatinine, Simvastatin, Glycated Hemoglobin A, lipids, Random Allocation, renal dialysis, Blood Pressure Determination, Blood Glucose, Cardiovascular Diseases, kidneyOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20182018-11-07November 07, 201810.2215/CJN.062005181555-90411555-905X2018-10-25T14:00:12-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1311111693162117021623
- Midterm eGFR and Adverse Pregnancy Outcomes: The Clinical Significance of Gestational Hyperfiltration10.2215/CJN.12101116Tue, 13 Jun 2017 06:19:30 GMT-07:00Midterm eGFR and Adverse Pregnancy Outcomes: The Clinical Significance of Gestational HyperfiltrationPark, SehoonLee, Seung MiPark, Joong ShinHong, Joon-SeokChin, Ho JunNa, Ki YoungKim, Dong KiOh, Kook-HwanJoo, Kwon WookKim, Yon SuLee, Hajeong2017-06-13T06:19:30-07:00doi:10.2215/CJN.12101116hwp:resource-id:clinjasn;12/7/1048American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHyperfiltration, pregnancy, chronic kidney disease, Cohort Studies, Confidence Intervals, creatinine, Female, Gestational Age, glomerular filtration rate, Hemodynamics, Humans, Infant, Low Birth Weight, Infant, Newborn, kidney, Mothers, Odds Ratio, Pre-Eclampsia, Pregnancy, Pregnancy Outcome, Pregnancy Trimester, Second, Premature Birth, Renal Insufficiency, Renal Insufficiency, Chronic, risk factorsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-07-07July 07, 201710.2215/CJN.121011161555-90411555-905X2017-06-13T06:19:30-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12771048102910561031
- Kidney Function Can Predict Pregnancy Outcomes10.2215/CJN.04970517Tue, 13 Jun 2017 06:19:30 GMT-07:00Kidney Function Can Predict Pregnancy OutcomesBjornstad, PetterCherney, David Z.I.2017-06-13T06:19:30-07:00doi:10.2215/CJN.04970517hwp:resource-id:clinjasn;12/7/1029American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypregnancy, hyperfiltration, outcomesEditorialsEditorialseditorial20172017-07-07July 07, 201710.2215/CJN.049705171555-90411555-905X2017-06-13T06:19:30-07:002017-07-07Clinical Journal of the American Society of NephrologyEditorials12771029104810311056
- Achieving Equity through Reducing Variability in Accepting Deceased Donor Kidney Offers10.2215/CJN.06220617Thu, 27 Jul 2017 09:44:23 GMT-07:00Achieving Equity through Reducing Variability in Accepting Deceased Donor Kidney OffersMohan, SumitChiles, Mariana C.2017-07-27T09:44:23-07:00doi:10.2215/CJN.06220617hwp:resource-id:clinjasn;12/8/1212American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, transplant outcomes, Epidemiology and outcomes, Death, Tissue Donors, DonorEditorialsEditorialseditorial20172017-08-07August 07, 201710.2215/CJN.062206171555-90411555-905X2017-07-27T09:44:23-07:002017-08-07Clinical Journal of the American Society of NephrologyEditorials12881212131112141320
- Soluble Urokinase Plasminogen Activator Receptor and Outcomes in Patients with Diabetes on Hemodialysis10.2215/CJN.10881016Thu, 11 May 2017 07:12:37 GMT-07:00Soluble Urokinase Plasminogen Activator Receptor and Outcomes in Patients with Diabetes on HemodialysisDrechsler, ChristianeHayek, Salim S.Wei, ChangliSever, SanjaGenser, BerndKrane, VeraMeinitzer, AndreasMärz, WinfriedWanner, ChristophReiser, Jochen2017-05-11T07:12:37-07:00doi:10.2215/CJN.10881016hwp:resource-id:clinjasn;12/8/1265American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, dialysis, urokinase, diabetes, Arginine, Cause of Death, Child, Preschool, Death, Sudden, Diabetes Mellitus, Type 2, Humans, Incidence, Kidney Failure, Chronic, Leukocyte Count, Male, oxidative stress, Proportional Hazards Models, Receptors, Urokinase Plasminogen Activator, renal dialysis, Renal Insufficiency, Chronic, risk factors, Stroke, Survival AnalysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-08-07August 07, 201710.2215/CJN.108810161555-90411555-905X2017-05-11T07:12:37-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12812651273
- Accessing the Access10.2215/CJN.08670812Thu, 13 Sep 2012 08:04:47 GMT-07:00Accessing the AccessZimmerman, DeborahLok, Charmaine E.2012-09-13T08:04:47-07:00doi:10.2215/CJN.08670812hwp:resource-id:clinjasn;7/10/1548American Society of NephrologyCopyright © 2012 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEditorialsEditorialseditorial20122012-10-01October 05, 201210.2215/CJN.086708121555-90411555-905X2012-09-13T08:04:47-07:002012-10Clinical Journal of the American Society of NephrologyEditorials710101548163215501638
- A Multicenter Cohort Study of Histologic Findings and Long-Term Outcomes of Kidney Disease in Women Who Have Been Pregnant10.2215/CJN.05610516Fri, 09 Dec 2016 06:58:12 GMT-08:00A Multicenter Cohort Study of Histologic Findings and Long-Term Outcomes of Kidney Disease in Women Who Have Been PregnantWebster, PhilipWebster, Louise M.Cook, H. TerenceHorsfield, CatherineSeed, Paul T.Vaz, RaquelSantos, ClaraLydon, IsabelleHomsy, MicheleLightstone, LizBramham, Kate2016-12-09T06:58:12-08:00doi:10.2215/CJN.05610516hwp:resource-id:clinjasn;12/3/408American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypregnancy, renal biopsy, preeclampsia, focal segmental glomerulosclerosis, biopsy, creatinine, female, follow-up studies, glomerulosclerosis, focal segmental, humans, kidney, odds ratio, postpartum period, pregnancy, renal insufficiency, chronic, urinalysis, urinary tract physiological phenomenaOriginal ArticlesChronic Kidney DiseasesOriginal ArticlesChronic Kidney Diseasesresearch-article20172017-03-07March 07, 201710.2215/CJN.056105161555-90411555-905X2016-12-09T06:58:12-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles123408416
- Racial Differences in Home Dialysis Utilization and Outcomes in Canada10.2215/CJN.03820417Wed, 23 Aug 2017 06:37:40 GMT-07:00Racial Differences in Home Dialysis Utilization and Outcomes in CanadaTrinh, EmilieNa, YingboSood, Manish M.Chan, Christopher T.Perl, Jeffrey2017-08-23T06:37:40-07:00doi:10.2215/CJN.03820417hwp:resource-id:clinjasn;12/11/1841American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyethnicity, ethnic disparities, home dialysis, home hemodialysis, patient survival, race, racial disparities, technique survival, Hemodialysis, Home, Minority Groups, Linear Models, Canada, European Continental Ancestry Group, African Continental Ancestry Group, peritoneal dialysis, Asian Continental Ancestry GroupOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-11-07November 07, 201710.2215/CJN.038204171555-90411555-905X2017-08-23T06:37:40-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121118411851
- The Use of a Multidimensional Measure of Dialysis Adequacy—Moving beyond Small Solute KineticsUrea removal has become a key measure of the intensity of dialysis treatment for kidney failure. Small solute removal, exemplified by Kt/Vurea, has been broadly applied as a means to quantify the dose of thrice weekly hemodialysis. Yet, the reliance on small solute clearances alone as a measure of dialysis adequacy fails fully to quantify the intended clinical effects of dialysis therapy. This review aims to (1) understand the strengths and limitations of small solute kinetics as a surrogate marker of dialysis dose, and (2) present the prospect of a more comprehensive construct for dialysis dose, one that considers more broadly the goals of ESRD care to maximize both quality of life and survival. On behalf of the American Society of Nephrology Dialysis Advisory Group, we propose the need to ascertain the validity and utility of a multidimensional measure that moves beyond small solute kinetics alone to quantify optimal dialysis derived from both patient-reported and comprehensive clinical and dialysis-related measures.10.2215/CJN.08460816Fri, 17 Mar 2017 08:04:16 GMT-07:00The Use of a Multidimensional Measure of Dialysis Adequacy—Moving beyond Small Solute KineticsUrea removal has become a key measure of the intensity of dialysis treatment for kidney failure. Small solute removal, exemplified by Kt/Vurea, has been broadly applied as a means to quantify the dose of thrice weekly hemodialysis. Yet, the reliance on small solute clearances alone as a measure of dialysis adequacy fails fully to quantify the intended clinical effects of dialysis therapy. This review aims to (1) understand the strengths and limitations of small solute kinetics as a surrogate marker of dialysis dose, and (2) present the prospect of a more comprehensive construct for dialysis dose, one that considers more broadly the goals of ESRD care to maximize both quality of life and survival. On behalf of the American Society of Nephrology Dialysis Advisory Group, we propose the need to ascertain the validity and utility of a multidimensional measure that moves beyond small solute kinetics alone to quantify optimal dialysis derived from both patient-reported and comprehensive clinical and dialysis-related measures.Perl, JeffreyDember, Laura M.Bargman, Joanne M.Browne, TeriCharytan, David M.Flythe, Jennifer E.Hickson, LaTonya J.Hung, Adriana M.Jadoul, MichelLee, Timmy ChangMeyer, Klemens B.Moradi, HamidShafi, TariqTeitelbaum, IsaacWong, Leslie P.Chan, Christopher T.,2017-03-17T08:04:16-07:00doi:10.2215/CJN.08460816hwp:resource-id:clinjasn;12/5/839American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDialysis dose, Urea Kinetics, Patient Reported Outcomes, Dialysis PhysiologyReviewReviewreview-article20172017-05-08May 08, 201710.2215/CJN.084608161555-90411555-905X2017-03-17T08:04:16-07:002017-05-08Clinical Journal of the American Society of NephrologyReview125839847
- Diagnosis, Treatment, and Prevention of Hemodialysis EmergenciesGiven the high comorbidity in patients on hemodialysis and the complexity of the dialysis treatment, it is remarkable how rarely a life-threatening complication occurs during dialysis. The low rate of dialysis emergencies can be attributed to numerous safety features in modern dialysis machines; meticulous treatment and testing of the dialysate solution to prevent exposure to trace elements, toxins, and pathogens; adherence to detailed treatment protocols; and extensive training of dialysis staff to handle medical emergencies. Most hemodialysis emergencies can be attributed to human error. A smaller number are due to rare idiosyncratic reactions. In this review, we highlight major emergencies that may occur during hemodialysis treatments, describe their pathogenesis, offer measures to minimize them, and provide specific interventions to prevent catastrophic consequences on the rare occasions when such emergencies arise. These emergencies include dialysis disequilibrium syndrome, venous air embolism, hemolysis, venous needle dislodgement, vascular access hemorrhage, major allergic reactions to the dialyzer or treatment medications, and disruption or contamination of the dialysis water system. Finally, we describe root cause analysis after a dialysis emergency has occurred to prevent a future recurrence.10.2215/CJN.05260516Wed, 09 Nov 2016 07:49:07 GMT-08:00Diagnosis, Treatment, and Prevention of Hemodialysis EmergenciesGiven the high comorbidity in patients on hemodialysis and the complexity of the dialysis treatment, it is remarkable how rarely a life-threatening complication occurs during dialysis. The low rate of dialysis emergencies can be attributed to numerous safety features in modern dialysis machines; meticulous treatment and testing of the dialysate solution to prevent exposure to trace elements, toxins, and pathogens; adherence to detailed treatment protocols; and extensive training of dialysis staff to handle medical emergencies. Most hemodialysis emergencies can be attributed to human error. A smaller number are due to rare idiosyncratic reactions. In this review, we highlight major emergencies that may occur during hemodialysis treatments, describe their pathogenesis, offer measures to minimize them, and provide specific interventions to prevent catastrophic consequences on the rare occasions when such emergencies arise. These emergencies include dialysis disequilibrium syndrome, venous air embolism, hemolysis, venous needle dislodgement, vascular access hemorrhage, major allergic reactions to the dialyzer or treatment medications, and disruption or contamination of the dialysis water system. Finally, we describe root cause analysis after a dialysis emergency has occurred to prevent a future recurrence.Saha, ManishAllon, Michael2016-11-09T07:49:07-08:00doi:10.2215/CJN.05260516hwp:resource-id:clinjasn;12/2/357American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis disequilibrium, air embolism, hemolysis, Clinical Protocols, Dialysis Solutions, Embolism, Air, Emergencies, Hemolysis, Humans, Hypersensitivity, Kidneys, Artificial, Needles, Pharmaceutical Solutions, Recurrence, renal dialysis, Root Cause Analysis, Trace Elements, WaterIn-Depth ReviewIn-Depth Reviewreview-article20172017-02-07February 07, 201710.2215/CJN.052605161555-90411555-905X2016-11-09T07:49:07-08:002017-02-07Clinical Journal of the American Society of NephrologyIn-Depth Review122357369
- Glomerular Density and Volume in Renal Biopsy Specimens of Children with Proteinuria Relative to Preterm Birth and Gestational Age10.2215/CJN.05650516Thu, 23 Mar 2017 07:14:53 GMT-07:00Glomerular Density and Volume in Renal Biopsy Specimens of Children with Proteinuria Relative to Preterm Birth and Gestational AgeKoike, KentaroIkezumi, YoheiTsuboi, NobuoKanzaki, GoHaruhara, KotaroOkabayashi, YusukeSasaki, TakayaOgura, MakotoSaitoh, AkihikoYokoo, Takashi2017-03-23T07:14:53-07:00doi:10.2215/CJN.05650516hwp:resource-id:clinjasn;12/4/585American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypremature birth, biopsy, kidney glomerulus, birth weight, blood pressure, body mass index, child, female, gestational age, glomerulosclerosis, focal segmental, humans, infant, low birth weight, infant, newborn, kidney, kidney glomerulus, nephrons, nephrosis, lipoid, pregnancy, premature birth, proteinuria, sclerosis, segmental glomerulosclerosisOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-04-03April 03, 201710.2215/CJN.056505161555-90411555-905X2017-03-23T07:14:53-07:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles1244585553590555
- Older Patients’ Perspectives on Managing Complexity in CKD Self-Management10.2215/CJN.06850616Fri, 07 Apr 2017 01:00:30 GMT-07:00Older Patients’ Perspectives on Managing Complexity in CKD Self-ManagementBowling, C. BarrettVandenberg, Ann E.Phillips, Lawrence S.McClellan, William M.Johnson, Theodore M.Echt, Katharina V.2017-04-07T13:00:30-07:00doi:10.2215/CJN.06850616hwp:resource-id:clinjasn;12/4/635American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, self-management, chronic kidney disease, adult, African Americans, blood pressure, comorbidity, diabetes mellitus, focus groups, gout, grounded theory, humans, hypertension, male, nephrology, qualitative research, renal insufficiency, chronic, self care, veteransOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20172017-04-03April 03, 201710.2215/CJN.068506161555-90411555-905X2017-04-07T13:00:30-07:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles1244635559643561
- SGLT2 Inhibition in the Diabetic Kidney—From Mechanisms to Clinical OutcomeDiabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously. Sodium-glucose cotransporter type 2 in the renal proximal tubule reabsorbs approximately 90% of filtered glucose. In type 2 diabetes, the maladaptive upregulation of sodium-glucose cotransporter type 2 contributes to the maintenance of hyperglycemia. Inhibiting these transporters has been shown to effectively improve glycemic control through inducing glycosuria and is generally well tolerated, although patients experience more genital infections. In addition, sodium-glucose cotransporter type 2 inhibitors favorably affect body weight, BP, serum uric acid, and glomerular hyperfiltration. Interestingly, in the recently reported first cardiovascular safety trial with a sodium-glucose cotransporter type 2 inhibitor, empagliflozin improved both renal and cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease. Because the benefits were seen rapidly after initiation of therapy and other glucose-lowering agents, with the exception of liraglutide and semaglutide, have not been able to improve cardiovascular outcome, these observations are most likely explained by effects beyond glucose lowering. In this mini review, we present the drug class of sodium-glucose cotransporter type 2 inhibitors, elaborate on currently available renal and cardiovascular outcome data, and discuss how the effects of these agents on renal physiology may explain the data.10.2215/CJN.06080616Thu, 02 Mar 2017 09:14:16 GMT-08:00SGLT2 Inhibition in the Diabetic Kidney—From Mechanisms to Clinical OutcomeDiabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously. Sodium-glucose cotransporter type 2 in the renal proximal tubule reabsorbs approximately 90% of filtered glucose. In type 2 diabetes, the maladaptive upregulation of sodium-glucose cotransporter type 2 contributes to the maintenance of hyperglycemia. Inhibiting these transporters has been shown to effectively improve glycemic control through inducing glycosuria and is generally well tolerated, although patients experience more genital infections. In addition, sodium-glucose cotransporter type 2 inhibitors favorably affect body weight, BP, serum uric acid, and glomerular hyperfiltration. Interestingly, in the recently reported first cardiovascular safety trial with a sodium-glucose cotransporter type 2 inhibitor, empagliflozin improved both renal and cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease. Because the benefits were seen rapidly after initiation of therapy and other glucose-lowering agents, with the exception of liraglutide and semaglutide, have not been able to improve cardiovascular outcome, these observations are most likely explained by effects beyond glucose lowering. In this mini review, we present the drug class of sodium-glucose cotransporter type 2 inhibitors, elaborate on currently available renal and cardiovascular outcome data, and discuss how the effects of these agents on renal physiology may explain the data.van Bommel, Erik J.M.Muskiet, Marcel H.A.Tonneijck, LennartKramer, Mark H.H.Nieuwdorp, Maxvan Raalte, Daniel H.2017-03-02T09:14:16-08:00doi:10.2215/CJN.06080616hwp:resource-id:clinjasn;12/4/700American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, cardiovascular disease, diabetes mellitus, Benzhydryl Compounds, blood pressure, Body Weight, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Dyslipidemias, Glucose, Glucose Transporter Type 2, Glucosides, Glycosuria, Humans, Hyperglycemia, hypertension, Kidney Failure, Chronic, Liraglutide, obesity, risk factors, Sodium, Sodium-Glucose Transporter 2, Up-Regulation, Uric AcidIn-Depth ReviewIn-Depth Reviewresearch-article20172017-04-03April 03, 201710.2215/CJN.060806161555-90411555-905X2017-03-02T09:14:16-08:002017-04-03Clinical Journal of the American Society of NephrologyIn-Depth Review124700710
- Temporal Trends in the Epidemiology of Biopsy-Proven Glomerular Diseases: An Alarming Increase in Diabetic Glomerulosclerosis10.2215/CJN.02190217Tue, 21 Mar 2017 08:44:16 GMT-07:00Temporal Trends in the Epidemiology of Biopsy-Proven Glomerular Diseases: An Alarming Increase in Diabetic GlomerulosclerosisHou, JeanHaas, Mark2017-03-21T08:44:16-07:00doi:10.2215/CJN.02190217hwp:resource-id:clinjasn;12/4/556American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic glomerulosclerosis, focal segmental glomerulosclerosis, renal biopsy, renal pathology, glomerular disease, Epidemiology and outcomes, Biopsy, Diabetic NephropathiesEditorialsEditorialseditorial20172017-04-03April 03, 201710.2215/CJN.021902171555-90411555-905X2017-03-21T08:44:16-07:002017-04-03Clinical Journal of the American Society of NephrologyEditorials1244556614558623
- A Perspective on Inherited Kidney Disease10.2215/CJN.11751017Thu, 16 Nov 2017 06:49:11 GMT-08:00A Perspective on Inherited Kidney DiseaseLemaire, MathieuParekh, Rulan S.2017-11-16T06:49:11-08:00doi:10.2215/CJN.11751017hwp:resource-id:clinjasn;12/12/1914American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinherited kidney disease, Penetrance, Genes, Modifier, Kidney Diseases, Kidney Glomerulus, kidney, Mutation, GenomicsEditorialsEditorialseditorial20172017-12-07December 07, 201710.2215/CJN.117510171555-90411555-905X2017-11-16T06:49:11-08:002017-12-07Clinical Journal of the American Society of NephrologyEditorials12121212191419621974191619731983
- Diabetes and CKD in the United States Population, 2009–201410.2215/CJN.03700417Fri, 20 Oct 2017 05:52:27 GMT-07:00Diabetes and CKD in the United States Population, 2009–2014Zelnick, Leila R.Weiss, Noel S.Kestenbaum, Bryan R.Robinson-Cohen, CassianneHeagerty, Patrick J.Tuttle, KatherineHall, Yoshio N.Hirsch, Irl B.de Boer, Ian H.2017-10-20T05:52:27-07:00doi:10.2215/CJN.03700417hwp:resource-id:clinjasn;12/12/1984American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, diabetic nephropathy, chronic kidney disease, Epidemiology and outcomes, albuminuria, Hemoglobin A, Glycosylated, Prevalence, Nutrition Surveys, Cross-Sectional Studies, blood pressure, creatinine, glomerular filtration rate, Confidence Intervals, Linear Models, Glucose, Renal Insufficiency, Chronic, diabetes mellitus, Blood Pressure Determination, hypertension, AlbuminsOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20172017-12-07December 07, 201710.2215/CJN.037004171555-90411555-905X2017-10-20T05:52:27-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1212121984191719901918
- Burden of Proof—When Is Kidney Disease Attributable to Diabetes?10.2215/CJN.10720917Fri, 20 Oct 2017 05:52:28 GMT-07:00Burden of Proof—When Is Kidney Disease Attributable to Diabetes?Saulnier, Pierre-JeanNelson, Robert G.2017-10-20T05:52:28-07:00doi:10.2215/CJN.10720917hwp:resource-id:clinjasn;12/12/1917American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, Kidney Diseases, diabetesEditorialsEditorialseditorial20172017-12-07December 07, 201710.2215/CJN.107209171555-90411555-905X2017-10-20T05:52:28-07:002017-12-07Clinical Journal of the American Society of NephrologyEditorials1212121917198419181990
- Effectiveness of Treatment Modalities on Kidney Stone RecurrenceNephrolithiasis is highly prevalent across all demographic groups in the Western world and beyond, and its incidence rates are rising. In addition to the morbidity of the acute event, stone disease often becomes a lifelong problem that requires preventative therapy to diminish ongoing morbidity. Across the majority of stone types, increased fluid intake and targeted dietary modifications are mainstays of therapy. Specific dietary interventions associated with reduced calcium stone risk include adequate dietary calcium intake and restriction of sodium, protein, and oxalate intake, among others. Pharmaceutical therapy may be required if lifestyle changes are insufficient to minimize risk of stone recurrence, and must be targeted to the specific metabolic abnormalities portending risk for a given patient. Therapeutic options for idiopathic calcium stone disease include thiazides, citrate salts, and uric acid–lowering agents. Alkali salts are also the treatment of choice for uric acid stone disease. Management of struvite stone disease is largely surgical, but acetohydroxamic acid is a proven second line therapy. Cystinuria requires lifestyle modifications and may call for thiol-binding agents. Significant heterogeneity of the clinical population with stone disease has previously limited opportunities for large randomized controlled trials. However, as clinical phenotypes and genotypes are increasingly clarified, there are mounting opportunities for targeted randomized controlled trials in stone prevention. In the meantime, the currently available evidence for both lifestyle and pharmacologic interventions is reviewed herein.10.2215/CJN.11201016Tue, 22 Aug 2017 06:23:24 GMT-07:00Effectiveness of Treatment Modalities on Kidney Stone RecurrenceNephrolithiasis is highly prevalent across all demographic groups in the Western world and beyond, and its incidence rates are rising. In addition to the morbidity of the acute event, stone disease often becomes a lifelong problem that requires preventative therapy to diminish ongoing morbidity. Across the majority of stone types, increased fluid intake and targeted dietary modifications are mainstays of therapy. Specific dietary interventions associated with reduced calcium stone risk include adequate dietary calcium intake and restriction of sodium, protein, and oxalate intake, among others. Pharmaceutical therapy may be required if lifestyle changes are insufficient to minimize risk of stone recurrence, and must be targeted to the specific metabolic abnormalities portending risk for a given patient. Therapeutic options for idiopathic calcium stone disease include thiazides, citrate salts, and uric acid–lowering agents. Alkali salts are also the treatment of choice for uric acid stone disease. Management of struvite stone disease is largely surgical, but acetohydroxamic acid is a proven second line therapy. Cystinuria requires lifestyle modifications and may call for thiol-binding agents. Significant heterogeneity of the clinical population with stone disease has previously limited opportunities for large randomized controlled trials. However, as clinical phenotypes and genotypes are increasingly clarified, there are mounting opportunities for targeted randomized controlled trials in stone prevention. In the meantime, the currently available evidence for both lifestyle and pharmacologic interventions is reviewed herein.Zisman, Anna L.2017-08-22T06:23:24-07:00doi:10.2215/CJN.11201016hwp:resource-id:clinjasn;12/10/1699American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrolithiasis, thiazide, citrate, Cystinuria, Uric Acid, acetohydroxamic acid, Sodium, Salts, Calcium, Dietary, Struvite, Thiazides, Incidence, Kidney Calculi, Hydroxamic Acids, Sodium, Dietary, Life Style, Oxalates, Western World, Genotype, Phenotype, Sulfhydryl Compounds, Disease Management, Citrates, AlkalisEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20172017-10-06October 06, 201710.2215/CJN.112010161555-90411555-905X2017-08-22T06:23:24-07:002017-10-06Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology121016991708
- Fluid First or Not So Fast: Ultrafiltration Rate and the ESRD Quality Incentive Program10.2215/CJN.05840616Wed, 22 Jun 2016 06:42:58 GMT-07:00Fluid First or Not So Fast: Ultrafiltration Rate and the ESRD Quality Incentive ProgramWeiner, Daniel E.Lacson, Eduardo2016-06-22T06:42:58-07:00doi:10.2215/CJN.05840616hwp:resource-id:clinjasn;11/8/1330American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, health care policy, quality metrics, Kidney Failure, Chronic, Motivation, Reimbursement, Incentive, renal dialysis, ultrafiltrationEditorialsEditorialseditorial20162016-08-08August 08, 201610.2215/CJN.058406161555-90411555-905X2016-06-22T06:42:58-07:002016-08-08Clinical Journal of the American Society of NephrologyEditorials11881330142213321433
- Ultrafiltration Rates and the Quality Incentive Program: Proposed Measure Definitions and Their Potential Dialysis Facility Implications10.2215/CJN.13441215Wed, 22 Jun 2016 06:42:59 GMT-07:00Ultrafiltration Rates and the Quality Incentive Program: Proposed Measure Definitions and Their Potential Dialysis Facility ImplicationsFlythe, Jennifer E.Assimon, Magdalene M.Wenger, Julia B.Wang, Lily2016-06-22T06:42:59-07:00doi:10.2215/CJN.13441215hwp:resource-id:clinjasn;11/8/1422American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, ultrafiltration, Epidemiology and outcomes, heart failure, Humans, Kidney Failure, Chronic, Medicaid, Medicare, Prospective Studies, renal dialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-08-08August 08, 201610.2215/CJN.134412151555-90411555-905X2016-06-22T06:42:59-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11881422133014331332
- Provider Knowledge, Attitudes, and Practices Surrounding Conservative Management for Patients with Advanced CKD10.2215/CJN.07180715Fri, 15 Apr 2016 09:07:54 GMT-07:00Provider Knowledge, Attitudes, and Practices Surrounding Conservative Management for Patients with Advanced CKDParvez, SanahAbdel-Kader, KhaledPankratz, V. ShaneSong, Mi-KyungUnruh, Mark2016-04-15T09:07:54-07:00doi:10.2215/CJN.07180715hwp:resource-id:clinjasn;11/5/812American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, geriatric nephrology, quality of life, hemodialysis, survival, attitude, humans, knowledge, renal insufficiency, chronic, surveys and questionnairesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.071807151555-90411555-905X2016-04-15T09:07:54-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles1155812750820752
- Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on Hemodialysis10.2215/CJN.04310416Mon, 03 Oct 2016 08:49:28 GMT-07:00Asymptomatic Intradialytic Supraventricular Arrhythmias and Adverse Outcomes in Patients on HemodialysisVerde, EduardoPérez de Prado, ArmandoLópez-Gómez, Juan M.Quiroga, BorjaGoicoechea, MarianGarcía-Prieto, AnaTorres, EstherReque, JavierLuño, José2016-10-03T08:49:28-07:00doi:10.2215/CJN.04310416hwp:resource-id:clinjasn;11/12/2210American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyArrhythmias, hemodialysis, atrial fibrillation, mortality, asymptomatic arrhythmias, end-stage renal disease, chronic dialysis, attention, C-Reactive Protein, Cause of Death, Confidence Intervals, diabetes mellitus, Electrocardiography, female, Follow-Up Studies, Heart Atria, Heart Conduction System, humans, hypertension, Incidence, male, Multivariate Analysis, Prevalence, Proportional Hazards Models, Prospective StudiesOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-12-07December 07, 201610.2215/CJN.043104161555-90411555-905X2016-10-03T08:49:28-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111222102217
- Managing Disruptive Behavior by Patients and Physicians: A Responsibility of the Dialysis Facility Medical DirectorThe Centers for Medicare & Medicaid Services’ Conditions for Coverage make the medical director of an ESRD facility responsible for all aspects of care, including high-quality health care delivery (e.g., safe, effective, timely, efficient, and patient centered). Because of the high-pressure environment of the dialysis facility, conflicts are common. Conflict frequently occurs when aberrant behaviors disrupt the dialysis facility. Patients, family members, friends, and, less commonly appreciated, nephrology clinicians (i.e., nephrologists and advanced care practitioners) may manifest disruptive behavior. Disruptive behavior in the dialysis facility impairs the ability to deliver high-quality care. Furthermore, disruptive behavior is the leading cause for involuntary discharge (IVD) or involuntary transfer (IVT) of a patient from a facility. IVD usually results in loss of continuity of care, increased emergency department visits, and increased unscheduled, acute dialysis treatments. A sufficient number of IVDs and IVTs also trigger an extensive review of the facility by the regional ESRD Networks, exposing the facility to possible Medicare-imposed sanctions. Medical directors must be equipped to recognize and correct disruptive behavior. Nephrology-based literature and tools exist to help dialysis facility medical directors successfully address and resolve disruptive behavior before medical directors must involuntarily discharge a patient or terminate an attending clinician.10.2215/CJN.05220514Mon, 17 Nov 2014 07:02:45 GMT-08:00Managing Disruptive Behavior by Patients and Physicians: A Responsibility of the Dialysis Facility Medical DirectorThe Centers for Medicare & Medicaid Services’ Conditions for Coverage make the medical director of an ESRD facility responsible for all aspects of care, including high-quality health care delivery (e.g., safe, effective, timely, efficient, and patient centered). Because of the high-pressure environment of the dialysis facility, conflicts are common. Conflict frequently occurs when aberrant behaviors disrupt the dialysis facility. Patients, family members, friends, and, less commonly appreciated, nephrology clinicians (i.e., nephrologists and advanced care practitioners) may manifest disruptive behavior. Disruptive behavior in the dialysis facility impairs the ability to deliver high-quality care. Furthermore, disruptive behavior is the leading cause for involuntary discharge (IVD) or involuntary transfer (IVT) of a patient from a facility. IVD usually results in loss of continuity of care, increased emergency department visits, and increased unscheduled, acute dialysis treatments. A sufficient number of IVDs and IVTs also trigger an extensive review of the facility by the regional ESRD Networks, exposing the facility to possible Medicare-imposed sanctions. Medical directors must be equipped to recognize and correct disruptive behavior. Nephrology-based literature and tools exist to help dialysis facility medical directors successfully address and resolve disruptive behavior before medical directors must involuntarily discharge a patient or terminate an attending clinician.Jones, Edward R.Goldman, Richard S.2014-11-17T07:02:45-08:00doi:10.2215/CJN.05220514hwp:resource-id:clinjasn;10/8/1470American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymedical director, disruptive behavior, patient, hemodialysisRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-08-07August 07, 201510.2215/CJN.052205141555-90411555-905X2014-11-17T07:02:45-08:002015-08-07Clinical Journal of the American Society of NephrologyRole of the Medical Director10814701475
- The Medical Director in Integrated Clinical Care ModelsIntegrated clinical care models, like Accountable Care Organizations and ESRD Seamless Care Organizations, present new opportunities for dialysis facility medical directors to affect changes in care that result in improved patient outcomes. Currently, there is little scholarly information on what role the medical director should play. In this opinion-based review, it is predicted that dialysis providers, the hospitals in which the medical director and staff physicians practice, and the payers with which they contract are going to insist that, as care becomes more integrated, dialysis facility medical directors participate in new ways to improve quality and decrease the costs of care. Six broad areas are proposed where dialysis unit medical directors can have the greatest effect on shifting the quality-care paradigm where integrated care models are used. The medical director will need to develop an awareness of the regional medical care delivery system, collect and analyze actionable data, determine patient outcomes to be targeted that are mutually agreed on by participating physicians and institutions, develop processes of care that result in improved patient outcomes, and lead and inform the medical staff. Three practical examples of patient-centered, quality-focused programs developed and implemented by dialysis unit medical directors and their practice partners that targeted dialysis access, modality choice, and fluid volume management are presented. Medical directors are encouraged to move beyond traditional roles and embrace responsibilities associated with integrated care.10.2215/CJN.05120514Tue, 28 Oct 2014 07:56:54 GMT-07:00The Medical Director in Integrated Clinical Care ModelsIntegrated clinical care models, like Accountable Care Organizations and ESRD Seamless Care Organizations, present new opportunities for dialysis facility medical directors to affect changes in care that result in improved patient outcomes. Currently, there is little scholarly information on what role the medical director should play. In this opinion-based review, it is predicted that dialysis providers, the hospitals in which the medical director and staff physicians practice, and the payers with which they contract are going to insist that, as care becomes more integrated, dialysis facility medical directors participate in new ways to improve quality and decrease the costs of care. Six broad areas are proposed where dialysis unit medical directors can have the greatest effect on shifting the quality-care paradigm where integrated care models are used. The medical director will need to develop an awareness of the regional medical care delivery system, collect and analyze actionable data, determine patient outcomes to be targeted that are mutually agreed on by participating physicians and institutions, develop processes of care that result in improved patient outcomes, and lead and inform the medical staff. Three practical examples of patient-centered, quality-focused programs developed and implemented by dialysis unit medical directors and their practice partners that targeted dialysis access, modality choice, and fluid volume management are presented. Medical directors are encouraged to move beyond traditional roles and embrace responsibilities associated with integrated care.Parker, Thomas F.Aronoff, George R.2014-10-28T07:56:54-07:00doi:10.2215/CJN.05120514hwp:resource-id:clinjasn;10/7/1282American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, chronic hemodialysis, medical director, care models, integrated careRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-07-07July 07, 201510.2215/CJN.051205141555-90411555-905X2014-10-28T07:56:54-07:002015-07-07Clinical Journal of the American Society of NephrologyRole of the Medical Director10712821286
- Infection Prevention and the Medical Director: Uncharted TerritoryInfections continue to be a major cause of disease and contributor to death in patients on dialysis. Despite our knowledge and acceptance that hemodialysis catheters should be avoided and eliminated, most patients who begin dialysis initiate treatment through a central vein hemodialysis catheter. Dialysis Medical Directors must be the instrument through which our industry changes. We must lead the charge to educate our dialysis staff and our dialysis patients. We must also educate ourselves so that we not only know that our facility policies are consistent with the best evidence available, but we must also know where local and federal regulations differ. When these differences impact on patient care, we must speak out and have these regulations changed. But it is not enough to know the rules and write them. We must lead by example and show our patients, our nephrology colleagues and our dialysis staff that we always follow these same policies. We need to practice what we preach and be willing and available to redirect those individuals who have difficulty following the rules. In order to effectively change process meaningful data must be collected, analyzed and acted upon. Dialysis Medical Directors must direct and lead the quality improvement process. We hope this review provides Dialysis Medical Directors with the necessary tools to effectively drive this process and improve care.10.2215/CJN.06050614Fri, 20 Feb 2015 06:37:53 GMT-08:00Infection Prevention and the Medical Director: Uncharted TerritoryInfections continue to be a major cause of disease and contributor to death in patients on dialysis. Despite our knowledge and acceptance that hemodialysis catheters should be avoided and eliminated, most patients who begin dialysis initiate treatment through a central vein hemodialysis catheter. Dialysis Medical Directors must be the instrument through which our industry changes. We must lead the charge to educate our dialysis staff and our dialysis patients. We must also educate ourselves so that we not only know that our facility policies are consistent with the best evidence available, but we must also know where local and federal regulations differ. When these differences impact on patient care, we must speak out and have these regulations changed. But it is not enough to know the rules and write them. We must lead by example and show our patients, our nephrology colleagues and our dialysis staff that we always follow these same policies. We need to practice what we preach and be willing and available to redirect those individuals who have difficulty following the rules. In order to effectively change process meaningful data must be collected, analyzed and acted upon. Dialysis Medical Directors must direct and lead the quality improvement process. We hope this review provides Dialysis Medical Directors with the necessary tools to effectively drive this process and improve care.Kapoian, TorosMeyer, Klemens B.Johnson, Douglas S.2015-02-20T06:37:53-08:00doi:10.2215/CJN.06050614hwp:resource-id:clinjasn;10/5/863American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, chronic hemodialysis, vascular access, dialysis access, immunologyRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-05-07May 07, 201510.2215/CJN.060506141555-90411555-905X2015-02-20T06:37:53-08:002015-05-07Clinical Journal of the American Society of NephrologyRole of the Medical Director105863874
- Associations of Posthemodialysis Weights above and below Target Weight with All-Cause and Cardiovascular Mortality10.2215/CJN.10201014Fri, 10 Apr 2015 10:00:22 GMT-07:00Associations of Posthemodialysis Weights above and below Target Weight with All-Cause and Cardiovascular MortalityFlythe, Jennifer E.Kshirsagar, Abhijit V.Falk, Ronald J.Brunelli, Steven M.2015-04-10T10:00:22-07:00doi:10.2215/CJN.10201014hwp:resource-id:clinjasn;10/5/808American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, cardiovascular, chronic hemodialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-05-07May 07, 201510.2215/CJN.102010141555-90411555-905X2015-04-10T10:00:22-07:002015-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1055808729816731
- Posthemodialysis Weights and Mortality: Another Narrow Range Target?10.2215/CJN.03110315Fri, 10 Apr 2015 10:00:24 GMT-07:00Posthemodialysis Weights and Mortality: Another Narrow Range Target?Jablonski, Kristen L.Chonchol, Michel2015-04-10T10:00:24-07:00doi:10.2215/CJN.03110315hwp:resource-id:clinjasn;10/5/729American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, mortality, clinical epidemiologyEditorialsEditorialseditorial20152015-05-07May 07, 201510.2215/CJN.031103151555-90411555-905X2015-04-10T10:00:24-07:002015-05-07Clinical Journal of the American Society of NephrologyEditorials1055729808731816
- What Medical Directors Need to Know about Dialysis Facility Water ManagementThe medical directors of dialysis facilities have many operational clinic responsibilities, which on first glance, may seem outside the realm of excellence in patient care. However, a smoothly running clinic is integral to positive patient outcomes. Of the conditions for coverage outlined by the Centers for Medicare and Medicaid Services, one most critical to quality dialysis treatment is the provision of safe purified dialysis water, because there are many published instances where clinic failure in this regard has resulted in patient harm. As the clinical leader of the facility, the medical director is obliged to have knowledge of his/her facility’s water treatment system to reliably ensure that the purified water used in dialysis will meet the standards for quality set by the Association for the Advancement of Medical Instrumentation and used by the Centers for Medicare and Medicaid Services for conditions for coverage. The methods used to both achieve and maintain these quality standards should be a part of quality assessment and performance improvement program meetings. The steps for water treatment, which include pretreatment, purification, and distribution, are largely the same, regardless of the system used. Each water treatment system component has a specific role in the process and requires individualized maintenance and monitoring. The medical director should provide leadership by being engaged with the process, knowing the facility’s source water, and understanding water treatment system operation as well as the clinical significance of system failure. Successful provision of quality water will be achieved by those medical directors who learn, know, and embrace the requirements of dialysis water purification and system maintenance.10.2215/CJN.11851214Fri, 15 May 2015 07:18:13 GMT-07:00What Medical Directors Need to Know about Dialysis Facility Water ManagementThe medical directors of dialysis facilities have many operational clinic responsibilities, which on first glance, may seem outside the realm of excellence in patient care. However, a smoothly running clinic is integral to positive patient outcomes. Of the conditions for coverage outlined by the Centers for Medicare and Medicaid Services, one most critical to quality dialysis treatment is the provision of safe purified dialysis water, because there are many published instances where clinic failure in this regard has resulted in patient harm. As the clinical leader of the facility, the medical director is obliged to have knowledge of his/her facility’s water treatment system to reliably ensure that the purified water used in dialysis will meet the standards for quality set by the Association for the Advancement of Medical Instrumentation and used by the Centers for Medicare and Medicaid Services for conditions for coverage. The methods used to both achieve and maintain these quality standards should be a part of quality assessment and performance improvement program meetings. The steps for water treatment, which include pretreatment, purification, and distribution, are largely the same, regardless of the system used. Each water treatment system component has a specific role in the process and requires individualized maintenance and monitoring. The medical director should provide leadership by being engaged with the process, knowing the facility’s source water, and understanding water treatment system operation as well as the clinical significance of system failure. Successful provision of quality water will be achieved by those medical directors who learn, know, and embrace the requirements of dialysis water purification and system maintenance.Kasparek, TedRodriguez, Oscar E.2015-05-15T07:18:13-07:00doi:10.2215/CJN.11851214hwp:resource-id:clinjasn;10/6/1061American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, dialysis, mortality, nephrologyRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-06-05June 05, 201510.2215/CJN.118512141555-90411555-905X2015-05-15T07:18:13-07:002015-06-05Clinical Journal of the American Society of NephrologyRole of the Medical Director10610611071
- American Society of Nephrology Quiz and Questionnaire 2014: RRTThe Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology (ASN). Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, end-stage renal disease/dialysis, and transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Prior to the meeting, program directors of U.S. nephrology training programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. They compared their answers in real time using audience response devices with the answers of the nephrology fellows and training program directors (TPDs). The correct and incorrect answers were then discussed after the audience responses and the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.10.2215/CJN.01490215Mon, 20 Apr 2015 09:20:15 GMT-07:00American Society of Nephrology Quiz and Questionnaire 2014: RRTThe Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology (ASN). Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, end-stage renal disease/dialysis, and transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Prior to the meeting, program directors of U.S. nephrology training programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. They compared their answers in real time using audience response devices with the answers of the nephrology fellows and training program directors (TPDs). The correct and incorrect answers were then discussed after the audience responses and the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.Mehrotra, RajnishPerazella, Mark A.Choi, Michael J.2015-04-20T09:20:15-07:00doi:10.2215/CJN.01490215hwp:resource-id:clinjasn;10/6/1100American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hemodialysis, ESRDSpecial FeatureSpecial Featureresearch-article20152015-06-05June 05, 201510.2215/CJN.014902151555-90411555-905X2015-04-20T09:20:15-07:002015-06-05Clinical Journal of the American Society of NephrologySpecial Feature10611001106
- Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis10.2215/CJN.08760914Fri, 10 Apr 2015 10:00:21 GMT-07:00Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after HemodialysisOgna, AdamForni Ogna, ValentinaMihalache, AlexandraPruijm, MennoHalabi, GeorgesPhan, OlivierCornette, FrançoiseBassi, IsabelleHaba Rubio, JoséBurnier, MichelHeinzer, Raphaël2015-04-10T10:00:21-07:00doi:10.2215/CJN.08760914hwp:resource-id:clinjasn;10/6/1002American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, hemodialysis, nocturnal hypoxemia, ultrafiltration, water-electrolyte balanceOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-06-05June 05, 201510.2215/CJN.087609141555-90411555-905X2015-04-10T10:00:21-07:002015-06-05Clinical Journal of the American Society of NephrologyOriginal Articles10610021010
- Maintaining Safety in the Dialysis FacilityErrors in dialysis care can cause harm and death. While dialysis machines are rarely a major cause of morbidity, human factors at the machine interface and suboptimal communication among caregivers are common sources of error. Major causes of potentially reversible adverse outcomes include medication errors, infections, hyperkalemia, access-related errors, and patient falls. Root cause analysis of adverse events and "near misses" can illuminate care processes and show system changes to improve safety. Human factors engineering and simulation exercises have strong potential to define common clinical team purpose, and improve processes of care. Patient observations and their participation in error reduction increase the effectiveness of patient safety efforts.10.2215/CJN.08960914Thu, 06 Nov 2014 06:42:34 GMT-08:00Maintaining Safety in the Dialysis FacilityErrors in dialysis care can cause harm and death. While dialysis machines are rarely a major cause of morbidity, human factors at the machine interface and suboptimal communication among caregivers are common sources of error. Major causes of potentially reversible adverse outcomes include medication errors, infections, hyperkalemia, access-related errors, and patient falls. Root cause analysis of adverse events and "near misses" can illuminate care processes and show system changes to improve safety. Human factors engineering and simulation exercises have strong potential to define common clinical team purpose, and improve processes of care. Patient observations and their participation in error reduction increase the effectiveness of patient safety efforts.Kliger, Alan S.2014-11-06T06:42:34-08:00doi:10.2215/CJN.08960914hwp:resource-id:clinjasn;10/4/688American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, patient safety, medication errorsRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-04-07April 07, 201510.2215/CJN.089609141555-90411555-905X2014-11-06T06:42:34-08:002015-04-07Clinical Journal of the American Society of NephrologyRole of the Medical Director104688695
- The Medical Director and Quality Requirements in the Dialysis FacilityFour decades after the successful implementation of the ESRD program currently providing life-saving dialysis therapy to >430,000 patients, the definitions of and demands for a high-quality program have evolved and increased at the same time. Through substantial technological advances ESRD care improved, with a predominant focus on the technical aspects of care and the introduction of medications such as erythropoiesis-stimulating agents and active vitamin D for anemia and bone disease management. Despite many advances, the size of the program and the increasingly older and multimorbid patient population have contributed to continuing challenges for providing consistently high-quality care. Medicare's Final Rule of the Conditions for Coverage (April 2008) define the medical director of the dialysis center as the leader of the interdisciplinary team and the person ultimately accountable for quality, safety, and care provided in the center. Knowledge and active leadership with a hands-on approach in the quality assessment and performance improvement process (QAPI) is essential for the achievement of high-quality outcomes in dialysis centers. A collaborative approach between the dialysis provider and medical director is required to optimize outcomes and deliver evidence-based quality care. In 2011 the Centers for Medicare & Medicaid Services introduced a pay-for-performance program—the ESRD quality incentive program (QIP)— with yearly varying quality metrics that result in payment reductions in subsequent years when targets are not achieved during the performance period. Success with the QIP requires a clear understanding of the structure, metrics, and scoring methods. Information on achievement and nonachievement is publicly available, both in facilities (through the facility performance score card) and on public websites (including Medicare’s Dialysis Facility Compare). By assuming the leadership role in the quality program of dialysis facilities, the medical director is given an important opportunity to improve patients’ lives and effect true change in a patient population dealing with a very challenging chronic disease. This article in the series on the role of the medical director summarizes the medical director’s specific role in the quality improvement process in the dialysis facility and the associated requirements and programs, including QAPI and QIP.10.2215/CJN.05810614Thu, 06 Nov 2014 06:42:32 GMT-08:00The Medical Director and Quality Requirements in the Dialysis FacilityFour decades after the successful implementation of the ESRD program currently providing life-saving dialysis therapy to >430,000 patients, the definitions of and demands for a high-quality program have evolved and increased at the same time. Through substantial technological advances ESRD care improved, with a predominant focus on the technical aspects of care and the introduction of medications such as erythropoiesis-stimulating agents and active vitamin D for anemia and bone disease management. Despite many advances, the size of the program and the increasingly older and multimorbid patient population have contributed to continuing challenges for providing consistently high-quality care. Medicare's Final Rule of the Conditions for Coverage (April 2008) define the medical director of the dialysis center as the leader of the interdisciplinary team and the person ultimately accountable for quality, safety, and care provided in the center. Knowledge and active leadership with a hands-on approach in the quality assessment and performance improvement process (QAPI) is essential for the achievement of high-quality outcomes in dialysis centers. A collaborative approach between the dialysis provider and medical director is required to optimize outcomes and deliver evidence-based quality care. In 2011 the Centers for Medicare & Medicaid Services introduced a pay-for-performance program—the ESRD quality incentive program (QIP)— with yearly varying quality metrics that result in payment reductions in subsequent years when targets are not achieved during the performance period. Success with the QIP requires a clear understanding of the structure, metrics, and scoring methods. Information on achievement and nonachievement is publicly available, both in facilities (through the facility performance score card) and on public websites (including Medicare’s Dialysis Facility Compare). By assuming the leadership role in the quality program of dialysis facilities, the medical director is given an important opportunity to improve patients’ lives and effect true change in a patient population dealing with a very challenging chronic disease. This article in the series on the role of the medical director summarizes the medical director’s specific role in the quality improvement process in the dialysis facility and the associated requirements and programs, including QAPI and QIP.Schiller, Brigitte2014-11-06T06:42:32-08:00doi:10.2215/CJN.05810614hwp:resource-id:clinjasn;10/3/493American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, quality improvement, Medical Director, QIP, QAPIRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-03-06March 06, 201510.2215/CJN.058106141555-90411555-905X2014-11-06T06:42:32-08:002015-03-06Clinical Journal of the American Society of NephrologyRole of the Medical Director103493499
- Disparities in Electronic Health Record Patient Portal Use in Nephrology Clinics10.2215/CJN.01640215Thu, 22 Oct 2015 07:05:21 GMT-07:00Disparities in Electronic Health Record Patient Portal Use in Nephrology ClinicsJhamb, ManishaCavanaugh, Kerri L.Bian, AihuaChen, GuanhuaIkizler, T. AlpUnruh, Mark L.Abdel-Kader, Khaled2015-10-22T07:05:21-07:00doi:10.2215/CJN.01640215hwp:resource-id:clinjasn;10/11/2013American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhealthcare disparities, personalized health record, chronic kidney disease, electronic health record, patient portalOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20152015-11-06November 06, 201510.2215/CJN.016402151555-90411555-905X2015-10-22T07:05:21-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles1011112013189720221899
- Introduction: Role of the Medical Director Series10.2215/CJN.11811214Mon, 12 Jan 2015 06:54:16 GMT-08:00Introduction: Role of the Medical Director SeriesProvenzano, RobertHymes, Jeffrey L.2015-01-12T06:54:16-08:00doi:10.2215/CJN.11811214hwp:resource-id:clinjasn;10/2/325American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, dialysis, chronic dialysisRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-02-06February 06, 201510.2215/CJN.118112141555-90411555-905X2015-01-12T06:54:16-08:002015-02-06Clinical Journal of the American Society of NephrologyRole of the Medical Director102325325
- The Evolving Role of the Medical Director of a Dialysis FacilityThe medical director has been a part of the fabric of Medicare’s ESRD program since entitlement was extended under Section 299I of Public Law 92-603, passed on October 30, 1972, and implemented with the Conditions for Coverage that set out rules for administration and oversight of the care provided in the dialysis facility. The role of the medical director has progressively increased over time to effectively extend to the physicians serving in this role both the responsibility and accountability for the performance and reliability related to the care provided in the dialysis facility. This commentary provides context to the nature and expected competencies and behaviors of these medical director roles that remain central to the delivery of high-quality, safe, and efficient delivery of RRT, which has become much more intensive as the dialysis industry has matured.10.2215/CJN.04920514Thu, 02 Oct 2014 12:56:17 GMT-07:00The Evolving Role of the Medical Director of a Dialysis FacilityThe medical director has been a part of the fabric of Medicare’s ESRD program since entitlement was extended under Section 299I of Public Law 92-603, passed on October 30, 1972, and implemented with the Conditions for Coverage that set out rules for administration and oversight of the care provided in the dialysis facility. The role of the medical director has progressively increased over time to effectively extend to the physicians serving in this role both the responsibility and accountability for the performance and reliability related to the care provided in the dialysis facility. This commentary provides context to the nature and expected competencies and behaviors of these medical director roles that remain central to the delivery of high-quality, safe, and efficient delivery of RRT, which has become much more intensive as the dialysis industry has matured.Maddux, Franklin W.Nissenson, Allen R.2014-10-02T12:56:17-07:00doi:10.2215/CJN.04920514hwp:resource-id:clinjasn;10/2/326American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, chronic dialysis, nephrologyRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-02-06February 06, 201510.2215/CJN.049205141555-90411555-905X2014-10-02T12:56:17-07:002015-02-06Clinical Journal of the American Society of NephrologyRole of the Medical Director102326330
- Leukocyte Cell–Derived Chemotaxin 2–Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic CharacteristicsAmyloidosis derived from leukocyte cell–derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell–derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell–derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell–derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis as Ig light chain–derived amyloidosis to avoid harmful chemotherapy.10.2215/CJN.12551214Tue, 14 Apr 2015 10:56:29 GMT-07:00Leukocyte Cell–Derived Chemotaxin 2–Associated Amyloidosis: A Recently Recognized Disease with Distinct Clinicopathologic CharacteristicsAmyloidosis derived from leukocyte cell–derived chemotaxin 2 is a recently recognized form of amyloidosis, and it has already been established as a frequent form of systemic amyloidosis in the United States, with predominant involvement of kidney and liver. The disease has a strong ethnic bias, affecting mainly Hispanics (particularly Mexicans). Additional ethnic groups prone to develop amyloidosis derived from leukocyte cell–derived chemotaxin 2 include Punjabis, First Nations people in British Columbia, and Native Americans. Most patients are elderly who present with chronic renal insufficiency and bland urinary sediment. Proteinuria is variable, being absent altogether in about one third of patients. Liver involvement is frequently an incidental finding. Amyloidosis derived from leukocyte cell–derived chemotaxin 2 deposits shows a characteristic distribution: in the kidney, there is consistent involvement of cortical interstitium, whereas in the liver, there is a preferential involvement of periportal and pericentral vein regions. Concurrent renal disease is frequent, with diabetic nephropathy and IgA nephropathy being the most common. Patient survival is excellent, likely because of the rarity of cardiac involvement, whereas renal survival is guarded, with a median renal survival of 62 months in those without concurrent renal disease. There is currently no efficacious therapy for amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis. Renal transplantation seems to be a reasonable treatment for patients with advanced renal failure, although the disease may recur in the allograft. The pathogenesis of amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis has not yet been elucidated. It could be a result of leukocyte cell–derived chemotaxin 2 overexpression by hepatocytes either constitutively (controlled by yet-uncharacterized genetic defects) or secondary to hepatocellular damage. It is critical not to misdiagnose amyloidosis derived from leukocyte cell–derived chemotaxin 2 amyloidosis as Ig light chain–derived amyloidosis to avoid harmful chemotherapy.Nasr, Samih H.Dogan, AhmetLarsen, Christopher P.2015-04-14T10:56:29-07:00doi:10.2215/CJN.12551214hwp:resource-id:clinjasn;10/11/2084American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyleukocyte cell–derived chemotaxin 2, kidney biopsy, renal amyloidosis, liver amyloidosis, ALECT2 amyloidosisMini-ReviewMini-Reviewreview-article20152015-11-06November 06, 201510.2215/CJN.125512141555-90411555-905X2015-04-14T10:56:29-07:002015-11-06Clinical Journal of the American Society of NephrologyMini-Review101120842093
- Medical Director Responsibilities to the ESRD NetworkThe 18 regional ESRD Networks are established in legislation and contract with the Centers for Medicare and Medicaid Services to improve the quality and safety of dialysis, maximize patient rehabilitation, encourage collaboration among and between providers toward common quality goals, and improve the reliability and the use of data in pursuit of quality improvement. The Networks are funded by a $0.50 per treatment fee deducted from the reimbursement to dialysis providers, and their deliverables are determined by a statement of work, which is updated in a new contract every 3 years. The Conditions for Coverage require dialysis providers to participate in Network activities, and failure to do so can be the basis for sanctions against the provider. However, the Networks attempt to foster a collegial relationship with dialysis facilities by offering tools, educational activities, and other resources to assist the facilities in meeting the evolving requirements by the Centers for Medicare and Medicaid Services on the basis of national aims and domains for quality improvement in health care that transcend the ESRD program. Because of his/her responsibility for implementing the quality assessment and performance improvement activities in the facility, the medical director has much to gain by actively participating in Network activities, especially those focused on quality, safety, patient grievance, patient engagement, and coordination of care. Membership on Network committees can also foster the professional growth of the medical director through participation in quality improvement activity development and implementation, authorship of articles in peer-reviewed journals, creation of educational tools and presentations, and application of Network-sponsored materials to improve patient outcomes, engagement, and satisfaction in the medical director’s facility. The improvement of care of patients on dialysis will be beneficial to the facility in achieving its goals of quality, safety, and financial viability.10.2215/CJN.05350514Thu, 25 Sep 2014 04:42:28 GMT-07:00Medical Director Responsibilities to the ESRD NetworkThe 18 regional ESRD Networks are established in legislation and contract with the Centers for Medicare and Medicaid Services to improve the quality and safety of dialysis, maximize patient rehabilitation, encourage collaboration among and between providers toward common quality goals, and improve the reliability and the use of data in pursuit of quality improvement. The Networks are funded by a $0.50 per treatment fee deducted from the reimbursement to dialysis providers, and their deliverables are determined by a statement of work, which is updated in a new contract every 3 years. The Conditions for Coverage require dialysis providers to participate in Network activities, and failure to do so can be the basis for sanctions against the provider. However, the Networks attempt to foster a collegial relationship with dialysis facilities by offering tools, educational activities, and other resources to assist the facilities in meeting the evolving requirements by the Centers for Medicare and Medicaid Services on the basis of national aims and domains for quality improvement in health care that transcend the ESRD program. Because of his/her responsibility for implementing the quality assessment and performance improvement activities in the facility, the medical director has much to gain by actively participating in Network activities, especially those focused on quality, safety, patient grievance, patient engagement, and coordination of care. Membership on Network committees can also foster the professional growth of the medical director through participation in quality improvement activity development and implementation, authorship of articles in peer-reviewed journals, creation of educational tools and presentations, and application of Network-sponsored materials to improve patient outcomes, engagement, and satisfaction in the medical director’s facility. The improvement of care of patients on dialysis will be beneficial to the facility in achieving its goals of quality, safety, and financial viability.DeOreo, Peter B.Wish, Jay B.2014-09-25T04:42:28-07:00doi:10.2215/CJN.05350514hwp:resource-id:clinjasn;10/10/1852American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, chronic dialysis, outcomesRole of the Medical DirectorRole of the Medical Directorresearch-article20152015-10-07October 07, 201510.2215/CJN.053505141555-90411555-905X2014-09-25T04:42:28-07:002015-10-07Clinical Journal of the American Society of NephrologyRole of the Medical Director101018521858
- Developing Risk Prediction Models for Kidney Injury and Assessing Incremental Value for Novel BiomarkersThe field of nephrology is actively involved in developing biomarkers and improving models for predicting patients’ risks of AKI and CKD and their outcomes. However, some important aspects of evaluating biomarkers and risk models are not widely appreciated, and statistical methods are still evolving. This review describes some of the most important statistical concepts for this area of research and identifies common pitfalls. Particular attention is paid to metrics proposed within the last 5 years for quantifying the incremental predictive value of a new biomarker.10.2215/CJN.10351013Thu, 22 May 2014 09:35:47 GMT-07:00Developing Risk Prediction Models for Kidney Injury and Assessing Incremental Value for Novel BiomarkersThe field of nephrology is actively involved in developing biomarkers and improving models for predicting patients’ risks of AKI and CKD and their outcomes. However, some important aspects of evaluating biomarkers and risk models are not widely appreciated, and statistical methods are still evolving. This review describes some of the most important statistical concepts for this area of research and identifies common pitfalls. Particular attention is paid to metrics proposed within the last 5 years for quantifying the incremental predictive value of a new biomarker.Kerr, Kathleen F.Meisner, AllisonThiessen-Philbrook, HeatherCoca, Steven G.Parikh, Chirag R.2014-05-22T09:35:47-07:00doi:10.2215/CJN.10351013hwp:resource-id:clinjasn;9/8/1488American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybiomarkers, risk prediction, kidney injury, net reclassification improvement, AUCMini-ReviewMini-Reviewreview-article20142014-08-07August 07, 201410.2215/CJN.103510131555-90411555-905X2014-05-22T09:35:47-07:002014-08-07Clinical Journal of the American Society of NephrologyMini-Review9814881496
- Vascular Effects of Exercise Training in CKD: Current Evidence and Pathophysiological MechanismsCardiovascular disease remains the main cause of morbidity and mortality in patients with CKD, an observation that cannot be explained by the coexistence of traditional risk factors alone. Recently, other mechanisms, such as alterations in nitric oxide bioavailability, impaired endothelial repair mechanisms, inflammation, and oxidative stress (all characteristic in CKD), have gained much attention as mediators for the increased cardiovascular risk. Regular physical training is a valuable nonpharmacological intervention for primary and secondary prevention of cardiovascular disease. Likewise, the benefits of exercise training on exercise capacity and quality of life are increasingly recognized in patients with CKD. Furthermore, exercise training could also influence potential reversible mechanisms involved in atherosclerosis and arteriosclerosis. After discussing briefly the general concepts of vascular disease in CKD, this review provides an overview of the current evidence for the effects of exercise training at both clinical and preclinical levels. It concludes with some practical considerations on exercise training in this specific patient group.10.2215/CJN.13031213Thu, 15 May 2014 08:29:57 GMT-07:00Vascular Effects of Exercise Training in CKD: Current Evidence and Pathophysiological MechanismsCardiovascular disease remains the main cause of morbidity and mortality in patients with CKD, an observation that cannot be explained by the coexistence of traditional risk factors alone. Recently, other mechanisms, such as alterations in nitric oxide bioavailability, impaired endothelial repair mechanisms, inflammation, and oxidative stress (all characteristic in CKD), have gained much attention as mediators for the increased cardiovascular risk. Regular physical training is a valuable nonpharmacological intervention for primary and secondary prevention of cardiovascular disease. Likewise, the benefits of exercise training on exercise capacity and quality of life are increasingly recognized in patients with CKD. Furthermore, exercise training could also influence potential reversible mechanisms involved in atherosclerosis and arteriosclerosis. After discussing briefly the general concepts of vascular disease in CKD, this review provides an overview of the current evidence for the effects of exercise training at both clinical and preclinical levels. It concludes with some practical considerations on exercise training in this specific patient group.Van Craenenbroeck, Amaryllis H.Van Craenenbroeck, Emeline M.Kouidi, EvangeliaVrints, Christiaan J.Couttenye, Marie M.Conraads, Viviane M.2014-05-15T08:29:57-07:00doi:10.2215/CJN.13031213hwp:resource-id:clinjasn;9/7/1305American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal physiology, glomerulus, glomerular filtrationMini-ReviewMini-Reviewreview-article20142014-07-07July 07, 201410.2215/CJN.130312131555-90411555-905X2014-05-15T08:29:57-07:002014-07-07Clinical Journal of the American Society of NephrologyMini-Review9713051318
- Which Patients Benefit from Initiation of Dialysis for AKI?10.2215/CJN.01730214Thu, 20 Mar 2014 11:56:15 GMT-07:00Which Patients Benefit from Initiation of Dialysis for AKI?Pannu, Neesh2014-03-20T11:56:15-07:00doi:10.2215/CJN.01730214hwp:resource-id:clinjasn;9/4/635American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of NephrologyARF, dialysis, epidemiology, outcomesEditorialsEditorialseditorial20142014-04-07April 07, 201410.2215/CJN.017302141555-90411555-905X2014-03-20T11:56:15-07:002014-04-07Clinical Journal of the American Society of NephrologyEditorials944635673637681
- Propagating the Nephrology Research Workforce: A Kidney Research National Dialogue Training CommentaryThe National Institute of Diabetes and Digestive and Kidney Diseases conducted the Kidney Research National Dialogue as an interactive means to formulate and prioritize research goals necessary to address the needs of patients with renal disease. This commentary summarizes the discussion and priorities arising from the training domain of the dialogue and posits three overall strategies to broaden the nephrology research workforce pipeline. The community needs to recruit and provide support for mentors in nephrology, target medical and graduate students earlier in their education for exposure to renal research, and expand the research workforce to include basic scientists from many disciplines as well as under-represented minorities.10.2215/CJN.01070114Thu, 13 Mar 2014 09:35:09 GMT-07:00Propagating the Nephrology Research Workforce: A Kidney Research National Dialogue Training CommentaryThe National Institute of Diabetes and Digestive and Kidney Diseases conducted the Kidney Research National Dialogue as an interactive means to formulate and prioritize research goals necessary to address the needs of patients with renal disease. This commentary summarizes the discussion and priorities arising from the training domain of the dialogue and posits three overall strategies to broaden the nephrology research workforce pipeline. The community needs to recruit and provide support for mentors in nephrology, target medical and graduate students earlier in their education for exposure to renal research, and expand the research workforce to include basic scientists from many disciplines as well as under-represented minorities.Kohan, Donald E.Parker, Mark G.Furth, Susan L.Hudson, Billy G.Warburton, Karen M.Rys-Sikora, Krystyna E.Rankin, Tracy L.2014-03-13T09:35:09-07:00doi:10.2215/CJN.01070114hwp:resource-id:clinjasn;9/6/1144American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, workforce, education, diversity, career choiceSpecial FeaturesSpecial Featuresresearch-article20142014-06-06June 06, 201410.2215/CJN.010701141555-90411555-905X2014-03-13T09:35:09-07:002014-06-06Clinical Journal of the American Society of NephrologySpecial Features9611441147
- Improving Outcomes for ESRD Patients: Shifting the Quality ParadigmThe availability of life-saving dialysis therapy has been one of the great successes of medicine in the past four decades. Over this time period, despite treatment of hundreds of thousands of patients, the overall quality of life for patients with ESRD has not substantially improved. A narrow focus by clinicians and regulators on basic indicators of care, like dialysis adequacy and anemia, has consumed time and resources but not resulted in significantly improved survival; also, frequent hospitalizations and dissatisfaction with the care experience continue to be seen. A new quality paradigm is needed to help guide clinicians, providers, and regulators to ensure that patients’ lives are improved by the technically complex and costly therapy that they are receiving. This paradigm can be envisioned as a quality pyramid: the foundation is the basic indicators (outstanding performance on these indicators is necessary but not sufficient to drive the primary outcomes). Overall, these basics are being well managed currently, but there remains an excessive focus on them, largely because of publically reported data and regulatory requirements. With a strong foundation, it is now time to focus on the more complex intermediate clinical outcomes—fluid management, infection control, diabetes management, medication management, and end-of-life care among others. Successfully addressing these intermediate outcomes will drive improvements in the primary outcomes, better survival, fewer hospitalizations, better patient experience with the treatment, and ultimately, improved quality of life. By articulating this view of quality in the ESRD program (pushing up the quality pyramid), the discussion about quality is reframed, and also, clinicians can better target their facilities in the direction of regulatory oversight and requirements about quality. Clinicians owe it to their patients, as the ESRD program celebrates its 40th anniversary, to rekindle the aspirations of the creators of the program, whose primary goal was to improve the lives of the patients afflicted with this devastating condition.10.2215/CJN.05980613Thu, 07 Nov 2013 03:34:02 GMT-08:00Improving Outcomes for ESRD Patients: Shifting the Quality ParadigmThe availability of life-saving dialysis therapy has been one of the great successes of medicine in the past four decades. Over this time period, despite treatment of hundreds of thousands of patients, the overall quality of life for patients with ESRD has not substantially improved. A narrow focus by clinicians and regulators on basic indicators of care, like dialysis adequacy and anemia, has consumed time and resources but not resulted in significantly improved survival; also, frequent hospitalizations and dissatisfaction with the care experience continue to be seen. A new quality paradigm is needed to help guide clinicians, providers, and regulators to ensure that patients’ lives are improved by the technically complex and costly therapy that they are receiving. This paradigm can be envisioned as a quality pyramid: the foundation is the basic indicators (outstanding performance on these indicators is necessary but not sufficient to drive the primary outcomes). Overall, these basics are being well managed currently, but there remains an excessive focus on them, largely because of publically reported data and regulatory requirements. With a strong foundation, it is now time to focus on the more complex intermediate clinical outcomes—fluid management, infection control, diabetes management, medication management, and end-of-life care among others. Successfully addressing these intermediate outcomes will drive improvements in the primary outcomes, better survival, fewer hospitalizations, better patient experience with the treatment, and ultimately, improved quality of life. By articulating this view of quality in the ESRD program (pushing up the quality pyramid), the discussion about quality is reframed, and also, clinicians can better target their facilities in the direction of regulatory oversight and requirements about quality. Clinicians owe it to their patients, as the ESRD program celebrates its 40th anniversary, to rekindle the aspirations of the creators of the program, whose primary goal was to improve the lives of the patients afflicted with this devastating condition.Nissenson, Allen R.2013-11-07T15:34:02-08:00doi:10.2215/CJN.05980613hwp:resource-id:clinjasn;9/2/430American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPublic Policy SeriesPublic Policy Seriesresearch-article20142014-02-07February 07, 201410.2215/CJN.059806131555-90411555-905X2013-11-07T15:34:02-08:002014-02-07Clinical Journal of the American Society of NephrologyPublic Policy Series92430434
- Use of Desmopressin Acetate in Severe Hyponatremia in the Intensive Care Unit10.2215/CJN.00950113Thu, 21 Nov 2013 12:17:41 GMT-08:00Use of Desmopressin Acetate in Severe Hyponatremia in the Intensive Care UnitRafat, CédricSchortgen, FrédériqueGaudry, StéphaneBertrand, FabriceMiguel-Montanes, RomainLabbé, VincentRicard, Jean-DamienHajage, DavidDreyfuss, Didier2013-11-21T12:17:41-08:00doi:10.2215/CJN.00950113hwp:resource-id:clinjasn;9/2/229American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20142014-02-07February 07, 201410.2215/CJN.009501131555-90411555-905X2013-11-21T12:17:41-08:002014-02-07Clinical Journal of the American Society of NephrologyOriginal Articles92229237
- Intradialytic Hypotension and Risk of Cardiovascular Disease10.2215/CJN.02680314Thu, 06 Nov 2014 06:42:34 GMT-08:00Intradialytic Hypotension and Risk of Cardiovascular DiseaseStefánsson, Bergur V.Brunelli, Steven M.Cabrera, ClaudiaRosenbaum, DavidAnum, EmmanuelRamakrishnan, KarthikJensen, Donna E.Stålhammar, Nils-Olov2014-11-06T06:42:34-08:00doi:10.2215/CJN.02680314hwp:resource-id:clinjasn;9/12/2124American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, hemodialysis, ESRD, hypotensionOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20142014-12-05December 05, 201410.2215/CJN.026803141555-90411555-905X2014-11-06T06:42:34-08:002014-12-05Clinical Journal of the American Society of NephrologyOriginal Articles912122124203321322035
- Fluid Management: The Challenge of Defining Standards of Care10.2215/CJN.10341014Thu, 06 Nov 2014 06:42:34 GMT-08:00Fluid Management: The Challenge of Defining Standards of CareFlythe, Jennifer E.Brookhart, M. Alan2014-11-06T06:42:34-08:00doi:10.2215/CJN.10341014hwp:resource-id:clinjasn;9/12/2033American Society of NephrologyCopyright © 2014 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBP, hemodialysis, cardiovascular, epidemiology, outcomesEditorialsEditorialseditorial20142014-12-05December 05, 201410.2215/CJN.103410141555-90411555-905X2014-11-06T06:42:34-08:002014-12-05Clinical Journal of the American Society of NephrologyEditorials912122033212420352132
- Association of Left Ventricular Longitudinal Strain with Mortality among Stable Hemodialysis Patients with Preserved Left Ventricular Ejection Fraction10.2215/CJN.10671012Thu, 23 May 2013 06:39:38 GMT-07:00Association of Left Ventricular Longitudinal Strain with Mortality among Stable Hemodialysis Patients with Preserved Left Ventricular Ejection FractionLiu, Yen-WenSu, Chi-TingSung, Junne-MingWang, Saprina P.H.Su, Yu-RuYang, Chun-ShinTsai, Liang-MiinChen, Jyh-HongTsai, Wei-Chuan2013-05-23T06:39:38-07:00doi:10.2215/CJN.10671012hwp:resource-id:clinjasn;8/9/1564American Society of NephrologyCopyright © 2013 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20132013-09-06September 06, 201310.2215/CJN.106710121555-90411555-905X2013-05-23T06:39:38-07:002013-09-06Clinical Journal of the American Society of NephrologyOriginal Articles8915641574
- Time to Improve Fluid Management in Hemodialysis: Should We Abandon Clinical Assessment and Routinely Use Bioimpedance?10.2215/CJN.06930613Thu, 15 Aug 2013 07:48:54 GMT-07:00Time to Improve Fluid Management in Hemodialysis: Should We Abandon Clinical Assessment and Routinely Use Bioimpedance?Covic, AdrianOnofriescu, Mihai2013-08-15T07:48:54-07:00doi:10.2215/CJN.06930613hwp:resource-id:clinjasn;8/9/1474American Society of NephrologyCopyright © 2013 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEditorialsEditorialseditorial20132013-09-06September 06, 201310.2215/CJN.069306131555-90411555-905X2013-08-15T07:48:54-07:002013-09-06Clinical Journal of the American Society of NephrologyEditorials8991474157514751582
- Bioimpedance-Guided Fluid Management in Hemodialysis Patients10.2215/CJN.12411212Thu, 15 Aug 2013 07:48:55 GMT-07:00Bioimpedance-Guided Fluid Management in Hemodialysis PatientsMoissl, UlrichArias-Guillén, MartaWabel, PeterFontseré, NéstorCarrera, MontserratCampistol, José MariaMaduell, Francisco2013-08-15T07:48:55-07:00doi:10.2215/CJN.12411212hwp:resource-id:clinjasn;8/9/1575American Society of NephrologyCopyright © 2013 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20132013-09-06September 06, 201310.2215/CJN.124112121555-90411555-905X2013-08-15T07:48:55-07:002013-09-06Clinical Journal of the American Society of NephrologyOriginal Articles8991575147415821475
- Type 2 Translational Research for CKDStrategies to effectively treat people with CKD have been identified by conventional clinical research. Despite this evidence, awareness, screening, detection, diagnosis, risk factor control, treatment, and outcomes remain substandard. Translating clinical evidence into actionable measures that reduce the burden of CKD is a pressing need. Expansion from a “bench-to-bedside” paradigm (conventional type 1 translation) to research that encompasses “clinic and community” is the core concept of type 2 translation. Specifically, this is the discipline of identifying factors and using strategies that lead to adoption, maintenance, and sustainability of science-based interventions in practice. This review identifies key elements of type 2 translational research and highlights the current scope of this type of research for CKD. For type 2 translation to achieve the goals of providing high-quality care and better health outcomes, key facilitators (e.g., theory-based frameworks, adaptable interventions, and inclusion of sustainability and evaluation metrics) and essential elements (e.g., multidisciplinary team care, health information technology, and stakeholder engagement) must be integrated. The National Institute of Diabetes and Digestive and Kidney Diseases recently funded five proposals that aim to improve outcomes for people with CKD, focusing on diverse components of the healthcare continuum: patient safety and transitions; delivery of high-quality, evidence-based CKD care; and elimination of disparities. The need for type 2 translational research in CKD is urgent because of preventable human suffering and unsustainable costs of providing care. Focus on the theory, framework, and approaches we have suggested may help us meet that challenge.10.2215/CJN.00130113Thu, 25 Apr 2013 08:56:42 GMT-07:00Type 2 Translational Research for CKDStrategies to effectively treat people with CKD have been identified by conventional clinical research. Despite this evidence, awareness, screening, detection, diagnosis, risk factor control, treatment, and outcomes remain substandard. Translating clinical evidence into actionable measures that reduce the burden of CKD is a pressing need. Expansion from a “bench-to-bedside” paradigm (conventional type 1 translation) to research that encompasses “clinic and community” is the core concept of type 2 translation. Specifically, this is the discipline of identifying factors and using strategies that lead to adoption, maintenance, and sustainability of science-based interventions in practice. This review identifies key elements of type 2 translational research and highlights the current scope of this type of research for CKD. For type 2 translation to achieve the goals of providing high-quality care and better health outcomes, key facilitators (e.g., theory-based frameworks, adaptable interventions, and inclusion of sustainability and evaluation metrics) and essential elements (e.g., multidisciplinary team care, health information technology, and stakeholder engagement) must be integrated. The National Institute of Diabetes and Digestive and Kidney Diseases recently funded five proposals that aim to improve outcomes for people with CKD, focusing on diverse components of the healthcare continuum: patient safety and transitions; delivery of high-quality, evidence-based CKD care; and elimination of disparities. The need for type 2 translational research in CKD is urgent because of preventable human suffering and unsustainable costs of providing care. Focus on the theory, framework, and approaches we have suggested may help us meet that challenge.Tuttle, Katherine R.Tuot, Delphine S.Corbett, Cynthia L.Setter, Stephen M.Powe, Neil R.2013-04-25T08:56:42-07:00doi:10.2215/CJN.00130113hwp:resource-id:clinjasn;8/10/1829American Society of NephrologyCopyright © 2013 by the American Society of NephrologyClinical Journal of the American Society of NephrologySpecial FeatureSpecial Featureresearch-article20132013-10-07October 07, 201310.2215/CJN.001301131555-90411555-905X2013-04-25T08:56:42-07:002013-10-07Clinical Journal of the American Society of NephrologySpecial Feature81018291838
- Antiplatelet Therapy in the Management of Cardiovascular Disease in Patients with CKD: What Is the Evidence?Antiplatelet agents (APAs) are proven to reduce risk of major cardiovascular events in patients with cardiovascular disease and normal kidney function. With recent post hoc analyses of large trials questioning the safety and efficacy of APAs in CKD, major gaps exist in our understanding of platelet aggregability and the effects of APAs on thrombosis and bleeding in CKD. Clinical practice guidelines are ambiguous about use of such agents in CKD patients, because patients with moderate to advanced CKD were systematically excluded from clinical trials of APAs. CKD patients experience excessive rates of cardiovascular thrombotic events, yet paradoxically are at higher risk for major bleeding while receiving APAs. Furthermore, observational studies suggest that CKD patients may exhibit poor response to APAs. High residual platelet aggregability, as determined by inhibition of platelet aggregation, is associated with increased risk for cardiovascular events. In addition, metabolism of certain APAs may be altered in CKD patients. It is, therefore, imperative to explore the mechanisms responsible for poor response to APAs in CKD patients in order to use these drugs more safely and effectively. This review identifies the knowledge gaps and future trials needed to address those issues with the use of APAs in CKD patients.10.2215/CJN.06790712Thu, 27 Sep 2012 12:51:56 GMT-07:00Antiplatelet Therapy in the Management of Cardiovascular Disease in Patients with CKD: What Is the Evidence?Antiplatelet agents (APAs) are proven to reduce risk of major cardiovascular events in patients with cardiovascular disease and normal kidney function. With recent post hoc analyses of large trials questioning the safety and efficacy of APAs in CKD, major gaps exist in our understanding of platelet aggregability and the effects of APAs on thrombosis and bleeding in CKD. Clinical practice guidelines are ambiguous about use of such agents in CKD patients, because patients with moderate to advanced CKD were systematically excluded from clinical trials of APAs. CKD patients experience excessive rates of cardiovascular thrombotic events, yet paradoxically are at higher risk for major bleeding while receiving APAs. Furthermore, observational studies suggest that CKD patients may exhibit poor response to APAs. High residual platelet aggregability, as determined by inhibition of platelet aggregation, is associated with increased risk for cardiovascular events. In addition, metabolism of certain APAs may be altered in CKD patients. It is, therefore, imperative to explore the mechanisms responsible for poor response to APAs in CKD patients in order to use these drugs more safely and effectively. This review identifies the knowledge gaps and future trials needed to address those issues with the use of APAs in CKD patients.Jain, NishankHedayati, S. SusanSarode, RavindraBanerjee, SubhashReilly, Robert F.2012-09-27T12:51:56-07:00doi:10.2215/CJN.06790712hwp:resource-id:clinjasn;8/4/665American Society of NephrologyCopyright © 2013 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20132013-04-05April 05, 201310.2215/CJN.067907121555-90411555-905X2012-09-27T12:51:56-07:002013-04-05Clinical Journal of the American Society of NephrologyMini-Review84665674
- Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development.10.2215/CJN.03490413Thu, 29 Aug 2013 12:30:42 GMT-07:00Novel Paradigms for Dialysis Vascular Access: Downstream Vascular Biology–Is There a Final Common Pathway?Vascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development.Lee, Timmy2013-08-29T12:30:42-07:00doi:10.2215/CJN.03490413hwp:resource-id:clinjasn;8/12/2194American Society of NephrologyCopyright © 2013 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMoving Points in NephrologyMoving Points in Nephrologyresearch-article20132013-12-06December 06, 201310.2215/CJN.034904131555-90411555-905X2013-08-29T12:30:42-07:002013-12-06Clinical Journal of the American Society of NephrologyMoving Points in Nephrology81221942201
- Ongoing Clinical Trials in AKIAKI is an important public health issue. AKI is a common hospital complication associated with increased in-hospital and long-term mortality, extensive morbidity (including prolonged hospital length of stay), and an estimated annual cost of at least $10 billion in the United States. At present, no specific therapy has been developed to prevent AKI, hasten recovery of kidney function, or abrogate the deleterious systemic effects of AKI. However, recent progress includes establishing a consensus definition of AKI and discovery of novel biomarkers that may allow early detection of AKI. Furthermore, significant insights into the pathophysiology of AKI and its deleterious systemic effects have been gleaned from animal studies. Urgently needed are large, definitive randomized clinical trials testing interventions to prevent and/or treat AKI. This review summarizes and analyzes current ongoing clinical trials registered with clinicaltrials.gov that address prevention or management of AKI. The purpose of this review is to provide a resource for people interested in potential prophylactic and therapeutic approaches to patient care and investigators hoping to plan and execute the next round of randomized clinical trials. Finally, this review discusses research needs that are not addressed by the current clinical trials portfolio and suggests key areas for future research in AKI.10.2215/CJN.12191111Thu, 22 Mar 2012 06:16:04 GMT-07:00Ongoing Clinical Trials in AKIAKI is an important public health issue. AKI is a common hospital complication associated with increased in-hospital and long-term mortality, extensive morbidity (including prolonged hospital length of stay), and an estimated annual cost of at least $10 billion in the United States. At present, no specific therapy has been developed to prevent AKI, hasten recovery of kidney function, or abrogate the deleterious systemic effects of AKI. However, recent progress includes establishing a consensus definition of AKI and discovery of novel biomarkers that may allow early detection of AKI. Furthermore, significant insights into the pathophysiology of AKI and its deleterious systemic effects have been gleaned from animal studies. Urgently needed are large, definitive randomized clinical trials testing interventions to prevent and/or treat AKI. This review summarizes and analyzes current ongoing clinical trials registered with clinicaltrials.gov that address prevention or management of AKI. The purpose of this review is to provide a resource for people interested in potential prophylactic and therapeutic approaches to patient care and investigators hoping to plan and execute the next round of randomized clinical trials. Finally, this review discusses research needs that are not addressed by the current clinical trials portfolio and suggests key areas for future research in AKI.Faubel, SarahChawla, Lakhmir S.Chertow, Glenn M.Goldstein, Stuart L.Jaber, Bertrand L.Liu, Kathleen D.,2012-03-22T06:16:04-07:00doi:10.2215/CJN.12191111hwp:resource-id:clinjasn;7/5/861American Society of NephrologyCopyright © 2012 by the American Society of NephrologyClinical Journal of the American Society of NephrologySpecial FeaturesSpecial Featuresresearch-article20122012-05-01May 07, 201210.2215/CJN.121911111555-90411555-905X2012-03-22T06:16:04-07:002012-05Clinical Journal of the American Society of NephrologySpecial Features75861873
- Design of Clinical Trials in Acute Kidney Injury: Report from an NIDDK Workshop on Trial MethodologyAcute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients’ health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled “Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers” in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.10.2215/CJN.12791211Thu, 22 Mar 2012 06:16:03 GMT-07:00Design of Clinical Trials in Acute Kidney Injury: Report from an NIDDK Workshop on Trial MethodologyAcute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients’ health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled “Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers” in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.Palevsky, Paul M.Molitoris, Bruce A.Okusa, Mark D.Levin, AdeeraWaikar, Sushrut S.Wald, RonChertow, Glenn M.Murray, Patrick T.Parikh, Chirag R.Shaw, Andrew D.Go, Alan S.Faubel, Sarah G.Kellum, John A.Chinchilli, Vernon M.Liu, Kathleen D.Cheung, Alfred K.Weisbord, Steven D.Chawla, Lakhmir S.Kaufman, James S.Devarajan, PrasadToto, Robert M.Hsu, Chi-yuanGreene, TomMehta, Ravindra L.Stokes, John B.Thompson, Aliza M.Thompson, B. TaylorWestenfelder, Christof S.Tumlin, James A.Warnock, David G.Shah, Sudhir V.Xie, YiningDuggan, Emily G.Kimmel, Paul L.Star, Robert A.2012-03-22T06:16:03-07:00doi:10.2215/CJN.12791211hwp:resource-id:clinjasn;7/5/844American Society of NephrologyCopyright © 2012 by the American Society of NephrologyClinical Journal of the American Society of NephrologySpecial FeaturesSpecial Featuresresearch-article20122012-05-01May 07, 201210.2215/CJN.127912111555-90411555-905X2012-03-22T06:16:03-07:002012-05Clinical Journal of the American Society of NephrologySpecial Features75844850
- Obstetric Nephrology: Pregnancy in Women with Diabetic Nephropathy—The Role of Antihypertensive TreatmentThis review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.10.2215/CJN.00920112Thu, 23 Aug 2012 10:13:11 GMT-07:00Obstetric Nephrology: Pregnancy in Women with Diabetic Nephropathy—The Role of Antihypertensive TreatmentThis review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.Mathiesen, Elisabeth R.Ringholm, LeneFeldt-Rasmussen, BoClausen, PeterDamm, Peter2012-08-23T10:13:11-07:00doi:10.2215/CJN.00920112hwp:resource-id:clinjasn;7/12/2081American Society of NephrologyCopyright © 2012 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMoving Points in NephrologyMoving Points in Nephrologyresearch-article20122012-12-01December 07, 201210.2215/CJN.009201121555-90411555-905X2012-08-23T10:13:11-07:002012-12Clinical Journal of the American Society of NephrologyMoving Points in Nephrology71220812088
- Obstetric Nephrology: AKI and Thrombotic Microangiopathies in PregnancyAKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).10.2215/CJN.13121211Thu, 09 Aug 2012 06:07:33 GMT-07:00Obstetric Nephrology: AKI and Thrombotic Microangiopathies in PregnancyAKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab).Fakhouri, FadiVercel, CarolineFrémeaux-Bacchi, Véronique2012-08-09T06:07:33-07:00doi:10.2215/CJN.13121211hwp:resource-id:clinjasn;7/12/2100American Society of NephrologyCopyright © 2012 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMoving Points in NephrologyMoving Points in Nephrologyresearch-article20122012-12-01December 07, 201210.2215/CJN.131212111555-90411555-905X2012-08-09T06:07:33-07:002012-12Clinical Journal of the American Society of NephrologyMoving Points in Nephrology71221002106
- Early Start of Dialysis: A Critical Review10.2215/CJN.09301010Mon, 09 May 2011 09:47:43 GMT-07:00Early Start of Dialysis: A Critical ReviewRosansky, StevenGlassock, Richard J.Clark, William F.2011-05-09T09:47:43-07:00doi:10.2215/CJN.09301010hwp:resource-id:clinjasn;6/5/1222American Society of NephrologyCopyright © 2011 by the American Society of NephrologyClinical Journal of the American Society of NephrologySpecial FeatureSpecial Featureresearch-article20112011-05-0110.2215/CJN.093010101555-90411555-905X2011-05-09T09:47:43-07:002011-05Clinical Journal of the American Society of NephrologySpecial Feature6512221228
- Prevention and Control of Phosphate Retention/Hyperphosphatemia in CKD-MBD: What Is Normal, When to Start, and How to Treat?Phosphate retention and, later, hyperphosphatemia are key contributors to chronic kidney disease (CKD)–mineral and bone disorder (MBD). Phosphate homeostatic mechanisms maintain normal phosphorus levels until late-stage CKD, because of early increases in parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23). Increased serum phosphorus, and these other mineral abnormalities, individually and collectively contribute to bone disease, vascular calcification, and cardiovascular disease. Earlier phosphate control may, therefore, help reduce the early clinical consequences of CKD-MBD, and help control hyperphosphatemia and secondary hyperparathyroidism in late-stage CKD. Indeed, it is now widely accepted that achieving normal phosphorus levels is associated with distinct clinical benefits. This therapeutic goal is achievable in CKD stages 3 to 5 but more difficult in dialysis patients. Currently, phosphate control is only initiated when hyperphosphatemia occurs, but a potentially beneficial and simple approach may be to intervene earlier, for example, when tubular phosphate reabsorption is substantially diminished. Early CKD-MBD management includes dietary phosphate restriction, phosphate binder therapy, and vitamin D supplementation. Directly treating phosphorus may be the most beneficial approach because this can reduce serum phosphorus, PTH, and FGF-23. This involves dietary measures, but these are not always sufficient, and it can be more effective to also consider phosphate binder use. Vitamin D sterols can improve vitamin D deficiency and PTH levels but may worsen phosphate retention and increase FGF-23 levels, and thus, may also require concomitant phosphate binder therapy. This article discusses when and how to optimize phosphate control to provide the best clinical outcomes in CKD-MBD patients.10.2215/CJN.05130610Thu, 03 Feb 2011 07:44:55 GMT-08:00Prevention and Control of Phosphate Retention/Hyperphosphatemia in CKD-MBD: What Is Normal, When to Start, and How to Treat?Phosphate retention and, later, hyperphosphatemia are key contributors to chronic kidney disease (CKD)–mineral and bone disorder (MBD). Phosphate homeostatic mechanisms maintain normal phosphorus levels until late-stage CKD, because of early increases in parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23). Increased serum phosphorus, and these other mineral abnormalities, individually and collectively contribute to bone disease, vascular calcification, and cardiovascular disease. Earlier phosphate control may, therefore, help reduce the early clinical consequences of CKD-MBD, and help control hyperphosphatemia and secondary hyperparathyroidism in late-stage CKD. Indeed, it is now widely accepted that achieving normal phosphorus levels is associated with distinct clinical benefits. This therapeutic goal is achievable in CKD stages 3 to 5 but more difficult in dialysis patients. Currently, phosphate control is only initiated when hyperphosphatemia occurs, but a potentially beneficial and simple approach may be to intervene earlier, for example, when tubular phosphate reabsorption is substantially diminished. Early CKD-MBD management includes dietary phosphate restriction, phosphate binder therapy, and vitamin D supplementation. Directly treating phosphorus may be the most beneficial approach because this can reduce serum phosphorus, PTH, and FGF-23. This involves dietary measures, but these are not always sufficient, and it can be more effective to also consider phosphate binder use. Vitamin D sterols can improve vitamin D deficiency and PTH levels but may worsen phosphate retention and increase FGF-23 levels, and thus, may also require concomitant phosphate binder therapy. This article discusses when and how to optimize phosphate control to provide the best clinical outcomes in CKD-MBD patients.Martin, Kevin J.González, Esther A.2011-02-03T07:44:55-08:00doi:10.2215/CJN.05130610hwp:resource-id:clinjasn;6/2/440American Society of NephrologyCopyright © 2011 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20112011-02-0110.2215/CJN.051306101555-90411555-905X2011-02-03T07:44:55-08:002011-02Clinical Journal of the American Society of NephrologyMini-Review62440446
- Hemodialysis Treatment Time: A Fresh Perspective10.2215/CJN.00970211Thu, 01 Sep 2011 11:25:15 GMT-07:00Hemodialysis Treatment Time: A Fresh PerspectiveLacson, EduardoBrunelli, Steven M.2011-09-01T11:25:15-07:00doi:10.2215/CJN.00970211hwp:resource-id:clinjasn;6/10/2522American Society of NephrologyCopyright © 2011 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCommentaryCommentaryarticle-commentary20112011-10-0110.2215/CJN.009702111555-90411555-905X2011-09-01T11:25:15-07:002011-10Clinical Journal of the American Society of NephrologyCommentary61025222530
- Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental GlomerulosclerosisCirculating permeability factors may be important in idiopathic nephrotic syndrome (INS) including focal segmental glomerulosclerosis (FSGS) and in recurrence after renal transplantation. Evidence for plasma factors includes posttransplant recurrence of proteinuria and its response to plasmapheresis or immunoadsorption and induction of proteinuria in experimental animals by infusion of patient plasma or its fractions. The authors and other investigators have used proteomic techniques to seek pathogenic molecules. The authors have recently proposed cardiotrophin-like cytokine-1 (CLC-1) as an active factor in FSGS. Other potential permeability factors include hemopexin and vascular permeability factor in minimal change nephrotic syndrome (MCNS) and soluble urokinase receptor in FSGS. In the authors' studies, in vitro plasma permeability activity is blocked by diverse substances that may decrease levels of active molecules or block the effects of circulating permeability factors. It has been shown that the simple sugar galactose blocks the effect of FSGS serum on albumin permeability in vitro and decreases permeability activity when administered to patients. Because identities of permeability factors and their mechanisms of action are not well defined, therapy of INS/FSGS is empiric. Corticosteroids are the mainstay of initial therapy whereas calcineurin inhibitors such as cyclosporine A (CsA) and immunosuppressive medications provide adjunctive therapy. Nonspecific therapies such as blocking the renin-angiotensin system and controlling blood pressure and plasma lipids may also diminish proteinuria and slow progression. Identification of molecules that initiate proteinuria and application of findings from in vitro studies may lead to development of new treatments to arrest progression and prevent recurrence after transplantation.10.2215/CJN.03800609Thu, 21 Oct 2010 08:49:13 GMT-07:00Circulating Permeability Factors in Idiopathic Nephrotic Syndrome and Focal Segmental GlomerulosclerosisCirculating permeability factors may be important in idiopathic nephrotic syndrome (INS) including focal segmental glomerulosclerosis (FSGS) and in recurrence after renal transplantation. Evidence for plasma factors includes posttransplant recurrence of proteinuria and its response to plasmapheresis or immunoadsorption and induction of proteinuria in experimental animals by infusion of patient plasma or its fractions. The authors and other investigators have used proteomic techniques to seek pathogenic molecules. The authors have recently proposed cardiotrophin-like cytokine-1 (CLC-1) as an active factor in FSGS. Other potential permeability factors include hemopexin and vascular permeability factor in minimal change nephrotic syndrome (MCNS) and soluble urokinase receptor in FSGS. In the authors' studies, in vitro plasma permeability activity is blocked by diverse substances that may decrease levels of active molecules or block the effects of circulating permeability factors. It has been shown that the simple sugar galactose blocks the effect of FSGS serum on albumin permeability in vitro and decreases permeability activity when administered to patients. Because identities of permeability factors and their mechanisms of action are not well defined, therapy of INS/FSGS is empiric. Corticosteroids are the mainstay of initial therapy whereas calcineurin inhibitors such as cyclosporine A (CsA) and immunosuppressive medications provide adjunctive therapy. Nonspecific therapies such as blocking the renin-angiotensin system and controlling blood pressure and plasma lipids may also diminish proteinuria and slow progression. Identification of molecules that initiate proteinuria and application of findings from in vitro studies may lead to development of new treatments to arrest progression and prevent recurrence after transplantation.McCarthy, Ellen T.Sharma, MukutSavin, Virginia J.2010-10-21T08:49:13-07:00doi:10.2215/CJN.03800609hwp:resource-id:clinjasn;5/11/2115American Society of NephrologyCopyright © 2010 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20102010-11-0110.2215/CJN.038006091555-90411555-905X2010-10-21T08:49:13-07:002010-11Clinical Journal of the American Society of NephrologyMini-Review51121152121
- The Spectrum of MYH9-Associated NephropathyCauses of the excess incidence rates of chronic kidney disease in the African American population have long been under study. Recently, polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) have been associated with nondiabetic kidney diseases in African- and European-derived populations. Risk variants in MYH9 contribute to approximately 70% of nondiabetic forms of ESRD in African Americans and 40 to 45% of all ESRD in this ethnic group, with lesser effects in European Americans. It is clear that MYH9 polymorphisms have a significant impact on the incidence rates of kidney disease in African Americans. This article describes the current spectrum of biopsy-proven MYH9-associated kidney diseases, along with potential effects of MYH9 on ethnic differences in clinical outcome. MYH9 risk variants exhibit the most impressive association with any common complex kidney disease yet identified.10.2215/CJN.08721209Thu, 18 Mar 2010 08:28:00 GMT-07:00The Spectrum of MYH9-Associated NephropathyCauses of the excess incidence rates of chronic kidney disease in the African American population have long been under study. Recently, polymorphisms in the nonmuscle myosin heavy chain 9 gene (MYH9) have been associated with nondiabetic kidney diseases in African- and European-derived populations. Risk variants in MYH9 contribute to approximately 70% of nondiabetic forms of ESRD in African Americans and 40 to 45% of all ESRD in this ethnic group, with lesser effects in European Americans. It is clear that MYH9 polymorphisms have a significant impact on the incidence rates of kidney disease in African Americans. This article describes the current spectrum of biopsy-proven MYH9-associated kidney diseases, along with potential effects of MYH9 on ethnic differences in clinical outcome. MYH9 risk variants exhibit the most impressive association with any common complex kidney disease yet identified.Bostrom, Meredith A.Freedman, Barry I.2010-03-18T08:28:00-07:00doi:10.2215/CJN.08721209hwp:resource-id:clinjasn;5/6/1107American Society of NephrologyCopyright © 2010 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20102010-06-0110.2215/CJN.087212091555-90411555-905X2010-03-18T08:28:00-07:002010-06Clinical Journal of the American Society of NephrologyMini-Review5611071113
- Control of Secondary Hyperparathyroidism by Vitamin D Receptor Agonists in Chronic Kidney DiseaseEffective treatment options for managing secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) have advanced steadily since the early 1980s, from surgical removal of the parathyroid gland to pharmacologic intervention focused on reestablishing hormonal and mineral balances. In addition, earlier recognition of CKD via estimated GFR and educational efforts have led to advancements in diagnosis and treatment of elevated parathyroid hormone (PTH) and vitamin D deficiency. Clinical studies support the efficacy and safety of vitamin D receptor (VDR) agonists as effective treatments for SHPT. A number of considerations to ensure optimal SHPT control in CKD patients are apparent. VDR agonists effectively treat SHPT and vitamin D deficiency, but dosing needs to be optimized for each patient because the patient responds in an individualized manner to treatment to suppress and stabilize PTH levels. VDR agonist therapy should be continuous to ensure continued PTH suppression, coupled with strict monitoring of calcium and phosphorus to ensure compliance within target ranges. Awareness of the complex and beneficial effects of VDR agonists contributes to improved benefits in bone mineral disease and lower mortality risks.10.2215/CJN.03850609Thu, 04 Feb 2010 09:20:21 GMT-08:00Control of Secondary Hyperparathyroidism by Vitamin D Receptor Agonists in Chronic Kidney DiseaseEffective treatment options for managing secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) have advanced steadily since the early 1980s, from surgical removal of the parathyroid gland to pharmacologic intervention focused on reestablishing hormonal and mineral balances. In addition, earlier recognition of CKD via estimated GFR and educational efforts have led to advancements in diagnosis and treatment of elevated parathyroid hormone (PTH) and vitamin D deficiency. Clinical studies support the efficacy and safety of vitamin D receptor (VDR) agonists as effective treatments for SHPT. A number of considerations to ensure optimal SHPT control in CKD patients are apparent. VDR agonists effectively treat SHPT and vitamin D deficiency, but dosing needs to be optimized for each patient because the patient responds in an individualized manner to treatment to suppress and stabilize PTH levels. VDR agonist therapy should be continuous to ensure continued PTH suppression, coupled with strict monitoring of calcium and phosphorus to ensure compliance within target ranges. Awareness of the complex and beneficial effects of VDR agonists contributes to improved benefits in bone mineral disease and lower mortality risks.Sprague, Stuart M.Coyne, Daniel2010-02-04T09:20:21-08:00doi:10.2215/CJN.03850609hwp:resource-id:clinjasn;5/3/512American Society of NephrologyCopyright © 2010 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20102010-03-0110.2215/CJN.038506091555-90411555-905X2010-02-04T09:20:21-08:002010-03Clinical Journal of the American Society of NephrologyMini-Review53512518
- Hepcidin for CliniciansDespite the use of erythropoiesis-stimulating agents (ESAs), the anemia of chronic kidney disease (CKD) can be resistant to therapy. Both absolute and functional iron deficiency along with inflammation can contribute to ESA resistance and can be difficult to identify with current-day markers of iron storage. Hepcidin, a small peptide produced by the liver, is a recently discovered key regulator of iron homeostasis. Via regulation of ferroportin, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. Because of its renal elimination and regulation by inflammation, it is possible that progressive renal insufficiency leads to altered hepcidin metabolism, subsequently affecting enteric absorption of iron and the availability of iron stores. Thus, hepcidin likely plays a major role in the anemia of CKD as well as ESA resistance. This article discusses the biologic actions and regulation of hepcidin along with reviewing studies of hepcidin in CKD.10.2215/CJN.02190309Thu, 25 Jun 2009 08:16:47 GMT-07:00Hepcidin for CliniciansDespite the use of erythropoiesis-stimulating agents (ESAs), the anemia of chronic kidney disease (CKD) can be resistant to therapy. Both absolute and functional iron deficiency along with inflammation can contribute to ESA resistance and can be difficult to identify with current-day markers of iron storage. Hepcidin, a small peptide produced by the liver, is a recently discovered key regulator of iron homeostasis. Via regulation of ferroportin, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. Because of its renal elimination and regulation by inflammation, it is possible that progressive renal insufficiency leads to altered hepcidin metabolism, subsequently affecting enteric absorption of iron and the availability of iron stores. Thus, hepcidin likely plays a major role in the anemia of CKD as well as ESA resistance. This article discusses the biologic actions and regulation of hepcidin along with reviewing studies of hepcidin in CKD.Young, BrianZaritsky, Joshua2009-06-25T08:16:47-07:00doi:10.2215/CJN.02190309hwp:resource-id:clinjasn;4/8/1384American Society of NephrologyCopyright © 2009 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewreview-article20092009-08-0110.2215/CJN.021903091555-90411555-905X2009-06-25T08:16:47-07:002009-08Clinical Journal of the American Society of NephrologyMini-Review4813841387
- Phosphate Levels and Cardiovascular Disease in the General PopulationPhosphate levels are consistently linked with cardiac calcification, cardiovascular disease (CVD), and death in populations with chronic kidney disease. In addition, mechanistic insights suggest that phosphate levels that span the conventional normal range could lead to CVD. Examining these associations in the general population may be relevant because several interventions that may be suitable for primary or secondary prevention trials already exist. This review summarizes findings described from several community-based, prospective, observational studies. Graded associations with cardiac calcification, left ventricular hypertrophy, cardiovascular events, and death were evident, and cardiovascular risk seemed to accelerate with phosphate >3.5 to 4.0 mg/dl. Although the cause of these associations remains to be determined, several existing interventions may allow in-depth examination of the hypothesis that reducing phosphate levels could prevent CVD in the general population. Even as proof-of-concept trials and mechanistic studies are awaited, phosphate levels may be useful for cardiovascular risk stratification in adults without overt kidney disease.10.2215/CJN.01660309Thu, 07 May 2009 08:21:41 GMT-07:00Phosphate Levels and Cardiovascular Disease in the General PopulationPhosphate levels are consistently linked with cardiac calcification, cardiovascular disease (CVD), and death in populations with chronic kidney disease. In addition, mechanistic insights suggest that phosphate levels that span the conventional normal range could lead to CVD. Examining these associations in the general population may be relevant because several interventions that may be suitable for primary or secondary prevention trials already exist. This review summarizes findings described from several community-based, prospective, observational studies. Graded associations with cardiac calcification, left ventricular hypertrophy, cardiovascular events, and death were evident, and cardiovascular risk seemed to accelerate with phosphate >3.5 to 4.0 mg/dl. Although the cause of these associations remains to be determined, several existing interventions may allow in-depth examination of the hypothesis that reducing phosphate levels could prevent CVD in the general population. Even as proof-of-concept trials and mechanistic studies are awaited, phosphate levels may be useful for cardiovascular risk stratification in adults without overt kidney disease.Foley, Robert N.2009-05-07T08:21:41-07:00doi:10.2215/CJN.01660309hwp:resource-id:clinjasn;4/6/1136American Society of NephrologyCopyright © 2009 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewother20092009-06-01June 200910.2215/CJN.016603091555-90411555-905X2009-05-07T08:21:41-07:002009-06Clinical Journal of the American Society of NephrologyMini-Review4611361139
- Impact of Renal Failure on the Outcome of Dengue Viral InfectionBackground and objectives: In the 2002 dengue outbreak in Taiwan, some fatal cases had the underlying disease of renal failure (RF). Physicians faced difficulty in diagnosis and treatment of these patients; however, the impacts of RF on the clinical presentations and outcomes of dengue infection have not been reported previously. Design, setting, participants, & measurements: A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared. Results: From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group. Conclusions: The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.10.2215/CJN.00020108Wed, 30 Jul 2008 11:41:41 GMT-07:00Impact of Renal Failure on the Outcome of Dengue Viral InfectionBackground and objectives: In the 2002 dengue outbreak in Taiwan, some fatal cases had the underlying disease of renal failure (RF). Physicians faced difficulty in diagnosis and treatment of these patients; however, the impacts of RF on the clinical presentations and outcomes of dengue infection have not been reported previously. Design, setting, participants, & measurements: A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared. Results: From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group. Conclusions: The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.Kuo, Mei-ChuanLu, Po-LiangChang, Jer-MingLin, Ming-YenTsai, Jih-JinChen, Yen-HsuChang, KoChen, Hung-ChunHwang, Shang-Jyh2008-07-30T11:41:41-07:00doi:10.2215/CJN.00020108hwp:resource-id:clinjasn;3/5/1350American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyClinical NephrologyClinical Nephrologyresearch-article20082008-09-01September 200810.2215/CJN.000201081555-90411555-905X2008-07-30T11:41:41-07:002008-09Clinical Journal of the American Society of NephrologyClinical Nephrology3513501356
- Interpreting Results of Clinical Trials: A Conceptual Framework10.2215/CJN.03580807Tue, 26 Aug 2008 10:01:51 GMT-07:00Interpreting Results of Clinical Trials: A Conceptual FrameworkSingh, Ajay K.Kelley, KenAgarwal, Rajiv2008-08-26T10:01:51-07:00doi:10.2215/CJN.03580807hwp:resource-id:clinjasn;3/5/1246American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEditorialsEditorialseditorial20082008-09-01September 200810.2215/CJN.035808071555-90411555-905X2008-08-26T10:01:51-07:002008-09Clinical Journal of the American Society of NephrologyEditorials3512461252
- Utility and Limitations of a Multicenter Nocturnal Home Hemodialysis CohortNocturnal home hemodialysis (NHD) is the most intensive dialysis strategy among dialytic renal replacement options and is receiving increased attention as more research reveals its physiologic restorative potential compared with conventional hemodialysis; however, a significant gap in knowledge remains concerning the predictors of program success and the clinical outcomes of NHD. This review aims to highlight the methodologic strengths and pitfalls of various study designs as they pertain to NHD research and lays the foundation for the CANandian Slow Long nightly ExtEnded dialysis Programs (CAN-SLEEP), a multicenter NHD research network aimed to facilitate investigation of NHD.10.2215/CJN.00890208Wed, 01 Oct 2008 11:43:18 GMT-07:00Utility and Limitations of a Multicenter Nocturnal Home Hemodialysis CohortNocturnal home hemodialysis (NHD) is the most intensive dialysis strategy among dialytic renal replacement options and is receiving increased attention as more research reveals its physiologic restorative potential compared with conventional hemodialysis; however, a significant gap in knowledge remains concerning the predictors of program success and the clinical outcomes of NHD. This review aims to highlight the methodologic strengths and pitfalls of various study designs as they pertain to NHD research and lays the foundation for the CANandian Slow Long nightly ExtEnded dialysis Programs (CAN-SLEEP), a multicenter NHD research network aimed to facilitate investigation of NHD.Pauly, Robert P.Copland, MichaelKomenda, PaulLevin, AdeeraPierratos, AndreasChan, Christopher T.2008-10-01T11:43:18-07:00doi:10.2215/CJN.00890208hwp:resource-id:clinjasn;3/6/1846American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMini-ReviewMini-Reviewother20082008-11-01November 200810.2215/CJN.008902081555-90411555-905X2008-10-01T11:43:18-07:002008-11Clinical Journal of the American Society of NephrologyMini-Review3618461851
- Commentary on Risks of Living Kidney Donation10.2215/CJN.01650219Mon, 11 Mar 2019 07:56:01 GMT-07:00Commentary on Risks of Living Kidney DonationKestenbaum, Bryan R.Seliger, Stephen L.2019-03-11T07:56:01-07:00doi:10.2215/CJN.01650219hwp:resource-id:clinjasn;14/4/609American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and outcomes, kidney transplantation, Tissue Donors, kidney, Tissue and Organ HarvestingCommentaryCommentaryarticle-commentary20192019-04-05April 05, 201910.2215/CJN.016502191555-90411555-905X2019-03-11T07:56:01-07:002019-04-05Clinical Journal of the American Society of NephrologyCommentary1444609597610608
- Correction10.2215/CJN.01680219Mon, 18 Mar 2019 09:56:34 GMT-07:00CorrectionAmerican Society of Nephrology2019-03-18T09:56:34-07:00doi:10.2215/CJN.01680219hwp:resource-id:clinjasn;14/4/586American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCorrection, erratumErratumErratumcorrection20192019-04-05April 05, 201910.2215/CJN.016802191555-90411555-905X2019-03-18T09:56:34-07:002019-04-05Clinical Journal of the American Society of NephrologyErratum1441158619965862005
- Dynamics of Organic Anion Transporter-Mediated Tubular Secretion during Postnatal Human Kidney Development and Maturation10.2215/CJN.10350818Mon, 18 Mar 2019 09:56:34 GMT-07:00Dynamics of Organic Anion Transporter-Mediated Tubular Secretion during Postnatal Human Kidney Development and MaturationMomper, Jeremiah D.Yang, JinGockenbach, MaryVaida, FlorinNigam, Sanjay K.2019-03-18T09:56:34-07:00doi:10.2215/CJN.10350818hwp:resource-id:clinjasn;14/4/540American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, drug transporter, kidney development, pediatric nephrology, tubular secretion, Infant, Newborn, Adolescent, Renal Plasma Flow, Effective, Organic Anion Transporters, glomerular filtration rate, diuretics, Anti-Bacterial Agents, Antiviral Agents, Anti-Inflammatory Agents, Non-Steroidal, Vulnerable Populations, Kidney Tubules, Proximal, kidney, Cephapirin, Hippurates, Drug-Related Side Effects and Adverse Reactions, AnionsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20192019-04-05April 05, 201910.2215/CJN.103508181555-90411555-905X2019-03-18T09:56:34-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles144540548
- Complex Decision Making about Dialysis in Critically Ill Older Adults with AKI10.2215/CJN.01870219Thu, 21 Mar 2019 08:05:29 GMT-07:00Complex Decision Making about Dialysis in Critically Ill Older Adults with AKIButler, Catherine R.O’Hare, Ann M.2019-03-21T08:05:29-07:00doi:10.2215/CJN.01870219hwp:resource-id:clinjasn;14/4/485American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyintensive care unit, shared decision making, Critical Illness, renal dialysis, Acute Kidney Injury, Decision MakingEditorialsEditorialseditorial20192019-04-05April 05, 201910.2215/CJN.018702191555-90411555-905X2019-03-21T08:05:29-07:002019-04-05Clinical Journal of the American Society of NephrologyEditorials1444485496487505
- Prediction Models for AKI10.2215/CJN.02250219Wed, 27 Mar 2019 07:03:06 GMT-07:00Prediction Models for AKIKwong, Yuenting DianaLiu, Kathleen D.2019-03-27T07:03:06-07:00doi:10.2215/CJN.02250219hwp:resource-id:clinjasn;14/4/488American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, risk factorsEditorialsEditorialseditorial20192019-04-05April 05, 201910.2215/CJN.022502191555-90411555-905X2019-03-27T07:03:06-07:002019-04-05Clinical Journal of the American Society of NephrologyEditorials1444488506490514
- Patient Perspective of Smartphone-Based Apps for CKD Self-Care10.2215/CJN.02220219Thu, 21 Mar 2019 08:05:30 GMT-07:00Patient Perspective of Smartphone-Based Apps for CKD Self-CareRogers, Dale2019-03-21T08:05:30-07:00doi:10.2215/CJN.02220219hwp:resource-id:clinjasn;14/4/483American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologySmartphone, Self Care, Renal Insufficiency, ChronicPatient VoicePatient Voiceeditorial20192019-04-05April 05, 201910.2215/CJN.022202191555-90411555-905X2019-03-21T08:05:30-07:002019-04-05Clinical Journal of the American Society of NephrologyPatient Voice14444483491523484492529
- Risks of Living Kidney DonationIn the past decade, there have been increasing efforts to better define and quantify the short- and long-term risks of living kidney donation. Recent studies have expanded upon the previous literature by focusing on outcomes that are important to potential and previous donors, applying unique databases and/or registries to follow large cohorts of donors for longer periods of time, and comparing outcomes with healthy nondonor controls to estimate attributable risks of donation. Leading outcomes important to living kidney donors include kidney health, surgical risks, and psychosocial effects of donation. Recent data support that living donors may experience a small increased risk of severe CKD and ESKD compared with healthy nondonors. For most donors, the 15-year risk of kidney failure is <1%, but for certain populations, such as young, black men, this risk may be higher. New risk prediction tools that combine the effects of demographic and health factors, and innovations in genetic risk markers are improving kidney risk stratification. Minor perioperative complications occur in 10%–20% of donor nephrectomy cases, but major complications occur in <3%, and the risk of perioperative death is <0.03%. Generally, living kidney donors have similar or improved psychosocial outcomes, such as quality of life, after donation compared with before donation and compared with nondonors. Although the donation process should be financially neutral, living kidney donors may experience out-of-pocket expenses and lost wages that may or may not be completely covered through regional or national reimbursement programs, and may face difficulties arranging subsequent life and health insurance. Living kidney donors should be fully informed of the perioperative and long-term risks before making their decision to donate. Follow-up care allows for preventative care measures to mitigate risk and ongoing surveillance and reporting of donor outcomes to inform prior and future living kidney donors.10.2215/CJN.11220918Mon, 11 Mar 2019 07:56:01 GMT-07:00Risks of Living Kidney DonationIn the past decade, there have been increasing efforts to better define and quantify the short- and long-term risks of living kidney donation. Recent studies have expanded upon the previous literature by focusing on outcomes that are important to potential and previous donors, applying unique databases and/or registries to follow large cohorts of donors for longer periods of time, and comparing outcomes with healthy nondonor controls to estimate attributable risks of donation. Leading outcomes important to living kidney donors include kidney health, surgical risks, and psychosocial effects of donation. Recent data support that living donors may experience a small increased risk of severe CKD and ESKD compared with healthy nondonors. For most donors, the 15-year risk of kidney failure is <1%, but for certain populations, such as young, black men, this risk may be higher. New risk prediction tools that combine the effects of demographic and health factors, and innovations in genetic risk markers are improving kidney risk stratification. Minor perioperative complications occur in 10%–20% of donor nephrectomy cases, but major complications occur in <3%, and the risk of perioperative death is <0.03%. Generally, living kidney donors have similar or improved psychosocial outcomes, such as quality of life, after donation compared with before donation and compared with nondonors. Although the donation process should be financially neutral, living kidney donors may experience out-of-pocket expenses and lost wages that may or may not be completely covered through regional or national reimbursement programs, and may face difficulties arranging subsequent life and health insurance. Living kidney donors should be fully informed of the perioperative and long-term risks before making their decision to donate. Follow-up care allows for preventative care measures to mitigate risk and ongoing surveillance and reporting of donor outcomes to inform prior and future living kidney donors.Lentine, Krista L.Lam, Ngan N.Segev, Dorry L.2019-03-11T07:56:01-07:00doi:10.2215/CJN.11220918hwp:resource-id:clinjasn;14/4/597American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyLiving donation, outcomes, Patient-centered care, Living Donors, Health Expenditures, Aftercare, quality of life, Kidney Failure, Chronic, kidney, Renal Insufficiency, Chronic, Insurance, Health, Registries, Nephrectomy, Salaries and Fringe BenefitsEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20192019-04-05April 05, 201910.2215/CJN.112209181555-90411555-905X2019-03-11T07:56:01-07:002019-04-05Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology1444597609608610
- Recommendations for the Care of Patients Receiving Conservative Kidney ManagementConservative kidney management is increasingly accepted as an appropriate treatment option for patients with eGFR category 5 CKD who are unlikely to benefit from dialysis and/or who choose a nondialysis care option. However, there remains great variation in the delivery of their care. As part of the development of a conservative kidney management pathway that is undergoing evaluation, a set of recommendations specific to conservative kidney management for managing the complications of CKD and common symptoms was developed. These recommendations focus on the patient’s values and preferences and aim to optimize comfort and quality of life. Explanations for the interventions are provided to support the shared decision-making process between health care professionals, patients, and family members. The recommendations generally emphasize the preservation of function (cognitive, physical, and kidney) and address symptom burden, acknowledging that management priorities can change over time. The recommendations should be used in conjunction with other key elements of conservative kidney management, including clear communication and shared decision making for choosing conservative kidney management, advance care planning, and psychosocial support. Although there are limitations to the existing evidence specific to conservative kidney management, these recommendations are intended as a starting point toward reaching consensus and generating further evidence.10.2215/CJN.10510917Thu, 28 Feb 2019 07:48:11 GMT-08:00Recommendations for the Care of Patients Receiving Conservative Kidney ManagementConservative kidney management is increasingly accepted as an appropriate treatment option for patients with eGFR category 5 CKD who are unlikely to benefit from dialysis and/or who choose a nondialysis care option. However, there remains great variation in the delivery of their care. As part of the development of a conservative kidney management pathway that is undergoing evaluation, a set of recommendations specific to conservative kidney management for managing the complications of CKD and common symptoms was developed. These recommendations focus on the patient’s values and preferences and aim to optimize comfort and quality of life. Explanations for the interventions are provided to support the shared decision-making process between health care professionals, patients, and family members. The recommendations generally emphasize the preservation of function (cognitive, physical, and kidney) and address symptom burden, acknowledging that management priorities can change over time. The recommendations should be used in conjunction with other key elements of conservative kidney management, including clear communication and shared decision making for choosing conservative kidney management, advance care planning, and psychosocial support. Although there are limitations to the existing evidence specific to conservative kidney management, these recommendations are intended as a starting point toward reaching consensus and generating further evidence.Davison, Sara N.Tupala, BethWasylynuk, Betty AnnSiu, ValerieSinnarajah, AynharanTriscott, Jean2019-02-28T07:48:11-08:00doi:10.2215/CJN.10510917hwp:resource-id:clinjasn;14/4/626American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdvance Care Planning, chronic kidney disease, Cognition, Consensus, Conservative Kidney Management, Conservative Treatment, Decision Making, end stage kidney disease, glomerular filtration rate, Humans, Palliative Care, quality of life, Recommendations, renal dialysis, Renal Insufficiency, Chronic, SymptomsFeaturesFeaturesresearch-article20192019-04-05April 05, 201910.2215/CJN.105109171555-90411555-905X2019-02-28T07:48:11-08:002019-04-05Clinical Journal of the American Society of NephrologyFeatures144626634
- Estimation of Kidney Function in OncologyEstimation of kidney function in patients with cancer directly affects drug dosing, agent selection, and eligibility for clinical trials of novel agents. Overestimation of kidney function may lead to overdosing or inappropriate agent selection and corresponding toxicity. Conversely, underestimation of kidney function may lead to underdosing or inappropriate agent exclusion and subsequent therapeutic failure. It would seem obvious that the most accurate estimates of kidney function should be used to reduce variability in decision making and ultimately, the therapeutic outcomes of toxicity and clinical benefit. However, clinical decision making is often more complex. The Cockcroft–Gault formula remains the most universally implemented estimator of kidney function in patients with cancer, despite its relative inaccuracy compared with the Chronic Kidney Disease Epidemiology Collaboration equation. The Chronic Kidney Disease Epidemiology Collaboration equation is a more precise estimator of kidney function; however, many currently used kidney function cutoff values were determined before the development of the Chronic Kidney Disease Epidemiology Collaboration equation and creatinine assay standardization using Cockcroft–Gault estimates. There is a need for additional studies investigating the validity of currently used estimates of kidney function in patients with cancer and the applicability of traditional anticancer dosing and eligibility guidelines to modern and more accurate estimates of kidney function. In this review, we consider contemporary calculation methods used to estimate kidney function in patients with cancer. We discuss the clinical implications of using these various methods, including the potential influence on drug dosing, drug selection, and clinical trial eligibility, using carboplatin and cisplatin as case studies.10.2215/CJN.11721018Tue, 19 Mar 2019 06:55:43 GMT-07:00Estimation of Kidney Function in OncologyEstimation of kidney function in patients with cancer directly affects drug dosing, agent selection, and eligibility for clinical trials of novel agents. Overestimation of kidney function may lead to overdosing or inappropriate agent selection and corresponding toxicity. Conversely, underestimation of kidney function may lead to underdosing or inappropriate agent exclusion and subsequent therapeutic failure. It would seem obvious that the most accurate estimates of kidney function should be used to reduce variability in decision making and ultimately, the therapeutic outcomes of toxicity and clinical benefit. However, clinical decision making is often more complex. The Cockcroft–Gault formula remains the most universally implemented estimator of kidney function in patients with cancer, despite its relative inaccuracy compared with the Chronic Kidney Disease Epidemiology Collaboration equation. The Chronic Kidney Disease Epidemiology Collaboration equation is a more precise estimator of kidney function; however, many currently used kidney function cutoff values were determined before the development of the Chronic Kidney Disease Epidemiology Collaboration equation and creatinine assay standardization using Cockcroft–Gault estimates. There is a need for additional studies investigating the validity of currently used estimates of kidney function in patients with cancer and the applicability of traditional anticancer dosing and eligibility guidelines to modern and more accurate estimates of kidney function. In this review, we consider contemporary calculation methods used to estimate kidney function in patients with cancer. We discuss the clinical implications of using these various methods, including the potential influence on drug dosing, drug selection, and clinical trial eligibility, using carboplatin and cisplatin as case studies.Casal, Morgan A.Nolin, Thomas D.Beumer, Jan H.2019-03-19T06:55:43-07:00doi:10.2215/CJN.11721018hwp:resource-id:clinjasn;14/4/587American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, chemotherapy, cisplatin, clinical trial, Cockcroft-Gault, creatinine clearance, creatinine, glomerular filtration rate, kidney dysfunction, pharmacokinetics, renal dysfunctionNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20192019-04-05April 05, 201910.2215/CJN.117210181555-90411555-905X2019-03-19T06:55:43-07:002019-04-05Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician144587595
- A Conceptual Framework of Palliative Care across the Continuum of Advanced Kidney DiseaseKidney palliative care is a growing discipline within nephrology. Kidney palliative care specifically addresses the stress and burden of advanced kidney disease through the provision of expert symptom management, caregiver support, and advance care planning with the goal of optimizing quality of life for patients and families. The integration of palliative care principles is necessary to address the multidimensional impact of advanced kidney disease on patients. In particular, patients with advanced kidney disease have a high symptom burden and experience greater intensity of care at the end of life compared with other chronic serious illnesses. Currently, access to kidney palliative care is lacking, whether delivered by trained kidney care professionals or by palliative care clinicians. These barriers include a gap in training and workforce, policies limiting access to hospice and outpatient palliative care services for patients with ESKD, resistance to integrating palliative care within the nephrology community, and the misconception that palliative care is synonymous with end-of-life care. As such, addressing kidney palliative care needs on a population level will require not only access to specialized kidney palliative care initiatives, but also equipping kidney care professionals with the skills to address basic kidney palliative care needs. This article will address the role of kidney palliative care for patients with advanced kidney disease, describe models of care including primary and specialty kidney palliative care, and outline strategies to improve kidney palliative care on a provider and system level.10.2215/CJN.09330818Wed, 06 Feb 2019 07:08:09 GMT-08:00A Conceptual Framework of Palliative Care across the Continuum of Advanced Kidney DiseaseKidney palliative care is a growing discipline within nephrology. Kidney palliative care specifically addresses the stress and burden of advanced kidney disease through the provision of expert symptom management, caregiver support, and advance care planning with the goal of optimizing quality of life for patients and families. The integration of palliative care principles is necessary to address the multidimensional impact of advanced kidney disease on patients. In particular, patients with advanced kidney disease have a high symptom burden and experience greater intensity of care at the end of life compared with other chronic serious illnesses. Currently, access to kidney palliative care is lacking, whether delivered by trained kidney care professionals or by palliative care clinicians. These barriers include a gap in training and workforce, policies limiting access to hospice and outpatient palliative care services for patients with ESKD, resistance to integrating palliative care within the nephrology community, and the misconception that palliative care is synonymous with end-of-life care. As such, addressing kidney palliative care needs on a population level will require not only access to specialized kidney palliative care initiatives, but also equipping kidney care professionals with the skills to address basic kidney palliative care needs. This article will address the role of kidney palliative care for patients with advanced kidney disease, describe models of care including primary and specialty kidney palliative care, and outline strategies to improve kidney palliative care on a provider and system level.Lam, Daniel Y.Scherer, Jennifer S.Brown, MarkGrubbs, VanessaSchell, Jane O.2019-02-06T07:08:09-08:00doi:10.2215/CJN.09330818hwp:resource-id:clinjasn;14/4/635American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney palliative care, renal supportive care, person-centered care, quality of life, symptom management, palliative care, nephrology, outpatient care, ambulatory careFeaturesFeaturesresearch-article20192019-04-05April 05, 201910.2215/CJN.093308181555-90411555-905X2019-02-06T07:08:09-08:002019-04-05Clinical Journal of the American Society of NephrologyFeatures144635641
- Got CKD? There's an App for That!10.2215/CJN.02350219Thu, 21 Mar 2019 08:05:30 GMT-07:00Got CKD? There's an App for That!Topf, Joel M.Hiremath, Swapnil2019-03-21T08:05:30-07:00doi:10.2215/CJN.02350219hwp:resource-id:clinjasn;14/4/491American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymedical education, mobile app, patient-centered care, chronic kidney diseaseEditorialsEditorialseditorial20192019-04-05April 05, 201910.2215/CJN.023502191555-90411555-905X2019-03-21T08:05:30-07:002019-04-05Clinical Journal of the American Society of NephrologyEditorials14444491483523492484529
- Usability Testing of a Sick-Day Protocol in CKD10.2215/CJN.13221118Wed, 13 Mar 2019 08:02:19 GMT-07:00Usability Testing of a Sick-Day Protocol in CKDDoerfler, Rebecca M.Diamantidis, Clarissa J.Wagner, Lee-AnnScism, Beth M.Vaughn-Cooke, MonifaFink, Wanda J.Blakeman, ThomasFink, Jeffrey C.2019-03-13T08:02:19-07:00doi:10.2215/CJN.13221118hwp:resource-id:clinjasn;14/4/583American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Sick-Day Protocol, self-management, usability testing, acute kidney injury, Sick Leave, User-Computer Interface, Renal Insufficiency, ChronicResearch LetterResearch Letterresearch-article20192019-04-05April 05, 201910.2215/CJN.132211181555-90411555-905X2019-03-13T08:02:19-07:002019-04-05Clinical Journal of the American Society of NephrologyResearch Letter144583585
- Estimated Glomerular Filtration Rate and the Risk of Cancer10.2215/CJN.10820918Thu, 14 Mar 2019 06:59:51 GMT-07:00Estimated Glomerular Filtration Rate and the Risk of CancerXu, HongMatsushita, KunihiroSu, GuobinTrevisan, MarcoÄrnlöv, JohanBarany, PeterLindholm, BengtElinder, Carl-GustafLambe, MatsCarrero, Juan-Jesus2019-03-14T06:59:51-07:00doi:10.2215/CJN.10820918hwp:resource-id:clinjasn;14/4/530American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCancer, chronic kidney disease, estimated glomerular filtration rate, detection bias, reverse causation, Incidence, glomerular filtration rate, Confidence Intervals, International Classification of Diseases, Follow-Up Studies, Renal Insufficiency, Chronic, Risk, Proportional Hazards Models, Urogenital Neoplasms, Bias, Hematologic Neoplasms, Prostatic NeoplasmsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-04-05April 05, 201910.2215/CJN.108209181555-90411555-905X2019-03-14T06:59:51-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles144530539
- Secondhand Smoke and CKD10.2215/CJN.09540818Thu, 07 Mar 2019 07:45:10 GMT-08:00Secondhand Smoke and CKDJhee, Jong HyunJoo, Young SuKee, Youn KyungJung, Su-YoungPark, SeohyunYoon, Chang-YunHan, Seung HyeokYoo, Tae-HyunKang, Shin-WookPark, Jung Tak2019-03-07T07:45:10-08:00doi:10.2215/CJN.09540818hwp:resource-id:clinjasn;14/4/515American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, glomerular filtration rate, risk factors, Tobacco Smoke Pollution, Odds Ratio, Cross-Sectional Studies, Prevalence, Confidence Intervals, Follow-Up Studies, Smokers, Smoking, Risk, Epidemiologic Studies, Renal Insufficiency, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-04-05April 05, 201910.2215/CJN.095408181555-90411555-905X2019-03-07T07:45:10-08:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles144515522
- Rates of Cardiac Rhythm Abnormalities in Patients with CKD and Diabetes10.2215/CJN.09420818Tue, 19 Mar 2019 06:55:45 GMT-07:00Rates of Cardiac Rhythm Abnormalities in Patients with CKD and DiabetesAkoum, NazemZelnick, Leila R.de Boer, Ian H.Hirsch, Irl B.Trence, DaceHenry, ConnorRobinson, NicoleBansal, Nisha2019-03-19T06:55:45-07:00doi:10.2215/CJN.09420818hwp:resource-id:clinjasn;14/4/549American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, electrophysiology, Atrial Fibrillation, glomerular filtration rate, Diabetes Mellitus, Type 2, Ventricular Premature Complexes, Prospective Studies, renal dialysis, Cardiac Conduction System Disease, Renal Insufficiency, Chronic, Heart AtriaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-04-05April 05, 201910.2215/CJN.094208181555-90411555-905X2019-03-19T06:55:45-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles144549556
- Patients’ and Nephrologists’ Evaluation of Patient-Facing Smartphone Apps for CKD10.2215/CJN.10370818Thu, 21 Mar 2019 08:05:30 GMT-07:00Patients’ and Nephrologists’ Evaluation of Patient-Facing Smartphone Apps for CKDSingh, KarandeepDiamantidis, Clarissa J.Ramani, ShreyasBhavsar, Nrupen A.Mara, PeterWarner, JuliaRodriguez, JorgeWang, TianshiWright-Nunes, Julie2019-03-21T08:05:30-07:00doi:10.2215/CJN.10370818hwp:resource-id:clinjasn;14/4/523American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymobile health, chronic kidney disease, end stage kidney disease, Smartphone, Self Care, Methyltestosterone, Malus, kidney transplantation, Patient Participation, blood pressure, dialysis, Mobile Applications, kidney, Renal Insufficiency, Chronic, Chronic Disease, Telemedicine, ExerciseOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-04-05April 05, 201910.2215/CJN.103708181555-90411555-905X2019-03-21T08:05:30-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles14444523483491529484492
- A Prediction Model for Severe AKI in Critically Ill Adults That Incorporates Clinical and Biomarker Data10.2215/CJN.04100318Wed, 27 Mar 2019 07:03:06 GMT-07:00A Prediction Model for Severe AKI in Critically Ill Adults That Incorporates Clinical and Biomarker DataBhatraju, Pavan KumarZelnick, Leila R.Katz, RonitMikacenic, CarmenKosamo, SusannaHahn, William O.Dmyterko, VictoriaKestenbaum, BryanChristiani, David C.Liles, W. ConradHimmelfarb, JonathanWurfel, Mark M.2019-03-27T07:03:06-07:00doi:10.2215/CJN.04100318hwp:resource-id:clinjasn;14/4/506American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinflammation, acute kidney injury, prediction, Critical Illness, Disease Progression, Systemic Inflammatory Response Syndrome, Biomarkers, Liver Cirrhosis, Demography, Intensive Care Units, Receptors, Tumor Necrosis Factor, Cohort StudiesOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20192019-04-05April 05, 201910.2215/CJN.041003181555-90411555-905X2019-03-27T07:03:06-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles1444506488514490
- Selection and Receipt of Kidney Replacement in Critically Ill Older Patients with AKI10.2215/CJN.05530518Thu, 21 Mar 2019 08:05:29 GMT-07:00Selection and Receipt of Kidney Replacement in Critically Ill Older Patients with AKIBagshaw, Sean M.Adhikari, Neill K.J.Burns, Karen E.A.Friedrich, Jan O.Bouchard, JoséeLamontagne, FrancoisMcIntrye, Lauralyn A.Cailhier, Jean-FrançoisDodek, PeterStelfox, Henry T.Herridge, MargaretLapinsky, StephenMuscedere, JohnBarton, JamesGriesdale, DonaldSoth, MarkAmbosta, AltheaLebovic, GeraldWald, Ron,Bagshaw, Sean M.Gibney, R.T. NoelBaig, NadiaAdhikari, Neill K.J.Marinoff, NicolePerez, AdicBurns, KarenFriedrich, JanLee, JuliaLee, YoonSalway, KurtisSandhu, GyanSmith, OrlaWald, RonWang, MelissaBouchard, JoséeDuca, AnatolieLamontagne, FrancoisBérubé, PatrickFournier, HélèneMcIntrye, LauralynWatpool, IrenePorteus, RebeccaGomes, BrigetteCailhier, Jean-FrançoisBenettaib, FatnaDodek, PeterAshley, Betty JeanAlcuaz, VictoriaStelfox, Henry T.Ruddell, StaceyHerridge, MargaretMatte, AndreaLapinsky, StephenShah, SumeshMuscedere, JohnHunt, MirandaGeorgescu, IlincaBarton, JamesPolewicz, DorotaGriesdale, DonaldFoster, DeniseSoth, MarkWachmann, Kristine2019-03-21T08:05:29-07:00doi:10.2215/CJN.05530518hwp:resource-id:clinjasn;14/4/496American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, renal replacement therapy, intensive care unit, mortality, decision-making, Anuria, Critical Illness, Respiration, Artificial, Patient Preference, Prospective Studies, quality of life, Frailty, Kidney Failure, Chronic, Critical Care, Comorbidity, Diagnosis-Related Groups, Survivors, Intensive Care UnitsOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20192019-04-05April 05, 201910.2215/CJN.055305181555-90411555-905X2019-03-21T08:05:29-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles1444496485505487
- Kidney Xenotransplantation10.2215/CJN.12471018Wed, 06 Feb 2019 07:08:08 GMT-08:00Kidney XenotransplantationShaw, Brian I.Kirk, Allan D.2019-02-06T07:08:08-08:00doi:10.2215/CJN.12471018hwp:resource-id:clinjasn;14/4/620American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTransplantation, Heterologous, Heterografts, kidneyPerspectivesPerspectivesresearch-article20192019-04-05April 05, 201910.2215/CJN.124710181555-90411555-905X2019-02-06T07:08:08-08:002019-04-05Clinical Journal of the American Society of NephrologyPerspectives144620622
- Stopping RAS Inhibitors to Minimize AKI10.2215/CJN.14021118Wed, 27 Feb 2019 07:36:18 GMT-08:00Stopping RAS Inhibitors to Minimize AKITomson, CharlesTomlinson, Laurie A.2019-02-27T07:36:18-08:00doi:10.2215/CJN.14021118hwp:resource-id:clinjasn;14/4/617American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAngiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Renin-Angiotensin System, Hypovolemia, Stroke Volume, Acute Kidney Injury, Renal Insufficiency, Chronic, heart failure, Ventricular Dysfunction, Left, PrognosisPerspectivesPerspectivesresearch-article20192019-04-05April 05, 201910.2215/CJN.140211181555-90411555-905X2019-02-27T07:36:18-08:002019-04-05Clinical Journal of the American Society of NephrologyPerspectives144617619
- From Patient-Centered to Person-Centered Care for Kidney Diseases10.2215/CJN.10380818Wed, 27 Feb 2019 07:36:18 GMT-08:00From Patient-Centered to Person-Centered Care for Kidney DiseasesMorton, Rachael L.Sellars, Marcus2019-02-27T07:36:18-08:00doi:10.2215/CJN.10380818hwp:resource-id:clinjasn;14/4/623American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPersons, Patients, Renal Insufficiency, Chronic, dialysis, Kidney Diseases, Patient-Centered CarePerspectivesPerspectivesresearch-article20192019-04-05April 05, 201910.2215/CJN.103808181555-90411555-905X2019-02-27T07:36:18-08:002019-04-05Clinical Journal of the American Society of NephrologyPerspectives144623625
- Management of the Hemodialysis Patient with Catheter-Related Bloodstream Infection10.2215/CJN.13171118Tue, 05 Mar 2019 06:39:32 GMT-08:00Management of the Hemodialysis Patient with Catheter-Related Bloodstream InfectionFarrington, Crystal A.Allon, Michael2019-03-05T06:39:32-08:00doi:10.2215/CJN.13171118hwp:resource-id:clinjasn;14/4/611American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinfection, Catheter-Related Infections, renal dialysis, Catheters, BacteremiaKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20192019-04-05April 05, 201910.2215/CJN.131711181555-90411555-905X2019-03-05T06:39:32-08:002019-04-05Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat144611613
- Frailty and Cognitive Deficits Limit Access to Kidney Transplantation10.2215/CJN.02390219Tue, 19 Mar 2019 06:55:45 GMT-07:00Frailty and Cognitive Deficits Limit Access to Kidney TransplantationHarhay, Meera N.Reese, Peter P.2019-03-19T06:55:45-07:00doi:10.2215/CJN.02390219hwp:resource-id:clinjasn;14/4/493American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Frailty, Cognitive Dysfunction, Cognition Disorders, CognitionEditorialsEditorialseditorial20192019-04-05April 05, 201910.2215/CJN.023902191555-90411555-905X2019-03-19T06:55:45-07:002019-04-05Clinical Journal of the American Society of NephrologyEditorials14444493567576495575582
- Kidney Transplantation in a HIV-Positive Recipient10.2215/CJN.14051118Mon, 18 Mar 2019 09:56:33 GMT-07:00Kidney Transplantation in a HIV-Positive RecipientSawinski, DeirdreLocke, Jayme E.2019-03-18T09:56:33-07:00doi:10.2215/CJN.14051118hwp:resource-id:clinjasn;14/4/614American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, HIV Seropositivity, Graft SurvivalKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20192019-04-05April 05, 201910.2215/CJN.140511181555-90411555-905X2019-03-18T09:56:33-07:002019-04-05Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat144614616
- Subclinical Cognitive Impairment and Listing for Kidney Transplantation10.2215/CJN.11010918Tue, 19 Mar 2019 06:55:44 GMT-07:00Subclinical Cognitive Impairment and Listing for Kidney TransplantationGupta, AditiMontgomery, Robert N.Bedros, VictorLesko, JohnMahnken, Jonathan D.Chakraborty, ShwetaDrew, DavidKlein, Jeffrey A.Thomas, Tashra S.Ilahe, AmnaBudhiraja, PoojaBrooks, William M.Schmitt, Timothy M.Sarnak, Mark J.Burns, Jeffrey M.Cibrik, Diane M.2019-03-19T06:55:44-07:00doi:10.2215/CJN.11010918hwp:resource-id:clinjasn;14/4/567American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycognition, eligibility, ESKD, Cohort Studies, Cognitive Dysfunction, coronary artery disease, kidney transplantation, Kaplan-Meier Estimate, Proportional Hazards Models, Smokers, Longitudinal Studies, Cognition, diabetes mellitus, Kidney Diseases, Smoking, Mental Status and Dementia TestsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20192019-04-05April 05, 201910.2215/CJN.110109181555-90411555-905X2019-03-19T06:55:44-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles14444567493576575495582
- Frailty and Access to Kidney Transplantation10.2215/CJN.12921118Tue, 19 Mar 2019 06:55:44 GMT-07:00Frailty and Access to Kidney TransplantationHaugen, Christine E.Chu, Nadia M.Ying, HaoWarsame, FatimaHolscher, Courtenay M.Desai, Niraj M.Jones, Miranda R.Norman, Silas P.Brennan, Daniel C.Garonzik-Wang, JacquelineWalston, Jeremy D.Bingaman, Adam W.Segev, Dorry L.McAdams-DeMarco, Mara2019-03-19T06:55:44-07:00doi:10.2215/CJN.12921118hwp:resource-id:clinjasn;14/4/576American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyoutcomes, renal dialysis, kidney transplantation, Walking Speed, Accidental Falls, Outpatients, Prospective Studies, Frailty, Weight Loss, risk factors, Incidence, Kidney Failure, Chronic, Comorbidity, hospitalization, Transplants, Cognition, Hand Strength, CounselingOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20192019-04-05April 05, 201910.2215/CJN.129211181555-90411555-905X2019-03-19T06:55:44-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles14444576493567582495575
- Etiology and Outcomes of Thrombotic Microangiopathies10.2215/CJN.11470918Tue, 12 Mar 2019 06:22:29 GMT-07:00Etiology and Outcomes of Thrombotic MicroangiopathiesBayer, Guillaumevon Tokarski, FlorentThoreau, BenjaminBauvois, AdelineBarbet, ChristelleCloarec, SylvieMérieau, ElodieLachot, SébastienGarot, DenisBernard, LouisGyan, EmmanuelPerrotin, FranckPouplard, ClaireMaillot, FrançoisGatault, PhilippeSautenet, BénédicteRusch, EmmanuelBuchler, MatthiasVigneau, CécileFakhouri, FadiHalimi, Jean-Michel2019-03-12T06:22:29-07:00doi:10.2215/CJN.11470918hwp:resource-id:clinjasn;14/4/557American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPregnancy, Purpura, Thrombotic Thrombocytopenic, Shiga Toxin, Odds Ratio, Escherichia coli, Incidence, Logistic Models, Hypertension, Malignant, Retrospective Studies, Glucosephosphate Dehydrogenase Deficiency, Confidence Intervals, Acute Coronary Syndrome, Cognitive Dysfunction, renal dialysis, Thrombotic Microangiopathies, Anemia, Sickle Cell, Stroke, hospitalization, Epilepsy, heart failure, Immune System Diseases, Neoplasms, Folic AcidOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20192019-04-05April 05, 201910.2215/CJN.114709181555-90411555-905X2019-03-12T06:22:29-07:002019-04-05Clinical Journal of the American Society of NephrologyOriginal Articles144557566
- Authors’ Reply10.1681/ASN.2019010049Wed, 13 Feb 2019 06:28:49 GMT-08:00Authors’ ReplyHaddock, Bryan T.Larsson, HenrikAndersen, Ulrik2019-02-13T06:28:49-08:00doi:10.1681/ASN.2019010049hwp:resource-id:jnephrol;30/4/711-aAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal hemodynamics, renal nerve, renal blood flow, MRI, PerfusionLetters to the EditorLetters to the Editorletter20192019-04-01April 201910.1681/ASN.20190100491046-66731533-34502019-02-13T06:28:49-08:002019-04Journal of the American Society of NephrologyLetters to the Editor3044711711712711
- The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial Cells10.1681/ASN.2018090914Wed, 13 Mar 2019 08:05:07 GMT-07:00The RNA-Protein Interactome of Differentiated Kidney Tubular Epithelial CellsIgnarski, MichaelRill, ConstantinKaiser, Rainer W.J.Kaldirim, MadlenNeuhaus, RenéEsmaillie, RezaLi, XinpingKlein, CorinnaBohl, KatrinPetersen, MaikeFrese, Christian K.Höhne, MartinAtanassov, IlianRinschen, Markus M.Höpker, KatjaSchermer, BernhardBenzing, ThomasDieterich, ChristophFabretti, FrancescaMüller, Roman-Ulrich2019-03-13T08:05:07-07:00doi:10.1681/ASN.2018090914hwp:resource-id:jnephrol;30/4/564American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyRNA-binding protein, RBP, hypoxia, HIF, tubule cells, ciliaBasic ResearchBasic Researchresearch-article20192019-04-01April 201910.1681/ASN.20180909141046-66731533-34502019-03-13T08:05:07-07:002019-04Journal of the American Society of NephrologyBasic Research304564576
- Complementary Roles for Single-Nucleus and Single-Cell RNA Sequencing in Kidney Disease Research10.1681/ASN.2019020112Wed, 13 Mar 2019 08:05:05 GMT-07:00Complementary Roles for Single-Nucleus and Single-Cell RNA Sequencing in Kidney Disease ResearchO’Sullivan, Eoin D.Mylonas, Katie J.Hughes, JeremyFerenbach, David A.2019-03-13T08:05:05-07:00doi:10.1681/ASN.2019020112hwp:resource-id:jnephrol;30/4/712American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, obstructive nephropathy, cell activation, immunology, lymphocytes, macrophagesLetters to the EditorLetters to the Editorletter20192019-04-01April 201910.1681/ASN.20190201121046-66731533-34502019-03-13T08:05:05-07:002019-04Journal of the American Society of NephrologyLetters to the Editor3044712714713714
- Renal Perfusion and Renal Nerve Activity10.1681/ASN.2018121226Wed, 13 Feb 2019 06:28:49 GMT-08:00Renal Perfusion and Renal Nerve ActivityLifschitz, Meyer D.2019-02-13T06:28:49-08:00doi:10.1681/ASN.2018121226hwp:resource-id:jnephrol;30/4/711American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal hemodynamics, renal blood flow, renal nerve activityLetters to the EditorLetters to the Editorletter20192019-04-01April 201910.1681/ASN.20181212261046-66731533-34502019-02-13T06:28:49-08:002019-04Journal of the American Society of NephrologyLetters to the Editor3044711711711711
- DNMT1 in Six2 Progenitor Cells Is Essential for Transposable Element Silencing and Kidney Development10.1681/ASN.2018070687Fri, 08 Mar 2019 01:16:28 GMT-08:00DNMT1 in Six2 Progenitor Cells Is Essential for Transposable Element Silencing and Kidney DevelopmentLi, Szu-YuanPark, JihwanGuan, YutingChung, KiwungShrestha, RojeshPalmer, Matthew B.Susztak, Katalin2019-03-08T13:16:28-08:00doi:10.1681/ASN.2018070687hwp:resource-id:jnephrol;30/4/594American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyDNA methylation, DNMT, podocyte, kidney development, Transposable elementBasic ResearchBasic Researchresearch-article20192019-04-01April 201910.1681/ASN.20180706871046-66731533-34502019-03-08T13:16:28-08:002019-04Journal of the American Society of NephrologyBasic Research304594609
- Authors’ Reply10.1681/ASN.2019020178Wed, 13 Mar 2019 08:05:06 GMT-07:00Authors’ ReplyWu, HaojiaKirita, YuheiDonnelly, Erinn L.Humphreys, Benjamin D.2019-03-13T08:05:06-07:00doi:10.1681/ASN.2019020178hwp:resource-id:jnephrol;30/4/714American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyRNA-sequencing, Cell dissociation, fibrosisLetters to the EditorLetters to the Editorletter20192019-04-01April 201910.1681/ASN.20190201781046-66731533-34502019-03-13T08:05:06-07:002019-04Journal of the American Society of NephrologyLetters to the Editor3044714712714713
- Piecing Together the Risk of Sudden Cardiac Death on Dialysis10.1681/ASN.2019020185Mon, 18 Mar 2019 09:03:42 GMT-07:00Piecing Together the Risk of Sudden Cardiac Death on DialysisWeinhandl, Eric D.2019-03-18T09:03:42-07:00doi:10.1681/ASN.2019020185hwp:resource-id:jnephrol;30/4/521American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologysudden cardiac death, hemodialysis, survival, QT-interval prolongation, SSRI, depressionUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-04-01April 201910.1681/ASN.20190201851046-66731533-34502019-03-18T09:03:42-07:002019-04Journal of the American Society of NephrologyUp Front Matters3044521611523623
- Patient-Reported Outcomes: Toward Better Measurement of Patient-Centered Care in CKD10.1681/ASN.2019020169Thu, 21 Mar 2019 08:05:38 GMT-07:00Patient-Reported Outcomes: Toward Better Measurement of Patient-Centered Care in CKDWu, Albert W.Predmore, Zachary S.2019-03-21T08:05:38-07:00doi:10.1681/ASN.2019020169hwp:resource-id:jnephrol;30/4/523American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, quality of life, dialysis, Patient self-assessmentUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-04-01April 201910.1681/ASN.20190201691046-66731533-34502019-03-21T08:05:38-07:002019-04Journal of the American Society of NephrologyUp Front Matters30444523654664525663677
- Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study10.1681/ASN.2018100990Thu, 07 Mar 2019 07:45:23 GMT-08:00Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height StudyShroff, RukshanaSmith, ColetteRanchin, BrunoBayazit, Aysun K.Stefanidis, Constantinos J.Askiti, VarvaraAzukaitis, KarolisCanpolat, NurAğbaş, AyşeAitkenhead, HelenAnarat, AliAoun, BilalAofolaju, DaleyBakkaloglu, Sevcan AzimeBhowruth, DevinaBorzych-Dużałka, DagmaraBulut, Ipek KaplanBüscher, RainerDeanfield, JohnDempster, ClaireDuzova, AliHabbig, SandraHayes, WesleyHegde, ShivramKrid, SaoussenLicht, ChristophLitwin, MieczyslawMayes, MarkMir, SevgiNemec, RoseObrycki, LukaszPaglialonga, FabioPicca, StefanoSamaille, CharlotteShenoy, MohanSinha, Manish D.Spasojevic, BrankicaStronach, LynseyVidal, EnricoVondrák, KarelYilmaz, AlevZaloszyc, ArianeFischbach, MichelSchmitt, Claus PeterSchaefer, Franz2019-03-07T07:45:23-08:00doi:10.1681/ASN.2018100990hwp:resource-id:jnephrol;30/4/678American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, hemodiafiltration (HDF), carotid intima-media thickness, growth, cardiovascular disease, childrenClinical ResearchClinical Researchresearch-article20192019-04-01April 201910.1681/ASN.20181009901046-66731533-34502019-03-07T07:45:23-08:002019-04Journal of the American Society of NephrologyClinical Research304678691
- Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during Hyperglycemia10.1681/ASN.2018080844Wed, 13 Mar 2019 08:05:06 GMT-07:00Macula Densa SGLT1-NOS1-Tubuloglomerular Feedback Pathway, a New Mechanism for Glomerular Hyperfiltration during HyperglycemiaZhang, JieWei, JinJiang, ShanXu, LanWang, LeiCheng, FengBuggs, JacenthaKoepsell, HermannVallon, VolkerLiu, Ruisheng2019-03-13T08:05:06-07:00doi:10.1681/ASN.2018080844hwp:resource-id:jnephrol;30/4/578American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular hyperfiltration, hyperglycemia, SGLT1, NOS1, tubuloglomerular feedbackBasic ResearchBasic Researchresearch-article20192019-04-01April 201910.1681/ASN.20180808441046-66731533-34502019-03-13T08:05:06-07:002019-04Journal of the American Society of NephrologyBasic Research3044578519593521
- Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis10.1681/ASN.2018101032Mon, 18 Mar 2019 09:03:42 GMT-07:00Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance HemodialysisAssimon, Magdalene M.Brookhart, M. AlanFlythe, Jennifer E.2019-03-18T09:03:42-07:00doi:10.1681/ASN.2018101032hwp:resource-id:jnephrol;30/4/611American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, SSRIs, Safety, Sudden cardiac deathClinical EpidemiologyClinical Epidemiologyresearch-article20192019-04-01April 201910.1681/ASN.20181010321046-66731533-34502019-03-18T09:03:42-07:002019-04Journal of the American Society of NephrologyClinical Epidemiology3044611521623523
- Improving CKD-Specific Patient-Reported Measures of Health-Related Quality of Life10.1681/ASN.2018080814Thu, 21 Mar 2019 08:05:39 GMT-07:00Improving CKD-Specific Patient-Reported Measures of Health-Related Quality of LifeWare, John E.Richardson, Michelle M.Meyer, Klemens B.Gandek, Barbara2019-03-21T08:05:39-07:00doi:10.1681/ASN.2018080814hwp:resource-id:jnephrol;30/4/664American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, quality of life, KDQOL, SF-12 Health Survey, Patient-Reported OutcomesClinical ResearchClinical Researchresearch-article20192019-04-01April 201910.1681/ASN.20180808141046-66731533-34502019-03-21T08:05:39-07:002019-04Journal of the American Society of NephrologyClinical Research3044664523677525
- Kidney Disease Quality of Life 36-Item Short Form Survey (KDQOL-36) Normative Values for the United States Dialysis Population and New Single Summary Score10.1681/ASN.2018100994Thu, 21 Mar 2019 08:05:38 GMT-07:00Kidney Disease Quality of Life 36-Item Short Form Survey (KDQOL-36) Normative Values for the United States Dialysis Population and New Single Summary ScorePeipert, John D.Nair, DevikaKlicko, KristiSchatell, Dorian R.Hays, Ron D.2019-03-21T08:05:38-07:00doi:10.1681/ASN.2018100994hwp:resource-id:jnephrol;30/4/654American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyquality of life, Patient self-assessment, dialysis, outcomesClinical ResearchClinical Researchresearch-article20192019-04-01April 201910.1681/ASN.20181009941046-66731533-34502019-03-21T08:05:38-07:002019-04Journal of the American Society of NephrologyClinical Research3044654523663525
- Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial10.1681/ASN.2018080832Thu, 07 Mar 2019 07:45:22 GMT-08:00Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 TrialBlock, Geoffrey A.Rosenbaum, David P.Yan, AndrewChertow, Glenn M.2019-03-07T07:45:22-08:00doi:10.1681/ASN.2018080832hwp:resource-id:jnephrol;30/4/641American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologytenapanor, hyperphosphatemia, NHE3, hemodialysis, phosphateClinical ResearchClinical Researchresearch-article20192019-04-01April 201910.1681/ASN.20180808321046-66731533-34502019-03-07T07:45:22-08:002019-04Journal of the American Society of NephrologyClinical Research304641652
- This Month's Highlights10.1681/ASN.2019020184Fri, 29 Mar 2019 10:00:27 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2019-03-29T10:00:27-07:00doi:10.1681/ASN.2019020184hwp:resource-id:jnephrol;30/4/iAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20192019-04-01April 201910.1681/ASN.20190201841046-66731533-34502019-03-29T10:00:27-07:002019-04Journal of the American Society of NephrologyThis Month’s Highlights304ii
- LRG1 Promotes Diabetic Kidney Disease Progression by Enhancing TGF-β–Induced Angiogenesis10.1681/ASN.2018060599Mon, 11 Mar 2019 07:58:43 GMT-07:00LRG1 Promotes Diabetic Kidney Disease Progression by Enhancing TGF-β–Induced AngiogenesisHong, QuanZhang, LuFu, JiaVerghese, Divya A.Chauhan, KinsukNadkarni, Girish N.Li, ZhengzheJu, WenjunKretzler, MatthiasCai, Guang-YanChen, Xiang-MeiD’Agati, Vivette D.Coca, Steven G.Schlondorff, DetlefHe, John C.Lee, Kyung2019-03-11T07:58:43-07:00doi:10.1681/ASN.2018060599hwp:resource-id:jnephrol;30/4/546American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular endothelial cells, TGF-beta, diabetic nephropathy, proteinuriaBasic ResearchBasic Researchresearch-article20192019-04-01April 201910.1681/ASN.20180605991046-66731533-34502019-03-11T07:58:43-07:002019-04Journal of the American Society of NephrologyBasic Research304546562
- Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney Disease10.1681/ASN.2018090896Thu, 07 Mar 2019 07:45:22 GMT-08:00Single-Cell RNA Profiling of Glomerular Cells Shows Dynamic Changes in Experimental Diabetic Kidney DiseaseFu, JiaAkat, Kemal M.Sun, ZeguoZhang, WeijiaSchlondorff, DetlefLiu, ZhihongTuschl, ThomasLee, KyungHe, John Cijiang2019-03-07T07:45:22-08:00doi:10.1681/ASN.2018090896hwp:resource-id:jnephrol;30/4/533American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulus, diabetic nephropathy, transcriptional profiling, mesangial cells, glomerular endothelial cells, macrophagesBasic ResearchBasic Researchresearch-article20192019-04-01April 201910.1681/ASN.20180908961046-66731533-34502019-03-07T07:45:22-08:002019-04Journal of the American Society of NephrologyBasic Research304533545
- The Other Glucose Transporter, SGLT1 – Also a Potential Trouble Maker in Diabetes?10.1681/ASN.2019020171Wed, 13 Mar 2019 08:05:05 GMT-07:00The Other Glucose Transporter, SGLT1 – Also a Potential Trouble Maker in Diabetes?Carlström, Mattias2019-03-13T08:05:05-07:00doi:10.1681/ASN.2019020171hwp:resource-id:jnephrol;30/4/519American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes, glomerular hyperfiltration, renal function, nitric oxideUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-04-01April 201910.1681/ASN.20190201711046-66731533-34502019-03-13T08:05:05-07:002019-04Journal of the American Society of NephrologyUp Front Matters3044519578521593
- Expanding the Patient’s Voice in Nephrology with Patient-Reported Outcomes10.1681/ASN.2019010019Thu, 07 Mar 2019 07:45:22 GMT-08:00Expanding the Patient’s Voice in Nephrology with Patient-Reported OutcomesPeipert, John D.Hays, Ron D.2019-03-07T07:45:22-08:00doi:10.1681/ASN.2019010019hwp:resource-id:jnephrol;30/4/530American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyquality of life, outcomes, dialysis, patient-centered careUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20192019-04-01April 201910.1681/ASN.20190100191046-66731533-34502019-03-07T07:45:22-08:002019-04Journal of the American Society of NephrologyUp Front Matters304530532
- You Are Just Now Telling Us About This? African American Perspectives of Testing for Genetic Susceptibility to Kidney Disease10.1681/ASN.2018111091Mon, 11 Mar 2019 07:58:42 GMT-07:00You Are Just Now Telling Us About This? African American Perspectives of Testing for Genetic Susceptibility to Kidney DiseaseUmeukeje, Ebele M.Young, Bessie A.Fullerton, Stephanie M.Cavanaugh, KerriOwens, DeliaWilson, James G.Burke, WylieBlacksher, Erika2019-03-11T07:58:42-07:00doi:10.1681/ASN.2018111091hwp:resource-id:jnephrol;30/4/526American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyethnicity, APOL1 testing, community engagement, African American, racial disparitiesUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20192019-04-01April 201910.1681/ASN.20181110911046-66731533-34502019-03-11T07:58:42-07:002019-04Journal of the American Society of NephrologyUp Front Matters304526530
- Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens10.1681/ASN.2018080868Fri, 08 Mar 2019 01:16:28 GMT-08:00Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell AntigensDelville, MarianneLamarthée, BaptistePagie, SylvainSee, Sarah B.Rabant, MarionBurger, CaroleGatault, PhilippeGiral, MagaliThaunat, OlivierArzouk, NadiaHertig, AlexandreHazzan, MarcMatignon, MarieMariat, ChristopheCaillard, SophieKamar, NassimSayegh, JohnnyWesteel, Pierre-FrançoisGarrouste, CyrilLadrière, MarcVuiblet, VincentRivalan, JosephMerville, PierreBertrand, DominiqueLe Moine, AlainVan Huyen, Jean Paul DuongCesbron, AnneCagnard, NicolasAlibeu, OlivierSatchell, Simon C.Legendre, ChristopheZorn, EmmanuelTaupin, Jean-LucCharreau, BéatriceAnglicheau, Dany2019-03-08T13:16:28-08:00doi:10.1681/ASN.2018080868hwp:resource-id:jnephrol;30/4/692American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute microvascular rejection, AECAs, acute rejection, antibody mediated rejectionClinical ResearchClinical Researchresearch-article20192019-04-01April 201910.1681/ASN.20180808681046-66731533-34502019-03-08T13:16:28-08:002019-04Journal of the American Society of NephrologyClinical Research304692709
- Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival10.1681/ASN.2018070777Thu, 14 Mar 2019 07:25:56 GMT-07:00Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft SurvivalAubert, OlivierHiggins, SarahBouatou, YassineYoo, DanielRaynaud, MarcViglietti, DenisRabant, MarionHidalgo, LuisGlotz, DenisLegendre, ChristopheDelahousse, MichelShah, NikhilSis, BanuCampbell, PatriciaMengel, MichaelJouven, XavierVan Huyen, Jean-Paul DuongLefaucheur, CarmenLoupy, Alexandre2019-03-14T07:25:56-07:00doi:10.1681/ASN.2018070777hwp:resource-id:jnephrol;30/4/625American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant glomerulopathy, Archetype, antibody-mediated rejection, transplant outcomes, kidney transplantation, donor-specific anti-HLA antibodyClinical ResearchClinical Researchresearch-article20192019-04-01April 201910.1681/ASN.20180707771046-66731533-34502019-03-14T07:25:56-07:002019-04Journal of the American Society of NephrologyClinical Research304625639
- Requirements for Procedural Skills in Nephrology Training Programs10.2215/CJN.02210218Fri, 15 Jun 2018 07:25:43 GMT-07:00Requirements for Procedural Skills in Nephrology Training ProgramsNorby, Suzanne M.2018-06-15T07:25:43-07:00doi:10.2215/CJN.02210218hwp:resource-id:clinjasn;13/7/1096American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyoutcomes, renal biopsy, vascular access, fellowship training, temporary dialysis catheter, graduate medical education, nephrology education, nephrology fellowship, trainingPerspectivesPerspectivesresearch-article20182018-07-06July 06, 201810.2215/CJN.022102181555-90411555-905X2018-06-15T07:25:43-07:002018-07-06Clinical Journal of the American Society of NephrologyPerspectives13777710961099110211051098110111041106
- Training Nephrology Fellows in Temporary Hemodialysis Catheters and Kidney Biopsies Is Not Needed and Should Not Be Required10.2215/CJN.01260118Fri, 15 Jun 2018 07:25:44 GMT-07:00Training Nephrology Fellows in Temporary Hemodialysis Catheters and Kidney Biopsies Is Not Needed and Should Not Be RequiredShankland, Stuart J.2018-06-15T07:25:44-07:00doi:10.2215/CJN.01260118hwp:resource-id:clinjasn;13/7/1102American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNephrology, Fellowships and Scholarships, Catheterization, renal dialysis, Nephrectomy, BiopsyPerspectivesPerspectivesresearch-article20182018-07-06July 06, 201810.2215/CJN.012601181555-90411555-905X2018-06-15T07:25:44-07:002018-07-06Clinical Journal of the American Society of NephrologyPerspectives13777711021096109911051104109811011106
- Kidney Biopsy Training and the Future of Nephrology10.2215/CJN.05870518Fri, 15 Jun 2018 07:25:46 GMT-07:00Kidney Biopsy Training and the Future of NephrologyBrown, Robert S.2018-06-15T07:25:46-07:00doi:10.2215/CJN.05870518hwp:resource-id:clinjasn;13/7/1105American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, nephrology training, patient care, ACGME requirements, ABIM requirementsPerspectivesPerspectivesresearch-article20182018-07-06July 06, 201810.2215/CJN.058705181555-90411555-905X2018-06-15T07:25:46-07:002018-07-06Clinical Journal of the American Society of NephrologyPerspectives13777711051096109911021106109811011104
- Mandating Staffing Ratios in Hemodialysis Facilities10.2215/CJN.03030318Wed, 06 Jun 2018 06:00:25 GMT-07:00Mandating Staffing Ratios in Hemodialysis FacilitiesRastogi, AnjayChertow, Glenn M.2018-06-06T06:00:25-07:00doi:10.2215/CJN.03030318hwp:resource-id:clinjasn;13/7/1110American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, Workload, Staffing, Personnel Staffing and SchedulingPerspectivesPerspectivesresearch-article20182018-07-06July 06, 201810.2215/CJN.030303181555-90411555-905X2018-06-06T06:00:25-07:002018-07-06Clinical Journal of the American Society of NephrologyPerspectives13711101112
- Burden of Proof for Tolvaptan in ADPKD10.2215/CJN.00190118Fri, 13 Apr 2018 07:18:23 GMT-07:00Burden of Proof for Tolvaptan in ADPKDMustafa, Reem A.Yu, Alan S.L.2018-04-13T07:18:23-07:00doi:10.2215/CJN.00190118hwp:resource-id:clinjasn;13/7/1107American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, Benzazepines, Biological Phenomena, chronic kidney disease, clinical trial, Cysts, Humans, Kidney Failure, Chronic, Polycystic Kidney, Autosomal Dominant, Tolvaptan, United States, Urinary Tract Physiological PhenomenaPerspectivesPerspectivesresearch-article20182018-07-06July 06, 201810.2215/CJN.001901181555-90411555-905X2018-04-13T07:18:23-07:002018-07-06Clinical Journal of the American Society of NephrologyPerspectives13711071109
- Training Nephrology Fellows in Temporary Hemodialysis Catheter Placement and Kidney Biopsies is Needed and Should be Required10.2215/CJN.00040118Fri, 15 Jun 2018 07:25:43 GMT-07:00Training Nephrology Fellows in Temporary Hemodialysis Catheter Placement and Kidney Biopsies is Needed and Should be RequiredBerns, Jeffrey S.2018-06-15T07:25:43-07:00doi:10.2215/CJN.00040118hwp:resource-id:clinjasn;13/7/1099American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTraining, Fellowships and Scholarships, nephrology, Consensus, Education, Medical, Graduate, Accreditation, Internal Medicine, renal dialysis, peritoneal dialysis, Surveys and Questionnaires, Attitude, BiopsyPerspectivesPerspectivesresearch-article20182018-07-06July 06, 201810.2215/CJN.000401181555-90411555-905X2018-06-15T07:25:43-07:002018-07-06Clinical Journal of the American Society of NephrologyPerspectives13777710991096110211051101109811041106
- Contrast-Induced Acute Kidney Injury in the PRESERVE Trial10.2215/CJN.01060118Thu, 19 Apr 2018 07:58:39 GMT-07:00Contrast-Induced Acute Kidney Injury in the PRESERVE TrialSiew, Edward D.Liu, Kathleen D.2018-04-19T07:58:39-07:00doi:10.2215/CJN.01060118hwp:resource-id:clinjasn;13/6/949American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcetylcysteine, Acute Kidney Injury, clinical trial, Contrast-induced Nephropathy, creatinine, Intravenous Fluids, Preservation, BiologicalPerspectivesPerspectivesresearch-article20182018-06-07June 07, 201810.2215/CJN.010601181555-90411555-905X2018-04-19T07:58:39-07:002018-06-07Clinical Journal of the American Society of NephrologyPerspectives136949951
- Trial Design Innovations to Accelerate Therapeutic Advances in Chronic Kidney Disease10.2215/CJN.01290118Thu, 26 Apr 2018 06:24:14 GMT-07:00Trial Design Innovations to Accelerate Therapeutic Advances in Chronic Kidney DiseaseHeerspink, Hiddo J.L.Perkovic, Vlado2018-04-26T06:24:14-07:00doi:10.2215/CJN.01290118hwp:resource-id:clinjasn;13/6/946American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCardiovascular Diseases, Diabetic Nephropathies, diabetic nephropathy, Disease Progression, Humans, kidney, Mortality, Premature, nephrology, Personalized Medicine, Platform Trial, Prevalence, randomized controlled trials, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20182018-06-07June 07, 201810.2215/CJN.012901181555-90411555-905X2018-04-26T06:24:14-07:002018-06-07Clinical Journal of the American Society of NephrologyPerspectives136946948
- Treatment of Depression in CKD Patients with an SSRI10.2215/CJN.14421217Fri, 13 Apr 2018 07:18:23 GMT-07:00Treatment of Depression in CKD Patients with an SSRICukor, DanielKimmel, Paul L.2018-04-13T07:18:23-07:00doi:10.2215/CJN.14421217hwp:resource-id:clinjasn;13/6/943American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Depression, Depressive Disorder, Major, Kidney Failure, Chronic, Publications, ResearchPerspectivesPerspectivesresearch-article20182018-06-07June 07, 201810.2215/CJN.144212171555-90411555-905X2018-04-13T07:18:23-07:002018-06-07Clinical Journal of the American Society of NephrologyPerspectives136943945
- Need to Reclassify Etiologies of ESRD on the CMS 2728 Medical Evidence Report10.2215/CJN.08310817Tue, 17 Oct 2017 06:48:10 GMT-07:00Need to Reclassify Etiologies of ESRD on the CMS 2728 Medical Evidence ReportTucker, Bryan M.Freedman, Barry I.2017-10-17T06:48:10-07:00doi:10.2215/CJN.08310817hwp:resource-id:clinjasn;13/3/477American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, clinical nephrology, diabetic nephropathy, Epidemiology and outcomes, ESRD, hypertension, Humans, United States, Medicaid, Centers for Medicare and Medicaid Services (U.S.), Kidney Failure, Chronic, Medicare, Renal Replacement Therapy, Medical Records, Registries, Documentation, renal dialysisPerspectivesPerspectivesresearch-article20182018-03-07March 07, 201810.2215/CJN.083108171555-90411555-905X2017-10-17T06:48:10-07:002018-03-07Clinical Journal of the American Society of NephrologyPerspectives133477479
- A View of the Bundle from a Home Dialysis Perspective10.2215/CJN.04570417Mon, 18 Dec 2017 06:42:07 GMT-08:00A View of the Bundle from a Home Dialysis PerspectiveGolper, Thomas A.2017-12-18T06:42:07-08:00doi:10.2215/CJN.04570417hwp:resource-id:clinjasn;13/3/471American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBundle, Economics, Hemodialysis, Home, Humans, renal dialysis, peritoneal dialysisPerspectivesPerspectivesresearch-article20182018-03-07March 07, 201810.2215/CJN.045704171555-90411555-905X2017-12-18T06:42:07-08:002018-03-07Clinical Journal of the American Society of NephrologyPerspectives1333471474473476
- The Affordable Care Act, Medicaid Expansion, and Disparities in Kidney Disease10.2215/CJN.10520917Thu, 14 Dec 2017 06:26:35 GMT-08:00The Affordable Care Act, Medicaid Expansion, and Disparities in Kidney DiseaseTrivedi, Amal N.Sommers, Benjamin D.2017-12-14T06:26:35-08:00doi:10.2215/CJN.10520917hwp:resource-id:clinjasn;13/3/480American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal diseasePerspectivesPerspectivesresearch-article20182018-03-07March 07, 201810.2215/CJN.105209171555-90411555-905X2017-12-14T06:26:35-08:002018-03-07Clinical Journal of the American Society of NephrologyPerspectives133480482
- Striving to Achieve an Integrated Home Dialysis System10.2215/CJN.06900617Thu, 14 Dec 2017 06:26:35 GMT-08:00Striving to Achieve an Integrated Home Dialysis SystemMcCormick, Brendan B.Chan, Christopher T.,2017-12-14T06:26:35-08:00doi:10.2215/CJN.06900617hwp:resource-id:clinjasn;13/3/468American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHome Dialysis, Home Hemodialysis, peritoneal dialysis, Home TransitionPerspectivesPerspectivesresearch-article20182018-03-07March 07, 201810.2215/CJN.069006171555-90411555-905X2017-12-14T06:26:35-08:002018-03-07Clinical Journal of the American Society of NephrologyPerspectives133468470
- The Dialysis Facility Compare Five-Star Rating System at 2 Years10.2215/CJN.11231017Mon, 18 Dec 2017 06:42:08 GMT-08:00The Dialysis Facility Compare Five-Star Rating System at 2 YearsPozniak, AlyssaPearson, Jeffrey2017-12-18T06:42:08-08:00doi:10.2215/CJN.11231017hwp:resource-id:clinjasn;13/3/474American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, Patient Protection and Affordable Care Act, Centers for Medicare and Medicaid Services (U.S.), renal dialysis, Medicare, Nursing Homes, Physicians, Home Care Agencies, hospitalization, Surveys and QuestionnairesPerspectivesPerspectivesresearch-article20182018-03-07March 07, 201810.2215/CJN.112310171555-90411555-905X2017-12-18T06:42:08-08:002018-03-07Clinical Journal of the American Society of NephrologyPerspectives1333474471476473
- Integrated Care in ESKD10.2215/CJN.13081118Tue, 29 Jan 2019 08:36:57 GMT-08:00Integrated Care in ESKDBrady, Brian M.Erickson, Kevin F.2019-01-29T08:36:57-08:00doi:10.2215/CJN.13081118hwp:resource-id:clinjasn;14/3/451American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, clinical nephrology, Kidney Failure, Chronic, risk factorsPerspectivesPerspectivesresearch-article20192019-03-07March 07, 201910.2215/CJN.130811181555-90411555-905X2019-01-29T08:36:57-08:002019-03-07Clinical Journal of the American Society of NephrologyPerspectives143451453
- Integrated Care for People with Kidney Disease10.2215/CJN.13641118Tue, 29 Jan 2019 08:36:57 GMT-08:00Integrated Care for People with Kidney DiseaseJohnson, Douglas S.Meyer, Klemens B.2019-01-29T08:36:57-08:00doi:10.2215/CJN.13641118hwp:resource-id:clinjasn;14/3/448American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEconomic Impact, chronic kidney disease, kidney transplantation, end stage kidney disease, public policy, for profit, not for profit, care coordination, insurance, costPerspectivesPerspectivesresearch-article20192019-03-07March 07, 201910.2215/CJN.136411181555-90411555-905X2019-01-29T08:36:57-08:002019-03-07Clinical Journal of the American Society of NephrologyPerspectives143448450
- Integrated Care in ESKD10.2215/CJN.08300718Tue, 29 Jan 2019 08:36:57 GMT-08:00Integrated Care in ESKDBecker, Bryan N.Nissenson, Allen R.2019-01-29T08:36:57-08:00doi:10.2215/CJN.08300718hwp:resource-id:clinjasn;14/3/445American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney care, integrated care, policy, dialysis, Kidney Failure, ChronicPerspectivesPerspectivesresearch-article20192019-03-07March 07, 201910.2215/CJN.083007181555-90411555-905X2019-01-29T08:36:57-08:002019-03-07Clinical Journal of the American Society of NephrologyPerspectives143445447
- Urinary Potassium Excretion and Progression of CKD10.2215/CJN.07820618Thu, 14 Feb 2019 05:53:09 GMT-08:00Urinary Potassium Excretion and Progression of CKDKim, Hyung WooPark, Jung TakYoo, Tae-HyunLee, JoongyubChung, WookyungLee, Kyu-BeckChae, Dong-WanAhn, CurieKang, Shin-WookChoi, Kyu HunHan, Seung Hyeok,2019-02-14T05:53:09-08:00doi:10.2215/CJN.07820618hwp:resource-id:clinjasn;14/3/330American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Urinary potassium excretion, creatinine, glomerular filtration rate, Proportional Hazards Models, Potassium, Confidence Intervals, Follow-Up Studies, Renal Insufficiency, Chronic, Kidney Failure, Chronic, Disease Progression, kidneyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-03-07March 7, 201910.2215/CJN.078206181555-90411555-905X2019-02-14T05:53:09-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1433330319340320
- Serum Metabolomic Alterations Associated with Proteinuria in CKD10.2215/CJN.10010818Thu, 07 Feb 2019 06:03:10 GMT-08:00Serum Metabolomic Alterations Associated with Proteinuria in CKDLuo, ShengyuanCoresh, JosefTin, AdrienneRebholz, Casey M.Appel, Lawrence J.Chen, JingshaVasan, Ramachandran S.Anderson, Amanda H.Feldman, Harold I.Kimmel, Paul L.Waikar, Sushrut S.Köttgen, AnnaEvans, Anne M.Levey, Andrew S.Inker, Lesley A.Sarnak, Mark J.Grams, Morgan Erika,2019-02-07T06:03:10-08:00doi:10.2215/CJN.10010818hwp:resource-id:clinjasn;14/3/342American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, metabolism, glomerular filtration rate, creatinine, Cross-Sectional Studies, phosphatidylethanolamine, Linear Models, risk factors, proteinuria, Renal Insufficiency, Chronic, hypertension, DietOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-03-07March 07, 201910.2215/CJN.100108181555-90411555-905X2019-02-07T06:03:10-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles143342353
- Hypernatremia10.2215/CJN.12141018Wed, 06 Feb 2019 07:08:09 GMT-08:00HypernatremiaQian, Qi2019-02-06T07:08:09-08:00doi:10.2215/CJN.12141018hwp:resource-id:clinjasn;14/3/432American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypernatremia, water regulation, sodium regulation, pathophysiology, diagnosis, treatment, Sodium, Potassium, Dehydration, diabetes insipidus, Ions, Acids, NoncarboxylicKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20192019-03-07March 7, 201910.2215/CJN.121410181555-90411555-905X2019-02-06T07:08:09-08:002019-03-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat143432434
- Complement Gene Variants and Shiga Toxin–Producing Escherichia coli–Associated Hemolytic Uremic Syndrome10.2215/CJN.05830518Wed, 23 Jan 2019 05:42:18 GMT-08:00Complement Gene Variants and Shiga Toxin–Producing Escherichia coli–Associated Hemolytic Uremic SyndromeFrémeaux-Bacchi, VéroniqueSellier-Leclerc, Anne-LaureVieira-Martins, PaulaLimou, SophieKwon, TheresaLahoche, AnnieNovo, RobertLlanas, BrigitteNobili, FrançoisRoussey, GwenaëlleCailliez, MathildeUlinski, TimDeschênes, GeorgesAlberti, CorinneWeill, François-XavierMariani, PatriciaLoirat, Chantal2019-01-23T05:42:18-08:00doi:10.2215/CJN.05830518hwp:resource-id:clinjasn;14/3/364American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyComplement, hemolytic uremic syndrome, pathogenic variants, Atypical Hemolytic Uremic Syndrome, complement factor H, human, Complement Factor H, Shiga Toxin, CD46 protein, human, Membrane Cofactor Protein, Escherichia coli, Genetic Background, High-Throughput Nucleotide Sequencing, Complement System Proteins, Complement Activation, Kidney Failure, Chronic, Genotype, Gene Frequency, BiomarkersOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20192019-03-07March 07, 201910.2215/CJN.058305181555-90411555-905X2019-01-23T05:42:18-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles143364377
- MicroRNAs in AKI and Kidney TransplantationMicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation.10.2215/CJN.08020718Wed, 02 Jan 2019 07:01:12 GMT-08:00MicroRNAs in AKI and Kidney TransplantationMicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation.Ledeganck, Kristien J.Gielis, Els M.Abramowicz, DanielStenvinkel, PeterShiels, Paul G.Van Craenenbroeck, Amaryllis H.2019-01-02T07:01:12-08:00doi:10.2215/CJN.08020718hwp:resource-id:clinjasn;14/3/454American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, MicroRNAs, Prospective Studies, Acute Kidney Injury, Biomarkers, Body Fluids, HomeostasisReviewReviewreview-article20192019-03-07March 07, 201910.2215/CJN.080207181555-90411555-905X2019-01-02T07:01:12-08:002019-03-07Clinical Journal of the American Society of NephrologyReview143454468
- Are Generic Immunosuppressive Drugs the Solution for Providing Lifelong Medication Coverage to Transplant Recipients?10.2215/CJN.00960119Thu, 28 Feb 2019 07:48:11 GMT-08:00Are Generic Immunosuppressive Drugs the Solution for Providing Lifelong Medication Coverage to Transplant Recipients?Potter, Lisa M.2019-02-28T07:48:11-08:00doi:10.2215/CJN.00960119hwp:resource-id:clinjasn;14/3/327American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunosuppression, Economic Impact, kidney transplantation, Transplant Recipients, Immunosuppressive Agents, Drugs, GenericEditorialEditorialeditorial20192019-03-07March 07, 201910.2215/CJN.009601191555-90411555-905X2019-02-28T07:48:11-08:002019-03-07Clinical Journal of the American Society of NephrologyEditorial14333327317421329318430
- Cost of Immunosuppressive Drugs and the Patient with a Kidney Transplant10.2215/CJN.00760119Thu, 28 Feb 2019 07:48:11 GMT-08:00Cost of Immunosuppressive Drugs and the Patient with a Kidney TransplantThomas, Cher2019-02-28T07:48:11-08:00doi:10.2215/CJN.00760119hwp:resource-id:clinjasn;14/3/317American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Costs and Cost Analysis, Immunosuppressive Agents, Patient, Patient VoicePatient VoicePatient Voiceeditorial20192019-03-07March 07, 201910.2215/CJN.007601191555-90411555-905X2019-02-28T07:48:11-08:002019-03-07Clinical Journal of the American Society of NephrologyPatient Voice14333317327421318329430
- Secular Trends in the Cost of Immunosuppressants after Solid Organ Transplantation in the United States10.2215/CJN.10590918Thu, 28 Feb 2019 07:48:11 GMT-08:00Secular Trends in the Cost of Immunosuppressants after Solid Organ Transplantation in the United StatesHelmuth, Margaret E.Liu, QianTurenne, Marc N.Park, Jeong M.Oguntimein, MurewaDutcher, Sarah K.Balkrishnan, RajeshSharma, PratimaZee, JarcyLeichtman, Alan B.Smith, Abigail R.2019-02-28T07:48:11-08:00doi:10.2215/CJN.10590918hwp:resource-id:clinjasn;14/3/421American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, kidney, liver failure, heart disease, end-stage renal disease, Mycophenolic Acid, tacrolimus, Medicare Part D, Immunosuppressive Agents, Health Expenditures, Cost Savings, Insurance Carriers, Transplant Recipients, Linear Models, Drugs, Generic, Prescription Drugs, Heart TransplantationOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20192019-03-07March 07, 201910.2215/CJN.105909181555-90411555-905X2019-02-28T07:48:11-08:002019-03-07Clinical Journal of the American Society of NephrologyOriginal Articles14333421317327430318329
- Cultivating a Research-Ready Dialysis Community10.1681/ASN.2018101059Fri, 08 Feb 2019 05:19:08 GMT-08:00Cultivating a Research-Ready Dialysis CommunityFlythe, Jennifer E.Narendra, Julia H.Hilliard, TandreaFrazier, KarenIkeler, KourtneyAmolegbe, AndrewMitchell, DeniseDorough, AdelineLee, Shoou-Yih DanielOrdish, AntoinetteWilkie, CarolineDember, Laura M.,2019-02-08T05:19:08-08:00doi:10.1681/ASN.2018101059hwp:resource-id:jnephrol;30/3/375American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, dialysis, clinical trialUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20192019-03-01March 201910.1681/ASN.20181010591046-66731533-34502019-02-08T05:19:08-08:002019-03Journal of the American Society of NephrologyUp Front Matters303375380
- Staying the Course: Through End of Life in ESRD10.1681/ASN.2019010020Tue, 19 Feb 2019 06:47:10 GMT-08:00Staying the Course: Through End of Life in ESRDPerry, EricaJoy, SallySwartz, Richard2019-02-19T06:47:10-08:00doi:10.1681/ASN.2019010020hwp:resource-id:jnephrol;30/3/373American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, end of life, dialysisUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20192019-03-01March 201910.1681/ASN.20190100201046-66731533-34502019-02-19T06:47:10-08:002019-03Journal of the American Society of NephrologyUp Front Matters3033373481374491
- Overall and Site-Specific Cancer Mortality in Patients on Dialysis and after Kidney TransplantBackground Patients with ESRD have a substantially increased cancer risk, but few studies have examined the patterns of cancer mortality along a patient's journey from dialysis to transplantation.10.1681/ASN.2018090906Thu, 14 Feb 2019 06:15:05 GMT-08:00Overall and Site-Specific Cancer Mortality in Patients on Dialysis and after Kidney TransplantBackground Patients with ESRD have a substantially increased cancer risk, but few studies have examined the patterns of cancer mortality along a patient's journey from dialysis to transplantation.Au, Eric H.Chapman, Jeremy R.Craig, Jonathan C.Lim, Wai H.Teixeira-Pinto, ArmandoUllah, ShahidMcDonald, StephenWong, Germaine2019-02-14T06:15:05-08:00doi:10.1681/ASN.2018090906hwp:resource-id:jnephrol;30/3/471American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, cancer, dialysis, transplantation, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20192019-03-01March 201910.1681/ASN.20180909061046-66731533-34502019-02-14T06:15:05-08:002019-03Journal of the American Society of NephrologyClinical Epidemiology303471480
- The Case for a Bariatric-Centered Approach to CKD Care10.2215/CJN.12061018Thu, 10 Jan 2019 12:47:19 GMT-08:00The Case for a Bariatric-Centered Approach to CKD CareFriedman, Allon N.2019-01-10T12:47:19-08:00doi:10.2215/CJN.12061018hwp:resource-id:clinjasn;14/2/291American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyObesity, chronic kidney disease, clinical nephrology, Renal Insufficiency, Chronic, Bariatric SurgeryPerspectivesPerspectivesresearch-article20192019-02-07February 07, 201910.2215/CJN.120610181555-90411555-905X2019-01-10T12:47:19-08:002019-02-07Clinical Journal of the American Society of NephrologyPerspectives142291293
- Mentorship in the Digital Age10.2215/CJN.09970818Tue, 15 Jan 2019 05:33:01 GMT-08:00Mentorship in the Digital AgeShah, SilviTopf, Joel2019-01-15T05:33:01-08:00doi:10.2215/CJN.09970818hwp:resource-id:clinjasn;14/2/294American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMentorship, Social Media, Internship, Mentors, Internship and ResidencyPerspectivesPerspectivesresearch-article20192019-02-07February 07, 201910.2215/CJN.099708181555-90411555-905X2019-01-15T05:33:01-08:002019-02-07Clinical Journal of the American Society of NephrologyPerspectives142294296
- Patient Entrepreneurs to Drive Health Care Innovation for Kidney Disease10.2215/CJN.13731118Mon, 21 Jan 2019 07:45:33 GMT-08:00Patient Entrepreneurs to Drive Health Care Innovation for Kidney DiseaseHehenberger, Karin2019-01-21T07:45:33-08:00doi:10.2215/CJN.13731118hwp:resource-id:clinjasn;14/2/288American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDelivery of Health Care, Kidney Diseases, Organizational Innovation, Healthcare, InnovationPerspectivesPerspectivesresearch-article20192019-02-07February 07, 201910.2215/CJN.137311181555-90411555-905X2019-01-21T07:45:33-08:002019-02-07Clinical Journal of the American Society of NephrologyPerspectives142288290
- Assessment and Management of Hypertension among Patients on Peritoneal DialysisApproximately 7%–10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.10.2215/CJN.07480618Fri, 19 Oct 2018 08:18:09 GMT-07:00Assessment and Management of Hypertension among Patients on Peritoneal DialysisApproximately 7%–10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.Vaios, VasiliosGeorgianos, Panagiotis I.Liakopoulos, VassiliosAgarwal, Rajiv2018-10-19T08:18:09-07:00doi:10.2215/CJN.07480618hwp:resource-id:clinjasn;14/2/297American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, end stage kidney disease, icodextrin, blood pressure, renal dialysis, Sodium, Sodium, Dietary, Antihypertensive Agents, Prognosis, Glucans, Glucose, Kidney Failure, Chronic, hypertension, Peritonitis, DiuresisReviewsReviewsreview-article20192019-02-07February 07, 201910.2215/CJN.074806181555-90411555-905X2018-10-19T08:18:09-07:002019-02-07Clinical Journal of the American Society of NephrologyReviews142297305
- Patients,’ Nephrologists,’ and Predicted Estimations of ESKD Risk Compared with 2-Year Incidence of ESKD10.2215/CJN.07970718Thu, 10 Jan 2019 12:47:20 GMT-08:00Patients,’ Nephrologists,’ and Predicted Estimations of ESKD Risk Compared with 2-Year Incidence of ESKDPotok, O. AlisonNguyen, Hoang AnhAbdelmalek, Joseph A.Beben, TomaszWoodell, Tyler B.Rifkin, Dena E.2019-01-10T12:47:20-08:00doi:10.2215/CJN.07970718hwp:resource-id:clinjasn;14/2/206American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, dialysis, Progression of Kidney Failure, kidney failure, ESKD, glomerular filtration rate, Incidence, Prospective Studies, Prognosis, Calibration, Veterans, Renal Insufficiency, Chronic, Kidney Failure, Chronic, Renal Insufficiency, Disease ProgressionOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-02-07February 07, 201910.2215/CJN.079707181555-90411555-905X2019-01-10T12:47:20-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles142206212
- Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD10.2215/CJN.10710918Thu, 10 Jan 2019 12:47:20 GMT-08:00Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKDBathini, LavanyaJandoc, RacquelKuwornu, PaulMcArthur, EricWeir, Matthew A.Sood, Manish M.Battistella, MarisaMuanda, Flory T.Liu, AidenJain, Arsh K.Garg, Amit X.2019-01-10T12:47:20-08:00doi:10.2215/CJN.10710918hwp:resource-id:clinjasn;14/2/197American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAged, Aged, 80 and over, cefprozil, Cefuroxime, Anti-Bacterial Agents, Cephalexin, Odds Ratio, glomerular filtration rate, Outpatients, Confidence Intervals, Retrospective Studies, renal dialysis, Cephalosporins, Renal Insufficiency, Chronic, Treatment Failure, Risk, hospitalization, Emergency Service, HospitalOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-02-07February 07, 201910.2215/CJN.107109181555-90411555-905X2019-01-10T12:47:20-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles142197205
- Incidence and Risk Factors of Early Onset Neonatal AKI10.2215/CJN.03670318Thu, 31 Jan 2019 09:00:35 GMT-08:00Incidence and Risk Factors of Early Onset Neonatal AKICharlton, Jennifer R.Boohaker, LouisAskenazi, DavidBrophy, Patrick D.D’Angio, CarlFuloria, MamtaGien, JasonGriffin, RussellHingorani, SangeetaIngraham, SusanMian, AyesaOhls, Robin K.Rastogi, ShantanuRhee, Christopher J.Revenis, MarySarkar, SubrataSmith, AlexandraStarr, MichelleKent, Alison L.,Ambalavanan, NamasivayamSelewski, David T.Fletcher, JefferyAbitbol, Carolyn LGuillet, RonnieDeFreitas, MarissaDuara, ShahnazRademacher, ErinMhanna, Maroun J.Raina, RupeshKumar, DeepakArikan, Ayse AkcanGoldstein, Stuart L.Nathan, Amy T.Kupferman, Juan C.Bhutada, AlokBonachea, ElizabethMahan, JohnNada, ArwaJetton, JenniferColaizy, Tarah T.Klein, Jonathan M.Cole, F. SessionsDavis, T. KeefeDower, JoshuaMilner, LawrenceReidy, KimberlyKaskel, Frederick J.Gist, Katja M.Hanna, Mina H.Wong, Craig S.Joseph, CatherineDuPont, TaraStaples, AmyKhokhar, SurenderPerazzo, SofiaRay, Patricio E.Mammen, CherrySynnes, AnneWintermark, PiaZappitelli, MichaelSethi, Sidharth K.Wazir, SanjayRohatgi, SmritiSoranno, Danielle E.Chishti, Aftab S.Woroniecki, RobertSwanson, Jonathan R.Sridhar, Shanty2019-01-31T09:00:35-08:00doi:10.2215/CJN.03670318hwp:resource-id:clinjasn;14/2/184American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChildren, neonatal kidney collaborative, Infant, Newborn, child, Pregnancy, Incidence, methylxanthine, Gestational Age, creatinine, Intensive Care Units, Neonatal, diuretics, risk factors, Anti-Infective Agents, Retrospective Studies, Mating Factor, Xanthines, Acute Kidney Injury, Vasoconstrictor Agents, Epinephrine, hospitalization, Cesarean Section, HyperbilirubinemiaOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20192019-02-07February 07, 201910.2215/CJN.036703181555-90411555-905X2019-01-31T09:00:35-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1422184172195174
- Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka10.2215/CJN.07430618Fri, 18 Jan 2019 08:36:27 GMT-08:00Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri LankaAnand, ShuchiMontez-Rath, Maria E.Adasooriya, DinukaRatnatunga, NeelakanthiKambham, NeerajaWazil, AbdoolWijetunge, SulcohanaBadurdeen, ZeidRatnayake, CharakaKarunasena, NishamaniSchensul, Stephen L.Valhos, PennyHaider, LalarukhBhalla, VivekLevin, AdeeraWise, Paul H.Chertow, Glenn M.Barry, MicheleFire, Andrew Z.Nanayakkara, Nishantha2019-01-18T08:36:27-08:00doi:10.2215/CJN.07430618hwp:resource-id:clinjasn;14/2/224American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyProspective Studies, Tobacco, risk factors, Logistic Models, Farmers, Serum Albumin, Consensus, Sri Lanka, nephrology, Nephritis, Interstitial, kidney, Renal Insufficiency, Chronic, Biopsy, hypertension, diabetes mellitus, Life StyleOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20192019-02-07February 07, 201910.2215/CJN.074306181555-90411555-905X2019-01-18T08:36:27-08:002019-02-07Clinical Journal of the American Society of NephrologyOriginal Articles142224232
- Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving Hemodialysis10.1681/ASN.2018080858Thu, 03 Jan 2019 08:29:50 GMT-08:00Prior Hospitalization Burden and the Relatedness of 30-Day Readmissions in Patients Receiving HemodialysisLin, EugeneBhattacharya, JayChertow, Glenn M.2019-01-03T08:29:50-08:00doi:10.1681/ASN.2018080858hwp:resource-id:jnephrol;30/2/323American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, Epidemiology and outcomes, United States Renal, Data SystemClinical EpidemiologyClinical Epidemiologyresearch-article20192019-02-01February 201910.1681/ASN.20180808581046-66731533-34502019-01-03T08:29:50-08:002019-02Journal of the American Society of NephrologyClinical Epidemiology3022323184335186
- Kir4.1/Kir5.1 Activity Is Essential for Dietary Sodium Intake–Induced Modulation of Na-Cl Cotransporter10.1681/ASN.2018080799Mon, 17 Dec 2018 07:27:16 GMT-08:00Kir4.1/Kir5.1 Activity Is Essential for Dietary Sodium Intake–Induced Modulation of Na-Cl CotransporterWu, PengGao, Zhong-XiuziSu, Xiao-TongWang, Ming-XiaoWang, Wen-HuiLin, Dao-Hong2018-12-17T07:27:16-08:00doi:10.1681/ASN.2018080799hwp:resource-id:jnephrol;30/2/216American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologypotassium channels, epithelial sodium transport, hypertensionBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180807991046-66731533-34502018-12-17T07:27:16-08:002019-02Journal of the American Society of NephrologyBasic Research302216227
- New Insights into the Mechanism of NO3- Selectivity in the Human Kidney Chloride Channel ClC-Ka and the CLC Protein Family10.1681/ASN.2018060593Fri, 11 Jan 2019 09:16:33 GMT-08:00New Insights into the Mechanism of NO3- Selectivity in the Human Kidney Chloride Channel ClC-Ka and the CLC Protein FamilyLagostena, LauraZifarelli, GiovanniPicollo, Alessandra2019-01-11T09:16:33-08:00doi:10.1681/ASN.2018060593hwp:resource-id:jnephrol;30/2/293American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyion channel, electrophysiology, Bartter-s syndrome, ion transport, kidney tubuleBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180605931046-66731533-34502019-01-11T09:16:33-08:002019-02Journal of the American Society of NephrologyBasic Research302293302
- Producing Purer Podocytes10.1681/ASN.2018101045Fri, 11 Jan 2019 09:16:34 GMT-08:00Producing Purer PodocytesFreedman, Benjamin S.2019-01-11T09:16:34-08:00doi:10.1681/ASN.2018101045hwp:resource-id:jnephrol;30/2/183American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, organoids, kidney developmentUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-02-01February 201910.1681/ASN.20181010451046-66731533-34502019-01-11T09:16:34-08:002019-02Journal of the American Society of NephrologyUp Front Matters3022183304184321
- Readmissions Metrics in Hemodialysis: Do the Specifics Matter?10.1681/ASN.2018101033Thu, 03 Jan 2019 08:29:50 GMT-08:00Readmissions Metrics in Hemodialysis: Do the Specifics Matter?Dad, TaimurWeiner, Daniel E.2019-01-03T08:29:50-08:00doi:10.1681/ASN.2018101033hwp:resource-id:jnephrol;30/2/184American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, ESRD, hospitalization, payment, policy, MedicareUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-02-01February 201910.1681/ASN.20181010331046-66731533-34502019-01-03T08:29:50-08:002019-02Journal of the American Society of NephrologyUp Front Matters3022184323186335
- Activation and Proliferation of PD-1+ Kidney Double-Negative T Cells Is Dependent on Nonclassical MHC Proteins and IL-210.1681/ASN.2018080815Tue, 08 Jan 2019 07:41:33 GMT-08:00Activation and Proliferation of PD-1+ Kidney Double-Negative T Cells Is Dependent on Nonclassical MHC Proteins and IL-2Sadasivam, MohanrajNoel, SanjeevLee, Sul A.Gong, JingAllaf, Mohamad E.Pierorazio, PhillipRabb, HamidHamad, Abdel Rahim A.2019-01-08T07:41:33-08:00doi:10.1681/ASN.2018080815hwp:resource-id:jnephrol;30/2/277American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, ischemia-reperfusion, T cellsBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180808151046-66731533-34502019-01-08T07:41:33-08:002019-02Journal of the American Society of NephrologyBasic Research302277292
- IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice10.1681/ASN.2018090901Tue, 08 Jan 2019 07:41:33 GMT-08:00IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr MiceWada, YukihiroGonzalez-Sanchez, Hilda M.Weinmann-Menke, JuliaIwata, YasunoriAjay, Amrendra K.Meineck, MyriamKelley, Vicki R.2019-01-08T07:41:33-08:00doi:10.1681/ASN.2018090901hwp:resource-id:jnephrol;30/2/244American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologylupus nephritis, macrophages, IL-34, MRL-<i>Fas<sup>lpr</sup></i>, miceBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180909011046-66731533-34502019-01-08T07:41:33-08:002019-02Journal of the American Society of NephrologyBasic Research302244259
- This Month’s Highlights10.1681/ASN.2018121271Thu, 31 Jan 2019 10:00:30 GMT-08:00This Month’s HighlightsAmerican Society of Nephrology2019-01-31T10:00:30-08:00doi:10.1681/ASN.2018121271hwp:resource-id:jnephrol;30/2/iAmerican Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20192019-02-01February 201910.1681/ASN.20181212711046-66731533-34502019-01-31T10:00:30-08:002019-02Journal of the American Society of NephrologyThis Month’s Highlights302ii
- Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population10.1681/ASN.2018060581Thu, 24 Jan 2019 06:22:31 GMT-08:00Excess Deaths Attributable to Influenza-Like Illness in the ESRD PopulationGilbertson, David T.Rothman, Kenneth J.Chertow, Glenn M.Bradbury, Brian D.Brookhart, M. AlanLiu, JiannongWinkelmayer, Wolfgang C.Stürmer, TilMonda, Keri L.Herzog, Charles A.Ashfaq, AkhtarCollins, Allan J.Wetmore, James B.2019-01-24T06:22:31-08:00doi:10.1681/ASN.2018060581hwp:resource-id:jnephrol;30/2/346American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, influenza, influenza-like illness, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20192019-02-01February 201910.1681/ASN.20180605811046-66731533-34502019-01-24T06:22:31-08:002019-02Journal of the American Society of NephrologyClinical Epidemiology302346353
- Hepatocyte Growth Factor–Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKD10.1681/ASN.2018050556Fri, 11 Jan 2019 09:16:34 GMT-08:00Hepatocyte Growth Factor–Secreting Mesothelial Cell Sheets Suppress Progressive Fibrosis in a Rat Model of CKDOka, MasatoshiSekiya, SachikoSakiyama, RyoichiShimizu, TatsuyaNitta, Kosaku2019-01-11T09:16:34-08:00doi:10.1681/ASN.2018050556hwp:resource-id:jnephrol;30/2/261American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, chronic kidney disease, HGF, cell sheet, obstructive nephropathyBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180505561046-66731533-34502019-01-11T09:16:34-08:002019-02Journal of the American Society of NephrologyBasic Research302261276
- Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem Cells10.1681/ASN.2018070747Fri, 11 Jan 2019 09:16:35 GMT-08:00Manipulation of Nephron-Patterning Signals Enables Selective Induction of Podocytes from Human Pluripotent Stem CellsYoshimura, YasuhiroTaguchi, AtsuhiroTanigawa, ShunsukeYatsuda, JunjiKamba, TomomiTakahashi, SatoruKurihara, HidetakeMukoyama, MasashiNishinakamura, Ryuichi2019-01-11T09:16:35-08:00doi:10.1681/ASN.2018070747hwp:resource-id:jnephrol;30/2/304American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, nephron patterning, podocyte, pluripotent stem cell, directed differentiation, cell resourceBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180707471046-66731533-34502019-01-11T09:16:35-08:002019-02Journal of the American Society of NephrologyBasic Research30332211304183253253321184253253
- Lipid Peroxidation Drives Renal Cyst Growth In Vitro through Activation of TMEM16A10.1681/ASN.2018010039Thu, 03 Jan 2019 08:29:51 GMT-08:00Lipid Peroxidation Drives Renal Cyst Growth In Vitro through Activation of TMEM16ASchreiber, RainerBuchholz, BjörnKraus, AndreSchley, GunnarScholz, JuliaOusingsawat, JirapornKunzelmann, Karl2019-01-03T08:29:51-08:00doi:10.1681/ASN.2018010039hwp:resource-id:jnephrol;30/2/228American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, TMEM16A, reactive oxygen species, lipid peroxidation, ferroptosis, anoctamin 1Basic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180100391046-66731533-34502019-01-03T08:29:51-08:002019-02Journal of the American Society of NephrologyBasic Research302228242
- Therapeutic Inhibition of VEGF Signaling and Associated NephrotoxicitiesInhibition of vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a common therapeutic strategy in oncology, with new drugs continuously in development. In this review, we consider the experimental and clinical evidence behind the diverse nephrotoxicities associated with the inhibition of this pathway. We also review the renal effects of VEGF inhibition’s mediation of key downstream signaling pathways, specifically MAPK/ERK1/2, endothelial nitric oxide synthase, and mammalian target of rapamycin (mTOR). Direct VEGFA inhibition via antibody binding or VEGF trap (a soluble decoy receptor) is associated with renal-specific thrombotic microangiopathy (TMA). Reports also indicate that tyrosine kinase inhibition of the VEGF receptors is preferentially associated with glomerulopathies such as minimal change disease and FSGS. Inhibition of the downstream pathway RAF/MAPK/ERK has largely been associated with tubulointerstitial injury. Inhibition of mTOR is most commonly associated with albuminuria and podocyte injury, but has also been linked to renal-specific TMA. In all, we review the experimentally validated mechanisms by which VEGFA-VEGFR2 inhibitors contribute to nephrotoxicity, as well as the wide range of clinical manifestations that have been reported with their use. We also highlight potential avenues for future research to elucidate mechanisms for minimizing nephrotoxicity while maintaining therapeutic efficacy.10.1681/ASN.2018080853Mon, 14 Jan 2019 08:13:21 GMT-08:00Therapeutic Inhibition of VEGF Signaling and Associated NephrotoxicitiesInhibition of vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling is a common therapeutic strategy in oncology, with new drugs continuously in development. In this review, we consider the experimental and clinical evidence behind the diverse nephrotoxicities associated with the inhibition of this pathway. We also review the renal effects of VEGF inhibition’s mediation of key downstream signaling pathways, specifically MAPK/ERK1/2, endothelial nitric oxide synthase, and mammalian target of rapamycin (mTOR). Direct VEGFA inhibition via antibody binding or VEGF trap (a soluble decoy receptor) is associated with renal-specific thrombotic microangiopathy (TMA). Reports also indicate that tyrosine kinase inhibition of the VEGF receptors is preferentially associated with glomerulopathies such as minimal change disease and FSGS. Inhibition of the downstream pathway RAF/MAPK/ERK has largely been associated with tubulointerstitial injury. Inhibition of mTOR is most commonly associated with albuminuria and podocyte injury, but has also been linked to renal-specific TMA. In all, we review the experimentally validated mechanisms by which VEGFA-VEGFR2 inhibitors contribute to nephrotoxicity, as well as the wide range of clinical manifestations that have been reported with their use. We also highlight potential avenues for future research to elucidate mechanisms for minimizing nephrotoxicity while maintaining therapeutic efficacy.Estrada, Chelsea C.Maldonado, AlejandroMallipattu, Sandeep K.2019-01-14T08:13:21-08:00doi:10.1681/ASN.2018080853hwp:resource-id:jnephrol;30/2/187American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologysignaling, nitric oxide, VEGF, proteinuria, hypertensionUp Front MattersReviewUp Front MattersReviewbrief-report20192019-02-01February 201910.1681/ASN.20180808531046-66731533-34502019-01-14T08:13:21-08:002019-02Journal of the American Society of NephrologyUp Front Matters302187200
- A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation10.1681/ASN.2018060656Thu, 03 Jan 2019 08:29:51 GMT-08:00A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney TransplantationMarques, Igor Denizarde BacelarAraújo, Maria Júlia Correia Lima NepomucenoGraciolli, Fabiana Giorgettidos Reis, Luciene MachadoPereira, Rosa Maria R.Alvarenga, Jackeline C.Custódio, Melani RibeiroJorgetti, VandaElias, Rosilene MottaMoysés, Rosa Maria AffonsoDavid-Neto, Elias2019-01-03T08:29:51-08:00doi:10.1681/ASN.2018060656hwp:resource-id:jnephrol;30/2/355American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologymineral metabolism, kidney disease, kidney transplantation, bone biopsy, zoledronic acid, renal osteodystrophyClinical ResearchClinical Researchresearch-article20192019-02-01February 201910.1681/ASN.20180606561046-66731533-34502019-01-03T08:29:51-08:002019-02Journal of the American Society of NephrologyClinical Research302355365
- Frailty and Changes in Cognitive Function after Kidney Transplantation10.1681/ASN.2018070726Thu, 24 Jan 2019 06:22:32 GMT-08:00Frailty and Changes in Cognitive Function after Kidney TransplantationChu, Nadia M.Gross, Alden L.Shaffer, Ashton A.Haugen, Christine E.Norman, Silas P.Xue, Qian-LiSharrett, A. RicheyCarlson, Michelle C.Bandeen-Roche, KarenSegev, Dorry L.McAdams-DeMarco, Mara A.2019-01-24T06:22:32-08:00doi:10.1681/ASN.2018070726hwp:resource-id:jnephrol;30/2/336American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, frailty, cognitionClinical EpidemiologyClinical Epidemiologyresearch-article20192019-02-01February 201910.1681/ASN.20180707261046-66731533-34502019-01-24T06:22:32-08:002019-02Journal of the American Society of NephrologyClinical Epidemiology302336345
- Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients10.1681/ASN.2018060575Thu, 17 Jan 2019 11:46:29 GMT-08:00Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant RecipientsMann, NinaBraun, Daniela A.Amann, KassaundraTan, WeizhenShril, ShirleeConnaughton, Dervla M.Nakayama, MakikoSchneider, RonenKitzler, Thomas M.van der Ven, Amelie T.Chen, JingItyel, HadasVivante, AsafMajmundar, Amar J.Daga, AnkanaWarejko, Jillian K.Lovric, SvjetlanaAshraf, ShaziaJobst-Schwan, TilmanWidmeier, EugenHugo, HannahMane, Shrikant M.Spaneas, LeslieSomers, Michael J.G.Ferguson, Michael A.Traum, Avram Z.Stein, Deborah R.Baum, Michelle A.Daouk, Ghaleb H.Lifton, Richard P.Manzi, ShannonVakili, KhashayarKim, Heung BaeRodig, Nancy M.Hildebrandt, Friedhelm2019-01-17T11:46:29-08:00doi:10.1681/ASN.2018060575hwp:resource-id:jnephrol;30/2/201American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, end-stage renal disease, genetic renal disease, chronic kidney disease, human geneticsBasic ResearchBasic Researchresearch-article20192019-02-01February 201910.1681/ASN.20180605751046-66731533-34502019-01-17T11:46:29-08:002019-02Journal of the American Society of NephrologyBasic Research302201215
- Women in Nephrology Today10.2215/CJN.07650618Mon, 22 Oct 2018 07:26:58 GMT-07:00Women in Nephrology TodayLederer, Eleanor2018-10-22T07:26:58-07:00doi:10.2215/CJN.07650618hwp:resource-id:clinjasn;13/11/1755American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGender inequity, Cultural Mores, Career obstacles, Female, nephrology, Physicians, WomenPerspectivesPerspectivesresearch-article20182018-11-07November 07, 201810.2215/CJN.076506181555-90411555-905X2018-10-22T07:26:58-07:002018-11-07Clinical Journal of the American Society of NephrologyPerspectives131117551756
- The New HHS Kidney Innovation Accelerator10.2215/CJN.04800418Thu, 25 Oct 2018 11:00:08 GMT-07:00The New HHS Kidney Innovation AcceleratorFowler, Kevin JohnConway, Paul T.2018-10-25T11:00:08-07:00doi:10.2215/CJN.04800418hwp:resource-id:clinjasn;13/11/1747American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinnovation, HHS, kidney disease, chronic kidney disease, dialysis, kidney transplant, quality of life, african americans, hispanic, disproportionate, cost, outcomes, ESKD, end stage kidney diseasePerspectivesPerspectivesresearch-article20182018-11-07November 07, 201810.2215/CJN.048004181555-90411555-905X2018-10-25T11:00:08-07:002018-11-07Clinical Journal of the American Society of NephrologyPerspectives1311111747175017491752
- The Kidney Accelerator10.2215/CJN.04720418Thu, 25 Oct 2018 11:00:08 GMT-07:00The Kidney AcceleratorWatnick, Suzanne2018-10-25T11:00:08-07:00doi:10.2215/CJN.04720418hwp:resource-id:clinjasn;13/11/1750American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, dialysis, end stage kidney disease, nephrology, quality of lifePerspectivesPerspectivesresearch-article20182018-11-07November 07, 201810.2215/CJN.047204181555-90411555-905X2018-10-25T11:00:08-07:002018-11-07Clinical Journal of the American Society of NephrologyPerspectives1311111750174717521749
- Extracorporeal Removal of Light Chains10.2215/CJN.05100418Mon, 22 Oct 2018 07:26:59 GMT-07:00Extracorporeal Removal of Light ChainsFinkel, Kevin W.Gallieni, Maurizio2018-10-22T07:26:59-07:00doi:10.2215/CJN.05100418hwp:resource-id:clinjasn;13/11/1753American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMyosins, Immunoglobulin Light ChainsPerspectivesPerspectivesresearch-article20182018-11-07November 07, 201810.2215/CJN.051004181555-90411555-905X2018-10-22T07:26:59-07:002018-11-07Clinical Journal of the American Society of NephrologyPerspectives131117531754
- Persistent Bias: A Threat to Diversity among Health Care Leaders10.2215/CJN.07290618Tue, 07 Aug 2018 08:07:06 GMT-07:00Persistent Bias: A Threat to Diversity among Health Care LeadersCrews, Deidra C.Wesson, Donald Everett2018-08-07T08:07:06-07:00doi:10.2215/CJN.07290618hwp:resource-id:clinjasn;13/11/1757American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyethnicity, chronic kidney disease, nephrology, Leadership, BiasPerspectivesPerspectivesresearch-article20182018-11-07November 07, 201810.2215/CJN.072906181555-90411555-905X2018-08-07T08:07:06-07:002018-11-07Clinical Journal of the American Society of NephrologyPerspectives131117571759
- Inclusion of Phosphorus in the Nutrition Facts Label10.2215/CJN.07230618Fri, 30 Nov 2018 06:20:11 GMT-08:00Inclusion of Phosphorus in the Nutrition Facts LabelBorgi, Lea2018-11-30T06:20:11-08:00doi:10.2215/CJN.07230618hwp:resource-id:clinjasn;14/1/139American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPhosphorus, Dietary, Food Labeling, nutritionPerspectivesPerspectivesresearch-article20192019-01-07January 07, 201910.2215/CJN.072306181555-90411555-905X2018-11-30T06:20:11-08:002019-01-07Clinical Journal of the American Society of NephrologyPerspectives141139140
- Plant-Based Diets in CKD10.2215/CJN.08960718Wed, 26 Dec 2018 11:00:42 GMT-08:00Plant-Based Diets in CKDClegg, Deborah J.Hill Gallant, Kathleen M.2018-12-26T11:00:42-08:00doi:10.2215/CJN.08960718hwp:resource-id:clinjasn;14/1/141American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hyperkalemia, potassium, diet, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20192019-01-07January 07, 201910.2215/CJN.089607181555-90411555-905X2018-12-26T11:00:42-08:002019-01-07Clinical Journal of the American Society of NephrologyPerspectives141141143
- Kidneys on Chips10.2215/CJN.06690518Mon, 01 Oct 2018 08:12:25 GMT-07:00Kidneys on ChipsYeung, Catherine K.Himmelfarb, Jonathan2018-10-01T08:12:25-07:00doi:10.2215/CJN.06690518hwp:resource-id:clinjasn;14/1/144American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymicrofluidic, organs on chips, in vitro modelling, Technology, kidneyPerspectivesPerspectivesresearch-article20192019-01-07January 07, 201910.2215/CJN.066905181555-90411555-905X2018-10-01T08:12:25-07:002019-01-07Clinical Journal of the American Society of NephrologyPerspectives141144146
- Timing of Kidney Replacement Therapy in Acute Kidney Injury10.2215/CJN.08810718Fri, 30 Nov 2018 06:20:11 GMT-08:00Timing of Kidney Replacement Therapy in Acute Kidney InjuryZarbock, AlexanderMehta, Ravindra L.2018-11-30T06:20:11-08:00doi:10.2215/CJN.08810718hwp:resource-id:clinjasn;14/1/147American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, clinical nephrology, dialysis, renal dialysisPerspectivesPerspectivesresearch-article20192019-01-07January 07, 201910.2215/CJN.088107181555-90411555-905X2018-11-30T06:20:11-08:002019-01-07Clinical Journal of the American Society of NephrologyPerspectives141147149
- Blood Pressure Goals in Patients with CKDHypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade, a number of hypertension guidelines have been published with varying recommendations for BP goals in patients with CKD. Most recently, the American College of Cardiology/American Heart Association 2017 hypertension guidelines set a BP goal of <130/80 mm Hg for patients with CKD and others at elevated cardiovascular risk. These guidelines were heavily influenced by the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which documented that an intensive BP goal to a systolic BP <120 mm Hg decreased the risk of cardiovascular disease and mortality in nondiabetic adults at high cardiovascular risk, many of whom had CKD; the intensive BP goal did not retard CKD progression. It is noteworthy that SPRINT measured BP with automated devices (5-minute wait period, average of three readings) often without observers, a technique that potentially results in BP values that are lower than what is typically measured in the office. Still, results from SPRINT along with long-term follow-up data from the Modification of Diet in Renal Disease and the African American Study of Kidney Disease and Hypertension suggest that a BP goal <130/80 mm Hg will reduce mortality in patients with CKD. Unfortunately, data are more limited in patients with diabetes or stage 4–5 CKD. Increased adverse events, including electrolyte abnormalities and decreased eGFR, necessitate careful laboratory monitoring. In conclusion, a BP goal of <130/80 is a reasonable, evidence-based BP goal in patients with CKD. Implementation of this intensive BP target will require increased attention to measuring BP accurately, assessing patient preferences and concurrent medical conditions, and monitoring for adverse effects of therapy.10.2215/CJN.07440618Mon, 19 Nov 2018 07:17:42 GMT-08:00Blood Pressure Goals in Patients with CKDHypertension affects the vast majority of patients with CKD and increases the risk of cardiovascular disease, ESKD, and death. Over the past decade, a number of hypertension guidelines have been published with varying recommendations for BP goals in patients with CKD. Most recently, the American College of Cardiology/American Heart Association 2017 hypertension guidelines set a BP goal of <130/80 mm Hg for patients with CKD and others at elevated cardiovascular risk. These guidelines were heavily influenced by the landmark Systolic Blood Pressure Intervention Trial (SPRINT), which documented that an intensive BP goal to a systolic BP <120 mm Hg decreased the risk of cardiovascular disease and mortality in nondiabetic adults at high cardiovascular risk, many of whom had CKD; the intensive BP goal did not retard CKD progression. It is noteworthy that SPRINT measured BP with automated devices (5-minute wait period, average of three readings) often without observers, a technique that potentially results in BP values that are lower than what is typically measured in the office. Still, results from SPRINT along with long-term follow-up data from the Modification of Diet in Renal Disease and the African American Study of Kidney Disease and Hypertension suggest that a BP goal <130/80 mm Hg will reduce mortality in patients with CKD. Unfortunately, data are more limited in patients with diabetes or stage 4–5 CKD. Increased adverse events, including electrolyte abnormalities and decreased eGFR, necessitate careful laboratory monitoring. In conclusion, a BP goal of <130/80 is a reasonable, evidence-based BP goal in patients with CKD. Implementation of this intensive BP target will require increased attention to measuring BP accurately, assessing patient preferences and concurrent medical conditions, and monitoring for adverse effects of therapy.Chang, Alex R.Lóser, MeghanMalhotra, RakeshAppel, Lawrence J.2018-11-19T07:17:42-08:00doi:10.2215/CJN.07440618hwp:resource-id:clinjasn;14/1/161American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, chronic kidney disease, clinical hypertension, clinical, nephrology, hypertension, systolic blood pressure, cardiovascular diseaseReviewReviewreview-article20192019-01-07January 07, 201910.2215/CJN.074406181555-90411555-905X2018-11-19T07:17:42-08:002019-01-07Clinical Journal of the American Society of NephrologyReview141161169
- Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis10.2215/CJN.04530418Mon, 17 Dec 2018 07:27:02 GMT-08:00Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasisde Jong, Maarten A.Petrykiv, Sergei I.Laverman, Gozewijn D.van Herwaarden, Antonius E.de Zeeuw, DickBakker, Stephan J.L.Heerspink, Hiddo J.L.de Borst, Martin H.2018-12-17T07:27:02-08:00doi:10.2215/CJN.04530418hwp:resource-id:clinjasn;14/1/66American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPhosphate homeostasis, Diabetic kidney disease, SGLT-2 inhibitors, FGF23, fibroblast growth factor 23, Diabetic Nephropathies, creatinine, Glycated Hemoglobin A, Diabetes Mellitus, Type 2, Renin-Angiotensin System, Cross-Over Studies, Double-Blind Method, Fibroblast Growth Factors, Calcifediol, parathyroid hormone, 25-hydroxyvitamin D, Vitamin D, Phosphates, Homeostasis, Albumins, Glucose, SodiumOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20192019-01-07January 07, 201910.2215/CJN.045304181555-90411555-905X2018-12-17T07:27:02-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1411667739
- Variability of Two Metabolomic Platforms in CKD10.2215/CJN.07070618Thu, 20 Dec 2018 08:52:58 GMT-08:00Variability of Two Metabolomic Platforms in CKDRhee, Eugene P.Waikar, Sushrut S.Rebholz, Casey M.Zheng, ZihePerichon, RegisClish, Clary B.Evans, Anne M.Avila, JulianDenburg, Michelle R.Anderson, Amanda HyreVasan, Ramachandran S.Feldman, Harold I.Kimmel, Paul L.Coresh, Josef,2018-12-20T08:52:58-08:00doi:10.2215/CJN.07070618hwp:resource-id:clinjasn;14/1/40American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, metabolomics, biomarker, glomerular filtration rate, Molecular Weight, proteinuria, Renal Insufficiency, Chronic, EGFR protein, human, Receptor, Epidermal Growth FactorOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-01-07January 07, 201910.2215/CJN.070706181555-90411555-905X2018-12-20T08:52:58-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1414048
- Patterns of Beverages Consumed and Risk of Incident Kidney Disease10.2215/CJN.06380518Thu, 27 Dec 2018 07:36:18 GMT-08:00Patterns of Beverages Consumed and Risk of Incident Kidney DiseaseRebholz, Casey M.Young, Bessie A.Katz, RonitTucker, Katherine L.Carithers, Teresa C.Norwood, Arnita F.Correa, Adolfo2018-12-27T07:36:18-08:00doi:10.2215/CJN.06380518hwp:resource-id:clinjasn;14/1/49American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Epidemiology and outcomes, nutrition, Beverages, Body Mass Index, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, diabetes mellitus, Energy Intake, Exercise, Fruit, glomerular filtration, rate, hypertension, kidney, Logistic Models, Nutrition Policy, Prospective, Studies, Renal Insufficiency, Chronic, Sex Education, Smoking, Sugars, Sweetening Agents, WaterOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-01-07January 07, 201910.2215/CJN.063805181555-90411555-905X2018-12-27T07:36:18-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1411149145626
- Effects of Molidustat in the Treatment of Anemia in CKD10.2215/CJN.02510218Mon, 17 Dec 2018 07:27:01 GMT-08:00Effects of Molidustat in the Treatment of Anemia in CKDMacdougall, Iain C.Akizawa, TadaoBerns, Jeffrey S.Bernhardt, ThomasKrueger, Thilo2018-12-17T07:27:01-08:00doi:10.2215/CJN.02510218hwp:resource-id:clinjasn;14/1/28American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, chronic kidney disease, hemoglobin, molidustat, Humans, Prolyl-Hydroxylase Inhibitors, Prolyl Hydroxylases, renal dialysis, Darbepoetin alfa, Epoetin Alfa, EPO protein, human, erythropoietin, Pyrazoles, Triazoles, Renal Insufficiency, Chronic, hypoxiaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20192019-01-07January 07, 201910.2215/CJN.025102181555-90411555-905X2018-12-17T07:27:01-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1414110281524391524
- Effects of the Potassium-Binding Polymer Patiromer on Markers of Mineral Metabolism10.2215/CJN.04500418Wed, 31 Oct 2018 10:53:46 GMT-07:00Effects of the Potassium-Binding Polymer Patiromer on Markers of Mineral MetabolismBushinsky, David A.Spiegel, David M.Yuan, JinweiWarren, SuzetteFogli, JeanenePergola, Pablo E.2018-10-31T10:53:46-07:00doi:10.2215/CJN.04500418hwp:resource-id:clinjasn;14/1/103American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHyperkalemia, patiromer, potassium, mineral metabolism, Sodium, fibroblast growth factor 23, creatinine, Magnesium, Fibroblast Growth Factors, Polymers, Calcifediol, 25-hydroxyvitamin D, Vitamin D, Phosphates, parathyroid hormone, Albumins, MineralsOriginal ArticlesMineral MetabolismOriginal ArticlesMineral Metabolismresearch-article20192019-01-07January 07, 201910.2215/CJN.045004181555-90411555-905X2018-10-31T10:53:46-07:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles141103110
- Population-Based Study of Risk of AKI with Levetiracetam10.2215/CJN.07490618Tue, 11 Dec 2018 08:43:42 GMT-08:00Population-Based Study of Risk of AKI with LevetiracetamYau, KevinBurneo, Jorge G.Jandoc, RacquelMcArthur, EricMuanda, Flory TsoboParikh, Chirag R.Wald, RonWeir, Matthew A.Garg, Amit X.2018-12-11T08:43:42-08:00doi:10.2215/CJN.07490618hwp:resource-id:clinjasn;14/1/17American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyevetiracetam, acute renal failure, drug nephrotoxicity, interstitial, nephritis, Retrospective Studies, Odds Ratio, Propensity Score, etiracetam, creatinine, Outpatients, Acute Kidney Injury, Renal, Insufficiency, Chronic, Piracetam, Seizures, Epilepsy, hospitalization, Emergency Service, HospitalOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20192019-01-07January 07, 201910.2215/CJN.074906181555-90411555-905X2018-12-11T08:43:42-08:002019-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1411726
- Screening Transplant Waitlist Candidates for Coronary Artery Disease10.2215/CJN.10510918Fri, 28 Dec 2018 08:27:50 GMT-08:00Screening Transplant Waitlist Candidates for Coronary Artery DiseaseGill, John S.2018-12-28T08:27:50-08:00doi:10.2215/CJN.10510918hwp:resource-id:clinjasn;14/1/112American Society of NephrologyCopyright © 2019 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycoronary artery disease, risk factors, Waiting Lists, kidney transplantation, Standard of Care, Canada, Tissue Donors, HeartKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20192019-01-07January 07, 201910.2215/CJN.105109181555-90411555-905X2018-12-28T08:27:50-08:002019-01-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat141112114
- The Quality of Reporting of Kidney Research: A Challenge to JASN10.1681/ASN.2018111132Thu, 13 Dec 2018 10:20:19 GMT-08:00The Quality of Reporting of Kidney Research: A Challenge to JASNBriggs, Josephine P.2018-12-13T10:20:19-08:00doi:10.1681/ASN.2018111132hwp:resource-id:jnephrol;30/1/1American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyresearch methods, ARRIVE, CONSORTUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-01-01January 201910.1681/ASN.20181111321046-66731533-34502018-12-13T10:20:19-08:002019-01Journal of the American Society of NephrologyUp Front Matters3011113222
- The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling10.1681/ASN.2018020209Mon, 10 Dec 2018 08:13:36 GMT-08:00The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 SignalingAndrikopoulos, PetrosKieswich, JuliusPacheco, SabrinaNadarajah, LuxmeHarwood, Steven MichaelO'Riordan, Caroline E.Thiemermann, ChristophYaqoob, Muhammad M.2018-12-10T08:13:36-08:00doi:10.1681/ASN.2018020209hwp:resource-id:jnephrol;30/1/33American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, ERK1/2, mTORC1, Trametinib, UUO, chronic kidney diseaseBasic ResearchBasic Researchresearch-article20192019-01-01January 201910.1681/ASN.20180202091046-66731533-34502018-12-10T08:13:36-08:002019-01Journal of the American Society of NephrologyBasic Research3013349
- DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and Differentiation10.1681/ASN.2018070736Wed, 05 Dec 2018 06:49:23 GMT-08:00DNA Methyltransferase 1 Controls Nephron Progenitor Cell Renewal and DifferentiationWanner, NicolaVornweg, JuliaCombes, AlexanderWilson, SeanPlappert, JuliaRafflenbeul, GesaPuelles, Victor G.Rahman, Raza-UrLiwinski, TimurLindner, SaskiaGrahammer, FlorianKretz, OliverWlodek, Mary E.Romano, TaniaMoritz, Karen M.Boerries, MelanieBusch, HaukeBonn, StefanLittle, Melissa H.Bechtel-Walz, WibkeHuber, Tobias B.2018-12-05T06:49:23-08:00doi:10.1681/ASN.2018070736hwp:resource-id:jnephrol;30/1/63American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyDnmt1, Dnmt3a/b, nephron progenitor cells, epigenetics, kidney development, DNA methylationBasic ResearchBasic Researchresearch-article20192019-01-01January 201910.1681/ASN.20180707361046-66731533-34502018-12-05T06:49:23-08:002019-01Journal of the American Society of NephrologyBasic Research3016378
- Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis10.1681/ASN.2018040440Tue, 04 Dec 2018 10:57:43 GMT-08:00Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water HomeostasisMukherjee, MalinideRiso, JenniferOtterpohl, KarlaRatnayake, IsharaKota, DivyaAhrenkiel, PhilChandrasekar, IndraSurendran, Kameswaran2018-12-04T10:57:43-08:00doi:10.1681/ASN.2018040440hwp:resource-id:jnephrol;30/1/110American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologytransdifferentiation, Notch Signaling, collecting duct, principal, intercalated, ionocyteBasic ResearchBasic Researchresearch-article20192019-01-01January 201910.1681/ASN.20180404401046-66731533-34502018-12-04T10:57:43-08:002019-01Journal of the American Society of NephrologyBasic Research301110126
- Survival among Veterans Obtaining Dialysis in VA and Non-VA Settings10.1681/ASN.2018050521Fri, 07 Dec 2018 04:11:08 GMT-08:00Survival among Veterans Obtaining Dialysis in VA and Non-VA SettingsWang, VirginiaCoffman, Cynthia J.Stechuchak, Karen M.Berkowitz, Theodore S.Z.Hebert, Paul L.Edelman, DavidO’Hare, Ann M.Crowley, Susan T.Weidenbacher, Hollis J.Maciejewski, Matthew L.2018-12-07T04:11:08-08:00doi:10.1681/ASN.2018050521hwp:resource-id:jnephrol;30/1/159American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, mortality, end-stage renal disease, Medicare, Veterans Affairs, community careClinical ResearchClinical Researchresearch-article20192019-01-01January 201910.1681/ASN.20180505211046-66731533-34502018-12-07T04:11:08-08:002019-01Journal of the American Society of NephrologyClinical Research301159168
- Morphological Processes of Foot Process Effacement in Puromycin Aminonucleoside Nephrosis Revealed by FIB/SEM Tomography10.1681/ASN.2018020139Tue, 04 Dec 2018 10:57:43 GMT-08:00Morphological Processes of Foot Process Effacement in Puromycin Aminonucleoside Nephrosis Revealed by FIB/SEM TomographyIchimura, KoichiroMiyaki, TakayukiKawasaki, YutoKinoshita, MuiKakuta, SoichiroSakai, Tatsuo2018-12-04T10:57:43-08:00doi:10.1681/ASN.2018020139hwp:resource-id:jnephrol;30/1/96American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, ultrastructure, foot process effacement, 3D electron microscopyBasic ResearchBasic Researchresearch-article20192019-01-01January 201910.1681/ASN.20180201391046-66731533-34502018-12-04T10:57:43-08:002019-01Journal of the American Society of NephrologyBasic Research30196108
- Growth of the ESKD Population: Progress or Peril?10.1681/ASN.2018111135Mon, 17 Dec 2018 07:27:17 GMT-08:00Growth of the ESKD Population: Progress or Peril?Collins, Allan J.2018-12-17T07:27:17-08:00doi:10.1681/ASN.2018111135hwp:resource-id:jnephrol;30/1/3American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, projections, mortality, access to organsUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-01-01January 201910.1681/ASN.20181111351046-66731533-34502018-12-17T07:27:17-08:002019-01Journal of the American Society of NephrologyUp Front Matters301131274135
- Sex-Related Disparities in CKD Progression10.1681/ASN.2018030296Mon, 03 Dec 2018 07:33:16 GMT-08:00Sex-Related Disparities in CKD ProgressionRicardo, Ana C.Yang, WeiSha, DaohangAppel, Lawrence J.Chen, JingKrousel-Wood, MarieManoharan, AnjellaSteigerwalt, SusanWright, JacksonRahman, MahboobRosas, Sylvia E.Saunders, MildaSharma, KumarDaviglus, Martha L.Lash, James P.,Appel, Lawrence J.Feldman, Harold I.Go, Alan S.He, JiangKusek, John W.Lash, James P.Ojo, AkinloluRahman, MahboobTownsend, Raymond R.2018-12-03T07:33:16-08:00doi:10.1681/ASN.2018030296hwp:resource-id:jnephrol;30/1/137American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyEpidemiology and outcomes, chronic kidney disease, mortality risk, ESRDClinical EpidemiologyClinical Epidemiologyresearch-article20192019-01-01January 201910.1681/ASN.20180302961046-66731533-34502018-12-03T07:33:16-08:002019-01Journal of the American Society of NephrologyClinical Epidemiology301137146
- Nucleophosmin Phosphorylation as a Diagnostic and Therapeutic Target for Ischemic AKIBackground Ischemic AKI lacks a urinary marker for early diagnosis and an effective therapy. Differential nucleophosmin (NPM) phosphorylation is a potential early marker of ischemic renal cell injury and a therapeutic target. Methods Differential NPM phosphorylation was assessed by mass spectrometry in NPM harvested from murine and human primary renal epithelial cells, fresh kidney tissue, and urine before and after ischemic injury. The biologic behavior and toxicity of NPM was assessed using phospho-NPM mutant proteins that either mimic stress-induced or normal NPM phosphorylation. Peptides designed to interfere with NPM function were used to explore NPM as a therapeutic target. Results Within hours of stress, virtually identical phosphorylation changes were detected at distinct serine/threonine sites in NPM harvested from primary renal cells, tissue, and urine. A phosphomimic NPM protein that replicated phosphorylation under stress localized to the cytosol, formed monomers that interacted with Bax, a cell death protein, coaccumulated with Bax in isolated mitochondria, and significantly increased cell death after stress; wild-type NPM or a phosphomimic NPM with a normal phosphorylation configuration did not. Three renal targeted peptides designed to interfere with NPM at distinct functional sites significantly protected against cell death, and a single dose of one peptide administered several hours after ischemia that would be lethal in untreated mice significantly reduced AKI severity and improved survival. Conclusions These findings establish phosphorylated NPM as a potential early marker of ischemic AKI that links early diagnosis with effective therapeutic interventions.10.1681/ASN.2018040401Thu, 20 Dec 2018 06:45:08 GMT-08:00Nucleophosmin Phosphorylation as a Diagnostic and Therapeutic Target for Ischemic AKIBackground Ischemic AKI lacks a urinary marker for early diagnosis and an effective therapy. Differential nucleophosmin (NPM) phosphorylation is a potential early marker of ischemic renal cell injury and a therapeutic target. Methods Differential NPM phosphorylation was assessed by mass spectrometry in NPM harvested from murine and human primary renal epithelial cells, fresh kidney tissue, and urine before and after ischemic injury. The biologic behavior and toxicity of NPM was assessed using phospho-NPM mutant proteins that either mimic stress-induced or normal NPM phosphorylation. Peptides designed to interfere with NPM function were used to explore NPM as a therapeutic target. Results Within hours of stress, virtually identical phosphorylation changes were detected at distinct serine/threonine sites in NPM harvested from primary renal cells, tissue, and urine. A phosphomimic NPM protein that replicated phosphorylation under stress localized to the cytosol, formed monomers that interacted with Bax, a cell death protein, coaccumulated with Bax in isolated mitochondria, and significantly increased cell death after stress; wild-type NPM or a phosphomimic NPM with a normal phosphorylation configuration did not. Three renal targeted peptides designed to interfere with NPM at distinct functional sites significantly protected against cell death, and a single dose of one peptide administered several hours after ischemia that would be lethal in untreated mice significantly reduced AKI severity and improved survival. Conclusions These findings establish phosphorylated NPM as a potential early marker of ischemic AKI that links early diagnosis with effective therapeutic interventions.Wang, ZhiyongSalih, ErdjanIgwebuike, ChinaemereMulhern, RyanBonegio, Ramon G.Havasi, AndreaBorkan, Steven C.2018-12-20T06:45:08-08:00doi:10.1681/ASN.2018040401hwp:resource-id:jnephrol;30/1/50American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, apoptosis, cell survival, proximal tubule, renal epithelial cellBasic ResearchBasic Researchresearch-article20192019-01-01January 201910.1681/ASN.20180404011046-66731533-34502018-12-20T06:45:08-08:002019-01Journal of the American Society of NephrologyBasic Research3015062
- Postoperative AKI—Prevention Is Better than Cure?10.1681/ASN.2018111127Tue, 18 Dec 2018 04:10:46 GMT-08:00Postoperative AKI—Prevention Is Better than Cure?Bell, SamiraProwle, John2018-12-18T04:10:46-08:00doi:10.1681/ASN.2018111127hwp:resource-id:jnephrol;30/1/4American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, risk score, post-operativeUp Front MattersEditorialsUp Front MattersEditorialseditorial20192019-01-01January 201910.1681/ASN.20181111271046-66731533-34502018-12-18T04:10:46-08:002019-01Journal of the American Society of NephrologyUp Front Matters301141706181
- Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients10.1681/ASN.2018050462Fri, 07 Dec 2018 04:11:09 GMT-08:00Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis PatientsFindlay, Mark DuncanDawson, JesseDickie, David AlexanderForbes, Kirsten P.McGlynn, DeborahQuinn, TerryMark, Patrick B.2018-12-07T04:11:09-08:00doi:10.1681/ASN.2018050462hwp:resource-id:jnephrol;30/1/147American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, cardiovascular disease, cognition, cerebrovascular diseaseClinical ResearchClinical Researchresearch-article20192019-01-01January 201910.1681/ASN.20180504621046-66731533-34502018-12-07T04:11:09-08:002019-01Journal of the American Society of NephrologyClinical Research301147158
- Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External Validation10.1681/ASN.2018070757Tue, 18 Dec 2018 04:10:47 GMT-08:00Simple Postoperative AKI Risk (SPARK) Classification before Noncardiac Surgery: A Prediction Index Development Study with External ValidationPark, SehoonCho, HyunjeongPark, SeokwooLee, SoojinKim, KwangsooYoon, Hyung JinPark, JiwonChoi, YunheeLee, SuehyunKim, Ju HanKim, SejoongChin, Ho JunKim, Dong KiJoo, Kwon WookKim, Yon SuLee, Hajeong2018-12-18T04:10:47-08:00doi:10.1681/ASN.2018070757hwp:resource-id:jnephrol;30/1/170American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, surgery, creatinineClinical ResearchClinical Researchresearch-article20192019-01-01January 201910.1681/ASN.20180707571046-66731533-34502018-12-18T04:10:47-08:002019-01Journal of the American Society of NephrologyClinical Research301117041816
- Projecting ESRD Incidence and Prevalence in the United States through 203010.1681/ASN.2018050531Mon, 17 Dec 2018 07:27:15 GMT-08:00Projecting ESRD Incidence and Prevalence in the United States through 2030McCullough, Keith P.Morgenstern, HalSaran, RajivHerman, William H.Robinson, Bruce M.2018-12-17T07:27:15-08:00doi:10.1681/ASN.2018050531hwp:resource-id:jnephrol;30/1/127American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyUnited States Renal Data System, end stage kidney disease, computer simulation, demographic trendsClinical EpidemiologyClinical Epidemiologyresearch-article20192019-01-01January 201910.1681/ASN.20180505311046-66731533-34502018-12-17T07:27:15-08:002019-01Journal of the American Society of NephrologyClinical Epidemiology301112731354
- Expression Profiling of Fibroblasts in Chronic and Acute Disease Models Reveals Novel Pathways in Kidney Fibrosis10.1681/ASN.2018060644Thu, 13 Dec 2018 10:20:20 GMT-08:00Expression Profiling of Fibroblasts in Chronic and Acute Disease Models Reveals Novel Pathways in Kidney FibrosisHigashi, Atsuko Y.Aronow, Bruce J.Dressler, Gregory R.2018-12-13T10:20:20-08:00doi:10.1681/ASN.2018060644hwp:resource-id:jnephrol;30/1/80American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, acute renal failure, prostaglandins, fibrosis, myofibroblastsBasic ResearchBasic Researchresearch-article20192019-01-01January 201910.1681/ASN.20180606441046-66731533-34502018-12-13T10:20:20-08:002019-01Journal of the American Society of NephrologyBasic Research3018094
- Improving Clinical Outcomes in the Era of Information Ubiquity10.1681/ASN.2018111128Thu, 20 Dec 2018 06:45:07 GMT-08:00Improving Clinical Outcomes in the Era of Information UbiquityCaliff, Robert M.2018-12-20T06:45:07-08:00doi:10.1681/ASN.2018111128hwp:resource-id:jnephrol;30/1/7American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical outcomes, life expectancy, precision medicineUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20192019-01-01January 201910.1681/ASN.20181111281046-66731533-34502018-12-20T06:45:07-08:002019-01Journal of the American Society of NephrologyUp Front Matters301712
- Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in Fibrosis10.1681/ASN.2018090912Mon, 03 Dec 2018 07:33:15 GMT-08:00Advantages of Single-Nucleus over Single-Cell RNA Sequencing of Adult Kidney: Rare Cell Types and Novel Cell States Revealed in FibrosisWu, HaojiaKirita, YuheiDonnelly, Erinn L.Humphreys, Benjamin D.2018-12-03T07:33:15-08:00doi:10.1681/ASN.2018090912hwp:resource-id:jnephrol;30/1/23American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of NephrologyRNA-sequencing, fibrosis, single cellRapid CommunicationRapid Communicationresearch-article20192019-01-01January 201910.1681/ASN.20180909121046-66731533-34502018-12-03T07:33:15-08:002019-01Journal of the American Society of NephrologyRapid Communication3012332
- Quantity and Reporting Quality of Kidney Research10.1681/ASN.2018050515Thu, 13 Dec 2018 10:20:19 GMT-08:00Quantity and Reporting Quality of Kidney ResearchChatzimanouil, Markos Kyriakos TomidisWilkens, LouiseAnders, Hans-Joachim2018-12-13T10:20:19-08:00doi:10.1681/ASN.2018050515hwp:resource-id:jnephrol;30/1/13American Society of NephrologyCopyright © 2019 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, kidney, clinical trialUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20192019-01-01January 201910.1681/ASN.20180505151046-66731533-34502018-12-13T10:20:19-08:002019-01Journal of the American Society of NephrologyUp Front Matters3011131222
- Intravenous Fluids10.2215/CJN.07850618Tue, 06 Nov 2018 08:25:14 GMT-08:00Intravenous FluidsPalevsky, Paul M.2018-11-06T08:25:14-08:00doi:10.2215/CJN.07850618hwp:resource-id:clinjasn;13/12/1912American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyintravenous fluids, acute kidney injury, isotonic saline, chloridePerspectivesPerspectivesresearch-article20182018-12-07December 07, 201810.2215/CJN.078506181555-90411555-905X2018-11-06T08:25:14-08:002018-12-07Clinical Journal of the American Society of NephrologyPerspectives131219121914
- Renal Fellow Network10.2215/CJN.06700518Fri, 14 Sep 2018 07:12:57 GMT-07:00Renal Fellow NetworkFarouk, SamiraSparks, Matthew A.2018-09-14T07:12:57-07:00doi:10.2215/CJN.06700518hwp:resource-id:clinjasn;13/12/1915American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEducation, Blogs, Fellow, Renal, kidneyPerspectivesPerspectivesresearch-article20182018-12-07December 07, 201810.2215/CJN.067005181555-90411555-905X2018-09-14T07:12:57-07:002018-12-07Clinical Journal of the American Society of NephrologyPerspectives131219151917
- Sleep Quality and Sleep Duration with CKD are Associated with Progression to ESKD10.2215/CJN.01340118Thu, 15 Nov 2018 07:47:59 GMT-08:00Sleep Quality and Sleep Duration with CKD are Associated with Progression to ESKDYamamoto, RyoheiShinzawa, MakiIsaka, YoshitakaYamakoshi, EtsukoImai, EnyuOhashi, YasuoHishida, Akira,2018-11-15T07:47:59-08:00doi:10.2215/CJN.01340118hwp:resource-id:clinjasn;13/12/1825American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and outcomes, chronic kidney disease, sleep hygiene, Sleep Deprivation, Hypnotics and Sedatives, Proportional Hazards Models, risk factors, Body Mass Index, glomerular filtration rate, Renin-Angiotensin System, Self Report, blood pressure, Prospective Studies, depression, Follow-Up Studies, Renal Insufficiency, Chronic, Sleep Initiation and Maintenance Disorders, diabetes mellitus, Cardiovascular Diseases, Metabolic Diseases, Smoking, AlbuminsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-12-07December 07, 201810.2215/CJN.013401181555-90411555-905X2018-11-15T07:47:59-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles131218251832
- Home-Based Kidney Care, Patient Activation, and Risk Factors for CKD Progression in Zuni Indians10.2215/CJN.06910618Thu, 15 Nov 2018 07:47:59 GMT-08:00Home-Based Kidney Care, Patient Activation, and Risk Factors for CKD Progression in Zuni IndiansNelson, Robert G.Pankratz, V. ShaneGhahate, Donica M.Bobelu, JeanetteFaber, ThomasShah, Vallabh O.2018-11-15T07:47:59-08:00doi:10.2215/CJN.06910618hwp:resource-id:clinjasn;13/12/1801American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, Epidemiology and outcomes, chronic kidney disease, outcomes, risk factors, C-Reactive Protein, Glycated Hemoglobin A, Patient Participation, Public Health, Vulnerable Populations, Linear Models, Body Mass Index, Mentoring, Renal Insufficiency, Chronic, Life Style, Chronic Disease, kidney, DietOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-12-07December 07, 201810.2215/CJN.069106181555-90411555-905X2018-11-15T07:47:59-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles13121212180117771779180917781780
- Association of Monoclonal Gammopathy with Progression to ESKD among US Veterans10.2215/CJN.06210518Thu, 15 Nov 2018 07:48:00 GMT-08:00Association of Monoclonal Gammopathy with Progression to ESKD among US VeteransBurwick, NicholasAdams, Scott V.Todd-Stenberg, Jeffrey A.Burrows, Nilka RiosPavkov, Meda E.O’Hare, Ann M.2018-11-15T07:48:00-08:00doi:10.2215/CJN.06210518hwp:resource-id:clinjasn;13/12/1810American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, renal failure, monoclonal gammopathy, multiple myeloma, Incidence, creatinine, Confidence Intervals, Retrospective Studies, Veterans, Semantic Web, Kidney Failure, Chronic, Paraproteins glomerular filtration rate, multiple myeloma M-proteins, Myeloma Proteins, Paraproteinemias, ScholarOne supportOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-12-07December 07, 201810.2215/CJN.062105181555-90411555-905X2018-11-15T07:48:00-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1312121810178118151782
- PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINT10.2215/CJN.05390518Tue, 13 Nov 2018 05:46:39 GMT-08:00PTH, FGF23, and Intensive Blood Pressure Lowering in Chronic Kidney Disease Participants in SPRINTGinsberg, CharlesCraven, Timothy E.Chonchol, Michel B.Cheung, Alfred K.Sarnak, Mark J.Ambrosius, Walter T.Killeen, Anthony A.Raphael, Kalani L.Bhatt, Udayan Y.Chen, JingChertow, Glenn M.Freedman, Barry I.Oparil, SuzannePapademetriou, VasiliosWall, Barry M.Wright, Clinton B.Ix, Joachim H.Shlipak, Michael G.,2018-11-13T05:46:39-08:00doi:10.2215/CJN.05390518hwp:resource-id:clinjasn;13/12/1816American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHypertension, parathyroid hormone, mineral metabolism, cardiovascular disease, congestive heart failureOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-12-07December 07, 201810.2215/CJN.053905181555-90411555-905X2018-11-13T05:46:39-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles131218161824
- BK Virus Nephropathy10.2215/CJN.04080318Fri, 21 Sep 2018 06:27:12 GMT-07:00BK Virus NephropathySawinski, DeirdreTrofe-Clark, Jennifer2018-09-21T06:27:12-07:00doi:10.2215/CJN.04080318hwp:resource-id:clinjasn;13/12/1893American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBK, kidney transplantation, BK Virus, Polyomavirus Infections, Kidney DiseasesKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-12-07December 07, 201810.2215/CJN.040803181555-90411555-905X2018-09-21T06:27:12-07:002018-12-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat131218931896
- Lung Ultrasonography in the Acutely Dyspneic Hemodialysis Patient10.2215/CJN.05190418Wed, 17 Oct 2018 08:58:13 GMT-07:00Lung Ultrasonography in the Acutely Dyspneic Hemodialysis PatientRoss, Daniel W.Jhaveri, Kenar D.2018-10-17T08:58:13-07:00doi:10.2215/CJN.05190418hwp:resource-id:clinjasn;13/12/1890American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyultrasound, lung ultrasound evidence to practice, Point of Care Ultrasound, B Lines, Dyspnea, dialysis, Patient Acuity, UltrasonographyKidney Case Conference: Attending RoundsKidney Case Conference: Attending Roundsresearch-article20182018-12-07December 07, 201810.2215/CJN.051904181555-90411555-905X2018-10-17T08:58:13-07:002018-12-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Attending Rounds131218901892
- Addressing Disparities in Living Donor Kidney Transplantation10.2215/CJN.06250518Wed, 14 Nov 2018 07:21:55 GMT-08:00Addressing Disparities in Living Donor Kidney TransplantationLentine, Krista L.Mandelbrot, Didier2018-11-14T07:21:55-08:00doi:10.2215/CJN.06250518hwp:resource-id:clinjasn;13/12/1909American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, living donation, kidney transplantation, disparities, Epidemiology and outcomes, Living Donors, Healthcare DisparitiesPerspectivesPerspectivesresearch-article20182018-12-07December 07, 201810.2215/CJN.062505181555-90411555-905X2018-11-14T07:21:55-08:002018-12-07Clinical Journal of the American Society of NephrologyPerspectives131219091911
- Helping More Patients Receive a Living Donor Kidney TransplantThe best treatment option for many patients with kidney failure is a kidney transplant from a living donor. Countries that successfully increase their rate of living kidney donation will decrease their reliance on dialysis, the most expensive and high-risk form of kidney replacement therapy. Outlined here are some barriers that prevent some patients from pursuing living kidney donation and current knowledge on some potential solutions to these barriers. Also described are strategies to promote living kidney donation in a defensible system of practice. Safely increasing the rate of living kidney donation will require better programs and policies to improve the experiences of living donors and their recipients, to safeguard the practice for years to come.10.2215/CJN.00760118Mon, 06 Aug 2018 05:55:05 GMT-07:00Helping More Patients Receive a Living Donor Kidney TransplantThe best treatment option for many patients with kidney failure is a kidney transplant from a living donor. Countries that successfully increase their rate of living kidney donation will decrease their reliance on dialysis, the most expensive and high-risk form of kidney replacement therapy. Outlined here are some barriers that prevent some patients from pursuing living kidney donation and current knowledge on some potential solutions to these barriers. Also described are strategies to promote living kidney donation in a defensible system of practice. Safely increasing the rate of living kidney donation will require better programs and policies to improve the experiences of living donors and their recipients, to safeguard the practice for years to come.Garg, Amit X.2018-08-06T05:55:05-07:00doi:10.2215/CJN.00760118hwp:resource-id:clinjasn;13/12/1918American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyLiving Donors, kidney transplantation, renal dialysis, Renal Insufficiency, Tissue and Organ Harvesting, Renal Replacement Therapy, kidneyFeaturesFeaturesresearch-article20182018-12-07December 07, 201810.2215/CJN.007601181555-90411555-905X2018-08-06T05:55:05-07:002018-12-07Clinical Journal of the American Society of NephrologyFeatures131219181923
- Acute Kidney Injury among Hospitalized Children in China10.2215/CJN.00800118Thu, 04 Oct 2018 06:09:52 GMT-07:00Acute Kidney Injury among Hospitalized Children in ChinaXu, XinNie, ShengZhang, AihuaMao, JianhuaLiu, Hai-PengXia, HuiminXu, HongLiu, ZhangsuoFeng, ShipinZhou, WeiLiu, XuemeiYang, YonghongTao, YuhongFeng, YunlinChen, ChunboWang, MoZha, YanFeng, Jian-HuaLi, QingchuGe, ShuwangChen, JianghuaHe, YongchengTeng, SiyuanHao, ChuanmingLiu, Bi-ChengTang, YingHe, WenjuanHe, PinghongHou, Fan Fan2018-10-04T06:09:52-07:00doi:10.2215/CJN.00800118hwp:resource-id:clinjasn;13/12/1791American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, children, clinical epidemiologyOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-12-07December 07, 201810.2215/CJN.008001181555-90411555-905X2018-10-04T06:09:52-07:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles131217911800
- Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome10.2215/CJN.06890618Thu, 15 Nov 2018 07:48:00 GMT-08:00Adrenocorticotropic Hormone for Childhood Nephrotic SyndromeWang, Chia-shiTravers, CurtisMcCracken, CourtneyLeong, TraciGbadegesin, RasheedQuiroga, AlejandroBenfield, Mark R.Hidalgo, GuillermoSrivastava, TarakLo, MeganYadin, OraMathias, RobertAraya, Carlos E.Khalid, MydaOrjuela, AlvaroZaritsky, JoshuaAl-Akash, SamharKamel, MargretGreenbaum, Larry A.2018-11-15T07:48:00-08:00doi:10.2215/CJN.06890618hwp:resource-id:clinjasn;13/12/1859American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, clinical trial, children, Adrenocorticotropic Hormone, Childhood Nephrotic SyndromeOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-12-07December 07, 201810.2215/CJN.068906181555-90411555-905X2018-11-15T07:48:00-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1312121859178818651790
- Duration of Treatment with Corticosteroids and Recovery of Kidney Function in Acute Interstitial Nephritis10.2215/CJN.01390118Mon, 05 Nov 2018 09:59:01 GMT-08:00Duration of Treatment with Corticosteroids and Recovery of Kidney Function in Acute Interstitial NephritisFernandez-Juarez, GemaPerez, Javier VillacortaCaravaca-Fontán, FernandoQuintana, LuisShabaka, AmirRodriguez, EvaGadola, Lilianade Lorenzo, AlbertoCobo, Maria AngelesOliet, AnianaSierra, MilagrosCobelo, CarmenIglesias, ElenaBlasco, MiguelGaleano, CristinaCordon, AlfredoOliva, JesusPraga, Manuel,2018-11-05T09:59:01-08:00doi:10.2215/CJN.01390118hwp:resource-id:clinjasn;13/12/1851American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCorticosteroids, treatment, drug induced acute interstitial nephritis, acute kidney disease, Prednisone, creatinine, Recovery of Function, renal dialysis, Nephritis, Interstitial, kidney, Kidney Function Tests, Urinary Tract Physiological Phenomena, Biopsy, Adrenal Cortex Hormones, Retrospective StudiesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-12-07December 07, 201810.2215/CJN.013901181555-90411555-905X2018-11-05T09:59:01-08:002018-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1312121851178518581787
- The Terrible Toll of the Kidney Shortage10.1681/ASN.2018101030Mon, 12 Nov 2018 08:03:51 GMT-08:00The Terrible Toll of the Kidney ShortageMcCormick, FrankHeld, Philip J.Chertow, Glenn M.2018-11-12T08:03:51-08:00doi:10.1681/ASN.2018101030hwp:resource-id:jnephrol;29/12/2775American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant, ESRD, costUp Front MattersEditorialUp Front MattersEditorialeditorial20182018-12-01December 201810.1681/ASN.20181010301046-66731533-34502018-11-12T08:03:51-08:002018-12Journal of the American Society of NephrologyUp Front Matters2912122775284727762857
- Authors’ Reply10.1681/ASN.2018101003Fri, 02 Nov 2018 05:06:10 GMT-07:00Authors’ ReplySethi, SanjeevRajkumar, VincentD'Agati, Vivette D.2018-11-02T05:06:10-07:00doi:10.1681/ASN.2018101003hwp:resource-id:jnephrol;29/12/2902American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, multiple myeloma, Renal pathologyLetter to the EditorLetter to the Editorletter20182018-12-01December 201810.1681/ASN.20181010031046-66731533-34502018-11-02T05:06:10-07:002018-12Journal of the American Society of NephrologyLetter to the Editor2912122902290129022901
- Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development10.1681/ASN.2017121278Tue, 30 Oct 2018 07:39:27 GMT-07:00Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney DevelopmentIde, ShintaroFiner, GalMaezawa, YoshiroOnay, TuncerSouma, TomokazuScott, RizaldyIde, KanaAkimoto, YoshihiroLi, ChengjinYe, MinghaoZhao, XiangminBaba, YusukeMinamizuka, TakuyaJin, JingTakemoto, MinoruYokote, KoutaroQuaggin, Susan E.2018-10-30T07:39:27-07:00doi:10.1681/ASN.2017121278hwp:resource-id:jnephrol;29/12/2795American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyUreteric bud branching, Transcription Factor 21, Congenital Anomalies of the Kidney and Urinary Tract, Renal stroma, Metanephric mesenchymeBasic ResearchBasic Researchresearch-article20182018-12-01December 201810.1681/ASN.20171212781046-66731533-34502018-10-30T07:39:27-07:002018-12Journal of the American Society of NephrologyBasic Research291227952808
- A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation10.1681/ASN.2018040392Thu, 25 Oct 2018 11:00:10 GMT-07:00A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell ProliferationMonteiro, Maria B.Ramm, SusanneChandrasekaran, VidyaBoswell, Sarah A.Weber, Elijah J.Lidberg, Kevin A.Kelly, Edward J.Vaidya, Vishal S.2018-10-25T11:00:10-07:00doi:10.1681/ASN.2018040392hwp:resource-id:jnephrol;29/12/2820American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAcute kidney injury, renal tubular epithelial cells, DYRK inhibitor, ID-8, Regenerative medicine, proliferationBasic ResearchBasic Researchresearch-article20182018-12-01December 201810.1681/ASN.20180403921046-66731533-34502018-10-25T11:00:10-07:002018-12Journal of the American Society of NephrologyBasic Research291228202833
- Financial Costs Incurred by Living Kidney Donors: A Prospective Cohort Study10.1681/ASN.2018040398Wed, 07 Nov 2018 09:13:02 GMT-08:00Financial Costs Incurred by Living Kidney Donors: A Prospective Cohort StudyPrzech, SebastianGarg, Amit X.Arnold, Jennifer B.Barnieh, LianneCuerden, Meaghan S.Dipchand, ChristineFeldman, LianeGill, John S.Karpinski, MartinKnoll, GregLok, CharmaineMiller, MatthewMonroy, MauricioNguan, ChrisPrasad, G.V. RameshSarma, SisiraSontrop, Jessica M.Storsley, LeroyKlarenbach, Scott,Arnold, JBBarnieh, LBoudville, NCuerden, MSDipchand, CFeldman, LGarg, AGill, JSKarpinski, MKlarenbach, SKnoll, GALok, CEMiller, MMonroy-Cuadros, MNguan, CPrasad, GV RameshSontrop, JMStorsley, LTreleaven, D2018-11-07T09:13:02-08:00doi:10.1681/ASN.2018040398hwp:resource-id:jnephrol;29/12/2847American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney donation, Economic Analysis, kidney transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20182018-12-01December 201810.1681/ASN.20180403981046-66731533-34502018-11-07T09:13:02-08:002018-12Journal of the American Society of NephrologyClinical Epidemiology2912122847277528572776
- Genetic Analysis of 400 Patients Refines Understanding and Implicates a New Gene in Atypical Hemolytic Uremic Syndrome10.1681/ASN.2018070759Tue, 30 Oct 2018 07:39:26 GMT-07:00Genetic Analysis of 400 Patients Refines Understanding and Implicates a New Gene in Atypical Hemolytic Uremic SyndromeBu, FengxiaoZhang, YuzhouWang, KaiBorsa, Nicolo GhiringhelliJones, Michael B.Taylor, Amanda O.Takanami, ErikaMeyer, Nicole C.Frees, KathyThomas, Christie P.Nester, CarlaSmith, Richard J.H.2018-10-30T07:39:26-07:00doi:10.1681/ASN.2018070759hwp:resource-id:jnephrol;29/12/2809American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, atypical hemolytic uremic syndrome, human geneticsBasic ResearchBasic Researchresearch-article20182018-12-01December 201810.1681/ASN.20180707591046-66731533-34502018-10-30T07:39:26-07:002018-12Journal of the American Society of NephrologyBasic Research291228092819
- This Month's Highlights10.1681/ASN.2018101020Fri, 30 Nov 2018 01:00:21 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2018-11-30T13:00:21-08:00doi:10.1681/ASN.2018101020hwp:resource-id:jnephrol;29/12/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-12-01December 201810.1681/ASN.20181010201046-66731533-34502018-11-30T13:00:21-08:002018-12Journal of the American Society of NephrologyThis Month’s Highlights2912ii
- Smoldering Myeloma Presenting with Renal Histopathology of Monoclonal Gammopathy of Renal Significance: Adding to the Complexity10.1681/ASN.2018080864Tue, 30 Oct 2018 07:39:28 GMT-07:00Smoldering Myeloma Presenting with Renal Histopathology of Monoclonal Gammopathy of Renal Significance: Adding to the ComplexityKousios, AndreasDuncan, NeillCharif, RawyaRoufosse, Candice2018-10-30T07:39:28-07:00doi:10.1681/ASN.2018080864hwp:resource-id:jnephrol;29/12/2901American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymyeloma, monoclonal immunoglobulin, monoclonal gammopathy of renal significance, smouldering myelomaLetter to the EditorLetter to the Editorletter20182018-12-01December 201810.1681/ASN.20180808641046-66731533-34502018-10-30T07:39:28-07:002018-12Journal of the American Society of NephrologyLetter to the Editor2912122901290229012902
- Dose-Dependent Effect of Enzyme Replacement Therapy on Neutralizing Antidrug Antibody Titers and Clinical Outcome in Patients with Fabry Disease10.1681/ASN.2018070740Thu, 01 Nov 2018 09:09:02 GMT-07:00Dose-Dependent Effect of Enzyme Replacement Therapy on Neutralizing Antidrug Antibody Titers and Clinical Outcome in Patients with Fabry DiseaseLenders, MalteNeußer, Leon PaulRudnicki, MichaelNordbeck, PeterCanaan-Kühl, SimaNowak, AlbinaCybulla, MarkusSchmitz, BorisLukas, JanWanner, ChristophBrand, Stefan-MartinBrand, Eva2018-11-01T09:09:02-07:00doi:10.1681/ASN.2018070740hwp:resource-id:jnephrol;29/12/2879American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Fabry disease, glomerular filtration rate, immune, complexes, left ventricular hypertrophyClinical ResearchClinical Researchresearch-article20182018-12-01December 201810.1681/ASN.20180707401046-66731533-34502018-11-01T09:09:02-07:002018-12Journal of the American Society of NephrologyClinical Research291228792889
- Cardiovascular Events after New-Onset Atrial Fibrillation in Adults with CKD: Results from the Chronic Renal Insufficiency Cohort (CRIC) Study10.1681/ASN.2018050514Tue, 30 Oct 2018 07:39:27 GMT-07:00Cardiovascular Events after New-Onset Atrial Fibrillation in Adults with CKD: Results from the Chronic Renal Insufficiency Cohort (CRIC) StudyBansal, NishaXie, DaweiSha, DaohangAppel, Lawrence J.Deo, RajatFeldman, Harold I.He, JiangJamerson, KennethKusek, John W.Messe, StevenNavaneethan, Sankar D.Rahman, MahboobRicardo, Ana CatherineSoliman, Elsayed Z.Townsend, RaymondGo, Alan S.2018-10-30T07:39:27-07:00doi:10.1681/ASN.2018050514hwp:resource-id:jnephrol;29/12/2859American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular events, chronic kidney disease, heart failureClinical ResearchClinical Researchresearch-article20182018-12-01December 201810.1681/ASN.20180505141046-66731533-34502018-10-30T07:39:27-07:002018-12Journal of the American Society of NephrologyClinical Research291228592869
- Health Outcome Priorities of Older Adults with Advanced CKD and Concordance with Their Nephrology Providers’ Perceptions10.1681/ASN.2018060657Thu, 01 Nov 2018 09:09:02 GMT-07:00Health Outcome Priorities of Older Adults with Advanced CKD and Concordance with Their Nephrology Providers’ PerceptionsRamer, Sarah J.McCall, Natalie N.Robinson-Cohen, CassianneSiew, Edward D.Salat, HuzaifahBian, AihuaStewart, Thomas G.El-Sourady, Maie H.Karlekar, MohanaLipworth, LorenIkizler, T. AlpAbdel-Kader, Khaled2018-11-01T09:09:02-07:00doi:10.1681/ASN.2018060657hwp:resource-id:jnephrol;29/12/2870American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, geriatric nephrology, quality of lifeClinical ResearchClinical Researchresearch-article20182018-12-01December 201810.1681/ASN.20180606571046-66731533-34502018-11-01T09:09:02-07:002018-12Journal of the American Society of NephrologyClinical Research291228702878
- Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age10.1681/ASN.2018030263Mon, 12 Nov 2018 08:03:52 GMT-08:00Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle AgeZheng, WenlingMu, JianjunChu, ChaoHu, JiawenYan, YuMa, QiongLv, YongboXu, XianjingWang, KekeWang, YangDeng, YingYan, BoYang, RuihaiYang, JunRen, YongYuan, Zuyi2018-11-12T08:03:52-08:00doi:10.1681/ASN.2018030263hwp:resource-id:jnephrol;29/12/2835American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure trajectory, eGFR, subclinical renal damage, prospective cohort study, uACRClinical EpidemiologyClinical Epidemiologyresearch-article20182018-12-01December 201810.1681/ASN.20180302631046-66731533-34502018-11-12T08:03:52-08:002018-12Journal of the American Society of NephrologyClinical Epidemiology291228352846
- The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial10.1681/ASN.2018040443Mon, 12 Nov 2018 08:03:52 GMT-08:00The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled TrialSaglimbene, ValeriaPalmer, Suetonia C.Ruospo, MarinellaNatale, PatriziaMaione, AusiliaNicolucci, AntonioVecchio, MariacristinaTognoni, GianniCraig, Jonathan C.Pellegrini, FabioLucisano, GiuseppeHegbrant, JörgenAriano, RosarioLamacchia, OlgaSasso, AntonioMorano, SusannaFilardi, TizianaDe Cosmo, SalvatorePugliese, GiuseppeProcaccini, Deni A.Gesualdo, LoretoPalasciano, GiuseppeJohnson, David W.Tonelli, MarcelloStrippoli, Giovanni F.M.,2018-11-12T08:03:52-08:00doi:10.1681/ASN.2018040443hwp:resource-id:jnephrol;29/12/2890American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, diabetic nephropathy, renin angiotensin system, mortality, end-stage renal disease, clinical trialClinical ResearchClinical Researchresearch-article20182018-12-01December 201810.1681/ASN.20180404431046-66731533-34502018-11-12T08:03:52-08:002018-12Journal of the American Society of NephrologyClinical Research291228902899
- Are Current Strategies for Building a Human Kidney Misguided? Speculative Alternatives10.1681/ASN.2018080822Tue, 30 Oct 2018 07:39:28 GMT-07:00Are Current Strategies for Building a Human Kidney Misguided? Speculative AlternativesFine, Leon G.2018-10-30T07:39:28-07:00doi:10.1681/ASN.2018080822hwp:resource-id:jnephrol;29/12/2780American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyKidney building, filtering organ, secreting organ, end-stage renal disease, stem cell, survival, glomerular endothelial cells, tubular epitheliumUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-12-01December 201810.1681/ASN.20180808221046-66731533-34502018-10-30T07:39:28-07:002018-12Journal of the American Society of NephrologyUp Front Matters291227802782
- Persistent Underrepresentation of Kidney Disease in Randomized, Controlled Trials of Cardiovascular Disease in the Contemporary Era10.1681/ASN.2018070674Fri, 02 Nov 2018 05:06:09 GMT-07:00Persistent Underrepresentation of Kidney Disease in Randomized, Controlled Trials of Cardiovascular Disease in the Contemporary EraMaini, RohitWong, David B.Addison, DanielChiang, ElizabethWeisbord, Steven D.Jneid, Hani2018-11-02T05:06:09-07:00doi:10.1681/ASN.2018070674hwp:resource-id:jnephrol;29/12/2782American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, chronic kidney disease, cardiovascular, cardiovascular disease, randomized controlled trialsUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-12-01December 201810.1681/ASN.20180706741046-66731533-34502018-11-02T05:06:09-07:002018-12Journal of the American Society of NephrologyUp Front Matters291227822786
- Evaluating the Evidence behind Policy Mandates in US Dialysis Care10.1681/ASN.2018090905Fri, 02 Nov 2018 05:06:10 GMT-07:00Evaluating the Evidence behind Policy Mandates in US Dialysis CareErickson, Kevin F.Winkelmayer, Wolfgang C.2018-11-02T05:06:10-07:00doi:10.1681/ASN.2018090905hwp:resource-id:jnephrol;29/12/2777American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, Economic Analysis, end stage kidney diseaseUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-12-01December 201810.1681/ASN.20180909051046-66731533-34502018-11-02T05:06:10-07:002018-12Journal of the American Society of NephrologyUp Front Matters291227772779
- Anticoagulant-Related NephropathyAnticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of “renal events” described in the post hoc analyses of three pivotal anticoagulation trials and three retrospective analyses of large clinical databases. Taken together, these analyses suggest that ARN is not a rare occurrence in the anticoagulated patient with atrial fibrillation. However, much work needs to be done to understand the condition, particularly prospective studies, to avoid the biases inherent in post hoc and retrospective analyses. Finally, we provide recommendations regarding the diagnosis and management of ARN on the basis of the best information available.10.1681/ASN.2018070741Mon, 12 Nov 2018 08:03:52 GMT-08:00Anticoagulant-Related NephropathyAnticoagulant-related nephropathy (ARN) is a newly recognized form of AKI in which overanticoagulation causes profuse glomerular hemorrhage, which manifests on renal biopsy as numerous renal tubules filled with red cells and red cell casts. The glomeruli show changes, but they are not sufficient to account for the glomerular hemorrhage. We were the first to study ARN, and since then, our work has been confirmed by numerous other investigators. Oral anticoagulants have been in widespread use since the 1950s; today, >2 million patients with atrial fibrillation take an oral anticoagulant. Despite this history of widespread and prolonged exposure to oral anticoagulants, ARN was discovered only recently, suggesting that the condition may be a rare occurrence. This review chronicles the discovery of ARN, its confirmation by others, and our animal model of ARN. We also provide new data on analysis of “renal events” described in the post hoc analyses of three pivotal anticoagulation trials and three retrospective analyses of large clinical databases. Taken together, these analyses suggest that ARN is not a rare occurrence in the anticoagulated patient with atrial fibrillation. However, much work needs to be done to understand the condition, particularly prospective studies, to avoid the biases inherent in post hoc and retrospective analyses. Finally, we provide recommendations regarding the diagnosis and management of ARN on the basis of the best information available.Brodsky, SergeyEikelboom, JohnHebert, Lee A.2018-11-12T08:03:52-08:00doi:10.1681/ASN.2018070741hwp:resource-id:jnephrol;29/12/2787American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, nephropathy, renal biopsyUp Front MattersReviewUp Front MattersReviewbrief-report20182018-12-01December 201810.1681/ASN.20180707411046-66731533-34502018-11-12T08:03:52-08:002018-12Journal of the American Society of NephrologyUp Front Matters291227872793
- BP in Dialysis: Results of a Pilot StudyThe optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110–140 mmHg (intensive arm) or 155–165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4–12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of −0.84 (−17.1 to 10.0) g and 1.4 (−11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.10.1681/ASN.2017020135Wed, 06 Dec 2017 08:02:19 GMT-08:00BP in Dialysis: Results of a Pilot StudyThe optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110–140 mmHg (intensive arm) or 155–165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4–12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of −0.84 (−17.1 to 10.0) g and 1.4 (−11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.Miskulin, Dana C.Gassman, JenniferSchrader, RonaldGul, AmbreenJhamb, ManishaPloth, David W.Negrea, LaviniaKwong, Raymond Y.Levey, Andrew S.Singh, Ajay K.Harford, AntoniaPaine, SusanKendrick, CynthiaRahman, MahboobZager, Philip2017-12-06T08:02:19-08:00doi:10.1681/ASN.2017020135hwp:resource-id:jnephrol;29/1/307American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, hypertension, randomized controlled trials, blood pressureClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170201351046-66731533-34502017-12-06T08:02:19-08:002018-01Journal of the American Society of NephrologyClinical Research291307316
- FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and ObesityBile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein–coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db mice with type 2 diabetes, and C57BL/6J mice with high-fat diet-induced obesity. We also examined the individual effects of the selective FXR agonist obeticholic acid (OCA) and the TGR5 agonist INT-777 in diabetic mice. The FXR agonist OCA and the TGR5 agonist INT-777 modulated distinct renal signaling pathways involved in the pathogenesis and treatment of diabetic nephropathy. Treatment of diabetic DBA/2J and db/db mice with the dual FXR/TGR5 agonist INT-767 improved proteinuria and prevented podocyte injury, mesangial expansion, and tubulointerstitial fibrosis. INT-767 exerted coordinated effects on multiple pathways, including stimulation of a signaling cascade involving AMP-activated protein kinase, sirtuin 1, PGC-1α, sirtuin 3, estrogen-related receptor-α, and Nrf-1; inhibition of endoplasmic reticulum stress; and inhibition of enhanced renal fatty acid and cholesterol metabolism. Additionally, in mice with diet-induced obesity, INT-767 prevented mitochondrial dysfunction and oxidative stress determined by fluorescence lifetime imaging of NADH and kidney fibrosis determined by second harmonic imaging microscopy. These results identify the renal signaling pathways regulated by FXR and TGR5, which may be promising targets for the treatment of nephropathy in diabetes and obesity.10.1681/ASN.2017020222Tue, 31 Oct 2017 07:51:28 GMT-07:00FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and ObesityBile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein–coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db mice with type 2 diabetes, and C57BL/6J mice with high-fat diet-induced obesity. We also examined the individual effects of the selective FXR agonist obeticholic acid (OCA) and the TGR5 agonist INT-777 in diabetic mice. The FXR agonist OCA and the TGR5 agonist INT-777 modulated distinct renal signaling pathways involved in the pathogenesis and treatment of diabetic nephropathy. Treatment of diabetic DBA/2J and db/db mice with the dual FXR/TGR5 agonist INT-767 improved proteinuria and prevented podocyte injury, mesangial expansion, and tubulointerstitial fibrosis. INT-767 exerted coordinated effects on multiple pathways, including stimulation of a signaling cascade involving AMP-activated protein kinase, sirtuin 1, PGC-1α, sirtuin 3, estrogen-related receptor-α, and Nrf-1; inhibition of endoplasmic reticulum stress; and inhibition of enhanced renal fatty acid and cholesterol metabolism. Additionally, in mice with diet-induced obesity, INT-767 prevented mitochondrial dysfunction and oxidative stress determined by fluorescence lifetime imaging of NADH and kidney fibrosis determined by second harmonic imaging microscopy. These results identify the renal signaling pathways regulated by FXR and TGR5, which may be promising targets for the treatment of nephropathy in diabetes and obesity.Wang, Xiaoxin X.Wang, DongLuo, YuhuanMyakala, KomuraiahDobrinskikh, EvgeniaRosenberg, Avi Z.Levi, JonathanKopp, Jeffrey B.Field, AmandaHill, AshleyLucia, ScottQiu, LiruJiang, TaoPeng, YingqiongOrlicky, DavidGarcia, GabrielHerman-Edelstein, MichalD’Agati, VivetteHenriksen, KammiAdorini, LucianoPruzanski, MarkXie, CenKrausz, Kristopher W.Gonzalez, Frank J.Ranjit, SumanDvornikov, AlexanderGratton, EnricoLevi, Moshe2017-10-31T07:51:28-07:00doi:10.1681/ASN.2017020222hwp:resource-id:jnephrol;29/1/118American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, metabolism, obesityBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170202221046-66731533-34502017-10-31T07:51:28-07:002018-01Journal of the American Society of NephrologyBasic Research291118137
- Neutralizing Antibody–Mediated Response and Risk of BK Virus–Associated NephropathyBK virus–associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype–specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; P=0.002). Each log10 increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients’ neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P=0.04). A NAb titer against the donor’s strain <4 log10 before transplant significantly associated with BKV replication after transplant (HR, 1.88; 95% CI, 1.06 to 3.45; P=0.03). BKV genotype–specific NAb titers may be a meaningful predictive marker that allows patient stratification by BKV disease risk before and after transplant.10.1681/ASN.2017050532Tue, 17 Oct 2017 06:48:31 GMT-07:00Neutralizing Antibody–Mediated Response and Risk of BK Virus–Associated NephropathyBK virus–associated nephropathy (BKVAN) causes renal allograft dysfunction. The current management of BKVAN relies on pre-emptive adaptation of immunosuppression according to viral load monitoring. However, this empiric strategy is not always successful. Therefore, pretransplant predictive markers are needed. In a prospective longitudinal study, we enrolled 168 kidney transplant recipients and 69 matched donors. To assess the value of BKV genotype–specific neutralizing antibody (NAb) titers as a predictive marker for BKV replication, we measured BKV DNA load and NAb titers at transplant and followed patients for 24 months. After transplant, 52 (31%) patients displayed BKV replication: 24 (46%) patients were viruric and 28 (54%) patients were viremic, including 13 with biopsy-confirmed BKVAN. At any time, patients with high NAb titers against the replicating strain had a lower risk of developing BKV viremia (hazard ratio [HR], 0.44; 95% confidence interval [95% CI], 0.26 to 0.73; P=0.002). Each log10 increase in NAb titer decreased the risk of developing viremia by 56%. Replicating strains were consistent with donor transmission in 95% of cases of early BKV replication. Genotype mismatch between recipients’ neutralization profiles before transplant and their subsequently replicating strain significantly increased the risk of developing viremia (HR, 2.27; 95% CI, 1.06 to 4.88; P=0.04). A NAb titer against the donor’s strain <4 log10 before transplant significantly associated with BKV replication after transplant (HR, 1.88; 95% CI, 1.06 to 3.45; P=0.03). BKV genotype–specific NAb titers may be a meaningful predictive marker that allows patient stratification by BKV disease risk before and after transplant.Solis, MorganeVelay, AuréliePorcher, RaphaëlDomingo-Calap, PilarSoulier, EricJoly, MélanieMeddeb, MariamKack-Kack, WallysMoulin, BrunoBahram, SiamakStoll-Keller, FrançoiseBarth, HeidiCaillard, SophieFafi-Kremer, Samira2017-10-17T06:48:31-07:00doi:10.1681/ASN.2017050532hwp:resource-id:jnephrol;29/1/326American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant outcomes, immunology, Viral infection, Predictive markerClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170505321046-66731533-34502017-10-17T06:48:31-07:002018-01Journal of the American Society of NephrologyClinical Research291326334
- Clusters Not Classifications: Making Sense of Complement-Mediated Kidney Injury10.1681/ASN.2017111183Mon, 11 Dec 2017 05:06:45 GMT-08:00Clusters Not Classifications: Making Sense of Complement-Mediated Kidney InjuryCook, H. TerencePickering, Matthew C.2017-12-11T05:06:45-08:00doi:10.1681/ASN.2017111183hwp:resource-id:jnephrol;29/1/9American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyC3 glomerulopathy, membranoproliferative glomerulonephritis (MPGN), dense deposit disease, glomerulonephritisUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-01-01January 201810.1681/ASN.20171111831046-66731533-34502017-12-11T05:06:45-08:002018-01Journal of the American Society of NephrologyUp Front Matters2911928312294
- Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 GeneThe bone-derived hormone fibroblast growth factor–23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1DT-cKO mice) resulted in left ventricular hypertrophy (LVH) and decreased kidney expression of α-Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na+-K+-2Cl− cotransporter. Notably, recombinant FGF-23 administration similarly decreased the kidney expression of α-Klotho and induced LVH in mice. Pharmacologic activation of FGFR1 with a monoclonal anti-FGFR1 antibody (R1MAb1) normalized BP and significantly attenuated LVH in the Hyp mouse model of excess FGF-23, but did not induce a response in FGFR1DT-cKO mice. The hearts of FGFR1DT-cKO mice showed increased expression of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6), consistent with cardiac effects of soluble Klotho deficiency. Moreover, administration of recombinant soluble Klotho lowered BP in the Hyp mice. Thus, FGFR1 in the DT regulates systemic hemodynamic responses opposite to those predicted by the actions of FGF-23. These cardiovascular effects appear to be mediated by paracrine FGF control of kidney FGFR1 and subsequent regulation of soluble Klotho and TRPC6. FGFR1 in the kidney may provide a new molecular target for treating hypertension.10.1681/ASN.2017040412Mon, 09 Oct 2017 10:43:41 GMT-07:00Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 GeneThe bone-derived hormone fibroblast growth factor–23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1DT-cKO mice) resulted in left ventricular hypertrophy (LVH) and decreased kidney expression of α-Klotho in association with enhanced BP, decreased expression of angiotensin converting enzyme 2, and increased expression of the Na+-K+-2Cl− cotransporter. Notably, recombinant FGF-23 administration similarly decreased the kidney expression of α-Klotho and induced LVH in mice. Pharmacologic activation of FGFR1 with a monoclonal anti-FGFR1 antibody (R1MAb1) normalized BP and significantly attenuated LVH in the Hyp mouse model of excess FGF-23, but did not induce a response in FGFR1DT-cKO mice. The hearts of FGFR1DT-cKO mice showed increased expression of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6), consistent with cardiac effects of soluble Klotho deficiency. Moreover, administration of recombinant soluble Klotho lowered BP in the Hyp mice. Thus, FGFR1 in the DT regulates systemic hemodynamic responses opposite to those predicted by the actions of FGF-23. These cardiovascular effects appear to be mediated by paracrine FGF control of kidney FGFR1 and subsequent regulation of soluble Klotho and TRPC6. FGFR1 in the kidney may provide a new molecular target for treating hypertension.Han, XiaobinRoss, JedKolumam, GaneshPi, MinSonoda, JunichiroKing, GwendalynQuarles, L. Darryl2017-10-09T10:43:41-07:00doi:10.1681/ASN.2017040412hwp:resource-id:jnephrol;29/1/69American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, heart disease, hypertension, hypertrophy, renin angiotensin system, distal tubuleBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170404121046-66731533-34502017-10-09T10:43:41-07:002018-01Journal of the American Society of NephrologyBasic Research2916980
- Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic PhenotypesMagnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10−13) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1×10−11), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene–environment interaction linking Mg2+ deficiency to insulin resistance and obesity.10.1681/ASN.2017030267Wed, 01 Nov 2017 06:17:43 GMT-07:00Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic PhenotypesMagnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10−13) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1×10−11), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene–environment interaction linking Mg2+ deficiency to insulin resistance and obesity.Corre, TanguyArjona, Francisco J.Hayward, CarolineYouhanna, Soniade Baaij, Jeroen H.F.Belge, HendricaNägele, NadineDebaix, HuguetteBlanchard, Maxime G.Traglia, MichelaHarris, Sarah E.Ulivi, SheilaRueedi, RicoLamparter, DavidMacé, AurélienSala, CinziaLenarduzzi, StefaniaPonte, BelenPruijm, MennoAckermann, DanielEhret, GeorgBaptista, DanielaPolasek, OzrenRudan, IgorHurd, Toby W.Hastie, Nicholas D.Vitart, VeroniqueWaeber, GeràrdKutalik, ZoltánBergmann, SvenVargas-Poussou, RosaKonrad, MartinGasparini, PaoloDeary, Ian J.Starr, John M.Toniolo, DanielaVollenweider, PeterHoenderop, Joost G.J.Bindels, René J.M.Bochud, MurielleDevuyst, Olivier2017-11-01T06:17:43-07:00doi:10.1681/ASN.2017030267hwp:resource-id:jnephrol;29/1/335American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyzebrafish, Genetic determinants, Magnesium homeostasis, Metabolic syndrome, Gene-environment interaction, Tubular transportMeta-AnalysisMeta-Analysisresearch-article20182018-01-01January 201810.1681/ASN.20170302671046-66731533-34502017-11-01T06:17:43-07:002018-01Journal of the American Society of NephrologyMeta-Analysis291335348
- Recent Advances in the Management of Autosomal Dominant Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.10.2215/CJN.03960318Thu, 26 Jul 2018 06:21:31 GMT-07:00Recent Advances in the Management of Autosomal Dominant Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by relentless development of kidney cysts, hypertension, and destruction of the kidney parenchyma. Over the past few years, major advancements in diagnosing, prognosticating, and understanding the pathogenesis and natural course of the disease have been made. Currently, no kidney disease is more suitable for nephron-protective strategies. Early nephrology referral and implementation of these strategies may have a substantial effect. Total kidney volume is a good prognostication marker and allows stratification of patients into slow or rapid progressing disease, with implications for their management. Measurement of total kidney volume, disease stratification, and prognostication are possible using readily available tools. Although some patients require only monitoring and basic optimized kidney protective measures, such as rigorous BP control and various lifestyle and dietary changes, others will benefit from disease-modifying treatments. Vasopressin V2 receptor antagonists, a likely disease-modifying treatment, has been approved in several countries and recently by the US Food and Drug Administration; other therapies, such as somatostatin analogs and other novel agents, are currently in clinical trials. The purpose of this article is to present our views on the optimal management to delay kidney disease progression in ADPKD.Chebib, Fouad T.Torres, Vicente E.2018-07-26T06:21:31-07:00doi:10.2215/CJN.03960318hwp:resource-id:clinjasn;13/11/1765American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, Dietary Sodium, vasopressin, Polycystic Kidney, Autosomal Dominant, blood pressure, Receptors, Vasopressin, United States Food and Drug Administration, Somatostatin, Kidney Failure, Chronic, Antidiuretic Hormone Receptor Antagonists, Nephrons, hypertension, Referral and Consultation, Disease Progression, CystsReviewsReviewsreview-article20182018-11-07November 07, 201810.2215/CJN.039603181555-90411555-905X2018-07-26T06:21:31-07:002018-11-07Clinical Journal of the American Society of NephrologyReviews131117651776
- CKD in Patients with Bilateral Oophorectomy10.2215/CJN.03990318Wed, 19 Sep 2018 07:31:58 GMT-07:00CKD in Patients with Bilateral OophorectomyKattah, Andrea G.Smith, Carin Y.Gazzuola Rocca, LilianaGrossardt, Brandon R.Garovic, Vesna D.Rocca, Walter A.2018-09-19T07:31:58-07:00doi:10.2215/CJN.03990318hwp:resource-id:clinjasn;13/11/1649American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOophorectomy, estrogen, chronic kidney disease, cohort study, modifiable risk factor, accelerated aging, Incidence, Cohort Studies, Proportional Hazards Models, Multiple Chronic Conditions, Body Mass Index, glomerular filtration rate, Menopause, Ovariectomy, Premenopause, Estrogens, Renal Insufficiency, Chronic, SmokingOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-11-07November 07, 201810.2215/CJN.039903181555-90411555-905X2018-09-19T07:31:58-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131116491658
- End-Stage Kidney Disease following Surgical Management of Kidney Cancer10.2215/CJN.06560518Fri, 28 Sep 2018 05:26:41 GMT-07:00End-Stage Kidney Disease following Surgical Management of Kidney CancerEllis, Robert J.Edey, Daniel P.Del Vecchio, Sharon J.McStea, MeganCampbell, Scott B.Hawley, Carmel M.Johnson, David W.Morais, ChristudasJordan, Susan J.Francis, Ross S.Wood, Simon T.Gobe, Glenda C.,2018-09-28T05:26:41-07:00doi:10.2215/CJN.06560518hwp:resource-id:clinjasn;13/11/1641American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, kidney cancer, glomerular filtration rate, renal cell carcinoma, end-stage kidney disease, Proportional Hazards Models, Incidence, International Classification of Diseases, Anesthesiologists, Renal Replacement Therapy, Kidney Failure, Chronic, Kidney Neoplasms, diabetes mellitus, Registries, hospitalization, NephrectomyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-11-07November 07, 201810.2215/CJN.065605181555-90411555-905X2018-09-28T05:26:41-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131116411648
- Patient Experience with Primary Care Physician and Risk for Hospitalization in Hispanics with CKD10.2215/CJN.03170318Thu, 18 Oct 2018 07:16:25 GMT-07:00Patient Experience with Primary Care Physician and Risk for Hospitalization in Hispanics with CKDCedillo-Couvert, Esteban A.Hsu, Jesse Y.Ricardo, Ana C.Fischer, Michael J.Gerber, Ben S.Horwitz, Edward J.Kusek, John W.Lustigova, EvaRenteria, AmadaRosas, Sylvia E.Saunders, MildaSha, DaohangSlaven, AnneLash, James P.,2018-10-18T07:16:25-07:00doi:10.2215/CJN.03170318hwp:resource-id:clinjasn;13/11/1659American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Female, Middle Aged, glomerular filtration rate, Prospective Studies, Language, Physicians, Primary Care, Follow-Up Studies, Proportional Hazards Models, Renal Insufficiency, Chronic, Kidney Failure, Chronic, Risk, Cause of Death, Hispanic Americans, hospitalization, Ambulatory Care, Surveys and Questionnaires, Health PromotionOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-11-07November 07, 201810.2215/CJN.031703181555-90411555-905X2018-10-18T07:16:25-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1311111659161916671620
- Kidney Biopsy–Related Complications in Hospitalized Patients with Acute Kidney Disease10.2215/CJN.04910418Mon, 22 Oct 2018 07:27:00 GMT-07:00Kidney Biopsy–Related Complications in Hospitalized Patients with Acute Kidney DiseaseMoledina, Dennis G.Luciano, Randy L.Kukova, LidiyaChan, LiliSaha, AparnaNadkarni, GirishAlfano, SandraWilson, F. PerryPerazella, Mark A.Parikh, Chirag R.2018-10-22T07:27:00-07:00doi:10.2215/CJN.04910418hwp:resource-id:clinjasn;13/11/1633American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinterventional nephrology, kidney biopsy, kidney failure, risk factors, ultrasonography, kidney pathology, blood transfusion, female, adult, prospective studies, multivariable analysis, Blood Urea Nitrogen, Confidence Intervals, Platelet Count, Angiography, Acute Kidney Injury, biopsy, Tomography, X-Ray Computed, Hematoma, hospitalization, Hemoglobins, Cohort StudiesOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-11-07November 07, 201810.2215/CJN.049104181555-90411555-905X2018-10-22T07:27:00-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1311111633161716401618
- Hepatitis C Virus Infection in ESKD Patients10.2215/CJN.03700318Tue, 31 Jul 2018 06:31:28 GMT-07:00Hepatitis C Virus Infection in ESKD PatientsLadino, MarcoRoth, David2018-07-31T06:31:28-07:00doi:10.2215/CJN.03700318hwp:resource-id:clinjasn;13/11/1735American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHCV, transplantation, ESKD, Hepacivirus, hepatitisKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-11-07November 07, 201810.2215/CJN.037003181555-90411555-905X2018-07-31T06:31:28-07:002018-11-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat131117351737
- The Patient Receiving Automated Peritoneal Dialysis with Volume Overload10.2215/CJN.02570218Mon, 10 Sep 2018 04:48:34 GMT-07:00The Patient Receiving Automated Peritoneal Dialysis with Volume OverloadTrinh, EmiliePerl, Jeffrey2018-09-10T04:48:34-07:00doi:10.2215/CJN.02570218hwp:resource-id:clinjasn;13/11/1732American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, dialysis volume, fluid overload, overhydration, pamidronate, Water-Electrolyte Imbalance, Acid-Base ImbalanceKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-11-07November 07, 201810.2215/CJN.025702181555-90411555-905X2018-09-10T04:48:34-07:002018-11-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat131117321734
- Acute Kidney Injury in Children with Kidney Transplantation10.2215/CJN.02440218Fri, 21 Sep 2018 06:27:14 GMT-07:00Acute Kidney Injury in Children with Kidney TransplantationAlkandari, OmarNguyen, LieukoHebert, DianeLanglois, ValerieJawa, Natasha A.Parekh, Rulan S.Robinson, Lisa A.2018-09-21T06:27:14-07:00doi:10.2215/CJN.02440218hwp:resource-id:clinjasn;13/11/1721American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAKI, children, kidney transplant, Child, Humans, kidney transplantation, Acute Kidney Injury, glomerular filtration rate, Incidence, creatinine, Retrospective Studies, risk factors, Renal Insufficiency, Chronic, Kidney Function Tests, Urinary Tract Infections, Regression AnalysisOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-11-07November 07, 201810.2215/CJN.024402181555-90411555-905X2018-09-21T06:27:14-07:002018-11-07Clinical Journal of the American Society of NephrologyOriginal Articles131117211729
- Regulatory T Cells and Kidney TransplantationThe ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.10.2215/CJN.01750218Tue, 22 May 2018 06:32:31 GMT-07:00Regulatory T Cells and Kidney TransplantationThe ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection. A key issue in clinical use of Tregs is how to effectively expand the number of Tregs, either through increasing numbers of endogenous Tregs or by the direct infusion of exogenously expanded Tregs. In order to realize the benefits of Treg therapy in solid organ transplantation, a number of outstanding challenges need to be overcome, including assuring an effective expansion of Tregs, improving long-term Treg stability and reduction of risk-related to off-target, nonspecific, immunosuppressive effects related specially to cancer.Martin-Moreno, Paloma LeticiaTripathi, SudiptaChandraker, Anil2018-05-22T06:32:31-07:00doi:10.2215/CJN.01750218hwp:resource-id:clinjasn;13/11/1760American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAllografts, Goals, IL2RA protein, human, immunosuppression, Interleukin-2 Receptor Alpha Subunit, Interleukins, kidney, kidney transplantation, Neoplasms, Receptors, Interleukin-2, T-lymphocytes, Regulatory, tolerance, transcription factors, transplantationReviewsReviewsreview-article20182018-11-07November 07, 201810.2215/CJN.017502181555-90411555-905X2018-05-22T06:32:31-07:002018-11-07Clinical Journal of the American Society of NephrologyReviews131117601764
- Maintenance of Certification10.2215/CJN.06330617Tue, 10 Oct 2017 07:48:57 GMT-07:00Maintenance of CertificationWeinstein, Adam2017-10-10T07:48:57-07:00doi:10.2215/CJN.06330617hwp:resource-id:clinjasn;13/1/170American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMaintenance of Certification, ABIM, MOC, Certification, Maintenance, Specialty BoardsPerspectivesPerspectivesresearch-article20182018-01-06January 06, 201810.2215/CJN.063306171555-90411555-905X2017-10-10T07:48:57-07:002018-01-06Clinical Journal of the American Society of NephrologyPerspectives131170171
- Maintenance of Certification10.2215/CJN.07950717Tue, 10 Oct 2017 07:48:57 GMT-07:00Maintenance of CertificationRosner, Mitchell H.2017-10-10T07:48:57-07:00doi:10.2215/CJN.07950717hwp:resource-id:clinjasn;13/1/161American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymaintenance of certification, nephrology, debate, continuing medical education, Certification, MaintenancePerspectivesPerspectivesresearch-article20182018-01-06January 06, 201810.2215/CJN.079507171555-90411555-905X2017-10-10T07:48:57-07:002018-01-06Clinical Journal of the American Society of NephrologyPerspectives131161163
- Coaching Nephrology Trainees Who Struggle with Clinical Performance10.2215/CJN.07270717Wed, 01 Nov 2017 06:17:31 GMT-07:00Coaching Nephrology Trainees Who Struggle with Clinical PerformanceWarburton, Karen M.Mahan, John D.2017-11-01T06:17:31-07:00doi:10.2215/CJN.07270717hwp:resource-id:clinjasn;13/1/172American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyeducation, remediation, struggling fellow, coaching, fellow assessment, professionalismPerspectivesPerspectivesresearch-article20182018-01-06January 06, 201810.2215/CJN.072707171555-90411555-905X2017-11-01T06:17:31-07:002018-01-06Clinical Journal of the American Society of NephrologyPerspectives131172174
- Transformation of ABIM and What the Changes Mean to Nephrologists10.2215/CJN.05700517Tue, 10 Oct 2017 07:48:57 GMT-07:00Transformation of ABIM and What the Changes Mean to NephrologistsIkizler, T. AlpBerns, Jeffrey S.2017-10-10T07:48:57-07:00doi:10.2215/CJN.05700517hwp:resource-id:clinjasn;13/1/164American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, Internal Medicine, Specialty Boards, NephrologistsPerspectivesPerspectivesresearch-article20182018-01-06January 06, 201810.2215/CJN.057005171555-90411555-905X2017-10-10T07:48:57-07:002018-01-06Clinical Journal of the American Society of NephrologyPerspectives131164166
- TESTING Corticosteroids in IgA Nephropathy10.2215/CJN.10560917Wed, 13 Dec 2017 07:16:50 GMT-08:00TESTING Corticosteroids in IgA NephropathyTam, Frederick W.K.Pusey, Charles D.2017-12-13T07:16:50-08:00doi:10.2215/CJN.10560917hwp:resource-id:clinjasn;13/1/158American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, corticosteroids, kidney function, adverse events, Humans, Glomerulonephritis, IGA, Hematuria, Prevalence, kidney, proteinuria, Kidney Failure, Chronic, glomerulonephritis, hypertension, Prognosis, Adrenal Cortex Hormones, Immunoglobulin A, BiopsyPerspectivesPerspectivesresearch-article20182018-01-06January 06, 201810.2215/CJN.105609171555-90411555-905X2017-12-13T07:16:50-08:002018-01-06Clinical Journal of the American Society of NephrologyPerspectives131158160
- Toward More Meaningful Accountability to the Public10.2215/CJN.07570717Tue, 10 Oct 2017 07:48:56 GMT-07:00Toward More Meaningful Accountability to the PublicRosenberg, Mark E.2017-10-10T07:48:56-07:00doi:10.2215/CJN.07570717hwp:resource-id:clinjasn;13/1/167American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyoutcomes, competence, MOC, education, Education, Medical, Graduate, Specialty Boards, Accreditation, Physicians, Medicine, Patient CarePerspectivesPerspectivesresearch-article20182018-01-06January 06, 201810.2215/CJN.075707171555-90411555-905X2017-10-10T07:48:56-07:002018-01-06Clinical Journal of the American Society of NephrologyPerspectives131167169
- Lessons from CKD-Related Genetic Association Studies–Moving ForwardOver the past decade, genetic association studies have uncovered numerous determinants of kidney function in the general, diabetic, hypertensive, CKD, ESRD, and GN-based study populations (e.g., IgA nephropathy, membranous nephropathy, FSGS). These studies have led to numerous novel and unanticipated findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. In this review, we report on major discoveries and advances resulting from this rapidly progressing research domain. We also predict some of the next steps the nephrology community should embrace to accelerate the identification of genetic and molecular processes leading to kidney dysfunction, pathophysiologically based disease subgroups, and specific therapeutic targets, as we attempt to transition toward a more precision-based medicine approach.10.2215/CJN.09030817Thu, 14 Dec 2017 06:26:34 GMT-08:00Lessons from CKD-Related Genetic Association Studies–Moving ForwardOver the past decade, genetic association studies have uncovered numerous determinants of kidney function in the general, diabetic, hypertensive, CKD, ESRD, and GN-based study populations (e.g., IgA nephropathy, membranous nephropathy, FSGS). These studies have led to numerous novel and unanticipated findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. In this review, we report on major discoveries and advances resulting from this rapidly progressing research domain. We also predict some of the next steps the nephrology community should embrace to accelerate the identification of genetic and molecular processes leading to kidney dysfunction, pathophysiologically based disease subgroups, and specific therapeutic targets, as we attempt to transition toward a more precision-based medicine approach.Limou, SophieVince, NicolasParsa, Afshin2017-12-14T06:26:34-08:00doi:10.2215/CJN.09030817hwp:resource-id:clinjasn;13/1/140American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, genetic renal disease, systems biology, genome wide association, precision medicine, nephrology, glomerulonephritis, Renal Insufficiency, Chronic, Hypertensive Nephropathy, Hypertension, Renal, nephritis, Kidney Failure, Chronic, diabetes mellitus, Genetic Association StudiesEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20182018-01-06January 06, 201810.2215/CJN.090308171555-90411555-905X2017-12-14T06:26:34-08:002018-01-06Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology1311140153152154
- SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts10.1681/ASN.2018060573Fri, 19 Oct 2018 08:18:17 GMT-07:00SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in AllograftsWei, ChengguoBanu, KhadijaGarzon, FelipeBasgen, John M.Philippe, NimrodYi, ZhengziLiu, RuijieChoudhuri, JuiFribourg, MiguelLiu, TongCumpelik, ArunWong, JennyKhan, MubeenDas, BhaskarKeung, KarenSalem, FadiCampbell, Kirk N.Kaufman, LewisCravedi, PaoloZhang, WeijiaO'Connell, Philip J.He, John CijiangMurphy, BarbaraMenon, Madhav C.2018-10-19T08:18:17-07:00doi:10.1681/ASN.2018060573hwp:resource-id:jnephrol;29/11/2641American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyCell Signaling, podocyte, renal transplantation, gene expressionBasic ResearchBasic Researchresearch-article20182018-11-01November 201810.1681/ASN.20180605731046-66731533-34502018-10-19T08:18:17-07:002018-11Journal of the American Society of NephrologyBasic Research291126412657
- Authors’ Reply10.1681/ASN.2018080811Fri, 21 Sep 2018 06:27:41 GMT-07:00Authors’ ReplyIshida, Julie H.McCulloch, Charles E.Steinman, Michael A.Grimes, Barbara A.Johansen, Kirsten L.2018-09-21T06:27:41-07:00doi:10.1681/ASN.2018080811hwp:resource-id:jnephrol;29/11/2771-aAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygabapentin, pregabalin, hemodialysis, United States Renal Data SystemLetter to the EditorLetter to the Editorletter20182018-11-01November 201810.1681/ASN.20180808111046-66731533-34502018-09-21T06:27:41-07:002018-11Journal of the American Society of NephrologyLetter to the Editor2911112771277127722771
- Gabepentinoids and Benzodiazepines in Medicare Part D10.1681/ASN.2018070745Fri, 21 Sep 2018 06:27:41 GMT-07:00Gabepentinoids and Benzodiazepines in Medicare Part DWeinhandl, Eric D.2018-09-21T06:27:41-07:00doi:10.1681/ASN.2018070745hwp:resource-id:jnephrol;29/11/2771American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygabapentin, pharmacoepidemiology, pregabalinLetter to the EditorLetter to the Editorletter20182018-11-01November 201810.1681/ASN.20180707451046-66731533-34502018-09-21T06:27:41-07:002018-11Journal of the American Society of NephrologyLetter to the Editor2911112771277127712772
- Peroxidasin—a Novel Autoantigen in Anti-GBM Disease?10.1681/ASN.2018090946Fri, 12 Oct 2018 07:42:18 GMT-07:00Peroxidasin—a Novel Autoantigen in Anti-GBM Disease?McAdoo, Stephen P.Pusey, Charles D.2018-10-12T07:42:18-07:00doi:10.1681/ASN.2018090946hwp:resource-id:jnephrol;29/11/2605-aAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, ANCA, Goodpasture-s syndrome, vasculitis, glomerulonephritisUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-11-01November 201810.1681/ASN.20180909461046-66731533-34502018-10-12T07:42:18-07:002018-11Journal of the American Society of NephrologyUp Front Matters2911112605261926072625
- This Month’s Highlights10.1681/ASN.2018090953Wed, 31 Oct 2018 01:00:28 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2018-10-31T13:00:28-07:00doi:10.1681/ASN.2018090953hwp:resource-id:jnephrol;29/11/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-11-01November 201810.1681/ASN.20180909531046-66731533-34502018-10-31T13:00:28-07:002018-11Journal of the American Society of NephrologyThis Month’s Highlights2911ii
- The Science of Fistula Maturation10.1681/ASN.2018090922Wed, 10 Oct 2018 09:16:33 GMT-07:00The Science of Fistula MaturationOliver, Matthew J.2018-10-10T09:16:33-07:00doi:10.1681/ASN.2018090922hwp:resource-id:jnephrol;29/11/2607American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyaccess blood flow, arteriovenous fistula, ESRDUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-11-01November 201810.1681/ASN.20180909221046-66731533-34502018-10-10T09:16:33-07:002018-11Journal of the American Society of NephrologyUp Front Matters2911112607273526092744
- Association of Soluble TNFR-1 Concentrations with Long-Term Decline in Kidney Function: The Multi-Ethnic Study of Atherosclerosis10.1681/ASN.2018070719Thu, 04 Oct 2018 06:10:07 GMT-07:00Association of Soluble TNFR-1 Concentrations with Long-Term Decline in Kidney Function: The Multi-Ethnic Study of AtherosclerosisBhatraju, Pavan K.Zelnick, Leila R.Shlipak, MichaelKatz, RonitKestenbaum, Bryan2018-10-04T06:10:07-07:00doi:10.1681/ASN.2018070719hwp:resource-id:jnephrol;29/11/2713American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, endothelium, Chronic inflammation, soluble tumor necrosis factor receptor-1Clinical EpidemiologyClinical Epidemiologyresearch-article20182018-11-01November 201810.1681/ASN.20180707191046-66731533-34502018-10-04T06:10:07-07:002018-11Journal of the American Society of NephrologyClinical Epidemiology291127132721
- DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS10.1681/ASN.2018010091Thu, 25 Oct 2018 09:30:09 GMT-07:00DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGSTrachtman, HowardNelson, PeterAdler, SharonCampbell, Kirk N.Chaudhuri, AbantiDerebail, Vimal KumarGambaro, GiovanniGesualdo, LoretoGipson, Debbie S.Hogan, JonathanLieberman, KennethMarder, BradMeyers, Kevin EdwardMustafa, EsmatRadhakrishnan, JaiSrivastava, TarakStepanians, MiganushTesar, VladimírZhdanova, OlgaKomers, Radko,,Alappan, RajendranAnand, SanjivAli, Nausheen BanoBaranski, JoelBissler, JohnCadnapaphornchai, Melissa,,,,Chorny, NataliyaDell, Katherine,Egidi, MariaElliott, MatthewEl-Shahawy, MohamedEsposito, CiroFeig, DanielFlynn, JosephFornoni, AlessiaGermain, MichaelGibson, Keisha,Haws, RobertJohnstone, DuncanKhosla, NeenooKopyt, NelsonKusnir, JorgeLane, PascaleMahan, JohnMcCarthy, EllenMercado, Carlos,Minetti, EnricoNester, CarlaNeu, AliciaParades, AnaPergola, PabloRaguram, ParthassarathyRaina, RupeshRheault, MichelleRobertson, JohnRychlik, IvanSanghani, NeilSprangers, BenUmanath, KausikWoroniecki, Robert,2018-10-25T09:30:09-07:00doi:10.1681/ASN.2018010091hwp:resource-id:jnephrol;29/11/2745American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyangiotensin II, endothelin, focal segmental glomerulosclerosis, proteinuria, sparsentanClinical ResearchClinical Researchresearch-article20182018-11-01November 201810.1681/ASN.20180100911046-66731533-34502018-10-25T09:30:09-07:002018-11Journal of the American Society of NephrologyClinical Research293011327455182754518
- Broadening Our Perspectives: CKD Care and the Dialysis Transition10.1681/ASN.2018090937Wed, 10 Oct 2018 09:16:32 GMT-07:00Broadening Our Perspectives: CKD Care and the Dialysis TransitionHostetter, ThomasBriggs, Josie P.2018-10-10T09:16:32-07:00doi:10.1681/ASN.2018090937hwp:resource-id:jnephrol;29/11/2605American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhealth care policy, health care delivery, PerspectivesUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-11-01November 201810.1681/ASN.20180909371046-66731533-34502018-10-10T09:16:32-07:002018-11Journal of the American Society of NephrologyUp Front Matters29111111260526102612260526122615
- Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal Syndromes10.1681/ASN.2018050519Tue, 02 Oct 2018 07:26:26 GMT-07:00Inhibitory Anti-Peroxidasin Antibodies in Pulmonary-Renal SyndromesMcCall, A. ScottBhave, GautamPedchenko, VadimHess, JacobFree, MeghanLittle, Dustin J.Baker, Thomas P.Pendergraft, William F.Falk, Ronald J.Olson, Stephen W.Hudson, Billy G.2018-10-02T07:26:26-07:00doi:10.1681/ASN.2018050519hwp:resource-id:jnephrol;29/11/2619American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyanti-GBM disease, ANCA, extracellular matrix, glomerulonephritis, Goodpasture-s syndrome, vasculitisRapid CommunicationRapid Communicationresearch-article20182018-11-01November 201810.1681/ASN.20180505191046-66731533-34502018-10-02T07:26:26-07:002018-11Journal of the American Society of NephrologyRapid Communication2911112619260526252607
- Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway10.1681/ASN.2018030333Tue, 09 Oct 2018 09:11:18 GMT-07:00Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling PathwayCornelius, Ryan J.Si, JingeCuevas, Catherina A.Nelson, Jonathan W.Gratreak, Brittany D.K.Pardi, RuggeroYang, Chao-LingEllison, David H.2018-10-09T09:11:18-07:00doi:10.1681/ASN.2018030333hwp:resource-id:jnephrol;29/11/2627American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal hypertension, Na transport, distal tubule, Cell & Transport PhysiologyBasic ResearchBasic Researchresearch-article20182018-11-01November 201810.1681/ASN.20180303331046-66731533-34502018-10-09T09:11:18-07:002018-11Journal of the American Society of NephrologyBasic Research291126272640
- Combined Structural and Functional Imaging of the Kidney Reveals Major Axial Differences in Proximal Tubule Endocytosis10.1681/ASN.2018050522Tue, 09 Oct 2018 09:11:19 GMT-07:00Combined Structural and Functional Imaging of the Kidney Reveals Major Axial Differences in Proximal Tubule EndocytosisSchuh, Claus D.Polesel, MarcelloPlatonova, EvgeniaHaenni, DominikGassama, AlkalyTokonami, NatsukoGhazi, SusanBugarski, MilicaDevuyst, OlivierZiegler, UrsHall, Andrew M.2018-10-09T09:11:19-07:00doi:10.1681/ASN.2018050522hwp:resource-id:jnephrol;29/11/2696American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyendocytosis, kidney anatomy, proximal tubule, proteinuria, ImagingBasic ResearchBasic Researchresearch-article20182018-11-01November 201810.1681/ASN.20180505221046-66731533-34502018-10-09T09:11:19-07:002018-11Journal of the American Society of NephrologyBasic Research291126962712
- Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2–Mediated Water Homeostasis10.1681/ASN.2018030271Wed, 10 Oct 2018 09:16:33 GMT-07:00Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2–Mediated Water HomeostasisLi, SuchunQiu, MiaojuanKong, YonglunZhao, XiaoduoChoi, Hyo-JungReich, MariaBunkelman, Brady H.Liu, QiaojuanHu, ShanHan, MengkeXie, HaixiaRosenberg, Avi Z.Keitel, VerenaKwon, Tae-HwanLevi, MosheLi, ChunlingWang, Weidong2018-10-10T09:16:33-07:00doi:10.1681/ASN.2018030271hwp:resource-id:jnephrol;29/11/2658American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyTGR5, AQP2, cAMP, lithiumBasic ResearchBasic Researchresearch-article20182018-11-01November 201810.1681/ASN.20180302711046-66731533-34502018-10-10T09:16:33-07:002018-11Journal of the American Society of NephrologyBasic Research291126582670
- Prediction of Arteriovenous Fistula Clinical Maturation from Postoperative Ultrasound Measurements: Findings from the Hemodialysis Fistula Maturation Study10.1681/ASN.2017111225Thu, 11 Oct 2018 05:54:44 GMT-07:00Prediction of Arteriovenous Fistula Clinical Maturation from Postoperative Ultrasound Measurements: Findings from the Hemodialysis Fistula Maturation StudyRobbin, Michelle L.Greene, TomAllon, MichaelDember, Laura M.Imrey, Peter B.Cheung, Alfred K.Himmelfarb, JonathanHuber, Thomas S.Kaufman, James S.Radeva, Milena K.Roy-Chaudhury, PrabirShiu, Yan-TingVazquez, Miguel A.Umphrey, Heidi R.Alexander, LaurenAbts, CarlBeck, Gerald J.Kusek, John W.Feldman, Harold I.,,Farber, L.M.D. A.,Stern, L.LeSage, P.Kivork, C.Soares, D.Malikova, M.Young, C.Taylor, M.Woodard, L.Mangadi, K.,Munda, R.Lee, T.Alloway, R.El-Khatib, M.Canaan, T.Pflum, A.Thieken, L.Campos-Naciff, B.,Berceli, S.Jansen, M.McCaslin, G.Trahan, Y.,Vongpatanasin, W.Davidson, I.Hwang, C.Lightfoot, T.Livingston, C.Valencia, A.Dolmatch, B.Fenves, A.Hawkins, N.,Kraiss, L.Kinikini, D.Treiman, G.Ihnat, D.Sarfati, M.,Terry, C.Lavasani, I.Maloney, M.Schlotfeldt, L.Buchanan, C.Clark, C.Crawford, C.Hamlett, J.Kundzins, J.Manahan, L.Wise, J.,Gassman, J.,Li, L.Alster, J.Li, M.MacKrell, J.,Weiss, B.Wiggins, K.Alpers, C.Hudkins, K.Wietecha, T.,Belt, L.Vita, J.Hamburg, N.Duess, M.Levit, A.Higgins, H.Ke, S.Mandaci, O.Snell, C.Gravley, J.Behnken, S.Mortensen, R.Chertow, G.Besarab, A.Brayman, K.Diener-West, M.Harrison, D.Inker, L.Louis, T.McClellan, W.Rubin, J.,Star, R.2018-10-11T05:54:44-07:00doi:10.1681/ASN.2017111225hwp:resource-id:jnephrol;29/11/2735American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyaccess blood flow, arteriovenous fistula, clinical trial, dialysis access, Ultrasonography, hemodialysisClinical ResearchClinical Researchresearch-article20182018-11-01November 201810.1681/ASN.20171112251046-66731533-34502018-10-11T05:54:44-07:002018-11Journal of the American Society of NephrologyClinical Research2931111132735260766527442609665
- Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss10.1681/ASN.2018040405Tue, 02 Oct 2018 07:26:26 GMT-07:00Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR LossZewinger, StephenRauen, ThomasRudnicki, MichaelFederico, GiuseppinaWagner, MartinaTriem, SarahSchunk, Stefan J.Petrakis, IoannisSchmit, DavidWagenpfeil, StefanHeine, Gunnar H.Mayer, GertFloege, JürgenFliser, DaniloGröne, Hermann-JosefSpeer, Thimoteus2018-10-02T07:26:26-07:00doi:10.1681/ASN.2018040405hwp:resource-id:jnephrol;29/11/2722American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical nephrology, IgA nephropathy, interstitial fibrosis, tubule cells, progression of chronic renal failureClinical EpidemiologyClinical Epidemiologyresearch-article20182018-11-01November 201810.1681/ASN.20180404051046-66731533-34502018-10-02T07:26:26-07:002018-11Journal of the American Society of NephrologyClinical Epidemiology291127222733
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- Genetic Contribution to Risk for Diabetic Kidney Disease10.2215/CJN.07240618Mon, 16 Jul 2018 07:44:51 GMT-07:00Genetic Contribution to Risk for Diabetic Kidney DiseaseRich, Stephen S.2018-07-16T07:44:51-07:00doi:10.2215/CJN.07240618hwp:resource-id:clinjasn;13/8/1135American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, MODY, exome sequencing, Diabetic Nephropathies, RiskEditorialsEditorialseditorial20182018-08-07August 07, 201810.2215/CJN.072406181555-90411555-905X2018-07-16T07:44:51-07:002018-08-07Clinical Journal of the American Society of NephrologyEditorials13881135116211371171
- Urgent: Stop Preventable Infections Now10.2215/CJN.10790917Thu, 22 Mar 2018 05:49:23 GMT-07:00Urgent: Stop Preventable Infections NowCollins, Allan J.Kliger, Alan S.2018-03-22T05:49:23-07:00doi:10.2215/CJN.10790917hwp:resource-id:clinjasn;13/4/663American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, infections, patient safety, nephrology, Nephrologists, renal dialysis, Centers for Disease Control and Prevention (U.S.), Cross Infection, hospitalization, Communicable Diseases, Cardiovascular Diseases, BacteremiaPerspectivesPerspectivesresearch-article20182018-04-06April 06, 201810.2215/CJN.107909171555-90411555-905X2018-03-22T05:49:23-07:002018-04-06Clinical Journal of the American Society of NephrologyPerspectives1344444663655666669671665662668670673
- 100% Use of Infection Control Procedures in Hemodialysis Facilities10.2215/CJN.11341017Thu, 22 Mar 2018 05:49:24 GMT-07:00100% Use of Infection Control Procedures in Hemodialysis FacilitiesVijayan, AnithaBoyce, John M.2018-03-22T05:49:24-07:00doi:10.2215/CJN.11341017hwp:resource-id:clinjasn;13/4/671American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, Infection prevention, renal dialysis, Centers for Medicare and Medicaid Services (U.S.), Physician Executives, Influenza, Human, Central Venous Catheters, Public Health, Infection Control, Centers for Disease Control and Prevention (U.S.), Disease Outbreaks, Bacterial Infections, Cardiovascular DiseasesPerspectivesPerspectivesresearch-article20182018-04-06April 06, 201810.2215/CJN.113410171555-90411555-905X2018-03-22T05:49:24-07:002018-04-06Clinical Journal of the American Society of NephrologyPerspectives1344444671655663666669673662665668670
- What We Learned from Ebola10.2215/CJN.11061017Thu, 22 Mar 2018 05:49:23 GMT-07:00What We Learned from EbolaBoyce, John M.Hymes, Jeffrey L.2018-03-22T05:49:23-07:00doi:10.2215/CJN.11061017hwp:resource-id:clinjasn;13/4/669American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Africa, Western, Body Fluids, Communicable Diseases, Emerging, Coronavirus Infections, Cross Infection, Diarrhea, Disease Outbreaks, Epidemics, Europe, hemodialysis, Hemorrhagic Fever, Ebola, Humans, Lassa Fever, Maintenance Hemodialysis, Outpatients, renal dialysis, Risk, SaudiPerspectivesPerspectivesresearch-article20182018-04-06April 06, 201810.2215/CJN.110610171555-90411555-905X2018-03-22T05:49:23-07:002018-04-06Clinical Journal of the American Society of NephrologyPerspectives1344444669655663666671670662665668673
- Addressing the Problem of Multidrug-Resistant Organisms in Dialysis10.2215/CJN.13781217Thu, 22 Mar 2018 05:49:23 GMT-07:00Addressing the Problem of Multidrug-Resistant Organisms in DialysisD’Agata, Erika M.C.2018-03-22T05:49:23-07:00doi:10.2215/CJN.13781217hwp:resource-id:clinjasn;13/4/666American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococci, Methicillin, Public Health, renal dialysis, Gram-Negative Bacteria, Vancomycin Resistance, Methicillin ResistancePerspectivesPerspectivesresearch-article20182018-04-06April 06, 201810.2215/CJN.137812171555-90411555-905X2018-03-22T05:49:23-07:002018-04-06Clinical Journal of the American Society of NephrologyPerspectives1344444666655663669671668662665670673
- Treatment Choices for Hepatitis C in Patients with Kidney Disease10.2215/CJN.12621117Fri, 09 Mar 2018 06:45:08 GMT-08:00Treatment Choices for Hepatitis C in Patients with Kidney DiseaseFabrizi, FabrizioMessa, Piergiorgio2018-03-09T06:45:08-08:00doi:10.2215/CJN.12621117hwp:resource-id:clinjasn;13/5/793American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, therapy, Humans, Hepacivirus, Prevalence, Developed Countries, Hepatitis C, Kidney Diseases, Fluid Therapy, Patient Selection, renal dialysisPerspectivesPerspectivesresearch-article20182018-05-07May 07, 201810.2215/CJN.126211171555-90411555-905X2018-03-09T06:45:08-08:002018-05-07Clinical Journal of the American Society of NephrologyPerspectives135793795
- Chimeric Antigen Receptor T Cell Therapy and the Kidney10.2215/CJN.12871117Fri, 09 Mar 2018 06:45:08 GMT-08:00Chimeric Antigen Receptor T Cell Therapy and the KidneyJhaveri, Kenar D.Rosner, Mitchell H.2018-03-09T06:45:08-08:00doi:10.2215/CJN.12871117hwp:resource-id:clinjasn;13/5/796American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCAR-T, onconephrology, drug nephrotoxicity, cytokines, adaptive cell transfer, chimeric receptor receptor therapyPerspectivesPerspectivesresearch-article20182018-05-07May 07, 201810.2215/CJN.128711171555-90411555-905X2018-03-09T06:45:08-08:002018-05-07Clinical Journal of the American Society of NephrologyPerspectives135796798
- Chronic Kidney Disease in India10.2215/CJN.09180817Tue, 30 Jan 2018 07:17:34 GMT-08:00Chronic Kidney Disease in IndiaVarughese, SantoshAbraham, Georgi2018-01-30T07:17:34-08:00doi:10.2215/CJN.09180817hwp:resource-id:clinjasn;13/5/802American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, India, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20182018-05-07May 07, 201810.2215/CJN.091808171555-90411555-905X2018-01-30T07:17:34-08:002018-05-07Clinical Journal of the American Society of NephrologyPerspectives135802804
- Protecting Donors and Safeguarding Altruism in the United States10.2215/CJN.13681217Fri, 09 Mar 2018 06:45:08 GMT-08:00Protecting Donors and Safeguarding Altruism in the United StatesWiseman, Alexander C.2018-03-09T06:45:08-08:00doi:10.2215/CJN.13681217hwp:resource-id:clinjasn;13/5/790American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, kidney donation, Economic Impact, Humans, United States, Living Donors, Altruism, Vulnerable Populations, Insurance, Long-Term Care, Goals, Tissue and Organ Procurement, Tissue and Organ Harvesting, Kidney Failure, ChronicPerspectivesPerspectivesresearch-article20182018-05-07May 07, 201810.2215/CJN.136812171555-90411555-905X2018-03-09T06:45:08-08:002018-05-07Clinical Journal of the American Society of NephrologyPerspectives135790792
- Perspectives on Funding Initiatives in Clinical Research in Kidney Disease in the United States10.2215/CJN.04520417Mon, 17 Jul 2017 08:58:14 GMT-07:00Perspectives on Funding Initiatives in Clinical Research in Kidney Disease in the United StatesMehrotra, Rajnish2017-07-17T08:58:14-07:00doi:10.2215/CJN.04520417hwp:resource-id:clinjasn;12/9/1543American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, kidney disease, Biomedical Research, Drive, Financial Support, Kidney Diseases, United StatesPerspectivesPerspectivesresearch-article20172017-09-07September 07, 201710.2215/CJN.045204171555-90411555-905X2017-07-17T08:58:14-07:002017-09-07Clinical Journal of the American Society of NephrologyPerspectives12915431543
- Sparking Innovation To Improve the Lives of People with Kidney Disease10.2215/CJN.04420417Mon, 17 Jul 2017 08:58:14 GMT-07:00Sparking Innovation To Improve the Lives of People with Kidney DiseaseCrowley, Susan T.Meyer, Laurence2017-07-17T08:58:14-07:00doi:10.2215/CJN.04420417hwp:resource-id:clinjasn;12/9/1548American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyInnovation, kidney disease, healthcare, Veterans Administration, rehabilitationPerspectivesPerspectivesresearch-article20172017-09-07September 07, 201710.2215/CJN.044204171555-90411555-905X2017-07-17T08:58:14-07:002017-09-07Clinical Journal of the American Society of NephrologyPerspectives12915481550
- Complementary Initiatives from the NIDDK to Advance Kidney Health10.2215/CJN.02120217Mon, 17 Jul 2017 08:58:15 GMT-07:00Complementary Initiatives from the NIDDK to Advance Kidney HealthNorton, Jenna M.Ketchum, Christian J.Narva, Andrew S.Star, Robert A.Rodgers, Griffin P.2017-07-17T08:58:15-07:00doi:10.2215/CJN.02120217hwp:resource-id:clinjasn;12/9/1544American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyprecision medicine, pragmatic trials, population health, health information technology, chronic kidney disease, acute kidney injury, kidney, United States, National Institute of Diabetes and Digestive and Kidney DiseasesPerspectivesPerspectivesresearch-article20172017-09-07September 07, 201710.2215/CJN.021202171555-90411555-905X2017-07-17T08:58:15-07:002017-09-07Clinical Journal of the American Society of NephrologyPerspectives12915441547
- Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate Binders10.2215/CJN.13091216Wed, 19 Jul 2017 07:55:16 GMT-07:00Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate BindersKomaba, HirotakaWang, MiaTaniguchi, MasatomoYamamoto, SuguruNomura, TakanobuSchaubel, Douglas E.Smith, Abigail R.Zee, JarcyKaraboyas, AngeloBieber, BrianFukagawa, MasafumiTentori, Francesca2017-07-19T07:55:16-07:00doi:10.2215/CJN.13091216hwp:resource-id:clinjasn;12/9/1489American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDialysis Outcomes and Practice Patterns Study (DOPPS): hemodialysis, hyperphosphatemia, sevelamer, survival, Calcium Phosphates, Calcium, Dietary, Confidence Intervals, Fluid Therapy, Humans, Phosphorus, Propensity Score, renal dialysis, Sevelamer, calcium phosphateOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-09-07September 07, 201710.2215/CJN.130912161555-90411555-905X2017-07-19T07:55:16-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914891497
- Hemolytic Uremic Syndrome in Pregnancy and Postpartum10.2215/CJN.00280117Thu, 08 Jun 2017 06:52:20 GMT-07:00Hemolytic Uremic Syndrome in Pregnancy and PostpartumBruel, AlexandraKavanagh, DavidNoris, MarinaDelmas, YahsouWong, Edwin K.S.Bresin, ElenaProvôt, FrançoisBrocklebank, VickyMele, CaterinaRemuzzi, GiuseppeLoirat, ChantalFrémeaux-Bacchi, VéroniqueFakhouri, Fadi2017-06-08T06:52:20-07:00doi:10.2215/CJN.00280117hwp:resource-id:clinjasn;12/8/1237American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemolytic uremic syndrome, complement, pregnancy, thrombotic microangiopathy, Antibodies, Monoclonal, Humanized, Atypical Hemolytic Uremic Syndrome, Complement Pathway, Alternative, Female, Follow-Up Studies, France, Humans, Italy, Kidney Failure, Chronic, kidney transplantation, Plasma Exchange, Postpartum Period, Pregnancy, Recurrence, renal dialysis, Retrospective Studies, Thrombotic Microangiopathies, United Kingdom, chemotactic factor inactivator, eculizumabOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-08-07August 07, 201710.2215/CJN.002801171555-90411555-905X2017-06-08T06:52:20-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12812371247
- Nephrology at a Crossroads10.2215/CJN.09070817Thu, 11 Jan 2018 11:50:00 GMT-08:00Nephrology at a Crossroadsde Boer, Ian H.2018-01-11T11:50:00-08:00doi:10.2215/CJN.09070817hwp:resource-id:clinjasn;13/2/324American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologynephrologyPerspectivesPerspectivesresearch-article20182018-02-07February 07, 201810.2215/CJN.090708171555-90411555-905X2018-01-11T11:50:00-08:002018-02-07Clinical Journal of the American Society of NephrologyPerspectives132222324325328331324327330334
- Effects of Diabetes Medications Targeting the Incretin System on the Kidney10.2215/CJN.10380917Wed, 10 Jan 2018 06:47:57 GMT-08:00Effects of Diabetes Medications Targeting the Incretin System on the KidneyMacIsaac, Richard J.Thomas, Merlin C.2018-01-10T06:47:57-08:00doi:10.2215/CJN.10380917hwp:resource-id:clinjasn;13/2/321American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, albuminuria, chronic kidney disease, diabetes, glomerular filtration rate, microalbuminuria, renal protection, Humans, Incretins, Glucagon-Like Peptide 1, Blood Glucose, DPP4 protein, human, Dipeptidyl Peptidase 4, Diabetes Mellitus, Type 2, Glucagon-Like Peptide-1 Receptor, Glucose, Peptide Hormones, kidney, Homeostasis, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20182018-02-07February 07, 201810.2215/CJN.103809171555-90411555-905X2018-01-10T06:47:57-08:002018-02-07Clinical Journal of the American Society of NephrologyPerspectives1322321318323320
- Burnout in Nephrology10.2215/CJN.09870917Thu, 11 Jan 2018 11:50:00 GMT-08:00Burnout in NephrologyRoberts, John K.2018-01-11T11:50:00-08:00doi:10.2215/CJN.09870917hwp:resource-id:clinjasn;13/2/328American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyburnout, fellowship, education, workforcePerspectivesPerspectivesresearch-article20182018-02-07February 07, 201810.2215/CJN.098709171555-90411555-905X2018-01-11T11:50:00-08:002018-02-07Clinical Journal of the American Society of NephrologyPerspectives132222328324325331330324327334
- Addressing Physician Burnout10.2215/CJN.06800617Thu, 11 Jan 2018 11:50:00 GMT-08:00Addressing Physician BurnoutWilliams, Amy W.2018-01-11T11:50:00-08:00doi:10.2215/CJN.06800617hwp:resource-id:clinjasn;13/2/325American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrisk factors, burnout, nephrology, Depersonalization, Nephrologists, Burnout, Professional, Work-Life Balance, Medicine, Physicians, Workplace, Surveys and QuestionnairesPerspectivesPerspectivesresearch-article20182018-02-07February 07, 201810.2215/CJN.068006171555-90411555-905X2018-01-11T11:50:00-08:002018-02-07Clinical Journal of the American Society of NephrologyPerspectives132222325324328331327324330334
- Are SGLT2 Inhibitors Ready for Prime Time for CKD?10.2215/CJN.07680717Mon, 11 Sep 2017 07:49:29 GMT-07:00Are SGLT2 Inhibitors Ready for Prime Time for CKD?Pecoits-Filho, RobertoPerkovic, Vlado2017-09-11T07:49:29-07:00doi:10.2215/CJN.07680717hwp:resource-id:clinjasn;13/2/318American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, chronic kidney disease, cardiovascular disease, sglt2 inhibitors, clinical trial, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20182018-02-07February 07, 201810.2215/CJN.076807171555-90411555-905X2017-09-11T07:49:29-07:002018-02-07Clinical Journal of the American Society of NephrologyPerspectives1322318321320323
- Transforming Nephrology10.2215/CJN.02310317Thu, 04 May 2017 01:22:15 GMT-07:00Transforming NephrologyRosner, Mitchell H.Berns, Jeffrey S.2017-05-04T13:22:15-07:00doi:10.2215/CJN.02310317hwp:resource-id:clinjasn;13/2/331American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology, transformation, practice, training, Career ChoicePerspectivesPerspectivesresearch-article20182018-02-07February 07, 201810.2215/CJN.023103171555-90411555-905X2017-05-04T13:22:15-07:002018-02-07Clinical Journal of the American Society of NephrologyPerspectives132222331324325328334324327330
- Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis10.2215/CJN.10601016Thu, 04 May 2017 01:22:15 GMT-07:00Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus NephritisRijnink, Emilie C.Teng, Y.K. OnnoWilhelmus, SuzanneAlmekinders, MathildeWolterbeek, RonCransberg, KarlienBruijn, Jan A.Bajema, Ingeborg M.2017-05-04T13:22:15-07:00doi:10.2215/CJN.10601016hwp:resource-id:clinjasn;12/5/734American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical pathology, evidence-based medicine, prognosis, atrophy, fibrosis, follow-up studies, glomerular filtration rate, humans, kidney, kidney failure, chronic, kidney glomerulus, lupus nephritis, renal insufficiency, chronicOriginal ArticlesClinical Immunology and PathologyOriginal ArticlesClinical Immunology and Pathologyresearch-article20172017-05-08May 08, 201710.2215/CJN.106010161555-90411555-905X2017-05-04T13:22:15-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1255734711743712
- Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal Function10.2215/CJN.10180916Thu, 16 Mar 2017 07:37:32 GMT-07:00Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal FunctionPetrykiv, SergeiSjöström, C. DavidGreasley, Peter J.Xu, JohnPersson, FrederikHeerspink, Hiddo J.L.2017-03-16T07:37:32-07:00doi:10.2215/CJN.10180916hwp:resource-id:clinjasn;12/5/751American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, cardiovascular, diabetic nephropathy, Benzhydryl Compounds, blood pressure, Body Weight, Cardiovascular Diseases, Diabetes Mellitus, Type 2, glomerular filtration rate, Glucosides, Hematocrit, Humans, Hypoglycemic Agents, Natriuresis, risk factorsOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20172017-05-08May 08, 201710.2215/CJN.101809161555-90411555-905X2017-03-16T07:37:32-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125751759
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- Considerations and Challenges in Selecting Patient-Reported Outcome Measures for Clinical Trials in Nephrology10.2215/CJN.06300617Mon, 28 Aug 2017 05:36:51 GMT-07:00Considerations and Challenges in Selecting Patient-Reported Outcome Measures for Clinical Trials in NephrologyJu, AngelaTong, Allison2017-08-28T05:36:51-07:00doi:10.2215/CJN.06300617hwp:resource-id:clinjasn;12/11/1882American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-centered care, quality of life, symptoms, nephrology, Patient Reported Outcome Measures, Humans, Outcome Assessment (Health Care)PerspectivesPerspectivesresearch-article20172017-11-07November 07, 201710.2215/CJN.063006171555-90411555-905X2017-08-28T05:36:51-07:002017-11-07Clinical Journal of the American Society of NephrologyPerspectives121118821884
- Using Patient-Reported Measures in Dialysis Clinics10.2215/CJN.02250217Wed, 14 Jun 2017 05:48:53 GMT-07:00Using Patient-Reported Measures in Dialysis ClinicsPeipert, John D.Hays, Ron D.2017-06-14T05:48:53-07:00doi:10.2215/CJN.02250217hwp:resource-id:clinjasn;12/11/1889American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, outcomes, quality of life, Fluid Therapy, Humans, Kidney Failure, Chronic, renal dialysisPerspectivesPerspectivesresearch-article20172017-11-07November 07, 201710.2215/CJN.022502171555-90411555-905X2017-06-14T05:48:53-07:002017-11-07Clinical Journal of the American Society of NephrologyPerspectives121118891891
- Time to Rethink Our Approach to Patient-Reported Outcome Measures for ESRD10.2215/CJN.04850517Mon, 28 Aug 2017 05:36:51 GMT-07:00Time to Rethink Our Approach to Patient-Reported Outcome Measures for ESRDFinkelstein, Fredric O.Finkelstein, Susan H.2017-08-28T05:36:51-07:00doi:10.2215/CJN.04850517hwp:resource-id:clinjasn;12/11/1885American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, Patient reported outcome measures, computerized adaptive testing, health related quality of life, chronic dialysis, Patient Reported Outcome Measures, Fluid Therapy, Humans, renal dialysis, Kidney Failure, ChronicPerspectivesPerspectivesresearch-article20172017-11-07November 07, 201710.2215/CJN.048505171555-90411555-905X2017-08-28T05:36:51-07:002017-11-07Clinical Journal of the American Society of NephrologyPerspectives121118851888
- Introduction to Patient-Reported Outcomes Perspectives Series10.2215/CJN.07700717Mon, 28 Aug 2017 05:36:51 GMT-07:00Introduction to Patient-Reported Outcomes Perspectives SeriesKurella Tamura, Manjula2017-08-28T05:36:51-07:00doi:10.2215/CJN.07700717hwp:resource-id:clinjasn;12/11/1881American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient reported outcomes, Patient Reported Outcome Measures, Humans, Outcome Assessment (Health Care)PerspectivesPerspectivesresearch-article20172017-11-07November 07, 201710.2215/CJN.077007171555-90411555-905X2017-08-28T05:36:51-07:002017-11-07Clinical Journal of the American Society of NephrologyPerspectives121118811881
- A Rebuttal to “The CKD Classification System in the Precision Medicine Era”10.2215/CJN.03970417Mon, 07 Aug 2017 06:33:22 GMT-07:00A Rebuttal to “The CKD Classification System in the Precision Medicine Era”Levey, Andrew S.Levin, Adeera2017-08-07T06:33:22-07:00doi:10.2215/CJN.03970417hwp:resource-id:clinjasn;12/10/1711American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPrecision Medicine, glomerular filtration rate, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20172017-10-06October 06, 201710.2215/CJN.039704171555-90411555-905X2017-08-07T06:33:22-07:002017-10-06Clinical Journal of the American Society of NephrologyPerspectives121017111713
- Perspective on Nephrology Fellowship in the United States10.2215/CJN.07060717Tue, 08 Aug 2017 05:41:09 GMT-07:00Perspective on Nephrology Fellowship in the United StatesChonchol, Michel2017-08-08T05:41:09-07:00doi:10.2215/CJN.07060717hwp:resource-id:clinjasn;12/10/1714American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUnited States, Fellowships and Scholarships, nephrology, Internship and ResidencyPerspectivesPerspectivesresearch-article20172017-10-06October 06, 201710.2215/CJN.070607171555-90411555-905X2017-08-08T05:41:09-07:002017-10-06Clinical Journal of the American Society of NephrologyPerspectives121017141714
- Perspectives on the Nephrology Match for Fellowship Applicants10.2215/CJN.03220317Tue, 08 Aug 2017 05:41:09 GMT-07:00Perspectives on the Nephrology Match for Fellowship ApplicantsRoss, Michael J.Braden, Gregory,2017-08-08T05:41:09-07:00doi:10.2215/CJN.03220317hwp:resource-id:clinjasn;12/10/1715American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, Fellowship, Match, Fellowships and Scholarships, nephrology, Education, Medical, Graduate, Internship and ResidencyPerspectivesPerspectivesresearch-article20172017-10-06October 06, 201710.2215/CJN.032203171555-90411555-905X2017-08-08T05:41:09-07:002017-10-06Clinical Journal of the American Society of NephrologyPerspectives121017151717
- Resizing Nephrology Training Programs10.2215/CJN.04740517Thu, 24 Aug 2017 06:58:16 GMT-07:00Resizing Nephrology Training ProgramsMelamed, Michal L.Campbell, Kirk N.Nickolas, Thomas L.2017-08-24T06:58:16-07:00doi:10.2215/CJN.04740517hwp:resource-id:clinjasn;12/10/1718American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFellowship, Education, nephrology, Education, Medical, Graduate, Fellowships and ScholarshipsPerspectivesPerspectivesresearch-article20172017-10-06October 06, 201710.2215/CJN.047405171555-90411555-905X2017-08-24T06:58:16-07:002017-10-06Clinical Journal of the American Society of NephrologyPerspectives121017181720
- The Journey to Full Health Care Responsibility for One ESCO Provider10.2215/CJN.05520517Mon, 30 Oct 2017 06:27:50 GMT-07:00The Journey to Full Health Care Responsibility for One ESCO ProviderMaddux, Franklin W.Ketchersid, Terry L.2017-10-30T06:27:50-07:00doi:10.2215/CJN.05520517hwp:resource-id:clinjasn;12/12/2050American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, ESCO, Value Based Care, dialysis, ACO, accountable care, CKD, transplantation, Humans, United States, Medicaid, Medicare, Kidney Failure, Chronic, Quality of Health Care, Comprehensive Health CarePerspectivesPerspectivesresearch-article20172017-12-07December 07, 201710.2215/CJN.055205171555-90411555-905X2017-10-30T06:27:50-07:002017-12-07Clinical Journal of the American Society of NephrologyPerspectives121220502052
- Perspectives on the Strengths and Weaknesses of the National Kidney Allocation System10.2215/CJN.08640817Tue, 21 Nov 2017 06:12:48 GMT-08:00Perspectives on the Strengths and Weaknesses of the National Kidney Allocation SystemFormica, Richard N.2017-11-21T06:12:48-08:00doi:10.2215/CJN.08640817hwp:resource-id:clinjasn;12/12/2056American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, cadaver organ transplantation, public policy, kidney allocation systemPerspectivesPerspectivesresearch-article20172017-12-07December 07, 201710.2215/CJN.086408171555-90411555-905X2017-11-21T06:12:48-08:002017-12-07Clinical Journal of the American Society of NephrologyPerspectives121220562056
- Early Experience with the New Kidney Allocation System10.2215/CJN.06380617Tue, 21 Nov 2017 06:12:48 GMT-08:00Early Experience with the New Kidney Allocation SystemStewart, Darren E.Klassen, David K.2017-11-21T06:12:48-08:00doi:10.2215/CJN.06380617hwp:resource-id:clinjasn;12/12/2063American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, Humans, Tissue and Organ Procurement, Tissue DonorsPerspectivesPerspectivesresearch-article20172017-12-07December 07, 201710.2215/CJN.063806171555-90411555-905X2017-11-21T06:12:48-08:002017-12-07Clinical Journal of the American Society of NephrologyPerspectives121220632065
- Early Experience with New Kidney Allocation System10.2215/CJN.06360617Tue, 21 Nov 2017 06:12:48 GMT-08:00Early Experience with New Kidney Allocation SystemO’Connor, Kevin J.Cmunt, Kevin2017-11-21T06:12:48-08:00doi:10.2215/CJN.06360617hwp:resource-id:clinjasn;12/12/2057American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, kidney donation, kidney allocation system, kidney discard rateOverviewPerspectivesPerspectivesresearch-article20172017-12-07December 07, 201710.2215/CJN.063606171555-90411555-905X2017-11-21T06:12:48-08:002017-12-07Clinical Journal of the American Society of NephrologyPerspectives121220572059
- Challenges in Developing New Therapies for Vascular Access Dysfunction10.2215/CJN.06650617Mon, 11 Sep 2017 07:49:30 GMT-07:00Challenges in Developing New Therapies for Vascular Access DysfunctionNath, Karl A.Allon, Michael2017-09-11T07:49:30-07:00doi:10.2215/CJN.06650617hwp:resource-id:clinjasn;12/12/2053American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, arteriovenous fistula, arteriovenous graft, Arteriovenous Shunt, Surgical, renal dialysisPerspectivesPerspectivesresearch-article20172017-12-07December 07, 201710.2215/CJN.066506171555-90411555-905X2017-09-11T07:49:30-07:002017-12-07Clinical Journal of the American Society of NephrologyPerspectives121220532055
- International Comparisons of Prevalence, Awareness, and Treatment of Pruritus in People on Hemodialysis10.2215/CJN.03280317Mon, 18 Sep 2017 12:49:22 GMT-07:00International Comparisons of Prevalence, Awareness, and Treatment of Pruritus in People on HemodialysisRayner, Hugh C.Larkina, MariaWang, MiaGraham-Brown, Matthewvan der Veer, Sabine N.Ecder, TevfikHasegawa, TakeshiKleophas, WernerBieber, Brian A.Tentori, FrancescaRobinson, Bruce M.Pisoni, Ronald L.2017-09-18T12:49:22-07:00doi:10.2215/CJN.03280317hwp:resource-id:clinjasn;12/12/2000American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, hemodialysis, outcomes, gabapentin, Phosphorus, renal dialysis, Prevalence, depression, Benchmarking, Physician Executives, quality of life, Cyclohexanecarboxylic Acids, gamma-Aminobutyric Acid, Histamine AntagonistsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-12-07December 07, 201710.2215/CJN.032803171555-90411555-905X2017-09-18T12:49:22-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121220002007
- Ultrafiltration Therapy for Heart Failure: Balancing Likely Benefits against Possible RisksHeart failure remains a major public health concern because of its high prevalence, morbidity, mortality, and financial burden. The poor clinical outcomes associated with acute decompensated heart failure, suboptimal efficacy and safety profile of conventional treatment regimens, and unsatisfactory experiences with the newer classes of pharmacologic therapy underlie the interest in the use of extracorporeal isolated ultrafiltration in this setting. In this article, selected mechanistic aspects of ultrafiltration therapy are briefly reviewed followed by a critical overview of the largest trials in this field. I will discuss the clinical relevance of renal dysfunction and decongestion as two commonly used end points of safety and efficacy in the ultrafiltration trials, with emphasis on the emerging pertinent notions that could challenge our conventional thinking. Finally, a number of practical recommendations (e.g., customization of ultrafiltration rates) are provided for ultrafiltration therapy in the setting of acute decompensated heart failure. Because of a paucity of evidence, universally accepted consensus guidelines cannot yet be generated. As such, when considering ultrafiltration therapy for acute decompensated heart failure, the likely benefits should be carefully balanced against the potential risks for an individual patient. A conceivable implication of the ultrafiltration trials is that collaborative heart failure programs benefiting from nephrology expertise and resources could improve the outcomes and reduce the cost.10.2215/CJN.13461215Thu, 31 Mar 2016 06:46:06 GMT-07:00Ultrafiltration Therapy for Heart Failure: Balancing Likely Benefits against Possible RisksHeart failure remains a major public health concern because of its high prevalence, morbidity, mortality, and financial burden. The poor clinical outcomes associated with acute decompensated heart failure, suboptimal efficacy and safety profile of conventional treatment regimens, and unsatisfactory experiences with the newer classes of pharmacologic therapy underlie the interest in the use of extracorporeal isolated ultrafiltration in this setting. In this article, selected mechanistic aspects of ultrafiltration therapy are briefly reviewed followed by a critical overview of the largest trials in this field. I will discuss the clinical relevance of renal dysfunction and decongestion as two commonly used end points of safety and efficacy in the ultrafiltration trials, with emphasis on the emerging pertinent notions that could challenge our conventional thinking. Finally, a number of practical recommendations (e.g., customization of ultrafiltration rates) are provided for ultrafiltration therapy in the setting of acute decompensated heart failure. Because of a paucity of evidence, universally accepted consensus guidelines cannot yet be generated. As such, when considering ultrafiltration therapy for acute decompensated heart failure, the likely benefits should be carefully balanced against the potential risks for an individual patient. A conceivable implication of the ultrafiltration trials is that collaborative heart failure programs benefiting from nephrology expertise and resources could improve the outcomes and reduce the cost.Kazory, Amir2016-03-31T06:46:06-07:00doi:10.2215/CJN.13461215hwp:resource-id:clinjasn;11/8/1463American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyheart failure, ultrafiltration, diuretics, clinical nephrology, Consensus, Humans, Morbidity, nephrology, Prevalence, Public Health, RiskMini-ReviewMini-Reviewreview-article20162016-08-08August 08, 201610.2215/CJN.134612151555-90411555-905X2016-03-31T06:46:06-07:002016-08-08Clinical Journal of the American Society of NephrologyMini-Review11814631471
- Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African Americans10.2215/CJN.12971215Thu, 19 May 2016 06:54:29 GMT-07:00Association Analysis of the Cubilin (CUBN) and Megalin (LRP2) Genes with ESRD in African AmericansMa, JunGuan, MeijianBowden, Donald W.Ng, Maggie C.Y.Hicks, Pamela J.Lea, Janice P.Ma, LijunGao, ChuanPalmer, Nicholette D.Freedman, Barry I.2016-05-19T06:54:29-07:00doi:10.2215/CJN.12971215hwp:resource-id:clinjasn;11/6/1034American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, diabetic nephropathy, end stage kidney disease, African Americans, albuminuria, Diabetes Mellitus, Type 2, Genotype, Humans, Polymorphism, Single Nucleotide, Renal Insufficiency, ChronicOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20162016-06-06June 06, 201610.2215/CJN.129712151555-90411555-905X2016-05-19T06:54:29-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles116610349281043931
- Health Education and General Practitioner Training in Hypertension Management: Long-Term Effects on Kidney Function10.2215/CJN.05300515Thu, 19 May 2016 06:54:27 GMT-07:00Health Education and General Practitioner Training in Hypertension Management: Long-Term Effects on Kidney FunctionJafar, Tazeen H.Allen, John C.Jehan, ImtiazHameed, AamirSaffari, Seyed EhsanEbrahim, ShahPoulter, NeilChaturvedi, Nish2016-05-19T06:54:27-07:00doi:10.2215/CJN.05300515hwp:resource-id:clinjasn;11/6/1044American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular filtration rate, home health education, training general practitioners, creatinine, follow-up studies, health education, humans, hypertension, Pakistan, renal insufficiencyOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20162016-06-06June 06, 201610.2215/CJN.053005151555-90411555-905X2016-05-19T06:54:27-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles116610449321053934
- Anxiety in Patients Treated with HemodialysisAnxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients’ perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD.10.2215/CJN.02590316Thu, 22 Sep 2016 06:35:07 GMT-07:00Anxiety in Patients Treated with HemodialysisAnxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients’ perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD.Cohen, Scott D.Cukor, DanielKimmel, Paul L.2016-09-22T06:35:07-07:00doi:10.2215/CJN.02590316hwp:resource-id:clinjasn;11/12/2250American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, anxiety, benzodiazepine, Anxiety Disorders, depression, Depressive Disorder, Dyspepsia, Dyspnea, Fear, Humans, Hypesthesia, Kidney Failure, Chronic, Prevalence, quality of life, renal dialysis, Tremor, Uncertainty, uremiaMini-ReviewMini-Reviewresearch-article20162016-12-07December 07, 201610.2215/CJN.025903161555-90411555-905X2016-09-22T06:35:07-07:002016-12-07Clinical Journal of the American Society of NephrologyMini-Review111222502255
- Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease?Type II diabetic kidney disease is devastating to patients and society alike. This review will evaluate bariatric surgery as a treatment for diabetic kidney disease primarily through its ability to induce and maintain regression of type II diabetes. The review begins by outlining the global challenge of diabetic kidney disease, its link to obesity, and the comparative benefits of bariatric surgery on weight and type II diabetes. It then surveys comprehensively the relevant literature, which reports that although bariatric surgery is associated with reductions in albuminuria, its effect on harder clinical end points like progression of diabetic kidney disease is not known. The review also includes a critical assessment of the risks and costs of bariatric surgery and concludes by acknowledging the major knowledge gaps in the field and providing research strategies to overcome them. Until these knowledge gaps are filled, clinicians will be forced to rely on their own subjective judgment in determining the benefit-risk ratio of bariatric surgery for patients with diabetic kidney disease.10.2215/CJN.07670715Thu, 08 Oct 2015 09:09:45 GMT-07:00Is Bariatric Surgery an Effective Treatment for Type II Diabetic Kidney Disease?Type II diabetic kidney disease is devastating to patients and society alike. This review will evaluate bariatric surgery as a treatment for diabetic kidney disease primarily through its ability to induce and maintain regression of type II diabetes. The review begins by outlining the global challenge of diabetic kidney disease, its link to obesity, and the comparative benefits of bariatric surgery on weight and type II diabetes. It then surveys comprehensively the relevant literature, which reports that although bariatric surgery is associated with reductions in albuminuria, its effect on harder clinical end points like progression of diabetic kidney disease is not known. The review also includes a critical assessment of the risks and costs of bariatric surgery and concludes by acknowledging the major knowledge gaps in the field and providing research strategies to overcome them. Until these knowledge gaps are filled, clinicians will be forced to rely on their own subjective judgment in determining the benefit-risk ratio of bariatric surgery for patients with diabetic kidney disease.Friedman, Allon N.Wolfe, Bruce2015-10-08T09:09:45-07:00doi:10.2215/CJN.07670715hwp:resource-id:clinjasn;11/3/528American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyobesity, diabetic nephropathy, diabetes, bariatric surgery, body weight, diabetes mellitus, type 2, diabetic nephropathies, humans, treatment outcomeMini-ReviewMini-Reviewreview-article20162016-03-07March 07, 201610.2215/CJN.076707151555-90411555-905X2015-10-08T09:09:45-07:002016-03-07Clinical Journal of the American Society of NephrologyMini-Review113528535
- Insights into the Role of Mucosal Immunity in IgA Nephropathy10.2215/CJN.04370418Tue, 31 Jul 2018 06:31:27 GMT-07:00Insights into the Role of Mucosal Immunity in IgA NephropathyZhang, Yue-miaoZhang, Hong2018-07-31T06:31:27-07:00doi:10.2215/CJN.04370418hwp:resource-id:clinjasn;13/10/1584American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, Mucosal immunity, Nefecon, Glomerulonephritis, IGA, Immunity, Mucosal, Immunoglobulin APerspectivesPerspectivesresearch-article20182018-10-08October 08, 201810.2215/CJN.043704181555-90411555-905X2018-07-31T06:31:27-07:002018-10-08Clinical Journal of the American Society of NephrologyPerspectives131015841586
- Defining Hypertension10.2215/CJN.05350418Fri, 21 Sep 2018 06:27:13 GMT-07:00Defining HypertensionToto, Robert D.2018-09-21T06:27:13-07:00doi:10.2215/CJN.05350418hwp:resource-id:clinjasn;13/10/1578American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, blood pressure, Blood Pressure Determination, Renal Insufficiency, Chronic, hypotensionPerspectivesPerspectivesresearch-article20182018-10-08October 08, 201810.2215/CJN.053504181555-90411555-905X2018-09-21T06:27:13-07:002018-10-08Clinical Journal of the American Society of NephrologyPerspectives13101010157815721575158015741577
- Intensive Blood Pressure Targets and Kidney Disease10.2215/CJN.02010218Thu, 24 May 2018 06:17:07 GMT-07:00Intensive Blood Pressure Targets and Kidney DiseaseChang, Tara I.Sarnak, Mark J.2018-05-24T06:17:07-07:00doi:10.2215/CJN.02010218hwp:resource-id:clinjasn;13/10/1575American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, kidneyPerspectivesPerspectivesresearch-article20182018-10-08October 08, 201810.2215/CJN.020102181555-90411555-905X2018-05-24T06:17:07-07:002018-10-08Clinical Journal of the American Society of NephrologyPerspectives13101010157515721578157715741580
- Target Blood Pressure for Cardiovascular Disease Prevention in Patients with CKD10.2215/CJN.02130218Thu, 24 May 2018 06:17:07 GMT-07:00Target Blood Pressure for Cardiovascular Disease Prevention in Patients with CKDChang, Alex R.Appel, Lawrence J.2018-05-24T06:17:07-07:00doi:10.2215/CJN.02130218hwp:resource-id:clinjasn;13/10/1572American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, Antihypertensive Agents, blood pressure, cardiovascular disease, chronic kidney disease, Humans, hypertension, mortality, Renal Insufficiency, ChronicPerspectivesPerspectivesresearch-article20182018-10-08October 08, 201810.2215/CJN.021302181555-90411555-905X2018-05-24T06:17:07-07:002018-10-08Clinical Journal of the American Society of NephrologyPerspectives13101010157215751578157415771580
- Clinical PharmacogenomicsPharmacogenomics is a tool for practitioners to provide precision pharmacotherapy using genomics. All providers are likely to encounter genomic data in practice with the expectation that they are able to successfully apply it to patient care. Pharmacogenomics tests for genetic variations in genes that are responsible for drug metabolism, transport, and targets of drug action. Variations can increase the risk for drug toxicity or poor efficacy. Pharmacogenomics can, therefore, be used to help select the best medication or aid in dosing. Nephrologists routinely treat cardiovascular disease and manage patients after kidney transplantation, two situations for which there are several high-evidence clinical recommendations for commonly used anticoagulants, antiplatelets, statins, and transplant medications. Successful use of pharmacogenomics in practice requires that providers are familiar with how to access and use pharmacogenomics resources. Similarly, clinical decision making related to whether to use existing data, whether to order testing, and if data should be used in practice is needed to deliver precision medicine. Pharmacogenomics is applicable to virtually every medical specialty, and nephrologists are well positioned to be implementation leaders.10.2215/CJN.02730218Wed, 23 May 2018 06:45:21 GMT-07:00Clinical PharmacogenomicsPharmacogenomics is a tool for practitioners to provide precision pharmacotherapy using genomics. All providers are likely to encounter genomic data in practice with the expectation that they are able to successfully apply it to patient care. Pharmacogenomics tests for genetic variations in genes that are responsible for drug metabolism, transport, and targets of drug action. Variations can increase the risk for drug toxicity or poor efficacy. Pharmacogenomics can, therefore, be used to help select the best medication or aid in dosing. Nephrologists routinely treat cardiovascular disease and manage patients after kidney transplantation, two situations for which there are several high-evidence clinical recommendations for commonly used anticoagulants, antiplatelets, statins, and transplant medications. Successful use of pharmacogenomics in practice requires that providers are familiar with how to access and use pharmacogenomics resources. Similarly, clinical decision making related to whether to use existing data, whether to order testing, and if data should be used in practice is needed to deliver precision medicine. Pharmacogenomics is applicable to virtually every medical specialty, and nephrologists are well positioned to be implementation leaders.Adams, Solomon M.Crisamore, Karryn R.Empey, Philip E.2018-05-23T06:45:21-07:00doi:10.2215/CJN.02730218hwp:resource-id:clinjasn;13/10/1561American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnticoagulants, Cardiovascular Diseases, Clinical Decision-making, drug metabolism, drug transporter, Drug-related Side Effects and Adverse Reactions, Genetic Variation, Genomics, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, kidney transplantation, Nephrologists, nephrology, Patient Care, Pharmacogenetics, Pharmacogenomics, pharmacokinetics, Precision MedicineNephropharmacology for the ClinicianNephropharmacology for the Clinicianresearch-article20182018-10-08October 08, 201810.2215/CJN.027302181555-90411555-905X2018-05-23T06:45:21-07:002018-10-08Clinical Journal of the American Society of NephrologyNephropharmacology for the Clinician131015611571
- Nephrotoxicity and Chinese Herbal MedicineChinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening.10.2215/CJN.11571017Tue, 03 Apr 2018 06:06:03 GMT-07:00Nephrotoxicity and Chinese Herbal MedicineChinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening.Yang, BoXie, YunGuo, MaojuanRosner, Mitchell H.Yang, HongtaoRonco, Claudio2018-04-03T06:06:03-07:00doi:10.2215/CJN.11571017hwp:resource-id:clinjasn;13/10/1605American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Alkaloids, Anthraquinones, Aristolochic Acids, chronic kidney disease, Drugs, Chinese Herbal, Fanconi Syndrome, Flavonoids, Glycosides, Herbal Medicine, Humans, Incidence, kidney, Metals, Heavy, Neoplasms, Nephrolithiasis, nephrotoxicity, Plants, Medicinal, Renal Insufficiency, Chronic, rhabdomyolysis, Traditional Chinese MedicineReviewsReviewsreview-article20182018-10-08October 08, 201810.2215/CJN.115710171555-90411555-905X2018-04-03T06:06:03-07:002018-10-08Clinical Journal of the American Society of NephrologyReviews131016051611
- Microbiome and Cardiovascular Disease in CKDPatients with CKD exhibit a disproportionate burden of cardiovascular mortality, which likely stems from the presence of unique, nontraditional risk factors that accompany deteriorating kidney function. Mounting evidence suggests that alterations to the intestinal microbiome in CKD may serve as one such risk factor. The human intestinal tract is home to >100 trillion micro-organisms made up of a collection of commensal, symbiotic, and pathogenic species. These species along with their local environment constitute the intestinal microbiome. Patients with CKD show intestinal dysbiosis, an alteration of the gut micro-organism composition and function. Recent evidence links byproducts of intestinal dysbiosis to vascular calcification, atherosclerosis formation, and adverse cardiovascular outcomes in CKD. CKD-associated intestinal dysbiosis may also be accompanied by defects in intestinal barrier function, which could further enhance the negative effects of pathogenic intestinal bacteria in the human host. Thus, intestinal dysbiosis, defective intestinal barrier function, and a reduced capacity for clearance by the kidney of absorbed bacterial byproducts may all potentiate the development of cardiovascular disease in CKD. This narrative review focuses on microbiome-mediated mechanisms associated with CKD that may promote atherosclerosis formation and cardiovascular disease. It includes (1) new data supporting the hypothesis that intestinal barrier dysfunction leads to bacterial translocation and endotoxemia that potentiate systemic inflammation, (2) information on the accumulation of dietary-derived bacterial byproducts that stimulate pathways promoting atheromatous changes in arteries and cardiovascular disease, and (3) potential interventions. Despite great scientific interest in and a rapidly growing body of literature on the relationship between the microbiome and cardiovascular disease in CKD, many important questions remain unanswered.10.2215/CJN.12691117Wed, 09 May 2018 06:55:46 GMT-07:00Microbiome and Cardiovascular Disease in CKDPatients with CKD exhibit a disproportionate burden of cardiovascular mortality, which likely stems from the presence of unique, nontraditional risk factors that accompany deteriorating kidney function. Mounting evidence suggests that alterations to the intestinal microbiome in CKD may serve as one such risk factor. The human intestinal tract is home to >100 trillion micro-organisms made up of a collection of commensal, symbiotic, and pathogenic species. These species along with their local environment constitute the intestinal microbiome. Patients with CKD show intestinal dysbiosis, an alteration of the gut micro-organism composition and function. Recent evidence links byproducts of intestinal dysbiosis to vascular calcification, atherosclerosis formation, and adverse cardiovascular outcomes in CKD. CKD-associated intestinal dysbiosis may also be accompanied by defects in intestinal barrier function, which could further enhance the negative effects of pathogenic intestinal bacteria in the human host. Thus, intestinal dysbiosis, defective intestinal barrier function, and a reduced capacity for clearance by the kidney of absorbed bacterial byproducts may all potentiate the development of cardiovascular disease in CKD. This narrative review focuses on microbiome-mediated mechanisms associated with CKD that may promote atherosclerosis formation and cardiovascular disease. It includes (1) new data supporting the hypothesis that intestinal barrier dysfunction leads to bacterial translocation and endotoxemia that potentiate systemic inflammation, (2) information on the accumulation of dietary-derived bacterial byproducts that stimulate pathways promoting atheromatous changes in arteries and cardiovascular disease, and (3) potential interventions. Despite great scientific interest in and a rapidly growing body of literature on the relationship between the microbiome and cardiovascular disease in CKD, many important questions remain unanswered.Jovanovich, AnnaIsakova, TamaraStubbs, Jason2018-05-09T06:55:46-07:00doi:10.2215/CJN.12691117hwp:resource-id:clinjasn;13/10/1598American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteries, Atherosclerosis, Bacteria, Bacterial Translocation, Cardiovascular Diseases, Dysbiosis, Endotoxemia, Gastrointestinal Microbiome, Humans, Intestines, Microbiota, Renal Insufficiency, Chronic, risk factors, vascular calcificationReviewsReviewsreview-article20182018-10-08October 08, 201810.2215/CJN.126911171555-90411555-905X2018-05-09T06:55:46-07:002018-10-08Clinical Journal of the American Society of NephrologyReviews131015981604
- Kidney Function Decline in Patients with CKD and Untreated Hepatitis C Infection10.2215/CJN.01530218Fri, 21 Sep 2018 06:27:12 GMT-07:00Kidney Function Decline in Patients with CKD and Untreated Hepatitis C InfectionTartof, Sara YeeHsu, Jin-WenWei, RongRubenstein, Kevin B.Hu, HaihongArduino, Jean MarieHorberg, MichaelDerose, Stephen F.Qian, LeiRodriguez, Carla V.2018-09-21T06:27:12-07:00doi:10.2215/CJN.01530218hwp:resource-id:clinjasn;13/10/1471American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, end-stage renal disease, Epidemiology and outcomes, ESRD, hepatitis, glomerular filtration rate, Proportional Hazards Models, Retrospective Studies, Renal Insufficiency, Chronic, Kidney Failure, Chronic, Hepatitis C, Disease ProgressionOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-10-08October 08, 201810.2215/CJN.015302181555-90411555-905X2018-09-21T06:27:12-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles131014711478
- Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD10.2215/CJN.00380118Thu, 20 Sep 2018 09:05:12 GMT-07:00Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKDKendrick, JessicaShah, PratikAndrews, EmilyYou, ZhiyingNowak, KristenPasch, AndreasChonchol, Michel2018-09-20T09:05:12-07:00doi:10.2215/CJN.00380118hwp:resource-id:clinjasn;13/10/1463American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, chronic metabolic acidosis, vascular disease, Sodium Bicarbonate, fibroblast growth factor 23, glomerular filtration rate, Cross-Over Studies, Bicarbonates, Control Groups, Phosphorus, Brachial Artery, Alkalies, Dilatation, Prospective Studies, Pilot Projects, Goals, Renal Insufficiency, Chronic, Phosphorus, Dietary, Calcification, Physiologic, acidosis, Inflammation, Bone Remodeling, Minerals, Fibroblast Growth FactorsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-10-08October 08, 201810.2215/CJN.003801181555-90411555-905X2018-09-20T09:05:12-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles1310101463145114701452
- Protein Energy Wasting in Hemodialysis Patients10.2215/CJN.02150218Thu, 28 Jun 2018 06:16:44 GMT-07:00Protein Energy Wasting in Hemodialysis PatientsSarav, MenakaKovesdy, Csaba Pal2018-06-28T06:16:44-07:00doi:10.2215/CJN.02150218hwp:resource-id:clinjasn;13/10/1558American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, dialysis, malnutrition, renal dialysis, hemodialysisKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-10-08October 08, 201810.2215/CJN.021502181555-90411555-905X2018-06-28T06:16:44-07:002018-10-08Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat131015581560
- Claudin-14 Gene Polymorphisms and Urine Calcium Excretion10.2215/CJN.01770218Wed, 19 Sep 2018 07:31:56 GMT-07:00Claudin-14 Gene Polymorphisms and Urine Calcium ExcretionArcidiacono, TeresaSimonini, MarcoLanzani, ChiaraCitterio, LorenaSalvi, ErikaBarlassina, CristinaSpotti, DonatellaCusi, DanieleManunta, PaoloVezzoli, Giuseppe2018-09-19T07:31:56-07:00doi:10.2215/CJN.01770218hwp:resource-id:clinjasn;13/10/1542American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclaudin-14, hypercalciuria, claudin-16, claudin-19, Polymorphism, Single Nucleotide, Antihypertensive Agents, Genome-Wide Association Study, Cations, Divalent, Sodium Chloride, Computational Biology, Retrospective Studies, Claudins, Kidney Calculi, Calcium, Dietary, Genotype, PermeabilityOriginal ArticlesMineral MetabolismOriginal ArticlesMineral Metabolismresearch-article20182018-10-08October 08, 201810.2215/CJN.017702181555-90411555-905X2018-09-19T07:31:56-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles1310101542146015491462
- Impact of Navigators on First Visit to a Transplant Center, Waitlisting, and Kidney Transplantation10.2215/CJN.03100318Wed, 22 Aug 2018 07:40:12 GMT-07:00Impact of Navigators on First Visit to a Transplant Center, Waitlisting, and Kidney TransplantationSullivan, Catherine M.Barnswell, Kitty V.Greenway, KateKamps, Cindy M.Wilson, DerrickAlbert, Jeffrey M.Dolata, JacquelineHuml, AnnePencak, Julie A.Ducker, John T.Gedaly, RobertoJones, Christopher M.Pesavento, ToddSehgal, Ashwini R.2018-08-22T07:40:12-07:00doi:10.2215/CJN.03100318hwp:resource-id:clinjasn;13/10/1550American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, kidney transplantation, Living Donors, Waiting Lists, Control Groups, Kidney Failure, Chronic, renal dialysis, Death, Referral and ConsultationOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-10-08October 08, 201810.2215/CJN.031003181555-90411555-905X2018-08-22T07:40:12-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles131015501555
- Minding the Missing Link10.2215/CJN.03730318Wed, 25 Jul 2018 10:04:31 GMT-07:00Minding the Missing LinkVinson, Amanda J.Tennankore, Karthik K.2018-07-25T10:04:31-07:00doi:10.2215/CJN.03730318hwp:resource-id:clinjasn;13/10/1581American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, kidney transplantation, Living DonorsPerspectivesPerspectivesresearch-article20182018-10-08October 08, 201810.2215/CJN.037303181555-90411555-905X2018-07-25T10:04:31-07:002018-10-08Clinical Journal of the American Society of NephrologyPerspectives131015811583
- Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus Nephritis10.2215/CJN.01070118Wed, 08 Aug 2018 09:28:22 GMT-07:00Peripheral Blood B Cell Depletion after Rituximab and Complete Response in Lupus NephritisGomez Mendez, Liliana MichelleCascino, Matthew D.Garg, JayKatsumoto, Tamiko R.Brakeman, PaulDall’Era, MariaLooney, Richard JohnRovin, BradDragone, LeonardBrunetta, Paul2018-08-08T09:28:22-07:00doi:10.2215/CJN.01070118hwp:resource-id:clinjasn;13/10/1502American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, rituximab, b cell depletion, LUNAR, renal response, systemic lupus erythematosusOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-10-08October 08, 201810.2215/CJN.010701181555-90411555-905X2018-08-08T09:28:22-07:002018-10-08Clinical Journal of the American Society of NephrologyOriginal Articles1310115021111509111
- Podocyte-Specific Induction of Krüppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney Disease10.1681/ASN.2018030324Fri, 24 Aug 2018 05:40:27 GMT-07:00Podocyte-Specific Induction of Krüppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney DiseaseGuo, YiqingPace, JesseLi, ZhengzheMa’ayan, AviWang, ZichenRevelo, Monica P.Chen, EdwardGu, XiangchenAttalah, AhmedYang, YaqiEstrada, ChelseaYang, Vincent W.He, John C.Mallipattu, Sandeep K.2018-08-24T05:40:27-07:00doi:10.1681/ASN.2018030324hwp:resource-id:jnephrol;29/10/2529American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyKrüppel-like factor, podocytes, glomerulosclerosis, proteinuria, kidney diseaseBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180303241046-66731533-34502018-08-24T05:40:27-07:002018-10Journal of the American Society of NephrologyBasic Research291025292545
- Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing It in Chronic Kidney Disease10.1681/ASN.2018050517Thu, 09 Aug 2018 09:22:51 GMT-07:00Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing It in Chronic Kidney DiseaseZhou, ChenchenMei, ChanglinDai, BingXue, Cheng2018-08-09T09:22:51-07:00doi:10.1681/ASN.2018050517hwp:resource-id:jnephrol;29/10/2602American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, fibroblast, chronic kidney diseaseLetters to the EditorLetters to the Editorletter20182018-10-01October 201810.1681/ASN.20180505171046-66731533-34502018-08-09T09:22:51-07:002018-10Journal of the American Society of NephrologyLetters to the Editor29101010260226012602260226012603
- Fibroblast Growth Factor-23 Is Not a Single Bystander in Chronic Kidney Disease Mortality10.1681/ASN.2018060583Fri, 13 Jul 2018 12:30:03 GMT-07:00Fibroblast Growth Factor-23 Is Not a Single Bystander in Chronic Kidney Disease MortalityPelletier, SolenneFouque, Denis2018-07-13T12:30:03-07:00doi:10.1681/ASN.2018060583hwp:resource-id:jnephrol;29/10/2601American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyfibroblast growth factor, klotho, cardiovascular events, hemodialysis, survivalLetters to the EditorLetters to the Editorletter20182018-10-01October 201810.1681/ASN.20180605831046-66731533-34502018-07-13T12:30:03-07:002018-10Journal of the American Society of NephrologyLetters to the Editor29101010260126022602260126022603
- Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise10.1681/ASN.2018030272Tue, 11 Sep 2018 07:32:46 GMT-07:00Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip ExerciseHaddock, Bryan ThomasFrancis, Susan T.Larsson, Henrik B.W.Andersen, Ulrik B.2018-09-11T07:32:46-07:00doi:10.1681/ASN.2018030272hwp:resource-id:jnephrol;29/10/2510American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, chronic hypoxia, Hemodynamics and Vascular Regulation, MRI, BOLD, ASLBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180302721046-66731533-34502018-09-11T07:32:46-07:002018-10Journal of the American Society of NephrologyBasic Research293010325105172517517
- This Month’s Highlights10.1681/ASN.2018080824Fri, 28 Sep 2018 01:00:27 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2018-09-28T13:00:27-07:00doi:10.1681/ASN.2018080824hwp:resource-id:jnephrol;29/10/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-10-01October 201810.1681/ASN.20180808241046-66731533-34502018-09-28T13:00:27-07:002018-10Journal of the American Society of NephrologyThis Month’s Highlights2910ii
- Authors’ Reply10.1681/ASN.2018060612Fri, 13 Jul 2018 12:30:04 GMT-07:00Authors’ ReplyHerrington, William G.Donovan, KillianMihaylova, Borislava2018-07-13T12:30:04-07:00doi:10.1681/ASN.2018060612hwp:resource-id:jnephrol;29/10/2602-aAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular, Epidemiology and outcomes, FGF-23Letters to the EditorLetters to the Editorletter20182018-10-01October 201810.1681/ASN.20180606121046-66731533-34502018-07-13T12:30:04-07:002018-10Journal of the American Society of NephrologyLetters to the Editor29101010260226022601260326022601
- Human-Specific Abnormal Alternative Splicing of Wild-Type PKD1 Induces Premature Termination of Polycystin-110.1681/ASN.2018040442Wed, 05 Sep 2018 07:37:45 GMT-07:00Human-Specific Abnormal Alternative Splicing of Wild-Type PKD1 Induces Premature Termination of Polycystin-1Lea, Wendy A.Parnell, Stephen C.Wallace, Darren P.Calvet, James P.Zelenchuk, Lesya V.Alvarez, Nehemiah S.Ward, Christopher J.2018-09-05T07:37:45-07:00doi:10.1681/ASN.2018040442hwp:resource-id:jnephrol;29/10/2482American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, kidney disease, genetic renal diseaseBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180404421046-66731533-34502018-09-05T07:37:45-07:002018-10Journal of the American Society of NephrologyBasic Research291024822492
- Racial Disparities in Nephrology Consultation and Disease Progression among Veterans with CKD: An Observational Cohort Study10.1681/ASN.2018040344Fri, 17 Aug 2018 06:31:17 GMT-07:00Racial Disparities in Nephrology Consultation and Disease Progression among Veterans with CKD: An Observational Cohort StudySuarez, JonathanCohen, Jordana B.Potluri, VishnuYang, WeiKaplan, David E.Serper, MarinaShah, Siddharth P.Reese, Peter Philip2018-08-17T06:31:17-07:00doi:10.1681/ASN.2018040344hwp:resource-id:jnephrol;29/10/2563American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, nephrology, outcomes, health disparitiesClinical EpidemiologyClinical Epidemiologyresearch-article20182018-10-01October 201810.1681/ASN.20180403441046-66731533-34502018-08-17T06:31:17-07:002018-10Journal of the American Society of NephrologyClinical Epidemiology291025632573
- Mechanism of Fibrosis in HNF1B-Related Autosomal Dominant Tubulointerstitial Kidney Disease10.1681/ASN.2018040437Fri, 10 Aug 2018 05:49:35 GMT-07:00Mechanism of Fibrosis in HNF1B-Related Autosomal Dominant Tubulointerstitial Kidney DiseaseChan, Siu ChiuZhang, YingShao, AnnieAvdulov, SvetlanaHerrera, JeremyAboudehen, KaramPontoglio, MarcoIgarashi, Peter2018-08-10T05:49:35-07:00doi:10.1681/ASN.2018040437hwp:resource-id:jnephrol;29/10/2493American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycystic kidney, genetic renal disease, gene transcription, renal fibrosis, transcription factorsBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180404371046-66731533-34502018-08-10T05:49:35-07:002018-10Journal of the American Society of NephrologyBasic Research291024932509
- Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2018050518Wed, 12 Sep 2018 11:25:23 GMT-07:00Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney DiseaseCassini, Marcelo F.Kakade, Vijayakumar R.Kurtz, ElizabethSulkowski, ParkerGlazer, PeterTorres, RichardSomlo, StefanCantley, Lloyd G.2018-09-12T11:25:23-07:00doi:10.1681/ASN.2018050518hwp:resource-id:jnephrol;29/10/2471American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, genetic renal disease, Immunology and pathology, kidney tubule, MCP-1, polycystic kidney diseaseBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180505181046-66731533-34502018-09-12T11:25:23-07:002018-10Journal of the American Society of NephrologyBasic Research2910102471244724812448
- Are Cyst-Associated Macrophages in Polycystic Kidney Disease the Equivalent to TAMs in Cancer?10.1681/ASN.2018080846Wed, 12 Sep 2018 11:25:22 GMT-07:00Are Cyst-Associated Macrophages in Polycystic Kidney Disease the Equivalent to TAMs in Cancer?Weimbs, Thomas2018-09-12T11:25:22-07:00doi:10.1681/ASN.2018080846hwp:resource-id:jnephrol;29/10/2447American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, macrophages, tumor-associated macrophages, renal cysts, innate immune system, fibrosisUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-10-01October 201810.1681/ASN.20180808461046-66731533-34502018-09-12T11:25:22-07:002018-10Journal of the American Society of NephrologyUp Front Matters2910102447247124482481
- Prevalence Estimates of Polycystic Kidney and Liver Disease by Population Sequencing10.1681/ASN.2018050493Wed, 22 Aug 2018 07:40:32 GMT-07:00Prevalence Estimates of Polycystic Kidney and Liver Disease by Population SequencingLanktree, Matthew B.Haghighi, AmirrezaGuiard, ElsaIliuta, Ioan-AndreiSong, XuewenHarris, Peter C.Paterson, Andrew D.Pei, York2018-08-22T07:40:32-07:00doi:10.1681/ASN.2018050493hwp:resource-id:jnephrol;29/10/2593American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, liver cysts, human genetics, genetic renal, disease, ADPKDClinical ResearchClinical Researchresearch-article20182018-10-01October 201810.1681/ASN.20180504931046-66731533-34502018-08-22T07:40:32-07:002018-10Journal of the American Society of NephrologyClinical Research291025932600
- The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates Sodium Excretion during Diabetic Kidney Disease10.1681/ASN.2018030323Wed, 05 Sep 2018 07:37:46 GMT-07:00The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates Sodium Excretion during Diabetic Kidney DiseaseEriguchi, MasahiroBernstein, Ellen A.Veiras, Luciana C.Khan, ZakirCao, Duo YaoFuchs, SebastienMcDonough, Alicia A.Toblli, Jorge E.Gonzalez-Villalobos, Romer A.Bernstein, Kenneth E.Giani, Jorge F.2018-09-05T07:37:46-07:00doi:10.1681/ASN.2018030323hwp:resource-id:jnephrol;29/10/2546American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyangiotensin II, AcSDKP, diabetic nephropathy, Angiotensin-converting enzyme, sodium transporters, ENaC cleavageBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180303231046-66731533-34502018-09-05T07:37:46-07:002018-10Journal of the American Society of NephrologyBasic Research291025462561
- In-Center Hemodialysis: Time for a Paradigm Shift10.1681/ASN.2018030269Wed, 05 Sep 2018 07:37:45 GMT-07:00In-Center Hemodialysis: Time for a Paradigm ShiftGul, AmbreenMiskulin, Dana C.Harford, AntoniaZager, Philip2018-09-05T07:37:45-07:00doi:10.1681/ASN.2018030269hwp:resource-id:jnephrol;29/10/2452American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyimproving hemodialysis outcomes, hemodialysis frequency, alternate day, hemodialysisUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-10-01October 201810.1681/ASN.20180302691046-66731533-34502018-09-05T07:37:45-07:002018-10Journal of the American Society of NephrologyUp Front Matters291024522454
- Hereditary Kidney Disease: All Family Members Are Affected10.1681/ASN.2018080854Tue, 11 Sep 2018 07:32:46 GMT-07:00Hereditary Kidney Disease: All Family Members Are AffectedFalke, Roberta M.Levey, Andrew S.2018-09-11T07:32:46-07:00doi:10.1681/ASN.2018080854hwp:resource-id:jnephrol;29/10/2451American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, family, transplantationUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-10-01October 201810.1681/ASN.20180808541046-66731533-34502018-09-11T07:32:46-07:002018-10Journal of the American Society of NephrologyUp Front Matters291024512452
- Perspective: Will We Ever Know the Optimal Hgb Level in ESRD?10.1681/ASN.2018040363Wed, 05 Sep 2018 07:37:46 GMT-07:00Perspective: Will We Ever Know the Optimal Hgb Level in ESRD?Wish, Jay B.2018-09-05T07:37:46-07:00doi:10.1681/ASN.2018040363hwp:resource-id:jnephrol;29/10/2454American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, hemoglobin, ESRD, erythropoietinUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-10-01October 201810.1681/ASN.20180403631046-66731533-34502018-09-05T07:37:46-07:002018-10Journal of the American Society of NephrologyUp Front Matters291024542457
- MicroRNA-214-3p in the Kidney Contributes to the Development of Hypertension10.1681/ASN.2018020117Thu, 26 Jul 2018 06:21:56 GMT-07:00MicroRNA-214-3p in the Kidney Contributes to the Development of HypertensionLiu, YongUsa, KristieWang, FengLiu, PengyuanGeurts, Aron M.Li, JunhuiWilliams, Anna MarieRegner, Kevin R.Kong, YiweiLiu, HanNie, JingLiang, Mingyu2018-07-26T06:21:56-07:00doi:10.1681/ASN.2018020117hwp:resource-id:jnephrol;29/10/2518American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, kidney, microRNA, nitric oxide, geneticsBasic ResearchBasic Researchresearch-article20182018-10-01October 201810.1681/ASN.20180201171046-66731533-34502018-07-26T06:21:56-07:002018-10Journal of the American Society of NephrologyBasic Research291025182528
- Genetic Variants Associated with Circulating Fibroblast Growth Factor 2310.1681/ASN.2018020192Fri, 14 Sep 2018 07:13:22 GMT-07:00Genetic Variants Associated with Circulating Fibroblast Growth Factor 23Robinson-Cohen, CassianneBartz, Traci M.Lai, DongbingIkizler, T. AlpPeacock, MunroImel, Erik A.Michos, Erin D.Foroud, Tatiana M.Akesson, KristinaTaylor, Kent D.Malmgren, LinneaMatsushita, KunihiroNethander, MariaEriksson, JoelOhlsson, ClaesMellström, DanielWolf, MylesLjunggren, OstenMcGuigan, FionaRotter, Jerome I.Karlsson, MagnusEcons, Michael J.Ix, Joachim H.Lutsey, Pamela L.Psaty, Bruce M.de Boer, Ian H.Kestenbaum, Bryan R.2018-09-14T07:13:22-07:00doi:10.1681/ASN.2018020192hwp:resource-id:jnephrol;29/10/2583American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhuman genetics, fibroblast growth factor 23, mineral metabolismClinical EpidemiologyClinical Epidemiologyresearch-article20182018-10-01October 201810.1681/ASN.20180201921046-66731533-34502018-09-14T07:13:22-07:002018-10Journal of the American Society of NephrologyClinical Epidemiology291025832592
- A Practical Guide for Treatment of Rapidly Progressive ADPKD with TolvaptanIn the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.10.1681/ASN.2018060590Tue, 18 Sep 2018 08:10:06 GMT-07:00A Practical Guide for Treatment of Rapidly Progressive ADPKD with TolvaptanIn the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.Chebib, Fouad T.Perrone, Ronald D.Chapman, Arlene B.Dahl, Neera K.Harris, Peter C.Mrug, MichalMustafa, Reem A.Rastogi, AnjayWatnick, TerryYu, Alan S.L.Torres, Vicente E.2018-09-18T08:10:06-07:00doi:10.1681/ASN.2018060590hwp:resource-id:jnephrol;29/10/2458American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, Tolvaptan, vasopressin, V2 Receptor Antagonist, polycystic kidney disease, hepatotoxicityUp Front MattersReviewUp Front MattersReviewbrief-report20182018-10-01October 201810.1681/ASN.20180605901046-66731533-34502018-09-18T08:10:06-07:002018-10Journal of the American Society of NephrologyUp Front Matters291024582470
- Kidney Transplantation Rates of Veterans Administration–Listed Patients Compared with Rates of Patients on Nonveteran Lists10.1681/ASN.2018080843Tue, 18 Sep 2018 08:10:06 GMT-07:00Kidney Transplantation Rates of Veterans Administration–Listed Patients Compared with Rates of Patients on Nonveteran ListsRamkumar, MohanCrowley, Susan T.2018-09-18T08:10:06-07:00doi:10.1681/ASN.2018080843hwp:resource-id:jnephrol;29/10/2449American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyKidney Transplant, Veterans, Access to CareUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-10-01October 201810.1681/ASN.20180808431046-66731533-34502018-09-18T08:10:06-07:002018-10Journal of the American Society of NephrologyUp Front Matters2910102449257424502582
- Significantly Lower Rates of Kidney Transplantation among Candidates Listed with the Veterans Administration: A National and Local Comparison10.1681/ASN.2017111204Fri, 13 Jul 2018 12:30:04 GMT-07:00Significantly Lower Rates of Kidney Transplantation among Candidates Listed with the Veterans Administration: A National and Local ComparisonAugustine, Joshua J.Arrigain, SusanaBalabhadrapatruni, KrishnaDesai, NirajSchold, Jesse D.2018-07-13T12:30:04-07:00doi:10.1681/ASN.2017111204hwp:resource-id:jnephrol;29/10/2574American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, cadaver organ transplantation, transplant outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20182018-10-01October 201810.1681/ASN.20171112041046-66731533-34502018-07-13T12:30:04-07:002018-10Journal of the American Society of NephrologyClinical Epidemiology2910102574244925822450
- Incident Atrial Fibrillation and the Risk of Stroke in Adults with Chronic Kidney Disease10.2215/CJN.04060318Fri, 20 Jul 2018 05:44:01 GMT-07:00Incident Atrial Fibrillation and the Risk of Stroke in Adults with Chronic Kidney DiseaseCarrero, Juan JesusTrevisan, MarcoSood, Manish M.Bárány, PeterXu, HongEvans, MarieFriberg, LeifSzummer, Karolina2018-07-20T05:44:01-07:00doi:10.2215/CJN.04060318hwp:resource-id:clinjasn;13/9/1314American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, Atrial Fibrillation, Incidence, Stroke, Follow-Up Studies, Brain Ischemia, Intracranial Hemorrhages, glomerular filtration rate, Renal Insufficiency, Chronic, Risk, Patient CareOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-09-07September 07, 201810.2215/CJN.040603181555-90411555-905X2018-07-20T05:44:01-07:002018-09-07Clinical Journal of the American Society of NephrologyOriginal Articles13913141320
- Management of the Incidental Kidney Mass in the Nephrology Clinic10.2215/CJN.00860118Fri, 13 Apr 2018 07:18:23 GMT-07:00Management of the Incidental Kidney Mass in the Nephrology ClinicHu, Susie L.Weiss, Robert H.2018-04-13T07:18:23-07:00doi:10.2215/CJN.00860118hwp:resource-id:clinjasn;13/9/1407American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCarcinoma, Renal Cell, chronic kidney disease, Humans, kidney, Kidney Neoplasms, Nephrologists, nephrology, Oncologists, Referral and Consultation, Renal Cell Carcinoma, Renal Insufficiency, Chronic, risk factors, UrologistsKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-09-07September 07, 201810.2215/CJN.008601181555-90411555-905X2018-04-13T07:18:23-07:002018-09-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat13914071409
- A Patient with Hemodialysis Access Problems10.2215/CJN.02610218Fri, 18 May 2018 07:33:48 GMT-07:00A Patient with Hemodialysis Access ProblemsNiyyar, Vandana DuaLok, Charmaine E.2018-05-18T07:33:48-07:00doi:10.2215/CJN.02610218hwp:resource-id:clinjasn;13/9/1410American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, hemodialysis access, interventional nephrology, arteriovenous fistula, chronic dialysis, Arteriovenous Shunt, Surgical, renal dialysisKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20182018-09-07September 07, 201810.2215/CJN.026102181555-90411555-905X2018-05-18T07:33:48-07:002018-09-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire13914101412
- This Month's Highlights10.1681/ASN.2018070711Fri, 31 Aug 2018 01:00:29 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2018-08-31T13:00:29-07:00doi:10.1681/ASN.2018070711hwp:resource-id:jnephrol;29/9/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-09-01September 201810.1681/ASN.20180707111046-66731533-34502018-08-31T13:00:29-07:002018-09Journal of the American Society of NephrologyThis Month’s Highlights299ii
- Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract10.1681/ASN.2017121265Fri, 24 Aug 2018 05:40:27 GMT-07:00Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tractvan der Ven, Amelie T.Connaughton, Dervla M.Ityel, HadasMann, NinaNakayama, MakikoChen, JingVivante, AsafHwang, Daw-yangSchulz, JulianBraun, Daniela A.Schmidt, Johanna MagdalenaSchapiro, DavidSchneider, RonenWarejko, Jillian K.Daga, AnkanaMajmundar, Amar J.Tan, WeizhenJobst-Schwan, TilmanHermle, TobiasWidmeier, EugenAshraf, ShaziaAmar, AliHoogstraaten, Charlotte A.Hugo, HannahKitzler, Thomas M.Kause, FranziskaKolvenbach, Caroline M.Dai, RufengSpaneas, LeslieAmann, KassaundraStein, Deborah R.Baum, Michelle A.Somers, Michael J.G.Rodig, Nancy M.Ferguson, Michael A.Traum, Avram Z.Daouk, Ghaleb H.Bogdanović, RadovanStajić, NatasaSoliman, Neveen A.Kari, Jameela A.El Desoky, SherifFathy, Hanan M.Milosevic, DankoAl-Saffar, MunaAwad, Hazem S.Eid, Loai A.Selvin, AravindSenguttuvan, PrabhaSanna-Cherchi, SimoneRehm, Heidi L.MacArthur, Daniel G.Lek, MonkolLaricchia, Kristen M.Wilson, Michael W.Mane, Shrikant M.Lifton, Richard P.Lee, Richard S.Bauer, Stuart B.Lu, WeiningReutter, Heiko M.Tasic, VeliborShril, ShirleeHildebrandt, Friedhelm2018-08-24T05:40:27-07:00doi:10.1681/ASN.2017121265hwp:resource-id:jnephrol;29/9/2348American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyCongenital Anomalies of the Kidney and Urinary Tract (CAKUT), Whole Exome Sequencing (WES), Vesico-ureteral Reflux (VUR), monogenic disease causation, renal developmental geneBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20171212651046-66731533-34502018-08-24T05:40:27-07:002018-09Journal of the American Society of NephrologyBasic Research29923482361
- Race, Ethnicity, and End-of-Life Care in Dialysis Patients in the United States10.1681/ASN.2017121297Thu, 09 Aug 2018 09:22:50 GMT-07:00Race, Ethnicity, and End-of-Life Care in Dialysis Patients in the United StatesFoley, Robert N.Sexton, Donal J.Drawz, PaulIshani, AreefReule, Scott2018-08-09T09:22:50-07:00doi:10.1681/ASN.2017121297hwp:resource-id:jnephrol;29/9/2387American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, dialysis, end-of-life, race, ethnicity, disparityClinical EpidemiologyClinical Epidemiologyresearch-article20182018-09-01September 201810.1681/ASN.20171212971046-66731533-34502018-08-09T09:22:50-07:002018-09Journal of the American Society of NephrologyClinical Epidemiology29923872399
- A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine10.1681/ASN.2018010090Fri, 27 Jul 2018 09:42:20 GMT-07:00A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum CreatinineXu, XinNie, ShengZhang, AihuaJianhua, MaoLiu, Hai-PengXia, HuiminXu, HongLiu, ZhangsuoFeng, ShipinZhou, WeiLiu, XuemeiYang, YonghongTao, YuhongFeng, YunlinChen, ChunboWang, MoZha, YanFeng, Jian-HuaLi, QingchuGe, ShuwangChen, JianghuaHe, YongchengTeng, SiyuanHao, ChuanmingLiu, Bi-ChengTang, YingWang, Li-JunQi, Jin-LeiHe, WenjuanHe, PinghongLiu, YouhuaHou, Fan Fan2018-07-27T09:42:20-07:00doi:10.1681/ASN.2018010090hwp:resource-id:jnephrol;29/9/2432American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychildren, acute kidney injury, criterionClinical ResearchClinical Researchresearch-article20182018-09-01September 201810.1681/ASN.20180100901046-66731533-34502018-07-27T09:42:20-07:002018-09Journal of the American Society of NephrologyClinical Research29992432225924422261
- Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector10.1681/ASN.2018040426Thu, 05 Jul 2018 05:18:05 GMT-07:00Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral VectorIkeda, YoichiroSun, ZhaoRu, XiaoVandenberghe, Luk H.Humphreys, Benjamin D.2018-07-05T05:18:05-07:00doi:10.1681/ASN.2018040426hwp:resource-id:jnephrol;29/9/2287American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyvirology, chronic kidney disease, gene therapyBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20180404261046-66731533-34502018-07-05T05:18:05-07:002018-09Journal of the American Society of NephrologyBasic Research29922872297
- Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth in Pkd1-Deficient Mice10.1681/ASN.2018010074Tue, 24 Jul 2018 01:47:13 GMT-07:00Interactions between Macrophages and Cyst-Lining Epithelial Cells Promote Kidney Cyst Growth in Pkd1-Deficient MiceYang, YangChen, MeihanZhou, JieLv, JiayiSong, ShuweiFu, LiLiChen, JiejianYang, MingMei, Changlin2018-07-24T13:47:13-07:00doi:10.1681/ASN.2018010074hwp:resource-id:jnephrol;29/9/2310American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, metabolism, arginine, proliferation, macrophageBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20180100741046-66731533-34502018-07-24T13:47:13-07:002018-09Journal of the American Society of NephrologyBasic Research29923102325
- MUC1 Makes Me Miserable10.1681/ASN.2018070742Fri, 17 Aug 2018 06:31:17 GMT-07:00MUC1 Makes Me MiserableGale, Daniel P.Kleta, Robert2018-08-17T06:31:17-07:00doi:10.1681/ASN.2018070742hwp:resource-id:jnephrol;29/9/2257American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymucin, adtkd, genetic renal diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-09-01September 201810.1681/ASN.20180707421046-66731533-34502018-08-17T06:31:17-07:002018-09Journal of the American Society of NephrologyUp Front Matters29999225722982418225823092431
- Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft FailureBackground Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.10.1681/ASN.2018020205Thu, 26 Jul 2018 06:21:56 GMT-07:00Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft FailureBackground Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non–C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non–C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non–C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%. Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.Kamburova, Elena G.Wisse, Bram W.Joosten, IrmaAllebes, Wil A.van der Meer, ArnoldHilbrands, Luuk B.Baas, Marije C.Spierings, EricHack, Cornelis E.van Reekum, Franka E.van Zuilen, Arjan D.Verhaar, Marianne C.Bots, Michiel L.Drop, Adriaan C.A.D.Plaisier, LoesSeelen, Marc A.J.Sanders, Jan StephanHepkema, Bouke G.Lambeck, Annechien J.A.Bungener, Laura B.Roozendaal, CarolineTilanus, Marcel G.J.Voorter, Christina E.Wieten, Lottevan Duijnhoven, Elly M.Gelens, Mariëlle A.C.J.Christiaans, Maarten H.L.van Ittersum, Frans J.Nurmohamed, Shaikh A.Lardy, Neubury M.Swelsen, Wendyvan der Pant, Karlijn A.M.I.van der Weerd, Neelke C.ten Berge, Ineke J.M.Bemelman, Frederike J.Hoitsma, Andries J.van der Boog, Paul J.M.de Fijter, Johan W.Betjes, Michiel G.H.Heidt, SebastiaanRoelen, Dave L.Claas, Frans H.Otten, Henny G.2018-07-26T06:21:56-07:00doi:10.1681/ASN.2018020205hwp:resource-id:jnephrol;29/9/2279American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic allograft failure, kidney transplantation, anti-HLA antibodies, complement-fixing antibodiesRapid CommunicationRapid Communicationresearch-article20182018-09-01September 201810.1681/ASN.20180202051046-66731533-34502018-07-26T06:21:56-07:002018-09Journal of the American Society of NephrologyRapid Communication29922792285
- Novel Approaches for Assessment of Bone Turnover in CKD: Is New Always Better?10.1681/ASN.2018050561Mon, 30 Jul 2018 04:57:36 GMT-07:00Novel Approaches for Assessment of Bone Turnover in CKD: Is New Always Better?Gosmanova, Elvira O.Gosmanov, Aidar R.2018-07-30T04:57:36-07:00doi:10.1681/ASN.2018050561hwp:resource-id:jnephrol;29/9/2443American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAlkaline Phosphatase, Bone Turnover, CKDLetter to the EditorLetter to the Editorletter20182018-09-01September 201810.1681/ASN.20180505611046-66731533-34502018-07-30T04:57:36-07:002018-09Journal of the American Society of NephrologyLetter to the Editor29992443244424442444
- Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease10.1681/ASN.2018020180Mon, 02 Jul 2018 07:45:59 GMT-07:00Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney DiseaseŽivná, MartinaKidd, KendrahPřistoupilová, AnnaBarešová, VeronikaDeFelice, MathewBlumenstiel, BrendanHarden, MaeganConlon, PeterLavin, PeterConnaughton, Dervla M.Hartmannová, HanaHodaňová, KateřinaStránecký, ViktorVrbacká, AlenaVyleťal, PetrŽivný, JanVotruba, MiroslavSovová, JanaHůlková, HelenaRobins, VictoriaPerry, RebeccaWenzel, AndreaBeck, Bodo B.Seeman, TomášViklický, OndřejRajnochová-Bloudíčková, SylviePapagregoriou, GregoryDeltas, Constantinos C.Alper, Seth L.Greka, AnnaBleyer, Anthony J.Kmoch, Stanislav2018-07-02T07:45:59-07:00doi:10.1681/ASN.2018020180hwp:resource-id:jnephrol;29/9/2418American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAutosomal Dominant Tubulo-Interstitial Kidney Disease, MUC1, Inherited, kidney disease, Mucin-1 Kidney Disease, immunostaining, diagnosisClinical ResearchClinical Researchresearch-article20182018-09-01September 201810.1681/ASN.20180201801046-66731533-34502018-07-02T07:45:59-07:002018-09Journal of the American Society of NephrologyClinical Research29319942418225789224312258892
- Authors' Reply10.1681/ASN.2018060647Mon, 30 Jul 2018 04:57:36 GMT-07:00Authors' ReplySalam, SyazrahKhwaja, ArifEastell, Richard2018-07-30T04:57:36-07:00doi:10.1681/ASN.2018060647hwp:resource-id:jnephrol;29/9/2444American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyalkaline phosphatase, CKD, bone biopsyLetter to the EditorLetter to the Editorletter20182018-09-01September 201810.1681/ASN.20180606471046-66731533-34502018-07-30T04:57:36-07:002018-09Journal of the American Society of NephrologyLetter to the Editor29992444244324442444
- Erratum10.1681/ASN.2018060653Fri, 31 Aug 2018 01:00:29 GMT-07:00ErratumAmerican Society of Nephrology2018-08-31T13:00:29-07:00doi:10.1681/ASN.2018060653hwp:resource-id:jnephrol;29/9/2445American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20182018-09-01September 201810.1681/ASN.20180606531046-66731533-34502018-08-31T13:00:29-07:002018-09Journal of the American Society of NephrologyErratum2929972445196024451969
- Structural Basis of Highly Specific Interaction between Nephrin and MAGI1 in Slit Diaphragm Assembly and Signaling10.1681/ASN.2017121275Fri, 13 Jul 2018 12:30:03 GMT-07:00Structural Basis of Highly Specific Interaction between Nephrin and MAGI1 in Slit Diaphragm Assembly and SignalingWeng, ZhuangfengShang, YuanJi, ZeyangYe, FeiLin, LinZhang, RongguangZhu, Jinwei2018-07-13T12:30:03-07:00doi:10.1681/ASN.2017121275hwp:resource-id:jnephrol;29/9/2362American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynephrin, nephrotic syndrome, glomerular filtration barrier, Cell Signaling, cell adhesionBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20171212751046-66731533-34502018-07-13T12:30:03-07:002018-09Journal of the American Society of NephrologyBasic Research29923622371
- Phosphorylation of Acetyl-CoA Carboxylase by AMPK Reduces Renal Fibrosis and Is Essential for the Anti-Fibrotic Effect of Metformin10.1681/ASN.2018010050Thu, 05 Jul 2018 05:18:06 GMT-07:00Phosphorylation of Acetyl-CoA Carboxylase by AMPK Reduces Renal Fibrosis and Is Essential for the Anti-Fibrotic Effect of MetforminLee, MardianaKaterelos, MarinaGleich, KurtGalic, SandraKemp, Bruce E.Mount, Peter F.Power, David A.2018-07-05T05:18:06-07:00doi:10.1681/ASN.2018010050hwp:resource-id:jnephrol;29/9/2326American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, renal fibrosis, metformin, ampk, fatty acid oxidationBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20180100501046-66731533-34502018-07-05T05:18:06-07:002018-09Journal of the American Society of NephrologyBasic Research29923262336
- EGF Receptor–Dependent YAP Activation Is Important for Renal Recovery from AKI10.1681/ASN.2017121272Thu, 02 Aug 2018 06:57:07 GMT-07:00EGF Receptor–Dependent YAP Activation Is Important for Renal Recovery from AKIChen, JianchunYou, HuaizhouLi, YanXu, YouHe, QianHarris, Raymond C.2018-08-02T06:57:07-07:00doi:10.1681/ASN.2017121272hwp:resource-id:jnephrol;29/9/2372American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyEGFR, YAP, Acute kidney injury, RecoveryBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20171212721046-66731533-34502018-08-02T06:57:07-07:002018-09Journal of the American Society of NephrologyBasic Research29923722385
- Biallelic Expression of Mucin-1 in Autosomal Dominant Tubulointerstitial Kidney Disease: Implications for Nongenetic Disease Recognition10.1681/ASN.2018030245Thu, 26 Jul 2018 06:21:55 GMT-07:00Biallelic Expression of Mucin-1 in Autosomal Dominant Tubulointerstitial Kidney Disease: Implications for Nongenetic Disease RecognitionKnaup, Karl X.Hackenbeck, ThomasPopp, BerntStoeckert, JohannaWenzel, AndreaBüttner-Herold, MaikePfister, FrederickSchueler, MarkusSeven, DidemMay, Annette M.Halbritter, JanGröne, Hermann-JosefReis, AndréBeck, Bodo B.Amann, KerstinEkici, Arif B.Wiesener, Michael S.2018-07-26T06:21:55-07:00doi:10.1681/ASN.2018030245hwp:resource-id:jnephrol;29/9/2298American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyMCKD, interstitial nephritis, TIN, IF/TA, CKDBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20180302451046-66731533-34502018-07-26T06:21:55-07:002018-09Journal of the American Society of NephrologyBasic Research29992298225723092258
- ABCC6 Deficiency Promotes Development of Randall Plaque10.1681/ASN.2017101148Tue, 10 Jul 2018 06:29:55 GMT-07:00ABCC6 Deficiency Promotes Development of Randall PlaqueLetavernier, EmmanuelKauffenstein, GillesHuguet, LéaNavasiolava, NastassiaBouderlique, EliseTang, EllieDelaitre, LéaBazin, Dominiquede Frutos, MartaGay, ClémentPerez, JoëlleVerpont, Marie-ChristineHaymann, Jean-PhilippePomozi, ViolaZoll, JannaLe Saux, OlivierDaudon, MichelLeftheriotis, GeorgesMartin, Ludovic2018-07-10T06:29:55-07:00doi:10.1681/ASN.2017101148hwp:resource-id:jnephrol;29/9/2337American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, genetic renal disease, mineral metabolismBasic ResearchBasic Researchresearch-article20182018-09-01September 201810.1681/ASN.20171011481046-66731533-34502018-07-10T06:29:55-07:002018-09Journal of the American Society of NephrologyBasic Research29923372347
- Association of Ambulatory Blood Pressure with All-Cause and Cardiovascular Mortality in Hemodialysis Patients: Effects of Heart Failure and Atrial Fibrillation10.1681/ASN.2018010086Wed, 25 Jul 2018 10:04:39 GMT-07:00Association of Ambulatory Blood Pressure with All-Cause and Cardiovascular Mortality in Hemodialysis Patients: Effects of Heart Failure and Atrial FibrillationMayer, Christopher C.Matschkal, JuliaSarafidis, Pantelis A.Hagmair, StefanLorenz, GeorgAngermann, SusanneBraunisch, Matthias C.Baumann, MarcusHeemann, UweWassertheurer, SiegfriedSchmaderer, Christoph2018-07-25T10:04:39-07:00doi:10.1681/ASN.2018010086hwp:resource-id:jnephrol;29/9/2409American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, pulse pressure, ESRD, hemodialysis, risk prediction, heart, diseaseClinical ResearchClinical Researchresearch-article20182018-09-01September 201810.1681/ASN.20180100861046-66731533-34502018-07-25T10:04:39-07:002018-09Journal of the American Society of NephrologyClinical Research29924092417
- A New Pediatric AKI Definition: Implications of Trying to Build the Perfect Mousetrap10.1681/ASN.2018070727Fri, 24 Aug 2018 05:40:28 GMT-07:00A New Pediatric AKI Definition: Implications of Trying to Build the Perfect MousetrapGoldstein, Stuart L.2018-08-24T05:40:28-07:00doi:10.1681/ASN.2018070727hwp:resource-id:jnephrol;29/9/2259American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAcute kidney injury, children, definitionUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-09-01September 201810.1681/ASN.20180707271046-66731533-34502018-08-24T05:40:28-07:002018-09Journal of the American Society of NephrologyUp Front Matters29992259243222612442
- Acute Declines in Renal Function during Intensive BP Lowering and Long-Term Risk of Death10.1681/ASN.2018040365Fri, 13 Jul 2018 12:30:04 GMT-07:00Acute Declines in Renal Function during Intensive BP Lowering and Long-Term Risk of DeathKu, ElaineIx, Joachim H.Jamerson, KennethTangri, NavdeepLin, FengGassman, JenniferSmogorzewski, MiroslawSarnak, Mark J.2018-07-13T12:30:04-07:00doi:10.1681/ASN.2018040365hwp:resource-id:jnephrol;29/9/2401American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic renal disease, hypertension, mortality riskClinical ResearchClinical Researchresearch-article20182018-09-01September 201810.1681/ASN.20180403651046-66731533-34502018-07-13T12:30:04-07:002018-09Journal of the American Society of NephrologyClinical Research29924012408
- What Is the Glomerular Ultrafiltration Barrier?10.1681/ASN.2018050490Fri, 20 Jul 2018 05:44:50 GMT-07:00What Is the Glomerular Ultrafiltration Barrier?Fissell, William H.Miner, Jeffrey H.2018-07-20T05:44:50-07:00doi:10.1681/ASN.2018050490hwp:resource-id:jnephrol;29/9/2262American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration barrier, nephrotic syndrome, podocyteUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20182018-09-01September 201810.1681/ASN.20180504901046-66731533-34502018-07-20T05:44:50-07:002018-09Journal of the American Society of NephrologyUp Front Matters29922622264
- Effects of Enzyme Replacement Therapy and Antidrug Antibodies in Patients with Fabry Disease10.1681/ASN.2018030329Thu, 09 Aug 2018 09:22:50 GMT-07:00Effects of Enzyme Replacement Therapy and Antidrug Antibodies in Patients with Fabry DiseaseLenders, MalteBrand, Eva2018-08-09T09:22:50-07:00doi:10.1681/ASN.2018030329hwp:resource-id:jnephrol;29/9/2265American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyantibodies, Fabry disease, immunosuppression, infusion associated reactions, treatmentUp Front MattersReviewUp Front MattersReviewbrief-report20182018-09-01September 201810.1681/ASN.20180303291046-66731533-34502018-08-09T09:22:50-07:002018-09Journal of the American Society of NephrologyUp Front Matters29922652278
- Mechanisms, Clinical Implications, and Treatment of Intradialytic HypotensionIndividuals with ESKD requiring maintenance hemodialysis face a unique hemodynamic challenge, typically on a thrice-weekly basis. In an effort to achieve some degree of euvolemia, ultrafiltration goals often involve removal of the equivalent of an entire plasma volume. Maintenance of adequate end-organ perfusion in this setting is dependent on the institution of a variety of complex compensatory mechanisms. Unfortunately, secondary to a myriad of patient- and dialysis-related factors, this compensation often falls short and results in intradialytic hypotension. Physicians and patients have developed a greater appreciation for the breadth of adverse outcomes associated with intradialytic hypotension, including higher cardiovascular and all-cause mortality. In this review, we summarize the evidence for adverse outcomes associated with intradialytic hypotension, explore the underlying pathophysiology, and use this as a basis to introduce potential strategies for its prevention and treatment.10.2215/CJN.12141017Mon, 26 Feb 2018 07:10:35 GMT-08:00Mechanisms, Clinical Implications, and Treatment of Intradialytic HypotensionIndividuals with ESKD requiring maintenance hemodialysis face a unique hemodynamic challenge, typically on a thrice-weekly basis. In an effort to achieve some degree of euvolemia, ultrafiltration goals often involve removal of the equivalent of an entire plasma volume. Maintenance of adequate end-organ perfusion in this setting is dependent on the institution of a variety of complex compensatory mechanisms. Unfortunately, secondary to a myriad of patient- and dialysis-related factors, this compensation often falls short and results in intradialytic hypotension. Physicians and patients have developed a greater appreciation for the breadth of adverse outcomes associated with intradialytic hypotension, including higher cardiovascular and all-cause mortality. In this review, we summarize the evidence for adverse outcomes associated with intradialytic hypotension, explore the underlying pathophysiology, and use this as a basis to introduce potential strategies for its prevention and treatment.Reeves, Patrick B.Mc Causland, Finnian R.2018-02-26T07:10:35-08:00doi:10.2215/CJN.12141017hwp:resource-id:clinjasn;13/8/1297American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, end-stage renal disease, blood pressure, Fluid Therapy, Goals, Hemodynamics, Humans, hypotension, Kidney Failure, Chronic, Physicians, Plasma Volume, renal dialysis, ultrafiltrationReviewsReviewsreview-article20182018-08-07August 07, 201810.2215/CJN.121410171555-90411555-905X2018-02-26T07:10:35-08:002018-08-07Clinical Journal of the American Society of NephrologyReviews13812971303
- Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial Fibrillation10.2215/CJN.13811217Thu, 12 Jul 2018 05:23:58 GMT-07:00Risks and Benefits of Direct Oral Anticoagulants across the Spectrum of GFR among Incident and Prevalent Patients with Atrial FibrillationShin, Jung-ImSecora, AlexAlexander, G. CalebInker, Lesley A.Coresh, JosefChang, Alex R.Grams, Morgan E.2018-07-12T05:23:58-07:00doi:10.2215/CJN.13811217hwp:resource-id:clinjasn;13/8/1144American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnticoagulants, Atrial Fibrillation, Brain Ischemia, chronic kidney disease, Confidence Intervals, Direct Oral Anticoagulants, Electronic Health Records, Female, Follow-up Studies, glomerular filtration rate, Hemorrhage, Humans, kidney, Propensity Score, Renal Insufficiency, Chronic, Risk Assessment, Stroke, WarfarinOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-08-07August 07, 201810.2215/CJN.138112171555-90411555-905X2018-07-12T05:23:58-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13811441152
- Opportunities for Increasing the Rate of Preemptive Kidney Transplantation10.2215/CJN.02480218Wed, 16 May 2018 08:01:29 GMT-07:00Opportunities for Increasing the Rate of Preemptive Kidney TransplantationFishbane, StevenNair, Vinay2018-05-16T08:01:29-07:00doi:10.2215/CJN.02480218hwp:resource-id:clinjasn;13/8/1280American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, Graft Survival, kidney transplantation, Living Donors, transplantationPerspectivesPerspectivesresearch-article20182018-08-07August 07, 201810.2215/CJN.024802181555-90411555-905X2018-05-16T08:01:29-07:002018-08-07Clinical Journal of the American Society of NephrologyPerspectives13812801282
- Expand the Pool of Living Donors for Kidney Transplantation10.2215/CJN.07310618Mon, 16 Jul 2018 07:44:51 GMT-07:00Expand the Pool of Living Donors for Kidney TransplantationLocke, Jayme E.2018-07-16T07:44:51-07:00doi:10.2215/CJN.07310618hwp:resource-id:clinjasn;13/8/1142American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyLiving Donors, kidney transplantation, Graft Survival, Kidney Failure, ChronicEditorialsEditorialseditorial20182018-08-07August 07, 201810.2215/CJN.073106181555-90411555-905X2018-07-16T07:44:51-07:002018-08-07Clinical Journal of the American Society of NephrologyEditorials13881142123411431243
- ABO-Incompatible Kidney Transplant Outcomes10.2215/CJN.00540118Mon, 16 Jul 2018 07:44:52 GMT-07:00ABO-Incompatible Kidney Transplant Outcomesde Weerd, Annelies E.Betjes, Michiel G.H.2018-07-16T07:44:52-07:00doi:10.2215/CJN.00540118hwp:resource-id:clinjasn;13/8/1234American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyABO Blood-group system, acute rejection, Antibodies, Bias, Blood Group Incompatibility, Cause of Death, Cohort Studies, Graft Survival, Humans, kidney transplantation, transplant outcomesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-08-07August 07, 201810.2215/CJN.005401181555-90411555-905X2018-07-16T07:44:52-07:002018-08-07Clinical Journal of the American Society of NephrologyOriginal Articles13881234114212431143
- Communication Strategies to Address Conflict about Dialysis Decision Making for Critically Ill Patients10.2215/CJN.00010118Mon, 16 Apr 2018 07:17:08 GMT-07:00Communication Strategies to Address Conflict about Dialysis Decision Making for Critically Ill PatientsSchell, Jane O.Cohen, Robert A.2018-04-16T07:17:08-07:00doi:10.2215/CJN.00010118hwp:resource-id:clinjasn;13/8/1248American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCommunication, Conflict Management, Critical Care, Critical Illness, Decision Making, dialysis, Humans, Nephrologists, Palliative Care, Prognosis, renal dialysis, ThinkingKidney Case Conference: Attending RoundsKidney Case Conference: Attending Roundsresearch-article20182018-08-07August 07, 201810.2215/CJN.000101181555-90411555-905X2018-04-16T07:17:08-07:002018-08-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Attending Rounds13812481250
- Thrombotic Microangiopathy in a Transplant Recipient10.2215/CJN.00020118Tue, 24 Jul 2018 01:47:03 GMT-07:00Thrombotic Microangiopathy in a Transplant RecipientMundra, Venkat Ram RakeshMannon, Roslyn Bernstein2018-07-24T13:47:03-07:00doi:10.2215/CJN.00020118hwp:resource-id:clinjasn;13/8/1251American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAllograft Failure, immunosuppression, kidney transplantation, Thrombotic Microangiopathies, Transplant RecipientsKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20182018-08-07August 07, 201810.2215/CJN.000201181555-90411555-905X2018-07-24T13:47:03-07:002018-08-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire13812511253
- BP Measurement TechniquesPatients with CKD typically have hypertension. Manual BP measurement in the office setting was used to define hypertension, establish eligibility, and assess BP targets in the epidemiologic studies and early randomized, controlled trials that inform current management of hypertension. Use of automated oscillometric devices has largely replaced manual BP measurement in the office and clinical trials. These newer devices may reduce the white coat effect and facilitate guideline-adherent measurement protocols. Obtaining BP measurements outside of the office with home and ambulatory BP monitoring is now more common. Out of office BPs are especially important in patients with CKD, because reduced GFR and proteinuria are associated with masked hypertension (normal office BP and elevated BP outside of the office), elevated nighttime BP, and abnormal diurnal variation in BP, all of which are associated with higher risk for target organ damage and adverse outcomes. Also, it is now feasible to routinely measure central BP and central hemodynamics. These measures are of greater importance to patients with CKD given the higher prevalence of increased sympathetic tone, arteriosclerosis, and inflammation as well as impaired sodium excretion and endothelial dysfunction, which lead to alterations in central BPs in this population. In this review, we describe various BP measurement techniques and how they apply to the care of patients with CKD.10.2215/CJN.12551117Mon, 26 Feb 2018 07:10:35 GMT-08:00BP Measurement TechniquesPatients with CKD typically have hypertension. Manual BP measurement in the office setting was used to define hypertension, establish eligibility, and assess BP targets in the epidemiologic studies and early randomized, controlled trials that inform current management of hypertension. Use of automated oscillometric devices has largely replaced manual BP measurement in the office and clinical trials. These newer devices may reduce the white coat effect and facilitate guideline-adherent measurement protocols. Obtaining BP measurements outside of the office with home and ambulatory BP monitoring is now more common. Out of office BPs are especially important in patients with CKD, because reduced GFR and proteinuria are associated with masked hypertension (normal office BP and elevated BP outside of the office), elevated nighttime BP, and abnormal diurnal variation in BP, all of which are associated with higher risk for target organ damage and adverse outcomes. Also, it is now feasible to routinely measure central BP and central hemodynamics. These measures are of greater importance to patients with CKD given the higher prevalence of increased sympathetic tone, arteriosclerosis, and inflammation as well as impaired sodium excretion and endothelial dysfunction, which lead to alterations in central BPs in this population. In this review, we describe various BP measurement techniques and how they apply to the care of patients with CKD.Thomas, GeorgeDrawz, Paul E.2018-02-26T07:10:35-08:00doi:10.2215/CJN.12551117hwp:resource-id:clinjasn;13/7/1124American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriosclerosis, blood pressure, Blood Pressure Determination, Blood Pressure Monitoring, Ambulatory, chronic renal disease, Epidemiologic Studies, glomerular filtration rate, Humans, hypertension, Inflammation, Masked Hypertension, Prevalence, proteinuria, randomized controlled trials, Renal Insufficiency, Chronic, SodiumReviewReviewreview-article20182018-07-06July 06, 201810.2215/CJN.125511171555-90411555-905X2018-02-26T07:10:35-08:002018-07-06Clinical Journal of the American Society of NephrologyReview13711241131
- Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD10.2215/CJN.00390118Tue, 19 Jun 2018 08:09:54 GMT-07:00Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKDStremke, Elizabeth R.McCabe, Linda D.McCabe, George P.Martin, Berdine R.Moe, Sharon M.Weaver, Connie M.Peacock, MunroHill Gallant, Kathleen M.2018-06-19T08:09:54-07:00doi:10.2215/CJN.00390118hwp:resource-id:clinjasn;13/7/1002American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiological Phenomena, Biomarkers, calcium, chronic kidney disease, creatinine, Humans, nutrition, Phosphorus, Phosphorus Absorption, Phosphorus, Dietary, Physiological Phenomena, Renal Insufficiency, Chronic, Reproducibility of Results, Urine Specimen CollectionOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-07-06July 06, 201810.2215/CJN.003901181555-90411555-905X2018-06-19T08:09:54-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137710029731012974
- Self-Reported Tobacco, Alcohol, and Illicit Drug Use and Progression of Chronic Kidney Disease10.2215/CJN.11121017Thu, 07 Jun 2018 06:24:03 GMT-07:00Self-Reported Tobacco, Alcohol, and Illicit Drug Use and Progression of Chronic Kidney DiseaseBundy, Joshua D.Bazzano, Lydia A.Xie, DaweiCohan, JanetDolata, JacquelineFink, Jeffrey C.Hsu, Chi-yuanJamerson, KennethLash, JamesMakos, GailSteigerwalt, SusanWang, XueMills, Katherine T.Chen, JingHe, Jiang,2018-06-07T06:24:03-07:00doi:10.2215/CJN.11121017hwp:resource-id:clinjasn;13/7/993American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlcohol Drinking, chronic kidney disease, Cocaine, Confidence Intervals, Disease Progression, Epidemiology and outcomes, Follow-up Studies, glomerular filtration rate, Heroin, Humans, Kidney Failure, Chronic, Marijuana Use, Methamphetamine, mortality, progression of chronic renal failure, Prospective Studies, Renal Insufficiency, Chronic, risk factors, Self Report, Street Drugs, Tobacco SmokingOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-07-06July 06, 201810.2215/CJN.111210171555-90411555-905X2018-06-07T06:24:03-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles1379931001
- Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD10.2215/CJN.13631217Thu, 14 Jun 2018 06:51:37 GMT-07:00Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKDLuo, ShengyuanCoresh, JosefTin, AdrienneRebholz, Casey M.Chen, Teresa K.Hayek, Salim S.Tracy, MelissaLipkowitz, Michael S.Appel, Lawrence J.Levey, Andrew S.Inker, Lesley A.Reiser, JochenGrams, Morgan Erika2018-06-14T06:51:37-07:00doi:10.2215/CJN.13631217hwp:resource-id:clinjasn;13/7/1013American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAfrican Americans, Alleles, Biomarkers, Black Americans, chronic kidney disease, creatinine, Demography, Follow-Up Studies, glomerular filtration rate, Humans, hypertension, Iothalamic Acid, kidney, Kidney Failure, Chronic, proteinuria, Random Allocation, Receptors, Urokinase Plasminogen Activator, Renal Insufficiency, Chronic, risk factors, United StatesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-07-06July 06, 201810.2215/CJN.136312171555-90411555-905X2018-06-14T06:51:37-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles13710131021
- Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport Syndrome10.1681/ASN.2018030228Fri, 29 Jun 2018 07:01:56 GMT-07:00Detection of Splicing Abnormalities and Genotype-Phenotype Correlation in X-linked Alport SyndromeHorinouchi, TomokoNozu, KandaiYamamura, TomohikoMinamikawa, ShogoOmori, TakashiNakanishi, KeitaFujimura, JunyaAshida, AkiraKitamura, MineakiKawano, MitsuhiroShimabukuro, WataruKitabayashi, ChizukoImafuku, AyaTamagaki, KeiichiKamei, KoichiOkamoto, KenjirouFujinaga, ShuichiroOka, MasafumiIgarashi, ToruMiyazono, AkinoriSawanobori, EmiFujimaru, RikaNakanishi, KoichiShima, YukoMatsuo, MasafumiYe, Ming JuanNozu, YoshimiMorisada, NaoyaKaito, HiroshiIijima, Kazumoto2018-06-29T07:01:56-07:00doi:10.1681/ASN.2018030228hwp:resource-id:jnephrol;29/8/2244American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyX-linked Alport syndrome, splicing abnormalities, genotype-phenotype correlation, transcript analysis, renal prognosisClinical ResearchClinical Researchresearch-article20182018-08-01August 201810.1681/ASN.20180302281046-66731533-34502018-06-29T07:01:56-07:002018-08Journal of the American Society of NephrologyClinical Research29822442254
- A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human SubjectsBackground Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption. Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function. Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity. Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.10.1681/ASN.2017121254Wed, 18 Jul 2018 06:18:28 GMT-07:00A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human SubjectsBackground Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption. Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function. Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity. Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity.Mohammad, JaberScanni, RobertoBestmann, LukasHulter, Henry N.Krapf, Reto2018-07-18T06:18:28-07:00doi:10.1681/ASN.2017121254hwp:resource-id:jnephrol;29/8/2089American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate, hypertension, hyperphosphatemia, FGF-23, Vitamin DBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20171212541046-66731533-34502018-07-18T06:18:28-07:002018-08Journal of the American Society of NephrologyBasic Research29820892098
- Erratum10.1681/ASN.2018060650Mon, 16 Jul 2018 07:45:00 GMT-07:00ErratumAmerican Society of Nephrology2018-07-16T07:45:00-07:00doi:10.1681/ASN.2018060650hwp:resource-id:jnephrol;29/8/2256American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20182018-08-01August 201810.1681/ASN.20180606501046-66731533-34502018-07-16T07:45:00-07:002018-08Journal of the American Society of NephrologyErrata2929842256131722561325
- AI: What Have You Done for Us Lately?10.1681/ASN.2018050566Tue, 19 Jun 2018 07:48:15 GMT-07:00AI: What Have You Done for Us Lately?Torres, RichardOlson, Eben2018-06-19T07:48:15-07:00doi:10.1681/ASN.2018050566hwp:resource-id:jnephrol;29/8/2031American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulus, renal morphology, pathology, machine learning collectionUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-08-01August 201810.1681/ASN.20180505661046-66731533-34502018-06-19T07:48:15-07:002018-08Journal of the American Society of NephrologyUp Front Matters29882031208120322088
- Erratum10.1681/ASN.2018060582Tue, 31 Jul 2018 01:00:38 GMT-07:00ErratumAmerican Society of Nephrology2018-07-31T13:00:38-07:00doi:10.1681/ASN.2018060582hwp:resource-id:jnephrol;29/8/2255American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20182018-08-01August 201810.1681/ASN.20180605821046-66731533-34502018-07-31T13:00:38-07:002018-08Journal of the American Society of NephrologyErrata2927892255290622552916
- Donald Seldin: A Transformative Leader in Medicine and Nephrology10.1681/ASN.2018060603Mon, 09 Jul 2018 06:47:28 GMT-07:00Donald Seldin: A Transformative Leader in Medicine and NephrologyAlpern, RobertGiebisch, Gerhard2018-07-09T06:47:28-07:00doi:10.1681/ASN.2018060603hwp:resource-id:jnephrol;29/8/2029American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyDonald Seldin, Obituary, JASNUp Front MattersObituaryUp Front MattersObituaryresearch-article20182018-08-01August 201810.1681/ASN.20180606031046-66731533-34502018-07-09T06:47:28-07:002018-08Journal of the American Society of NephrologyUp Front Matters29820292030
- Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese PopulationBackground Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown. Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay. Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10−23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10−25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10−9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10−12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10−11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor. Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.10.1681/ASN.2017080859Mon, 16 Jul 2018 07:44:59 GMT-07:00Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese PopulationBackground Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown. Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes (HLA-A, -C, -B, -DRB1, -DQB1, and -DPB1) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1/-DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay. Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined Pallelic=7.84×10−23; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined Pallelic=1.72×10−25; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 (Pc=1.82×10−9; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 (Pc=2.09×10−12; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 (Pc=7.01×10−11; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor. Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.Jia, XiaoyuanHorinouchi, TomokoHitomi, YukiShono, AkemiKhor, Seik-SoonOmae, YosukeKojima, KanameKawai, YosukeNagasaki, MasaoKaku, YoshitsuguOkamoto, TakayukiOhwada, YokoOhta, KazuhideOkuda, YusukeFujimaru, RikaHatae, KenKumagai, NaonoriSawanobori, EmiNakazato, HitoshiOhtsuka, YasufumiNakanishi, KoichiShima, YukoTanaka, RyojiroAshida, AkiraKamei, KoichiIshikura, KenjiNozu, KandaiTokunaga, KatsushiIijima, Kazumoto,Okamoto, TakayukiAoyagi, HayatoUeno, TomohikoNakanishi, MasanoriToita, NariakiUetake, KimiakiKobayashi, NorioFujita, ShojiTsuruga, KazushiKumagai, NaonoriKudo, HirokiTanaka, ErikoOkada, MariIshikuyra, KenjiKamei, KoichiOgura, MasaoSato, MaiKano, YujiMiura, KenichiroMotoyoshi, YaekoSawanobori, EmiKobayashi, AnnaKojika, ManabuOhwada, YokoHamada, RikuHataya, HiroshiGoto, MiwaOhta, KazuhideTamamura, SoichiMori, YukikoIijima, KazumotoNozu, KandaiKaito, HiroshiYamamura, TomohikoMinamikawa, ShogoNakanishi, KeitaFujimura, JunyaNagano, ChinaSakakibara, NanaTanaka, RyojiroKanda, KyokoNakagawa, TakuShibano, TakayukiMaekawa, KoheiHattori, MasujiHashimura, YuyaIshimori, ShingoFujimaru, RikaUeda, HiroakiAshida, AkiraMatsumura, HidekiSawai, ToshihiroSakai, TomoyukiOkuda, YusukeShima, YukoItoh, ShigeruNagatani, KojiKaku, YoshikazuNishimura, ManaoHatae, KenHinokiyama, MaikoKuroki, RieOhtsuka, YasufumiNishimura, ShinjiNakazato, HitoshiTamura, HiroshiNakanishi, Koichi2018-07-16T07:44:59-07:00doi:10.1681/ASN.2017080859hwp:resource-id:jnephrol;29/8/2189American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyidiopathic nephrotic syndrome, pediatric nephrology, polymorphisms, human leukocyte antigenClinical EpidemiologyClinical Epidemiologyresearch-article20182018-08-01August 201810.1681/ASN.20170808591046-66731533-34502018-07-16T07:44:59-07:002018-08Journal of the American Society of NephrologyClinical Epidemiology29821892199
- A Single-Cell Transcriptome Atlas of the Mouse GlomerulusBackground Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown. Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli. Results Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells that can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry images obtained from the Human Protein Atlas. Subclustering of endothelial cells revealed a subset of endothelium that expressed marker genes related to endothelial proliferation. By comparison, the podocyte population appeared more homogeneous but contained three smaller, previously unknown subpopulations. Conclusions Our study comprehensively characterized gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.10.1681/ASN.2018030238Thu, 24 May 2018 06:17:29 GMT-07:00A Single-Cell Transcriptome Atlas of the Mouse GlomerulusBackground Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown. Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli. Results Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells that can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry images obtained from the Human Protein Atlas. Subclustering of endothelial cells revealed a subset of endothelium that expressed marker genes related to endothelial proliferation. By comparison, the podocyte population appeared more homogeneous but contained three smaller, previously unknown subpopulations. Conclusions Our study comprehensively characterized gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.Karaiskos, NikosRahmatollahi, MahdiehBoltengagen, AnastasiyaLiu, HaiyueHoehne, MartinRinschen, MarkusSchermer, BernhardBenzing, ThomasRajewsky, NikolausKocks, ChristineKann, MartinMüller, Roman-Ulrich2018-05-24T06:17:29-07:00doi:10.1681/ASN.2018030238hwp:resource-id:jnephrol;29/8/2060American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulus, single-cell RNA sequencing, scRNAseq, podocyte, transcriptomeRapid CommunicationsRapid Communicationsresearch-article20182018-08-01August 201810.1681/ASN.20180302381046-66731533-34502018-05-24T06:17:29-07:002018-08Journal of the American Society of NephrologyRapid Communications29882060203620682038
- The Calcium-Dependent Protease Calpain-1 Links TRPC6 Activity to Podocyte Injury10.1681/ASN.2016111248Thu, 28 Jun 2018 06:16:55 GMT-07:00The Calcium-Dependent Protease Calpain-1 Links TRPC6 Activity to Podocyte InjuryVerheijden, Kim A.T.Sonneveld, RamonBakker-van Bebber, MarinkaWetzels, Jack F.M.van der Vlag, JohanNijenhuis, Tom2018-06-28T06:16:55-07:00doi:10.1681/ASN.2016111248hwp:resource-id:jnephrol;29/8/2099American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, intracellular signal, proteinuria, glomerular disease, cytoskeleton, ion channelBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20161112481046-66731533-34502018-06-28T06:16:55-07:002018-08Journal of the American Society of NephrologyBasic Research29820992109
- Somatic Mutations in Renal Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease10.1681/ASN.2017080878Tue, 24 Jul 2018 01:47:12 GMT-07:00Somatic Mutations in Renal Cyst Epithelium in Autosomal Dominant Polycystic Kidney DiseaseTan, Adrian Y.Zhang, TuoMichaeel, AlberBlumenfeld, JonLiu, GenyanZhang, WanyingZhang, ZhengmaoZhu, YiRennert, LiorMartin, CheXiang, JennySalvatore, Steven P.Robinson, Brian D.Kapur, SandipDonahue, StephanieBobb, Warren O.Rennert, Hanna2018-07-24T13:47:12-07:00doi:10.1681/ASN.2017080878hwp:resource-id:jnephrol;29/8/2139American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, molecular genetics, human geneticsBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20170808781046-66731533-34502018-07-24T13:47:12-07:002018-08Journal of the American Society of NephrologyBasic Research29821392156
- Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKI10.1681/ASN.2018030265Fri, 06 Jul 2018 07:36:46 GMT-07:00Mechanisms Underlying Increased TIMP2 and IGFBP7 Urinary Excretion in Experimental AKIJohnson, Ali C.M.Zager, Richard A.2018-07-06T07:36:46-07:00doi:10.1681/ASN.2018030265hwp:resource-id:jnephrol;29/8/2157American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, biomarkers, ischemia-reperfusion, maleate nephrotoxicity, glycerol-induced rhabdomyolysisBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20180302651046-66731533-34502018-07-06T07:36:46-07:002018-08Journal of the American Society of NephrologyBasic Research29821572167
- Prevention of Fatal C3 Glomerulopathy by Recombinant Complement Receptor of the Ig SuperfamilyBackground C3 glomerulopathy (C3G) is a life-threatening kidney disease caused by dysregulation of the alternative pathway of complement (AP) activation. No approved specific therapy is available for C3G, although an anti-C5 mAb has been used off-label in some patients with C3G, with mixed results. Thus, there is an unmet medical need to develop other inhibitors of complement for C3G. Methods We used a murine model of lethal C3G to test the potential efficacy of an Fc fusion protein of complement receptor of the Ig superfamily (CRIg-Fc) in the treatment of C3G. CRIg-Fc binds C3b and inhibits C3 and C5 convertases of the AP. Mice with mutations in the factor H and properdin genes (FHm/mP−/−) develop early-onset C3G, with AP consumption, high proteinuria, and lethal crescentic GN. Results Treatment of FHm/mP−/− mice with CRIg-Fc, but not a control IgG, inhibited AP activation and diminished the consumption of plasma C3, factor B, and C5. CRIg-Fc–treated FHm/mP−/− mice also had significantly improved survival and reduced proteinuria, hematuria, BUN, glomerular C3 fragment, C9 and fibrin deposition, and GN pathology scores. Conclusions Therapeutics developed on the basis of the mechanism of action of soluble CRIg may be effective for the treatment of C3G and should be explored clinically.10.1681/ASN.2018030270Tue, 12 Jun 2018 05:51:03 GMT-07:00Prevention of Fatal C3 Glomerulopathy by Recombinant Complement Receptor of the Ig SuperfamilyBackground C3 glomerulopathy (C3G) is a life-threatening kidney disease caused by dysregulation of the alternative pathway of complement (AP) activation. No approved specific therapy is available for C3G, although an anti-C5 mAb has been used off-label in some patients with C3G, with mixed results. Thus, there is an unmet medical need to develop other inhibitors of complement for C3G. Methods We used a murine model of lethal C3G to test the potential efficacy of an Fc fusion protein of complement receptor of the Ig superfamily (CRIg-Fc) in the treatment of C3G. CRIg-Fc binds C3b and inhibits C3 and C5 convertases of the AP. Mice with mutations in the factor H and properdin genes (FHm/mP−/−) develop early-onset C3G, with AP consumption, high proteinuria, and lethal crescentic GN. Results Treatment of FHm/mP−/− mice with CRIg-Fc, but not a control IgG, inhibited AP activation and diminished the consumption of plasma C3, factor B, and C5. CRIg-Fc–treated FHm/mP−/− mice also had significantly improved survival and reduced proteinuria, hematuria, BUN, glomerular C3 fragment, C9 and fibrin deposition, and GN pathology scores. Conclusions Therapeutics developed on the basis of the mechanism of action of soluble CRIg may be effective for the treatment of C3G and should be explored clinically.Wang, XiaoxuVan Lookeren Campagne, MennoKatschke, Kenneth J.Gullipalli, DamodarMiwa, TakashiUeda, YoshiyasuWang, YuanPalmer, MatthewXing, GuolanSong, Wen-Chao2018-06-12T05:51:03-07:00doi:10.1681/ASN.2018030270hwp:resource-id:jnephrol;29/8/2053American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, glomerulopathy, membranoproliferative glomerulonephritis (MPGN)Rapid CommunicationsRapid Communicationsresearch-article20182018-08-01August 201810.1681/ASN.20180302701046-66731533-34502018-06-12T05:51:03-07:002018-08Journal of the American Society of NephrologyRapid Communications29882053203220592033
- The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort StudyBackground Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data. Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT). Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m2. During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27). Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.10.1681/ASN.2017121260Mon, 04 Jun 2018 05:45:35 GMT-07:00The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort StudyBackground Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data. Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT). Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m2. During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27). Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.Srivastava, AnandPalsson, RagnarKaze, Arnaud D.Chen, Margaret E.Palacios, PollySabbisetti, VenkataBetensky, Rebecca A.Steinman, Theodore I.Thadhani, Ravi I.McMahon, Gearoid M.Stillman, Isaac E.Rennke, Helmut G.Waikar, Sushrut S.2018-06-04T05:45:35-07:00doi:10.1681/ASN.2017121260hwp:resource-id:jnephrol;29/8/2213American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, renal biopsy, histopathology, ESRDClinical ResearchClinical Researchresearch-article20182018-08-01August 201810.1681/ASN.20171212601046-66731533-34502018-06-04T05:45:35-07:002018-08Journal of the American Society of NephrologyClinical Research29822132224
- GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome10.1681/ASN.2017121312Fri, 29 Jun 2018 07:01:56 GMT-07:00GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic SyndromeHermle, TobiasSchneider, RonenSchapiro, DavidBraun, Daniela A.van der Ven, Amelie T.Warejko, Jillian K.Daga, AnkanaWidmeier, EugenNakayama, MakikoJobst-Schwan, TilmanMajmundar, Amar J.Ashraf, ShaziaRao, JiaFinn, Laura S.Tasic, VeliborHernandez, Joel D.Bagga, ArvindJalalah, Sawsan M.El Desoky, SherifKari, Jameela A.Laricchia, Kristen M.Lek, MonkolRehm, Heidi L.MacArthur, Daniel G.Mane, ShrikantLifton, Richard P.Shril, ShirleeHildebrandt, Friedhelm2018-06-29T07:01:56-07:00doi:10.1681/ASN.2017121312hwp:resource-id:jnephrol;29/8/2123American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, podocyte, nephrin, endocytosis, genetic renal disease, nephrocyteBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20171213121046-66731533-34502018-06-29T07:01:56-07:002018-08Journal of the American Society of NephrologyBasic Research29821232138
- The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in Podocytes10.1681/ASN.2017121338Thu, 12 Jul 2018 05:24:22 GMT-07:00The Human FSGS-Causing ANLN R431C Mutation Induces Dysregulated PI3K/AKT/mTOR/Rac1 Signaling in PodocytesHall, GentzonLane, Brandon M.Khan, KamalPediaditakis, IgorXiao, JianqiuWu, GuanghongWang, LimingKovalik, Maria E.Chryst-Stangl, MeganDavis, Erica E.Spurney, Robert F.Gbadegesin, Rasheed A.2018-07-12T05:24:22-07:00doi:10.1681/ASN.2017121338hwp:resource-id:jnephrol;29/8/2110American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, ANILLIN, ER-STRESS, MTOR, RAC1, AKTBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20171213381046-66731533-34502018-07-12T05:24:22-07:002018-08Journal of the American Society of NephrologyBasic Research29821102122
- This Month's Highlights10.1681/ASN.2018060634Tue, 31 Jul 2018 01:00:38 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2018-07-31T13:00:38-07:00doi:10.1681/ASN.2018060634hwp:resource-id:jnephrol;29/8/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-08-01August 201810.1681/ASN.20180606341046-66731533-34502018-07-31T13:00:38-07:002018-08Journal of the American Society of NephrologyThis Month’s Highlights298ii
- Now or Later? Understanding Timing of Dialysis Initiation beyond IDEAL10.1681/ASN.2018050534Mon, 18 Jun 2018 08:23:05 GMT-07:00Now or Later? Understanding Timing of Dialysis Initiation beyond IDEALRifkin, Dena E.2018-06-18T08:23:05-07:00doi:10.1681/ASN.2018050534hwp:resource-id:jnephrol;29/8/2033American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, geriatric nephrology, estimated GFRUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-08-01August 201810.1681/ASN.20180505341046-66731533-34502018-06-18T08:23:05-07:002018-08Journal of the American Society of NephrologyUp Front Matters29882033216920352177
- Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKDBackground Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function. Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65–74, 75–84, and ≥85 years), eGFR (<6, 6–<9, 9–<12, 12–<15, and 15–<29 ml/min per 1.73 m2), and provision of dialysis, and survival. Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65–74, 75–84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6–<9, <6, 9–<12, and 9–<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9–<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients. Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.10.1681/ASN.2017121273Tue, 22 May 2018 06:31:27 GMT-07:00Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKDBackground Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function. Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65–74, 75–84, and ≥85 years), eGFR (<6, 6–<9, 9–<12, 12–<15, and 15–<29 ml/min per 1.73 m2), and provision of dialysis, and survival. Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65–74, 75–84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6–<9, <6, 9–<12, and 9–<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9–<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients. Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.Kurella Tamura, ManjulaDesai, ManishaKapphahn, Kristopher I.Thomas, I-ChunAsch, Steven M.Chertow, Glenn M.2018-05-22T06:31:27-07:00doi:10.1681/ASN.2017121273hwp:resource-id:jnephrol;29/8/2169American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, end-stage renal disease, geriatric nephrologyClinical EpidemiologyClinical Epidemiologyresearch-article20182018-08-01August 201810.1681/ASN.20171212731046-66731533-34502018-05-22T06:31:27-07:002018-08Journal of the American Society of NephrologyClinical Epidemiology29882169203321772035
- Region-Based Convolutional Neural Nets for Localization of Glomeruli in Trichrome-Stained Whole Kidney SectionsBackground Histologic examination of fixed renal tissue is widely used to assess morphology and the progression of disease. Commonly reported metrics include glomerular number and injury. However, characterization of renal histology is a time-consuming and user-dependent process. To accelerate and improve the process, we have developed a glomerular localization pipeline for trichrome-stained kidney sections using a machine learning image classification algorithm. Methods We prepared 4-μm slices of kidneys from rats of various genetic backgrounds that were subjected to different experimental protocols and mounted the slices on glass slides. All sections used in this analysis were trichrome stained and imaged in bright field at a minimum resolution of 0.92 μm per pixel. The training and test datasets for the algorithm comprised 74 and 13 whole renal sections, respectively, totaling over 28,000 glomeruli manually localized. Additionally, because this localizer will be ultimately used for automated assessment of glomerular injury, we assessed bias of the localizer for preferentially identifying healthy or damaged glomeruli. Results Localizer performance achieved an average precision and recall of 96.94% and 96.79%, respectively, on whole kidney sections without evidence of bias for or against glomerular injury or the need for manual preprocessing. Conclusions This study presents a novel and robust application of convolutional neural nets for the localization of glomeruli in healthy and damaged trichrome-stained whole-renal section mounts and lays the groundwork for automated glomerular injury scoring.10.1681/ASN.2017111210Tue, 19 Jun 2018 07:48:15 GMT-07:00Region-Based Convolutional Neural Nets for Localization of Glomeruli in Trichrome-Stained Whole Kidney SectionsBackground Histologic examination of fixed renal tissue is widely used to assess morphology and the progression of disease. Commonly reported metrics include glomerular number and injury. However, characterization of renal histology is a time-consuming and user-dependent process. To accelerate and improve the process, we have developed a glomerular localization pipeline for trichrome-stained kidney sections using a machine learning image classification algorithm. Methods We prepared 4-μm slices of kidneys from rats of various genetic backgrounds that were subjected to different experimental protocols and mounted the slices on glass slides. All sections used in this analysis were trichrome stained and imaged in bright field at a minimum resolution of 0.92 μm per pixel. The training and test datasets for the algorithm comprised 74 and 13 whole renal sections, respectively, totaling over 28,000 glomeruli manually localized. Additionally, because this localizer will be ultimately used for automated assessment of glomerular injury, we assessed bias of the localizer for preferentially identifying healthy or damaged glomeruli. Results Localizer performance achieved an average precision and recall of 96.94% and 96.79%, respectively, on whole kidney sections without evidence of bias for or against glomerular injury or the need for manual preprocessing. Conclusions This study presents a novel and robust application of convolutional neural nets for the localization of glomeruli in healthy and damaged trichrome-stained whole-renal section mounts and lays the groundwork for automated glomerular injury scoring.Bukowy, John D.Dayton, AlexCloutier, DustinManis, Anna D.Staruschenko, AlexanderLombard, Julian H.Solberg Woods, Leah C.Beard, Daniel A.Cowley, Allen W.2018-06-19T07:48:15-07:00doi:10.1681/ASN.2017111210hwp:resource-id:jnephrol;29/8/2081American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal injury, renal morphology, Renal pathology, kidney disease, glomerular disease, glomerulus, machine learning collectionBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20171112101046-66731533-34502018-06-19T07:48:15-07:002018-08Journal of the American Society of NephrologyBasic Research29882081203120882032
- Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance HemodialysisBackground Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established. Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30-day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan–Meier methods. Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight >1.0 kg above the prescribed target weight in ≥30% (versus <30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations. Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis.10.1681/ASN.2018010004Wed, 23 May 2018 06:48:20 GMT-07:00Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance HemodialysisBackground Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established. Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30-day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan–Meier methods. Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight >1.0 kg above the prescribed target weight in ≥30% (versus <30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations. Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis.Assimon, Magdalene M.Wang, LilyFlythe, Jennifer E.2018-05-23T06:48:20-07:00doi:10.1681/ASN.2018010004hwp:resource-id:jnephrol;29/8/2178American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyED visits, hemodialysis, hospitalizations, target weightClinical EpidemiologyClinical Epidemiologyresearch-article20182018-08-01August 201810.1681/ASN.20180100041046-66731533-34502018-05-23T06:48:20-07:002018-08Journal of the American Society of NephrologyClinical Epidemiology29821782188
- Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican NephropathyBackground Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease. Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18–30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors. Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; −0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; −18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; −3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; −0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; −14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline. Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.10.1681/ASN.2018020151Fri, 15 Jun 2018 07:25:54 GMT-07:00Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican NephropathyBackground Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease. Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18–30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors. Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; −0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; −18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; −3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; −0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; −14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline. Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.Gonzalez-Quiroz, MarvinSmpokou, Evangelia-TheanoSilverwood, Richard J.Camacho, ArmandoFaber, DorienGarcia, Brenda La RosaOomatia, AminHill, MichaelGlaser, JasonLe Blond, JenniferWesseling, CatharinaAragon, AuroraSmeeth, LiamPearce, NeilNitsch, DorotheaCaplin, Ben2018-06-15T07:25:54-07:00doi:10.1681/ASN.2018020151hwp:resource-id:jnephrol;29/8/2200American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyCKDu, Endemic nephropathy, eGFR decline, MeN, CKD of unknown etiologyClinical EpidemiologyClinical Epidemiologyresearch-article20182018-08-01August 201810.1681/ASN.20180201511046-66731533-34502018-06-15T07:25:54-07:002018-08Journal of the American Society of NephrologyClinical Epidemiology29822002212
- Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 Glomerulopathies10.1681/ASN.2018050554Tue, 19 Jun 2018 07:48:15 GMT-07:00Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 GlomerulopathiesDaha, Mohamed R.Seelen, Marc2018-06-19T07:48:15-07:00doi:10.1681/ASN.2018050554hwp:resource-id:jnephrol;29/8/2032American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, C3G, inhibitorUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-08-01August 201810.1681/ASN.20180505541046-66731533-34502018-06-19T07:48:15-07:002018-08Journal of the American Society of NephrologyUp Front Matters29882032205320332059
- Early Proteinuria Lowering by Angiotensin-Converting Enzyme Inhibition Predicts Renal Survival in Children with CKDBackground Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD. Methods In total, 280 eligible children with CKD stages 2–4 (mean age 11.7 years old, median eGFR 46 ml/min per 1.73 m2, 71% congenital renal malformations) received a fixed dose of ramipril (6 mg/m2 per day) and were subsequently randomized to conventional or intensified BP control. We assessed initial proteinuria reduction from baseline to first measurement on ramipril (at 2.5±1.3 months). We used multivariable Cox modeling to estimate the association between initial proteinuria reduction and the risk of reaching a renal end point (50% eGFR decline or ESRD), which occurred in 80 patients during 5 years of observation. Results Ramipril therapy lowered proteinuria by a mean of 43.5% (95% confidence interval, 36.3% to 49.9%). Relative to proteinuria reduction <30%, 30%–60% and >60% reduction resulted in hazard ratios (95% confidence intervals) of 0.70 (0.40 to 1.22) and 0.42 (0.22 to 0.79), respectively. This association was independent of age, sex, CKD diagnosis, baseline eGFR, baseline proteinuria, initial BP, and concomitant BP reduction. Conclusions The early antiproteinuric effect of ACE inhibition is associated with long-term preservation of renal function in children with CKD. Proteinuria lowering should be considered an important target in the management of pediatric CKD.10.1681/ASN.2018010036Thu, 21 Jun 2018 08:05:05 GMT-07:00Early Proteinuria Lowering by Angiotensin-Converting Enzyme Inhibition Predicts Renal Survival in Children with CKDBackground Although pharmacotherapeutic proteinuria lowering was found to be nephroprotective in adults, the predictive value of early drug-induced proteinuria reduction for long-term renal survival in pediatric CKD is unknown. We analyzed data from the ESCAPE Trial for a potential association between initial antiproteinuric effect of standardized angiotensin-converting enzyme (ACE) inhibition and renal disease progression in children with CKD. Methods In total, 280 eligible children with CKD stages 2–4 (mean age 11.7 years old, median eGFR 46 ml/min per 1.73 m2, 71% congenital renal malformations) received a fixed dose of ramipril (6 mg/m2 per day) and were subsequently randomized to conventional or intensified BP control. We assessed initial proteinuria reduction from baseline to first measurement on ramipril (at 2.5±1.3 months). We used multivariable Cox modeling to estimate the association between initial proteinuria reduction and the risk of reaching a renal end point (50% eGFR decline or ESRD), which occurred in 80 patients during 5 years of observation. Results Ramipril therapy lowered proteinuria by a mean of 43.5% (95% confidence interval, 36.3% to 49.9%). Relative to proteinuria reduction <30%, 30%–60% and >60% reduction resulted in hazard ratios (95% confidence intervals) of 0.70 (0.40 to 1.22) and 0.42 (0.22 to 0.79), respectively. This association was independent of age, sex, CKD diagnosis, baseline eGFR, baseline proteinuria, initial BP, and concomitant BP reduction. Conclusions The early antiproteinuric effect of ACE inhibition is associated with long-term preservation of renal function in children with CKD. Proteinuria lowering should be considered an important target in the management of pediatric CKD.van den Belt, Sophie M.Heerspink, Hiddo J.L.Gracchi, Valentinade Zeeuw, DickWühl, ElkeSchaefer, Franz,Anarat, A.Bakkaloglu, A.Ozaltin, F.Peco-Antic, A.Querfeld, U.Gellermann, J.Sallay, P.Drozdz, D.Bonzel, K.-E.Wingen, A.-M.Zurowska, A.Balasz, I.Trivelli, A.Perfumo, F.Müller-Wiefel, D.E.Möller, K.Offner, G.Enke, B.Wühl, E.Gimpel, C.Mehls, O.Schaefer, F.Emre, S.Caliskan, S.Mir, S.Wygoda, S.Hohbach-Hohenfellner, K.Jeck, N.Klaus, G.Ardissino, G.Testa, S.Montini, G.Charbit, M.Niaudet, P.Caldas-Afonso, A.Fernandes-Teixeira, A.Dušek, J.Matteucci, M.C.Picca, S.Mastrostefano, A.Wigger, M.Berg, U.B.Celsi, G.Fischbach, M.Terzic, J.Fydryk, J.Urasinski, T.Coppo, R.Peruzzi, LiciaArbeiter, K.Jankauskiené, A.Grenda, R.Litwin, M.Janas, R.Laube, G.Neuhaus, T.J.2018-06-21T08:05:05-07:00doi:10.1681/ASN.2018010036hwp:resource-id:jnephrol;29/8/2225American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, chronic kidney disease, children, ACE inhibitionClinical ResearchClinical Researchresearch-article20182018-08-01August 201810.1681/ASN.20180100361046-66731533-34502018-06-21T08:05:05-07:002018-08Journal of the American Society of NephrologyClinical Research29822252233
- Single-Cell Sequencing the Glomerulus, Unraveling the Molecular Programs of Glomerular Filtration, One Cell at a Time10.1681/ASN.2018060626Thu, 12 Jul 2018 05:24:21 GMT-07:00Single-Cell Sequencing the Glomerulus, Unraveling the Molecular Programs of Glomerular Filtration, One Cell at a TimeKretzler, MatthiasMenon, Rajasree2018-07-12T05:24:21-07:00doi:10.1681/ASN.2018060626hwp:resource-id:jnephrol;29/8/2036American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologySingle cell transcriptomics, glomerular disease, kidney diseaseUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20182018-08-01August 201810.1681/ASN.20180606261046-66731533-34502018-07-12T05:24:21-07:002018-08Journal of the American Society of NephrologyUp Front Matters29888203620602069203820682080
- C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe HypertensionBackground Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control. Methods We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific ex vivo serum-based microvascular endothelial cell assay. Results Compared with normal human serum and samples from patients with hypertensive arterionephrosclerosis, 14 of 16 (87.5%) serum samples collected at presentation from 16 patients with hypertension-associated TMA induced abnormal C5b9 formation on microvascular endothelial cells. We detected rare variants in complement genes in eight of 17 (47%) patients. ESRD occurred in 14 of 17 (82%) patients, and recurrent TMA after transplant occurred in seven of 11 (64%) donor kidneys. Eculizumab improved the renal function in three patients and prevented TMA recurrence in an allograft recipient. Conclusions These observations point to complement defects as the key causative factor of ESRD and recurrent TMA after transplant in patients presenting with severe hypertension. Complement defects can be identified by measurements of complement activation on microvascular endothelial cells, which should substantially influence treatment and prognosis.10.1681/ASN.2018020184Fri, 01 Jun 2018 05:33:56 GMT-07:00C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe HypertensionBackground Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control. Methods We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific ex vivo serum-based microvascular endothelial cell assay. Results Compared with normal human serum and samples from patients with hypertensive arterionephrosclerosis, 14 of 16 (87.5%) serum samples collected at presentation from 16 patients with hypertension-associated TMA induced abnormal C5b9 formation on microvascular endothelial cells. We detected rare variants in complement genes in eight of 17 (47%) patients. ESRD occurred in 14 of 17 (82%) patients, and recurrent TMA after transplant occurred in seven of 11 (64%) donor kidneys. Eculizumab improved the renal function in three patients and prevented TMA recurrence in an allograft recipient. Conclusions These observations point to complement defects as the key causative factor of ESRD and recurrent TMA after transplant in patients presenting with severe hypertension. Complement defects can be identified by measurements of complement activation on microvascular endothelial cells, which should substantially influence treatment and prognosis.Timmermans, Sjoerd A.M.E.G.Abdul-Hamid, Myrurgia A.Potjewijd, JudithTheunissen, Ruud O.M.F.I.H.Damoiseaux, Jan G.M.C.Reutelingsperger, Chris P.van Paassen, Pieter,Christiaans, M.Fung, T.Gelens, M.Kooman, J.Leunissen, K.Litjens, E.van der Net, J.van der Sande, F.Duijnhoven, E.Boorsma, S.Huitema, J.Wirtz, J.de Heer, F.Krekels, M.Stifft, F.Verseput, G.ter Braak, N.Frenken, L.Gaertner, S.2018-06-01T05:33:56-07:00doi:10.1681/ASN.2018020184hwp:resource-id:jnephrol;29/8/2234American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemolytic uremic syndrome, complement, hypertension, renal biopsyClinical ResearchClinical Researchresearch-article20182018-08-01August 201810.1681/ASN.20180201841046-66731533-34502018-06-01T05:33:56-07:002018-08Journal of the American Society of NephrologyClinical Research29822342243
- Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory ResponseBackground Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing. Unsupervised clustering analysis of the biopsy specimen was performed to identify 16 distinct cell types, including all of the major immune cell types and most native kidney cell types, in this biopsy specimen, for which the histologic read was mixed rejection. Results Monocytes formed two subclusters representing a nonclassical CD16+ group and a classic CD16− group expressing dendritic cell maturation markers. The presence of both monocyte cell subtypes was validated by staining of independent transplant biopsy specimens. Comparison of healthy kidney epithelial transcriptomes with biopsy specimen counterparts identified novel segment-specific proinflammatory responses in rejection. Endothelial cells formed three distinct subclusters: resting cells and two activated endothelial cell groups. One activated endothelial cell group expressed Fc receptor pathway activation and Ig internalization genes, consistent with the pathologic diagnosis of antibody-mediated rejection. We mapped previously defined genes that associate with rejection outcomes to single cell types and generated a searchable online gene expression database. Conclusions We present the first step toward incorporation of single-cell transcriptomics into kidney biopsy specimen interpretation, describe a heterogeneous immune response in mixed rejection, and provide a searchable resource for the scientific community.10.1681/ASN.2018020125Fri, 06 Jul 2018 07:36:45 GMT-07:00Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory ResponseBackground Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing. Unsupervised clustering analysis of the biopsy specimen was performed to identify 16 distinct cell types, including all of the major immune cell types and most native kidney cell types, in this biopsy specimen, for which the histologic read was mixed rejection. Results Monocytes formed two subclusters representing a nonclassical CD16+ group and a classic CD16− group expressing dendritic cell maturation markers. The presence of both monocyte cell subtypes was validated by staining of independent transplant biopsy specimens. Comparison of healthy kidney epithelial transcriptomes with biopsy specimen counterparts identified novel segment-specific proinflammatory responses in rejection. Endothelial cells formed three distinct subclusters: resting cells and two activated endothelial cell groups. One activated endothelial cell group expressed Fc receptor pathway activation and Ig internalization genes, consistent with the pathologic diagnosis of antibody-mediated rejection. We mapped previously defined genes that associate with rejection outcomes to single cell types and generated a searchable online gene expression database. Conclusions We present the first step toward incorporation of single-cell transcriptomics into kidney biopsy specimen interpretation, describe a heterogeneous immune response in mixed rejection, and provide a searchable resource for the scientific community.Wu, HaojiaMalone, Andrew F.Donnelly, Erinn L.Kirita, YuheiUchimura, KoheiRamakrishnan, Sai M.Gaut, Joseph P.Humphreys, Benjamin D.2018-07-06T07:36:45-07:00doi:10.1681/ASN.2018020125hwp:resource-id:jnephrol;29/8/2069American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, rejection, transcriptional profilingBasic ResearchBasic Researchresearch-article20182018-08-01August 201810.1681/ASN.20180201251046-66731533-34502018-07-06T07:36:45-07:002018-08Journal of the American Society of NephrologyBasic Research29882069203620802038
- Nephrotoxicity of Cancer Immunotherapies: Past, Present and FutureNephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of “onco-nephrology” has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system–mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.10.1681/ASN.2018050488Fri, 29 Jun 2018 07:01:55 GMT-07:00Nephrotoxicity of Cancer Immunotherapies: Past, Present and FutureNephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of “onco-nephrology” has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system–mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.Perazella, Mark A.Shirali, Anushree C.2018-06-29T07:01:55-07:00doi:10.1681/ASN.2018050488hwp:resource-id:jnephrol;29/8/2039American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunotherapies, interferon, interleukin-2, immune checkpoint inhibitors, chimeric antigen receptor T-cells, acute kidney injuryUp Front MattersReviewUp Front MattersReviewbrief-report20182018-08-01August 201810.1681/ASN.20180504881046-66731533-34502018-06-29T07:01:55-07:002018-08Journal of the American Society of NephrologyUp Front Matters29820392052
- Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation10.2215/CJN.00100118Thu, 21 Jun 2018 08:02:42 GMT-07:00Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney TransplantationHarhay, Meera N.McKenna, Ryan M.Boyle, Suzanne M.Ranganna, KarthikMizrahi, Lissa LevinGuy, StephenMalat, Gregory E.Xiao, GaryReich, David J.Harhay, Michael O.2018-06-21T08:02:42-07:00doi:10.2215/CJN.00100118hwp:resource-id:clinjasn;13/7/1069American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Ethnic Groups, European Continental Ancestry Group, Hispanic Americans, Humans, Insurance, Health, kidney transplantation, Logistic Models, Medicaid, Patient Protection and Affordable Care Act, renal dialysis, Renal Insufficiency, Chronic, Retrospective Studies, United StatesOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-07-06July 06, 201810.2215/CJN.001001181555-90411555-905X2018-06-21T08:02:42-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137710699821078983
- The Affordable Care Act, Kidney Transplant Access, and Kidney Disease Care in the United States10.2215/CJN.06390518Thu, 21 Jun 2018 08:02:42 GMT-07:00The Affordable Care Act, Kidney Transplant Access, and Kidney Disease Care in the United StatesGoyal, NitenderWeiner, Daniel E.2018-06-21T08:02:42-07:00doi:10.2215/CJN.06390518hwp:resource-id:clinjasn;13/7/982American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUnited States, kidney transplantation, Patient Protection and Affordable Care Act, Kidney Diseases, Kidney Failure, ChronicEditorialsEditorialseditorial20182018-07-06July 06, 201810.2215/CJN.063905181555-90411555-905X2018-06-21T08:02:42-07:002018-07-06Clinical Journal of the American Society of NephrologyEditorials137798210699831078
- The Spectrum of Biopsy-Proven Glomerular Diseases among Children in China10.2215/CJN.11461017Mon, 18 Jun 2018 08:20:53 GMT-07:00The Spectrum of Biopsy-Proven Glomerular Diseases among Children in ChinaNie, ShengHe, WenjuanHuang, TingLiu, DiankunWang, GuobaoGeng, JianChen, NanXu, GangZhang, PingLuo, YangNie, JingXu, XinHou, Fan Fan2018-06-18T08:20:53-07:00doi:10.2215/CJN.11461017hwp:resource-id:clinjasn;13/7/1047American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdolescent, Biopsy, Child, China, Demography, Female, glomerular disease, glomerulonephritis, Glomerulonephritis, IgA, Glomerulonephritis, Membranous, Glomerulosclerosis, Focal Segmental, Humans, kidney, kidney biopsy, Kidney Glomerulus, lupus nephritis, Male, Nephrosis, Lipoid, nephrotic syndrome, pediatrics, Purpura, Schoenlein-Henoch, Referral and Consultation, Surveys and QuestionnairesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-07-06July 06, 201810.2215/CJN.114610171555-90411555-905X2018-06-18T08:20:53-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137710479771054978
- Heroin Use Is Associated with AA-Type Kidney Amyloidosis in the Pacific Northwest10.2215/CJN.13641217Fri, 15 Jun 2018 07:25:45 GMT-07:00Heroin Use Is Associated with AA-Type Kidney Amyloidosis in the Pacific NorthwestSharma, ArjunGovindan, PriyankaToukatly, MirnaHealy, JackHenry, ConnorSenter, SteveNajafian, BehzadKestenbaum, Bryan2018-06-15T07:25:45-07:00doi:10.2215/CJN.13641217hwp:resource-id:clinjasn;13/7/1030American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAbscess, Amyloidosis, Biopsy, Case-control Studies, chronic kidney disease, Confidence Intervals, Control Groups, dialysis, Heroin, Humans, kidney, Kidney Failure, Chronic, Logistic Models, nephrotic syndrome, Prednisolone, Prevalence, Soft Tissue Infections, WashingtonOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-07-06July 06, 201810.2215/CJN.136412171555-90411555-905X2018-06-15T07:25:45-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles137710309751036976
- Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative Disorders10.2215/CJN.13041117Wed, 30 May 2018 07:37:14 GMT-07:00Kidney Involvement of Patients with Waldenström Macroglobulinemia and Other IgM-Producing B Cell Lymphoproliferative DisordersHiggins, LarissaNasr, Samih H.Said, Samar M.Kapoor, PrashantDingli, DavidKing, Rebecca L.Rajkumar, S. VincentKyle, Robert A.Kourelis, TaxiarchisGertz, Morie A.Dispenzieri, AngelaLacy, Martha Q.Buadi, Francis K.Ansell, Stephen M.Gonsalves, Wilson I.Thompson, Carrie A.Fervenza, Fernando C.Zand, LadanHwa, Yi L.Jevremovic, DraganShi, MinLeung, Nelson2018-05-30T07:37:14-07:00doi:10.2215/CJN.13041117hwp:resource-id:clinjasn;13/7/1037American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Amyloidosis, Biopsy, B-Lymphocytes, Bone Marrow, glomerular disease, glomerulonephritis, Humans, IgM, Immunoglobulin M, Lymphoma, B-cell, Lymphoproliferative, MGRS, Monoclonal Gammopathy of Undetermined Significance, multiple myeloma, Myeloma Proteins, Paraproteinemias, Retrospective Studies, Waldenstrom MacroglobulinemiaOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-07-06July 06, 201810.2215/CJN.130411171555-90411555-905X2018-05-30T07:37:14-07:002018-07-06Clinical Journal of the American Society of NephrologyOriginal Articles13710371046
- Management of Nonadherence in ESKD Patients10.2215/CJN.13331117Wed, 30 May 2018 07:37:13 GMT-07:00Management of Nonadherence in ESKD PatientsCohen, Scott D.Kimmel, Paul L.2018-05-30T07:37:13-07:00doi:10.2215/CJN.13331117hwp:resource-id:clinjasn;13/7/1080American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, adherence, ESKD, behavioral adherenceKidney Case Conference: Attending RoundsKidney Case Conference: Attending Roundsresearch-article20182018-07-06July 06, 201810.2215/CJN.133311171555-90411555-905X2018-05-30T07:37:13-07:002018-07-06Clinical Journal of the American Society of NephrologyKidney Case Conference: Attending Rounds13710801082
- Management of Osteoporosis in CKDCKD mineral and bone disease is a common complication of kidney disease, and it affects the majority of patients with moderate to severe CKD. Recently, prospective studies have shown that measurement of bone mineral density by dual energy x-ray absorptiometry predicts incident fracture, providing nephrologists the ability to risk classify patients for skeletal fragility and targeted antifracture strategies for the first time. Furthermore, an expanding body of literature and anecdotal evidence suggest that pharmacologic agents used to treat osteoporosis in the general population can be safely used in patients with CKD. This review highlights the effects of the Kidney Disease Improving Global Outcomes updates on the management of CKD-associated osteoporosis, discusses recent investigations on the effects of antiosteoporotic agents in patients with CKD, and provides an overview of novel antiosteoporosis agents and the potential challenges related to their use in CKD.10.2215/CJN.11031017Tue, 27 Feb 2018 08:03:56 GMT-08:00Management of Osteoporosis in CKDCKD mineral and bone disease is a common complication of kidney disease, and it affects the majority of patients with moderate to severe CKD. Recently, prospective studies have shown that measurement of bone mineral density by dual energy x-ray absorptiometry predicts incident fracture, providing nephrologists the ability to risk classify patients for skeletal fragility and targeted antifracture strategies for the first time. Furthermore, an expanding body of literature and anecdotal evidence suggest that pharmacologic agents used to treat osteoporosis in the general population can be safely used in patients with CKD. This review highlights the effects of the Kidney Disease Improving Global Outcomes updates on the management of CKD-associated osteoporosis, discusses recent investigations on the effects of antiosteoporotic agents in patients with CKD, and provides an overview of novel antiosteoporosis agents and the potential challenges related to their use in CKD.Khairallah, PascaleNickolas, Thomas L.2018-02-27T08:03:56-08:00doi:10.2215/CJN.11031017hwp:resource-id:clinjasn;13/6/962American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOsteoporosis, renal osteodystrophy, Fracture, Absorptiometry, Photon, Bone Density, Nephrologists, Prospective Studies, Fractures, Bone, Bone Diseases, Renal Insufficiency, Chronic, MineralsReviewsReviewsreview-article20182018-06-07June 07, 201810.2215/CJN.110310171555-90411555-905X2018-02-27T08:03:56-08:002018-06-07Clinical Journal of the American Society of NephrologyReviews136962969
- Parathyroidectomy in the Management of Secondary HyperparathyroidismSecondary hyperparathyroidism develops in CKD due to a combination of vitamin D deficiency, hypocalcemia, and hyperphosphatemia, and it exists in nearly all patients at the time of dialysis initiation. There is insufficient data on whether to prefer vitamin D analogs compared with calcimimetics, but the available evidence suggests advantages with combination therapy. Calcium derangements, patient adherence, side effects, and cost limit the use of these agents. When parathyroid hormone level persists >800 pg/ml for >6 months, despite exhaustive medical interventions, monoclonal proliferation with nodular hyperplasia is likely present along with decreased expression of vitamin D and calcium-sensing receptors. Hence, surgical parathyroidectomy should be considered, especially if concomitant disorders exist, such as persistent hypercalcemia or hyperphosphatemia, tissue or vascular calcification including calciphylaxis, and/or worsening osteodystrophy. Parathyroidectomy is associated with 15%–57% greater survival in patients on dialysis, and it also improves hypercalcemia, hyperphosphatemia, tissue calcification, bone mineral density, and health-related quality of life. The parathyroidectomy rate in the United States declined to approximately seven per 1000 dialysis patient-years between 2002 and 2011 despite an increase in average parathyroid hormone levels, reflecting calcimimetics introduction and uncertainty regarding optimal parathyroid hormone targets. Hospitalization rates are 39% higher in the first postoperative year. Hungry bone syndrome occurs in approximately 25% of patients on dialysis, and profound hypocalcemia requires high doses of oral and intravenous calcium along with calcitriol supplementation. Total parathyroidectomy with autotransplantation carries a higher risk of permanent hypocalcemia, whereas risk of hyperparathyroidism recurrence is higher with subtotal parathyroidectomy. Given favorable long-term outcomes from observational parathyroidectomy cohorts, despite surgical risk and postoperative challenges, it is reasonable to consider parathyroidectomy in more patients with medically refractory secondary hyperparathyroidism.10.2215/CJN.10390917Fri, 09 Mar 2018 06:45:09 GMT-08:00Parathyroidectomy in the Management of Secondary HyperparathyroidismSecondary hyperparathyroidism develops in CKD due to a combination of vitamin D deficiency, hypocalcemia, and hyperphosphatemia, and it exists in nearly all patients at the time of dialysis initiation. There is insufficient data on whether to prefer vitamin D analogs compared with calcimimetics, but the available evidence suggests advantages with combination therapy. Calcium derangements, patient adherence, side effects, and cost limit the use of these agents. When parathyroid hormone level persists >800 pg/ml for >6 months, despite exhaustive medical interventions, monoclonal proliferation with nodular hyperplasia is likely present along with decreased expression of vitamin D and calcium-sensing receptors. Hence, surgical parathyroidectomy should be considered, especially if concomitant disorders exist, such as persistent hypercalcemia or hyperphosphatemia, tissue or vascular calcification including calciphylaxis, and/or worsening osteodystrophy. Parathyroidectomy is associated with 15%–57% greater survival in patients on dialysis, and it also improves hypercalcemia, hyperphosphatemia, tissue calcification, bone mineral density, and health-related quality of life. The parathyroidectomy rate in the United States declined to approximately seven per 1000 dialysis patient-years between 2002 and 2011 despite an increase in average parathyroid hormone levels, reflecting calcimimetics introduction and uncertainty regarding optimal parathyroid hormone targets. Hospitalization rates are 39% higher in the first postoperative year. Hungry bone syndrome occurs in approximately 25% of patients on dialysis, and profound hypocalcemia requires high doses of oral and intravenous calcium along with calcitriol supplementation. Total parathyroidectomy with autotransplantation carries a higher risk of permanent hypocalcemia, whereas risk of hyperparathyroidism recurrence is higher with subtotal parathyroidectomy. Given favorable long-term outcomes from observational parathyroidectomy cohorts, despite surgical risk and postoperative challenges, it is reasonable to consider parathyroidectomy in more patients with medically refractory secondary hyperparathyroidism.Lau, Wei LingObi, YoshitsuguKalantar-Zadeh, Kamyar2018-03-09T06:45:09-08:00doi:10.2215/CJN.10390917hwp:resource-id:clinjasn;13/6/952American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyparathyroidectomy, Secondary hyperparathyroidism, CKD-osteodystrophy, Bone Density, Calciphylaxis, Calcitriol, Humans, Hypercalcemia, Hyperparathyroidism, Secondary, hyperphosphatemia, Hyperplasia, Hypocalcemia, Parathyroidectomy, quality of life, Receptors, Calcium-Sensing, renal dialysis, Uncertainty, Vitamin DReviewsReviewsreview-article20182018-06-07June 07, 201810.2215/CJN.103909171555-90411555-905X2018-03-09T06:45:09-08:002018-06-07Clinical Journal of the American Society of NephrologyReviews136952961
- Family Consultation to Reduce Early Hospital Readmissions among Patients with End Stage Kidney Disease10.2215/CJN.08450817Tue, 10 Apr 2018 08:00:29 GMT-07:00Family Consultation to Reduce Early Hospital Readmissions among Patients with End Stage Kidney DiseaseJasinski, Matthew J.Lumley, Mark A.Soman, SandeepYee, JerryKetterer, Mark W.2018-04-10T08:00:29-07:00doi:10.2215/CJN.08450817hwp:resource-id:clinjasn;13/6/850American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Centers for Medicare and Medicaid Services (US), chronic kidney failure, Cognition, Cognitive Dysfunction, Emergency Service, Hospital, Humans, Inpatients, Kidney Failure, Chronic, Literacy, Logistic Models, Male, Medicaid, Medical Records, Medicare, Middle Aged, nephrology, Patient Discharge, Patient Readmission, Referral and Consultation, risk factors, Social Support, Telephone, United StatesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-06-07June 07, 201810.2215/CJN.084508171555-90411555-905X2018-04-10T08:00:29-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136850857
- Sleep Duration and Health-Related Quality of Life in Predialysis CKD10.2215/CJN.11351017Thu, 03 May 2018 06:45:14 GMT-07:00Sleep Duration and Health-Related Quality of Life in Predialysis CKDSung, Su-AhHyun, Young YoulLee, Kyu BeckPark, Hayne ChoChung, WookyungKim, Yeong HoonKim, Yong-SooPark, Sue KyungOh, Kook-HwanAhn, Curie,2018-05-03T06:45:14-07:00doi:10.2215/CJN.11351017hwp:resource-id:clinjasn;13/6/858American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, chronic kidney disease, Cohort Studies, Cross-sectional Studies, Humans, Logistic Models, Perception, quality of life, Renal Insufficiency, Chronic, Self Report, Sleep, Sleep Duration, Time FactorsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-06-07June 07, 201810.2215/CJN.113510171555-90411555-905X2018-05-03T06:45:14-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136858865
- IL-10 Receptor Signaling Empowers Regulatory T Cells to Control Th17 Responses and Protect from GNBackground Th17 cells are central pathogenic mediators of autoimmune disease, including many forms of GN. IL-10 receptor signaling (IL-10R) in regulatory T cells (Tregs) has been implicated in the downregulation of Th17 cells, but the underlying molecular mechanisms and functional relevance of this process remain unclear. Methods We generated mice with Treg-specific IL-10Ra deficiency and subjected these mice to nephrotoxic serum–induced nephritis as a model of crescentic GN. Immune responses and Treg phenotypes were extensively analyzed. Results Compared with controls, mice with IL-10Ra−/− Tregs showed a spontaneously overshooting Th17 immune response. This hyper-Th17 phenotype was further boosted during GN and associated with aggravated renal injury. Notably, abrogation of IL-10Ra signaling in Tregs increased dendritic cell activation and production of Th17-inducing cytokines. In contrast, Treg trafficking and expression of chemokine receptor CCR6 remained unaffected, indicating mechanisms of Th17 control, differing from those of previously identified CCR6+ Treg17 cells. Indeed, the capacity for direct in vitro suppression of Th17 responses by IL-10Ra−/− Tregs was significantly impaired. As underlying pathology, analyses conducted in vitro and in vivo using double-fluorescent reporter mice revealed strikingly decreased IL-10 production by IL-10Ra−/− Tregs. To assess, whether reduced IL-10 could explain the hyper Th17 phenotype, competitive cotransfer experiments were performed. Supporting our concept, IL-10Ra−/− T cells differentiated into Th17 cells at much higher frequencies than wild type T cells did during GN. Conclusions IL-10R engagement optimizes Treg-mediated suppression of Th17 immunity. We hypothesize a feed-forward loop, in which IL-10Ra signaling reinforces IL-10 secretion by Tregs which potently controls Th17 development via direct and indirect mechanisms. IL-10R thus may be a promising therapeutic target for the treatment of GN.10.1681/ASN.2017091044Mon, 04 Jun 2018 05:45:36 GMT-07:00IL-10 Receptor Signaling Empowers Regulatory T Cells to Control Th17 Responses and Protect from GNBackground Th17 cells are central pathogenic mediators of autoimmune disease, including many forms of GN. IL-10 receptor signaling (IL-10R) in regulatory T cells (Tregs) has been implicated in the downregulation of Th17 cells, but the underlying molecular mechanisms and functional relevance of this process remain unclear. Methods We generated mice with Treg-specific IL-10Ra deficiency and subjected these mice to nephrotoxic serum–induced nephritis as a model of crescentic GN. Immune responses and Treg phenotypes were extensively analyzed. Results Compared with controls, mice with IL-10Ra−/− Tregs showed a spontaneously overshooting Th17 immune response. This hyper-Th17 phenotype was further boosted during GN and associated with aggravated renal injury. Notably, abrogation of IL-10Ra signaling in Tregs increased dendritic cell activation and production of Th17-inducing cytokines. In contrast, Treg trafficking and expression of chemokine receptor CCR6 remained unaffected, indicating mechanisms of Th17 control, differing from those of previously identified CCR6+ Treg17 cells. Indeed, the capacity for direct in vitro suppression of Th17 responses by IL-10Ra−/− Tregs was significantly impaired. As underlying pathology, analyses conducted in vitro and in vivo using double-fluorescent reporter mice revealed strikingly decreased IL-10 production by IL-10Ra−/− Tregs. To assess, whether reduced IL-10 could explain the hyper Th17 phenotype, competitive cotransfer experiments were performed. Supporting our concept, IL-10Ra−/− T cells differentiated into Th17 cells at much higher frequencies than wild type T cells did during GN. Conclusions IL-10R engagement optimizes Treg-mediated suppression of Th17 immunity. We hypothesize a feed-forward loop, in which IL-10Ra signaling reinforces IL-10 secretion by Tregs which potently controls Th17 development via direct and indirect mechanisms. IL-10R thus may be a promising therapeutic target for the treatment of GN.Diefenhardt, PaulNosko, AnnaKluger, Malte A.Richter, Johannes V.Wegscheid, ClaudiaKobayashi, YasushiTiegs, GisaHuber, SamuelFlavell, Richard A.Stahl, Rolf A.K.Steinmetz, Oliver M.2018-06-04T05:45:36-07:00doi:10.1681/ASN.2017091044hwp:resource-id:jnephrol;29/7/1825American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, cytokines, Interleukin 10, IL-10R, Treg, IL-17Basic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20170910441046-66731533-34502018-06-04T05:45:36-07:002018-07Journal of the American Society of NephrologyBasic Research29718251837
- Residual Function Effectively Controls Plasma Concentrations of Secreted Solutes in Patients on Twice Weekly HemodialysisBackground Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis. Methods We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis. Results Compared with anuric patients on thrice weekly dialysis with the same standard Kt/Vurea, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and p-cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations. Conclusions Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.10.1681/ASN.2018010081Fri, 04 May 2018 05:56:20 GMT-07:00Residual Function Effectively Controls Plasma Concentrations of Secreted Solutes in Patients on Twice Weekly HemodialysisBackground Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis. Methods We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis. Results Compared with anuric patients on thrice weekly dialysis with the same standard Kt/Vurea, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and p-cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations. Conclusions Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.Leong, Sheldon C.Sao, Justin N.Taussig, AbigailPlummer, Natalie S.Meyer, Timothy W.Sirich, Tammy L.2018-05-04T05:56:20-07:00doi:10.1681/ASN.2018010081hwp:resource-id:jnephrol;29/7/1992American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, uremia, urea modellingClinical ResearchClinical Researchresearch-article20182018-07-01July 201810.1681/ASN.20180100811046-66731533-34502018-05-04T05:56:20-07:002018-07Journal of the American Society of NephrologyClinical Research29719921999
- The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK PathwayBackground Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle’s loop controls Ca2+ excretion and NaCl reabsorption in response to extracellular Ca2+. However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive 22Na+ uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd3+. In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca2+ in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca2+ reabsorption, further promoting hypercalciuria.10.1681/ASN.2017111155Wed, 30 May 2018 07:37:46 GMT-07:00The Calcium-Sensing Receptor Increases Activity of the Renal NCC through the WNK4-SPAK PathwayBackground Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle’s loop controls Ca2+ excretion and NaCl reabsorption in response to extracellular Ca2+. However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity. Because the KLHL3-WNK4-SPAK pathway is involved in regulating NaCl reabsorption in the DCT, we assessed the involvement of this pathway as well. Results Thiazide-sensitive 22Na+ uptake assays in Xenopus laevis oocytes revealed that NCC activity increased in a WNK4-dependent manner upon activation of CaSR with Gd3+. In HEK293 cells, treatment with the calcimimetic R-568 stimulated SPAK phosphorylation only in the presence of WNK4. The WNK4 inhibitor WNK463 also prevented this effect. Furthermore, CaSR activation in HEK293 cells led to phosphorylation of KLHL3 and WNK4 and increased WNK4 abundance and activity. Finally, acute oral administration of R-568 in mice led to the phosphorylation of NCC. Conclusions Activation of CaSR can increase NCC activity via the WNK4-SPAK pathway. It is possible that activation of CaSR by Ca2+ in the apical membrane of the DCT increases NaCl reabsorption by NCC, with the consequent, well known decrease of Ca2+ reabsorption, further promoting hypercalciuria.Bazúa-Valenti, SilvanaRojas-Vega, LorenaCastañeda-Bueno, MaríaBarrera-Chimal, JonatanBautista, RocíoCervantes-Pérez, Luz G.Vázquez, NormaPlata, ConsueloMurillo-de-Ozores, Adrián R.González-Mariscal, LorenzaEllison, David H.Riccardi, DanielaBobadilla, Norma A.Gamba, Gerardo2018-05-30T07:37:46-07:00doi:10.1681/ASN.2017111155hwp:resource-id:jnephrol;29/7/1838American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydistal tubule, diuretics, Na transport, hypertensionBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20171111551046-66731533-34502018-05-30T07:37:46-07:002018-07Journal of the American Society of NephrologyBasic Research29718381848
- This Month’s Highlights10.1681/ASN.2018050525Fri, 29 Jun 2018 01:05:02 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2018-06-29T13:05:02-07:00doi:10.1681/ASN.2018050525hwp:resource-id:jnephrol;29/7/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-07-01July 201810.1681/ASN.20180505251046-66731533-34502018-06-29T13:05:02-07:002018-07Journal of the American Society of NephrologyThis Month’s Highlights297ii
- Transformation in Immunosuppression: Are We Ready for it?10.1681/ASN.2018050491Fri, 08 Jun 2018 06:44:39 GMT-07:00Transformation in Immunosuppression: Are We Ready for it?Aala, AmtulBrennan, Daniel C.2018-06-08T06:44:39-07:00doi:10.1681/ASN.2018050491hwp:resource-id:jnephrol;29/7/1791American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologytacrolimus, randomized controlled trials, transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-07-01July 201810.1681/ASN.20180504911046-66731533-34502018-06-08T06:44:39-07:002018-07Journal of the American Society of NephrologyUp Front Matters29771791197917921991
- Clinical and Pathology Findings Associate Consistently with Larger Glomerular VolumeBackground Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities. Methods We studied kidney biopsy specimens from living kidney donors (n=2453) and patients who underwent radical nephrectomy for a renal tumor (n=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel–Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen. Results Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (P<0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis >25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume. Conclusions Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.10.1681/ASN.2017121305Tue, 22 May 2018 06:31:27 GMT-07:00Clinical and Pathology Findings Associate Consistently with Larger Glomerular VolumeBackground Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities. Methods We studied kidney biopsy specimens from living kidney donors (n=2453) and patients who underwent radical nephrectomy for a renal tumor (n=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel–Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen. Results Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (P<0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis >25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume. Conclusions Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.Denic, AleksandarMathew, JerryNagineni, Venkata V.Thompson, R. HoustonLeibovich, Bradley C.Lerman, Lilach O.Lieske, John C.Alexander, Mariam P.Augustine, Joshua J.Kremers, Walter K.Rule, Andrew D.2018-05-22T06:31:27-07:00doi:10.1681/ASN.2017121305hwp:resource-id:jnephrol;29/7/1960American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulus, Renal pathology, Epidemiology and outcomes, renal morphology, risk factors, glomerulosclerosisClinical EpidemiologyClinical Epidemiologyresearch-article20182018-07-01July 201810.1681/ASN.20171213051046-66731533-34502018-05-22T06:31:27-07:002018-07Journal of the American Society of NephrologyClinical Epidemiology2929791960244519692445
- Erratum10.1681/ASN.2018040439Wed, 23 May 2018 06:48:20 GMT-07:00ErratumAmerican Society of Nephrology2018-05-23T06:48:20-07:00doi:10.1681/ASN.2018040439hwp:resource-id:jnephrol;29/7/2028American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20182018-07-01July 201810.1681/ASN.20180404391046-66731533-34502018-05-23T06:48:20-07:002018-07Journal of the American Society of NephrologyErratum2928742028125920281268
- Caspase-3 Is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion InjuryBackground Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Here, we characterize the different modes of programmed cell death in the tubular and microvascular compartments during the various stages of IRI-induced AKI, and their relative importance to renal fibrogenesis. Methods We performed unilateral renal artery clamping for 30 minutes and contralateral nephrectomy in wild-type mice (C57BL/6) or caspase-3−/− mice. Results Compared with their wild-type counterparts, caspase-3−/− mice in the early stage of AKI had high urine cystatin C levels, tubular injury scores, and serum creatinine levels. Electron microscopy revealed evidence of tubular epithelial cell necrosis in caspase-3−/− mice, and immunohistochemistry showed upregulation of the necroptosis marker receptor-interacting serine/threonine-protein kinase 3 (RIPK3) in renal cortical sections. Western blot analysis further demonstrated enhanced levels of phosphorylated RIPK3 in the kidneys of caspase-3−/− mice. In contrast, caspase-3−/− mice had less microvascular congestion and activation in the early and extension phases of AKI. In the long term (3 weeks after IRI), caspase-3−/− mice had reduced microvascular rarefaction and renal fibrosis, as well as decreased expression of α-smooth muscle actin and reduced collagen deposition within peritubular capillaries. Moreover, caspase-3−/− mice exhibited signs of reduced tubular ischemia, including lower tubular expression of hypoxia-inducible factor-1α and improved tubular injury scores. Conclusions These results establish the pivotal importance of caspase-3 in regulating microvascular endothelial cell apoptosis and renal fibrosis after IRI. These findings also demonstrate the predominant role of microvascular over tubular injury as a driver of progressive renal damage and fibrosis after IRI.10.1681/ASN.2017050581Wed, 20 Jun 2018 07:19:36 GMT-07:00Caspase-3 Is a Pivotal Regulator of Microvascular Rarefaction and Renal Fibrosis after Ischemia-Reperfusion InjuryBackground Ischemia-reperfusion injury (IRI) is a major risk factor for chronic renal failure. Here, we characterize the different modes of programmed cell death in the tubular and microvascular compartments during the various stages of IRI-induced AKI, and their relative importance to renal fibrogenesis. Methods We performed unilateral renal artery clamping for 30 minutes and contralateral nephrectomy in wild-type mice (C57BL/6) or caspase-3−/− mice. Results Compared with their wild-type counterparts, caspase-3−/− mice in the early stage of AKI had high urine cystatin C levels, tubular injury scores, and serum creatinine levels. Electron microscopy revealed evidence of tubular epithelial cell necrosis in caspase-3−/− mice, and immunohistochemistry showed upregulation of the necroptosis marker receptor-interacting serine/threonine-protein kinase 3 (RIPK3) in renal cortical sections. Western blot analysis further demonstrated enhanced levels of phosphorylated RIPK3 in the kidneys of caspase-3−/− mice. In contrast, caspase-3−/− mice had less microvascular congestion and activation in the early and extension phases of AKI. In the long term (3 weeks after IRI), caspase-3−/− mice had reduced microvascular rarefaction and renal fibrosis, as well as decreased expression of α-smooth muscle actin and reduced collagen deposition within peritubular capillaries. Moreover, caspase-3−/− mice exhibited signs of reduced tubular ischemia, including lower tubular expression of hypoxia-inducible factor-1α and improved tubular injury scores. Conclusions These results establish the pivotal importance of caspase-3 in regulating microvascular endothelial cell apoptosis and renal fibrosis after IRI. These findings also demonstrate the predominant role of microvascular over tubular injury as a driver of progressive renal damage and fibrosis after IRI.Yang, BingLan, ShanshanDieudé, MélanieSabo-Vatasescu, Jean-PaulKarakeussian-Rimbaud, AnnieTurgeon, JulieQi, ShijieGunaratnam, LakshmanPatey, NatalieHébert, Marie-Josée2018-06-20T07:19:36-07:00doi:10.1681/ASN.2017050581hwp:resource-id:jnephrol;29/7/1900American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, caspase-3, apoptosis, acute kidney injuryBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20170505811046-66731533-34502018-06-20T07:19:36-07:002018-07Journal of the American Society of NephrologyBasic Research29719001916
- Epithelial and Endothelial Pannexin1 Channels Mediate AKIBackground Pannexin1 (Panx1), an ATP release channel, is present in most mammalian tissues, but the role of Panx1 in health and disease is not fully understood. Panx1 may serve to modulate AKI; ATP is a precursor to adenosine and may function to block inflammation, or ATP may act as a danger-associated molecular pattern and initiate inflammation. Methods We used pharmacologic and genetic approaches to evaluate the effect of Panx1 on kidney ischemia-reperfusion injury (IRI), a mouse model of AKI. Results Pharmacologic inhibition of gap junctions, including Panx1, by administration of carbenoxolone protected mice from IRI. Furthermore, global deletion of Panx1 preserved kidney function and morphology and diminished the expression of proinflammatory molecules after IRI. Analysis of bone marrow chimeric mice revealed that Panx1 expressed on parenchymal cells is necessary for ischemic injury, and both proximal tubule and vascular endothelial Panx1 tissue-specific knockout mice were protected from IRI. In vitro, Panx1-deficient proximal tubule cells released less and retained more ATP under hypoxic stress. Conclusions Panx1 is involved in regulating ATP release from hypoxic cells, and reducing this ATP release may protect kidneys from AKI.10.1681/ASN.2017121306Mon, 04 Jun 2018 05:45:34 GMT-07:00Epithelial and Endothelial Pannexin1 Channels Mediate AKIBackground Pannexin1 (Panx1), an ATP release channel, is present in most mammalian tissues, but the role of Panx1 in health and disease is not fully understood. Panx1 may serve to modulate AKI; ATP is a precursor to adenosine and may function to block inflammation, or ATP may act as a danger-associated molecular pattern and initiate inflammation. Methods We used pharmacologic and genetic approaches to evaluate the effect of Panx1 on kidney ischemia-reperfusion injury (IRI), a mouse model of AKI. Results Pharmacologic inhibition of gap junctions, including Panx1, by administration of carbenoxolone protected mice from IRI. Furthermore, global deletion of Panx1 preserved kidney function and morphology and diminished the expression of proinflammatory molecules after IRI. Analysis of bone marrow chimeric mice revealed that Panx1 expressed on parenchymal cells is necessary for ischemic injury, and both proximal tubule and vascular endothelial Panx1 tissue-specific knockout mice were protected from IRI. In vitro, Panx1-deficient proximal tubule cells released less and retained more ATP under hypoxic stress. Conclusions Panx1 is involved in regulating ATP release from hypoxic cells, and reducing this ATP release may protect kidneys from AKI.Jankowski, JakubPerry, Heather M.Medina, Christopher B.Huang, LipingYao, JunlanBajwa, AmandeepLorenz, Ulrike M.Rosin, Diane L.Ravichandran, Kodi S.Isakson, Brant E.Okusa, Mark D.2018-06-04T05:45:34-07:00doi:10.1681/ASN.2017121306hwp:resource-id:jnephrol;29/7/1887American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, ischemia-reperfusion, purinergic signaling, ATPBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20171213061046-66731533-34502018-06-04T05:45:34-07:002018-07Journal of the American Society of NephrologyBasic Research29317118872311899231
- Cellular Origin and Functional Relevance of Collagen I Production in the KidneyBackground Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow–derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal function are unclear. Methods We generated conditional cell type–specific collagen I knockout mice and used (reversible) unilateral ureteral obstruction and adenine-induced nephropathy to study renal fibrosis and function. Results In these mouse models, hematopoietic, bone marrow–derived cells contributed to 38%–50% of the overall deposition of collagen I in the kidney. The influence of fibrosis on renal function was dependent on the type of damage. In unilateral ureteral obstruction, collagen production by resident fibroblasts was essential to preserve renal function, whereas in the chronic model of adenine-induced nephropathy, collagen production was detrimental to renal function. Conclusions Our data show that hematopoietic cells are a major source of collagen and that antifibrotic therapies need to be carefully considered depending on the type of disease and the underlying cause of fibrosis.10.1681/ASN.2018020138Fri, 18 May 2018 07:34:02 GMT-07:00Cellular Origin and Functional Relevance of Collagen I Production in the KidneyBackground Interstitial fibrosis is associated with chronic renal failure. In addition to fibroblasts, bone marrow–derived cells and tubular epithelial cells have the capacity to produce collagen. However, the amount of collagen produced by each of these cell types and the relevance of fibrosis to renal function are unclear. Methods We generated conditional cell type–specific collagen I knockout mice and used (reversible) unilateral ureteral obstruction and adenine-induced nephropathy to study renal fibrosis and function. Results In these mouse models, hematopoietic, bone marrow–derived cells contributed to 38%–50% of the overall deposition of collagen I in the kidney. The influence of fibrosis on renal function was dependent on the type of damage. In unilateral ureteral obstruction, collagen production by resident fibroblasts was essential to preserve renal function, whereas in the chronic model of adenine-induced nephropathy, collagen production was detrimental to renal function. Conclusions Our data show that hematopoietic cells are a major source of collagen and that antifibrotic therapies need to be carefully considered depending on the type of disease and the underlying cause of fibrosis.Buchtler, SimoneGrill, AlexandraHofmarksrichter, StefanieStöckert, PetraSchiechl-Brachner, GabrielaRodriguez Gomez, ManuelNeumayer, SophiaSchmidbauer, KathrinTalke, YvonneKlinkhammer, Barbara M.Boor, PeterMedvinsky, AlexanderRenner, KerstinCastrop, HayoMack, Matthias2018-05-18T07:34:02-07:00doi:10.1681/ASN.2018020138hwp:resource-id:jnephrol;29/7/1859American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, chronic kidney disease, chronic renal failure, interstitial fibrosis, immunologyBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20180201381046-66731533-34502018-05-18T07:34:02-07:002018-07Journal of the American Society of NephrologyBasic Research29718591873
- Greater Burden of ESRD among Immigrants: Kwa nini?10.1681/ASN.2018050503Mon, 04 Jun 2018 05:45:35 GMT-07:00Greater Burden of ESRD among Immigrants: Kwa nini?Crews, Deidra C.2018-06-04T05:45:35-07:00doi:10.1681/ASN.2018050503hwp:resource-id:jnephrol;29/7/1789American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyEthnic minority, Epidemiology and outcomes, ESRDUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-07-01July 201810.1681/ASN.20180505031046-66731533-34502018-06-04T05:45:35-07:002018-07Journal of the American Society of NephrologyUp Front Matters29771789194817901959
- GATM Mutations Cause a Dominant Fibrillar Conformational Disease in Mitochondria—When Eternity Kills10.1681/ASN.2018040450Tue, 22 May 2018 06:31:28 GMT-07:00GATM Mutations Cause a Dominant Fibrillar Conformational Disease in Mitochondria—When Eternity KillsCourtoy, Pierre J.Henriet, Patrick2018-05-22T06:31:28-07:00doi:10.1681/ASN.2018040450hwp:resource-id:jnephrol;29/7/1787American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyFanconi, mitochondria, conformational diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-07-01July 201810.1681/ASN.20180404501046-66731533-34502018-05-22T06:31:28-07:002018-07Journal of the American Society of NephrologyUp Front Matters29771787184917891858
- Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-AnalysisBackground Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43–74 RU/ml and 38–47 pg/ml in 17 general population cohorts; 102–392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79–4212 RU/ml and 2526–5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies. Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure–response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.10.1681/ASN.2017121334Tue, 15 May 2018 10:06:29 GMT-07:00Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-AnalysisBackground Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. Methods We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Results Depending on the assay used, median FGF-23 concentrations were 43–74 RU/ml and 38–47 pg/ml in 17 general population cohorts; 102–392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79–4212 RU/ml and 2526–5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies. Conclusions The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure–response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.Marthi, AmarnathDonovan, KillianHaynes, RichardWheeler, David C.Baigent, ColinRooney, Christopher M.Landray, Martin J.Moe, Sharon M.Yang, JunHolland, Lisadi Giuseppe, RominaBouma-de Krijger, AnnetMihaylova, BorislavaHerrington, William G.2018-05-15T10:06:29-07:00doi:10.1681/ASN.2017121334hwp:resource-id:jnephrol;29/7/2015American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, dialysis, fibroblast, heart failure, FGF23Meta-AnalysisMeta-Analysisresearch-article20182018-07-01July 201810.1681/ASN.20171213341046-66731533-34502018-05-15T10:06:29-07:002018-07Journal of the American Society of NephrologyMeta-Analysis29720152027
- ESRD among Immigrants to Ontario, Canada: A Population-Based StudyBackground The epidemiology of ESRD requiring maintenance dialysis (ESRD-D) in large, diverse immigrant populations is unclear. Methods We estimated ESRD-D prevalence and incidence among immigrants in Ontario, Canada. Adults residing in Ontario in 2014 were categorized as long-term Canadian residents or immigrants according to administrative health and immigration datasets. We determined ESRD-D prevalence among these adults and calculated age-adjusted prevalence ratios (PRs) comparing immigrants to long-term residents. Among those who immigrated to Ontario between 1991 and 2012, age-adjusted ESRD-D incidence was calculated by world region and country of birth, with immigrants from Western nations as the referent group. Results Among 1,902,394 immigrants and 8,860,283 long-term residents, 1700 (0.09%) and 8909 (0.10%), respectively, presented with ESRD-D. Age-adjusted ESRD-D prevalence was higher among immigrants from sub-Saharan Africa (PR, 2.17; 95% confidence interval [95% CI], 1.84 to 2.57), Latin America and the Caribbean (PR, 2.11; 95% CI, 1.90 to 2.34), South Asia (PR, 1.45; 95% CI, 1.32 to 1.59), and East Asia and the Pacific (PR, 1.34; 95% CI, 1.22 to 1.46). Immigrants from Somalia (PR, 4.18; 95% CI, 3.11 to 5.61), Trinidad and Tobago (PR, 2.88; 95% CI, 2.23 to 3.73), Jamaica (PR, 2.88; 95% CI, 2.40 to 3.44), Sudan (PR, 2.84; 95% CI, 1.53 to 5.27), and Guyana (PR, 2.69; 95% CI, 2.19 to 3.29) had the highest age-adjusted ESRD-D PRs relative to long-term residents. Immigrants from these countries also exhibited higher age-adjusted ESKD-D incidence relative to Western Nations immigrants. Conclusions Among immigrants in Canada, those from sub-Saharan Africa and the Caribbean have the highest ESRD-D risk. Tailored kidney-protective interventions should be developed for these susceptible populations.10.1681/ASN.2017101055Wed, 02 May 2018 05:57:02 GMT-07:00ESRD among Immigrants to Ontario, Canada: A Population-Based StudyBackground The epidemiology of ESRD requiring maintenance dialysis (ESRD-D) in large, diverse immigrant populations is unclear. Methods We estimated ESRD-D prevalence and incidence among immigrants in Ontario, Canada. Adults residing in Ontario in 2014 were categorized as long-term Canadian residents or immigrants according to administrative health and immigration datasets. We determined ESRD-D prevalence among these adults and calculated age-adjusted prevalence ratios (PRs) comparing immigrants to long-term residents. Among those who immigrated to Ontario between 1991 and 2012, age-adjusted ESRD-D incidence was calculated by world region and country of birth, with immigrants from Western nations as the referent group. Results Among 1,902,394 immigrants and 8,860,283 long-term residents, 1700 (0.09%) and 8909 (0.10%), respectively, presented with ESRD-D. Age-adjusted ESRD-D prevalence was higher among immigrants from sub-Saharan Africa (PR, 2.17; 95% confidence interval [95% CI], 1.84 to 2.57), Latin America and the Caribbean (PR, 2.11; 95% CI, 1.90 to 2.34), South Asia (PR, 1.45; 95% CI, 1.32 to 1.59), and East Asia and the Pacific (PR, 1.34; 95% CI, 1.22 to 1.46). Immigrants from Somalia (PR, 4.18; 95% CI, 3.11 to 5.61), Trinidad and Tobago (PR, 2.88; 95% CI, 2.23 to 3.73), Jamaica (PR, 2.88; 95% CI, 2.40 to 3.44), Sudan (PR, 2.84; 95% CI, 1.53 to 5.27), and Guyana (PR, 2.69; 95% CI, 2.19 to 3.29) had the highest age-adjusted ESRD-D PRs relative to long-term residents. Immigrants from these countries also exhibited higher age-adjusted ESKD-D incidence relative to Western Nations immigrants. Conclusions Among immigrants in Canada, those from sub-Saharan Africa and the Caribbean have the highest ESRD-D risk. Tailored kidney-protective interventions should be developed for these susceptible populations.Perl, JeffreyMcArthur, EricTan, Vivian S.Nash, Danielle M.Garg, Amit X.Harel, ZivLi, Alvin H.Sood, Manish M.Ray, Joel G.Wald, Ron2018-05-02T05:57:02-07:00doi:10.1681/ASN.2017101055hwp:resource-id:jnephrol;29/7/1948American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, peritoneal dialysis, dialysis, clinical epidemiology, ESRDClinical EpidemiologyClinical Epidemiologyresearch-article20182018-07-01July 201810.1681/ASN.20171010551046-66731533-34502018-05-02T05:57:02-07:002018-07Journal of the American Society of NephrologyClinical Epidemiology29771948178919591790
- Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal MembraneBackground Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. Results In silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.10.1681/ASN.2017080828Tue, 29 May 2018 07:21:49 GMT-07:00Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal MembraneBackground Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated. Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin. Results In silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone. Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.Morelle, JohannSow, AmadouFustin, Charles-AndréFillée, CatherineGarcia-Lopez, ElviaLindholm, BengtGoffin, EricVandemaele, FrédericRippe, BengtÖberg, Carl M.Devuyst, Olivier2018-05-29T07:21:49-07:00doi:10.1681/ASN.2017080828hwp:resource-id:jnephrol;29/7/1875American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, aquaporin-1, ultrafiltration, membrane permeabilityBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20170808281046-66731533-34502018-05-29T07:21:49-07:002018-07Journal of the American Society of NephrologyBasic Research29718751886
- Leveraging Ancestral Heterogeneity to Map Shared Genetic Risk Loci in Pediatric Steroid-Sensitive Nephrotic Syndrome10.1681/ASN.2018050465Thu, 14 Jun 2018 06:51:54 GMT-07:00Leveraging Ancestral Heterogeneity to Map Shared Genetic Risk Loci in Pediatric Steroid-Sensitive Nephrotic SyndromeHjorten, RebeccaSkorecki, Karl2018-06-14T06:51:54-07:00doi:10.1681/ASN.2018050465hwp:resource-id:jnephrol;29/7/1793American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, GWAS, geneUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-07-01July 201810.1681/ASN.20180504651046-66731533-34502018-06-14T06:51:54-07:002018-07Journal of the American Society of NephrologyUp Front Matters29771793200017942013
- Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic ThrombophiliaBackground Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain. Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R), that causes aHUS and systemic thrombophilia with high mortality. Results P deficiency completely rescued FHR/R mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FHR/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FHR/R mice after 4 weeks of anti-P mAb treatment. One half of the FHR/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FHR/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice. Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit.10.1681/ASN.2017121244Fri, 01 Jun 2018 05:33:55 GMT-07:00Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic ThrombophiliaBackground Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain. Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R), that causes aHUS and systemic thrombophilia with high mortality. Results P deficiency completely rescued FHR/R mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FHR/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FHR/R mice after 4 weeks of anti-P mAb treatment. One half of the FHR/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FHR/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice. Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit.Ueda, YoshiyasuMiwa, TakashiGullipalli, DamodarSato, SayakaIto, DaisukeKim, HangsooPalmer, MatthewSong, Wen-Chao2018-06-01T05:33:55-07:00doi:10.1681/ASN.2017121244hwp:resource-id:jnephrol;29/7/1928American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, hemolytic uremic syndrome, Immunology and pathologyBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20171212441046-66731533-34502018-06-01T05:33:55-07:002018-07Journal of the American Society of NephrologyBasic Research29719281937
- Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD ProgressionBackground Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles—genetic variants associated with CKD risk commonly present in persons of African descent—may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) (n=588; Bonferroni significance threshold P<6.5×10−5) and replicated findings in 678 black participants with CKD in BioMe, an electronic medical record–linked biobank. We tested the metabolite association with CKD progression in AASK, BioMe, and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK (P=4.7×10−5) and replicated in BioMe (P=5.7×10−3) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and BioMe participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; BioMe, 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression.10.1681/ASN.2017101064Fri, 18 May 2018 07:34:03 GMT-07:00Serum 6-Bromotryptophan Levels Identified as a Risk Factor for CKD ProgressionBackground Metabolite levels reflect physiologic homeostasis and may serve as biomarkers of disease progression. Identifying metabolites associated with APOL1 risk alleles—genetic variants associated with CKD risk commonly present in persons of African descent—may reveal novel markers of CKD progression relevant to other populations. Methods We evaluated associations between the number of APOL1 risk alleles and 760 serum metabolites identified via untargeted profiling in participants of the African American Study of Kidney Disease and Hypertension (AASK) (n=588; Bonferroni significance threshold P<6.5×10−5) and replicated findings in 678 black participants with CKD in BioMe, an electronic medical record–linked biobank. We tested the metabolite association with CKD progression in AASK, BioMe, and the Modification of Diet in Renal Disease (MDRD) Study. Results One metabolite, 6-bromotryptophan, was significant in AASK (P=4.7×10−5) and replicated in BioMe (P=5.7×10−3) participants, with lower levels associated with more APOL1 risk alleles. Lower levels of 6-bromotryptophan were associated with CKD progression in AASK and BioMe participants and in white participants in the MDRD Study, independent of demographics and clinical characteristics, including baseline GFR (adjusted hazard ratio per two-fold higher 6-bromotryptophan level, AASK, 0.76; 95% confidence interval [95% CI], 0.64 to 0.91; BioMe, 0.61; 95% CI, 0.43 to 0.85; MDRD, 0.52; 95% CI, 0.34 to 0.79). The interaction between the APOL1 risk alleles and 6-bromotryptophan was not significant. The identity of 6-bromotryptophan was confirmed in experiments comparing its molecular signature with that of authentic standards of other bromotryptophan isomers. Conclusions Serum 6-bromotryptophan is a consistent and novel risk factor for CKD progression.Tin, AdrienneNadkarni, GirishEvans, Anne M.Winkler, Cheryl A.Bottinger, ErwinRebholz, Casey M.Sarnak, Mark J.Inker, Lesley A.Levey, Andrew S.Lipkowitz, Michael S.Appel, Lawrence J.Arking, Dan E.Coresh, JosefGrams, Morgan E.2018-05-18T07:34:03-07:00doi:10.1681/ASN.2017101064hwp:resource-id:jnephrol;29/7/1939American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, end stage kidney disease, renal function declineClinical EpidemiologyClinical Epidemiologyresearch-article20182018-07-01July 201810.1681/ASN.20171010641046-66731533-34502018-05-18T07:34:03-07:002018-07Journal of the American Society of NephrologyClinical Epidemiology29719391947
- Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis PatientsBackground Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking. Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0–100, >100–200, >200–300, and >300 mg) and pregabalin (>0–100 and >100 mg). Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%–41%) and fall (26%–30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively. Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.10.1681/ASN.2018010096Tue, 05 Jun 2018 06:51:04 GMT-07:00Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis PatientsBackground Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking. Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0–100, >100–200, >200–300, and >300 mg) and pregabalin (>0–100 and >100 mg). Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%–41%) and fall (26%–30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively. Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.Ishida, Julie H.McCulloch, Charles E.Steinman, Michael A.Grimes, Barbara A.Johansen, Kirsten L.2018-06-05T06:51:04-07:00doi:10.1681/ASN.2018010096hwp:resource-id:jnephrol;29/7/1970American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, United States Renal Data System, gabapentin, pregabalinClinical EpidemiologyClinical Epidemiologyresearch-article20182018-07-01July 201810.1681/ASN.20180100961046-66731533-34502018-06-05T06:51:04-07:002018-07Journal of the American Society of NephrologyClinical Epidemiology29719701978
- A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney DiseaseBackground Loss of glomerular podocytes is an indicator of diabetic kidney disease (DKD). The damage to these cells has been attributed in part to elevated intrarenal oxidative stress. The primary source of the renal reactive oxygen species, particularly H2O2, is NADPH oxidase 4 (NOX4). We hypothesized that NOX4-derived H2O2 contributes to podocyte damage in DKD via elevation of podocyte calcium. Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SSNox4−/−) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6. We performed whole animal studies and used biosensor measurements, electron microscopy, electrophysiology, and live calcium imaging experiments to evaluate the contribution of this pathway to the physiology of the podocytes in freshly isolated glomeruli. Results Upon induction of type 1 diabetes with streptozotocin, SSNox4−/− rats exhibited significantly lower basal intracellular Ca2+ levels in podocytes and less DKD-associated damage than SS rats did. Furthermore, the angiotensin II–elicited calcium flux was blunted in glomeruli isolated from diabetic SSNox4−/− rats compared with that in glomeruli from diabetic SS rats. H2O2 stimulated TRPC-dependent calcium influx in podocytes from wild-type mice, but this influx was blunted in podocytes from Trpc6-knockout mice and, in a similar manner, in podocytes from Trpc5/6 double-knockout mice. Finally, electron microscopy revealed that podocytes of glomeruli isolated from Trpc6-knockout or Trpc5/6 double-knockout mice were protected from damage induced by H2O2 to the same extent. Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.10.1681/ASN.2018030280Wed, 23 May 2018 06:48:21 GMT-07:00A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney DiseaseBackground Loss of glomerular podocytes is an indicator of diabetic kidney disease (DKD). The damage to these cells has been attributed in part to elevated intrarenal oxidative stress. The primary source of the renal reactive oxygen species, particularly H2O2, is NADPH oxidase 4 (NOX4). We hypothesized that NOX4-derived H2O2 contributes to podocyte damage in DKD via elevation of podocyte calcium. Methods We used Dahl salt-sensitive (SS) rats with a null mutation for the Nox4 gene (SSNox4−/−) and mice with knockout of the nonselective calcium channel TRPC6 or double knockout of TRPC5 and TRPC6. We performed whole animal studies and used biosensor measurements, electron microscopy, electrophysiology, and live calcium imaging experiments to evaluate the contribution of this pathway to the physiology of the podocytes in freshly isolated glomeruli. Results Upon induction of type 1 diabetes with streptozotocin, SSNox4−/− rats exhibited significantly lower basal intracellular Ca2+ levels in podocytes and less DKD-associated damage than SS rats did. Furthermore, the angiotensin II–elicited calcium flux was blunted in glomeruli isolated from diabetic SSNox4−/− rats compared with that in glomeruli from diabetic SS rats. H2O2 stimulated TRPC-dependent calcium influx in podocytes from wild-type mice, but this influx was blunted in podocytes from Trpc6-knockout mice and, in a similar manner, in podocytes from Trpc5/6 double-knockout mice. Finally, electron microscopy revealed that podocytes of glomeruli isolated from Trpc6-knockout or Trpc5/6 double-knockout mice were protected from damage induced by H2O2 to the same extent. Conclusions These data reveal a novel signaling mechanism involving NOX4 and TRPC6 in podocytes that could be pharmacologically targeted to abate the development of DKD.Ilatovskaya, Daria V.Blass, GregoryPalygin, OlegLevchenko, VladislavPavlov, Tengis S.Grzybowski, Michael N.Winsor, KristenShuyskiy, Leonid S.Geurts, Aron M.Cowley, Allen W.Birnbaumer, LutzStaruschenko, Alexander2018-05-23T06:48:21-07:00doi:10.1681/ASN.2018030280hwp:resource-id:jnephrol;29/7/1917American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, diabetic nephropathy, podocyte, reactive oxygen species, NADPH oxidase, ion channelBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20180302801046-66731533-34502018-05-23T06:48:21-07:002018-07Journal of the American Society of NephrologyBasic Research29719171927
- Right Heart Failure—Unrecognized Cause of Cardiorenal Syndrome10.1681/ASN.2018020224Tue, 15 May 2018 10:06:28 GMT-07:00Right Heart Failure—Unrecognized Cause of Cardiorenal SyndromeBansal, ShwetaPrasad, AnandLinas, Stuart2018-05-15T10:06:28-07:00doi:10.1681/ASN.2018020224hwp:resource-id:jnephrol;29/7/1795American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal dysfunction, Right heart failure, Neurohormonal activation, Pulmonary Hypertension, venous congestionUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20182018-07-01July 201810.1681/ASN.20180202241046-66731533-34502018-05-15T10:06:28-07:002018-07Journal of the American Society of NephrologyUp Front Matters29717951798
- Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic SyndromeBackground Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort. Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis-expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts. Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3′ untranslated region of HLA-DQB1 (P=9.3×10−23). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P=3.7×10−11) and in the 3′ untranslated region of BTNL2 (rs9348883, P=9.4×10−7) within introns of HCG23 and LOC101929163. These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1. Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification.10.1681/ASN.2017111185Thu, 14 Jun 2018 06:51:54 GMT-07:00Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic SyndromeBackground Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort. Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis-expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts. Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3′ untranslated region of HLA-DQB1 (P=9.3×10−23). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P=3.7×10−11) and in the 3′ untranslated region of BTNL2 (rs9348883, P=9.4×10−7) within introns of HCG23 and LOC101929163. These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1. Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification.Debiec, HannaDossier, ClaireLetouzé, EricGillies, Christopher E.Vivarelli, MarinaPutler, Rosemary K.Ars, ElisabetJacqz-Aigrain, EvelyneElie, ValeryColucci, ManuelaDebette, StéphanieAmouyel, PhilippeElalaoui, Siham C.Sefiani, AbdelazizDubois, ValérieSimon, TabassomeKretzler, MatthiasBallarin, JoseEmma, FrancescoSampson, Matthew G.Deschênes, GeorgesRonco, Pierre2018-06-14T06:51:54-07:00doi:10.1681/ASN.2017111185hwp:resource-id:jnephrol;29/7/2000American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, genetic renal disease, gene expression, focal segmental glomerulosclerosis, pediatrics, genome-wide association studyClinical ResearchClinical Researchresearch-article20182018-07-01July 201810.1681/ASN.20171111851046-66731533-34502018-06-14T06:51:54-07:002018-07Journal of the American Society of NephrologyClinical Research29772000179320131794
- Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney FailureBackground For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations. Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death. Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.10.1681/ASN.2017111179Fri, 13 Apr 2018 07:22:18 GMT-07:00Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney FailureBackground For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure. Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations. Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death. Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.Reichold, MarkusKlootwijk, Enriko D.Reinders, JoergOtto, Edgar A.Milani, MarioBroeker, CarstenLaing, ChrisWiesner, JuliaDevi, SulochanaZhou, WeibinSchmitt, RolandTegtmeier, InesSterner, ChristinaDoellerer, HannesRenner, KathrinOefner, Peter J.Dettmer, KatjaSimbuerger, Johann M.Witzgall, RalphStanescu, Horia C.Dumitriu, SimonaIancu, DanielaPatel, VakshaMozere, MonikaTekman, MehmetJaureguiberry, GracianaIssler, NaomiKesselheim, AnneWalsh, Stephen B.Gale, Daniel P.Howie, Alexander J.Martins, Joana R.Hall, Andrew M.Kasgharian, MichaelO’Brien, KevinFerreira, Carlos R.Atwal, Paldeep S.Jain, MahimHammers, AlexanderCharles-Edwards, GeoffreyChoe, Chi-UnIsbrandt, DirkCebrian-Serrano, AlbertoDavies, BenSandford, Richard N.Pugh, ChristopherKonecki, David S.Povey, SueBockenhauer, DetlefLichter-Konecki, UtaGahl, William A.Unwin, Robert J.Warth, RichardKleta, Robert2018-04-13T07:22:18-07:00doi:10.1681/ASN.2017111179hwp:resource-id:jnephrol;29/7/1849American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAGAT, mitochondriopathy, tubulopathy, protein deposits, fibrosisBasic ResearchBasic Researchresearch-article20182018-07-01July 201810.1681/ASN.20171111791046-66731533-34502018-04-13T07:22:18-07:002018-07Journal of the American Society of NephrologyBasic Research29771849178718581789
- The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal DiseasesMonoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a “benign” hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.10.1681/ASN.2017121319Fri, 27 Apr 2018 06:04:49 GMT-07:00The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal DiseasesMonoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a “benign” hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.Sethi, SanjeevRajkumar, S. VincentD’Agati, Vivette D.2018-04-27T06:04:49-07:00doi:10.1681/ASN.2017121319hwp:resource-id:jnephrol;29/7/1810American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, Renal pathology, multiple myelomaUp Front MattersReviewsUp Front MattersReviewsbrief-report20182018-07-01July 201810.1681/ASN.20171213191046-66731533-34502018-04-27T06:04:49-07:002018-07Journal of the American Society of NephrologyUp Front Matters29718101823
- Sirtuins in Renal Health and DiseaseSirtuins belong to an evolutionarily conserved family of NAD+-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1–7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress. Here, we provide an overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology. This review also details progress made in understanding the effect of sirtuins in the pathophysiology of chronic and acute kidney diseases, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets. In this context, the current pharmacologic approaches to enhancing the activity of SIRT1 and SIRT3 will be discussed.10.1681/ASN.2017111218Mon, 30 Apr 2018 07:14:45 GMT-07:00Sirtuins in Renal Health and DiseaseSirtuins belong to an evolutionarily conserved family of NAD+-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1–7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress. Here, we provide an overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology. This review also details progress made in understanding the effect of sirtuins in the pathophysiology of chronic and acute kidney diseases, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets. In this context, the current pharmacologic approaches to enhancing the activity of SIRT1 and SIRT3 will be discussed.Morigi, MarinaPerico, LucaBenigni, Ariela2018-04-30T07:14:45-07:00doi:10.1681/ASN.2017111218hwp:resource-id:jnephrol;29/7/1799American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologySirtuins, acute renal failure, chronic kidney disease, mitochondria, metabolism, sirtuin activatorsUp Front MattersReviewsUp Front MattersReviewsreview-article20182018-07-01July 201810.1681/ASN.20171112181046-66731533-34502018-04-30T07:14:45-07:002018-07Journal of the American Society of NephrologyUp Front Matters29717991809
- Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal TransplantationBackground Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin. Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, −1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, −1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events. Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.10.1681/ASN.2018010009Fri, 11 May 2018 06:12:23 GMT-07:00Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal TransplantationBackground Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin. Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, −1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, −1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events. Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.Pascual, JulioBerger, Stefan P.Witzke, OliverTedesco, HelioMulgaonkar, ShamkantQazi, YasirChadban, StevenOppenheimer, FedericoSommerer, ClaudiaOberbauer, RainerWatarai, YoshihikoLegendre, ChristopheCitterio, FrancoHenry, MitchellSrinivas, Titte R.Luo, Wen-LinMarti, AnaMariaBernhardt, PeterVincenti, Flavio,Jardine, AlanFriede, TimMaldonado, RafaelMassari, PabloAleman, SilvinaMaurich, SilviaGaite, Luis E.Raffaele, PabloImperiali, NoraCampbell, ScottChadban, StevenHughes, PeterIrish, AshleyKanellis, JohnLim, WaiO’Connell, Philip JRuss, GraemeEndre, ZoltanMount, PeterHengster, PaulNeudorfer, PeterOberbauer, RainerPratschke, JohannKuypers, DirkBosmans, Jean-LouisBroeders, Emine N.Weekers, LaurentSilva, Helio TedescoNeto, Elias D.Garcia, Valter D.Dimitrov, Emil P.Kompatzki, AlvaroBenavides, CarlosSchweineberg, JohannaJukic, Nikolina BasicKnotek, MladenRacki, SanjinViklicky, OndrejBakr, M.A.Legendre, ChristopheCassuto, ElisabethPernin, VincentVuiblet, VincentBuchler, MathiasSommerer, ClaudiaWeithofer, PeterRath, ThomasWitzke, Olivervan der Giet, MarkusArns, WolfgangRenders, LutzHabicht, AntjeSeehofer, DanielBanas, BernhardLehner, FrankPratschke, JohannBoletis, IoannisGoumenos, DimitriosPapanikolaou, VasileiosDrakopoulos, SpyrosKhullar, DineshGuptha, VeerbhadraJacob, ShibuAlmeida, Alan FernandesMor, EytanNakache, RichardCarmellini, MarioRigotti, PaoloColussi, GiacomoTisone, GiuseppeTodeschini, PaolaBiancone, LuigiCitterio, FrancoCantaluppi, VincenzoGesualdo, LoretoMaggiore, UmbertoWatarai, YoshihikoAkutsu, NaotakeKenmochi, TakashiHan, Duck JongKim, Myoung SooKim, Sung JooAlOtaibi, TorkiChelala, DaniaAbou Zeinab, HilalJaber, KhalilKutty, Ghazali AhmadWong, Hin SengRamos, Francisco Javier Monteonde Fijter, J.W.Berger, Stefan P.Bemelman, F.J.van Zuilen, A.D.Hilbrands, L.Christiaans, M.H.L.Hartmann, AndersDanguilan, RominaAmante, Angel JoaquinCiechanowski, KazimierzGlyda, MaciejKarczewski, MarekDebska-Slizien, AlicjaNolasco, FernandoGuerra, JoseSantos, JoanaMatias, Patricia JoaoFigueiredo, ArnaldoMoysyuk, Yan G.Pinchuk, Aleksey V.Aleksandrov, Ilya V.Zagainov, Vladimir E.Boretskaya, Elena I.Medvedev, Vladimir L.Attia, AshrafHabhab, WaelBugami, MetebVavic, NevenMitic, IgorPaunovic, GoranKee, TerenceBaltesova, TatianaLackova, EvaZilinska, ZuzanaDedinska, IvanaArnol, MihaMuller, ElmiPascual, JulioOppenheimer, FedericoSancho, AsuncionDalmau, Alex GutierrezMarrero, DomingoCruzado, Josep M.Belmonte, Amado AndresSan Millan, Juan Carlos RuizOsuna, AntonioFernandez, AnaWennberg, Larsvon Zur Muhlen, BengtGustafsson, BengtHuynh-Do, UyenTsai, Meng-KunWu, Ming JuChou, Tsung ChingRuangkanchanasetr, PrajejBunnag, SakarnIngsathit, AtipornTurmen, AydinCelik, Ahmet V.Kocak, HuseyinWiseman, AlexanderGauthier, PhillippeShihab, FuadBynon, StevensonFischbach, BernardKlintmalm, Goran B.Knight, RichardBrayman, Kenneth L.Wellen, JasonJordan, Stanley J.Qazi, YasirCotton, RonaldPeddi, VenkatLeeser, DavidAkoad, Mohamed E.Mulgaonkar, ShamkantPavlakis, MarthaGohh, ReginaldBratton, CharlesElias, NahelSudan, DebraWaybill, MaryHong, JohnnyNorman, SilasTzvetanov, IvoKim, DeanHenry, MitchellRogers, JeffreySanthanakrishnan, ChandrasekarLeca, NicolaeKozlowski, TomaszVincenti, FlavioAkalin, EnverKew, Clifton E.Shaffer, DavidKayler, Liise KSteinberg, StevenFlechner, Stuart M.Hricik, Donaldde Vera, MichaelMandelbrot, Didier2018-05-11T06:12:23-07:00doi:10.1681/ASN.2018010009hwp:resource-id:jnephrol;29/7/1979American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyeverolimus, calcineurin inhibitor, kidney transplantation, efficacy graft, function, randomizedClinical ResearchClinical Researchresearch-article20182018-07-01July 201810.1681/ASN.20180100091046-66731533-34502018-05-11T06:12:23-07:002018-07Journal of the American Society of NephrologyClinical Research29771979179119911792
- This Month’s Highlights10.1681/ASN.2018030250Mon, 30 Apr 2018 01:05:26 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2018-04-30T13:05:26-07:00doi:10.1681/ASN.2018030250hwp:resource-id:jnephrol;29/5/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-05-01May 201810.1681/ASN.20180302501046-66731533-34502018-04-30T13:05:26-07:002018-05Journal of the American Society of NephrologyThis Month’s Highlights295ii
- Insights into CKD from Metabolite GWAS10.1681/ASN.2018030291Tue, 10 Apr 2018 08:02:06 GMT-07:00Insights into CKD from Metabolite GWASLiu, LiliKiryluk, Krzysztof2018-04-10T08:02:06-07:00doi:10.1681/ASN.2018030291hwp:resource-id:jnephrol;29/5/1349American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolites, GWAS, chronic kidney disease, human genetics, QTL, metabolomeUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-05-01May 201810.1681/ASN.20180302911046-66731533-34502018-04-10T08:02:06-07:002018-05Journal of the American Society of NephrologyUp Front Matters29551349151313511524
- Repairing the GBM Step by Step10.1681/ASN.2018030294Thu, 12 Apr 2018 05:06:13 GMT-07:00Repairing the GBM Step by StepTufro, Alda2018-04-12T05:06:13-07:00doi:10.1681/ASN.2018030294hwp:resource-id:jnephrol;29/5/1346American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-05-01May 201810.1681/ASN.20180302941046-66731533-34502018-04-12T05:06:13-07:002018-05Journal of the American Society of NephrologyUp Front Matters29551346142613471436
- The Authors Reply10.1681/ASN.2017121242Fri, 09 Mar 2018 06:45:31 GMT-08:00The Authors ReplyKumar, VivekJha, Vivekanand2018-03-09T06:45:31-08:00doi:10.1681/ASN.2017121242hwp:resource-id:jnephrol;29/5/1579American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Vitamin D, cardiovascular disease, endotheliumLetters to the EditorLetters to the Editorletter20182018-05-01May 201810.1681/ASN.20171212421046-66731533-34502018-03-09T06:45:31-08:002018-05Journal of the American Society of NephrologyLetters to the Editor29551579157815801579
- Studying the Effect of Vitamin D Supplementation on Vascular Function in CKD: A Work in Progress10.1681/ASN.2017111222Fri, 09 Mar 2018 06:45:31 GMT-08:00Studying the Effect of Vitamin D Supplementation on Vascular Function in CKD: A Work in ProgressNwaohiri, Nnamdi Kelechi2018-03-09T06:45:31-08:00doi:10.1681/ASN.2017111222hwp:resource-id:jnephrol;29/5/1578American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyVitamin D, CKD, Vascular functionLetters to the EditorLetters to the Editorletter20182018-05-01May 201810.1681/ASN.20171112221046-66731533-34502018-03-09T06:45:31-08:002018-05Journal of the American Society of NephrologyLetters to the Editor29551578157915791580
- Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport MechanismsBackground The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions. Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD. Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios. These included associations already known from population-based studies. Additional findings included an association for the uremic toxin putrescine and variants upstream of an enzyme catalyzing the oxidative deamination of polyamines (AOC1, P-min=2.4×10−12), a relatively high carrier frequency (2%) for rare deleterious missense variants in ACADM that are collectively associated with serum ratios of medium-chain acylcarnitines (P-burden=6.6×10−16), and associations of a common variant in SLC7A9 with several ratios of lysine to neutral amino acids in urine, including the lysine/glutamine ratio (P=2.2×10−23). The associations of this SLC7A9 variant with ratios of lysine to specific neutral amino acids were much stronger than the association with lysine concentration alone. This finding is consistent with SLC7A9 functioning as an exchanger of urinary cationic amino acids against specific intracellular neutral amino acids at the apical membrane of proximal tubular cells. Conclusions Metabolomic indices of specific kidney functions in genetic studies may provide insight into human renal physiology.10.1681/ASN.2017101099Thu, 15 Mar 2018 07:06:24 GMT-07:00Genome-Wide Association Studies of Metabolites in Patients with CKD Identify Multiple Loci and Illuminate Tubular Transport MechanismsBackground The kidneys have a central role in the generation, turnover, transport, and excretion of metabolites, and these functions can be altered in CKD. Genetic studies of metabolite concentrations can identify proteins performing these functions. Methods We conducted genome-wide association studies and aggregate rare variant tests of the concentrations of 139 serum metabolites and 41 urine metabolites, as well as their pairwise ratios and fractional excretions in up to 1168 patients with CKD. Results After correction for multiple testing, genome-wide significant associations were detected for 25 serum metabolites, two urine metabolites, and 259 serum and 14 urinary metabolite ratios. These included associations already known from population-based studies. Additional findings included an association for the uremic toxin putrescine and variants upstream of an enzyme catalyzing the oxidative deamination of polyamines (AOC1, P-min=2.4×10−12), a relatively high carrier frequency (2%) for rare deleterious missense variants in ACADM that are collectively associated with serum ratios of medium-chain acylcarnitines (P-burden=6.6×10−16), and associations of a common variant in SLC7A9 with several ratios of lysine to neutral amino acids in urine, including the lysine/glutamine ratio (P=2.2×10−23). The associations of this SLC7A9 variant with ratios of lysine to specific neutral amino acids were much stronger than the association with lysine concentration alone. This finding is consistent with SLC7A9 functioning as an exchanger of urinary cationic amino acids against specific intracellular neutral amino acids at the apical membrane of proximal tubular cells. Conclusions Metabolomic indices of specific kidney functions in genetic studies may provide insight into human renal physiology.Li, YongSekula, PeggyWuttke, MatthiasWahrheit, JudithHausknecht, BirgitSchultheiss, Ulla T.Gronwald, WolframSchlosser, PascalTucci, SaraEkici, Arif B.Spiekerkoetter, UteKronenberg, FlorianEckardt, Kai-UweOefner, Peter J.Köttgen, Anna,2018-03-15T07:06:24-07:00doi:10.1681/ASN.2017101099hwp:resource-id:jnephrol;29/5/1513American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, genome-wide association studies, metabolites, renal tubular epithelial cellsClinical ResearchClinical Researchresearch-article20182018-05-01May 201810.1681/ASN.20171010991046-66731533-34502018-03-15T07:06:24-07:002018-05Journal of the American Society of NephrologyClinical Research29551513134915241351
- Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct ModelsBackground FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury. Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes. Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.10.1681/ASN.2017050475Fri, 23 Mar 2018 05:56:29 GMT-07:00Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct ModelsBackground FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury. Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes. Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.Embry, Addie E.Liu, ZhenanHenderson, Joel M.Byfield, F. JeffersonLiu, LipingYoon, JoonhoWu, ZhenzhenCruz, KatrinaMoradi, SaraGillombardo, C. BartonHussain, Rihanna Z.Doelger, RichardStuve, OlafChang, Audrey N.Janmey, Paul A.Bruggeman, Leslie A.Miller, R. Tyler2018-03-23T05:56:29-07:00doi:10.1681/ASN.2017050475hwp:resource-id:jnephrol;29/5/1501American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, biophysics, renal fibrosis, glomerulusBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20170504751046-66731533-34502018-03-23T05:56:29-07:002018-05Journal of the American Society of NephrologyBasic Research29515011512
- Antibodies Can Extenuate Polyomavirus Infections10.1681/ASN.2017111211Wed, 21 Feb 2018 06:32:22 GMT-08:00Antibodies Can Extenuate Polyomavirus InfectionsNickeleit, VolkerSingh, Harsharan K.Rivier, Lauraine H.2018-02-21T06:32:22-08:00doi:10.1681/ASN.2017111211hwp:resource-id:jnephrol;29/5/1577American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypolyomavirus, neutralizing antibodies, transplantationLetters to the EditorLetters to the Editorletter20182018-05-01May 201810.1681/ASN.20171112111046-66731533-34502018-02-21T06:32:22-08:002018-05Journal of the American Society of NephrologyLetters to the Editor29551577157815781578
- JASN this Month: Something Old, Something New10.1681/ASN.2018030278Wed, 04 Apr 2018 06:47:32 GMT-07:00JASN this Month: Something Old, Something NewBriggs, JosephinePalevsky, PaulKnepper, Mark2018-04-04T06:47:32-07:00doi:10.1681/ASN.2018030278hwp:resource-id:jnephrol;29/5/1345American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyJASN, editorial, newUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-05-01May 201810.1681/ASN.20180302781046-66731533-34502018-04-04T06:47:32-07:002018-05Journal of the American Society of NephrologyUp Front Matters29513451346
- Using Large Datasets to Understand CKD10.1681/ASN.2018030288Wed, 11 Apr 2018 04:32:52 GMT-07:00Using Large Datasets to Understand CKDDrysdale, Thomas A.2018-04-11T04:32:52-07:00doi:10.1681/ASN.2018030288hwp:resource-id:jnephrol;29/5/1351American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyBioinformatics, SHROOM3, chronic kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-05-01May 201810.1681/ASN.20180302881046-66731533-34502018-04-11T04:32:52-07:002018-05Journal of the American Society of NephrologyUp Front Matters29551351152513531535
- The Authors Reply10.1681/ASN.2018010027Wed, 21 Feb 2018 06:32:21 GMT-08:00The Authors ReplySolis, MorganeVelay, AurélieMoulin, BrunoCaillard, SophieFafi-Kremer, Samira2018-02-21T06:32:21-08:00doi:10.1681/ASN.2018010027hwp:resource-id:jnephrol;29/5/1578-aAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypolyomavirus, antibodies, infectionLetters to the EditorLetters to the Editorletter20182018-05-01May 201810.1681/ASN.20180100271046-66731533-34502018-02-21T06:32:21-08:002018-05Journal of the American Society of NephrologyLetters to the Editor29551578157715781578
- Gpr97 Exacerbates AKI by Mediating Sema3A SignalingBackground G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiologic and pathophysiologic roles in the regulation of renal function. We investigated the role of Gpr97, a newly identified member of the adhesion GPCR family, in AKI. Methods AKI was induced by ischemia–reperfusion or cisplatin treatment in Gpr97-deficient mice. We assessed renal injury in these models and in patients with acute tubular necrosis by histologic examination, and we conducted microarray analysis and in vitro assays to determine the molecular mechanisms of Gpr97 function. Results Gpr97 was upregulated in the kidneys from mice with AKI and patients with biopsy-proven acute tubular necrosis compared with healthy controls. In AKI models, Gpr97-deficient mice had significantly less renal injury and inflammation than wild-type mice. Gpr97 deficiency also attenuated the AKI-induced expression of semaphorin 3A (Sema3A), a potential early diagnostic biomarker of renal injury. In NRK-52E cells subjected to oxygen–glucose deprivation, siRNA-mediated knockdown of Gpr97 further increased the expression of survivin and phosphorylated STAT3 and reduced toll-like receptor 4 expression. Cotreatment with recombinant murine Sema3A protein counteracted these effects. Finally, additional in vivo and in vitro studies, including electrophoretic mobility shift assays and luciferase reporter assays, showed that Gpr97 deficiency attenuates ischemia–reperfusion-induced expression of the RNA-binding protein human antigen R, which post-transcriptionally regulates Sema3A expression. Conclusions Gpr97 is an important mediator of AKI, and pharmacologic targeting of Gpr97-mediated Sema3A signaling at multiple levels may provide a novel approach for the treatment of AKI.10.1681/ASN.2017080932Mon, 12 Mar 2018 05:59:02 GMT-07:00Gpr97 Exacerbates AKI by Mediating Sema3A SignalingBackground G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiologic and pathophysiologic roles in the regulation of renal function. We investigated the role of Gpr97, a newly identified member of the adhesion GPCR family, in AKI. Methods AKI was induced by ischemia–reperfusion or cisplatin treatment in Gpr97-deficient mice. We assessed renal injury in these models and in patients with acute tubular necrosis by histologic examination, and we conducted microarray analysis and in vitro assays to determine the molecular mechanisms of Gpr97 function. Results Gpr97 was upregulated in the kidneys from mice with AKI and patients with biopsy-proven acute tubular necrosis compared with healthy controls. In AKI models, Gpr97-deficient mice had significantly less renal injury and inflammation than wild-type mice. Gpr97 deficiency also attenuated the AKI-induced expression of semaphorin 3A (Sema3A), a potential early diagnostic biomarker of renal injury. In NRK-52E cells subjected to oxygen–glucose deprivation, siRNA-mediated knockdown of Gpr97 further increased the expression of survivin and phosphorylated STAT3 and reduced toll-like receptor 4 expression. Cotreatment with recombinant murine Sema3A protein counteracted these effects. Finally, additional in vivo and in vitro studies, including electrophoretic mobility shift assays and luciferase reporter assays, showed that Gpr97 deficiency attenuates ischemia–reperfusion-induced expression of the RNA-binding protein human antigen R, which post-transcriptionally regulates Sema3A expression. Conclusions Gpr97 is an important mediator of AKI, and pharmacologic targeting of Gpr97-mediated Sema3A signaling at multiple levels may provide a novel approach for the treatment of AKI.Fang, WeiWang, ZiyingLi, QuanxinWang, XiaojieZhang, YanSun, YuTang, WeiMa, ChunhongSun, JinpengLi, NingjunYi, Fan2018-03-12T05:59:02-07:00doi:10.1681/ASN.2017080932hwp:resource-id:jnephrol;29/5/1475American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, renal cell biology, ischemia-reperfusion, tubular epithelium, cisplatin nephrotoxicity, renal tubular epithelial cellsBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20170809321046-66731533-34502018-03-12T05:59:02-07:002018-05Journal of the American Society of NephrologyBasic Research29514751489
- The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous NephropathyBackground Thrombospondin type 1 domain–containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (MN). However, the THSD7A epitopes targeted by patient autoantibodies are unknown. Methods We performed an in silico analysis of the THSD7A multidomain structure, expressed the folded domains in HEK293 cells, and tested for domain reactivity with 31 serum samples from patients with THSD7A-associated MN using Western and native blotting. Immunogenicity of the antigen domains was further investigated by cDNA immunization of rabbits and mice. Results We characterized the extracellular topology of THSD7A as a tandem string of 21 thrombospondin type 1 domains. Overall, 28 serum samples (90%) recognized multiple epitope domains along the molecule. Detailed epitope mapping revealed that the complex consisting of the first and second N-terminal domains (amino acids 48–192) was recognized by 27 of 31 patient serum samples (87%). Serum recognizing one or two epitope domains showed lower anti-THSD7A antibody levels than serum recognizing three or more epitope domains. During follow-up, a loss of epitope recognition was observed in seven of 16 patients, and it was accompanied by decreasing antibody levels and remission of proteinuria. In four of 16 patients, epitope recognition patterns changed during follow-up. Notably, immunization experiments in rabbits and mice revealed that induced antibodies, like patient autoantibodies, preferentially bound to the most N-terminal domains of THSD7A. Conclusions Our data show that the immune response in THSD7A-associated MN is polyreactive and that autoantibodies predominantly target the most N-terminal part of THSD7A.10.1681/ASN.2017070805Mon, 19 Mar 2018 06:16:42 GMT-07:00The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous NephropathyBackground Thrombospondin type 1 domain–containing 7A (THSD7A) has been identified as a pathogenic autoantigen in membranous nephropathy (MN). However, the THSD7A epitopes targeted by patient autoantibodies are unknown. Methods We performed an in silico analysis of the THSD7A multidomain structure, expressed the folded domains in HEK293 cells, and tested for domain reactivity with 31 serum samples from patients with THSD7A-associated MN using Western and native blotting. Immunogenicity of the antigen domains was further investigated by cDNA immunization of rabbits and mice. Results We characterized the extracellular topology of THSD7A as a tandem string of 21 thrombospondin type 1 domains. Overall, 28 serum samples (90%) recognized multiple epitope domains along the molecule. Detailed epitope mapping revealed that the complex consisting of the first and second N-terminal domains (amino acids 48–192) was recognized by 27 of 31 patient serum samples (87%). Serum recognizing one or two epitope domains showed lower anti-THSD7A antibody levels than serum recognizing three or more epitope domains. During follow-up, a loss of epitope recognition was observed in seven of 16 patients, and it was accompanied by decreasing antibody levels and remission of proteinuria. In four of 16 patients, epitope recognition patterns changed during follow-up. Notably, immunization experiments in rabbits and mice revealed that induced antibodies, like patient autoantibodies, preferentially bound to the most N-terminal domains of THSD7A. Conclusions Our data show that the immune response in THSD7A-associated MN is polyreactive and that autoantibodies predominantly target the most N-terminal part of THSD7A.Seifert, LarissaHoxha, ElionEichhoff, Anna M.Zahner, GuntherDehde, SilkeReinhard, LindaKoch-Nolte, FriedrichStahl, Rolf A.K.Tomas, Nicola M.2018-03-19T06:16:42-07:00doi:10.1681/ASN.2017070805hwp:resource-id:jnephrol;29/5/1536American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, membranous nephropathy, clinical immunologyClinical ResearchClinical Researchresearch-article20182018-05-01May 201810.1681/ASN.20170708051046-66731533-34502018-03-19T06:16:42-07:002018-05Journal of the American Society of NephrologyClinical Research29515361548
- Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK PathwayBackground B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear. Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy. Results Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1–promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy. Conclusions Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.10.1681/ASN.2017090993Fri, 30 Mar 2018 07:04:25 GMT-07:00Nephrin-Binding Ephrin-B1 at the Slit Diaphragm Controls Podocyte Function through the JNK PathwayBackground B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear. Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy. Results Compared with controls, ephrin-B1 conditional knockout mice displayed altered podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Ephrin-B1 expressed in HEK293 cells immunoprecipitated with nephrin, which required the basal regions of the extracellular domains of both proteins. Treatment of cells with an anti-nephrin antibody promoted the phosphorylation of nephrin and ephrin-B1. However, phosphorylation of ephrin-B1 did not occur in cells expressing a mutant nephrin lacking the ephrin-B1 binding site or in cells treated with an Src kinase inhibitor. The phosphorylation of ephrin-B1 enhanced the phosphorylation of nephrin and promoted the phosphorylation of c-Jun N-terminal kinase (JNK), which was required for ephrin-B1–promoted cell motility in wound-healing assays. Notably, phosphorylated JNK was detected in the glomeruli of control mice but not ephrin-B1 conditional knockout mice. In rats, the phosphorylation of ephrin-B1, JNK, and nephrin occurred in the early phase (24 hours) of anti-nephrin antibody-induced nephropathy. Conclusions Through interactions with nephrin, ephrin-B1 maintains the structure and barrier function of the slit diaphragm. Moreover, phosphorylation of ephrin-B1 and, consequently, JNK are involved in the development of podocyte injury.Fukusumi, YoshiyasuZhang, YingYamagishi, RyoheiOda, KanakoWatanabe, ToruMatsui, KatsuyukiKawachi, Hiroshi2018-03-30T07:04:25-07:00doi:10.1681/ASN.2017090993hwp:resource-id:jnephrol;29/5/1462American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycell adhesion, Cell Signaling, glomerular filtration barrier, nephrin, podocyte, proteinuriaBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20170909931046-66731533-34502018-03-30T07:04:25-07:002018-05Journal of the American Society of NephrologyBasic Research29514621474
- Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKDBackground Interpreting genetic variants is one of the greatest challenges impeding analysis of rapidly increasing volumes of genomic data from patients. For example, SHROOM3 is an associated risk gene for CKD, yet causative mechanism(s) of SHROOM3 allele(s) are unknown. Methods We used our analytic pipeline that integrates genetic, computational, biochemical, CRISPR/Cas9 editing, molecular, and physiologic data to characterize coding and noncoding variants to study the human SHROOM3 risk locus for CKD. Results We identified a novel SHROOM3 transcriptional start site, which results in a shorter isoform lacking the PDZ domain and is regulated by a common noncoding sequence variant associated with CKD (rs17319721, allele frequency: 0.35). This variant disrupted allele binding to the transcription factor TCF7L2 in podocyte cell nuclear extracts and altered transcription levels of SHROOM3 in cultured cells, potentially through the loss of repressive looping between rs17319721 and the novel start site. Although common variant mechanisms are of high utility, sequencing is beginning to identify rare variants involved in disease; therefore, we used our biophysical tools to analyze an average of 112,849 individual human genome sequences for rare SHROOM3 missense variants, revealing 35 high-effect variants. The high-effect alleles include a coding variant (P1244L) previously associated with CKD (P=0.01, odds ratio=7.95; 95% CI, 1.53 to 41.46) that we find to be present in East Asian individuals at an allele frequency of 0.0027. We determined that P1244L attenuates the interaction of SHROOM3 with 14–3-3, suggesting alterations to the Hippo pathway, a known mediator of CKD. Conclusions These data demonstrate multiple new SHROOM3-dependent genetic/molecular mechanisms that likely affect CKD.10.1681/ASN.2017080856Fri, 23 Feb 2018 11:41:35 GMT-08:00Characterization of Coding/Noncoding Variants for SHROOM3 in Patients with CKDBackground Interpreting genetic variants is one of the greatest challenges impeding analysis of rapidly increasing volumes of genomic data from patients. For example, SHROOM3 is an associated risk gene for CKD, yet causative mechanism(s) of SHROOM3 allele(s) are unknown. Methods We used our analytic pipeline that integrates genetic, computational, biochemical, CRISPR/Cas9 editing, molecular, and physiologic data to characterize coding and noncoding variants to study the human SHROOM3 risk locus for CKD. Results We identified a novel SHROOM3 transcriptional start site, which results in a shorter isoform lacking the PDZ domain and is regulated by a common noncoding sequence variant associated with CKD (rs17319721, allele frequency: 0.35). This variant disrupted allele binding to the transcription factor TCF7L2 in podocyte cell nuclear extracts and altered transcription levels of SHROOM3 in cultured cells, potentially through the loss of repressive looping between rs17319721 and the novel start site. Although common variant mechanisms are of high utility, sequencing is beginning to identify rare variants involved in disease; therefore, we used our biophysical tools to analyze an average of 112,849 individual human genome sequences for rare SHROOM3 missense variants, revealing 35 high-effect variants. The high-effect alleles include a coding variant (P1244L) previously associated with CKD (P=0.01, odds ratio=7.95; 95% CI, 1.53 to 41.46) that we find to be present in East Asian individuals at an allele frequency of 0.0027. We determined that P1244L attenuates the interaction of SHROOM3 with 14–3-3, suggesting alterations to the Hippo pathway, a known mediator of CKD. Conclusions These data demonstrate multiple new SHROOM3-dependent genetic/molecular mechanisms that likely affect CKD.Prokop, Jeremy W.Yeo, Nan CherOttmann, ChristianChhetri, Surya B.Florus, Kacie L.Ross, Emily J.Sosonkina, NadiyaLink, Brian A.Freedman, Barry I.Coppola, Candice J.McDermott-Roe, ChrisLeysen, SeppeMilroy, Lech-GustavMeijer, Femke A.Geurts, Aron M.Rauscher, Frank J.Ramaker, RyneFlister, Michael J.Jacob, Howard J.Mendenhall, Eric M.Lazar, Jozef2018-02-23T11:41:35-08:00doi:10.1681/ASN.2017080856hwp:resource-id:jnephrol;29/5/1525American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologySHROOM3, GWAS, Genomic Variants, CRISPR/Cas9, TCF7L2, Rare VariantsClinical ResearchClinical Researchresearch-article20182018-05-01May 201810.1681/ASN.20170808561046-66731533-34502018-02-23T11:41:35-08:002018-05Journal of the American Society of NephrologyClinical Research29551525135115351353
- Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration10.1681/ASN.2017101069Fri, 23 Feb 2018 11:41:35 GMT-08:00Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular RegenerationSchiessl, Ina MariaGrill, AlexandraFremter, KatharinaSteppan, DominikHellmuth, Maj-KristinaCastrop, Hayo2018-02-23T11:41:35-08:00doi:10.1681/ASN.2017101069hwp:resource-id:jnephrol;29/5/1383American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyproliferation, renal stem cell, renal proximal tubule cell, tubular-interstitial crosstalkBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20171010691046-66731533-34502018-02-23T11:41:35-08:002018-05Journal of the American Society of NephrologyBasic Research29513831396
- Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian TubuleBackground With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule. Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux. Results In vitro, autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased. In conditions in which tubule intracellular chloride concentration decreased from 30 to 15 mM as measured using a transgenic sensor, Drosophila WNK activity acutely increased. Drosophila WNK activity in tubules also increased or decreased when bath potassium concentration decreased or increased, respectively. However, a mutation that reduces chloride sensitivity of Drosophila WNK failed to alter transepithelial ion transport in 30 mM chloride. We, therefore, examined a role for Mo25. In in vitro kinase assays, Drosophila Mo25 enhanced the activity of the Drosophila WNK downstream kinase Fray, the fly homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1). Knockdown of Drosophila Mo25 in the Malpighian tubule decreased transepithelial ion flux under stimulated but not basal conditions. Finally, whereas overexpression of wild-type Drosophila WNK, with or without Drosophila Mo25, did not affect transepithelial ion transport, Drosophila Mo25 overexpressed with chloride-insensitive Drosophila WNK increased ion flux. Conclusions Cooperative interactions between chloride and Mo25 regulate WNK signaling in a transporting renal epithelium.10.1681/ASN.2017101091Fri, 30 Mar 2018 07:04:24 GMT-07:00Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian TubuleBackground With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule. Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux. Results In vitro, autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased. In conditions in which tubule intracellular chloride concentration decreased from 30 to 15 mM as measured using a transgenic sensor, Drosophila WNK activity acutely increased. Drosophila WNK activity in tubules also increased or decreased when bath potassium concentration decreased or increased, respectively. However, a mutation that reduces chloride sensitivity of Drosophila WNK failed to alter transepithelial ion transport in 30 mM chloride. We, therefore, examined a role for Mo25. In in vitro kinase assays, Drosophila Mo25 enhanced the activity of the Drosophila WNK downstream kinase Fray, the fly homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1). Knockdown of Drosophila Mo25 in the Malpighian tubule decreased transepithelial ion flux under stimulated but not basal conditions. Finally, whereas overexpression of wild-type Drosophila WNK, with or without Drosophila Mo25, did not affect transepithelial ion transport, Drosophila Mo25 overexpressed with chloride-insensitive Drosophila WNK increased ion flux. Conclusions Cooperative interactions between chloride and Mo25 regulate WNK signaling in a transporting renal epithelium.Sun, QifeiWu, YipinJonusaite, SimaPleinis, John M.Humphreys, John M.He, HaixiaSchellinger, Jeffrey N.Akella, RadhaStenesen, DrewKrämer, HelmutGoldsmith, Elizabeth J.Rodan, Aylin R.2018-03-30T07:04:24-07:00doi:10.1681/ASN.2017101091hwp:resource-id:jnephrol;29/5/1449American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney, hypertension, hypokalemia, Cab39, Malpighian tubule, NKCCBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20171010911046-66731533-34502018-03-30T07:04:24-07:002018-05Journal of the American Society of NephrologyBasic Research29551449134714611349
- Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPβ in Vasopressin-Sensitive Collecting Duct CellsBackground Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene (Aqp2). Methods To identify enhancer regions likely to be involved in the regulation of Aqp2 and other principal cell–specific genes, we used several next generation DNA-sequencing techniques in a well characterized cultured cell model of collecting duct principal cells (mpkCCD). To locate enhancers, we performed the assay for transposase-accessible chromatin using sequencing (ATAC-Seq) to identify accessible regions of DNA and integrated the data with data generated by chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP-Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation, and RNA polymerase II. Results We identified two high-probability enhancers centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start site. Motif analysis of these regions and the Aqp2 promoter identified several potential transcription factor binding sites, including sites for two b-ZIP transcription factors: CCAAT/enhancer binding protein-β (C/EBPβ) and cAMP-responsive element binding protein (CREB). To identify genomic binding sites for both, we conducted ChIP-Seq using well characterized antibodies. In the presence of vasopressin, C/EBPβ, a pioneer transcription factor critical to cell-specific gene expression, bound strongly at the identified enhancer downstream from Aqp2. However, over multiple replicates, we found no detectable CREB binding sites within 390 kb of Aqp2. Thus, any role for CREB in the regulation of Aqp2 gene transcription is likely to be indirect. Conclusions The analysis identified two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and showed C/EBPβ (but not CREB) binding.10.1681/ASN.2017050545Fri, 23 Mar 2018 05:56:29 GMT-07:00Genome-Wide Mapping of DNA Accessibility and Binding Sites for CREB and C/EBPβ in Vasopressin-Sensitive Collecting Duct CellsBackground Renal water excretion is controlled by vasopressin, in part through regulation of the transcription of the aquaporin-2 gene (Aqp2). Methods To identify enhancer regions likely to be involved in the regulation of Aqp2 and other principal cell–specific genes, we used several next generation DNA-sequencing techniques in a well characterized cultured cell model of collecting duct principal cells (mpkCCD). To locate enhancers, we performed the assay for transposase-accessible chromatin using sequencing (ATAC-Seq) to identify accessible regions of DNA and integrated the data with data generated by chromatin immunoprecipitation followed by next generation DNA-sequencing (ChIP-Seq) for CCCTC binding factor (CTCF) binding, histone H3 lysine-27 acetylation, and RNA polymerase II. Results We identified two high-probability enhancers centered 81 kb upstream and 5.8 kb downstream from the Aqp2 transcriptional start site. Motif analysis of these regions and the Aqp2 promoter identified several potential transcription factor binding sites, including sites for two b-ZIP transcription factors: CCAAT/enhancer binding protein-β (C/EBPβ) and cAMP-responsive element binding protein (CREB). To identify genomic binding sites for both, we conducted ChIP-Seq using well characterized antibodies. In the presence of vasopressin, C/EBPβ, a pioneer transcription factor critical to cell-specific gene expression, bound strongly at the identified enhancer downstream from Aqp2. However, over multiple replicates, we found no detectable CREB binding sites within 390 kb of Aqp2. Thus, any role for CREB in the regulation of Aqp2 gene transcription is likely to be indirect. Conclusions The analysis identified two enhancer regions pertinent to transcriptional regulation of the Aqp2 gene and showed C/EBPβ (but not CREB) binding.Jung, Hyun JunRaghuram, ViswanathanLee, Jae WookKnepper, Mark A.2018-03-23T05:56:29-07:00doi:10.1681/ASN.2017050545hwp:resource-id:jnephrol;29/5/1490American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyChIP-Seq, transcription factors, water transport, water channels, aquaporin-2, ATAC-SeqBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20170505451046-66731533-34502018-03-23T05:56:29-07:002018-05Journal of the American Society of NephrologyBasic Research29514901500
- Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson SyndromeBackground Laminin α5β2γ1 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of Lamb2 mutant mice and restore glomerular permselectivity. Methods We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of Lamb2−/− pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture. Results Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM. Conclusions These studies show that GBM composition and function can be altered in vivo via vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired.10.1681/ASN.2017060690Thu, 22 Feb 2018 07:39:40 GMT-08:00Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson SyndromeBackground Laminin α5β2γ1 (LM-521) is a major component of the GBM. Mutations in LAMB2 that prevent LM-521 synthesis and/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of Lamb2 mutant mice and restore glomerular permselectivity. Methods We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of Lamb2−/− pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture. Results Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM. Conclusions These studies show that GBM composition and function can be altered in vivo via vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired.Lin, Meei-HuaMiller, Joseph B.Kikkawa, YamatoSuleiman, Hani Y.Tryggvason, KarlHodges, Bradley L.Miner, Jeffrey H.2018-02-22T07:39:40-08:00doi:10.1681/ASN.2017060690hwp:resource-id:jnephrol;29/5/1426American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration barrier, podocyte, laminin, glomerular basement membraneBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20170606901046-66731533-34502018-02-22T07:39:40-08:002018-05Journal of the American Society of NephrologyBasic Research29551426134614361347
- Biomarkers of AKI Progression after Pediatric Cardiac SurgeryBackground As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass. Methods On the first day of serum creatinine–defined AKI, we measured urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days). Results In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively. Conclusions If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.10.1681/ASN.2017090989Thu, 22 Feb 2018 07:39:41 GMT-08:00Biomarkers of AKI Progression after Pediatric Cardiac SurgeryBackground As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass. Methods On the first day of serum creatinine–defined AKI, we measured urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL], IL-18, kidney injury molecule 1, liver fatty acid binding protein [L-FABP], albumin, and cystatin C) and plasma biomarkers (IFN, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-α, NGAL, and cystatin C). We defined AKI progression as a worsening of AKI stage or persisting stage 3 AKI (≥2 consecutive days). Results In all, 176 of 408 (43%) children developed postoperative AKI. Among the children with AKI, we diagnosed stages 1, 2, and 3 AKI in 145 (82.5%), 25 (14%), and six (3.5%) children, respectively, on the first day of AKI; 28 (7%) children had AKI progression. On the first day of AKI, nine of 17 biomarkers were significantly higher in patients with than without AKI progression. Urine L-FABP (among injury biomarkers) and plasma IL-8 (among inflammatory biomarkers) had the highest discrimination for AKI progression: optimism-corrected area under the curve, 0.70; 95% confidence interval, 0.58 to 0.81 and optimism-corrected area under the curve, 0.80; 95% confidence interval, 0.69 to 0.91, respectively. Conclusions If validated in additional cohorts, plasma IL-8 could be used to improve clinical care and guide enrollment in therapeutic trials of AKI.Greenberg, Jason H.Zappitelli, MichaelJia, YaqiThiessen-Philbrook, Heather R.de Fontnouvelle, Christina A.Wilson, F. PerryCoca, StevenDevarajan, PrasadParikh, Chirag R.2018-02-22T07:39:41-08:00doi:10.1681/ASN.2017090989hwp:resource-id:jnephrol;29/5/1549American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, children, heart disease, pediatric nephrology, progression of renal failure, cytokinesClinical ResearchClinical Researchresearch-article20182018-05-01May 201810.1681/ASN.20170909891046-66731533-34502018-02-22T07:39:41-08:002018-05Journal of the American Society of NephrologyClinical Research29515491556
- Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal OsteodystrophyBackground Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry. Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD. Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested. Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.10.1681/ASN.2017050584Mon, 19 Mar 2018 06:16:42 GMT-07:00Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal OsteodystrophyBackground Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry. Methods We obtained fasting blood samples from 69 patients with CKD stages 4–5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD. Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested. Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX.Salam, SyazrahGallagher, OrlaGossiel, FatmaPaggiosi, MargaretKhwaja, ArifEastell, Richard2018-03-19T06:16:42-07:00doi:10.1681/ASN.2017050584hwp:resource-id:jnephrol;29/5/1557American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal osteodystrophy, mineral metabolism, parathyroid hormone, hyperparathyroidism, chronic kidney disease, chronic renal failureClinical ResearchClinical Researchresearch-article20182018-05-01May 201810.1681/ASN.20170505841046-66731533-34502018-03-19T06:16:42-07:002018-05Journal of the American Society of NephrologyClinical Research29551557135315651355
- The Quest for Better Biomarkers of Bone Turnover in CKD10.1681/ASN.2018030289Thu, 12 Apr 2018 05:06:13 GMT-07:00The Quest for Better Biomarkers of Bone Turnover in CKDNickolas, Thomas L.2018-04-12T05:06:13-07:00doi:10.1681/ASN.2018030289hwp:resource-id:jnephrol;29/5/1353American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal osteodystrophy, bone turnover, hyperparathyroidismUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-05-01May 201810.1681/ASN.20180302891046-66731533-34502018-04-12T05:06:13-07:002018-05Journal of the American Society of NephrologyUp Front Matters29551353155713551565
- WNKs on the Fly10.1681/ASN.2018030318Thu, 12 Apr 2018 05:06:13 GMT-07:00WNKs on the FlyWelling, Paul A.2018-04-12T05:06:13-07:00doi:10.1681/ASN.2018030318hwp:resource-id:jnephrol;29/5/1347American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, distal tubule, Na transport, Cell & Transport PhysiologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-05-01May 201810.1681/ASN.20180303181046-66731533-34502018-04-12T05:06:13-07:002018-05Journal of the American Society of NephrologyUp Front Matters29551347144913491461
- Mechanism of Hyperkalemia-Induced Metabolic AcidosisBackground Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines type 4 renal tubular acidosis (RTA), the most common RTA observed, but the molecular mechanisms underlying the associated metabolic acidosis are incompletely understood. We sought to determine whether hyperkalemia directly causes metabolic acidosis and, if so, the mechanisms through which this occurs. Methods We studied a genetic model of hyperkalemia that results from early distal convoluted tubule (DCT)–specific overexpression of constitutively active Ste20/SPS1-related proline-alanine–rich kinase (DCT-CA-SPAK). Results DCT-CA-SPAK mice developed hyperkalemia in association with metabolic acidosis and suppressed ammonia excretion; however, titratable acid excretion and urine pH were unchanged compared with those in wild-type mice. Abnormal ammonia excretion in DCT-CA-SPAK mice associated with decreased proximal tubule expression of the ammonia-generating enzymes phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase and overexpression of the ammonia-recycling enzyme glutamine synthetase. These mice also had decreased expression of the ammonia transporter family member Rhcg and decreased apical polarization of H+-ATPase in the inner stripe of the outer medullary collecting duct. Correcting the hyperkalemia by treatment with hydrochlorothiazide corrected the metabolic acidosis, increased ammonia excretion, and normalized ammoniagenic enzyme and Rhcg expression in DCT-CA-SPAK mice. In wild-type mice, induction of hyperkalemia by administration of the epithelial sodium channel blocker benzamil caused hyperkalemia and suppressed ammonia excretion. Conclusions Hyperkalemia decreases proximal tubule ammonia generation and collecting duct ammonia transport, leading to impaired ammonia excretion that causes metabolic acidosis.10.1681/ASN.2017111163Mon, 26 Feb 2018 07:11:49 GMT-08:00Mechanism of Hyperkalemia-Induced Metabolic AcidosisBackground Hyperkalemia in association with metabolic acidosis that are out of proportion to changes in glomerular filtration rate defines type 4 renal tubular acidosis (RTA), the most common RTA observed, but the molecular mechanisms underlying the associated metabolic acidosis are incompletely understood. We sought to determine whether hyperkalemia directly causes metabolic acidosis and, if so, the mechanisms through which this occurs. Methods We studied a genetic model of hyperkalemia that results from early distal convoluted tubule (DCT)–specific overexpression of constitutively active Ste20/SPS1-related proline-alanine–rich kinase (DCT-CA-SPAK). Results DCT-CA-SPAK mice developed hyperkalemia in association with metabolic acidosis and suppressed ammonia excretion; however, titratable acid excretion and urine pH were unchanged compared with those in wild-type mice. Abnormal ammonia excretion in DCT-CA-SPAK mice associated with decreased proximal tubule expression of the ammonia-generating enzymes phosphate-dependent glutaminase and phosphoenolpyruvate carboxykinase and overexpression of the ammonia-recycling enzyme glutamine synthetase. These mice also had decreased expression of the ammonia transporter family member Rhcg and decreased apical polarization of H+-ATPase in the inner stripe of the outer medullary collecting duct. Correcting the hyperkalemia by treatment with hydrochlorothiazide corrected the metabolic acidosis, increased ammonia excretion, and normalized ammoniagenic enzyme and Rhcg expression in DCT-CA-SPAK mice. In wild-type mice, induction of hyperkalemia by administration of the epithelial sodium channel blocker benzamil caused hyperkalemia and suppressed ammonia excretion. Conclusions Hyperkalemia decreases proximal tubule ammonia generation and collecting duct ammonia transport, leading to impaired ammonia excretion that causes metabolic acidosis.Harris, Autumn N.Grimm, P. RichardLee, Hyun-WookDelpire, EricFang, LijuanVerlander, Jill W.Welling, Paul A.Weiner, I. David2018-02-26T07:11:49-08:00doi:10.1681/ASN.2017111163hwp:resource-id:jnephrol;29/5/1411American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal tubular acidosis, chronic metabolic acidosis, proximal tubule, collecting ductsBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20171111631046-66731533-34502018-02-26T07:11:49-08:002018-05Journal of the American Society of NephrologyBasic Research29514111425
- Protein S Protects against Podocyte Injury in Diabetic NephropathyBackground Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose–induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose– and TNF-α–induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression.10.1681/ASN.2017030234Tue, 06 Mar 2018 06:04:32 GMT-08:00Protein S Protects against Podocyte Injury in Diabetic NephropathyBackground Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear. Methods To assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN. Results In human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose–induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose– and TNF-α–induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cells in vivo attenuated albuminuria and podocyte loss in diabetic OVE26 mice. Conclusions Our results support a protective role of PS against glomerular injury in DN progression.Zhong, FangChen, HaibingXie, YifanAzeloglu, Evren U.Wei, ChengguoZhang, WeijiaLi, ZhengzheChuang, Peter Y.Jim, BelindaLi, HongElmastour, FirasRiyad, Jalish M.Weber, ThomasChen, HongyuWang, YongjunZhang, AihuaJia, WeipingLee, KyungHe, John C.2018-03-06T06:04:32-08:00doi:10.1681/ASN.2017030234hwp:resource-id:jnephrol;29/5/1397American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, podocytes, Protein S, proteomeBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20170302341046-66731533-34502018-03-06T06:04:32-08:002018-05Journal of the American Society of NephrologyBasic Research29513971410
- Lipoxins Regulate the Early Growth Response–1 Network and Reverse Diabetic Kidney DiseaseBackground The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4) as therapeutics in a murine model of diabetic kidney disease, ApoE−/− mice treated with streptozotocin. Results Intraperitoneal injection of LXs attenuated the development of diabetes-induced albuminuria, mesangial expansion, and collagen deposition. Notably, LXs administered 10 weeks after disease onset also attenuated established kidney disease, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature (725 genes; false discovery rate P≤0.05). Comparison of this murine gene signature with that of human diabetic kidney disease identified shared renal proinflammatory/profibrotic signals (TNF-α, IL-1β, NF-κB). In diabetic mice, we identified 20 and 51 transcripts regulated by LXA4 and Benzo-LXA4, respectively, and pathway analysis identified established (TGF-β1, PDGF, TNF-α, NF-κB) and novel (early growth response–1 [EGR-1]) networks activated in diabetes and regulated by LXs. In cultured human renal epithelial cells, treatment with LXs attenuated TNF-α–driven Egr-1 activation, and Egr-1 depletion prevented cellular responses to TGF-β1 and TNF-α. Conclusions These data demonstrate that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation.10.1681/ASN.2017101112Wed, 28 Feb 2018 07:19:10 GMT-08:00Lipoxins Regulate the Early Growth Response–1 Network and Reverse Diabetic Kidney DiseaseBackground The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4) as therapeutics in a murine model of diabetic kidney disease, ApoE−/− mice treated with streptozotocin. Results Intraperitoneal injection of LXs attenuated the development of diabetes-induced albuminuria, mesangial expansion, and collagen deposition. Notably, LXs administered 10 weeks after disease onset also attenuated established kidney disease, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature (725 genes; false discovery rate P≤0.05). Comparison of this murine gene signature with that of human diabetic kidney disease identified shared renal proinflammatory/profibrotic signals (TNF-α, IL-1β, NF-κB). In diabetic mice, we identified 20 and 51 transcripts regulated by LXA4 and Benzo-LXA4, respectively, and pathway analysis identified established (TGF-β1, PDGF, TNF-α, NF-κB) and novel (early growth response–1 [EGR-1]) networks activated in diabetes and regulated by LXs. In cultured human renal epithelial cells, treatment with LXs attenuated TNF-α–driven Egr-1 activation, and Egr-1 depletion prevented cellular responses to TGF-β1 and TNF-α. Conclusions These data demonstrate that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation.Brennan, Eoin P.Mohan, MuthukumarMcClelland, AaronTikellis, ChristosZiemann, MarkKaspi, AntonyGray, Stephen P.Pickering, RaeleneTan, Sih MinAli-Shah, Syed TasadaqueGuiry, Patrick J.El-Osta, AssamJandeleit-Dahm, KarinCooper, Mark E.Godson, CatherineKantharidis, Phillip2018-02-28T07:19:10-08:00doi:10.1681/ASN.2017101112hwp:resource-id:jnephrol;29/5/1437American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyChronic inflammation, diabetic nephropathy, kidney dysfunction, transcriptional profiling, transgenic mouseBasic ResearchBasic Researchresearch-article20182018-05-01May 201810.1681/ASN.20171011121046-66731533-34502018-02-28T07:19:10-08:002018-05Journal of the American Society of NephrologyBasic Research29514371448
- The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRDCardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern; i.e., they occur more commonly during the last day of the long interdialytic interval and the first session of the week. The hemodialysis process causes acute decreases in cardiac chamber size and pulmonary circulation loading and acute diastolic dysfunction, possibly through myocardial stunning and other non–myocardial-related mechanisms; systolic function, in contrast, is largely unchanged. During interdialytic intervals volume overload, acid-base, and electrolyte shifts, as well as arterial and myocardial wall changes, result in dilatation of right cardiac chambers and pulmonary circulation overload. Recent studies suggest that these alterations are more extended during the long interdialytic interval or the first dialysis session of the week and are associated with excess volume overload or removal, respectively, thus adding a mechanism for the day-of-week pattern of mortality in patients receiving hemodialysis. This review summarizes the existing data from echocardiographic studies of cardiac morphology and function during the hemodialysis session, as well as during the interdialytic intervals.10.1681/ASN.2017101102Wed, 28 Mar 2018 06:47:48 GMT-07:00The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRDCardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern; i.e., they occur more commonly during the last day of the long interdialytic interval and the first session of the week. The hemodialysis process causes acute decreases in cardiac chamber size and pulmonary circulation loading and acute diastolic dysfunction, possibly through myocardial stunning and other non–myocardial-related mechanisms; systolic function, in contrast, is largely unchanged. During interdialytic intervals volume overload, acid-base, and electrolyte shifts, as well as arterial and myocardial wall changes, result in dilatation of right cardiac chambers and pulmonary circulation overload. Recent studies suggest that these alterations are more extended during the long interdialytic interval or the first dialysis session of the week and are associated with excess volume overload or removal, respectively, thus adding a mechanism for the day-of-week pattern of mortality in patients receiving hemodialysis. This review summarizes the existing data from echocardiographic studies of cardiac morphology and function during the hemodialysis session, as well as during the interdialytic intervals.Loutradis, CharalamposSarafidis, Pantelis A.Papadopoulos, Christodoulos E.Papagianni, AikateriniZoccali, Carmine2018-03-28T06:47:48-07:00doi:10.1681/ASN.2017101102hwp:resource-id:jnephrol;29/5/1372American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, interdialytic interval, echocardiography, diastolic dysfunction, myocardial stunning, pulmonary circulation overloadUp Front MattersReviewsUp Front MattersReviewsbrief-report20182018-05-01May 201810.1681/ASN.20171011021046-66731533-34502018-03-28T06:47:48-07:002018-05Journal of the American Society of NephrologyUp Front Matters29513721381
- HDL in CKD—The Devil Is in the DetailThe picture of HDL cholesterol (HDL-C) as the “good” cholesterol has eroded. This is even more surprising because there exists strong evidence that HDL-C is associated with cardiovascular disease (CVD) in the general population as well as in patients with impairment of kidney function and/or progression of CKD. However, drugs that dramatically increase HDL-C have mostly failed to decrease CVD events. Furthermore, genetic studies took the same line, as genetic variants that have a pronounced influence on HDL-C concentrations did not show an association with cardiovascular risk. For many, this was not surprising, given that an HDL particle is highly complex and carries >80 proteins and several hundred lipid species. Simply measuring cholesterol might not reflect the variety of biologic effects of heterogeneous HDL particles. Therefore, functional studies and the involvement of HDL components in the reverse cholesterol transport, including the cholesterol efflux capacity, have become a further focus of study during recent years. As also observed for other aspects, CKD populations behave differently compared with non-CKD populations. Although clear disturbances have been observed for the “functionality” of HDL particles in patients with CKD, this did not necessarily translate into clear-cut associations with outcomes.10.1681/ASN.2017070798Thu, 22 Feb 2018 07:39:41 GMT-08:00HDL in CKD—The Devil Is in the DetailThe picture of HDL cholesterol (HDL-C) as the “good” cholesterol has eroded. This is even more surprising because there exists strong evidence that HDL-C is associated with cardiovascular disease (CVD) in the general population as well as in patients with impairment of kidney function and/or progression of CKD. However, drugs that dramatically increase HDL-C have mostly failed to decrease CVD events. Furthermore, genetic studies took the same line, as genetic variants that have a pronounced influence on HDL-C concentrations did not show an association with cardiovascular risk. For many, this was not surprising, given that an HDL particle is highly complex and carries >80 proteins and several hundred lipid species. Simply measuring cholesterol might not reflect the variety of biologic effects of heterogeneous HDL particles. Therefore, functional studies and the involvement of HDL components in the reverse cholesterol transport, including the cholesterol efflux capacity, have become a further focus of study during recent years. As also observed for other aspects, CKD populations behave differently compared with non-CKD populations. Although clear disturbances have been observed for the “functionality” of HDL particles in patients with CKD, this did not necessarily translate into clear-cut associations with outcomes.Kronenberg, Florian2018-02-22T07:39:41-08:00doi:10.1681/ASN.2017070798hwp:resource-id:jnephrol;29/5/1356American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologylipids, cardiovascular disease, progression of chronic renal failure, reverse, cholesterol transport, high-density lipoproteinUp Front MattersReviewsUp Front MattersReviewsbrief-report20182018-05-01May 201810.1681/ASN.20170707981046-66731533-34502018-02-22T07:39:41-08:002018-05Journal of the American Society of NephrologyUp Front Matters29513561371
- The APOL1 Long-Term Kidney Transplantation Outcomes Network—APOLLO10.2215/CJN.01510218Fri, 27 Apr 2018 06:04:37 GMT-07:00The APOL1 Long-Term Kidney Transplantation Outcomes Network—APOLLOFreedman, Barry I.Moxey-Mims, Marva2018-04-27T06:04:37-07:00doi:10.2215/CJN.01510218hwp:resource-id:clinjasn;13/6/940American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAPOL1, Apolipoprotein L1, chronic kidney disease, Genetics, Genotype, Glomerulosclerosis, Focal Segmental, hypertension, kidney, Kidney Failure, Chronic, kidney transplantation, lupus nephritis, Prevalence, quality of life, Registries, renal dialysis, Retrospective Studies, Selection, Genetic, Tissue Donors, Transplant Recipients, Trypanosomiasis, AfricanPerspectivesPerspectivesresearch-article20182018-06-07June 07, 201810.2215/CJN.015102181555-90411555-905X2018-04-27T06:04:37-07:002018-06-07Clinical Journal of the American Society of NephrologyPerspectives136940942
- Changes in Glomerular Filtration Rate and Impact on Long-Term Survival among Adults after Hematopoietic Cell Transplantation10.2215/CJN.10630917Wed, 18 Apr 2018 07:10:54 GMT-07:00Changes in Glomerular Filtration Rate and Impact on Long-Term Survival among Adults after Hematopoietic Cell TransplantationHingorani, SangeetaPao, EmilyStevenson, PhilSchoch, GaryLaskin, Benjamin L.Gooley, TedMcDonald, George B.2018-04-18T07:10:54-07:00doi:10.2215/CJN.10630917hwp:resource-id:clinjasn;13/6/866American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, albuminuria, Behavior Therapy, Calcineurin Inhibitors, creatinine, diabetes mellitus, glomerular filtration rate, Graft versus Host Disease, Hematopoietic Stem Cell Transplantation, Humans, hypertension, kidney, kidney dysfunction, Male, mortality, Proportional Hazards Models, risk factors, Survivors, WashingtonOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20182018-06-07June 07, 201810.2215/CJN.106309171555-90411555-905X2018-04-18T07:10:54-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136866873
- Approach to the Young Patient with New-Onset Hypertension10.2215/CJN.13341217Fri, 23 Feb 2018 11:41:48 GMT-08:00Approach to the Young Patient with New-Onset HypertensionCohen, Debbie L.Townsend, Raymond R.2018-02-23T11:41:48-08:00doi:10.2215/CJN.13341217hwp:resource-id:clinjasn;13/6/929American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, blood pressure, Street Drugs, Muscle Cramp, Office Visits, Dyspnea, Chest Pain, Headache, fibromuscular dysplasia, renal artery stenosisKidney Case Conference: Attending RoundsKidney Case Conference: Attending Roundsresearch-article20182018-06-07June 07, 201810.2215/CJN.133412171555-90411555-905X2018-02-23T11:41:48-08:002018-06-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Attending Rounds136929932
- A Patient with Hemolytic Uremic Syndrome and Kidney Failure10.2215/CJN.13191117Mon, 19 Feb 2018 06:20:33 GMT-08:00A Patient with Hemolytic Uremic Syndrome and Kidney FailureThurman, Joshua M.2018-02-19T06:20:33-08:00doi:10.2215/CJN.13191117hwp:resource-id:clinjasn;13/6/933American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, complement, hemolytic uremic syndrome, Female, Humans, Pregnancy, Plasma Exchange, Platelet Count, HELLP Syndrome, creatinine, Platelet Transfusion, Hemolysis, blood pressure, Neutrophils, Blood Platelets, Purpura, Thrombotic Thrombocytopenic, Hemolytic-Uremic Syndrome, Anuria, Acute Kidney Injury, renal dialysis, Hemoglobins, Edema, Transaminases, Lower Extremity, LiverKidney Case Conference: Attending RoundsKidney Case Conference: Attending Roundsresearch-article20182018-06-07June 07, 201810.2215/CJN.131911171555-90411555-905X2018-02-19T06:20:33-08:002018-06-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Attending Rounds136933936
- A Case of Monoclonal Gammopathy of Renal Significance10.2215/CJN.00470118Fri, 18 May 2018 07:33:48 GMT-07:00A Case of Monoclonal Gammopathy of Renal SignificanceHogan, Jonathan J.2018-05-18T07:33:48-07:00doi:10.2215/CJN.00470118hwp:resource-id:clinjasn;13/6/937American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, glomerulonephritis, kidney, Monoclonal Gammopathy of Undetermined Significance, multiple myeloma, ParaproteinemiasKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20182018-06-07June 07, 201810.2215/CJN.004701181555-90411555-905X2018-05-18T07:33:48-07:002018-06-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire136937939
- Identification of Patients Expected to Benefit from Electronic Alerts for Acute Kidney Injury10.2215/CJN.13351217Thu, 29 Mar 2018 06:09:56 GMT-07:00Identification of Patients Expected to Benefit from Electronic Alerts for Acute Kidney InjuryBiswas, AdityaParikh, Chirag R.Feldman, Harold I.Garg, Amit X.Latham, StephenLin, HaiqunPalevsky, Paul M.Ugwuowo, UgochukwuWilson, F. Perry2018-03-29T06:09:56-07:00doi:10.2215/CJN.13351217hwp:resource-id:clinjasn;13/6/842American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Adult, Alert, Algorithms, Clinical Decision Support, creatinine, Female, Humans, outcomes, Personalized Medicine, Precision Medicine, Probability, Prognosis, Random AllocationOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-06-07June 07, 201810.2215/CJN.133512171555-90411555-905X2018-03-29T06:09:56-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles136842849
- Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events10.2215/CJN.12591117Thu, 17 May 2018 06:08:05 GMT-07:00Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic EventsGo, Alan S.Hsu, Chi-yuanYang, JingrongTan, Thida C.Zheng, SijieOrdonez, Juan D.Liu, Kathleen D.2018-05-17T06:08:05-07:00doi:10.2215/CJN.12591117hwp:resource-id:clinjasn;13/6/833American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Coronary Syndrome, Acute Kidney Injury, Adult, Brain Ischemia, cardiovascular disease, Comorbidity, creatinine, Electronic Health Records, Follow-up Studies, glomerular filtration rate, heart failure, Hospital Mortality, hospitalization, Inpatients, Intensive Care Units, Kidney Function Tests, Length Of Stay, mortality, Outpatients, Patient Discharge, Peripheral Arterial Disease, proteinuria, Retrospective Studies, Sepsis, StrokeOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-06-07June 07, 201810.2215/CJN.125911171555-90411555-905X2018-05-17T06:08:05-07:002018-06-07Clinical Journal of the American Society of NephrologyOriginal Articles1366833825841828
- Biomarkers Associated with Progression of Diabetic Kidney Disease: Do They Hold the Same Meaning for Blacks and Women?10.1681/ASN.2017121249Fri, 20 Apr 2018 07:37:29 GMT-07:00Biomarkers Associated with Progression of Diabetic Kidney Disease: Do They Hold the Same Meaning for Blacks and Women?Hickson, LaTonya J.Balls-Berry, Joyce E.Jaffe, Allan S.Rule, Andrew D.2018-04-20T07:37:29-07:00doi:10.1681/ASN.2017121249hwp:resource-id:jnephrol;29/6/1781American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, biomarker, diabetes mellitus, gender difference, raceLetters to the EditorLetters to the Editorletter20182018-06-01June 201810.1681/ASN.20171212491046-66731533-34502018-04-20T07:37:29-07:002018-06Journal of the American Society of NephrologyLetters to the Editor29661781178217811783
- Diet Patterns—A Neglected Aspect of Hemodialysis Care10.1681/ASN.2018050459Fri, 18 May 2018 07:34:02 GMT-07:00Diet Patterns—A Neglected Aspect of Hemodialysis CareLogan, Alexander G.Mente, Andrew2018-05-18T07:34:02-07:00doi:10.1681/ASN.2018050459hwp:resource-id:jnephrol;29/6/1581American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydiet patterns, hemodialysis, cardiovascular disease, Mediterranean diet, DASH diet, nutrition guidelinesUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-06-01June 201810.1681/ASN.20180504591046-66731533-34502018-05-18T07:34:02-07:002018-06Journal of the American Society of NephrologyUp Front Matters29661581174115821751
- This Month’s Highlights10.1681/ASN.2018040429Thu, 31 May 2018 01:05:08 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2018-05-31T13:05:08-07:00doi:10.1681/ASN.2018040429hwp:resource-id:jnephrol;29/6/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-06-01June 201810.1681/ASN.20180404291046-66731533-34502018-05-31T13:05:08-07:002018-06Journal of the American Society of NephrologyThis Month’s Highlights296ii
- The Authors Reply10.1681/ASN.2018020127Wed, 25 Apr 2018 06:25:11 GMT-07:00The Authors ReplyLv, Lin-LiFeng, YeLiu, Bi-Cheng2018-04-25T06:25:11-07:00doi:10.1681/ASN.2018020127hwp:resource-id:jnephrol;29/6/1784-aAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyexosome, urine, extracellular vesicleLetters to the EditorLetters to the Editorletter20182018-06-01June 201810.1681/ASN.20180201271046-66731533-34502018-04-25T06:25:11-07:002018-06Journal of the American Society of NephrologyLetters to the Editor29661784178417851784
- Nanoparticle Tracking Analysis of Urine to Detect Exosomes Can Be Confounded by Albuminuria10.1681/ASN.2018020115Wed, 25 Apr 2018 06:25:11 GMT-07:00Nanoparticle Tracking Analysis of Urine to Detect Exosomes Can Be Confounded by AlbuminuriaGleadle, JonathanMcNicholas, KymLi, JordanMichael, MichaelRojas-Canales, Darling2018-04-25T06:25:11-07:00doi:10.1681/ASN.2018020115hwp:resource-id:jnephrol;29/6/1784American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyexosome, artefact, nanoparticle tracking analysis (NTA), nanoparticle, albuminuriaLetters to the EditorLetters to the Editorletter20182018-06-01June 201810.1681/ASN.20180201151046-66731533-34502018-04-25T06:25:11-07:002018-06Journal of the American Society of NephrologyLetters to the Editor29661784178417841785
- NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRDBackground Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in children. However, little is known about the prevalence of NPH in adult-onset ESRD. Homozygous full gene deletions of the NPHP1 gene encoding nephrocystin-1 are a prominent cause of NPH. We determined the prevalence of NPH in adults by assessing homozygous NPHP1 full gene deletions in adult-onset ESRD. Methods Adult renal transplant recipients from five cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) underwent single-nucleotide polymorphism genotyping. After quality control, we determined autosomal copy number variants (such as deletions) on the basis of median log2 ratios and B-allele frequency patterns. The findings were independently validated in one cohort. Patients were included in the analysis if they had adult-onset ESRD, defined as start of RRT at ≥18 years old. Results We included 5606 patients with adult-onset ESRD; 26 (0.5%) showed homozygous NPHP1 deletions. No donor controls showed homozygosity for this deletion. Median age at ESRD onset was 30 (range, 18–61) years old for patients with NPH, with 54% of patients age ≥30 years old. Notably, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (n=11; 42%). Conclusions Considering that other mutation types in NPHP1 or mutations in other NPH-causing genes were not analyzed, NPH is a relatively frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not been clinically diagnosed with NPH, wider application of genetic testing in adult-onset ESRD may be warranted.10.1681/ASN.2017111200Fri, 13 Apr 2018 07:22:17 GMT-07:00NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRDBackground Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in children. However, little is known about the prevalence of NPH in adult-onset ESRD. Homozygous full gene deletions of the NPHP1 gene encoding nephrocystin-1 are a prominent cause of NPH. We determined the prevalence of NPH in adults by assessing homozygous NPHP1 full gene deletions in adult-onset ESRD. Methods Adult renal transplant recipients from five cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) underwent single-nucleotide polymorphism genotyping. After quality control, we determined autosomal copy number variants (such as deletions) on the basis of median log2 ratios and B-allele frequency patterns. The findings were independently validated in one cohort. Patients were included in the analysis if they had adult-onset ESRD, defined as start of RRT at ≥18 years old. Results We included 5606 patients with adult-onset ESRD; 26 (0.5%) showed homozygous NPHP1 deletions. No donor controls showed homozygosity for this deletion. Median age at ESRD onset was 30 (range, 18–61) years old for patients with NPH, with 54% of patients age ≥30 years old. Notably, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (n=11; 42%). Conclusions Considering that other mutation types in NPHP1 or mutations in other NPH-causing genes were not analyzed, NPH is a relatively frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not been clinically diagnosed with NPH, wider application of genetic testing in adult-onset ESRD may be warranted.Snoek, Rozemarijnvan Setten, JessicaKeating, Brendan J.Israni, Ajay K.Jacobson, Pamala A.Oetting, William S.Matas, Arthur J.Mannon, Roslyn B.Zhang, ZhongyangZhang, WeijiaHao, KeMurphy, BarbaraReindl-Schwaighofer, RomanHeinzl, AndreasOberbauer, RainerViklicky, OndrejConlon, Peter J.Stapleton, Caragh P.Bakker, Stephan J.L.Snieder, HaroldPeters, Edith D.J.van der Zwaag, BertKnoers, Nine V.A.M.de Borst, Martin H.van Eerde, Albertien M.2018-04-13T07:22:17-07:00doi:10.1681/ASN.2017111200hwp:resource-id:jnephrol;29/6/1772American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, transplantation, end-stage renal disease, human genetics, cystic kidneyClinical ResearchClinical Researchresearch-article20182018-06-01June 201810.1681/ASN.20171112001046-66731533-34502018-04-13T07:22:17-07:002018-06Journal of the American Society of NephrologyClinical Research29661772158317791584
- Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial FibrosisBackground Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo, in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro, stimulation of purified human kidney SCs and human kidney organoids with IL-1β recapitulated the molecular events observed in vivo, inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1β and metabolic switch in fibrosis initiation and progression and highlight IL-1β and MYC as potential therapeutic targets in tubulointerstitial diseases.10.1681/ASN.2017121283Tue, 08 May 2018 08:08:24 GMT-07:00Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial FibrosisBackground Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo, in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro, stimulation of purified human kidney SCs and human kidney organoids with IL-1β recapitulated the molecular events observed in vivo, inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1β and metabolic switch in fibrosis initiation and progression and highlight IL-1β and MYC as potential therapeutic targets in tubulointerstitial diseases.Lemos, Dario R.McMurdo, MichaelKaraca, GamzeWilflingseder, JuliaLeaf, Irina A.Gupta, NavinMiyoshi, TomoyaSusa, KoichiroJohnson, Bryce G.Soliman, KirolousWang, GuanghaiMorizane, RyujiBonventre, Joseph V.Duffield, Jeremy S.2018-05-08T08:08:24-07:00doi:10.1681/ASN.2017121283hwp:resource-id:jnephrol;29/6/1690American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyinterstitial fibrosis, Chronic inflammation, Cell SignalingBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20171212831046-66731533-34502018-05-08T08:08:24-07:002018-06Journal of the American Society of NephrologyBasic Research29616901705
- Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κBBackground The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear. Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD. Results In cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO4 increased the abundance of zinc-finger protein TNF-α–induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO4 supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO4 ameliorated the osteoinductive effects of uremic serum in VSMCs. Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.10.1681/ASN.2017050492Fri, 13 Apr 2018 07:22:16 GMT-07:00Zinc Inhibits Phosphate-Induced Vascular Calcification through TNFAIP3-Mediated Suppression of NF-κBBackground The high cardiovascular morbidity and mortality of patients with CKD may result in large part from medial vascular calcification, a process promoted by hyperphosphatemia and involving osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Reduced serum zinc levels have frequently been observed in patients with CKD, but the functional relevance of this remains unclear. Methods We performed experiments in primary human aortic VSMCs; klotho-hypomorphic (kl/kl), subtotal nephrectomy, and cholecalciferol-overload mouse calcification models; and serum samples from patients with CKD. Results In cultured VSMCs, treatment with zinc sulfate (ZnSO4) blunted phosphate-induced calcification, osteo-/chondrogenic signaling, and NF-κB activation. ZnSO4 increased the abundance of zinc-finger protein TNF-α–induced protein 3 (TNFAIP3, also known as A20), a suppressor of the NF-κB pathway, by zinc-sensing receptor ZnR/GPR39-dependent upregulation of TNFAIP3 gene expression. Silencing of TNFAIP3 in VSMCs blunted the anticalcific effects of ZnSO4 under high phosphate conditions. kl/kl mice showed reduced plasma zinc levels, and ZnSO4 supplementation strongly blunted vascular calcification and aortic osteoinduction and upregulated aortic Tnfaip3 expression. ZnSO4 ameliorated vascular calcification in mice with chronic renal failure and mice with cholecalciferol overload. In patients with CKD, serum zinc concentrations inversely correlated with serum calcification propensity. Finally, ZnSO4 ameliorated the osteoinductive effects of uremic serum in VSMCs. Conclusions Zinc supplementation ameliorates phosphate-induced osteo-/chondrogenic transdifferentiation of VSMCs and vascular calcification through an active cellular mechanism resulting from GPR39-dependent induction of TNFAIP3 and subsequent suppression of the NF-κB pathway. Zinc supplementation may be a simple treatment to reduce the burden of vascular calcification in CKD.Voelkl, JakobTuffaha, RashadLuong, Trang T.D.Zickler, DanielMasyout, JaberFeger, MartinaVerheyen, NicolasBlaschke, FlorianKuro-o, MakotoTomaschitz, AndreasPilz, StefanPasch, AndreasEckardt, Kai-UweScherberich, Juergen E.Lang, FlorianPieske, BurkertAlesutan, Ioana2018-04-13T07:22:16-07:00doi:10.1681/ASN.2017050492hwp:resource-id:jnephrol;29/6/1636American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyTNFAIP3, osteogenic signaling, vascular smooth muscle cells, GPR39, vascular calcification, zincBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20170504921046-66731533-34502018-04-13T07:22:16-07:002018-06Journal of the American Society of NephrologyBasic Research29616361648
- The Authors Reply10.1681/ASN.2018020164Fri, 20 Apr 2018 07:37:28 GMT-07:00The Authors ReplyCoca, Steven G.Nadkarni, Girish N.Chauhan, KinsukParikh, Chirag R.2018-04-20T07:37:28-07:00doi:10.1681/ASN.2018020164hwp:resource-id:jnephrol;29/6/1782American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologybiomarkers, ckd, diabetic nephropathyLetters to the EditorLetters to the Editorletter20182018-06-01June 201810.1681/ASN.20180201641046-66731533-34502018-04-20T07:37:28-07:002018-06Journal of the American Society of NephrologyLetters to the Editor29661782178117831781
- Oral Antibiotic Exposure and Kidney Stone DiseaseBackground Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown. Methods We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case–control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins. Results Exposure to any of five different antibiotic classes 3–12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3–6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3–5 years from exposure. Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.10.1681/ASN.2017111213Thu, 10 May 2018 08:01:16 GMT-07:00Oral Antibiotic Exposure and Kidney Stone DiseaseBackground Although intestinal and urinary microbiome perturbations are associated with nephrolithiasis, whether antibiotics are a risk factor for this condition remains unknown. Methods We determined the association between 12 classes of oral antibiotics and nephrolithiasis in a population-based, case–control study nested within 641 general practices providing electronic health record data for >13 million children and adults from 1994 to 2015 in the United Kingdom. We used incidence density sampling to match 25,981 patients with nephrolithiasis to 259,797 controls by age, sex, and practice at date of diagnosis (index date). Conditional logistic regression models were adjusted for the rate of health care encounters, comorbidities, urinary tract infections, and use of thiazide and loop diuretics, proton-pump inhibitors, and statins. Results Exposure to any of five different antibiotic classes 3–12 months before index date was associated with nephrolithiasis. The adjusted odds ratio (95% confidence interval) was 2.33 (2.19 to 2.48) for sulfas, 1.88 (1.75 to 2.01) for cephalosporins, 1.67 (1.54 to 1.81) for fluoroquinolones, 1.70 (1.55 to 1.88) for nitrofurantoin/methenamine, and 1.27 (1.18 to 1.36) for broad-spectrum penicillins. In exploratory analyses, the magnitude of associations was greatest for exposure at younger ages (P<0.001) and 3–6 months before index date (P<0.001), with all but broad-spectrum penicillins remaining statistically significant 3–5 years from exposure. Conclusions Oral antibiotics associated with increased odds of nephrolithiasis, with the greatest odds for recent exposure and exposure at younger age. These results have implications for disease pathogenesis and the rising incidence of nephrolithiasis, particularly among children.Tasian, Gregory E.Jemielita, ThomasGoldfarb, David S.Copelovitch, LawrenceGerber, Jeffrey S.Wu, QufeiDenburg, Michelle R.2018-05-10T08:01:16-07:00doi:10.1681/ASN.2017111213hwp:resource-id:jnephrol;29/6/1731American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney stones, antibiotic, microbiomeClinical EpidemiologyClinical Epidemiologyresearch-article20182018-06-01June 201810.1681/ASN.20171112131046-66731533-34502018-05-10T08:01:16-07:002018-06Journal of the American Society of NephrologyClinical Epidemiology29661731159017401592
- Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling PathwaysBackground Urine citrate is reabsorbed exclusively along the renal proximal tubule via the apical Na+-dicarboxylate cotransporter NaDC-1. We previously showed that an acid load in vivo and media acidification in vitro increase NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ETB) signaling. Here, we further examined the signaling pathway mediating acid-induced NaDC-1 activity. Methods We transiently transfected cultured opossum kidney cells, a model of the proximal tubule, with NaDC-1 and ETB and measured [14C]-citrate uptake after media acidification under various experimental conditions, including inactivation of Pyk2 and c-Src, which were previously shown to be activated by media acidification. Wild-type (Pyk2+/+) and Pyk2-null (Pyk2−/−) mice were exposed to NH4Cl loading and euthanized after various end points, at which time we harvested the kidneys for immunoblotting and brush border membrane NaDC-1 activity studies. Results Inhibition of Pyk2 or c-Src prevented acid stimulation but not ET-1 stimulation of NaDC-1 in vitro. Consistent with these results, NH4Cl loading stimulated NaDC-1 activity in kidneys of wild-type but not Pyk2−/− mice. In cultured cells and in mice, ERK1/2 was rapidly phosphorylated by acid loading, even after Pyk2 knockdown, and it was required for acid but not ET-1/ETB stimulation of NaDC-1 in vitro. Media acidification also induced the phosphorylation of Raf1 and p90RSK, components of the ERK1/2 pathway, and inhibition of these proteins blocked acid stimulation of NaDC-1 activity. Conclusions Acid stimulation of NaDC-1 activity involves Pyk2/c-Src and Raf1-ERK1/2-p90RSK signaling pathways, but these pathways are not downstream of ET-1/ETB in this process.10.1681/ASN.2017121268Fri, 20 Apr 2018 07:37:28 GMT-07:00Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling PathwaysBackground Urine citrate is reabsorbed exclusively along the renal proximal tubule via the apical Na+-dicarboxylate cotransporter NaDC-1. We previously showed that an acid load in vivo and media acidification in vitro increase NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ETB) signaling. Here, we further examined the signaling pathway mediating acid-induced NaDC-1 activity. Methods We transiently transfected cultured opossum kidney cells, a model of the proximal tubule, with NaDC-1 and ETB and measured [14C]-citrate uptake after media acidification under various experimental conditions, including inactivation of Pyk2 and c-Src, which were previously shown to be activated by media acidification. Wild-type (Pyk2+/+) and Pyk2-null (Pyk2−/−) mice were exposed to NH4Cl loading and euthanized after various end points, at which time we harvested the kidneys for immunoblotting and brush border membrane NaDC-1 activity studies. Results Inhibition of Pyk2 or c-Src prevented acid stimulation but not ET-1 stimulation of NaDC-1 in vitro. Consistent with these results, NH4Cl loading stimulated NaDC-1 activity in kidneys of wild-type but not Pyk2−/− mice. In cultured cells and in mice, ERK1/2 was rapidly phosphorylated by acid loading, even after Pyk2 knockdown, and it was required for acid but not ET-1/ETB stimulation of NaDC-1 in vitro. Media acidification also induced the phosphorylation of Raf1 and p90RSK, components of the ERK1/2 pathway, and inhibition of these proteins blocked acid stimulation of NaDC-1 activity. Conclusions Acid stimulation of NaDC-1 activity involves Pyk2/c-Src and Raf1-ERK1/2-p90RSK signaling pathways, but these pathways are not downstream of ET-1/ETB in this process.Zacchia, MiriamTian, XuefeiZona, EnricaAlpern, Robert J.Preisig, Patricia A.2018-04-20T07:37:28-07:00doi:10.1681/ASN.2017121268hwp:resource-id:jnephrol;29/6/1720American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyCell Signaling, urinary citrate, NaDC-1, chronic metabolic acidosis, ET-1/ETB signallingBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20171212681046-66731533-34502018-04-20T07:37:28-07:002018-06Journal of the American Society of NephrologyBasic Research29617201730
- The Role of Palladin in PodocytesBackground Podocyte loss and effacement of interdigitating podocyte foot processes are the major cause of a leaky filtration barrier and ESRD. Because the complex three-dimensional morphology of podocytes depends on the actin cytoskeleton, we studied the role in podocytes of the actin bundling protein palladin, which is highly expressed therein. Methods We knocked down palladin in cultured podocytes by siRNA transfection or in zebrafish embryos by morpholino injection and studied the effects by immunofluorescence and live imaging. We also investigated kidneys of mice with podocyte-specific knockout of palladin (PodoPalld−/− mice) by immunofluorescence and ultrastructural analysis and kidney biopsy specimens from patients by immunostaining for palladin. Results Compared with control-treated podocytes, palladin-knockdown podocytes had reduced actin filament staining, smaller focal adhesions, and downregulation of the podocyte-specific proteins synaptopodin and α-actinin-4. Furthermore, palladin-knockdown podocytes were more susceptible to disruption of the actin cytoskeleton with cytochalasin D, latrunculin A, or jasplakinolide and showed altered migration dynamics. In zebrafish embryos, palladin knockdown compromised the morphology and dynamics of epithelial cells at an early developmental stage. Compared with PodoPalld+/+ controls, PodoPalld−/− mice developed glomeruli with a disturbed morphology, an enlarged subpodocyte space, mild effacement, and significantly reduced expression of nephrin and vinculin. Furthermore, nephrotoxic serum injection led to significantly higher levels of proteinuria in PodoPalld−/− mice than in controls. Kidney biopsy specimens from patients with diabetic nephropathy and FSGS showed downregulation of palladin in podocytes as well. Conclusions Palladin has an important role in podocyte function in vitro and in vivo.10.1681/ASN.2017091039Wed, 02 May 2018 05:57:03 GMT-07:00The Role of Palladin in PodocytesBackground Podocyte loss and effacement of interdigitating podocyte foot processes are the major cause of a leaky filtration barrier and ESRD. Because the complex three-dimensional morphology of podocytes depends on the actin cytoskeleton, we studied the role in podocytes of the actin bundling protein palladin, which is highly expressed therein. Methods We knocked down palladin in cultured podocytes by siRNA transfection or in zebrafish embryos by morpholino injection and studied the effects by immunofluorescence and live imaging. We also investigated kidneys of mice with podocyte-specific knockout of palladin (PodoPalld−/− mice) by immunofluorescence and ultrastructural analysis and kidney biopsy specimens from patients by immunostaining for palladin. Results Compared with control-treated podocytes, palladin-knockdown podocytes had reduced actin filament staining, smaller focal adhesions, and downregulation of the podocyte-specific proteins synaptopodin and α-actinin-4. Furthermore, palladin-knockdown podocytes were more susceptible to disruption of the actin cytoskeleton with cytochalasin D, latrunculin A, or jasplakinolide and showed altered migration dynamics. In zebrafish embryos, palladin knockdown compromised the morphology and dynamics of epithelial cells at an early developmental stage. Compared with PodoPalld+/+ controls, PodoPalld−/− mice developed glomeruli with a disturbed morphology, an enlarged subpodocyte space, mild effacement, and significantly reduced expression of nephrin and vinculin. Furthermore, nephrotoxic serum injection led to significantly higher levels of proteinuria in PodoPalld−/− mice than in controls. Kidney biopsy specimens from patients with diabetic nephropathy and FSGS showed downregulation of palladin in podocytes as well. Conclusions Palladin has an important role in podocyte function in vitro and in vivo.Artelt, NadineLudwig, Tim A.Rogge, HenrikKavvadas, PanagiotisSiegerist, FlorianBlumenthal, Antjevan den Brandt, JensOtey, Carol A.Bang, Marie-LouiseAmann, KerstinChadjichristos, Christos E.Chatziantoniou, ChristosEndlich, KarlhansEndlich, Nicole2018-05-02T05:57:03-07:00doi:10.1681/ASN.2017091039hwp:resource-id:jnephrol;29/6/1662American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, palladin, actin filaments, cell migration, nephrin, proteinuriaBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20170910391046-66731533-34502018-05-02T05:57:03-07:002018-06Journal of the American Society of NephrologyBasic Research29616621678
- The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort StudyBackground Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain. Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category). Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients. Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.10.1681/ASN.2018010008Wed, 25 Apr 2018 06:25:11 GMT-07:00The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort StudyBackground Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain. Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category). Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients. Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.Saglimbene, Valeria M.Wong, GermaineCraig, Jonathan C.Ruospo, MarinellaPalmer, Suetonia C.Campbell, KatrinaGarcia-Larsen, VanessaNatale, PatriziaTeixeira-Pinto, ArmandoCarrero, Juan-JesusStenvinkel, PeterGargano, LetiziaMurgo, Angelo M.Johnson, David W.Tonelli, MarcelloGelfman, RubénCelia, EduardoEcder, TevfikBernat, Amparo G.Del Castillo, DomingoTimofte, DeliaTörök, MariettaBednarek-Skublewska, AnnaDuława, JanStroumza, PaulHoischen, SusanneHansis, MartinFabricius, ElisabethFelaco, PaoloWollheim, CharlottaHegbrant, JörgenStrippoli, Giovanni F.M.2018-04-25T06:25:11-07:00doi:10.1681/ASN.2018010008hwp:resource-id:jnephrol;29/6/1741American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyDietary patterns, Mediterranean diet, DASH diet, mortality, hemodialysis, end-stage kidney diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20182018-06-01June 201810.1681/ASN.20180100081046-66731533-34502018-04-25T06:25:11-07:002018-06Journal of the American Society of NephrologyClinical Epidemiology29661741158117511582
- Cooperation of Antiporter LAT2/CD98hc with Uniporter TAT1 for Renal Reabsorption of Neutral Amino AcidsBackground Reabsorption of amino acids (AAs) across the renal proximal tubule is crucial for intracellular and whole organism AA homeostasis. Although the luminal transport step is well understood, with several diseases caused by dysregulation of this process, the basolateral transport step is not understood. In humans, only cationic aminoaciduria due to malfunction of the basolateral transporter y+LAT1/CD98hc (SLC7A7/SLC3A2), which mediates the export of cationic AAs, has been described. Thus, the physiologic roles of basolateral transporters of neutral AAs, such as the antiporter LAT2/CD98hc (SLC7A8/SLC3A2), a heterodimer that exports most neutral AAs, and the uniporter TAT1 (SLC16A10), which exports only aromatic AAs, remain unclear. Functional cooperation between TAT1 and LAT2/CD98hc has been suggested by in vitro studies but has not been evaluated in vivo. Methods To study the functional relationship of TAT1 and LAT2/CD98hc in vivo, we generated a double-knockout mouse model lacking TAT1 and LAT2, the catalytic subunit of LAT2/CD98hc (dKO LAT2-TAT1 mice). Results Compared with mice lacking only TAT1 or LAT2, dKO LAT2-TAT1 mice lost larger amounts of aromatic and other neutral AAs in their urine due to a tubular reabsorption defect. Notably, dKO mice also displayed decreased tubular reabsorption of cationic AAs and increased expression of y+LAT1/CD98hc. Conclusions The LAT2/CD98hc and TAT1 transporters functionally cooperate in vivo, and y+LAT1/CD98hc may compensate for the loss of LAT2/CD98hc and TAT1, functioning as a neutral AA exporter at the expense of some urinary loss of cationic AAs. Cooperative and compensatory mechanisms of AA transporters may explain the lack of basolateral neutral aminoacidurias in humans.10.1681/ASN.2017111205Mon, 02 Apr 2018 06:38:35 GMT-07:00Cooperation of Antiporter LAT2/CD98hc with Uniporter TAT1 for Renal Reabsorption of Neutral Amino AcidsBackground Reabsorption of amino acids (AAs) across the renal proximal tubule is crucial for intracellular and whole organism AA homeostasis. Although the luminal transport step is well understood, with several diseases caused by dysregulation of this process, the basolateral transport step is not understood. In humans, only cationic aminoaciduria due to malfunction of the basolateral transporter y+LAT1/CD98hc (SLC7A7/SLC3A2), which mediates the export of cationic AAs, has been described. Thus, the physiologic roles of basolateral transporters of neutral AAs, such as the antiporter LAT2/CD98hc (SLC7A8/SLC3A2), a heterodimer that exports most neutral AAs, and the uniporter TAT1 (SLC16A10), which exports only aromatic AAs, remain unclear. Functional cooperation between TAT1 and LAT2/CD98hc has been suggested by in vitro studies but has not been evaluated in vivo. Methods To study the functional relationship of TAT1 and LAT2/CD98hc in vivo, we generated a double-knockout mouse model lacking TAT1 and LAT2, the catalytic subunit of LAT2/CD98hc (dKO LAT2-TAT1 mice). Results Compared with mice lacking only TAT1 or LAT2, dKO LAT2-TAT1 mice lost larger amounts of aromatic and other neutral AAs in their urine due to a tubular reabsorption defect. Notably, dKO mice also displayed decreased tubular reabsorption of cationic AAs and increased expression of y+LAT1/CD98hc. Conclusions The LAT2/CD98hc and TAT1 transporters functionally cooperate in vivo, and y+LAT1/CD98hc may compensate for the loss of LAT2/CD98hc and TAT1, functioning as a neutral AA exporter at the expense of some urinary loss of cationic AAs. Cooperative and compensatory mechanisms of AA transporters may explain the lack of basolateral neutral aminoacidurias in humans.Vilches, ClaraBoiadjieva-Knöpfel, EmiliaBodoy, SusannaCamargo, SimoneLópez de Heredia, MiguelPrat, EstherOrmazabal, AidaArtuch, RafaelZorzano, AntonioVerrey, FrançoisNunes, VirginiaPalacín, Manuel2018-04-02T06:38:35-07:00doi:10.1681/ASN.2017111205hwp:resource-id:jnephrol;29/6/1624American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAGAT, mitochondriopathy, tubulopathy, protein deposits, fibrosisBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20171112051046-66731533-34502018-04-02T06:38:35-07:002018-06Journal of the American Society of NephrologyBasic Research29616241635
- A Novel Method for Rapid Bedside Measurement of GFRBackground Direct quantitative measurement of GFR (mGFR) remains a specialized task primarily performed in research settings. Multiple formulas for estimating GFR have been developed that use the readily available endogenous biomarkers creatinine and/or cystatin C. However, eGFR formulas have limitations, and an accurate mGFR is necessary in some clinical situations and for certain patient populations. We conducted a prospective, open-label study to evaluate a novel rapid technique for determining plasma volume and mGFR. Methods We developed a new exogenous biomarker, visible fluorescent injectate (VFI), consisting of a large 150-kD rhodamine derivative and small 5-kD fluorescein carboxymethylated dextrans. After a single intravenous injection of VFI, plasma volume and mGFR can be determined on the basis of the plasma pharmacokinetics of the rhodamine derivative and fluorescein carboxymethylated dextrans, respectively. In this study involving 32 adults with normal kidney function (n=16), CKD stage 3 (n=8), or CKD stage 4 (n=8), we compared VFI-based mGFR values with values obtained by measuring iohexol plasma disappearance. VFI-based mGFR required three 0.5-ml blood draws over 3 hours; iohexol-based mGFR required five samples taken over 6 hours. Eight healthy participants received repeat VFI injections at 24 hours. Results VFI-based mGFR values showed close linear correlation with the iohexol-based mGFR values in all participants. Injections were well tolerated, including when given on consecutive days. No serious adverse events were reported. VFI-based mGFR was highly reproducible. Conclusions The VFI-based approach allows for the rapid determination of mGFR at the bedside while maintaining patient safety and measurement accuracy and reproducibility.10.1681/ASN.2018020160Thu, 10 May 2018 08:01:14 GMT-07:00A Novel Method for Rapid Bedside Measurement of GFRBackground Direct quantitative measurement of GFR (mGFR) remains a specialized task primarily performed in research settings. Multiple formulas for estimating GFR have been developed that use the readily available endogenous biomarkers creatinine and/or cystatin C. However, eGFR formulas have limitations, and an accurate mGFR is necessary in some clinical situations and for certain patient populations. We conducted a prospective, open-label study to evaluate a novel rapid technique for determining plasma volume and mGFR. Methods We developed a new exogenous biomarker, visible fluorescent injectate (VFI), consisting of a large 150-kD rhodamine derivative and small 5-kD fluorescein carboxymethylated dextrans. After a single intravenous injection of VFI, plasma volume and mGFR can be determined on the basis of the plasma pharmacokinetics of the rhodamine derivative and fluorescein carboxymethylated dextrans, respectively. In this study involving 32 adults with normal kidney function (n=16), CKD stage 3 (n=8), or CKD stage 4 (n=8), we compared VFI-based mGFR values with values obtained by measuring iohexol plasma disappearance. VFI-based mGFR required three 0.5-ml blood draws over 3 hours; iohexol-based mGFR required five samples taken over 6 hours. Eight healthy participants received repeat VFI injections at 24 hours. Results VFI-based mGFR values showed close linear correlation with the iohexol-based mGFR values in all participants. Injections were well tolerated, including when given on consecutive days. No serious adverse events were reported. VFI-based mGFR was highly reproducible. Conclusions The VFI-based approach allows for the rapid determination of mGFR at the bedside while maintaining patient safety and measurement accuracy and reproducibility.Rizk, Dana V.Meier, DanielSandoval, Ruben M.Chacana, TeresaReilly, Erinn S.Seegmiller, Jesse C.DeNoia, EmmanuelStrickland, James S.Muldoon, JosephMolitoris, Bruce A.2018-05-10T08:01:14-07:00doi:10.1681/ASN.2018020160hwp:resource-id:jnephrol;29/6/1609American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyBiomarker, FAST BioMedical, acute kidney injury, chronic kidney disease, fluorescent glomerular filtration rate measurement, kidney functionRapid CommunicationRapid CommunicationRapid Communication20182018-06-01June 201810.1681/ASN.20180201601046-66731533-34502018-05-10T08:01:14-07:002018-06Journal of the American Society of NephrologyRapid Communication29616091613
- Hydroxyproline Metabolism and Oxalate Synthesis in Primary HyperoxaluriaBackground Endogenous oxalate synthesis contributes to calcium oxalate stone disease and is markedly increased in the inherited primary hyperoxaluria (PH) disorders. The incomplete knowledge regarding oxalate synthesis complicates discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the formation of oxalate and glycolate. However, the relative contribution of Hyp metabolism to endogenous oxalate and glycolate synthesis is not known. Methods To define this contribution, we performed primed, continuous, intravenous infusions of the stable isotope [15N,13C5]-Hyp in nine healthy subjects and 19 individuals with PH and quantified the levels of urinary 13C2-oxalate and 13C2-glycolate formed using ion chromatography coupled to mass detection. Results The total urinary oxalate-to-creatinine ratio during the infusion was 73.1, 70.8, 47.0, and 10.6 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3 and controls, respectively. Hyp metabolism accounted for 12.8, 32.9, and 14.8 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3, respectively, compared with 1.6 mg oxalate/g creatinine in controls. The contribution of Hyp to urinary oxalate was 15% in controls and 18%, 47%, and 33% in subjects with PH1, PH2, and PH3, respectively. The contribution of Hyp to urinary glycolate was 57% in controls, 30% in subjects with PH1, and <13% in subjects with PH2 or PH3. Conclusions Hyp metabolism differs among PH types and is a major source of oxalate synthesis in individuals with PH2 and PH3. In patients with PH1, who have the highest urinary excretion of oxalate, the major sources of oxalate remain to be identified.10.1681/ASN.2017040390Tue, 27 Mar 2018 05:53:05 GMT-07:00Hydroxyproline Metabolism and Oxalate Synthesis in Primary HyperoxaluriaBackground Endogenous oxalate synthesis contributes to calcium oxalate stone disease and is markedly increased in the inherited primary hyperoxaluria (PH) disorders. The incomplete knowledge regarding oxalate synthesis complicates discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the formation of oxalate and glycolate. However, the relative contribution of Hyp metabolism to endogenous oxalate and glycolate synthesis is not known. Methods To define this contribution, we performed primed, continuous, intravenous infusions of the stable isotope [15N,13C5]-Hyp in nine healthy subjects and 19 individuals with PH and quantified the levels of urinary 13C2-oxalate and 13C2-glycolate formed using ion chromatography coupled to mass detection. Results The total urinary oxalate-to-creatinine ratio during the infusion was 73.1, 70.8, 47.0, and 10.6 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3 and controls, respectively. Hyp metabolism accounted for 12.8, 32.9, and 14.8 mg oxalate/g creatinine in subjects with PH1, PH2, and PH3, respectively, compared with 1.6 mg oxalate/g creatinine in controls. The contribution of Hyp to urinary oxalate was 15% in controls and 18%, 47%, and 33% in subjects with PH1, PH2, and PH3, respectively. The contribution of Hyp to urinary glycolate was 57% in controls, 30% in subjects with PH1, and <13% in subjects with PH2 or PH3. Conclusions Hyp metabolism differs among PH types and is a major source of oxalate synthesis in individuals with PH2 and PH3. In patients with PH1, who have the highest urinary excretion of oxalate, the major sources of oxalate remain to be identified.Fargue, SoniaMilliner, Dawn S.Knight, JohnOlson, Julie B.Lowther, W. ToddHolmes, Ross P.2018-03-27T05:53:05-07:00doi:10.1681/ASN.2017040390hwp:resource-id:jnephrol;29/6/1615American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, kidney stones, metabolism, oxalate, primary hyperoxaluria, hydroxyprolineBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20170403901046-66731533-34502018-03-27T05:53:05-07:002018-06Journal of the American Society of NephrologyBasic Research29616151623
- The Underestimated Burden of Monogenic Diseases in Adult-Onset ESRD10.1681/ASN.2018040441Wed, 16 May 2018 08:01:45 GMT-07:00The Underestimated Burden of Monogenic Diseases in Adult-Onset ESRDCornec-Le Gall, EmilieHarris, Peter C.2018-05-16T08:01:45-07:00doi:10.1681/ASN.2018040441hwp:resource-id:jnephrol;29/6/1583American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyNPHP, Adult ESRD, Molecular DiagnosticsUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-06-01June 201810.1681/ASN.20180404411046-66731533-34502018-05-16T08:01:45-07:002018-06Journal of the American Society of NephrologyUp Front Matters29661583177215841779
- Depletion of Gprc5a Promotes Development of Diabetic NephropathyBackground Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression. Methods To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein–coupled receptors (GPCRs) using human glomeruli. Results We identified an orphan GPCR, Gprc5a, as a highly podocyte-specific gene, the expression of which was significantly downregulated in glomeruli of patients with DN compared with those without DN. Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement membrane and activation of mesangial cells, which are two hallmark features of DN in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated increased albuminuria and more severe histologic changes after induction of diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF-β signaling and activation of the EGF receptor in cultured podocytes. Conclusions Gprc5a has an important role in the pathogenesis of DN, and further study of the podocyte-specific signaling activity of this protein is warranted.10.1681/ASN.2017101135Tue, 10 Apr 2018 08:02:07 GMT-07:00Depletion of Gprc5a Promotes Development of Diabetic NephropathyBackground Renal glomeruli are the primary target of injury in diabetic nephropathy (DN), and the glomerular podocyte has a key role in disease progression. Methods To identify potential novel therapeutic targets for DN, we performed high-throughput molecular profiling of G protein–coupled receptors (GPCRs) using human glomeruli. Results We identified an orphan GPCR, Gprc5a, as a highly podocyte-specific gene, the expression of which was significantly downregulated in glomeruli of patients with DN compared with those without DN. Inactivation of Gprc5a in mice resulted in thickening of the glomerular basement membrane and activation of mesangial cells, which are two hallmark features of DN in humans. Compared with wild-type mice, Gprc5a-deficient animals demonstrated increased albuminuria and more severe histologic changes after induction of diabetes with streptozotocin. Mechanistically, Gprc5a modulated TGF-β signaling and activation of the EGF receptor in cultured podocytes. Conclusions Gprc5a has an important role in the pathogenesis of DN, and further study of the podocyte-specific signaling activity of this protein is warranted.Ma, XiaojieSchwarz, AngelinaSevilla, Sonia ZambranoLevin, AnnaHultenby, KjellWernerson, AnnikaLal, MarkPatrakka, Jaakko2018-04-10T08:02:07-07:00doi:10.1681/ASN.2017101135hwp:resource-id:jnephrol;29/6/1679American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, diabetic nephropathy, TGF-beta, EGFRBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20171011351046-66731533-34502018-04-10T08:02:07-07:002018-06Journal of the American Society of NephrologyBasic Research29616791689
- Does the Receipt of Antibiotics for Common Infectious Diseases Predispose to Kidney Stones? A Cautionary Note for All Health Care Practitioners10.1681/ASN.2018040402Thu, 10 May 2018 08:01:15 GMT-07:00Does the Receipt of Antibiotics for Common Infectious Diseases Predispose to Kidney Stones? A Cautionary Note for All Health Care PractitionersNazzal, LamaBlaser, Martin J.2018-05-10T08:01:15-07:00doi:10.1681/ASN.2018040402hwp:resource-id:jnephrol;29/6/1590American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney stones, microbiome, nephrolithiasis, antibioticsUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-06-01June 201810.1681/ASN.20180404021046-66731533-34502018-05-10T08:01:15-07:002018-06Journal of the American Society of NephrologyUp Front Matters29661590173115921740
- Metabolomics Research in Chronic Kidney Disease10.1681/ASN.2018030256Thu, 03 May 2018 06:45:34 GMT-07:00Metabolomics Research in Chronic Kidney DiseaseGrams, Morgan E.Shafi, TariqRhee, Eugene P.2018-05-03T06:45:34-07:00doi:10.1681/ASN.2018030256hwp:resource-id:jnephrol;29/6/1588American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-06-01June 201810.1681/ASN.20180302561046-66731533-34502018-05-03T06:45:34-07:002018-06Journal of the American Society of NephrologyUp Front Matters29615881590
- Protein Mass Spectrometry Made Simple10.1681/ASN.2018030244Thu, 03 May 2018 06:45:34 GMT-07:00Protein Mass Spectrometry Made SimpleKlein, Jon B.A. Knepper, Mark2018-05-03T06:45:34-07:00doi:10.1681/ASN.2018030244hwp:resource-id:jnephrol;29/6/1585American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymass spectrometry, proteomics, pathologyUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-06-01June 201810.1681/ASN.20180302441046-66731533-34502018-05-03T06:45:34-07:002018-06Journal of the American Society of NephrologyUp Front Matters29615851587
- Vascularizing the Kidney in the Embryo and Organoid: Questioning Assumptions about Renal Vasculogenesis10.1681/ASN.2018020179Thu, 10 May 2018 08:01:14 GMT-07:00Vascularizing the Kidney in the Embryo and Organoid: Questioning Assumptions about Renal VasculogenesisMunro, David A.D.Davies, Jamie A.2018-05-10T08:01:14-07:00doi:10.1681/ASN.2018020179hwp:resource-id:jnephrol;29/6/1593American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyangiogenesis, vasculogenesis, blood vessels, vascular, endothelial cellsUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-06-01June 201810.1681/ASN.20180201791046-66731533-34502018-05-10T08:01:14-07:002018-06Journal of the American Society of NephrologyUp Front Matters29615931595
- The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter ExpressionBackground Nedd4–2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4–2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4–2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4–2 knockout mice using Cre-lox technology and produced global pendrin/Nedd4–2 null mice by breeding global Nedd4–2 null (Nedd4–2−/−) mice with global pendrin null (Slc26a4−/−) mice. Mice ate a diet with 1%–4% NaCl; BP was measured by tail cuff and radiotelemetry. We measured transepithelial transport of Cl− and total CO2 and transepithelial voltage in cortical collecting ducts perfused in vitro. Transporter abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry. Results IC Nedd4–2 gene ablation markedly increased electroneutral Cl−/HCO3− exchange in the cortical collecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little. IC Nedd4–2 gene ablation did not increase the abundance of type B IC transporters, such as AE4 (Slc4a9), H+-ATPase, barttin, or the Na+-dependent Cl−/HCO3− exchanger (Slc4a8). However, IC Nedd4–2 gene ablation increased CIC-5 total protein abundance, apical plasma membrane pendrin abundance, and the ratio of pendrin expression on the apical membrane to the cytoplasm. IC Nedd4–2 gene ablation increased BP by approximately 10 mm Hg. Moreover, pendrin gene ablation eliminated the increase in BP observed in global Nedd4–2 knockout mice. Conclusions IC Nedd4–2 regulates Cl−/HCO3− exchange in ICs., Nedd4–2 gene ablation increases BP in part through its action in these cells.10.1681/ASN.2017080826Thu, 17 May 2018 06:08:17 GMT-07:00The Role of Intercalated Cell Nedd4–2 in BP Regulation, Ion Transport, and Transporter ExpressionBackground Nedd4–2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4–2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4–2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4–2 knockout mice using Cre-lox technology and produced global pendrin/Nedd4–2 null mice by breeding global Nedd4–2 null (Nedd4–2−/−) mice with global pendrin null (Slc26a4−/−) mice. Mice ate a diet with 1%–4% NaCl; BP was measured by tail cuff and radiotelemetry. We measured transepithelial transport of Cl− and total CO2 and transepithelial voltage in cortical collecting ducts perfused in vitro. Transporter abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry. Results IC Nedd4–2 gene ablation markedly increased electroneutral Cl−/HCO3− exchange in the cortical collecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little. IC Nedd4–2 gene ablation did not increase the abundance of type B IC transporters, such as AE4 (Slc4a9), H+-ATPase, barttin, or the Na+-dependent Cl−/HCO3− exchanger (Slc4a8). However, IC Nedd4–2 gene ablation increased CIC-5 total protein abundance, apical plasma membrane pendrin abundance, and the ratio of pendrin expression on the apical membrane to the cytoplasm. IC Nedd4–2 gene ablation increased BP by approximately 10 mm Hg. Moreover, pendrin gene ablation eliminated the increase in BP observed in global Nedd4–2 knockout mice. Conclusions IC Nedd4–2 regulates Cl−/HCO3− exchange in ICs., Nedd4–2 gene ablation increases BP in part through its action in these cells.Nanami, MasayoshiPham, Truyen D.Kim, Young HeeYang, BaoliSutliff, Roy L.Staub, OlivierKlein, Janet D.Lopez-Cayuqueo, Karen I.Chambrey, ReginePark, Annie Y.Wang, XiaonanPech, VladimirVerlander, Jill W.Wall, Susan M.2018-05-17T06:08:17-07:00doi:10.1681/ASN.2017080826hwp:resource-id:jnephrol;29/6/1706American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, chloride, intercalated cells, cortical collecting duct, pendrinBasic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20170808261046-66731533-34502018-05-17T06:08:17-07:002018-06Journal of the American Society of NephrologyBasic Research29617061719
- An Engineered Complement Factor H Construct for Treatment of C3 GlomerulopathyBackground C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for C3G remain limited. Complement factor H (FH) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of FH makes generation of full-length FH far from trivial. We previously generated a mini-FH construct, with FH short consensus repeats 1–5 linked to repeats 18–20 (FH1–5^18–20), that was effective in experimental C3G. However, the serum t1/2 of FH1–5^18–20 was significantly shorter than that of serum-purified FH. Methods We introduced the oligomerization domain of human FH-related protein 1 (denoted by R1–2) at the carboxy or amino terminus of human FH1–5^18–20 to generate two homodimeric mini-FH constructs (FHR1–2^1–5^18–20 and FH1–5^18–20^R1–2, respectively) in Chinese hamster ovary cells and tested these constructs using binding, fluid-phase, and erythrocyte lysis assays, followed by experiments in FH-deficient Cfh−/− mice. Results FHR1–2^1–5^18–20 and FH1–5^18–20^R1–2 homodimerized in solution and displayed avid binding profiles on clustered C3b surfaces, particularly FHR1–2^1–5^18–20. Each construct was >10-fold more effective than FH at inhibiting cell surface complement activity in vitro and restricted glomerular basement membrane C3 deposition in vivo significantly better than FH or FH1–5^18–20. FH1–5^18–20^R1–2 had a C3 breakdown fragment binding profile similar to that of FH, a >5-fold increase in serum t1/2 compared with that of FH1–5^18–20, and significantly better retention in the kidney than FH or FH1–5^18–20. Conclusions FH1–5^18–20^R1–2 may have utility as a treatment option for C3G or other complement-mediated diseases.10.1681/ASN.2017091006Tue, 27 Mar 2018 05:53:06 GMT-07:00An Engineered Complement Factor H Construct for Treatment of C3 GlomerulopathyBackground C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for C3G remain limited. Complement factor H (FH) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of FH makes generation of full-length FH far from trivial. We previously generated a mini-FH construct, with FH short consensus repeats 1–5 linked to repeats 18–20 (FH1–5^18–20), that was effective in experimental C3G. However, the serum t1/2 of FH1–5^18–20 was significantly shorter than that of serum-purified FH. Methods We introduced the oligomerization domain of human FH-related protein 1 (denoted by R1–2) at the carboxy or amino terminus of human FH1–5^18–20 to generate two homodimeric mini-FH constructs (FHR1–2^1–5^18–20 and FH1–5^18–20^R1–2, respectively) in Chinese hamster ovary cells and tested these constructs using binding, fluid-phase, and erythrocyte lysis assays, followed by experiments in FH-deficient Cfh−/− mice. Results FHR1–2^1–5^18–20 and FH1–5^18–20^R1–2 homodimerized in solution and displayed avid binding profiles on clustered C3b surfaces, particularly FHR1–2^1–5^18–20. Each construct was >10-fold more effective than FH at inhibiting cell surface complement activity in vitro and restricted glomerular basement membrane C3 deposition in vivo significantly better than FH or FH1–5^18–20. FH1–5^18–20^R1–2 had a C3 breakdown fragment binding profile similar to that of FH, a >5-fold increase in serum t1/2 compared with that of FH1–5^18–20, and significantly better retention in the kidney than FH or FH1–5^18–20. Conclusions FH1–5^18–20^R1–2 may have utility as a treatment option for C3G or other complement-mediated diseases.Yang, YiDenton, HarrietDavies, Owen R.Smith-Jackson, KateKerr, HeatherHerbert, Andrew P.Barlow, Paul N.Pickering, Matthew C.Marchbank, Kevin J.2018-03-27T05:53:06-07:00doi:10.1681/ASN.2017091006hwp:resource-id:jnephrol;29/6/1649American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, glomerulopathy, Immunology and pathology, membranoproliferative glomerulonephritis (MPGN)Basic ResearchBasic Researchresearch-article20182018-06-01June 201810.1681/ASN.20170910061046-66731533-34502018-03-27T05:53:06-07:002018-06Journal of the American Society of NephrologyBasic Research29616491661
- Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKDCardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.10.1681/ASN.2018010068Tue, 17 Apr 2018 05:50:06 GMT-07:00Circulating Bacterial Fragments as Cardiovascular Risk Factors in CKDCardiovascular disease (CVD) is a major cause of mortality and morbidity in patients with CKD. In the past decade, intestinal dysbiosis and altered gut epithelial barrier function are increasingly recognized in CKD. Uremic patients have slow intestinal transit time, impaired protein assimilation, and decreased consumption of dietary fiber. The use of multiple medications also may contribute to the proliferation of dysbiotic bacteria, which affect the barrier function of intestinal epithelium. In addition, fluid overload and uremic toxins per se directly reduce the gut barrier function. The major consequence of these alterations, the translocation of bacterial fragments from bowel lumen to systemic circulation, can lead to diverse biologic effects and probably represents an important nontraditional CVD risk factor in CKD. Among all bacterial fragments, endotoxin is the most well studied. Plasma endotoxin levels are markedly elevated in both patients with CKD and those on dialysis, and are associated with the systemic inflammatory state, accelerated atherosclerosis, and clinical CVD in patients on dialysis. Optimization of BP control and the use of ultrapure dialysate can reduce plasma endotoxin levels, with probable metabolic and cardiovascular benefits. The benefit of synbiotic therapy is not confirmed, although results from animal studies are impressive. The biologic effects and clinical relevance of other bacterial fragments, such as bacterial DNA fragments, are less well defined. Further studies are needed to delineate the pathogenic relation between circulating bacterial fragments and CVD, and to define the role of the plasma bacterial fragment level as a prognostic indicator of CKD.Szeto, Cheuk-ChunMcIntyre, Christopher WilliamLi, Philip Kam-Tao2018-04-17T05:50:06-07:00doi:10.1681/ASN.2018010068hwp:resource-id:jnephrol;29/6/1601American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyDialysis, cardiovascular disease, infection, survivalUp Front MattersReviewsUp Front MattersReviewsbrief-report20182018-06-01June 201810.1681/ASN.20180100681046-66731533-34502018-04-17T05:50:06-07:002018-06Journal of the American Society of NephrologyUp Front Matters29616011608
- Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term SurvivalBackground The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens. Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde. Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss. Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.10.1681/ASN.2017111157Fri, 30 Mar 2018 07:04:24 GMT-07:00Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term SurvivalBackground The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens. Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde. Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss. Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.See, Sarah B.Aubert, OlivierLoupy, AlexandreVeras, YokarlaLebreton, XavierGao, BaoshanLegendre, ChristopheAnglicheau, DanyZorn, Emmanuel2018-03-30T07:04:24-07:00doi:10.1681/ASN.2017111157hwp:resource-id:jnephrol;29/6/1761American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynon-HLA antibodies, DSA, oxidation-specific epitopes, natural polyreactive antibodies, natural antibodiesClinical ResearchClinical Researchresearch-article20182018-06-01June 201810.1681/ASN.20171111571046-66731533-34502018-03-30T07:04:24-07:002018-06Journal of the American Society of NephrologyClinical Research29617611770
- Four-Dimensional Imaging of T Cells in Kidney Transplant RejectionKidney transplantation is the treatment of choice for ESRD but is complicated by the response of the recipient’s immune system to nonself histocompatibility antigens on the graft, resulting in rejection. Multiphoton intravital microscopy, referred to as four-dimensional imaging because it records dynamic events in three-dimensional tissue volumes, has emerged as a powerful tool to study immunologic processes in living animals. Here, we will review advances in understanding the complex mechanisms of T cell–mediated rejection made possible by four-dimensional imaging of mouse renal allografts. We will summarize recent data showing that activated (effector) T cell migration to the graft is driven by cognate antigen presented by dendritic cells that surround and penetrate peritubular capillaries, and that T cell–dendritic cell interactions persist in the graft over time, maintaining the immune response in the tissue.10.1681/ASN.2017070800Fri, 13 Apr 2018 07:22:17 GMT-07:00Four-Dimensional Imaging of T Cells in Kidney Transplant RejectionKidney transplantation is the treatment of choice for ESRD but is complicated by the response of the recipient’s immune system to nonself histocompatibility antigens on the graft, resulting in rejection. Multiphoton intravital microscopy, referred to as four-dimensional imaging because it records dynamic events in three-dimensional tissue volumes, has emerged as a powerful tool to study immunologic processes in living animals. Here, we will review advances in understanding the complex mechanisms of T cell–mediated rejection made possible by four-dimensional imaging of mouse renal allografts. We will summarize recent data showing that activated (effector) T cell migration to the graft is driven by cognate antigen presented by dendritic cells that surround and penetrate peritubular capillaries, and that T cell–dendritic cell interactions persist in the graft over time, maintaining the immune response in the tissue.Hughes, Andrew D.Lakkis, Fadi G.Oberbarnscheidt, Martin H.2018-04-13T07:22:17-07:00doi:10.1681/ASN.2017070800hwp:resource-id:jnephrol;29/6/1596American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, rejection, lymphocytes, intravital multiphoton microscopy, effector CD8 T cells, dendritic cellsUp Front MattersReviewsUp Front MattersReviewsbrief-report20182018-06-01June 201810.1681/ASN.20170708001046-66731533-34502018-04-13T07:22:17-07:002018-06Journal of the American Society of NephrologyUp Front Matters29615961600
- Incidence, Risk Factors, and Sequelae of Post-kidney Transplant DeliriumBackground Frail kidney transplant (KT) recipients may be particularly vulnerable to surgical stressors, resulting in delirium and subsequent adverse outcomes. We sought to identify the incidence, risk factors, and sequelae of post-KT delirium. Methods We studied 125,304 adult KT recipients (1999–2014) to estimate delirium incidence in national registry claims. Additionally, we used a validated chart abstraction algorithm to identify post-KT delirium in 893 adult recipients (2009–2017) from a cohort study of frailty. Delirium sequelae were identified using adjusted logistic regression (length of stay ≥2 weeks and institutional discharge [skilled nursing or rehabilitation facility]) and adjusted Cox regression (death-censored graft loss and mortality). Results Only 0.8% of KT recipients had a delirium claim. In the cohort study, delirium incidence increased with age (18–49 years old: 2.0%; 50–64 years old: 4.6%; 65–75 years old: 9.2%; and ≥75 years old: 13.8%) and frailty (9.0% versus 3.9%); 20.0% of frail recipients aged ≥75 years old experienced delirium. Frailty was independently associated with delirium (odds ratio [OR], 2.05; 95% confidence interval [95% CI], 1.02 to 4.13; P=0.04), but premorbid global cognitive function was not. Recipients with delirium had increased risks of ≥2-week length of stay (OR, 5.42; 95% CI, 2.76 to 10.66; P<0.001), institutional discharge (OR, 22.41; 95% CI, 7.85 to 63.98; P<0.001), graft loss (hazard ratio [HR], 2.73; 95% CI, 1.14 to 6.53; P=0.03), and mortality (HR, 3.12; 95% CI, 1.76 to 5.54; P<0.001). Conclusions Post-KT delirium is a strong risk factor for subsequent adverse outcomes, yet it is a clinical entity that is often missed.10.1681/ASN.2018010064Mon, 23 Apr 2018 05:36:58 GMT-07:00Incidence, Risk Factors, and Sequelae of Post-kidney Transplant DeliriumBackground Frail kidney transplant (KT) recipients may be particularly vulnerable to surgical stressors, resulting in delirium and subsequent adverse outcomes. We sought to identify the incidence, risk factors, and sequelae of post-KT delirium. Methods We studied 125,304 adult KT recipients (1999–2014) to estimate delirium incidence in national registry claims. Additionally, we used a validated chart abstraction algorithm to identify post-KT delirium in 893 adult recipients (2009–2017) from a cohort study of frailty. Delirium sequelae were identified using adjusted logistic regression (length of stay ≥2 weeks and institutional discharge [skilled nursing or rehabilitation facility]) and adjusted Cox regression (death-censored graft loss and mortality). Results Only 0.8% of KT recipients had a delirium claim. In the cohort study, delirium incidence increased with age (18–49 years old: 2.0%; 50–64 years old: 4.6%; 65–75 years old: 9.2%; and ≥75 years old: 13.8%) and frailty (9.0% versus 3.9%); 20.0% of frail recipients aged ≥75 years old experienced delirium. Frailty was independently associated with delirium (odds ratio [OR], 2.05; 95% confidence interval [95% CI], 1.02 to 4.13; P=0.04), but premorbid global cognitive function was not. Recipients with delirium had increased risks of ≥2-week length of stay (OR, 5.42; 95% CI, 2.76 to 10.66; P<0.001), institutional discharge (OR, 22.41; 95% CI, 7.85 to 63.98; P<0.001), graft loss (hazard ratio [HR], 2.73; 95% CI, 1.14 to 6.53; P=0.03), and mortality (HR, 3.12; 95% CI, 1.76 to 5.54; P<0.001). Conclusions Post-KT delirium is a strong risk factor for subsequent adverse outcomes, yet it is a clinical entity that is often missed.Haugen, Christine E.Mountford, AlexandraWarsame, FatimaBerkowitz, RachelBae, SunjaeG. Thomas, AlvinBrown, Charles H.Brennan, Daniel C.Neufeld, Karin J.Carlson, Michelle C.Segev, Dorry L.McAdams-DeMarco, Mara2018-04-23T05:36:58-07:00doi:10.1681/ASN.2018010064hwp:resource-id:jnephrol;29/6/1752American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygeriatric nephrology, kidney transplantation, transplant outcomes, clinical, epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20182018-06-01June 201810.1681/ASN.20180100641046-66731533-34502018-04-23T05:36:58-07:002018-06Journal of the American Society of NephrologyClinical Epidemiology29617521759
- Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction ObstructionIntrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm–derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2+ cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm–derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.10.1681/ASN.2017050482Mon, 06 Nov 2017 06:04:24 GMT-08:00Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction ObstructionIntrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm–derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2+ cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm–derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.Sheybani-Deloui, SepidehChi, LijunStaite, Marian V.Cain, Jason E.Nieman, Brian J.Henkelman, R. MarkWainwright, Brandon J.Potter, S. StevenBagli, Darius J.Lorenzo, Armando J.Rosenblum, Norman D.2017-11-06T06:04:24-08:00doi:10.1681/ASN.2017050482hwp:resource-id:jnephrol;29/2/532American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, transgenic mouse, signaling, pediatrics, obstructive, nephropathyBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170504821046-66731533-34502017-11-06T06:04:24-08:002018-02Journal of the American Society of NephrologyBasic Research292532544
- The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical CorrelationsPolyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1–3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.10.1681/ASN.2017050477Tue, 26 Dec 2017 06:09:47 GMT-08:00The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: Morphologic Definitions and Clinical CorrelationsPolyomavirus nephropathy (PVN) is a common viral infection of renal allografts, with biopsy-proven incidence of approximately 5%. A generally accepted morphologic classification of definitive PVN that groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses is lacking. Here, we report a morphologic classification scheme for definitive PVN from the Banff Working Group on Polyomavirus Nephropathy, comprising nine transplant centers in the United States and Europe. This study represents the largest systematic analysis of definitive PVN undertaken thus far. In a retrospective fashion, clinical data were collected from 192 patients and correlated with morphologic findings from index biopsies at the time of initial PVN diagnosis. Histologic features were centrally scored according to Banff guidelines, including additional semiquantitative histologic assessment of intrarenal polyomavirus replication/load levels. In-depth statistical analyses, including mixed effects repeated measures models and logistic regression, revealed two independent histologic variables to be most significantly associated with clinical presentation: intrarenal polyomavirus load levels and Banff interstitial fibrosis ci scores. These two statistically determined histologic variables formed the basis for the definition of three PVN classes that correlated strongest with three clinical parameters: presentation at time of index biopsy, serum creatinine levels/renal function over 24 months of follow-up, and graft failure. The PVN classes 1–3 as described here can easily be recognized in routine renal biopsy specimens. We recommend using this morphologic PVN classification scheme for diagnostic communication, especially at the time of index diagnosis, and in scientific studies to improve comparative data analysis.Nickeleit, VolkerSingh, Harsharan K.Randhawa, ParmjeetDrachenberg, Cinthia B.Bhatnagar, RamneeshBracamonte, ErikaChang, AnthonyChon, W. JamesDadhania, DarshanaDavis, Vicki G.Hopfer, HelmutMihatsch, Michael J.Papadimitriou, John C.Schaub, StefanStokes, Michael B.Tungekar, Mohammad F.Seshan, Surya V.,Nickeleit, VolkerSingh, Harsharan K.Randhawa, ParmjeetDrachenberg, Cinthia B.Bhatnagar, RamneeshBracamonte, ErikaChang, AnthonyChon, W. JamesDadhania, DarshanaDavis, Vicki G.Hopfer, HelmutMihatsch, Michael J.Papadimitriou, John C.Schaub, StefanStokes, Michael B.Tungekar, Mohammad F.Seshan, Surya V.2017-12-26T06:09:47-08:00doi:10.1681/ASN.2017050477hwp:resource-id:jnephrol;29/2/680American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyPolyomavirus Nephropathy, Intra renal polyomavirus load/replication level, Simian Virus 40 large T antigen, mixed-effects repeated measures model, Interquartile range, immunohistochemistryClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170504771046-66731533-34502017-12-26T06:09:47-08:002018-02Journal of the American Society of NephrologyClinical Research2922680354693355
- Extracellular Adenosine Stimulates Vacuolar ATPase–Dependent Proton Secretion in Medullary Intercalated CellsAcidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H+ secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration–approved drug, but very little is known about the effect of adenosine on IC function. Therefore, we investigated the role of adenosine in the regulation of V-ATPase in ICs. Intravenous treatment of mice with adenosine or agonists of ADORA2A and ADORA2B purinergic P1 receptors induced V-ATPase apical membrane accumulation in medullary A-ICs but not in cortical A-ICs or other IC subtypes. Both receptors are located in A-IC apical membranes, and adenosine injection increased urine adenosine concentration and decreased urine pH. Cell fractionation showed that adenosine or an ADORA2A or ADORA2B agonist induced V-ATPase translocation from vesicles to the plasma membrane and increased protein kinase A (PKA)–dependent protein phosphorylation in purified medullary ICs that were isolated from mice. Either ADORA2A or ADORA2B antagonists or the PKA inhibitor mPKI blocked these effects. Finally, a fluorescence pH assay showed that adenosine activates V-ATPase in isolated medullary ICs. Our study shows that medullary A-ICs respond to luminal adenosine through ADORA2A and ADORA2B receptors in a cAMP/PKA pathway–dependent mechanism to induce V-ATPase–dependent H+ secretion.10.1681/ASN.2017060643Fri, 08 Dec 2017 08:43:45 GMT-08:00Extracellular Adenosine Stimulates Vacuolar ATPase–Dependent Proton Secretion in Medullary Intercalated CellsAcidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H+ secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration–approved drug, but very little is known about the effect of adenosine on IC function. Therefore, we investigated the role of adenosine in the regulation of V-ATPase in ICs. Intravenous treatment of mice with adenosine or agonists of ADORA2A and ADORA2B purinergic P1 receptors induced V-ATPase apical membrane accumulation in medullary A-ICs but not in cortical A-ICs or other IC subtypes. Both receptors are located in A-IC apical membranes, and adenosine injection increased urine adenosine concentration and decreased urine pH. Cell fractionation showed that adenosine or an ADORA2A or ADORA2B agonist induced V-ATPase translocation from vesicles to the plasma membrane and increased protein kinase A (PKA)–dependent protein phosphorylation in purified medullary ICs that were isolated from mice. Either ADORA2A or ADORA2B antagonists or the PKA inhibitor mPKI blocked these effects. Finally, a fluorescence pH assay showed that adenosine activates V-ATPase in isolated medullary ICs. Our study shows that medullary A-ICs respond to luminal adenosine through ADORA2A and ADORA2B receptors in a cAMP/PKA pathway–dependent mechanism to induce V-ATPase–dependent H+ secretion.Battistone, Maria A.Nair, Anil V.Barton, Claire R.Liberman, Rachel N.Peralta, Maria A.Capen, Diane E.Brown, DennisBreton, Sylvie2017-12-08T08:43:45-08:00doi:10.1681/ASN.2017060643hwp:resource-id:jnephrol;29/2/545American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyadenosine, V-ATPase, intercalated cells, proton secretion, acid/base balance, ADORA2A and ADORA2BBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170606431046-66731533-34502017-12-08T08:43:45-08:002018-02Journal of the American Society of NephrologyBasic Research292545556
- Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated RejectionNo tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (P<0.001) and presence of interstitial fibrosis/tubular atrophy (P=0.003) at diagnosis and changes in GFR (P<0.001), peritubular capillaritis Banff score (P=0.002), and DSA mean fluorescence intensity (P<0.001) after treatment. Overall, this model showed good calibration and discrimination (C-statistic=0.84). The ABMR prognostic score derived from the prediction model identified three risk strata with 6-year kidney allograft survival rates of 6.0% (high-risk group, n=40), 44.9% (intermediate-risk group, n=36), and 84.4% (low-risk group, n=202), and it provided greater net clinical benefit to patients than did considering them all to have the same level of risk of allograft loss. The performance of the ABMR prognostic score was validated in an independent cohort of 202 kidney recipients with ABMR (C-statistic=0.79). The ABMR prognostic score could be used to inform therapeutic decisions in clinical practice and for the design of clinical trials.10.1681/ASN.2017070749Mon, 18 Dec 2017 06:53:04 GMT-08:00Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated RejectionNo tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (P<0.001) and presence of interstitial fibrosis/tubular atrophy (P=0.003) at diagnosis and changes in GFR (P<0.001), peritubular capillaritis Banff score (P=0.002), and DSA mean fluorescence intensity (P<0.001) after treatment. Overall, this model showed good calibration and discrimination (C-statistic=0.84). The ABMR prognostic score derived from the prediction model identified three risk strata with 6-year kidney allograft survival rates of 6.0% (high-risk group, n=40), 44.9% (intermediate-risk group, n=36), and 84.4% (low-risk group, n=202), and it provided greater net clinical benefit to patients than did considering them all to have the same level of risk of allograft loss. The performance of the ABMR prognostic score was validated in an independent cohort of 202 kidney recipients with ABMR (C-statistic=0.79). The ABMR prognostic score could be used to inform therapeutic decisions in clinical practice and for the design of clinical trials.Viglietti, DenisLoupy, AlexandreAubert, OlivierBestard, OriolVan Huyen, Jean-Paul DuongTaupin, Jean-LucGlotz, DenisLegendre, ChristopheJouven, XavierDelahousse, MichelKamar, NassimLefaucheur, Carmen2017-12-18T06:53:04-08:00doi:10.1681/ASN.2017070749hwp:resource-id:jnephrol;29/2/606American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, outcomes, rejectionClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170707491046-66731533-34502017-12-18T06:53:04-08:002018-02Journal of the American Society of NephrologyClinical Research2922606350619352
- MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial FunctionMitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709 ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further analyses showed that mitochondrial transcriptional factor A (TFAM) is a target gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial dysfunction and cell injury induced by cisplatin or miR-709 overexpression in vitro. Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice. Collectively, our results suggest that miR-709 has an important role in mediating cisplatin-induced AKI via negative regulation of TFAM and subsequent mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in acute tubular injury and suggest a novel target for the treatment of AKI.10.1681/ASN.2017040381Tue, 17 Oct 2017 06:48:30 GMT-07:00MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial FunctionMitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709 ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further analyses showed that mitochondrial transcriptional factor A (TFAM) is a target gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial dysfunction and cell injury induced by cisplatin or miR-709 overexpression in vitro. Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice. Collectively, our results suggest that miR-709 has an important role in mediating cisplatin-induced AKI via negative regulation of TFAM and subsequent mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in acute tubular injury and suggest a novel target for the treatment of AKI.Guo, YanNi, JiajiaChen, ShuangBai, MiLin, JiajuanDing, GuixiaZhang, YueSun, PingpingJia, ZhanjunHuang, SongmingYang, LiZhang, Aihua2017-10-17T06:48:30-07:00doi:10.1681/ASN.2017040381hwp:resource-id:jnephrol;29/2/449American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologymiR-709, mitochondria, TFAM, acute kidney injury, proximal tubular cellBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170403811046-66731533-34502017-10-17T06:48:30-07:002018-02Journal of the American Society of NephrologyBasic Research292449461
- BP Measurement in Clinical Practice: Time to SPRINT to Guideline-Recommended ProtocolsHypertension is the leading chronic disease risk factor in the world and is especially important in patients with CKD, nearly 90% of whom have hypertension. Recently, in the Systolic BP Intervention Trial (SPRINT), intensive lowering of clinic systolic BP to a target <120 mm Hg, compared with a standard BP target of <140 mm Hg, reduced risk for cardiovascular disease and all-cause mortality. However, because BP was measured unobserved using an automated device, some investigators have questioned the ability to translate SPRINT results into routine clinical practice, in which measurement of BP is typically less standardized. In this review, we discuss the BP measurement techniques used in major observational studies and clinical trials that form the evidence base for our current approach to treating hypertension, evaluate the effect of measurement technique on BP readings, and explore how ambulatory BP data from the SPRINT trial may inform this discussion. We conclude by arguing for implementation of guideline-recommended BP measurement techniques in routine clinical practice.10.1681/ASN.2017070753Thu, 19 Oct 2017 07:00:07 GMT-07:00BP Measurement in Clinical Practice: Time to SPRINT to Guideline-Recommended ProtocolsHypertension is the leading chronic disease risk factor in the world and is especially important in patients with CKD, nearly 90% of whom have hypertension. Recently, in the Systolic BP Intervention Trial (SPRINT), intensive lowering of clinic systolic BP to a target <120 mm Hg, compared with a standard BP target of <140 mm Hg, reduced risk for cardiovascular disease and all-cause mortality. However, because BP was measured unobserved using an automated device, some investigators have questioned the ability to translate SPRINT results into routine clinical practice, in which measurement of BP is typically less standardized. In this review, we discuss the BP measurement techniques used in major observational studies and clinical trials that form the evidence base for our current approach to treating hypertension, evaluate the effect of measurement technique on BP readings, and explore how ambulatory BP data from the SPRINT trial may inform this discussion. We conclude by arguing for implementation of guideline-recommended BP measurement techniques in routine clinical practice.Drawz, Paul E.Ix, Joachim H.2017-10-19T07:00:07-07:00doi:10.1681/ASN.2017070753hwp:resource-id:jnephrol;29/2/383American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, blood pressure, quality improvementUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-02-01February 201810.1681/ASN.20170707531046-66731533-34502017-10-19T07:00:07-07:002018-02Journal of the American Society of NephrologyUp Front Matters292383388
- Metabolic Acidosis and Subclinical Metabolic Acidosis in CKDMetabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO2 at ≥22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO2 and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.10.1681/ASN.2017040422Fri, 13 Oct 2017 06:12:18 GMT-07:00Metabolic Acidosis and Subclinical Metabolic Acidosis in CKDMetabolic acidosis is not uncommon in CKD and is linked with bone demineralization, muscle catabolism, and higher risks of CKD progression and mortality. Clinical practice guidelines recommend maintaining serum total CO2 at ≥22 mEq/L to help prevent these complications. Although a definitive trial testing whether correcting metabolic acidosis improves clinical outcomes has not been conducted, results from small, single-center studies support this notion. Furthermore, biologic plausibility supports the notion that a subset of patients with CKD have acid-mediated organ injury despite having a normal serum total CO2 and might benefit from oral alkali before overt acidosis develops. Identifying these individuals with subclinical metabolic acidosis is challenging, but recent results suggest that urinary acid excretion measurements may be helpful. The dose of alkali to provide in this setting is unknown as well. The review discusses these topics and the prevalence and risk factors of metabolic acidosis, mechanisms of acid-mediated organ injury, results from interventional studies, and potential harms of alkali therapy in CKD.Raphael, Kalani L.2017-10-13T06:12:18-07:00doi:10.1681/ASN.2017040422hwp:resource-id:jnephrol;29/2/376American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic metabolic acidosis, chronic kidney disease, ESRD, acidosis, mortalityUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-02-01February 201810.1681/ASN.20170404221046-66731533-34502017-10-13T06:12:18-07:002018-02Journal of the American Society of NephrologyUp Front Matters292376382
- Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney DiseaseThe association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m2 who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18.5–24.9 kg/m2; reference; n=192), overweight (25.0–29.9 kg/m2; n=168), or obese (≥30 kg/m2; n=81). We evaluated the longitudinal (5-year) association of overweight/obesity with change in total kidney volume (TKV) by magnetic resonance imaging using linear regression and multinomial logistic regression models. Among participants, mean±SD age was 37±8 years, annual percent change in TKV was 7.4%±5.1%, and BMI was 26.3±4.9 kg/m2. The annual percent change in TKV increased with increasing BMI category (normal weight: 6.1%±4.7%, overweight: 7.9%±4.8%, obese: 9.4%±6.2%; P<0.001). In the fully adjusted model, higher BMI associated with greater annual percent change in TKV (β=0.79; 95% confidence interval [95% CI], 0.18 to 1.39, per 5-unit increase in BMI). Overweight and obesity associated with increased odds of annual percent change in TKV ≥7% compared with <5% (overweight: odds ratio, 2.02; 95% CI, 1.15 to 3.56; obese: odds ratio, 3.76; 95% CI, 1.81 to 7.80). Obesity also independently associated with greater eGFR decline (slope) versus normal weight (fully adjusted β =−0.08; 95% CI, −0.15 to −0.02). In conclusion, overweight and, particularly, obesity are strongly and independently associated with rate of progression in early-stage ADPKD.10.1681/ASN.2017070819Wed, 08 Nov 2017 06:11:36 GMT-08:00Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney DiseaseThe association of overweight/obesity with disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) remains untested. We hypothesized that overweight/obesity associates with faster progression in early-stage ADPKD. Overall, 441 nondiabetic participants with ADPKD and an eGFR>60 ml/min per 1.73 m2 who participated in the Halt Progression of Polycystic Kidney Disease Study A were categorized on the basis of body mass index (BMI; calculated using nonkidney and nonliver weight) as normal weight (18.5–24.9 kg/m2; reference; n=192), overweight (25.0–29.9 kg/m2; n=168), or obese (≥30 kg/m2; n=81). We evaluated the longitudinal (5-year) association of overweight/obesity with change in total kidney volume (TKV) by magnetic resonance imaging using linear regression and multinomial logistic regression models. Among participants, mean±SD age was 37±8 years, annual percent change in TKV was 7.4%±5.1%, and BMI was 26.3±4.9 kg/m2. The annual percent change in TKV increased with increasing BMI category (normal weight: 6.1%±4.7%, overweight: 7.9%±4.8%, obese: 9.4%±6.2%; P<0.001). In the fully adjusted model, higher BMI associated with greater annual percent change in TKV (β=0.79; 95% confidence interval [95% CI], 0.18 to 1.39, per 5-unit increase in BMI). Overweight and obesity associated with increased odds of annual percent change in TKV ≥7% compared with <5% (overweight: odds ratio, 2.02; 95% CI, 1.15 to 3.56; obese: odds ratio, 3.76; 95% CI, 1.81 to 7.80). Obesity also independently associated with greater eGFR decline (slope) versus normal weight (fully adjusted β =−0.08; 95% CI, −0.15 to −0.02). In conclusion, overweight and, particularly, obesity are strongly and independently associated with rate of progression in early-stage ADPKD.Nowak, Kristen L.You, ZhiyingGitomer, BereniceBrosnahan, GodelaTorres, Vicente E.Chapman, Arlene B.Perrone, Ronald D.Steinman, Theodore I.Abebe, Kaleab Z.Rahbari-Oskoui, Frederic F.Yu, Alan S.L.Harris, Peter C.Bae, Kyongtae T.Hogan, MarieMiskulin, DanaChonchol, Michel2017-11-08T06:11:36-08:00doi:10.1681/ASN.2017070819hwp:resource-id:jnephrol;29/2/571American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, clinical epidemiology, obesity, renal function decline, total kidney volumeClinical EpidemiologyClinical Epidemiologyresearch-article20182018-02-01February 201810.1681/ASN.20170708191046-66731533-34502017-11-08T06:11:36-08:002018-02Journal of the American Society of NephrologyClinical Epidemiology292571578
- Perioperative THR-184 and AKI after Cardiac SurgeryAKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%–79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%–20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.10.1681/ASN.2017020217Mon, 04 Dec 2017 08:31:59 GMT-08:00Perioperative THR-184 and AKI after Cardiac SurgeryAKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%–79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%–20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.Himmelfarb, JonathanChertow, Glenn M.McCullough, Peter A.Mesana, ThierryShaw, Andrew D.Sundt, Thoralf M.Brown, CraigCortville, DavidDagenais, Françoisde Varennes, BenoitFontes, ManuelRossert, JeromeTardif, Jean-Claude2017-12-04T08:31:59-08:00doi:10.1681/ASN.2017020217hwp:resource-id:jnephrol;29/2/670American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, bone morphogenetic protein, randomized controlled trialsClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170202171046-66731533-34502017-12-04T08:31:59-08:002018-02Journal of the American Society of NephrologyClinical Research292670679
- Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin IMeasures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification. Renal function did not significantly affect sensitivity or negative predictive values. Specificity decreased with impaired renal function from 93%–95% with normal function (eGFR≥90 ml/min per 1.73 m2; n=722) to 57%–61% with severely impaired renal function (eGFR<30 ml/min per 1.73 m2; n=81) and 40%–41% on dialysis (n=78). Positive predictive values decreased with decreasing renal function from 51%–57% with normal function to 27%–42% with severely impaired function and 15%–32% on dialysis. Receiver operating characteristic curve areas trended lower at baseline and 3 hours with renal impairment. Mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, and 10.4%, respectively). Patients with hs-cTnI concentration exceeding concentrations in the 99th percentiles had a mortality rate (11.7%) significantly higher than that of patients with concentrations between 99th percentile concentrations and limit of detection (6.2%) or below limit of detection (1.1%). Renal dysfunction and dialysis reduced the rule-in performance but not the rule-out performance of hs-cTnI for myocardial infarction, and mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction.10.1681/ASN.2017030341Fri, 27 Oct 2017 06:06:36 GMT-07:00Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin IMeasures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification. Renal function did not significantly affect sensitivity or negative predictive values. Specificity decreased with impaired renal function from 93%–95% with normal function (eGFR≥90 ml/min per 1.73 m2; n=722) to 57%–61% with severely impaired renal function (eGFR<30 ml/min per 1.73 m2; n=81) and 40%–41% on dialysis (n=78). Positive predictive values decreased with decreasing renal function from 51%–57% with normal function to 27%–42% with severely impaired function and 15%–32% on dialysis. Receiver operating characteristic curve areas trended lower at baseline and 3 hours with renal impairment. Mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, and 10.4%, respectively). Patients with hs-cTnI concentration exceeding concentrations in the 99th percentiles had a mortality rate (11.7%) significantly higher than that of patients with concentrations between 99th percentile concentrations and limit of detection (6.2%) or below limit of detection (1.1%). Renal dysfunction and dialysis reduced the rule-in performance but not the rule-out performance of hs-cTnI for myocardial infarction, and mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction.Gunsolus, IanSandoval, YaderSmith, Stephen W.Sexter, AnneSchulz, KarenHerzog, Charles A.Apple, Fred S.2017-10-27T06:06:36-07:00doi:10.1681/ASN.2017030341hwp:resource-id:jnephrol;29/2/636American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, cardiac troponin, myocardial infarction, outcomesClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170303411046-66731533-34502017-10-27T06:06:36-07:002018-02Journal of the American Society of NephrologyClinical Research292636643
- Clinical Decision Support for In-Hospital AKIAKI carries a significant mortality and morbidity risk. Use of a clinical decision support system (CDSS) might improve outcomes. We conducted a multicenter, sequential period analysis of 528,108 patients without ESRD before admission, from October of 2012 to September of 2015, to determine whether use of a CDSS reduces hospital length of stay and in-hospital mortality for patients with AKI. We compared patients treated 12 months before (181,696) and 24 months after (346,412) implementation of the CDSS. Coprimary outcomes were hospital mortality and length of stay adjusted by demographics and comorbidities. AKI was diagnosed in 64,512 patients (12.2%). Crude mortality rate fell from 10.2% before to 9.4% after CDSS implementation (odds ratio, 0.91; 95% confidence interval [95% CI], 0.86 to 0.96; P=0.001) for patients with AKI but did not change in patients without AKI (from 1.5% to 1.4%). Mean hospital duration decreased from 9.3 to 9.0 days (P<0.001) for patients with AKI, with no change for patients without AKI. In multivariate mixed-effects models, the adjusted odds ratio (95% CI) was 0.76 (0.70 to 0.83) for mortality and 0.66 (0.61 to 0.72) for dialysis (P<0.001). Change in adjusted hospital length of stay was also significant (incidence rate ratio, 0.91; 95% CI, 0.89 to 0.92), decreasing from 7.2 to 6.0 days for patients with AKI. Results were robust to sensitivity analyses and were sustained for the duration of follow-up. Hence, implementation of a CDSS for AKI resulted in a small but sustained decrease in hospital mortality, dialysis use, and length of stay.10.1681/ASN.2017070765Thu, 02 Nov 2017 02:30:09 GMT-07:00Clinical Decision Support for In-Hospital AKIAKI carries a significant mortality and morbidity risk. Use of a clinical decision support system (CDSS) might improve outcomes. We conducted a multicenter, sequential period analysis of 528,108 patients without ESRD before admission, from October of 2012 to September of 2015, to determine whether use of a CDSS reduces hospital length of stay and in-hospital mortality for patients with AKI. We compared patients treated 12 months before (181,696) and 24 months after (346,412) implementation of the CDSS. Coprimary outcomes were hospital mortality and length of stay adjusted by demographics and comorbidities. AKI was diagnosed in 64,512 patients (12.2%). Crude mortality rate fell from 10.2% before to 9.4% after CDSS implementation (odds ratio, 0.91; 95% confidence interval [95% CI], 0.86 to 0.96; P=0.001) for patients with AKI but did not change in patients without AKI (from 1.5% to 1.4%). Mean hospital duration decreased from 9.3 to 9.0 days (P<0.001) for patients with AKI, with no change for patients without AKI. In multivariate mixed-effects models, the adjusted odds ratio (95% CI) was 0.76 (0.70 to 0.83) for mortality and 0.66 (0.61 to 0.72) for dialysis (P<0.001). Change in adjusted hospital length of stay was also significant (incidence rate ratio, 0.91; 95% CI, 0.89 to 0.92), decreasing from 7.2 to 6.0 days for patients with AKI. Results were robust to sensitivity analyses and were sustained for the duration of follow-up. Hence, implementation of a CDSS for AKI resulted in a small but sustained decrease in hospital mortality, dialysis use, and length of stay.Al-Jaghbeer, MohammedDealmeida, DilhariBilderback, AndrewAmbrosino, RichardKellum, John A.2017-11-02T14:30:09-07:00doi:10.1681/ASN.2017070765hwp:resource-id:jnephrol;29/2/654American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyElectronic medical record, electronic health record, electronic alerts, radio contrast, nephrotoxicity, acute renal failureClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170707651046-66731533-34502017-11-02T14:30:09-07:002018-02Journal of the American Society of NephrologyClinical Research2922654352660354
- Progressive Renal Disease Established by Renin-Coding Adeno-Associated Virus–Driven Hypertension in Diverse Diabetic ModelsProgress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV). Compared with LacZAAV-treated counterparts, ReninAAV-treated type 1 diabetic Akita/129 mice exhibited a substantial increase in albumin-to-creatinine ratio (ACR) and serum creatinine level and more severe renal lesions. In type 2 models of diabetes (C57BKLS db/db and BTBR ob/ob mice), compared with LacZAAV, ReninAAV induced significant elevations in ACR and increased the incidence and severity of histopathologic findings, with increased serum creatinine detected only in the ReninAAV-treated db/db mice. The uninephrectomized ReninAAV db/db model was the most progressive model examined and further characterized. In this model, separate treatment of hyperglycemia with rosiglitazone or hypertension with lisinopril partially reduced ACR, consistent with independent contributions of these disorders to renal disease. Microarray analysis and comparison with human DKD showed common pathways affected in human disease and this model. These results identify novel models of progressive DKD that provide researchers with a facile and reliable method to study disease pathogenesis and support the development of therapeutics.10.1681/ASN.2017040385Mon, 23 Oct 2017 06:02:12 GMT-07:00Progressive Renal Disease Established by Renin-Coding Adeno-Associated Virus–Driven Hypertension in Diverse Diabetic ModelsProgress in research and developing therapeutics to prevent diabetic kidney disease (DKD) is limited by a lack of animal models exhibiting progressive kidney disease. Chronic hypertension, a driving factor of disease progression in human patients, is lacking in most available models of diabetes. We hypothesized that superimposition of hypertension on diabetic mouse models would accelerate DKD. To test this possibility, we induced persistent hypertension in three mouse models of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus delivery of renin (ReninAAV). Compared with LacZAAV-treated counterparts, ReninAAV-treated type 1 diabetic Akita/129 mice exhibited a substantial increase in albumin-to-creatinine ratio (ACR) and serum creatinine level and more severe renal lesions. In type 2 models of diabetes (C57BKLS db/db and BTBR ob/ob mice), compared with LacZAAV, ReninAAV induced significant elevations in ACR and increased the incidence and severity of histopathologic findings, with increased serum creatinine detected only in the ReninAAV-treated db/db mice. The uninephrectomized ReninAAV db/db model was the most progressive model examined and further characterized. In this model, separate treatment of hyperglycemia with rosiglitazone or hypertension with lisinopril partially reduced ACR, consistent with independent contributions of these disorders to renal disease. Microarray analysis and comparison with human DKD showed common pathways affected in human disease and this model. These results identify novel models of progressive DKD that provide researchers with a facile and reliable method to study disease pathogenesis and support the development of therapeutics.Harlan, Shannon M.Heinz-Taheny, Kathleen M.Sullivan, John M.Wei, TaoBaker, Hana E.Jaqua, Dianna L.Qi, ZhonghuaCramer, Martin S.Shiyanova, Tatiyana L.Breyer, Matthew D.Heuer, Josef G.2017-10-23T06:02:12-07:00doi:10.1681/ASN.2017040385hwp:resource-id:jnephrol;29/2/477American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic diabetic complications, diabetic nephropathy, diabetic glomerulopathy, electron microscopy, hypertensionBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170403851046-66731533-34502017-10-23T06:02:12-07:002018-02Journal of the American Society of NephrologyBasic Research292477491
- Segmental Sclerosis and Extracapillary Hypercellularity Predict Diabetic ESRDPathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking. We characterized the prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011 with diabetic glomerulosclerosis as the only glomerular disease diagnosis (n=109). Biopsy specimens were analyzed according to standard methods, including determination of diabetic nephropathy class, as defined by the Renal Pathology Society. Clinical data were extracted from electronic medical records. We used competing risk models, with death as the competing risk, to estimate subdistribution hazard ratios (HRs) for ESRD. All multivariable models included age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic characteristics achieving P<0.1 were added into successively complex models. ESRD occurred in 56% of patients, and 26% of patients died before reaching ESRD. In univariate analyses, diabetic nephropathy class was not statistically significant in predicting time to ESRD. The final multivariable model (n=106) showed a borderline association between mild mesangial expansion and decreased risk for ESRD (subdistribution HR, 0.64; 95% confidence interval, 0.40 to 1.00). Poor prognostic factors in the final model included segmental sclerosis and extracapillary hypercellularity (subdistribution HR, 2.04; 95% confidence interval, 1.36 to 3.05; and subdistribution HR, 2.21; 95% confidence interval, 1.19 to 4.11, respectively). In conclusion, we identified segmental sclerosis and extracapillary hypercellularity as novel, poor prognostic indicators of time from DKD to ESRD. Whether these indicators represent a distinct pathogenetic phenotype of DKD will require a large study with a broad spectrum of disease severity.10.1681/ASN.2017020192Mon, 27 Nov 2017 06:42:39 GMT-08:00Segmental Sclerosis and Extracapillary Hypercellularity Predict Diabetic ESRDPathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking. We characterized the prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011 with diabetic glomerulosclerosis as the only glomerular disease diagnosis (n=109). Biopsy specimens were analyzed according to standard methods, including determination of diabetic nephropathy class, as defined by the Renal Pathology Society. Clinical data were extracted from electronic medical records. We used competing risk models, with death as the competing risk, to estimate subdistribution hazard ratios (HRs) for ESRD. All multivariable models included age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic characteristics achieving P<0.1 were added into successively complex models. ESRD occurred in 56% of patients, and 26% of patients died before reaching ESRD. In univariate analyses, diabetic nephropathy class was not statistically significant in predicting time to ESRD. The final multivariable model (n=106) showed a borderline association between mild mesangial expansion and decreased risk for ESRD (subdistribution HR, 0.64; 95% confidence interval, 0.40 to 1.00). Poor prognostic factors in the final model included segmental sclerosis and extracapillary hypercellularity (subdistribution HR, 2.04; 95% confidence interval, 1.36 to 3.05; and subdistribution HR, 2.21; 95% confidence interval, 1.19 to 4.11, respectively). In conclusion, we identified segmental sclerosis and extracapillary hypercellularity as novel, poor prognostic indicators of time from DKD to ESRD. Whether these indicators represent a distinct pathogenetic phenotype of DKD will require a large study with a broad spectrum of disease severity.Mottl, Amy K.Gasim, AdilSchober, Fernanda PayanHu, YichunDunnon, Askia K.Hogan, Susan L.Jennette, J. Charles2017-11-27T06:42:39-08:00doi:10.1681/ASN.2017020192hwp:resource-id:jnephrol;29/2/694American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic glomerulosclerosis, pathology, extracapillary hypercellularity, end stage, renal disease, segmental sclerosisClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170201921046-66731533-34502017-11-27T06:42:39-08:002018-02Journal of the American Society of NephrologyClinical Research292694703
- Bardoxolone—the Phoenix?10.1681/ASN.2017121317Thu, 25 Jan 2018 06:04:03 GMT-08:00Bardoxolone—the Phoenix?Toto, Robert D.2018-01-25T06:04:03-08:00doi:10.1681/ASN.2017121317hwp:resource-id:jnephrol;29/2/360American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAlport-s syndrome, Chronic inflammation, chronic kidney disease, BardoxoloneUp Front MattersPerspectivesUp Front MattersPerspectiveseditorial20182018-02-01February 201810.1681/ASN.20171213171046-66731533-34502018-01-25T06:04:03-08:002018-02Journal of the American Society of NephrologyUp Front Matters29222360355357361356359
- Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the Treatment of Diabetic NephropathyAltered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice. Inhibition of CB1R also downregulated GLUT2 expression, affected the dynamic translocation of GLUT2 to the brush border membrane of RPTCs, and reduced glucose reabsorption. Thus, targeting peripheral CB1R or inhibiting GLUT2 dynamics in RPTCs has the potential to treat and ameliorate DN. These findings may support the rationale for the clinical testing of peripherally restricted CB1R antagonists or the development of novel renal-specific GLUT2 inhibitors against DN.10.1681/ASN.2017040371Fri, 13 Oct 2017 06:12:18 GMT-07:00Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the Treatment of Diabetic NephropathyAltered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice. Inhibition of CB1R also downregulated GLUT2 expression, affected the dynamic translocation of GLUT2 to the brush border membrane of RPTCs, and reduced glucose reabsorption. Thus, targeting peripheral CB1R or inhibiting GLUT2 dynamics in RPTCs has the potential to treat and ameliorate DN. These findings may support the rationale for the clinical testing of peripherally restricted CB1R antagonists or the development of novel renal-specific GLUT2 inhibitors against DN.Hinden, LiadUdi, ShiranDrori, AdiGammal, AsaadNemirovski, AlinaHadar, RivkaBaraghithy, SajaPermyakova, AnnaGeron, MatanCohen, MeravTsytkin-Kirschenzweig, SabinaRiahi, YaelLeibowitz, GilNahmias, YaakovPriel, AviTam, Joseph2017-10-13T06:12:18-07:00doi:10.1681/ASN.2017040371hwp:resource-id:jnephrol;29/2/434American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyEndocannabinoids, GLUT2, diabetic nephropathy, Renal Proximal Tubule Cells, CB1 ReceptorBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170403711046-66731533-34502017-10-13T06:12:18-07:002018-02Journal of the American Society of NephrologyBasic Research292434448
- Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous NephropathyThe phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). At baseline, the epitope profile (CysR, CysRC1, CysRC7, or CysRC1C7) did not correlate with age, sex, time from diagnosis, proteinuria, or serum albumin, but epitope spreading strongly correlated with PLA2R1-Ab titer (P<0.001). Ten (58.8%) of the 17 patients who had epitope spreading at baseline and were treated with rituximab showed reversal of epitope spreading at month 6. In adjusted analysis, epitope spreading at baseline was associated with a decreased remission rate at month 6 (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.72; P=0.02) and last follow-up (median, 23 months; odds ratio, 0.14; 95% confidence interval, 0.03 to 0.64; P=0.01), independently from age, sex, baseline PLA2R1-Ab level, and treatment group. We propose that epitope spreading at baseline be considered in the decision for early therapeutic intervention in patients with primary membranous nephropathy.10.1681/ASN.2017070734Tue, 07 Nov 2017 08:42:44 GMT-08:00Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous NephropathyThe phospholipase A2 receptor (PLA2R1) is the major autoantigen in primary membranous nephropathy. Several PLA2R1 epitopes have been characterized, and a retrospective study identified PLA2R1 epitope spreading as a potential indicator of poor prognosis. Here, we analyzed the predictive value of anti-PLA2R1 antibody (PLA2R1-Ab) titers and epitope spreading in a prospective cohort of 58 patients positive for PLA2R1-Ab randomly allocated to rituximab (n=29) or antiproteinuric therapy alone (n=29). At baseline, the epitope profile (CysR, CysRC1, CysRC7, or CysRC1C7) did not correlate with age, sex, time from diagnosis, proteinuria, or serum albumin, but epitope spreading strongly correlated with PLA2R1-Ab titer (P<0.001). Ten (58.8%) of the 17 patients who had epitope spreading at baseline and were treated with rituximab showed reversal of epitope spreading at month 6. In adjusted analysis, epitope spreading at baseline was associated with a decreased remission rate at month 6 (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.72; P=0.02) and last follow-up (median, 23 months; odds ratio, 0.14; 95% confidence interval, 0.03 to 0.64; P=0.01), independently from age, sex, baseline PLA2R1-Ab level, and treatment group. We propose that epitope spreading at baseline be considered in the decision for early therapeutic intervention in patients with primary membranous nephropathy.Seitz-Polski, BarbaraDebiec, HannaRousseau, AlexandraDahan, KarineZaghrini, ChristellePayré, ChristineEsnault, Vincent L.M.Lambeau, GérardRonco, Pierre2017-11-07T08:42:44-08:00doi:10.1681/ASN.2017070734hwp:resource-id:jnephrol;29/2/401American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical immunology, membranous nephropathy, Immunology and pathology, immunosuppression, randomized controlled trialsBrief CommunicationsBrief Communicationsbrief-report20182018-02-01February 201810.1681/ASN.20170707341046-66731533-34502017-11-07T08:42:44-08:002018-02Journal of the American Society of NephrologyBrief Communications292401408
- Chromatin Conformation Links Distal Target Genes to CKD LociGenome-wide association studies (GWASs) have identified many genetic risk factors for CKD. However, linking common variants to genes that are causal for CKD etiology remains challenging. By adapting self-transcribing active regulatory region sequencing, we evaluated the effect of genetic variation on DNA regulatory elements (DREs). Variants in linkage with the CKD-associated single-nucleotide polymorphism rs11959928 were shown to affect DRE function, illustrating that genes regulated by DREs colocalizing with CKD-associated variation can be dysregulated and therefore, considered as CKD candidate genes. To identify target genes of these DREs, we used circular chromosome conformation capture (4C) sequencing on glomerular endothelial cells and renal tubular epithelial cells. Our 4C analyses revealed interactions of CKD-associated susceptibility regions with the transcriptional start sites of 304 target genes. Overlap with multiple databases confirmed that many of these target genes are involved in kidney homeostasis. Expression quantitative trait loci analysis revealed that mRNA levels of many target genes are genotype dependent. Pathway analyses showed that target genes were enriched in processes crucial for renal function, identifying dysregulated geranylgeranyl diphosphate biosynthesis as a potential disease mechanism. Overall, our data annotated multiple genes to previously reported CKD-associated single-nucleotide polymorphisms and provided evidence for interaction between these loci and target genes. This pipeline provides a novel technique for hypothesis generation and complements classic GWAS interpretation. Future studies are required to specify the implications of our dataset and further reveal the complex roles that common variants have in complex diseases, such as CKD.10.1681/ASN.2016080875Wed, 01 Nov 2017 06:17:44 GMT-07:00Chromatin Conformation Links Distal Target Genes to CKD LociGenome-wide association studies (GWASs) have identified many genetic risk factors for CKD. However, linking common variants to genes that are causal for CKD etiology remains challenging. By adapting self-transcribing active regulatory region sequencing, we evaluated the effect of genetic variation on DNA regulatory elements (DREs). Variants in linkage with the CKD-associated single-nucleotide polymorphism rs11959928 were shown to affect DRE function, illustrating that genes regulated by DREs colocalizing with CKD-associated variation can be dysregulated and therefore, considered as CKD candidate genes. To identify target genes of these DREs, we used circular chromosome conformation capture (4C) sequencing on glomerular endothelial cells and renal tubular epithelial cells. Our 4C analyses revealed interactions of CKD-associated susceptibility regions with the transcriptional start sites of 304 target genes. Overlap with multiple databases confirmed that many of these target genes are involved in kidney homeostasis. Expression quantitative trait loci analysis revealed that mRNA levels of many target genes are genotype dependent. Pathway analyses showed that target genes were enriched in processes crucial for renal function, identifying dysregulated geranylgeranyl diphosphate biosynthesis as a potential disease mechanism. Overall, our data annotated multiple genes to previously reported CKD-associated single-nucleotide polymorphisms and provided evidence for interaction between these loci and target genes. This pipeline provides a novel technique for hypothesis generation and complements classic GWAS interpretation. Future studies are required to specify the implications of our dataset and further reveal the complex roles that common variants have in complex diseases, such as CKD.Brandt, Maarten M.Meddens, Claartje A.Louzao-Martinez, Lauravan den Dungen, Noortje A.M.Lansu, Nico R.Nieuwenhuis, Edward E.S.Duncker, Dirk J.Verhaar, Marianne C.Joles, Jaap A.Mokry, MichalCheng, Caroline2017-11-01T06:17:44-07:00doi:10.1681/ASN.2016080875hwp:resource-id:jnephrol;29/2/462American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, circular chromosome conformation capture (4C) sequencing, DNA regulatory elements, 3D chromatin structure, transcriptional regulation, STARR-seqBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20160808751046-66731533-34502017-11-01T06:17:44-07:002018-02Journal of the American Society of NephrologyBasic Research292462476
- Should We Increase GFR with Bardoxolone in Alport Syndrome?10.1681/ASN.2017101062Thu, 25 Jan 2018 06:04:05 GMT-08:00Should We Increase GFR with Bardoxolone in Alport Syndrome?Baigent, ColinLennon, Rachel2018-01-25T06:04:05-08:00doi:10.1681/ASN.2017101062hwp:resource-id:jnephrol;29/2/357American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAlport-s syndrome, glomerular hyperfiltration, progression of chronic renal failure, renin angiotensin systemUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-02-01February 201810.1681/ASN.20171010621046-66731533-34502018-01-25T06:04:05-08:002018-02Journal of the American Society of NephrologyUp Front Matters29222357355360359356361
- Longitudinal FGF23 Trajectories and Mortality in Patients with CKDElevated fibroblast growth factor 23 (FGF23) levels, measured at a single time, are strongly associated with increased risk of mortality in patients with CKD. There are minimal data on serial FGF23 measurements in CKD. In a prospective case-cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two to five annual time points (mean 4.0±1.2) in a randomly selected subcohort of 1135 participants, of whom 203 died, and all remaining 390 participants who died through mid-2013. Higher FGF23 was independently associated with increased risk of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median FGF23 was stable over 5 years of follow-up, but its gradually right-skewed distribution suggested a subpopulation with markedly elevated FGF23. Trajectory analysis revealed three distinct trajectories: stable FGF23 in the majority of participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49-fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24 to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three annual FGF23 measurements yielded qualitatively similar results. In conclusion, FGF23 levels are stable over time in the majority of patients with CKD, but serial measurements identify subpopulations with rising levels and exceptionally high risk of death.10.1681/ASN.2017070772Wed, 22 Nov 2017 07:51:13 GMT-08:00Longitudinal FGF23 Trajectories and Mortality in Patients with CKDElevated fibroblast growth factor 23 (FGF23) levels, measured at a single time, are strongly associated with increased risk of mortality in patients with CKD. There are minimal data on serial FGF23 measurements in CKD. In a prospective case-cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two to five annual time points (mean 4.0±1.2) in a randomly selected subcohort of 1135 participants, of whom 203 died, and all remaining 390 participants who died through mid-2013. Higher FGF23 was independently associated with increased risk of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median FGF23 was stable over 5 years of follow-up, but its gradually right-skewed distribution suggested a subpopulation with markedly elevated FGF23. Trajectory analysis revealed three distinct trajectories: stable FGF23 in the majority of participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49-fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24 to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three annual FGF23 measurements yielded qualitatively similar results. In conclusion, FGF23 levels are stable over time in the majority of patients with CKD, but serial measurements identify subpopulations with rising levels and exceptionally high risk of death.Isakova, TamaraCai, XuanLee, JungwhaXie, DaweiWang, XueMehta, RupalAllen, Norrina B.Scialla, Julia J.Pencina, Michael J.Anderson, Amanda H.Talierco, JohnChen, JingFischer, Michael J.Steigerwalt, Susan P.Leonard, Mary B.Hsu, Chi-yuande Boer, Ian H.Kusek, John W.Feldman, Harold I.Wolf, Myles,Appel, Lawrence J.Go, Alan S.He, JiangLash, James P.Ojo, AkinloluRahman, MahboobTownsend, Raymond R.2017-11-22T07:51:13-08:00doi:10.1681/ASN.2017070772hwp:resource-id:jnephrol;29/2/579American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, FGF23, mortality riskClinical EpidemiologyClinical Epidemiologyresearch-article20182018-02-01February 201810.1681/ASN.20170707721046-66731533-34502017-11-22T07:51:13-08:002018-02Journal of the American Society of NephrologyClinical Epidemiology292579590
- Exploring the Clinical Relevance of Providing Increased Removal of Large Middle MoleculesDialysis technologies have continued to advance over recent decades; however, these advancements have not always been met with improved patient outcomes. In part, the high morbidity and mortality associated with dialysis have been attributed to a group of uremic toxins, which are described as “difficult to remove.” With a new generation of hemodialysis membranes now making meaningful clearance of these molecules possible, it is an apt time to review the clinical relevance of these middle molecules. Our review describes the developments in membrane technology that enable the removal of large middle molecules (molecular mass >15 kD) that is limited with high-flux dialysis membranes. Of the known 58 middle molecules, a literature search identified 27 that have molecular mass >15 kD. This group contains cytokines, adipokines, hormones, and other proteins. These molecules are implicated in chronic inflammation, atherosclerosis, structural heart disease, and secondary immunodeficiency in the literature. Single-center safety and efficacy studies have identified that use of these membranes in maintenance dialysis populations is associated with limited loss of albumin and increased clearance of large middle molecules. Larger, robustly conducted, multicenter studies are now evaluating these findings. After completion of these safety and efficacy studies, the perceived clinical benefits of providing clearance of large middle molecules must be assessed in rigorously conducted, randomized clinical studies.10.2215/CJN.10110917Mon, 05 Mar 2018 07:48:22 GMT-08:00Exploring the Clinical Relevance of Providing Increased Removal of Large Middle MoleculesDialysis technologies have continued to advance over recent decades; however, these advancements have not always been met with improved patient outcomes. In part, the high morbidity and mortality associated with dialysis have been attributed to a group of uremic toxins, which are described as “difficult to remove.” With a new generation of hemodialysis membranes now making meaningful clearance of these molecules possible, it is an apt time to review the clinical relevance of these middle molecules. Our review describes the developments in membrane technology that enable the removal of large middle molecules (molecular mass >15 kD) that is limited with high-flux dialysis membranes. Of the known 58 middle molecules, a literature search identified 27 that have molecular mass >15 kD. This group contains cytokines, adipokines, hormones, and other proteins. These molecules are implicated in chronic inflammation, atherosclerosis, structural heart disease, and secondary immunodeficiency in the literature. Single-center safety and efficacy studies have identified that use of these membranes in maintenance dialysis populations is associated with limited loss of albumin and increased clearance of large middle molecules. Larger, robustly conducted, multicenter studies are now evaluating these findings. After completion of these safety and efficacy studies, the perceived clinical benefits of providing clearance of large middle molecules must be assessed in rigorously conducted, randomized clinical studies.Wolley, MartinJardine, MegHutchison, Colin A.2018-03-05T07:48:22-08:00doi:10.2215/CJN.10110917hwp:resource-id:clinjasn;13/5/805American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, uremia, cardiovascular disease, immune deficiency, malnutrition, Chronic inflammation, chronic dialysis, cytokines, Molecular Weight, Adipokines, renal dialysis, Kidneys, Artificial, Albumins, Atherosclerosis, Inflammation, Heart DiseasesReviewsReviewsreview-article20182018-05-07May 07, 201810.2215/CJN.101109171555-90411555-905X2018-03-05T07:48:22-08:002018-05-07Clinical Journal of the American Society of NephrologyReviews135805814
- Glucocorticoids in the Treatment of Glomerular DiseasesGlucocorticoids exert anti-inflammatory and immunosuppressive activities by genomic and nongenomic effects. The classic genomic effects are mediated by cytosolic glucocorticoid receptors that can upregulate the expression of anti-inflammatory proteins in the nucleus (transactivation) or repress the translocation of proinflammatory transcription factors from the cytosol into the nucleus (transrepression). The nongenomic effects are probably mediated by membrane glucocorticoid receptors. Glucocorticoid receptors are expressed also in podocytes and experimental data suggest that glucocorticoids may protect from podocyte injury. Glucocorticoids have a low therapeutic index and may exert a number of time-dependent and dose-dependent side effects. Measures to prevent or attenuate side effects include single-morning administration of short-acting glucocorticoids, dietetic counseling, increasing physical activity, frequent monitoring, and adapting the doses to the clinical conditions of the patient. Synthetic glucocorticoids, either given alone or in combination with other immunosuppressive drugs, are still the cornerstone therapy in multiple glomerular disorders. However, glucocorticoids are of little benefit in C3 glomerulopathy and may be potentially deleterious in patients with maladaptive focal glomerulosclerosis. Their efficacy depends not only on the type and severity of glomerular disease, but also on the timeliness of administration, the dosage, and the duration of treatment. Whereas an excessive use of glucocorticoids can be responsible for severe toxicity, too low a dosage and too short duration of glucocorticoid treatment can result in false steroid resistance.10.2215/CJN.12991117Fri, 23 Feb 2018 11:41:48 GMT-08:00Glucocorticoids in the Treatment of Glomerular DiseasesGlucocorticoids exert anti-inflammatory and immunosuppressive activities by genomic and nongenomic effects. The classic genomic effects are mediated by cytosolic glucocorticoid receptors that can upregulate the expression of anti-inflammatory proteins in the nucleus (transactivation) or repress the translocation of proinflammatory transcription factors from the cytosol into the nucleus (transrepression). The nongenomic effects are probably mediated by membrane glucocorticoid receptors. Glucocorticoid receptors are expressed also in podocytes and experimental data suggest that glucocorticoids may protect from podocyte injury. Glucocorticoids have a low therapeutic index and may exert a number of time-dependent and dose-dependent side effects. Measures to prevent or attenuate side effects include single-morning administration of short-acting glucocorticoids, dietetic counseling, increasing physical activity, frequent monitoring, and adapting the doses to the clinical conditions of the patient. Synthetic glucocorticoids, either given alone or in combination with other immunosuppressive drugs, are still the cornerstone therapy in multiple glomerular disorders. However, glucocorticoids are of little benefit in C3 glomerulopathy and may be potentially deleterious in patients with maladaptive focal glomerulosclerosis. Their efficacy depends not only on the type and severity of glomerular disease, but also on the timeliness of administration, the dosage, and the duration of treatment. Whereas an excessive use of glucocorticoids can be responsible for severe toxicity, too low a dosage and too short duration of glucocorticoid treatment can result in false steroid resistance.Ponticelli, ClaudioLocatelli, Francesco2018-02-23T11:41:48-08:00doi:10.2215/CJN.12991117hwp:resource-id:clinjasn;13/5/815American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyprimary glomerulonephritis, cortisol, immunosuppression, Humans, Glucocorticoids, Anti-Inflammatory Agents, Counseling, Cytosol, Dietetics, Exercise, Genomics, Glomerulosclerosis, Focal Segmental, Immunosuppressive Agents, Kidney Glomerulus, Podocytes, Receptors, Glucocorticoid, Steroids, Therapeutic Index, transcription factors, Transcriptional ActivationReviewsReviewsreview-article20182018-05-07May 07, 201810.2215/CJN.129911171555-90411555-905X2018-02-23T11:41:48-08:002018-05-07Clinical Journal of the American Society of NephrologyReviews135815822
- Time-Centered Approach to Understanding Risk Factors for the Progression of CKD10.2215/CJN.10360917Fri, 30 Mar 2018 07:04:05 GMT-07:00Time-Centered Approach to Understanding Risk Factors for the Progression of CKDKu, ElaineJohansen, Kirsten L.McCulloch, Charles E.2018-03-30T07:04:05-07:00doi:10.2215/CJN.10360917hwp:resource-id:clinjasn;13/5/693American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChronic Kidney Disease, Diabetes, Disease Progression, Follow-Up Studies, Humans, Hypertension, Proteinuria, Renal Insufficiency, Chronic, Risk FactorsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-05-07May 07, 201810.2215/CJN.103609171555-90411555-905X2018-03-30T07:04:05-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles135693701
- Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid Arthritis10.2215/CJN.11781017Mon, 16 Apr 2018 07:17:07 GMT-07:00Hydroxychloroquine Use and Risk of CKD in Patients with Rheumatoid ArthritisWu, Chia-LinChang, Chia-ChuKor, Chew-TengYang, Tao-HsiangChiu, Ping-FangTarng, Der-CherngHsu, Chih-Cheng2018-04-16T07:17:07-07:00doi:10.2215/CJN.11781017hwp:resource-id:clinjasn;13/5/702American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hydroxychloroquine, rheumatoid arthritis, Humans, Hydroxychloroquine, Cohort Studies, Confidence Intervals, Incidence, Taiwan, Risk, Arthritis, Rheumatoid, Proportional Hazards Models, Renal Insufficiency, Chronic, National Health ProgramsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-05-07May 07, 201810.2215/CJN.117810171555-90411555-905X2018-04-16T07:17:07-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1355702679709680
- Management of Membranous Nephropathy in the PLA2R Era10.2215/CJN.12461117Mon, 29 Jan 2018 05:14:35 GMT-08:00Management of Membranous Nephropathy in the PLA2R EraBomback, Andrew S.2018-01-29T05:14:35-08:00doi:10.2215/CJN.12461117hwp:resource-id:clinjasn;13/5/784American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyidiopathic nephrotic syndrome, membranous nephropathy, Humans, PLA2R1 protein, human, Receptors, Phospholipase A2, Glomerulonephritis, Membranous, Antigen-Antibody Complex, Podocytes, Glomerular Basement Membrane, Autoantigens, Epitopes, Autoantibodies, Group IV Phospholipases A2, Phospholipases A2, Thrombospondins, BiopsyKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-05-07May 07, 201810.2215/CJN.124611171555-90411555-905X2018-01-29T05:14:35-08:002018-05-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat135784786
- Management of Severe Hyponatremia with Continuous Renal Replacement Therapies10.2215/CJN.13281117Tue, 20 Feb 2018 07:08:13 GMT-08:00Management of Severe Hyponatremia with Continuous Renal Replacement TherapiesRosner, Mitchell H.Connor, Michael J.2018-02-20T07:08:13-08:00doi:10.2215/CJN.13281117hwp:resource-id:clinjasn;13/5/787American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycontinuous dialysis, hyponatremia, dialysis, Fluid Therapy, Renal Replacement Therapy, HemofiltrationKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20182018-05-07May 07, 201810.2215/CJN.132811171555-90411555-905X2018-02-20T07:08:13-08:002018-05-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire135878712477891247
- Immunoglobulin G–Degrading Enzyme of Streptococcus pyogenes (IdeS), Desensitization, and the Kidney Allocation System10.2215/CJN.12031017Fri, 09 Mar 2018 06:45:08 GMT-08:00Immunoglobulin G–Degrading Enzyme of Streptococcus pyogenes (IdeS), Desensitization, and the Kidney Allocation SystemHuang, EdmundJordan, Stanley C.2018-03-09T06:45:08-08:00doi:10.2215/CJN.12031017hwp:resource-id:clinjasn;13/5/799American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydesensitization, KAS, IdeS, IVIGPerspectivesPerspectivesresearch-article20182018-05-07May 07, 201810.2215/CJN.120310171555-90411555-905X2018-03-09T06:45:08-08:002018-05-07Clinical Journal of the American Society of NephrologyPerspectives1356799908801908
- Secular Trends in Infection-Related Mortality after Kidney Transplantation10.2215/CJN.11511017Thu, 05 Apr 2018 06:42:12 GMT-07:00Secular Trends in Infection-Related Mortality after Kidney TransplantationKinnunen, SusannaKarhapää, PauliJuutilainen, AuniFinne, PatrikHelanterä, Ilkka2018-04-05T06:42:12-07:00doi:10.2215/CJN.11511017hwp:resource-id:clinjasn;13/5/755American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, mortality risk, infections, risk factors, Pneumocystis carinii, Cause of Death, Listeria monocytogenes, Mycobacterium tuberculosis, creatinine, cytomegalovirus, Herpesvirus 3, Human, Fungal Viruses, Follow-Up Studies, Incidence, Finland, Sepsis, Bacterial Infections, Mycoses, Pneumonia, Meningoencephalitis, Encephalitis, Albumins, diabetes mellitus, Kidney Failure, Chronic, SimplexvirusOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-05-07May 07, 201810.2215/CJN.115110171555-90411555-905X2018-04-05T06:42:12-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles135755762
- Awareness of Racial Disparities in Kidney Transplantation among Health Care Providers in Dialysis Facilities10.2215/CJN.09920917Thu, 12 Apr 2018 05:03:52 GMT-07:00Awareness of Racial Disparities in Kidney Transplantation among Health Care Providers in Dialysis FacilitiesKim, Joyce J.Basu, MohuaPlantinga, LauraPastan, Stephen O.Mohan, SumitSmith, KaylaMelanson, TaylorEscoffery, CamPatzer, Rachel E.2018-04-12T05:03:52-07:00doi:10.2215/CJN.09920917hwp:resource-id:clinjasn;13/5/772American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAfrican Americans, Awareness, Censuses, Cross-sectional Studies, dialysis, ESKD, ESRD, Humans, kidney, Kidney Failure, Chronic, kidney transplantation, Nurse Administrators, organ transplant, Perception, Physician Executives, renal dialysis, Surveys and Questionnaires, transplantation, United States, United States Renal Data SystemOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-05-07May 07, 201810.2215/CJN.099209171555-90411555-905X2018-04-12T05:03:52-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles135772781
- HLA-DQ Mismatching and Kidney Transplant Outcomes10.2215/CJN.10860917Mon, 23 Apr 2018 05:36:44 GMT-07:00HLA-DQ Mismatching and Kidney Transplant OutcomesLeeaphorn, NapatPena, Jeremy Ryan A.Thamcharoen, NatanongKhankin, Eliyahu V.Pavlakis, MarthaCardarelli, Francesca2018-04-23T05:36:44-07:00doi:10.2215/CJN.10860917hwp:resource-id:clinjasn;13/5/763American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, Cold Ischemia, Epitopes, Graft Survival, HLA-DQ Antigens, Humans, Incidence, kidney transplantation, Living Donors, Odds Ratio, Tissue and Organ ProcurementOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-05-07May 07, 201810.2215/CJN.108609171555-90411555-905X2018-04-23T05:36:44-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1355763683771684
- Healthcare Utilization after Acute Kidney Injury in the Pediatric Intensive Care Unit10.2215/CJN.09350817Fri, 20 Apr 2018 07:37:15 GMT-07:00Healthcare Utilization after Acute Kidney Injury in the Pediatric Intensive Care UnitHessey, ErinMorissette, GenevièveLacroix, JacquesPerreault, SylvieSamuel, SusanDorais, MarcPhan, VéroniqueJouvet, PhilippeLafrance, Jean-PhilippeLeLorier, JacquesPalijan, AnaPizzi, MichaelRoy, LouiseZappitelli, Michael2018-04-20T07:37:15-07:00doi:10.2215/CJN.09350817hwp:resource-id:clinjasn;13/5/685American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, children, clinical epidemiology, Epidemiology and outcomes, pediatric nephrology, pediatrics, creatinine, Risk, Confidence Intervals, Retrospective Studies, Patient Discharge, Acute Kidney Injury, hospitalization, Intensive Care Units, Pediatric, Emergency Service, HospitalOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-05-07May 07, 201810.2215/CJN.093508171555-90411555-905X2018-04-20T07:37:15-07:002018-05-07Clinical Journal of the American Society of NephrologyOriginal Articles1355685677692678
- Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft InjuryBackground Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury. Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n=13), after implantation and reperfusion (postischemia; n=13), and at 3 or 12 months after transplant (n=5 each); a cross-sectional cohort with preimplantation biopsy specimens (n=82); and a cross-sectional cohort with postreperfusion biopsy specimens (n=46). Results Analysis of the paired preischemia and postischemia specimens revealed that methylation increased drastically in all allografts on ischemia. Hypermethylation was caused by loss of 5-hydroxymethylcytosine, the product of TET activity, and it was stable 1 year after transplant. In the preimplantation cohort, CpG hypermethylation directly correlated with ischemia time and for some CpGs, increased 2.6% per additional hour of ischemia. Hypermethylation preferentially affected and reduced the expression of genes involved in suppressing kidney injury and fibrosis. Moreover, CpG hypermethylation in preimplantation specimens predicted chronic injury, particularly fibrosis and glomerulosclerosis, 1 year after transplant. This finding was validated in the independent postreperfusion cohort, in which hypermethylation also predicted reduced allograft function 1 year after transplant, outperforming established clinical variables. Conclusions We highlight a novel epigenetic basis for ischemia-induced chronic allograft injury with biomarker potential.10.1681/ASN.2017091027Mon, 02 Apr 2018 06:38:35 GMT-07:00Ischemia-Induced DNA Hypermethylation during Kidney Transplant Predicts Chronic Allograft InjuryBackground Ischemia during kidney transplant causes chronic allograft injury and adversely affects outcome, but the underlying mechanisms are incompletely understood. In tumors, oxygen shortage reduces the DNA demethylating activity of the ten-11 translocation (TET) enzymes, yielding hypermethylated genomes that promote tumor progression. We investigated whether ischemia similarly induces DNA hypermethylation in kidney transplants and contributes to chronic injury. Methods We profiled genome-wide DNA methylation in three cohorts of brain-dead donor kidney allograft biopsy specimens: a longitudinal cohort with paired biopsy specimens obtained at allograft procurement (preischemia; n=13), after implantation and reperfusion (postischemia; n=13), and at 3 or 12 months after transplant (n=5 each); a cross-sectional cohort with preimplantation biopsy specimens (n=82); and a cross-sectional cohort with postreperfusion biopsy specimens (n=46). Results Analysis of the paired preischemia and postischemia specimens revealed that methylation increased drastically in all allografts on ischemia. Hypermethylation was caused by loss of 5-hydroxymethylcytosine, the product of TET activity, and it was stable 1 year after transplant. In the preimplantation cohort, CpG hypermethylation directly correlated with ischemia time and for some CpGs, increased 2.6% per additional hour of ischemia. Hypermethylation preferentially affected and reduced the expression of genes involved in suppressing kidney injury and fibrosis. Moreover, CpG hypermethylation in preimplantation specimens predicted chronic injury, particularly fibrosis and glomerulosclerosis, 1 year after transplant. This finding was validated in the independent postreperfusion cohort, in which hypermethylation also predicted reduced allograft function 1 year after transplant, outperforming established clinical variables. Conclusions We highlight a novel epigenetic basis for ischemia-induced chronic allograft injury with biomarker potential.Heylen, LineThienpont, BernardNaesens, MaartenBusschaert, PieterDepreeuw, JeroenSmeets, DominiekJochmans, InaMonbaliu, DiethardPirenne, JacquesLerut, EvelyneGhesquiere, BartKuypers, DirkLambrechts, DietherSprangers, Ben2018-04-02T06:38:35-07:00doi:10.1681/ASN.2017091027hwp:resource-id:jnephrol;29/5/1566American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, ischemia, fibrosis, epigenetics, chronic allograft nephropathy, DNA methylationClinical ResearchClinical Researchresearch-article20182018-05-01May 201810.1681/ASN.20170910271046-66731533-34502018-04-02T06:38:35-07:002018-05Journal of the American Society of NephrologyClinical Research29515661576
- Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients10.2215/CJN.07980717Thu, 08 Mar 2018 10:12:42 GMT-08:00Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease PatientsBozic, MilicaBetriu, AngelsBermudez-Lopez, MarcelinoOrtiz, AlbertoFernandez, ElviraValdivielso, Jose M.,2018-03-08T10:12:42-08:00doi:10.2215/CJN.07980717hwp:resource-id:clinjasn;13/4/577American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAtherosclerosis, cardiovascular disease, Humans, Plaque, Atherosclerotic, Fibroblast Growth Factor 2, Prospective Studies, Logistic Models, Atherosclerosis, Renal Insufficiency, Chronic, Disease Progression, arteries, renal dialysisOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-04-06April 06, 201810.2215/CJN.079807171555-90411555-905X2018-03-08T10:12:42-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134577584
- Associations of Plasma Amino Acid and Acylcarnitine Profiles with Incident Reduced Glomerular Filtration Rate10.2215/CJN.07650717Thu, 08 Mar 2018 10:12:41 GMT-08:00Associations of Plasma Amino Acid and Acylcarnitine Profiles with Incident Reduced Glomerular Filtration RateWang, FeijieSun, LiangSun, QiLiang, LimingGao, XianfuLi, RongxiaPan, AnLi, HuaixingDeng, YueyiHu, Frank B.Wu, JiaruiZeng, RongLin, Xu2018-03-08T10:12:41-08:00doi:10.2215/CJN.07650717hwp:resource-id:clinjasn;13/4/560American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Incidence, Metabolomics, risk factors, acylcarnitine, Cysteine, Metabolome, Amino Acids, glomerular filtration rate, Principal Component Analysis, Follow-Up Studies, Genetic Background, Carnitine, Chromatography, Liquid, Renal Insufficiency, Chronic, Mass Spectrometry, Biomarkers, Environmental Exposure, HumansOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-04-06April 06, 201810.2215/CJN.076507171555-90411555-905X2018-03-08T10:12:41-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134560568
- Black Americans’ Perspectives of Barriers and Facilitators of Community Screening for Kidney Disease10.2215/CJN.07580717Thu, 15 Mar 2018 06:59:34 GMT-07:00Black Americans’ Perspectives of Barriers and Facilitators of Community Screening for Kidney DiseaseUmeukeje, Ebele M.Wild, Marcus G.Maripuri, SaugarDavidson, TeresaRutherford, MargaretAbdel-Kader, KhaledLewis, JuliaWilkins, Consuelo H.Cavanaugh, Kerri2018-03-15T06:59:34-07:00doi:10.2215/CJN.07580717hwp:resource-id:clinjasn;13/4/551American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical nephrology, ethnicity, Adult, United States, Female, Prevalence, Incidence, Focus Groups, Motivation, Research Personnel, Tennessee, African Americans, Kidney Diseases, Kidney Failure, Chronic, kidney, Fear, EmotionsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-04-06April 06, 201810.2215/CJN.075807171555-90411555-905X2018-03-15T06:59:34-07:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles1344551521559523
- Association of Nonoxidized Parathyroid Hormone with Cardiovascular and Kidney Disease Outcomes in Chronic Kidney Disease10.2215/CJN.06620617Mon, 05 Mar 2018 07:48:21 GMT-08:00Association of Nonoxidized Parathyroid Hormone with Cardiovascular and Kidney Disease Outcomes in Chronic Kidney DiseaseSeiler-Mussler, SarahLimbach, Anne S.Emrich, Insa E.Pickering, John W.Roth, Heinz J.Fliser, DaniloHeine, Gunnar H.2018-03-05T07:48:21-08:00doi:10.2215/CJN.06620617hwp:resource-id:clinjasn;13/4/569American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, clinical epidemiology, Humans, albuminuria, parathyroid hormone, risk factors, creatinine, Renal Insufficiency, Chronic, kidney, Cause of Death, Disease Progression, Renal Replacement Therapy, heart failureOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-04-06April 06, 201810.2215/CJN.066206171555-90411555-905X2018-03-05T07:48:21-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles1344569524576526
- Transplant Center Patient Navigator and Access to Transplantation among High-Risk Population10.2215/CJN.08600817Mon, 26 Mar 2018 06:08:26 GMT-07:00Transplant Center Patient Navigator and Access to Transplantation among High-Risk PopulationBasu, MohuaPetgrave-Nelson, LisaSmith, Kayla D.Perryman, Jennie P.Clark, KevinPastan, Stephen O.Pearson, Thomas C.Larsen, Christian P.Paul, SudeshnaPatzer, Rachel E.2018-03-26T06:08:26-07:00doi:10.2215/CJN.08600817hwp:resource-id:clinjasn;13/4/620American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, transplant outcomes, risk factors, kidney transplantation, Humans, Living Donors, Patient Navigation, Proportional Hazards Models, Waiting Lists, Vulnerable Populations, Follow-Up Studies, kidney, Minority Groups, Transplants, Referral and Consultation, Social ClassOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-04-06April 06, 201810.2215/CJN.086008171555-90411555-905X2018-03-26T06:08:26-07:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles13444620519529627520530
- Association of Serious Fall Injuries among United States End Stage Kidney Disease Patients with Access to Kidney Transplantation10.2215/CJN.10330917Tue, 06 Mar 2018 06:04:23 GMT-08:00Association of Serious Fall Injuries among United States End Stage Kidney Disease Patients with Access to Kidney TransplantationPlantinga, Laura C.Lynch, Raymond J.Patzer, Rachel E.Pastan, Stephen O.Bowling, C. Barrett2018-03-06T06:04:23-08:00doi:10.2215/CJN.10330917hwp:resource-id:clinjasn;13/4/628American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESKD, geriatric nephrology, kidney transplantation, Adult, Humans, United States, Incidence, Accidental Falls, Proportional Hazards Models, Inpatients, Follow-Up Studies, Kidney Failure, Chronic, Waiting Lists, Tissue Donors, Fractures, Bone, Joint Dislocations, Emergency Service, Hospital, Craniocerebral Trauma, renal dialysisOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-04-06April 06, 201810.2215/CJN.103309171555-90411555-905X2018-03-06T06:04:23-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134628637
- What Else Can We Do to Ensure Transplant Equity for High-Risk Patients?10.2215/CJN.02120218Mon, 26 Mar 2018 06:08:25 GMT-07:00What Else Can We Do to Ensure Transplant Equity for High-Risk Patients?Waterman, Amy D.Beaumont, Jennifer L.2018-03-26T06:08:25-07:00doi:10.2215/CJN.02120218hwp:resource-id:clinjasn;13/4/529American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEuropean Continental Ancestry Group, Georgia, Humans, Kidney Failure, Chronic, Patient Navigation, Transplants, United Network of Organ Sharing, United States, Vulnerable Populations, Waiting ListsEditorialsEditorialseditorial20182018-04-06April 06, 201810.2215/CJN.021202181555-90411555-905X2018-03-26T06:08:25-07:002018-04-06Clinical Journal of the American Society of NephrologyEditorials13444529519620530520627
- An Evolving Continuum of Care for the Kidney Disease Patient Will Help the Transplant Center Patient Navigator10.2215/CJN.02300218Mon, 26 Mar 2018 06:08:25 GMT-07:00An Evolving Continuum of Care for the Kidney Disease Patient Will Help the Transplant Center Patient NavigatorKnight, Richard A.2018-03-26T06:08:25-07:00doi:10.2215/CJN.02300218hwp:resource-id:clinjasn;13/4/519American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyContinuity of Patient Care, diabetes mellitus, Disparities, Humans, hypertension, Insurance Coverage, kidney, Kidney Diseases, kidney transplantation, Minority, Patient Engagement, Patient Navigation, Poverty, proteinuria, renal dialysis, Renal Replacement Therapy, renal transplantation, Social Class, Transplant Center, Waiting ListsPatient VoicePatient Voiceresearch-article20182018-04-06April 06, 201810.2215/CJN.023002181555-90411555-905X2018-03-26T06:08:25-07:002018-04-06Clinical Journal of the American Society of NephrologyPatient Voice13444519529620520530627
- Correlation of Urine Ammonium and Urine Osmolal Gap in Kidney Transplant Recipients10.2215/CJN.13311117Thu, 08 Mar 2018 10:12:41 GMT-08:00Correlation of Urine Ammonium and Urine Osmolal Gap in Kidney Transplant RecipientsRaphael, Kalani L.Ix, Joachim H.2018-03-08T10:12:41-08:00doi:10.2215/CJN.13311117hwp:resource-id:clinjasn;13/4/638American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyammonium, urine osmolal gap, Acid-Base Equilibrium, Magnesium, Diabetic Ketoacidosis, Ammonium Compounds, Glucose, risk factors, kidney transplantation, acidosis, Osmolar Concentration, Sodium, Calcium, Dietary, Anions, Cations, Renal Insufficiency, Chronic, Phosphates, Sulfates, urea, NitrogenResearch LetterResearch Letterletter20182018-04-06April 06, 201810.2215/CJN.133111171555-90411555-905X2018-03-08T10:12:41-08:002018-04-06Clinical Journal of the American Society of NephrologyResearch Letter134638640
- Evaluation and Management of CKD in the Nonkidney Solid Organ Transplant Recipient10.2215/CJN.10730917Thu, 11 Jan 2018 11:49:58 GMT-08:00Evaluation and Management of CKD in the Nonkidney Solid Organ Transplant RecipientWarburton, Karen M.Doyle, Alden M.2018-01-11T11:49:58-08:00doi:10.2215/CJN.10730917hwp:resource-id:clinjasn;13/4/652American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, nonrenal solid organ transplant, liver transplant, lung transplant, heart transplant, immunosuppressionKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-04-06April 06, 201810.2215/CJN.107309171555-90411555-905X2018-01-11T11:49:58-08:002018-04-06Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat134652654
- Fibroblast Growth Factor 23 Associates with Death in Critically Ill Patients10.2215/CJN.10810917Thu, 08 Mar 2018 10:12:43 GMT-08:00Fibroblast Growth Factor 23 Associates with Death in Critically Ill PatientsLeaf, David E.Siew, Edward D.Eisenga, Michele F.Singh, KarandeepMc Causland, Finnian R.Srivastava, AnandAlp Ikizler, T.Ware, Lorraine B.Ginde, Adit A.Kellum, John A.Palevsky, Paul M.Wolf, MylesWaikar, Sushrut S.2018-03-08T10:12:43-08:00doi:10.2215/CJN.10810917hwp:resource-id:clinjasn;13/4/531American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, Vitamin D, renal dialysis, Humans, fibroblast growth factor 23, parathyroid hormone, Critical Illness, Osteocytes, Confidence Intervals, Renal Replacement Therapy, Fibroblast Growth Factors, Acute Kidney Injury, Calcium, Dietary, Biomarkers, Minerals, Comorbidity, Acute Lung Injury, Demography, Phosphates, Cohort StudiesOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-04-06April 06, 201810.2215/CJN.108109171555-90411555-905X2018-03-08T10:12:43-08:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134531541
- Attributable Risk and Time Course of Colistin-Associated Acute Kidney Injury10.2215/CJN.06980717Thu, 15 Mar 2018 06:59:35 GMT-07:00Attributable Risk and Time Course of Colistin-Associated Acute Kidney InjuryMiano, Todd A.Lautenbach, EbbingWilson, F. PerryGuo, WenshengBorovskiy, YuliyaHennessy, Sean2018-03-15T06:59:35-07:00doi:10.2215/CJN.06980717hwp:resource-id:clinjasn;13/4/542American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydrug nephrotoxicity, acute renal failure, anemia, colistin, polymixin, acute kidney injury, sepsis, gram negative, multidrug resistantOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-04-06April 06, 201810.2215/CJN.069807171555-90411555-905X2018-03-15T06:59:35-07:002018-04-06Clinical Journal of the American Society of NephrologyOriginal Articles134542550
- Targeting Zero Infections in Dialysis: New Devices, Yes, but also Guidelines, Checklists, and a Culture of Safety10.1681/ASN.2018020132Mon, 05 Mar 2018 07:48:41 GMT-08:00Targeting Zero Infections in Dialysis: New Devices, Yes, but also Guidelines, Checklists, and a Culture of SafetyKliger, Alan S.2018-03-05T07:48:41-08:00doi:10.1681/ASN.2018020132hwp:resource-id:jnephrol;29/4/1083American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis access, infection, Hemodialysis hazardsUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-04-01April 201810.1681/ASN.20180201321046-66731533-34502018-03-05T07:48:41-08:002018-04Journal of the American Society of NephrologyUp Front Matters29441083133610841343
- Evaluation of Potential Living Kidney Donors in the APOL1 Era10.1681/ASN.2018020137Fri, 09 Mar 2018 06:45:32 GMT-08:00Evaluation of Potential Living Kidney Donors in the APOL1 EraFreedman, Barry I.Julian, Bruce A.2018-03-09T06:45:32-08:00doi:10.1681/ASN.2018020137hwp:resource-id:jnephrol;29/4/1079American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAfrican American, APOL1, chronic kidney disease, kidney donation, safety, transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-04-01April 201810.1681/ASN.20180201371046-66731533-34502018-03-09T06:45:32-08:002018-04Journal of the American Society of NephrologyUp Front Matters29441079130910811316
- We AIM2 Inflame10.1681/ASN.2018020116Tue, 06 Mar 2018 06:04:32 GMT-08:00We AIM2 InflameLinkermann, AndreasParmentier, Simon P.Hugo, Christian2018-03-06T06:04:32-08:00doi:10.1681/ASN.2018020116hwp:resource-id:jnephrol;29/4/1077American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynecroptosis, ferroptosis, pyroptosis, apoptosis, InflammasomeUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-04-01April 201810.1681/ASN.20180201161046-66731533-34502018-03-06T06:04:32-08:002018-04Journal of the American Society of NephrologyUp Front Matters29441077116510791181
- Gender Disparities and Financial Barriers to Living Kidney Donation10.1681/ASN.2018020158Thu, 08 Mar 2018 10:12:55 GMT-08:00Gender Disparities and Financial Barriers to Living Kidney DonationMatas, Arthur J.Hays, Rebecca E.2018-03-08T10:12:55-08:00doi:10.1681/ASN.2018020158hwp:resource-id:jnephrol;29/4/1081American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologydonor, disparity, transplantUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-04-01April 201810.1681/ASN.20180201581046-66731533-34502018-03-08T10:12:55-08:002018-04Journal of the American Society of NephrologyUp Front Matters29441081130110831308
- Wnt9a Promotes Renal Fibrosis by Accelerating Cellular Senescence in Tubular Epithelial CellsCellular senescence is associated with renal disease progression, and accelerated tubular cell senescence promotes the pathogenesis of renal fibrosis. However, the underlying mechanism is unknown. We assessed the potential role of Wnt9a in tubular cell senescence and renal fibrosis. Compared with tubular cells of normal subjects, tubular cells of humans with a variety of nephropathies and those of several mouse models of CKD expressed high levels of Wnt9a that colocalized with the senescence-related protein p16INK4A. Wnt9a expression level correlated with the extent of renal fibrosis, decline of eGFR, and expression of p16INK4A. Furthermore, ectopic expression of Wnt9a after ischemia-reperfusion injury (IRI) induced activation of β-catenin and exacerbated renal fibrosis. Overexpression of Wnt9a exacerbated tubular senescence, evidenced by increased detection of p16INK4A expression and senescence-associated β-galactosidase activity. Conversely, shRNA-mediated knockdown of Wnt9a repressed IRI-induced renal fibrosis in vivo and impeded the growth of senescent tubular epithelial cells in culture. Notably, Wnt9a-induced renal fibrosis was inhibited by shRNA-mediated silencing of p16INK4A in the IRI mouse model. In a human proximal tubular epithelial cell line and primary renal tubular cells, Wnt9a remarkably upregulated levels of senescence-related p16INK4A, p19ARF, p53, and p21 and decreased the phosphorylation of retinoblastoma protein. Wnt9a also induced senescent tubular cells to produce TGF-β1, which promoted proliferation and activation in normal rat kidney fibroblasts. Thus, Wnt9a drives tubular senescence and fibroblast activation. Furthermore, the Wnt9a–TGF-β pathway appears to create a reciprocal activation loop between senescent tubular cells and activated fibroblasts that promotes and accelerates the pathogenesis of renal fibrosis.10.1681/ASN.2017050574Mon, 12 Feb 2018 11:24:00 GMT-08:00Wnt9a Promotes Renal Fibrosis by Accelerating Cellular Senescence in Tubular Epithelial CellsCellular senescence is associated with renal disease progression, and accelerated tubular cell senescence promotes the pathogenesis of renal fibrosis. However, the underlying mechanism is unknown. We assessed the potential role of Wnt9a in tubular cell senescence and renal fibrosis. Compared with tubular cells of normal subjects, tubular cells of humans with a variety of nephropathies and those of several mouse models of CKD expressed high levels of Wnt9a that colocalized with the senescence-related protein p16INK4A. Wnt9a expression level correlated with the extent of renal fibrosis, decline of eGFR, and expression of p16INK4A. Furthermore, ectopic expression of Wnt9a after ischemia-reperfusion injury (IRI) induced activation of β-catenin and exacerbated renal fibrosis. Overexpression of Wnt9a exacerbated tubular senescence, evidenced by increased detection of p16INK4A expression and senescence-associated β-galactosidase activity. Conversely, shRNA-mediated knockdown of Wnt9a repressed IRI-induced renal fibrosis in vivo and impeded the growth of senescent tubular epithelial cells in culture. Notably, Wnt9a-induced renal fibrosis was inhibited by shRNA-mediated silencing of p16INK4A in the IRI mouse model. In a human proximal tubular epithelial cell line and primary renal tubular cells, Wnt9a remarkably upregulated levels of senescence-related p16INK4A, p19ARF, p53, and p21 and decreased the phosphorylation of retinoblastoma protein. Wnt9a also induced senescent tubular cells to produce TGF-β1, which promoted proliferation and activation in normal rat kidney fibroblasts. Thus, Wnt9a drives tubular senescence and fibroblast activation. Furthermore, the Wnt9a–TGF-β pathway appears to create a reciprocal activation loop between senescent tubular cells and activated fibroblasts that promotes and accelerates the pathogenesis of renal fibrosis.Luo, CongweiZhou, ShanZhou, ZhanmeiLiu, YahongYang, LiLiu, JiafengZhang, YunfangLi, HongyanLiu, YouhuaHou, Fan FanZhou, Lili2018-02-12T11:24:00-08:00doi:10.1681/ASN.2017050574hwp:resource-id:jnephrol;29/4/1238American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyWnt9a, tubular cells, cell senescence, fibroblasts, renal fibrosisBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170505741046-66731533-34502018-02-12T11:24:00-08:002018-04Journal of the American Society of NephrologyBasic Research29412381256
- Macrophage Uptake of Necrotic Cell DNA Activates the AIM2 Inflammasome to Regulate a Proinflammatory Phenotype in CKDNonmicrobial inflammation contributes to CKD progression and fibrosis. Absent in melanoma 2 (AIM2) is an inflammasome-forming receptor for double-stranded DNA. AIM2 is expressed in the kidney and activated mainly by macrophages. We investigated the potential pathogenic role of the AIM2 inflammasome in kidney disease. In kidneys from patients with diabetic or nondiabetic CKD, immunofluorescence showed AIM2 expression in glomeruli, tubules, and infiltrating leukocytes. In a mouse model of unilateral ureteral obstruction (UUO), Aim2 deficiency attenuated the renal injury, fibrosis, and inflammation observed in wild-type (WT) littermates. In bone marrow chimera studies, UUO induced substantially more tubular injury and IL-1β cleavage in Aim2−/− or WT mice that received WT bone marrow than in WT mice that received Aim2−/− bone marrow. Intravital microscopy of the kidney in LysM(gfp/gfp) mice 5–6 days after UUO demonstrated the significant recruitment of GFP+ proinflammatory macrophages that crawled along injured tubules, engulfed DNA from necrotic cells, and expressed active caspase-1. DNA uptake occurred in large vacuolar structures within recruited macrophages but not resident CX3CR1+ renal phagocytes. In vitro, macrophages that engulfed necrotic debris showed AIM2-dependent activation of caspase-1 and IL-1β, as well as the formation of AIM2+ ASC specks. ASC specks are a hallmark of inflammasome activation. Cotreatment with DNaseI attenuated the increase in IL-1β levels, confirming that DNA was the principal damage-associated molecular pattern in this process. Therefore, the activation of the AIM2 inflammasome by DNA from necrotic cells drives a proinflammatory phenotype that contributes to chronic injury in the kidney.10.1681/ASN.2017080863Fri, 09 Feb 2018 06:41:55 GMT-08:00Macrophage Uptake of Necrotic Cell DNA Activates the AIM2 Inflammasome to Regulate a Proinflammatory Phenotype in CKDNonmicrobial inflammation contributes to CKD progression and fibrosis. Absent in melanoma 2 (AIM2) is an inflammasome-forming receptor for double-stranded DNA. AIM2 is expressed in the kidney and activated mainly by macrophages. We investigated the potential pathogenic role of the AIM2 inflammasome in kidney disease. In kidneys from patients with diabetic or nondiabetic CKD, immunofluorescence showed AIM2 expression in glomeruli, tubules, and infiltrating leukocytes. In a mouse model of unilateral ureteral obstruction (UUO), Aim2 deficiency attenuated the renal injury, fibrosis, and inflammation observed in wild-type (WT) littermates. In bone marrow chimera studies, UUO induced substantially more tubular injury and IL-1β cleavage in Aim2−/− or WT mice that received WT bone marrow than in WT mice that received Aim2−/− bone marrow. Intravital microscopy of the kidney in LysM(gfp/gfp) mice 5–6 days after UUO demonstrated the significant recruitment of GFP+ proinflammatory macrophages that crawled along injured tubules, engulfed DNA from necrotic cells, and expressed active caspase-1. DNA uptake occurred in large vacuolar structures within recruited macrophages but not resident CX3CR1+ renal phagocytes. In vitro, macrophages that engulfed necrotic debris showed AIM2-dependent activation of caspase-1 and IL-1β, as well as the formation of AIM2+ ASC specks. ASC specks are a hallmark of inflammasome activation. Cotreatment with DNaseI attenuated the increase in IL-1β levels, confirming that DNA was the principal damage-associated molecular pattern in this process. Therefore, the activation of the AIM2 inflammasome by DNA from necrotic cells drives a proinflammatory phenotype that contributes to chronic injury in the kidney.Komada, TakanoriChung, HyunjaeLau, ArthurPlatnich, Jaye M.Beck, Paul L.Benediktsson, HallgrimurDuff, Henry J.Jenne, Craig N.Muruve, Daniel A.2018-02-09T06:41:55-08:00doi:10.1681/ASN.2017080863hwp:resource-id:jnephrol;29/4/1165American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Immunology and pathology, macrophagesBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170808631046-66731533-34502018-02-09T06:41:55-08:002018-04Journal of the American Society of NephrologyBasic Research29441165107711811079
- Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during AgingDefects in the renal fatty acid oxidation (FAO) pathway have been implicated in the development of renal fibrosis. Although, compared with young kidneys, aged kidneys show significantly increased fibrosis with impaired kidney function, the mechanisms underlying the effects of aging on renal fibrosis have not been investigated. In this study, we investigated peroxisome proliferator–activated receptor α (PPARα) and the FAO pathway as regulators of age-associated renal fibrosis. The expression of PPARα and the FAO pathway–associated proteins significantly decreased with the accumulation of lipids in the renal tubular epithelial region during aging in rats. In particular, decreased PPARα protein expression associated with increased expression of PPARα-targeting microRNAs. Among the microRNAs with increased expression during aging, miR-21 efficiently decreased PPARα expression and impaired FAO when ectopically expressed in renal epithelial cells. In cells pretreated with oleic acid to induce lipid stress, miR-21 treatment further enhanced lipid accumulation. Furthermore, treatment with miR-21 significantly exacerbated the TGF-β–induced fibroblast phenotype of epithelial cells. We verified the physiologic importance of our findings in a calorie restriction model. Calorie restriction rescued the impaired FAO pathway during aging and slowed fibrosis development. Finally, compared with kidneys of aged littermate controls, kidneys of aged PPARα−/− mice showed exaggerated lipid accumulation, with decreased activity of the FAO pathway and a severe fibrosis phenotype. Our results suggest that impaired renal PPARα signaling during aging aggravates renal fibrosis development, and targeting PPARα is useful for preventing age-associated CKD.10.1681/ASN.2017070802Mon, 12 Feb 2018 11:23:59 GMT-08:00Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during AgingDefects in the renal fatty acid oxidation (FAO) pathway have been implicated in the development of renal fibrosis. Although, compared with young kidneys, aged kidneys show significantly increased fibrosis with impaired kidney function, the mechanisms underlying the effects of aging on renal fibrosis have not been investigated. In this study, we investigated peroxisome proliferator–activated receptor α (PPARα) and the FAO pathway as regulators of age-associated renal fibrosis. The expression of PPARα and the FAO pathway–associated proteins significantly decreased with the accumulation of lipids in the renal tubular epithelial region during aging in rats. In particular, decreased PPARα protein expression associated with increased expression of PPARα-targeting microRNAs. Among the microRNAs with increased expression during aging, miR-21 efficiently decreased PPARα expression and impaired FAO when ectopically expressed in renal epithelial cells. In cells pretreated with oleic acid to induce lipid stress, miR-21 treatment further enhanced lipid accumulation. Furthermore, treatment with miR-21 significantly exacerbated the TGF-β–induced fibroblast phenotype of epithelial cells. We verified the physiologic importance of our findings in a calorie restriction model. Calorie restriction rescued the impaired FAO pathway during aging and slowed fibrosis development. Finally, compared with kidneys of aged littermate controls, kidneys of aged PPARα−/− mice showed exaggerated lipid accumulation, with decreased activity of the FAO pathway and a severe fibrosis phenotype. Our results suggest that impaired renal PPARα signaling during aging aggravates renal fibrosis development, and targeting PPARα is useful for preventing age-associated CKD.Chung, Ki WungLee, Eun KyeongLee, Mi KyungOh, Goo TaegYu, Byung PalChung, Hae Young2018-02-12T11:23:59-08:00doi:10.1681/ASN.2017070802hwp:resource-id:jnephrol;29/4/1223American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAging, PPARα, Fatty acid oxidation, fibrosis, miR21Basic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170708021046-66731533-34502018-02-12T11:23:59-08:002018-04Journal of the American Society of NephrologyBasic Research29412231237
- The Change in Living Kidney Donation in Women and Men in the United States (2005–2015): A Population-Based AnalysisThe factors underlying the decline in living kidney donation in the United States since 2005 must be understood to inform strategies to ensure access to this option for future patients. Population-based estimates provide a better assessment of donation activity than do trends in the number of living donor transplants. Using data from the Scientific Registry of Transplant Recipients and the United States Census, we determined longitudinal changes in living kidney donation between 2005 and 2015, focusing on the effect of sex and income. We used multilevel Poisson models to adjust for differences in age, race, the incidence of ESRD, and geographic factors (including population density, urbanization, and daily commuting). During the study period, the unadjusted rate of donation was 30.1 and 19.3 per million population in women and men, respectively, and the adjusted incidence of donation was 44% higher in women (incidence rate ratio [IRR], 1.44; 95% confidence interval [95% CI], 1.39 to 1.49). The incidence of donation was stable in women (IRR, 0.95; 95% CI, 0.84 to 1.07) but declined in men (IRR, 0.75; 95% CI, 0.68 to 0.83). Income was associated with longitudinal changes in donation in both sexes, yet donation was stable in the highest two population income quartiles in women but only in the highest income quartile in men. In both sexes, living related donations declined, irrespective of income. In conclusion, living donation declined in men but remained stable in women between 2005 and 2015, and income appeared to have a greater effect on living donation in men.10.1681/ASN.2017111160Thu, 08 Mar 2018 10:12:55 GMT-08:00The Change in Living Kidney Donation in Women and Men in the United States (2005–2015): A Population-Based AnalysisThe factors underlying the decline in living kidney donation in the United States since 2005 must be understood to inform strategies to ensure access to this option for future patients. Population-based estimates provide a better assessment of donation activity than do trends in the number of living donor transplants. Using data from the Scientific Registry of Transplant Recipients and the United States Census, we determined longitudinal changes in living kidney donation between 2005 and 2015, focusing on the effect of sex and income. We used multilevel Poisson models to adjust for differences in age, race, the incidence of ESRD, and geographic factors (including population density, urbanization, and daily commuting). During the study period, the unadjusted rate of donation was 30.1 and 19.3 per million population in women and men, respectively, and the adjusted incidence of donation was 44% higher in women (incidence rate ratio [IRR], 1.44; 95% confidence interval [95% CI], 1.39 to 1.49). The incidence of donation was stable in women (IRR, 0.95; 95% CI, 0.84 to 1.07) but declined in men (IRR, 0.75; 95% CI, 0.68 to 0.83). Income was associated with longitudinal changes in donation in both sexes, yet donation was stable in the highest two population income quartiles in women but only in the highest income quartile in men. In both sexes, living related donations declined, irrespective of income. In conclusion, living donation declined in men but remained stable in women between 2005 and 2015, and income appeared to have a greater effect on living donation in men.Gill, JagbirJoffres, YayukRose, CarenLesage, JulieLandsberg, DavidKadatz, MatthewGill, John2018-03-08T10:12:55-08:00doi:10.1681/ASN.2017111160hwp:resource-id:jnephrol;29/4/1301American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyliving kidney donation, sex, gender difference, income, kidney transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20182018-04-01April 201810.1681/ASN.20171111601046-66731533-34502018-03-08T10:12:55-08:002018-04Journal of the American Society of NephrologyClinical Epidemiology29441301108113081083
- NBCe1-A Regulates Proximal Tubule Ammonia Metabolism under Basal Conditions and in Response to Metabolic AcidosisRenal ammonia metabolism is the primary mechanism through which the kidneys maintain acid-base homeostasis, but the molecular mechanisms regulating renal ammonia generation are unclear. In these studies, we evaluated the role of the proximal tubule basolateral plasma membrane electrogenic sodium bicarbonate cotransporter 1 variant A (NBCe1-A) in this process. Deletion of the NBCe1-A gene caused severe spontaneous metabolic acidosis in mice. Despite this metabolic acidosis, which normally causes a dramatic increase in ammonia excretion, absolute urinary ammonia concentration was unaltered. Additionally, NBCe1-A deletion almost completely blocked the ability to increase ammonia excretion after exogenous acid loading. Under basal conditions and during acid loading, urine pH was more acidic in mice with NBCe1-A deletion than in wild-type controls, indicating that the abnormal ammonia excretion was not caused by a primary failure of urine acidification. Instead, NBCe1-A deletion altered the expression levels of multiple enzymes involved in proximal tubule ammonia generation, including phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and glutamine synthetase, under basal conditions and after exogenous acid loading. Deletion of NBCe1-A did not impair expression of key proteins involved in collecting duct ammonia secretion. These studies demonstrate that the integral membrane protein NBCe1-A has a critical role in basal and acidosis-stimulated ammonia metabolism through the regulation of proximal tubule ammonia-metabolizing enzymes.10.1681/ASN.2017080935Mon, 26 Feb 2018 07:11:48 GMT-08:00NBCe1-A Regulates Proximal Tubule Ammonia Metabolism under Basal Conditions and in Response to Metabolic AcidosisRenal ammonia metabolism is the primary mechanism through which the kidneys maintain acid-base homeostasis, but the molecular mechanisms regulating renal ammonia generation are unclear. In these studies, we evaluated the role of the proximal tubule basolateral plasma membrane electrogenic sodium bicarbonate cotransporter 1 variant A (NBCe1-A) in this process. Deletion of the NBCe1-A gene caused severe spontaneous metabolic acidosis in mice. Despite this metabolic acidosis, which normally causes a dramatic increase in ammonia excretion, absolute urinary ammonia concentration was unaltered. Additionally, NBCe1-A deletion almost completely blocked the ability to increase ammonia excretion after exogenous acid loading. Under basal conditions and during acid loading, urine pH was more acidic in mice with NBCe1-A deletion than in wild-type controls, indicating that the abnormal ammonia excretion was not caused by a primary failure of urine acidification. Instead, NBCe1-A deletion altered the expression levels of multiple enzymes involved in proximal tubule ammonia generation, including phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and glutamine synthetase, under basal conditions and after exogenous acid loading. Deletion of NBCe1-A did not impair expression of key proteins involved in collecting duct ammonia secretion. These studies demonstrate that the integral membrane protein NBCe1-A has a critical role in basal and acidosis-stimulated ammonia metabolism through the regulation of proximal tubule ammonia-metabolizing enzymes.Lee, Hyun-WookOsis, GunarsHarris, Autumn N.Fang, LijuanRomero, Michael F.Handlogten, Mary E.Verlander, Jill W.Weiner, I. David2018-02-26T07:11:48-08:00doi:10.1681/ASN.2017080935hwp:resource-id:jnephrol;29/4/1182American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis, chronic metabolic acidosis, renal tubular acidosis, proximal tubuleBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170809351046-66731533-34502018-02-26T07:11:48-08:002018-04Journal of the American Society of NephrologyBasic Research29411821197
- APOL1 Genotype and Renal Function of Black Living DonorsBlack living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.10.1681/ASN.2017060658Tue, 16 Jan 2018 06:24:50 GMT-08:00APOL1 Genotype and Renal Function of Black Living DonorsBlack living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.Doshi, Mona D.Ortigosa-Goggins, MariellaGarg, Amit X.Li, LihuaPoggio, Emilio D.Winkler, Cheryl A.Kopp, Jeffrey B.2018-01-16T06:24:50-08:00doi:10.1681/ASN.2017060658hwp:resource-id:jnephrol;29/4/1309American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney donation, renal function, human geneticsClinical ResearchClinical Researchresearch-article20182018-04-01April 201810.1681/ASN.20170606581046-66731533-34502018-01-16T06:24:50-08:002018-04Journal of the American Society of NephrologyClinical Research29441309107913161081
- IL-17C/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular InflammationThe IL-17 cytokine family and the cognate receptors thereof have a unique role in organ-specific autoimmunity. Most studies have focused on the founding member of the IL-17 family, IL-17A, as the central mediator of diseases. Indeed, although pathogenic functions have been ascribed to IL-17A and IL-17F in the context of immune-mediated glomerular diseases, the specific functions of the other IL-17 family members in immunity and inflammatory kidney diseases is largely unknown. Here, we report that compared with healthy controls, patients with acute Anti-neutrophil cytoplasmatic antibody (ANCA)-associated crescentic glomerulonephritis (GN) had significantly elevated serum levels of IL-17C (but not IL-17A, F, or E). In mouse models of crescentic GN (nephrotoxic nephritis) and pristane-induced lupus nephritis, deficiency in IL-17C significantly ameliorated the course of GN in terms of renal tissue injury and kidney function. Deficiency of the unique IL-17C receptor IL-17 receptor E (IL-17RE) provided similar protection against crescentic GN. These protective effects associated with a reduced TH17 response. Bone marrow transplantation experiments revealed that IL-17C is produced by tissue-resident cells, but not by lymphocytes. Finally, IL-17RE was highly expressed by CD4+ TH17 cells, and loss of this expression prevented the TH17 responses and subsequent tissue injury in crescentic GN. Our findings indicate that IL-17C promotes TH17 cell responses and immune-mediated kidney disease via IL-17RE expressed on CD4+ TH17 cells. Targeting the IL-17C/IL-17RE pathway may present an intriguing therapeutic strategy for TH17-induced autoimmune disorders.10.1681/ASN.2017090949Mon, 26 Feb 2018 07:11:49 GMT-08:00IL-17C/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular InflammationThe IL-17 cytokine family and the cognate receptors thereof have a unique role in organ-specific autoimmunity. Most studies have focused on the founding member of the IL-17 family, IL-17A, as the central mediator of diseases. Indeed, although pathogenic functions have been ascribed to IL-17A and IL-17F in the context of immune-mediated glomerular diseases, the specific functions of the other IL-17 family members in immunity and inflammatory kidney diseases is largely unknown. Here, we report that compared with healthy controls, patients with acute Anti-neutrophil cytoplasmatic antibody (ANCA)-associated crescentic glomerulonephritis (GN) had significantly elevated serum levels of IL-17C (but not IL-17A, F, or E). In mouse models of crescentic GN (nephrotoxic nephritis) and pristane-induced lupus nephritis, deficiency in IL-17C significantly ameliorated the course of GN in terms of renal tissue injury and kidney function. Deficiency of the unique IL-17C receptor IL-17 receptor E (IL-17RE) provided similar protection against crescentic GN. These protective effects associated with a reduced TH17 response. Bone marrow transplantation experiments revealed that IL-17C is produced by tissue-resident cells, but not by lymphocytes. Finally, IL-17RE was highly expressed by CD4+ TH17 cells, and loss of this expression prevented the TH17 responses and subsequent tissue injury in crescentic GN. Our findings indicate that IL-17C promotes TH17 cell responses and immune-mediated kidney disease via IL-17RE expressed on CD4+ TH17 cells. Targeting the IL-17C/IL-17RE pathway may present an intriguing therapeutic strategy for TH17-induced autoimmune disorders.Krohn, SonjaNies, Jasper F.Kapffer, SonjaSchmidt, TilmanRiedel, Jan-HendrikKaffke, AnnaPeters, AnettBorchers, AlinaSteinmetz, Oliver M.Krebs, Christian F.Turner, Jan-EricBrix, Silke R.Paust, Hans-JoachimStahl, Rolf A. K.Panzer, Ulf2018-02-26T07:11:49-08:00doi:10.1681/ASN.2017090949hwp:resource-id:jnephrol;29/4/1210American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, glomerulonephritis, lupus nephritis, cytokines, immunology, Th17 responseBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170909491046-66731533-34502018-02-26T07:11:49-08:002018-04Journal of the American Society of NephrologyBasic Research29412101222
- Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an AlarminInflammation is a prominent feature of ischemia-reperfusion injury (IRI), which is characterized by leukocyte infiltration and renal tubular injury. However, signals that initiate these events remain poorly understood. We examined the role of the nuclear alarmin IL-33 in tissue injury and innate immune response triggered by experimental kidney ischemia-reperfusion. In wild-type mice, we found that IL-33 was constitutively expressed throughout the kidney in peritubular and periglomerular spaces, mainly by microvascular endothelial cells, from which it was released immediately during IRI. Compared with wild-type mice, mice lacking IL-33 (IL-33Gt/Gt) exhibited reductions in early tubular cell injury and subsequent renal infiltration of IFN-γ/IL-17A–producing neutrophils, with preservation of renal functions. This protection associated with decreased renal recruitment of myeloid dendritic cells, natural killer (NK) cells, and invariant natural killer T (iNKT) cells, the latter of which were reported as deleterious in IRI. Increases in the level of circulating IL-12, a key IL-33 cofactor, and the expression of ST2, an IL-33–specific receptor, on the surface of iNKT cells preceded the IL-33– and iNKT cell–dependent phase of neutrophil infiltration. Furthermore, IL-33 directly targeted iNKT cells in vitro, inducing IFN-γ and IL-17A production. We propose that endogenous IL-33 is released as an alarmin and contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Our findings show a novel molecular mediator contributing to innate immune cell recruitment induced by renal ischemia-reperfusion and may provide therapeutic insights into AKI associated with renal transplantation.10.1681/ASN.2017060650Wed, 07 Feb 2018 06:14:32 GMT-08:00Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an AlarminInflammation is a prominent feature of ischemia-reperfusion injury (IRI), which is characterized by leukocyte infiltration and renal tubular injury. However, signals that initiate these events remain poorly understood. We examined the role of the nuclear alarmin IL-33 in tissue injury and innate immune response triggered by experimental kidney ischemia-reperfusion. In wild-type mice, we found that IL-33 was constitutively expressed throughout the kidney in peritubular and periglomerular spaces, mainly by microvascular endothelial cells, from which it was released immediately during IRI. Compared with wild-type mice, mice lacking IL-33 (IL-33Gt/Gt) exhibited reductions in early tubular cell injury and subsequent renal infiltration of IFN-γ/IL-17A–producing neutrophils, with preservation of renal functions. This protection associated with decreased renal recruitment of myeloid dendritic cells, natural killer (NK) cells, and invariant natural killer T (iNKT) cells, the latter of which were reported as deleterious in IRI. Increases in the level of circulating IL-12, a key IL-33 cofactor, and the expression of ST2, an IL-33–specific receptor, on the surface of iNKT cells preceded the IL-33– and iNKT cell–dependent phase of neutrophil infiltration. Furthermore, IL-33 directly targeted iNKT cells in vitro, inducing IFN-γ and IL-17A production. We propose that endogenous IL-33 is released as an alarmin and contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Our findings show a novel molecular mediator contributing to innate immune cell recruitment induced by renal ischemia-reperfusion and may provide therapeutic insights into AKI associated with renal transplantation.Ferhat, MarouaRobin, AurélieGiraud, SébastienSena, SandraGoujon, Jean-MichelTouchard, GuyHauet, ThierryGirard, Jean-PhilippeGombert, Jean-MarcHerbelin, AndréThierry, Antoine2018-02-07T06:14:32-08:00doi:10.1681/ASN.2017060650hwp:resource-id:jnephrol;29/4/1272American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycell activation, cytokines, immunology, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170606501046-66731533-34502018-02-07T06:14:32-08:002018-04Journal of the American Society of NephrologyBasic Research29412721288
- Unique Gene Expression in Developing Ascending Vasa Recta: A Tale of Tie10.1681/ASN.2018020190Mon, 12 Mar 2018 05:59:02 GMT-07:00Unique Gene Expression in Developing Ascending Vasa Recta: A Tale of TieBasile, David P.Yoder, Mervin C.2018-03-12T05:59:02-07:00doi:10.1681/ASN.2018020190hwp:resource-id:jnephrol;29/4/1073American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyendothelial cells, renal development, vasa rectaUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-04-01April 201810.1681/ASN.20180201901046-66731533-34502018-03-12T05:59:02-07:002018-04Journal of the American Society of NephrologyUp Front Matters29441073109710741107
- This Month’s Highlights10.1681/ASN.2018020185Fri, 30 Mar 2018 01:00:46 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2018-03-30T13:00:46-07:00doi:10.1681/ASN.2018020185hwp:resource-id:jnephrol;29/4/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-04-01April 201810.1681/ASN.20180201851046-66731533-34502018-03-30T13:00:46-07:002018-04Journal of the American Society of NephrologyThis Month’s Highlights294ii
- Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly PatientsThe initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [15O]H2O positron emission tomography–computed tomography (PET-CT). During a single hemodialysis session, three [15O]H2O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, −4.1 ml/100 g per minute; 95% confidence interval, −7.3 to −0.9 ml/100 g per minute; P=0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.10.1681/ASN.2017101088Thu, 01 Mar 2018 10:55:01 GMT-08:00Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly PatientsThe initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [15O]H2O positron emission tomography–computed tomography (PET-CT). During a single hemodialysis session, three [15O]H2O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, −4.1 ml/100 g per minute; 95% confidence interval, −7.3 to −0.9 ml/100 g per minute; P=0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.Polinder-Bos, Harmke A.García, David VállezKuipers, JohannaElting, Jan Willem J.Aries, Marcel J.H.Krijnen, Wim P.Groen, HenkWillemsen, Antoon T.M.van Laar, Peter J.Strijkert, FijanneLuurtsema, GertSlart, Riemer H.J.A.Westerhuis, RalfGansevoort, Ron T.Gaillard, Carlo A.J.M.Franssen, Casper F.M.2018-03-01T10:55:01-08:00doi:10.1681/ASN.2017101088hwp:resource-id:jnephrol;29/4/1317American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygeriatric nephrology, brain perfusion, chronic renal failure, [15O]H2O PET, executive functionClinical ResearchClinical Researchresearch-article20182018-04-01April 201810.1681/ASN.20171010881046-66731533-34502018-03-01T10:55:01-08:002018-04Journal of the American Society of NephrologyClinical Research2929448131710872256132510892256
- Maintenance and Breakdown of Glomerular Tuft Architecture10.1681/ASN.2018020200Tue, 13 Mar 2018 06:18:15 GMT-07:00Maintenance and Breakdown of Glomerular Tuft ArchitectureKriz, Wilhelm2018-03-13T06:18:15-07:00doi:10.1681/ASN.2018020200hwp:resource-id:jnephrol;29/4/1075American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyGBM, mesangial cell, adhesion complexUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-04-01April 201810.1681/ASN.20180202001046-66731533-34502018-03-13T06:18:15-07:002018-04Journal of the American Society of NephrologyUp Front Matters29441075112810771140
- Protein Kinase 2β Is Expressed in Neural Crest-Derived Urinary Pacemaker Cells and Required for Pyeloureteric ContractionNonobstructive hydronephrosis, defined as dilatation of the renal pelvis with or without dilatation of the ureter, is the most common antenatal abnormality detected by fetal ultrasound. Yet, the etiology of nonobstructive hydronephrosis is poorly defined. We previously demonstrated that defective development of urinary tract pacemaker cells (utPMCs) expressing hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) and the stem cell marker cKIT causes abnormal ureteric peristalsis and nonobstructive hydronephrosis. However, further investigation of utPMC development and function is limited by lack of knowledge regarding the embryonic derivation, development, and molecular apparatus of these cells. Here, we used lineage tracing in mice to identify cells that give rise to utPMCs. Neural crest cells (NCCs) indelibly labeled with tdTomato expressed HCN3 and cKIT. Furthermore, purified HCN3+ and cKIT+ utPMCs were enriched in Sox10 and Tfap-2α, markers of NCCs. Sequencing of purified RNA from HCN3+ cells revealed enrichment of a small subset of RNAs, including RNA encoding protein kinase 2β (PTK2β), a Ca2+-dependent tyrosine kinase that regulates ion channel activity in neurons. Immunofluorescence analysis in situ revealed PTK2β expression in NCCs as early as embryonic day 12.5 and in HCN3+ and cKIT+ utPMCs as early as embryonic day 15.5, with sustained expression in HCN3+ utPMCs until postnatal week 8. Pharmacologic inhibition of PTK2β in murine pyeloureteral tissue explants inhibited contraction frequency. Together, these results demonstrate that utPMCs are derived from NCCs, identify new markers of utPMCs, and demonstrate a functional contribution of PTK2β to utPMC function.10.1681/ASN.2017090951Wed, 07 Feb 2018 06:14:32 GMT-08:00Protein Kinase 2β Is Expressed in Neural Crest-Derived Urinary Pacemaker Cells and Required for Pyeloureteric ContractionNonobstructive hydronephrosis, defined as dilatation of the renal pelvis with or without dilatation of the ureter, is the most common antenatal abnormality detected by fetal ultrasound. Yet, the etiology of nonobstructive hydronephrosis is poorly defined. We previously demonstrated that defective development of urinary tract pacemaker cells (utPMCs) expressing hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) and the stem cell marker cKIT causes abnormal ureteric peristalsis and nonobstructive hydronephrosis. However, further investigation of utPMC development and function is limited by lack of knowledge regarding the embryonic derivation, development, and molecular apparatus of these cells. Here, we used lineage tracing in mice to identify cells that give rise to utPMCs. Neural crest cells (NCCs) indelibly labeled with tdTomato expressed HCN3 and cKIT. Furthermore, purified HCN3+ and cKIT+ utPMCs were enriched in Sox10 and Tfap-2α, markers of NCCs. Sequencing of purified RNA from HCN3+ cells revealed enrichment of a small subset of RNAs, including RNA encoding protein kinase 2β (PTK2β), a Ca2+-dependent tyrosine kinase that regulates ion channel activity in neurons. Immunofluorescence analysis in situ revealed PTK2β expression in NCCs as early as embryonic day 12.5 and in HCN3+ and cKIT+ utPMCs as early as embryonic day 15.5, with sustained expression in HCN3+ utPMCs until postnatal week 8. Pharmacologic inhibition of PTK2β in murine pyeloureteral tissue explants inhibited contraction frequency. Together, these results demonstrate that utPMCs are derived from NCCs, identify new markers of utPMCs, and demonstrate a functional contribution of PTK2β to utPMC function.Iskander, Samir M.Feeney, Meghan M.Yee, KirbyRosenblum, Norman D.2018-02-07T06:14:32-08:00doi:10.1681/ASN.2017090951hwp:resource-id:jnephrol;29/4/1198American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycell biology and structure, genetics and development, hydronephrosis, pacemaker functionBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170909511046-66731533-34502018-02-07T06:14:32-08:002018-04Journal of the American Society of NephrologyBasic Research29411981209
- Effect of Bariatric Surgery on CKD RiskObesity is linked to the development and progression of CKD, but whether bariatric surgery protects against CKD is poorly understood. We, therefore, examined whether bariatric surgery influences CKD risk. The study included 2144 adults who underwent bariatric surgery from March of 2006 to April of 2009 and participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort. The primary outcome was CKD risk categories as assessed by the Kidney Disease Improving Global Outcomes (KDIGO) consortium criteria using a combination of eGFR and albuminuria. Patients were 79% women and 87% white, with a median age of 46 years old. Improvements were observed in CKD risk at 1 and 7 years after surgery in patients with moderate baseline CKD risk (63% and 53%, respectively), high baseline risk (78% and 56%, respectively), and very high baseline risk (59% and 23%, respectively). The proportion of patients whose CKD risk worsened was ≤10%; five patients developed ESRD. Sensitivity analyses using year 1 as baseline to minimize the effect of weight loss on serum creatinine and differing eGFR equations offered qualitatively similar results. Treatment with bariatric surgery associated with an improvement in CKD risk categories in a large proportion of patients for up to 7 years, especially in those with moderate and high baseline risk. These findings support consideration of CKD risk in evaluation for bariatric surgery and further study of bariatric surgery as a treatment for high-risk obese patients with CKD.10.1681/ASN.2017060707Mon, 15 Jan 2018 09:38:15 GMT-08:00Effect of Bariatric Surgery on CKD RiskObesity is linked to the development and progression of CKD, but whether bariatric surgery protects against CKD is poorly understood. We, therefore, examined whether bariatric surgery influences CKD risk. The study included 2144 adults who underwent bariatric surgery from March of 2006 to April of 2009 and participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort. The primary outcome was CKD risk categories as assessed by the Kidney Disease Improving Global Outcomes (KDIGO) consortium criteria using a combination of eGFR and albuminuria. Patients were 79% women and 87% white, with a median age of 46 years old. Improvements were observed in CKD risk at 1 and 7 years after surgery in patients with moderate baseline CKD risk (63% and 53%, respectively), high baseline risk (78% and 56%, respectively), and very high baseline risk (59% and 23%, respectively). The proportion of patients whose CKD risk worsened was ≤10%; five patients developed ESRD. Sensitivity analyses using year 1 as baseline to minimize the effect of weight loss on serum creatinine and differing eGFR equations offered qualitatively similar results. Treatment with bariatric surgery associated with an improvement in CKD risk categories in a large proportion of patients for up to 7 years, especially in those with moderate and high baseline risk. These findings support consideration of CKD risk in evaluation for bariatric surgery and further study of bariatric surgery as a treatment for high-risk obese patients with CKD.Friedman, Allon N.Wahed, Abdus S.Wang, JunyaoCourcoulas, Anita P.Dakin, GregoryHinojosa, Marcelo W.Kimmel, Paul L.Mitchell, James E.Pomp, AlfonsPories, Walter J.Purnell, Jonathan Q.le Roux, CarelSpaniolas, KonstantinosSteffen, Kristine J.Thirlby, RichardWolfe, Bruce2018-01-15T09:38:15-08:00doi:10.1681/ASN.2017060707hwp:resource-id:jnephrol;29/4/1289American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, CKD, bariatric surgery, prognosis, chronic kidney disease, weight, lossClinical EpidemiologyClinical Epidemiologyresearch-article20182018-04-01April 201810.1681/ASN.20170607071046-66731533-34502018-01-15T09:38:15-08:002018-04Journal of the American Society of NephrologyClinical Epidemiology29441289108513001086
- Nephronectin Regulates Mesangial Cell Adhesion and Behavior in GlomeruliA critical aspect of kidney function occurs at the glomerulus, the capillary network that filters the blood. The glomerular basement membrane (GBM) is a key component of filtration, yet our understanding of GBM interactions with mesangial cells, specialized pericytes that provide structural stability to glomeruli, is limited. We investigated the role of nephronectin (Npnt), a GBM component and known ligand of α8β1 integrin. Immunolocalization and in situ hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM. Conditional deletion of Npnt from nephron progenitors caused a pronounced increase in mesangial cell number and mesangial sclerosis. Nephronectin colocalized with α8β1 integrin to novel, specialized adhesion structures that occurred at sites of mesangial cell protrusion at the base of the capillary loops. Absence of nephronectin disrupted these adhesion structures, leading to mislocalization of α8β1. Podocyte-specific deletion of Npnt also led to mesangial sclerosis in mice. These results demonstrate a novel role for nephronectin and α8β1 integrin in a newly described adhesion complex and begin to uncover the molecular interactions between the GBM and mesangial cells, which govern mesangial cell behavior and may have a role in pathologic states.10.1681/ASN.2017070752Mon, 15 Jan 2018 09:38:16 GMT-08:00Nephronectin Regulates Mesangial Cell Adhesion and Behavior in GlomeruliA critical aspect of kidney function occurs at the glomerulus, the capillary network that filters the blood. The glomerular basement membrane (GBM) is a key component of filtration, yet our understanding of GBM interactions with mesangial cells, specialized pericytes that provide structural stability to glomeruli, is limited. We investigated the role of nephronectin (Npnt), a GBM component and known ligand of α8β1 integrin. Immunolocalization and in situ hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM. Conditional deletion of Npnt from nephron progenitors caused a pronounced increase in mesangial cell number and mesangial sclerosis. Nephronectin colocalized with α8β1 integrin to novel, specialized adhesion structures that occurred at sites of mesangial cell protrusion at the base of the capillary loops. Absence of nephronectin disrupted these adhesion structures, leading to mislocalization of α8β1. Podocyte-specific deletion of Npnt also led to mesangial sclerosis in mice. These results demonstrate a novel role for nephronectin and α8β1 integrin in a newly described adhesion complex and begin to uncover the molecular interactions between the GBM and mesangial cells, which govern mesangial cell behavior and may have a role in pathologic states.Zimmerman, Susan E.Hiremath, ChitkaleTsunezumi, JunYang, ZhufengFinney, BronwynMarciano, Denise K.2018-01-15T09:38:16-08:00doi:10.1681/ASN.2017070752hwp:resource-id:jnephrol;29/4/1128American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycell-matrix-interactions, nephronectin, glomerular basement membrane, mesangial cells, cell biology and structureBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170707521046-66731533-34502018-01-15T09:38:16-08:002018-04Journal of the American Society of NephrologyBasic Research29441128107511401077
- Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream InfectionCentral venous catheters (CVCs) contribute disproportionately to bloodstream infection (BSI) and, by extension, to infection-related hospitalization, mortality, and health care costs in patients undergoing dialysis. Recent product advancements may reduce BSIs, but a sufficiently powered comparative-effectiveness study is needed to facilitate evidence-based patient care decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps (ClearGuard group) with those in facilities using Tego hemodialysis connectors plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities in the United States were pair-matched by BSI rate, number of patients using CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all adult patients undergoing dialysis with CVCs at these facilities, except those allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the study, accruing >183,000 CVC-days. The study outcome was positive blood culture (PBC) rate as an indicator of BSI rate. We calculated results at the cluster level and adjusted for the facility cluster effect. During a 3-month run-in period immediately before study interventions, the groups had similar BSI rates (P=0.8). During the 13-month intervention period that immediately followed, the ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P=0.001). No device-related adverse events were reported. In conclusion, compared with Tego connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps significantly lowered the rate of catheter-related BSIs in patients undergoing hemodialysis using CVCs, representing an important advancement in hemodialysis patient care.10.1681/ASN.2017080870Thu, 22 Feb 2018 07:39:40 GMT-08:00Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream InfectionCentral venous catheters (CVCs) contribute disproportionately to bloodstream infection (BSI) and, by extension, to infection-related hospitalization, mortality, and health care costs in patients undergoing dialysis. Recent product advancements may reduce BSIs, but a sufficiently powered comparative-effectiveness study is needed to facilitate evidence-based patient care decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps (ClearGuard group) with those in facilities using Tego hemodialysis connectors plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities in the United States were pair-matched by BSI rate, number of patients using CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all adult patients undergoing dialysis with CVCs at these facilities, except those allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the study, accruing >183,000 CVC-days. The study outcome was positive blood culture (PBC) rate as an indicator of BSI rate. We calculated results at the cluster level and adjusted for the facility cluster effect. During a 3-month run-in period immediately before study interventions, the groups had similar BSI rates (P=0.8). During the 13-month intervention period that immediately followed, the ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P=0.001). No device-related adverse events were reported. In conclusion, compared with Tego connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps significantly lowered the rate of catheter-related BSIs in patients undergoing hemodialysis using CVCs, representing an important advancement in hemodialysis patient care.Brunelli, Steven M.Van Wyck, David B.Njord, LeviZiebol, Robert J.Lynch, Laurie E.Killion, Douglas P.2018-02-22T07:39:40-08:00doi:10.1681/ASN.2017080870hwp:resource-id:jnephrol;29/4/1336American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis access, vascular access, dialysis access, hemodialysisClinical ResearchClinical Researchresearch-article20182018-04-01April 201810.1681/ASN.20170808701046-66731533-34502018-02-22T07:39:40-08:002018-04Journal of the American Society of NephrologyClinical Research29441336108313431084
- The MFHR1 Fusion Protein Is a Novel Synthetic Multitarget Complement Inhibitor with Therapeutic PotentialThe complement system is essential for host defense, but uncontrolled complement system activation leads to severe, mostly renal pathologies, such as atypical hemolytic uremic syndrome or C3 glomerulopathy. Here, we investigated a novel combinational approach to modulate complement activation by targeting C3 and the terminal pathway simultaneously. The synthetic fusion protein MFHR1 links the regulatory domains of complement factor H (FH) with the C5 convertase/C5b-9 inhibitory fragment of the FH-related protein 1. In vitro, MFHR1 showed cofactor and decay acceleration activity and inhibited C5 convertase activation and C5b-9 assembly, which prevented C3b deposition and reduced C3a/C5a and C5b-9 generation. Furthermore, this fusion protein showed the ability to escape deregulation by FH-related proteins and form multimeric complexes with increased inhibitory activity. In addition to substantially inhibiting alternative and classic pathway activation, MFHR1 blocked hemolysis mediated by serum from a patient with aHUS expressing truncated FH. In FH−/− mice, MFHR1 administration augmented serum C3 levels, reduced abnormal glomerular C3 deposition, and ameliorated C3 glomerulopathy. Taking the unique design of MFHR1 into account, we suggest that the combination of proximal and terminal cascade inhibition together with the ability to form multimeric complexes explain the strong inhibitory capacity of MFHR1, which offers a novel basis for complement therapeutics.10.1681/ASN.2017070738Mon, 15 Jan 2018 09:38:14 GMT-08:00The MFHR1 Fusion Protein Is a Novel Synthetic Multitarget Complement Inhibitor with Therapeutic PotentialThe complement system is essential for host defense, but uncontrolled complement system activation leads to severe, mostly renal pathologies, such as atypical hemolytic uremic syndrome or C3 glomerulopathy. Here, we investigated a novel combinational approach to modulate complement activation by targeting C3 and the terminal pathway simultaneously. The synthetic fusion protein MFHR1 links the regulatory domains of complement factor H (FH) with the C5 convertase/C5b-9 inhibitory fragment of the FH-related protein 1. In vitro, MFHR1 showed cofactor and decay acceleration activity and inhibited C5 convertase activation and C5b-9 assembly, which prevented C3b deposition and reduced C3a/C5a and C5b-9 generation. Furthermore, this fusion protein showed the ability to escape deregulation by FH-related proteins and form multimeric complexes with increased inhibitory activity. In addition to substantially inhibiting alternative and classic pathway activation, MFHR1 blocked hemolysis mediated by serum from a patient with aHUS expressing truncated FH. In FH−/− mice, MFHR1 administration augmented serum C3 levels, reduced abnormal glomerular C3 deposition, and ameliorated C3 glomerulopathy. Taking the unique design of MFHR1 into account, we suggest that the combination of proximal and terminal cascade inhibition together with the ability to form multimeric complexes explain the strong inhibitory capacity of MFHR1, which offers a novel basis for complement therapeutics.Michelfelder, StefanFischer, FriederickeWäldin, AstridHörle, Kim V.Pohl, MartinParsons, JulianaReski, RalfDecker, Eva L.Zipfel, Peter F.Skerka, ChristineHäffner, Karsten2018-01-15T09:38:14-08:00doi:10.1681/ASN.2017070738hwp:resource-id:jnephrol;29/4/1141American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, therapeutics, atypical hemolytic uremic syndrome, C3 Glomerulopathy, factor H-related protein, factor HBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170707381046-66731533-34502018-01-15T09:38:14-08:002018-04Journal of the American Society of NephrologyBasic Research29411411153
- Ascending Vasa Recta Are Angiopoietin/Tie2-Dependent Lymphatic-Like VesselsUrinary concentrating ability is central to mammalian water balance and depends on a medullary osmotic gradient generated by a countercurrent multiplication mechanism. Medullary hyperosmolarity is protected from washout by countercurrent exchange and efficient removal of interstitial fluid resorbed from the loop of Henle and collecting ducts. In most tissues, lymphatic vessels drain excess interstitial fluid back to the venous circulation. However, the renal medulla is devoid of classic lymphatics. Studies have suggested that the fenestrated ascending vasa recta (AVRs) drain the interstitial fluid in this location, but this function has not been conclusively shown. We report that late gestational deletion of the angiopoietin receptor endothelial tyrosine kinase 2 (Tie2) or both angiopoietin-1 and angiopoietin-2 prevents AVR formation in mice. The absence of AVR associated with rapid accumulation of fluid and cysts in the medullary interstitium, loss of medullary vascular bundles, and decreased urine concentrating ability. In transgenic reporter mice with normal angiopoietin-Tie2 signaling, medullary AVR exhibited an unusual hybrid endothelial phenotype, expressing lymphatic markers (prospero homeobox protein 1 and vascular endothelial growth factor receptor 3) as well as blood endothelial markers (CD34, endomucin, platelet endothelial cell adhesion molecule 1, and plasmalemmal vesicle–associated protein). Taken together, our data redefine the AVRs as Tie2 signaling–dependent specialized hybrid vessels and provide genetic evidence of the critical role of AVR in the countercurrent exchange mechanism and the structural integrity of the renal medulla.10.1681/ASN.2017090962Wed, 13 Dec 2017 07:17:02 GMT-08:00Ascending Vasa Recta Are Angiopoietin/Tie2-Dependent Lymphatic-Like VesselsUrinary concentrating ability is central to mammalian water balance and depends on a medullary osmotic gradient generated by a countercurrent multiplication mechanism. Medullary hyperosmolarity is protected from washout by countercurrent exchange and efficient removal of interstitial fluid resorbed from the loop of Henle and collecting ducts. In most tissues, lymphatic vessels drain excess interstitial fluid back to the venous circulation. However, the renal medulla is devoid of classic lymphatics. Studies have suggested that the fenestrated ascending vasa recta (AVRs) drain the interstitial fluid in this location, but this function has not been conclusively shown. We report that late gestational deletion of the angiopoietin receptor endothelial tyrosine kinase 2 (Tie2) or both angiopoietin-1 and angiopoietin-2 prevents AVR formation in mice. The absence of AVR associated with rapid accumulation of fluid and cysts in the medullary interstitium, loss of medullary vascular bundles, and decreased urine concentrating ability. In transgenic reporter mice with normal angiopoietin-Tie2 signaling, medullary AVR exhibited an unusual hybrid endothelial phenotype, expressing lymphatic markers (prospero homeobox protein 1 and vascular endothelial growth factor receptor 3) as well as blood endothelial markers (CD34, endomucin, platelet endothelial cell adhesion molecule 1, and plasmalemmal vesicle–associated protein). Taken together, our data redefine the AVRs as Tie2 signaling–dependent specialized hybrid vessels and provide genetic evidence of the critical role of AVR in the countercurrent exchange mechanism and the structural integrity of the renal medulla.Kenig-Kozlovsky, YaelScott, Rizaldy P.Onay, TuncerCarota, Isabel AnnaThomson, Benjamin R.Gil, Hyea JinRamirez, VeronicaYamaguchi, ShinjiTanna, Christine E.Heinen, StefanWu, ChristineStan, Radu V.Klein, Janet D.Sands, Jeff M.Oliver, GuillermoQuaggin, Susan E.2017-12-13T07:17:02-08:00doi:10.1681/ASN.2017090962hwp:resource-id:jnephrol;29/4/1097American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyangiopoietin, Tie2, ascending vasa recta, lymphatic, countercurrent exchange, fluid homeostasisBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170909621046-66731533-34502017-12-13T07:17:02-08:002018-04Journal of the American Society of NephrologyBasic Research29441097107311071074
- Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning ProtectionIschemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine (P<0.05) observed in controls and increased the mitochondria membrane potential (P<0.05), maximal respiratory capacity (P<0.05), and intracellular ATP levels (P<0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning.10.1681/ASN.2017060675Thu, 25 Jan 2018 06:04:04 GMT-08:00Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning ProtectionIschemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine (P<0.05) observed in controls and increased the mitochondria membrane potential (P<0.05), maximal respiratory capacity (P<0.05), and intracellular ATP levels (P<0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning.Kolb, Alexander L.Corridon, Peter R.Zhang, ShijunXu, WeiminWitzmann, Frank A.Collett, Jason A.Rhodes, George J.Winfree, SethBready, DevinPfeffenberger, Zechariah J.Pomerantz, Jeremy M.Hato, TakashiNagami, Glenn T.Molitoris, Bruce A.Basile, David P.Atkinson, Simon J.Bacallao, Robert L.2018-01-25T06:04:04-08:00doi:10.1681/ASN.2017060675hwp:resource-id:jnephrol;29/4/1154American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, retrograde renal vein injection, ischemic preconditioningBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170606751046-66731533-34502018-01-25T06:04:04-08:002018-04Journal of the American Society of NephrologyBasic Research29411541164
- Fibroblast-Specific β-Catenin Signaling Dictates the Outcome of AKIAKI is a devastating condition with high morbidity and mortality. The pathologic features of AKI are characterized by tubular injury, inflammation, and vascular impairment. Whether fibroblasts in the renal interstitium have a role in the pathogenesis of AKI is unknown. In this study, we investigated the role of fibroblast-specific β-catenin signaling in dictating the outcome of AKI, using conditional knockout mice in which β-catenin was specifically ablated in fibroblasts (Gli1-β-cat−/−). After ischemia-reperfusion injury (IRI), Gli1-β-cat−/− mice had lower serum creatinine levels and less morphologic injury than Gli1-β-cat+/+ littermate controls. Moreover, we detected fewer apoptotic cells, as well as decreased cytochrome C release; reduced expression of Bax, FasL, and p53; and increased phosphorylation of Akt, in the Gli1-β-cat−/− kidneys. Gli1-β-cat−/− kidneys also exhibited upregulated expression of proliferating cell nuclear antigen and Ki-67, which are markers of cell proliferation. Furthermore, Gli1-β-cat−/− kidneys displayed suppressed NF-κB signaling and cytokine expression and reduced infiltration of inflammatory cells. Notably, loss of β-catenin in fibroblasts induced renal expression of hepatocyte growth factor (HGF) and augmented the tyrosine phosphorylation of c-met receptor after IRI. In vitro, treatment with Wnt ligands or ectopic expression of active β-catenin inhibited HGF mRNA and protein expression and repressed HGF promoter activity. Collectively, these results suggest that fibroblast-specific β-catenin signaling can control tubular injury and repair in AKI by modulating HGF expression. Our studies uncover a previously unrecognized role for interstitial fibroblasts in the pathogenesis of AKI.10.1681/ASN.2017080903Wed, 17 Jan 2018 06:23:40 GMT-08:00Fibroblast-Specific β-Catenin Signaling Dictates the Outcome of AKIAKI is a devastating condition with high morbidity and mortality. The pathologic features of AKI are characterized by tubular injury, inflammation, and vascular impairment. Whether fibroblasts in the renal interstitium have a role in the pathogenesis of AKI is unknown. In this study, we investigated the role of fibroblast-specific β-catenin signaling in dictating the outcome of AKI, using conditional knockout mice in which β-catenin was specifically ablated in fibroblasts (Gli1-β-cat−/−). After ischemia-reperfusion injury (IRI), Gli1-β-cat−/− mice had lower serum creatinine levels and less morphologic injury than Gli1-β-cat+/+ littermate controls. Moreover, we detected fewer apoptotic cells, as well as decreased cytochrome C release; reduced expression of Bax, FasL, and p53; and increased phosphorylation of Akt, in the Gli1-β-cat−/− kidneys. Gli1-β-cat−/− kidneys also exhibited upregulated expression of proliferating cell nuclear antigen and Ki-67, which are markers of cell proliferation. Furthermore, Gli1-β-cat−/− kidneys displayed suppressed NF-κB signaling and cytokine expression and reduced infiltration of inflammatory cells. Notably, loss of β-catenin in fibroblasts induced renal expression of hepatocyte growth factor (HGF) and augmented the tyrosine phosphorylation of c-met receptor after IRI. In vitro, treatment with Wnt ligands or ectopic expression of active β-catenin inhibited HGF mRNA and protein expression and repressed HGF promoter activity. Collectively, these results suggest that fibroblast-specific β-catenin signaling can control tubular injury and repair in AKI by modulating HGF expression. Our studies uncover a previously unrecognized role for interstitial fibroblasts in the pathogenesis of AKI.Zhou, DongFu, HaiyanXiao, LiangxiangMo, HongyanZhuo, HuiTian, XiaojunLin, LinXing, JianhuaLiu, Youhua2018-01-17T06:23:40-08:00doi:10.1681/ASN.2017080903hwp:resource-id:jnephrol;29/4/1257American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, apoptosis, fibroblast, signaling, Wnt, HGFBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170809031046-66731533-34502018-01-17T06:23:40-08:002018-04Journal of the American Society of NephrologyBasic Research29412571271
- The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 DiabetesAdiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor–α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase kinase–β (CaMKKβ) and numbers of phosphorylated liver kinase B1 (LKB1)– and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKKβ, phosphorylated Ser431LKB1, phosphorylated Thr172AMPK, and PPARα expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose–treated human GECs and murine podocytes, AdipoRon increased intracellular Ca2+ levels that activated a CaMKKβ/phosphorylated Ser431LKB1/phosphorylated Thr172AMPK/PPARα pathway and downstream signaling, thus decreasing high-glucose–induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARα pathway, suggesting its efficacy for treating type 2 diabetes–associated DN.10.1681/ASN.2017060627Fri, 12 Jan 2018 07:47:04 GMT-08:00The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a Model of Type 2 DiabetesAdiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor–α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial fibrosis correlated with renal function deterioration in human kidneys. Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase kinase–β (CaMKKβ) and numbers of phosphorylated liver kinase B1 (LKB1)– and AMPK-positive cells significantly decreased in the glomeruli of early stage human DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice. AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1 and AdipoR2, which increased CaMKKβ, phosphorylated Ser431LKB1, phosphorylated Thr172AMPK, and PPARα expression independently of the systemic effects of adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress and inhibition of apoptosis in the kidneys ameliorated relevant intracellular pathways associated with lipid accumulation and endothelial dysfunction. In high-glucose–treated human GECs and murine podocytes, AdipoRon increased intracellular Ca2+ levels that activated a CaMKKβ/phosphorylated Ser431LKB1/phosphorylated Thr172AMPK/PPARα pathway and downstream signaling, thus decreasing high-glucose–induced oxidative stress and apoptosis and improving endothelial dysfunction. AdipoRon further produced cardioprotective effects through the same pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARα pathway, suggesting its efficacy for treating type 2 diabetes–associated DN.Kim, YaeniLim, Ji HeeKim, Min YoungKim, Eun NimYoon, Hye EunShin, Seok JoonChoi, Bum SoonKim, Yong-SooChang, Yoon SikPark, Cheol Whee2018-01-12T07:47:04-08:00doi:10.1681/ASN.2017060627hwp:resource-id:jnephrol;29/4/1108American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAdipoRon, Lipotoxicity, diabetic nephropathy, oxidative stressBasic ResearchBasic Researchresearch-article20182018-04-01April 201810.1681/ASN.20170606271046-66731533-34502018-01-12T07:47:04-08:002018-04Journal of the American Society of NephrologyBasic Research29411081127
- Filtering the Evidence: Is There a Cognitive Cost of Hemodialysis?10.1681/ASN.2018010077Thu, 01 Mar 2018 10:55:02 GMT-08:00Filtering the Evidence: Is There a Cognitive Cost of Hemodialysis?Wolfgram, Dawn F.2018-03-01T10:55:02-08:00doi:10.1681/ASN.2018010077hwp:resource-id:jnephrol;29/4/1087American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycognitive impairment, cerebral perfusion, hemodialysisUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-04-01April 201810.1681/ASN.20180100771046-66731533-34502018-03-01T10:55:02-08:002018-04Journal of the American Society of NephrologyUp Front Matters29441087131710891325
- Bariatric Surgery and Kidney Health10.1681/ASN.2018020176Mon, 12 Mar 2018 05:59:03 GMT-07:00Bariatric Surgery and Kidney HealthLieske, John C.2018-03-12T05:59:03-07:00doi:10.1681/ASN.2018020176hwp:resource-id:jnephrol;29/4/1085American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, glomerular filtration rate, albuminuria, kidney stones, chronic kidney diseaseUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20182018-04-01April 201810.1681/ASN.20180201761046-66731533-34502018-03-12T05:59:03-07:002018-04Journal of the American Society of NephrologyUp Front Matters29441085128910861300
- Blood HER2 and Uromodulin as Causal Mediators of CKDMany biomarkers have been epidemiologically linked with CKD; however, the possibility that such associations are due to reverse causation or confounding limits the utility of these biomarkers. To overcome this limitation, we used a Mendelian randomization (MR) approach to identify causal mediators of CKD. We performed MR by first identifying genetic determinants of 227 serum protein biomarkers assayed in 4147 participants of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial who had early or prediabetes, and assessing the effects of these biomarkers on CKD in the CKD genetics consortium (n=117,165; 12,385 cases) using the inverse-variance weighted (fixed-effects) method. We then estimated the relationship between the serum concentration of each biomarker identified and incident CKD in ORIGIN participants. MR identified uromodulin (UMOD) and human EGF receptor 2 (HER2) as novel, causal mediators of CKD (UMOD: odds ratio [OR], 1.30 per SD; 95% confidence interval [95% CI], 1.25 to 1.35; P<5×10−20; HER2: OR, 1.30 per SD; 95% CI, 1.14 to 1.48; P=8.0×10−5). Consistent with these findings, blood HER2 concentration associated with CKD events in ORIGIN participants (OR, 1.07 per SD; 95% CI, 1.01 to 1.13; P=0.01). Additional exploratory MR analyses identified angiotensin-converting enzyme (ACE) as a regulator of HER2 levels (β=0.13 per SD; 95% CI, 0.08 to 0.16; P=2.5×10−7). This finding was corroborated by an inverse relationship between ACE inhibitor use and HER2 levels. Thus, UMOD and HER2 are independent causal mediators of CKD in humans, and serum HER2 levels are regulated in part by ACE. These biomarkers are potential therapeutic targets for CKD prevention.10.1681/ASN.2017070812Tue, 06 Mar 2018 06:04:33 GMT-08:00Blood HER2 and Uromodulin as Causal Mediators of CKDMany biomarkers have been epidemiologically linked with CKD; however, the possibility that such associations are due to reverse causation or confounding limits the utility of these biomarkers. To overcome this limitation, we used a Mendelian randomization (MR) approach to identify causal mediators of CKD. We performed MR by first identifying genetic determinants of 227 serum protein biomarkers assayed in 4147 participants of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial who had early or prediabetes, and assessing the effects of these biomarkers on CKD in the CKD genetics consortium (n=117,165; 12,385 cases) using the inverse-variance weighted (fixed-effects) method. We then estimated the relationship between the serum concentration of each biomarker identified and incident CKD in ORIGIN participants. MR identified uromodulin (UMOD) and human EGF receptor 2 (HER2) as novel, causal mediators of CKD (UMOD: odds ratio [OR], 1.30 per SD; 95% confidence interval [95% CI], 1.25 to 1.35; P<5×10−20; HER2: OR, 1.30 per SD; 95% CI, 1.14 to 1.48; P=8.0×10−5). Consistent with these findings, blood HER2 concentration associated with CKD events in ORIGIN participants (OR, 1.07 per SD; 95% CI, 1.01 to 1.13; P=0.01). Additional exploratory MR analyses identified angiotensin-converting enzyme (ACE) as a regulator of HER2 levels (β=0.13 per SD; 95% CI, 0.08 to 0.16; P=2.5×10−7). This finding was corroborated by an inverse relationship between ACE inhibitor use and HER2 levels. Thus, UMOD and HER2 are independent causal mediators of CKD in humans, and serum HER2 levels are regulated in part by ACE. These biomarkers are potential therapeutic targets for CKD prevention.Sjaarda, JenniferGerstein, Hertzel C.Yusuf, SalimTreleaven, DarinWalsh, MichaelMann, Johannes F.E.Hess, SibylleParé, Guillaume2018-03-06T06:04:33-08:00doi:10.1681/ASN.2017070812hwp:resource-id:jnephrol;29/4/1326American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygenetics, Mendelian randomization, biomarker, chronic kidney diseaseClinical ResearchClinical Researchresearch-article20182018-04-01April 201810.1681/ASN.20170708121046-66731533-34502018-03-06T06:04:33-08:002018-04Journal of the American Society of NephrologyClinical Research29413261335
- HIV-Positive Kidney Donor Selection for HIV-Positive Transplant RecipientsThe risks associated with transplanting HIV-positive kidneys into HIV-positive recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV-positive deceased donors have been transplanted into patients who are HIV positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to trauma. The average age for donors was 34 (interquartile range, 19–52) years old. In some donors, only one kidney was used because of a limited number of suitable recipients on the waiting list. Only two donors had been previously exposed to antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status was not known before the time of death. Initial concerns about transplanting HIV-positive allografts into HIV-positive recipients in this clinic revolved around the possibility of HIV superinfection. However, all recipients remained virally suppressed several years after the transplant. Only one recipient experienced an increased viral load after the transplant, which was related to a period of noncompliance on her medication. After counseling and improved compliance, the viral load decreased and became suppressed again. Herein, we discuss the findings of this study and review the literature available on this crucial topic.10.1681/ASN.2017080853Fri, 12 Jan 2018 07:47:04 GMT-08:00HIV-Positive Kidney Donor Selection for HIV-Positive Transplant RecipientsThe risks associated with transplanting HIV-positive kidneys into HIV-positive recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV-positive deceased donors have been transplanted into patients who are HIV positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to trauma. The average age for donors was 34 (interquartile range, 19–52) years old. In some donors, only one kidney was used because of a limited number of suitable recipients on the waiting list. Only two donors had been previously exposed to antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status was not known before the time of death. Initial concerns about transplanting HIV-positive allografts into HIV-positive recipients in this clinic revolved around the possibility of HIV superinfection. However, all recipients remained virally suppressed several years after the transplant. Only one recipient experienced an increased viral load after the transplant, which was related to a period of noncompliance on her medication. After counseling and improved compliance, the viral load decreased and became suppressed again. Herein, we discuss the findings of this study and review the literature available on this crucial topic.Muller, ElmiBarday, Zunaid2018-01-12T07:47:04-08:00doi:10.1681/ASN.2017080853hwp:resource-id:jnephrol;29/4/1090American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyHIV nephropathy, kidney transplantation, cadaver organ transplantationUp Front MattersBrief ReviewUp Front MattersBrief Reviewbrief-report20182018-04-01April 201810.1681/ASN.20170808531046-66731533-34502018-01-12T07:47:04-08:002018-04Journal of the American Society of NephrologyUp Front Matters29410901095
- ApoL1 Overexpression Drives Variant-Independent CytotoxicityCoding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy was monitored biochemically and cell death was measured using multiple assays. We measured intracellular Na+ and K+ content with atomic absorption spectroscopy and APOL1-dependent currents with whole-cell patch clamping. Neither reference nor variant APOL1s induced autophagy. At high expression levels, APOL1-G0, -G1, and -G2 inserted into the plasma membrane and formed pH-sensitive cation channels, causing collapse of cellular Na+ and K+ gradients, phosphorylation of p38 mitogen-activated protein kinase, and cell death, without variant-dependent differences. APOL1-G0 and -G2 exhibited similar channel properties in whole-cell patch clamp experiments. At low expression levels, neither reference nor variant APOL1s localized on the plasma membrane, Na+ and K+ gradients were maintained, and cells remained viable. Our results indicate that APOL1-mediated pore formation is critical for the trypanolytic activity of APOL1 and drives APOL1-mediated cytotoxicity in overexpression systems. The absence of cytotoxicity at physiologic expression levels suggests variant-dependent intracellular K+ loss and cytotoxicity does not drive kidney disease progression.10.1681/ASN.2016121322Mon, 27 Nov 2017 06:42:42 GMT-08:00ApoL1 Overexpression Drives Variant-Independent CytotoxicityCoding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy was monitored biochemically and cell death was measured using multiple assays. We measured intracellular Na+ and K+ content with atomic absorption spectroscopy and APOL1-dependent currents with whole-cell patch clamping. Neither reference nor variant APOL1s induced autophagy. At high expression levels, APOL1-G0, -G1, and -G2 inserted into the plasma membrane and formed pH-sensitive cation channels, causing collapse of cellular Na+ and K+ gradients, phosphorylation of p38 mitogen-activated protein kinase, and cell death, without variant-dependent differences. APOL1-G0 and -G2 exhibited similar channel properties in whole-cell patch clamp experiments. At low expression levels, neither reference nor variant APOL1s localized on the plasma membrane, Na+ and K+ gradients were maintained, and cells remained viable. Our results indicate that APOL1-mediated pore formation is critical for the trypanolytic activity of APOL1 and drives APOL1-mediated cytotoxicity in overexpression systems. The absence of cytotoxicity at physiologic expression levels suggests variant-dependent intracellular K+ loss and cytotoxicity does not drive kidney disease progression.O'Toole, John F.Schilling, WilliamKunze, DianaMadhavan, Sethu M.Konieczkowski, MarthaGu, YapingLuo, LipingWu, ZhenzhenBruggeman, Leslie A.Sedor, John R.2017-11-27T06:42:42-08:00doi:10.1681/ASN.2016121322hwp:resource-id:jnephrol;29/3/869American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, autophagy, cell death, kidneyBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20161213221046-66731533-34502017-11-27T06:42:42-08:002018-03Journal of the American Society of NephrologyBasic Research293869879
- The Era of Human Developmental Nephrology10.1681/ASN.2017121280Thu, 15 Feb 2018 11:05:40 GMT-08:00The Era of Human Developmental NephrologyNishinakamura, Ryuichi2018-02-15T11:05:40-08:00doi:10.1681/ASN.2017121280hwp:resource-id:jnephrol;29/3/705American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, genetics and development, pediatric nephrologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-03-01March 201810.1681/ASN.20171212801046-66731533-34502018-02-15T11:05:40-08:002018-03Journal of the American Society of NephrologyUp Front Matters293333705785806825706805824840
- This Month’s Highlights10.1681/ASN.2018010067Wed, 28 Feb 2018 01:00:48 GMT-08:00This Month’s HighlightsAmerican Society of Nephrology2018-02-28T13:00:48-08:00doi:10.1681/ASN.2018010067hwp:resource-id:jnephrol;29/3/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-03-01March 201810.1681/ASN.20180100671046-66731533-34502018-02-28T13:00:48-08:002018-03Journal of the American Society of NephrologyThis Month’s Highlights293ii
- Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport SyndromePierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient’s nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3−/− mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5+/− females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α3α4α5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.10.1681/ASN.2017090997Wed, 20 Dec 2017 07:39:15 GMT-08:00Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport SyndromePierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient’s nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3−/− mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5+/− females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α3α4α5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans.Funk, Steven D.Bayer, Raymond H.Malone, Andrew F.McKee, Karen K.Yurchenco, Peter D.Miner, Jeffrey H.2017-12-20T07:39:15-08:00doi:10.1681/ASN.2017090997hwp:resource-id:jnephrol;29/3/949American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular basement membrane, nephrotic syndrome, Alport syndrome, lamininBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170909971046-66731533-34502017-12-20T07:39:15-08:002018-03Journal of the American Society of NephrologyBasic Research293949960
- Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor SignalingIn patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2. We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters. This effect depended on the aryl hydrocarbon receptor pathway. Presence of human albumin at physiologic concentration in the culture medium did not abolish the effect of IS. In two mouse models of CKD, the decline in renal function associated with the accumulation of IS in serum and the specific upregulation of Abcb1a in the liver. Additionally, among 109 heart or kidney transplant recipients with CKD, those with higher serum levels of IS needed higher doses of cyclosporin, a P-gp substrate, to obtain the cyclosporin target blood concentration. This need associated with serum levels of IS independent of renal function. These findings suggest that increased activity of P-gp could be responsible for increased hepatic cyclosporin clearance. Altogether, these results suggest that uremic toxins, such as IS, through effects on drug transporters, may modify the nonrenal clearance of drugs in patients with CKD.10.1681/ASN.2017030361Fri, 08 Dec 2017 08:43:46 GMT-08:00Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor SignalingIn patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2. We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters. This effect depended on the aryl hydrocarbon receptor pathway. Presence of human albumin at physiologic concentration in the culture medium did not abolish the effect of IS. In two mouse models of CKD, the decline in renal function associated with the accumulation of IS in serum and the specific upregulation of Abcb1a in the liver. Additionally, among 109 heart or kidney transplant recipients with CKD, those with higher serum levels of IS needed higher doses of cyclosporin, a P-gp substrate, to obtain the cyclosporin target blood concentration. This need associated with serum levels of IS independent of renal function. These findings suggest that increased activity of P-gp could be responsible for increased hepatic cyclosporin clearance. Altogether, these results suggest that uremic toxins, such as IS, through effects on drug transporters, may modify the nonrenal clearance of drugs in patients with CKD.Santana Machado, TacyPoitevin, StéphanePaul, PascaleMcKay, NathalieJourde-Chiche, NoémieLegris, TristanMouly-Bandini, AnnickDignat-George, FrançoiseBrunet, PhilippeMasereeuw, RosalindeBurtey, StéphaneCerini, Claire2017-12-08T08:43:46-08:00doi:10.1681/ASN.2017030361hwp:resource-id:jnephrol;29/3/906American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, ABC transporter, drug transporter, cyclosporineBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170303611046-66731533-34502017-12-08T08:43:46-08:002018-03Journal of the American Society of NephrologyBasic Research293906918
- Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the KidneyTamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP−/− mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of THP stimulated the proliferation of human macrophage cells in culture and partially restored the number of kidney MPCs when administered to THP−/− mice. Furthermore, resident renal MPCs had impaired phagocytic activity in the absence of THP. After ischemia-reperfusion injury, THP−/− mice, compared with wild-type mice, exhibited aggravated injury and an impaired transition of renal macrophages toward an M2 healing phenotype. However, treatment of THP−/− mice with truncated THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI.10.1681/ASN.2017040409Mon, 27 Nov 2017 06:42:41 GMT-08:00Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the KidneyTamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP−/− mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of THP stimulated the proliferation of human macrophage cells in culture and partially restored the number of kidney MPCs when administered to THP−/− mice. Furthermore, resident renal MPCs had impaired phagocytic activity in the absence of THP. After ischemia-reperfusion injury, THP−/− mice, compared with wild-type mice, exhibited aggravated injury and an impaired transition of renal macrophages toward an M2 healing phenotype. However, treatment of THP−/− mice with truncated THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI.Micanovic, RadmilaKhan, ShehnazJanosevic, DanielleLee, Maya E.Hato, TakashiSrour, Edward F.Winfree, SethGhosh, JoydeepTong, YanRice, Susan E.Dagher, Pierre C.Wu, Xue-RuEl-Achkar, Tarek M.2017-11-27T06:42:41-08:00doi:10.1681/ASN.2017040409hwp:resource-id:jnephrol;29/3/841American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymacrophages, acute renal failure, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170404091046-66731533-34502017-11-27T06:42:41-08:002018-03Journal of the American Society of NephrologyBasic Research293841856
- Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion InjuryThe IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.10.1681/ASN.2017070774Tue, 02 Jan 2018 09:07:55 GMT-08:00Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion InjuryThe IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.Cao, QiWang, YipingNiu, ZhiguoWang, ChengshiWang, RuifengZhang, ZhiqiangChen, TitiWang, Xin MaggieLi, QingLee, Vincent W.S.Huang, QingsongTan, JingGuo, MinghaoWang, Yuan MinZheng, GuopingYu, DiAlexander, Stephen I.Wang, HuiHarris, David C.H.2018-01-02T09:07:55-08:00doi:10.1681/ASN.2017070774hwp:resource-id:jnephrol;29/3/961American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia/reperfusion injury, IL-33, innate lymphoid cells, macrophages, immunotherapyBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170707741046-66731533-34502018-01-02T09:07:55-08:002018-03Journal of the American Society of NephrologyBasic Research293961976
- Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse KidneyCellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1, were readily detected within SIX2+ NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2+ NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2, are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs.10.1681/ASN.2017080890Thu, 15 Feb 2018 11:05:40 GMT-08:00Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse KidneyCellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1, were readily detected within SIX2+ NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2+ NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2, are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs.Lindström, Nils O.Guo, JinjinKim, Albert D.Tran, TracyGuo, QiuyuDe Sena Brandine, GuilhermeRansick, AndrewParvez, Riana K.Thornton, Matthew E.Basking, LaurenceGrubbs, BrendanMcMahon, Jill A.Smith, Andrew D.McMahon, Andrew P.2018-02-15T11:05:40-08:00doi:10.1681/ASN.2017080890hwp:resource-id:jnephrol;29/3/806American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, human genetics, nephronBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170808901046-66731533-34502018-02-15T11:05:40-08:002018-03Journal of the American Society of NephrologyBasic Research29333806705706824706709
- Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial InflammationAlbuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding. Notably, the internalization of purified TEC exosomes by cultured macrophages increased if TECs were exposed to BSA. Macrophage internalization of exosomes from BSA-treated TECs led to an enhanced inflammatory response and macrophage migration, but CCL2 silencing in TECs prevented these effects. Using a GFP-CCL2 fusion mRNA construct, we observed direct transfer of CCL2 mRNA from TEC exosomes to macrophages. Mice subjected to tail vein injection of purified BSA-treated TEC exosomes developed tubular injury with renal inflammatory cell infiltration. However, injection of exosomes from BSA-treated CCL2-deficient TECs induced less severe kidney inflammation. Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.10.1681/ASN.2017050523Tue, 02 Jan 2018 09:07:53 GMT-08:00Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial InflammationAlbuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding. Notably, the internalization of purified TEC exosomes by cultured macrophages increased if TECs were exposed to BSA. Macrophage internalization of exosomes from BSA-treated TECs led to an enhanced inflammatory response and macrophage migration, but CCL2 silencing in TECs prevented these effects. Using a GFP-CCL2 fusion mRNA construct, we observed direct transfer of CCL2 mRNA from TEC exosomes to macrophages. Mice subjected to tail vein injection of purified BSA-treated TEC exosomes developed tubular injury with renal inflammatory cell infiltration. However, injection of exosomes from BSA-treated CCL2-deficient TECs induced less severe kidney inflammation. Finally, in patients with IgA nephropathy, the increase of proteinuria correlated with augmented urinary excretion of exosomes with exaggerated expression of CCL2 mRNA. Moreover, the level of CCL2 mRNA in urinary exosomes correlated closely with levels of renal interstitial macrophage infiltration in these patients. Our studies demonstrate that the increasing release of exosomes that transfer CCL2 mRNA from TECs to macrophages constitutes a critical mechanism of albumin-induced tubulointerstitial inflammation.Lv, Lin-LiFeng, YeWen, YiWu, Wei-JunNi, Hai-FengLi, Zuo-LinZhou, Le-TingWang, BinZhang, Jian-DongCrowley, Steven D.Liu, Bi-Cheng2018-01-02T09:07:53-08:00doi:10.1681/ASN.2017050523hwp:resource-id:jnephrol;29/3/919American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyexosome, CCL2, mRNA, extracellular vesicle, albuminuria, macrophagesBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170505231046-66731533-34502018-01-02T09:07:53-08:002018-03Journal of the American Society of NephrologyBasic Research293919935
- Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron PatterningThe nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal–distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, we identified a novel nephron subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature nephron. Significant conservation was observed between human and mouse patterning. We also determined the time at which markers for mature nephron cell types first emerge—critical data for the renal organoid field. These findings have conceptual implications for the evolutionary processes driving the diversity of mammalian organ systems. Furthermore, these findings provide practical insights beyond those gained with mouse and rat models that will guide in vitro efforts to harness the developmental programs necessary to build human kidney structures.10.1681/ASN.2017091036Thu, 15 Feb 2018 11:05:41 GMT-08:00Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron PatterningThe nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal–distal axis of the developing nephron and benchmark expectations for localization of functionally important transcription factors, which revealed unanticipated cellular diversity. Moreover, we identified a novel nephron subdomain marked by Wnt4 expression that we fate-mapped to the proximal mature nephron. Significant conservation was observed between human and mouse patterning. We also determined the time at which markers for mature nephron cell types first emerge—critical data for the renal organoid field. These findings have conceptual implications for the evolutionary processes driving the diversity of mammalian organ systems. Furthermore, these findings provide practical insights beyond those gained with mouse and rat models that will guide in vitro efforts to harness the developmental programs necessary to build human kidney structures.Lindström, Nils O.Tran, TracyGuo, JinjinRutledge, ElisabethParvez, Riana K.Thornton, Matthew E.Grubbs, BrendanMcMahon, Jill A.McMahon, Andrew P.2018-02-15T11:05:41-08:00doi:10.1681/ASN.2017091036hwp:resource-id:jnephrol;29/3/825American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyhuman genetics, nephron, kidney developmentBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170910361046-66731533-34502018-02-15T11:05:41-08:002018-03Journal of the American Society of NephrologyBasic Research29333825705706840706709
- Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous FistulasThe frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P=0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population’s median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.10.1681/ASN.2017050559Tue, 02 Jan 2018 09:07:54 GMT-08:00Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous FistulasThe frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P=0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population’s median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.Martinez, LaiselDuque, Juan C.Tabbara, MarwanPaez, AngelaSelman, GuillermoHernandez, Diana R.Sundberg, Chad A.Tey, Jason Chieh ShengShiu, Yan-TingCheung, Alfred K.Allon, MichaelVelazquez, Omaida C.Salman, Loay H.Vazquez-Padron, Roberto I.2018-01-02T09:07:54-08:00doi:10.1681/ASN.2017050559hwp:resource-id:jnephrol;29/3/1030American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, fibrosis, vascular accessClinical ResearchClinical Researchresearch-article20182018-03-01March 201810.1681/ASN.20170505591046-66731533-34502018-01-02T09:07:54-08:002018-03Journal of the American Society of NephrologyClinical Research29310301040
- Causes of Death after a Hospitalization with AKIMortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.10.1681/ASN.2017080882Thu, 14 Dec 2017 06:26:49 GMT-08:00Causes of Death after a Hospitalization with AKIMortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.Silver, Samuel A.Harel, ZivMcArthur, EricNash, Danielle M.Acedillo, ReyKitchlu, AbhijatGarg, Amit X.Chertow, Glenn M.Bell, Chaim M.Wald, Ron2017-12-14T06:26:49-08:00doi:10.1681/ASN.2017080882hwp:resource-id:jnephrol;29/3/1001American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cancer, cardiovascularClinical EpidemiologyClinical Epidemiologyresearch-article20182018-03-01March 201810.1681/ASN.20170808821046-66731533-34502017-12-14T06:26:49-08:002018-03Journal of the American Society of NephrologyClinical Epidemiology29310011010
- Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca FusionThe epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to which PI3K- or ERK-activating proteins dock, or Y1015, to which PLCγ docks, has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F mutants, in which WD tips reached the cloaca but did not fuse. Moreover, inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD-specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal fusion in vivo. Thus, cloacal apoptosis requires direct contact and signals from the WD tip and is necessary for WD-cloacal fusion. These findings may explain the mechanisms of many CAKUT.10.1681/ASN.2017040380Thu, 11 Jan 2018 11:50:12 GMT-08:00Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca FusionThe epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to which PI3K- or ERK-activating proteins dock, or Y1015, to which PLCγ docks, has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F mutants, in which WD tips reached the cloaca but did not fuse. Moreover, inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD-specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal fusion in vivo. Thus, cloacal apoptosis requires direct contact and signals from the WD tip and is necessary for WD-cloacal fusion. These findings may explain the mechanisms of many CAKUT.Hoshi, MasatoReginensi, AntoineJoens, Matthew S.Fitzpatrick, James A. J.McNeill, HelenJain, Sanjay2018-01-11T11:50:12-08:00doi:10.1681/ASN.2017040380hwp:resource-id:jnephrol;29/3/775American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyapoptosis, kidney development, ureteric bud, CAKUT, nephric duct, Wolffian ductBrief CommunicationBrief Communicationbrief-report20182018-03-01March 201810.1681/ASN.20170403801046-66731533-34502018-01-11T11:50:12-08:002018-03Journal of the American Society of NephrologyBrief Communication293775783
- CHIP Regulates Aquaporin-2 Quality Control and Body Water HomeostasisThe importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches, we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein t1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2. CHIP knockdown increased the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIP E3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We did not observe significant changes in other water- or sodium-transporting proteins in the gene-modified mice. In summary, these results suggest that CHIP regulates AQP2 and subsequently, renal water handling.10.1681/ASN.2017050526Thu, 14 Dec 2017 06:26:48 GMT-08:00CHIP Regulates Aquaporin-2 Quality Control and Body Water HomeostasisThe importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches, we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein t1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 and phosphorylated AQP2. CHIP knockdown increased the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIP E3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We did not observe significant changes in other water- or sodium-transporting proteins in the gene-modified mice. In summary, these results suggest that CHIP regulates AQP2 and subsequently, renal water handling.Wu, QiMoeller, Hanne B.Stevens, Donté A.Sanchez-Hodge, RebekahChilders, GabrielleKortenoeven, Marleen L.A.Cheng, LeiRosenbaek, Lena L.Rubel, CarriePatterson, CamPisitkun, TrairakSchisler, Jonathan C.Fenton, Robert A.2017-12-14T06:26:48-08:00doi:10.1681/ASN.2017050526hwp:resource-id:jnephrol;29/3/936American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyCHIP, AQP2, Protein Quality Control, kidney, Proteomics, Water handlingBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170505261046-66731533-34502017-12-14T06:26:48-08:002018-03Journal of the American Society of NephrologyBasic Research293936948
- Acidosis and Deafness in Patients with Recessive Mutations in FOXI1Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.10.1681/ASN.2017080840Thu, 14 Dec 2017 06:26:49 GMT-08:00Acidosis and Deafness in Patients with Recessive Mutations in FOXI1Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.Enerbäck, SvenNilsson, DanielEdwards, NoelHeglind, MikaelAlkanderi, SumayaAshton, EmmaDeeb, AsmaKokash, Feras E.B.Bakhsh, Abdul R.A.van’t Hoff, WilliamWalsh, Stephen B.D’Arco, FeliceDaryadel, ArezooBourgeois, SolineWagner, Carsten A.Kleta, RobertBockenhauer, DetlefSayer, John A.2017-12-14T06:26:49-08:00doi:10.1681/ASN.2017080840hwp:resource-id:jnephrol;29/3/1041American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic metabolic acidosis, genetic renal disease, ion transportClinical ResearchClinical Researchresearch-article20182018-03-01March 201810.1681/ASN.20170808401046-66731533-34502017-12-14T06:26:49-08:002018-03Journal of the American Society of NephrologyClinical Research29310411048
- Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in HumansIndividuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute–AHR–TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2–3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis.10.1681/ASN.2017080929Wed, 17 Jan 2018 06:23:41 GMT-08:00Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in HumansIndividuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic solute–AHR–TF thrombosis axis in two human cohorts, using a targeted metabolomics approach to probe a set of tryptophan products and high-throughput assays to measure AHR and TF activity. Analysis of baseline serum samples was performed from 473 participants with advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early AV Fistula Thrombosis trial. Participants with subsequent arteriovenous thrombosis had significantly higher levels of indoxyl sulfate and kynurenine, another uremic solute, and greater activity of AHR and TF, than those without thrombosis. Pattern recognition analysis using the components of the thrombosis axis facilitated clustering of the thrombotic and nonthrombotic groups. We further validated these findings using 377 baseline samples from participants in the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2–3. Mechanistic probing revealed that kynurenine enhances thrombosis after vascular injury in an animal model and regulates thrombosis in an AHR-dependent manner. This human validation of the solute-AHR-TF axis supports further studies probing its utility in risk stratification of patients with CKD and exploring its role in other diseases with heightened risk of thrombosis.Kolachalama, Vijaya B.Shashar, MosheAlousi, FaisalShivanna, SowmyaRijal, KeshabBelghasem, Mostafa E.Walker, JoshuaMatsuura, ShinobuChang, Gary H.Gibson, C. MichaelDember, Laura M.Francis, Jean M.Ravid, KatyaChitalia, Vipul C.2018-01-17T06:23:41-08:00doi:10.1681/ASN.2017080929hwp:resource-id:jnephrol;29/3/1063American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyuremic solute, thrombosis, Aryl hydrocarbon, tissue factorClinical ResearchClinical Researchresearch-article20182018-03-01March, 201810.1681/ASN.20170809291046-66731533-34502018-01-17T06:23:41-08:002018-03Journal of the American Society of NephrologyClinical Research29310631072
- Evolution and Kidney Development: A Rosetta Stone for Nephrology10.1681/ASN.2018010013Thu, 15 Feb 2018 11:05:41 GMT-08:00Evolution and Kidney Development: A Rosetta Stone for NephrologyChevalier, Robert L.2018-02-15T11:05:41-08:00doi:10.1681/ASN.2018010013hwp:resource-id:jnephrol;29/3/706American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, evolutionary medicine, chronic kidney disease, aging, embryoUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-03-01March 201810.1681/ASN.20180100131046-66731533-34502018-02-15T11:05:41-08:002018-03Journal of the American Society of NephrologyUp Front Matters293333706785825806709805840824
- Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC KnockoutThe amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γENaC subunit in the PHA-I phenotype. Nephron-specific γENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or βΕΝaC, an HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase NCC activation. However, when K+ was eliminated from the diet at the time that γENaC was deleted, plasma K+ concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced βENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K+ concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na+ balance in γENaC-deficient mice.10.1681/ASN.2017030345Thu, 25 Jan 2018 06:04:05 GMT-08:00Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC KnockoutThe amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γENaC subunit in the PHA-I phenotype. Nephron-specific γENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or βΕΝaC, an HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase NCC activation. However, when K+ was eliminated from the diet at the time that γENaC was deleted, plasma K+ concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced βENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K+ concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na+ balance in γENaC-deficient mice.Boscardin, EmiliePerrier, RomainSergi, ChloéMaillard, Marc P.Loffing, JohannesLoffing-Cueni, DominiqueKoesters, RobertRossier, Bernard C.Hummler, Edith2018-01-25T06:04:05-08:00doi:10.1681/ASN.2017030345hwp:resource-id:jnephrol;29/3/977American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyepithelial sodium channel, Pseudohypoaldosteronism, thiazide-sensitive, Na+/Cl- co-transporter, SPAKBasic ResearchBasic Researchresearch-article20182018-03-01March, 201810.1681/ASN.20170303451046-66731533-34502018-01-25T06:04:05-08:002018-03Journal of the American Society of NephrologyBasic Research293977990
- Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational PerspectivesThe unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (heterogeneous populations, among others), the data suggest that memory B and plasma cells represent two engines of autoimmunity, with variable involvement in these diseases. Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments. These conclusions have implications for the future development of targeted therapeutics in immune-mediated renal disease.10.1681/ASN.2017040367Thu, 11 Jan 2018 11:50:12 GMT-08:00Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational PerspectivesThe unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (heterogeneous populations, among others), the data suggest that memory B and plasma cells represent two engines of autoimmunity, with variable involvement in these diseases. Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments. These conclusions have implications for the future development of targeted therapeutics in immune-mediated renal disease.Schrezenmeier, EvaJayne, DavidDörner, Thomas2018-01-11T11:50:12-08:00doi:10.1681/ASN.2017040367hwp:resource-id:jnephrol;29/3/741American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, systemic lupus erythematosus, chronic allograft rejection, immunologyUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-03-01March 201810.1681/ASN.20170403671046-66731533-34502018-01-11T11:50:12-08:002018-03Journal of the American Society of NephrologyUp Front Matters293741758
- Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic SyndromeAtypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated aHUS (p-aHUS), of which three appeared to be provoked by infection, bleeding, and curettage, and three individuals were considered to have preeclampsia/HELLP syndrome before the definitive diagnosis of p-aHUS was made. Mutations in genes that encode the complement alternative pathway proteins or the molecules that regulate this pathway were detected in 71% of the women, with no relationship to pregnancy outcome. Twenty-one pregnancies (78%) resulted in a live birth, two preterm infants were stillborn, and four pregnancies resulted in early spontaneous abortions. Although short-term renal outcome was good in most women, long-term renal outcome was poor; among the 14 women, four had CKD stage 1–4, five had received a renal allograft, and three were dialysis-dependent at study end. We prospectively followed nine pregnancies of four women and treated six of these pregnancies with prophylactic plasma infusions (one pregnancy resulted in p-aHUS, one intrauterine fetal death occurred, and seven pregancies were uneventful). Our study emphasizes the frequency of successful pregnancies in women with aHUS. Close monitoring of such pregnancies for episodes of thrombotic microangiopathy is essential but, the best strategy to prevent these episodes remains unclear.10.1681/ASN.2016090995Wed, 27 Dec 2017 06:38:23 GMT-08:00Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic SyndromeAtypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated aHUS (p-aHUS), of which three appeared to be provoked by infection, bleeding, and curettage, and three individuals were considered to have preeclampsia/HELLP syndrome before the definitive diagnosis of p-aHUS was made. Mutations in genes that encode the complement alternative pathway proteins or the molecules that regulate this pathway were detected in 71% of the women, with no relationship to pregnancy outcome. Twenty-one pregnancies (78%) resulted in a live birth, two preterm infants were stillborn, and four pregnancies resulted in early spontaneous abortions. Although short-term renal outcome was good in most women, long-term renal outcome was poor; among the 14 women, four had CKD stage 1–4, five had received a renal allograft, and three were dialysis-dependent at study end. We prospectively followed nine pregnancies of four women and treated six of these pregnancies with prophylactic plasma infusions (one pregnancy resulted in p-aHUS, one intrauterine fetal death occurred, and seven pregancies were uneventful). Our study emphasizes the frequency of successful pregnancies in women with aHUS. Close monitoring of such pregnancies for episodes of thrombotic microangiopathy is essential but, the best strategy to prevent these episodes remains unclear.Gaggl, MartinaAigner, ChristofCsuka, DorottyaSzilágyi, ÁgnesProhászka, ZoltánKain, RenateHaninger, NataljaKnechtelsdorfer, MaartenSunder-Plassmann, RauteSunder-Plassmann, GereSchmidt, Alice2017-12-27T06:38:23-08:00doi:10.1681/ASN.2016090995hwp:resource-id:jnephrol;29/3/1020American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyatypical hemolytic uremic syndrome, aHUS, pregnancy, TMA, complement-mediatedClinical ResearchClinical Researchresearch-article20182018-03-01March, 201810.1681/ASN.20160909951046-66731533-34502017-12-27T06:38:23-08:002018-03Journal of the American Society of NephrologyClinical Research29310201029
- Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKIWhether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P< 0.001). The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, −19.6%; 95% CI, −32.0% to −7.2%; P<0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, −34.8%; 95% CI, −54.6% to −15.0%; P=0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.10.1681/ASN.2017060694Fri, 01 Dec 2017 06:02:23 GMT-08:00Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKIWhether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P< 0.001). The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, −19.6%; 95% CI, −32.0% to −7.2%; P<0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, −34.8%; 95% CI, −54.6% to −15.0%; P=0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.Meersch, MelanieKüllmar, MiraSchmidt, ChristophGerss, JoachimWeinhage, ToniMargraf, AndreasErmert, ThomasKellum, John A.Zarbock, Alexander2017-12-01T06:02:23-08:00doi:10.1681/ASN.2017060694hwp:resource-id:jnephrol;29/3/1011American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, hemodialysis, survivalClinical ResearchClinical Researchresearch-article20182018-03-01March 201810.1681/ASN.20170606941046-66731533-34502017-12-01T06:02:23-08:002018-03Journal of the American Society of NephrologyClinical Research29310111019
- Magnesium and Risk of Hip Fracture among Patients Undergoing HemodialysisMagnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis in Japan. During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The crude incidence rate was significantly higher among patients in the lower quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1–Q4, respectively; P<0.001 for trend). The range of serum magnesium levels (in milligrams per deciliter) in each quartile was as follows: Q1, <2.3; Q2, 2.4–2.6; Q3, 2.7–2.8, and Q4, >2.9. After adjustment for demographic and clinical factors, patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95% confidence interval, 1.06 to 1.44; P<0.01). Similarly, an inverse probability weighting analysis showed an increased risk of hip fracture among patients in the lower magnesium quartiles. We did not observe significant effect modifications in subgroup analyses. The population-attributable fraction of serum magnesium level for incident hip fractures was 13.7% (95% confidence interval, 3.7% to 22.7%), which was much higher than that of serum calcium, serum phosphate, and parathyroid hormone levels. Thus, mild hypermagnesemia is associated with a lower risk of hip fracture among patients undergoing hemodialysis.10.1681/ASN.2017080849Thu, 30 Nov 2017 06:22:04 GMT-08:00Magnesium and Risk of Hip Fracture among Patients Undergoing HemodialysisMagnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis in Japan. During a 2-year follow-up, a total of 2305 (2%) new hip fractures occurred. The crude incidence rate was significantly higher among patients in the lower quartiles of serum magnesium levels (2.63%, 2.08%, 1.76%, and 1.49% in Q1–Q4, respectively; P<0.001 for trend). The range of serum magnesium levels (in milligrams per deciliter) in each quartile was as follows: Q1, <2.3; Q2, 2.4–2.6; Q3, 2.7–2.8, and Q4, >2.9. After adjustment for demographic and clinical factors, patients in Q1 had a 1.23-fold higher risk for hip fracture than those in Q4 (95% confidence interval, 1.06 to 1.44; P<0.01). Similarly, an inverse probability weighting analysis showed an increased risk of hip fracture among patients in the lower magnesium quartiles. We did not observe significant effect modifications in subgroup analyses. The population-attributable fraction of serum magnesium level for incident hip fractures was 13.7% (95% confidence interval, 3.7% to 22.7%), which was much higher than that of serum calcium, serum phosphate, and parathyroid hormone levels. Thus, mild hypermagnesemia is associated with a lower risk of hip fracture among patients undergoing hemodialysis.Sakaguchi, YusukeHamano, TakayukiWada, AtsushiHoshino, JunichiMasakane, Ikuto2017-11-30T06:22:04-08:00doi:10.1681/ASN.2017080849hwp:resource-id:jnephrol;29/3/991American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymagnesium, hip fracture, hemodialysis, mineral and bone disordersClinical EpidemiologyClinical Epidemiologyresearch-article20182018-03-01March 201810.1681/ASN.20170808491046-66731533-34502017-11-30T06:22:04-08:002018-03Journal of the American Society of NephrologyClinical Epidemiology293991999
- Salt-Losing Tubulopathies in Children: What’s New, What’s Controversial?Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle’s loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.10.1681/ASN.2017060600Wed, 13 Dec 2017 07:17:03 GMT-08:00Salt-Losing Tubulopathies in Children: What’s New, What’s Controversial?Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences. Salt-losing tubulopathies can affect all tubular segments, from the proximal tubule to the collecting duct. But the more frequently observed disorders are Bartter and Gitelman syndrome, which affect salt transport in the thick ascending limb of Henle’s loop and/or the distal convoluted tubule, and these disorders generate the greatest controversies regarding management. Here, we review clinical and molecular aspects of salt-losing tubulopathies and discuss novel insights provided mainly by genetic investigations and retrospective clinical reviews. Additionally, we discuss controversial topics in the management of these disorders to highlight areas of importance for future clinical trials. International collaboration will be required to perform clinical studies to inform the treatment of these rare disorders.Kleta, RobertBockenhauer, Detlef2017-12-13T07:17:03-08:00doi:10.1681/ASN.2017060600hwp:resource-id:jnephrol;29/3/727American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney tubule, children, Bartter-s syndrome, Cell & Transport Physiology, Gitelman-s syndromeUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-03-01March 201810.1681/ASN.20170606001046-66731533-34502017-12-13T07:17:03-08:002018-03Journal of the American Society of NephrologyUp Front Matters293727739
- Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic ApproachFSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.10.1681/ASN.2017090958Wed, 10 Jan 2018 06:48:09 GMT-08:00Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic ApproachFSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among these FSGS types, classification of patients is often challenging. This review summarizes the clinical and histologic features, including the onset and severity of proteinuria as well as the presence of nephrotic syndrome, that may aid in identifying the specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis and must be differentiated from nonspecific focal global glomerulosclerosis. No light microscopic features are pathognomonic for a particular FSGS subcategory. The characteristics of podocyte foot process effacement on electron microscopy, while helpful in discriminating between primary and maladaptive FSGS, may be of little utility in detecting genetic forms of FSGS. When FSGS cannot be classified by clinicopathologic assessment, genetic analysis should be offered. Next generation DNA sequencing enables cost-effective screening of multiple genes simultaneously, but determining the pathogenicity of a detected genetic variant may be challenging. A more systematic evaluation of patients, as suggested herein, will likely improve therapeutic outcomes and the design of future trials in FSGS.De Vriese, An S.Sethi, SanjeevNath, Karl A.Glassock, Richard J.Fervenza, Fernando C.2018-01-10T06:48:09-08:00doi:10.1681/ASN.2017090958hwp:resource-id:jnephrol;29/3/759American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyFSGS, Primary, Secondary, genetic renal disease, nephrotic syndromeUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-03-01March 201810.1681/ASN.20170909581046-66731533-34502018-01-10T06:48:09-08:002018-03Journal of the American Society of NephrologyUp Front Matters293759774
- The Benefits of Tubular Proteinuria: An Evolutionary Perspective10.1681/ASN.2017111197Thu, 25 Jan 2018 06:04:04 GMT-08:00The Benefits of Tubular Proteinuria: An Evolutionary PerspectiveSimons, Matias2018-01-25T06:04:04-08:00doi:10.1681/ASN.2017111197hwp:resource-id:jnephrol;29/3/710American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, genetic renal disease, proximal tubule, progression of renal failureUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20182018-03-01March 201810.1681/ASN.20171111971046-66731533-34502018-01-25T06:04:04-08:002018-03Journal of the American Society of NephrologyUp Front Matters293710712
- Conserved and Divergent Features of Human and Mouse Kidney OrganogenesisHuman kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34–37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4–23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.10.1681/ASN.2017080887Thu, 15 Feb 2018 11:05:42 GMT-08:00Conserved and Divergent Features of Human and Mouse Kidney OrganogenesisHuman kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34–37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4–23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species.Lindström, Nils O.McMahon, Jill A.Guo, JinjinTran, TracyGuo, QiuyuRutledge, ElisabethParvez, Riana K.Saribekyan, GoharSchuler, Robert E.Liao, ChristopherKim, Albert D.Abdelhalim, AhmedRuffins, Seth W.Thornton, Matthew E.Basking, LaurenceGrubbs, BrendanKesselman, CarlMcMahon, Andrew P.2018-02-15T11:05:42-08:00doi:10.1681/ASN.2017080887hwp:resource-id:jnephrol;29/3/785American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, human genetics, nephronBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170808871046-66731533-34502018-02-15T11:05:42-08:002018-03Journal of the American Society of NephrologyBasic Research29333785705706805706709
- The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney DiseaseThe identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of UMOD for CKD is clear, because the encoded protein, uromodulin (Tamm–Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemical properties that mediate important functions in the kidney and urine. Rare mutations in UMOD are the major cause of autosomal dominant tubulointerstitial kidney disease, a condition that leads to CKD and ESRD. In this brief review, we use the UMOD paradigm to describe how population genetic studies can yield insight into the pathogenesis and prognosis of kidney diseases.10.1681/ASN.2017070716Mon, 27 Nov 2017 06:42:41 GMT-08:00The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney DiseaseThe identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The relevance of UMOD for CKD is clear, because the encoded protein, uromodulin (Tamm–Horsfall protein), is exclusively produced by the kidney tubule and has specific biochemical properties that mediate important functions in the kidney and urine. Rare mutations in UMOD are the major cause of autosomal dominant tubulointerstitial kidney disease, a condition that leads to CKD and ESRD. In this brief review, we use the UMOD paradigm to describe how population genetic studies can yield insight into the pathogenesis and prognosis of kidney diseases.Devuyst, OlivierPattaro, Cristian2017-11-27T06:42:41-08:00doi:10.1681/ASN.2017070716hwp:resource-id:jnephrol;29/3/713American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-03-01March 201810.1681/ASN.20170707161046-66731533-34502017-11-27T06:42:41-08:002018-03Journal of the American Society of NephrologyUp Front Matters293713726
- GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal OsmoregulationCollecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this strong collecting duct epithelial barrier is unresolved. Here, we report that collecting duct–specific deletion of an epithelial transcription factor, grainyhead-like 2 (GRHL2), in mice led to reduced expression of tight junction–associated barrier components, reduced collecting duct transepithelial resistance, and defective renal medullary accumulation of sodium and other osmolytes. In vitro, Grhl2-deficient collecting duct cells displayed increased paracellular flux of sodium, chloride, and urea. Consistent with these effects, Grhl2-deficient mice had diabetes insipidus, produced dilute urine, and failed to adequately concentrate their urine after water restriction, resulting in susceptibility to prerenal azotemia. These data indicate a direct functional link between collecting duct epithelial barrier characteristics, which appear to prevent leakage of interstitial osmolytes into urine, and body water homeostasis.10.1681/ASN.2017030353Wed, 13 Dec 2017 07:17:06 GMT-08:00GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal OsmoregulationCollecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions composed of barrier-enforcing claudins and exhibits a higher transepithelial resistance than other segments of the renal tubule exhibit. However, the functional relevance of this strong collecting duct epithelial barrier is unresolved. Here, we report that collecting duct–specific deletion of an epithelial transcription factor, grainyhead-like 2 (GRHL2), in mice led to reduced expression of tight junction–associated barrier components, reduced collecting duct transepithelial resistance, and defective renal medullary accumulation of sodium and other osmolytes. In vitro, Grhl2-deficient collecting duct cells displayed increased paracellular flux of sodium, chloride, and urea. Consistent with these effects, Grhl2-deficient mice had diabetes insipidus, produced dilute urine, and failed to adequately concentrate their urine after water restriction, resulting in susceptibility to prerenal azotemia. These data indicate a direct functional link between collecting duct epithelial barrier characteristics, which appear to prevent leakage of interstitial osmolytes into urine, and body water homeostasis.Hinze, ChristianRuffert, JanettWalentin, KatharinaHimmerkus, NinaNikpey, ElhamTenstad, OlavWiig, HelgeMutig, KerimYurtdas, Zeliha YesimKlein, Janet D.Sands, Jeff M.Branchi, FedericaSchumann, MichaelBachmann, SebastianBleich, MarkusSchmidt-Ott, Kai M.2017-12-13T07:17:06-08:00doi:10.1681/ASN.2017030353hwp:resource-id:jnephrol;29/3/857American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyepithelial barrier function, renal collecting duct epithelium, urinary concentration, diabetes insipidus, prerenal azotemia, grainyhead-like 2 transcription factorBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170303531046-66731533-34502017-12-13T07:17:06-08:002018-03Journal of the American Society of NephrologyBasic Research293857868
- Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric ObstructionIncreased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.10.1681/ASN.2017050479Tue, 30 Jan 2018 07:20:49 GMT-08:00Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric ObstructionIncreased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed a global proteomic approach to identify binding partners of TG2 responsible for TG2 externalization in kidneys subjected to unilateral ureteric obstruction (UUO) using TG2 knockout kidneys as negative controls. We report a robust and unbiased analysis of the membrane interactome of TG2 in fibrotic kidneys relative to the entire proteome after UUO, detected by SWATH mass spectrometry. The data have been deposited to the ProteomeXchange with identifier PXD008173. Clusters of exosomal proteins in the TG2 interactome supported the hypothesis that TG2 is secreted by extracellular membrane vesicles during fibrosis progression. In established TEC lines, we found TG2 in vesicles of both endosomal (exosomes) and plasma membrane origin (microvesicles/ectosomes), and TGF-β1 stimulated TG2 secretion. Knockout of syndecan-4 (SDC4) greatly impaired TG2 exosomal secretion. TG2 coprecipitated with SDC4 from exosome lysate but not ectosome lysate. Ex vivo, EGFP-tagged TG2 accumulated in globular elements (blebs) protruding/retracting from the plasma membrane of primary cortical TECs, and SDC4 knockout impaired bleb formation, affecting TG2 release. Through this combined in vivo and in vitro approach, we have dissected the pathway through which TG2 is secreted from TECs in CKD.Furini, GiuliaSchroeder, NinaHuang, LinghongBoocock, DavidScarpellini, AlessandraCoveney, ClareTonoli, ElisaRamaswamy, RaghavendranBall, GrahamVerderio, ClaudiaJohnson, Timothy S.Verderio, Elisabetta A.M.2018-01-30T07:20:49-08:00doi:10.1681/ASN.2017050479hwp:resource-id:jnephrol;29/3/880American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, fibrosis, UUO, extracellular vesicles, transglutaminase, interactomeBasic ResearchBasic Researchresearch-article20182018-03-01March 201810.1681/ASN.20170504791046-66731533-34502018-01-30T07:20:49-08:002018-03Journal of the American Society of NephrologyBasic Research293880905
- Changes in Albuminuria and Subsequent Risk of Incident Kidney Disease10.2215/CJN.02720317Mon, 11 Sep 2017 07:49:29 GMT-07:00Changes in Albuminuria and Subsequent Risk of Incident Kidney DiseaseSumida, KeiichiMolnar, Miklos Z.Potukuchi, Praveen K.George, KoshyThomas, FridtjofLu, Jun LingYamagata, KunihiroKalantar-Zadeh, KamyarKovesdy, Csaba P.2017-09-11T07:49:29-07:00doi:10.2215/CJN.02720317hwp:resource-id:clinjasn;12/12/1941American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, chronic kidney disease, microalbuminuria, Odds Ratio, Proportional Hazards Models, Logistic Models, glomerular filtration rate, Veterans, Renal Insufficiency, Chronic, kidney, diabetes mellitusOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-12-07December 07, 201710.2215/CJN.027203171555-90411555-905X2017-09-11T07:49:29-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121219411949
- Urinary Fibrinogen as a Predictor of Progression of CKD10.2215/CJN.01360217Wed, 13 Sep 2017 06:51:20 GMT-07:00Urinary Fibrinogen as a Predictor of Progression of CKDWang, HongtianZheng, ChunxiaLu, YinghuiJiang, QiYin, RuZhu, PingZhou, MinlinLiu, Zhihong2017-09-13T06:51:20-07:00doi:10.2215/CJN.01360217hwp:resource-id:clinjasn;12/12/1922American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, fibrinogen, predictor, progression, Glomerulonephritis, IGA, Podocytes, Glomerulonephritis, Membranous, risk factors, Diabetic Nephropathies, creatinine, blood pressure, Glomerulosclerosis, Focal Segmental, glomerular filtration rate, Confidence Intervals, Renal Insufficiency, Chronic, Blood Pressure Determination, Disease Progression, Kidney Failure, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-12-07December 07, 201710.2215/CJN.013602171555-90411555-905X2017-09-13T06:51:20-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121219221929
- Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast Growth Factor 23 in CKD10.2215/CJN.03030317Thu, 26 Oct 2017 06:38:05 GMT-07:00Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast Growth Factor 23 in CKDLiabeuf, SophieRyckelynck, Jean-PhilippeEl Esper, NajehUreña, PabloCombe, ChristianDussol, BertrandFouque, DenisVanhille, PhilippeFrimat, LucThervet, EricMentaverri, RomualdPrié, DominiqueChoukroun, Gabriel,2017-10-26T06:38:05-07:00doi:10.2215/CJN.03030317hwp:resource-id:clinjasn;12/12/1930American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, fibroblast, mineral metabolism, KLOTHO, FGF23, phosphate binders, randomized controlled trials, sevelamer, fibroblast growth factor 23, Phosphorus, Cholesterol, LDL, creatinine, Cholecalciferol, Double-Blind Method, glomerular filtration rate, Fasting, Random Allocation, Fibroblast Growth Factors, Hypophosphatemia, Familial, Renal Insufficiency, Chronic, Phosphates, Epidemiologic StudiesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-12-07December 07, 201710.2215/CJN.030303171555-90411555-905X2017-10-26T06:38:05-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1212121930191119401913
- Person-Centered Integrated Care for Chronic Kidney Disease10.2215/CJN.09960917Fri, 09 Feb 2018 06:41:42 GMT-08:00Person-Centered Integrated Care for Chronic Kidney DiseaseValentijn, Pim P.Pereira, Fernando AbdallaRuospo, MarinellaPalmer, Suetonia C.Hegbrant, JörgenSterner, Christina W.Vrijhoef, Hubertus J.M.Ruwaard, DirkStrippoli, Giovanni F.M.2018-02-09T06:41:42-08:00doi:10.2215/CJN.09960917hwp:resource-id:clinjasn;13/3/375American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIntegrated care, randomized controlled trials, systematic review, Patient-centered care, Care coordination, Managed care programs, Patient care management, collaborative care, comprehensive care, Case management, Risk, creatinine, Confidence Intervals, blood pressure, quality of life, Follow-Up Studies, Climacteric, Renal Insufficiency, Chronic, Blood Pressure Determination, EGFR protein, human, Receptor, Epidermal Growth Factor, chronic kidney disease, Renal Replacement Therapy, hospitalizationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-03-07March 07, 201810.2215/CJN.099609171555-90411555-905X2018-02-09T06:41:42-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133375386
- Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy10.2215/CJN.09080817Thu, 11 Jan 2018 11:49:59 GMT-08:00Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 GlomerulopathyAvasare, Rupali S.Canetta, Pietro A.Bomback, Andrew S.Marasa, MaddalenaCaliskan, YasarOzluk, YaseminLi, YifuGharavi, Ali G.Appel, Gerald B.2018-01-11T11:49:59-08:00doi:10.2215/CJN.09080817hwp:resource-id:clinjasn;13/3/406American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, complement, mycophenolate mofetil, Humans, Mycophenolic Acid, creatinine, Complement Membrane Attack Complex, Retrospective Studies, Follow-Up Studies, Universities, Immunosuppressive Agents, glomerulonephritis, proteinuria, immunosuppression, Recurrence, RegistriesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-03-07March 07, 201810.2215/CJN.090808171555-90411555-905X2018-01-11T11:49:59-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133406413
- An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis10.2215/CJN.04780517Wed, 22 Nov 2017 07:50:17 GMT-08:00An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental GlomerulosclerosisTroost, Jonathan P.Trachtman, HowardNachman, Patrick H.Kretzler, MatthiasSpino, CathieKomers, RadkoTuller, SarahPerumal, KalyaniMassengill, Susan F.Kamil, Elaine S.Oh, GiaSelewski, David T.Gipson, PatrickGipson, Debbie S.2017-11-22T07:50:17-08:00doi:10.2215/CJN.04780517hwp:resource-id:clinjasn;13/3/414American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFSGS, proteinuria, surrogate endpoint, Humans, Glomerulosclerosis, Focal Segmental, glomerular filtration rate, creatinine, Proportional Hazards Models, Propensity Score, Goals, kidney, Renal Insufficiency, Kidney Failure, Chronic, Prognosis, Cohort StudiesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-03-07March 07, 201810.2215/CJN.047805171555-90411555-905X2017-11-22T07:50:17-08:002018-03-07Clinical Journal of the American Society of NephrologyOriginal Articles133414421
- Diagnosis and Treatment of Intradialytic Hypotension in Maintenance Hemodialysis Patients10.2215/CJN.11131017Fri, 02 Feb 2018 06:08:05 GMT-08:00Diagnosis and Treatment of Intradialytic Hypotension in Maintenance Hemodialysis PatientsMcIntyre, Christopher W.Salerno, Fabio R.2018-02-02T06:08:05-08:00doi:10.2215/CJN.11131017hwp:resource-id:clinjasn;13/3/486American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, intradialytic hypotension, cardiovascular disease, Humans, Cognitive Dysfunction, Diagnosis, Differential, renal dialysis, hypotension, heart failure, Patient Care, Arrhythmias, CardiacKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-03-07March 07, 201810.2215/CJN.111310171555-90411555-905X2018-02-02T06:08:05-08:002018-03-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat133486489
- Crafting the Prescription for Patients Starting Peritoneal Dialysis10.2215/CJN.10770917Tue, 30 Jan 2018 07:17:34 GMT-08:00Crafting the Prescription for Patients Starting Peritoneal DialysisTeitelbaum, Isaac2018-01-30T07:17:34-08:00doi:10.2215/CJN.10770917hwp:resource-id:clinjasn;13/3/483American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, Humans, renal dialysis, Prescriptions, Kidney Failure, ChronicKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20182018-03-07March 07, 201810.2215/CJN.107709171555-90411555-905X2018-01-30T07:17:34-08:002018-03-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat133483485
- Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell CrosstalkGeneration of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated. Here, we analyzed the effect of Belatacept on different steps of the B cell–mediated response in humans. In vitro, Belatacept reduced plasmablast differentiation, Ig production, and the expression of the major transcription factor involved in plasma cell function, Blimp-1, in a T cell–independent manner. Moreover, Belatacept induced activation of the STAT3 transcription factor in stimulated B cells and reduced the expression of CD86. Additionally, Belatacept blocked CD28-mediated activation of T follicular helper cells (Tfhs) in an autologous Tfh-memory B cells model. We then validated these observations in KTRs treated with Belatacept, who had a reduced proportion of blood effector B cells and activated Tfh (PD1+ICOS+) compared with control-treated KTRs. Our in vitro and in vivo results suggest that Belatacept modulates B cell function directly and at the level of B cell-Tfh interaction. These mechanisms likely account for the optimal control of humoral responses observed in KTRs treated with Belatacept.10.1681/ASN.2017060679Wed, 10 Jan 2018 06:48:10 GMT-08:00Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell CrosstalkGeneration of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a lower proportion of dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral responses by Belatacept remain to be investigated. Here, we analyzed the effect of Belatacept on different steps of the B cell–mediated response in humans. In vitro, Belatacept reduced plasmablast differentiation, Ig production, and the expression of the major transcription factor involved in plasma cell function, Blimp-1, in a T cell–independent manner. Moreover, Belatacept induced activation of the STAT3 transcription factor in stimulated B cells and reduced the expression of CD86. Additionally, Belatacept blocked CD28-mediated activation of T follicular helper cells (Tfhs) in an autologous Tfh-memory B cells model. We then validated these observations in KTRs treated with Belatacept, who had a reduced proportion of blood effector B cells and activated Tfh (PD1+ICOS+) compared with control-treated KTRs. Our in vitro and in vivo results suggest that Belatacept modulates B cell function directly and at the level of B cell-Tfh interaction. These mechanisms likely account for the optimal control of humoral responses observed in KTRs treated with Belatacept.Leibler, ClaireThiolat, AllanHénique, CaroleSamson, ChloéPilon, CarolineTamagne, MariePirenne, FranceVingert, BenoitCohen, José L.Grimbert, Philippe2018-01-10T06:48:10-08:00doi:10.1681/ASN.2017060679hwp:resource-id:jnephrol;29/3/1049American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, Belatacept (CTLA4-Ig), B cells, T follicular helper cellsClinical ResearchClinical Researchresearch-article20182018-03-01March 201810.1681/ASN.20170606791046-66731533-34502018-01-10T06:48:10-08:002018-03Journal of the American Society of NephrologyClinical Research29310491062
- Left Ventricular Assist Devices and the KidneyLeft ventricular assist devices (LVADs) are common and implantation carries risk of AKI. LVADs are used as a bridge to heart transplantation or as destination therapy. Patients with refractory heart failure that develop chronic cardiorenal syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility of CKD is hard to predict. After LVAD placement, significant GFR increases may be followed by a late return to near baseline GFR levels, and in some patients, a decline in GFR. In this review, we discuss changes in GFR after LVAD placement, the incidence of AKI and associated mortality after LVAD placement, the management of AKI requiring RRT, and lastly, we review salient features about cardiorenal syndrome learned from the LVAD experience. In light of the growing number of patients using LVADs as a destination therapy, it is important to understand the effect of these devices on the kidney. Additional research and long-term data are required to better understand the relationship between the LVAD and the kidney.10.2215/CJN.04670417Wed, 25 Oct 2017 05:57:25 GMT-07:00Left Ventricular Assist Devices and the KidneyLeft ventricular assist devices (LVADs) are common and implantation carries risk of AKI. LVADs are used as a bridge to heart transplantation or as destination therapy. Patients with refractory heart failure that develop chronic cardiorenal syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility of CKD is hard to predict. After LVAD placement, significant GFR increases may be followed by a late return to near baseline GFR levels, and in some patients, a decline in GFR. In this review, we discuss changes in GFR after LVAD placement, the incidence of AKI and associated mortality after LVAD placement, the management of AKI requiring RRT, and lastly, we review salient features about cardiorenal syndrome learned from the LVAD experience. In light of the growing number of patients using LVADs as a destination therapy, it is important to understand the effect of these devices on the kidney. Additional research and long-term data are required to better understand the relationship between the LVAD and the kidney.Ross, Daniel W.Stevens, Gerin R.Wanchoo, RimdaMajure, David T.Jauhar, SandeepFernandez, Harold A.Merzkani, MassiniJhaveri, Kenar D.2017-10-25T05:57:25-07:00doi:10.2215/CJN.04670417hwp:resource-id:clinjasn;13/2/348American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyLVAD, cardiovascular disease, cardiorenal, congestive heart failure, Cardio-Renal Syndrome, glomerular filtration rate, Heart-Assist Devices, Incidence, Acute Kidney Injury, Renal Replacement Therapy, Renal Insufficiency, Chronic, kidney, Heart Transplantation, HumansReviewReviewreview-article20182018-02-07February 07, 201810.2215/CJN.046704171555-90411555-905X2017-10-25T05:57:25-07:002018-02-07Clinical Journal of the American Society of NephrologyReview132348355
- Association between Urine Ammonium and Urine TGF-β1 in CKD10.2215/CJN.07510717Thu, 16 Nov 2017 06:49:10 GMT-08:00Association between Urine Ammonium and Urine TGF-β1 in CKDRaphael, Kalani L.Gilligan, SarahHostetter, Thomas H.Greene, TomBeddhu, Srinivasan2017-11-16T06:49:10-08:00doi:10.2215/CJN.07510717hwp:resource-id:clinjasn;13/2/223American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic metabolic acidosis, chronic kidney disease, renal fibrosis, Humans, Male, Animals, Aged, creatinine, glomerular filtration rate, Bicarbonates, Ammonia, Ammonium Compounds, Linear Models, Cross-Sectional Studies, Renal Insufficiency, Chronic, Kidney Function Tests, proteinuria, diabetes mellitus, Transforming Growth Factors, Models, Animal, Hydrogen-Ion ConcentrationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-02-07February 07, 201810.2215/CJN.075107171555-90411555-905X2017-11-16T06:49:10-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles132223230
- Nondepressive Psychosocial Factors and CKD Outcomes in Black Americans10.2215/CJN.06430617Wed, 03 Jan 2018 06:33:22 GMT-08:00Nondepressive Psychosocial Factors and CKD Outcomes in Black AmericansLunyera, JosephDavenport, Clemontina A.Bhavsar, Nrupen A.Sims, MarioScialla, JuliaPendergast, JaneHall, RasheedaTyson, Crystal C.Russell, Jennifer St. ClairWang, WeiCorrea, AdolfoBoulware, L. EbonyDiamantidis, Clarissa J.2018-01-03T06:33:22-08:00doi:10.2215/CJN.06430617hwp:resource-id:clinjasn;13/2/213American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Epidemiology and outcomes, ethnicity, risk factors, psychosocial factors, weathering hypothesis, Female, Odds Ratio, glomerular filtration rate, Hostility, African Americans, Prevalence, Spirituality, Confidence Intervals, Comorbidity, Principal Component Analysis, Follow-Up Studies, Pessimism, Renal Insufficiency, Chronic, Social Support, Adaptation, Psychological, Anger, HumansOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-02-07February 07, 201810.2215/CJN.064306171555-90411555-905X2018-01-03T06:33:22-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles132213222
- Medication Therapy Management after Hospitalization in CKD10.2215/CJN.06790617Tue, 02 Jan 2018 10:59:16 GMT-08:00Medication Therapy Management after Hospitalization in CKDTuttle, Katherine R.Alicic, Radica Z.Short, Robert A.Neumiller, Joshua J.Gates, Brian J.Daratha, Kenn B.Barbosa-Leiker, CelestinaMcPherson, Sterling M.Chaytor, Naomi S.Dieter, Brad P.Setter, Stephen M.Corbett, Cynthia F.2018-01-02T10:59:16-08:00doi:10.2215/CJN.06790617hwp:resource-id:clinjasn;13/2/231American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMedication Therapy Management, hospitalization, Renal Insufficiency, Chronic, Humans, Medication Adherence, Hospital readmission, Acute illness, Medication management, Transitional care, chronic kidney diseaseOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-02-07February 07, 201810.2215/CJN.067906171555-90411555-905X2018-01-02T10:59:16-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1322231198241200
- Standardized Transplantation Referral Ratio to Assess Performance of Transplant Referral among Dialysis Facilities10.2215/CJN.04690417Thu, 25 Jan 2018 06:03:52 GMT-08:00Standardized Transplantation Referral Ratio to Assess Performance of Transplant Referral among Dialysis FacilitiesPaul, SudeshnaPlantinga, Laura C.Pastan, Stephen O.Gander, Jennifer C.Mohan, SumitPatzer, Rachel E.2018-01-25T06:03:52-08:00doi:10.2215/CJN.04690417hwp:resource-id:clinjasn;13/2/282American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, evaluation referral, quality measure, end stage renal disease, Proportional Hazards Models, Risk Adjustment, Comorbidity, Confidence Intervals, Follow-Up Studies, Reproducibility of Results, Kidney Failure, Chronic, kidney, Probability, Referral and Consultation, Demography, Diagnosis-Related Groups, renal dialysisOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-02-07February 07, 201810.2215/CJN.046904171555-90411555-905X2018-01-25T06:03:52-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1322282193289194
- Accountability of Dialysis Facilities in Transplant Referral10.2215/CJN.13741217Thu, 25 Jan 2018 06:03:51 GMT-08:00Accountability of Dialysis Facilities in Transplant ReferralFowler, Kevin John2018-01-25T06:03:51-08:00doi:10.2215/CJN.13741217hwp:resource-id:clinjasn;13/2/193American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient voice, Humans, United States, Medicaid, kidney transplantation, tetraethylpyrazine, Centers for Medicare and Medicaid Services (U.S.), Medicare, kidney, Social Responsibility, Health Personnel, Kidney Failure, Chronic, Referral and Consultation, renal dialysisPatient VoicePatient Voiceeditorial20182018-02-07February 07, 201810.2215/CJN.137412171555-90411555-905X2018-01-25T06:03:51-08:002018-02-07Clinical Journal of the American Society of NephrologyPatient Voice1322193282194289
- A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in Cytomegalovirus High-Risk Kidney Transplant Recipients10.2215/CJN.05080517Thu, 12 Oct 2017 06:36:24 GMT-07:00A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in Cytomegalovirus High-Risk Kidney Transplant RecipientsPuttarajappa, Chethan M.Hariharan, SundaramSmith, Kenneth J.2017-10-12T06:36:24-07:00doi:10.2215/CJN.05080517hwp:resource-id:clinjasn;13/2/290American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycytomegalovirus, Screening, Decision analysis, Hybrid strategy, high-risk, Quality-Adjusted Life Years, Cost-Benefit Analysis, Viremia, Incidence, Kinetics, kidney transplantation, Cytomegalovirus Infections, Antiviral Agents, Decision Support Techniques, hospitalization, Immunoglobulin GOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-02-07February 07, 201810.2215/CJN.050805171555-90411555-905X2017-10-12T06:36:24-07:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles132290298
- Sepsis-Associated AKI10.2215/CJN.07310717Wed, 25 Oct 2017 05:57:26 GMT-07:00Sepsis-Associated AKIProwle, J.R.2017-10-25T05:57:26-07:00doi:10.2215/CJN.07310717hwp:resource-id:clinjasn;13/2/339American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, critical care, sepsis, risk factors, Acute Kidney Injury, Intensive Care Units, Treatment Outcome, Kidney Failure, Chronic, Renal, Insufficiency, Chronic, HemodynamicsKidney Case ConferencesAttending RoundsKidney Case ConferencesAttending Roundsresearch-article20182018-02-07February 07, 201810.2215/CJN.073107171555-90411555-905X2017-10-25T05:57:26-07:002018-02-07Clinical Journal of the American Society of NephrologyKidney Case Conferences132339342
- Diabetic Kidney Disease10.2215/CJN.04650417Wed, 18 Oct 2017 06:20:27 GMT-07:00Diabetic Kidney DiseaseTong, LiliAdler, Sharon G.2017-10-18T06:20:27-07:00doi:10.2215/CJN.04650417hwp:resource-id:clinjasn;13/2/335American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Angiotensin-Converting Enzyme Inhibitors, Diabetic Nephropathies, albuminuria, Renin-Angiotensin System, Peptidyl-Dipeptidase A, Mineralocorticoid Receptor Antagonists, Angiotensin Receptor Antagonists, Diabetes Mellitus, Type 2, blood pressure, coronary artery disease, Peripheral Arterial Disease, Gastroparesis, Smoking Cessation, Cardiovascular Diseases, Weight Loss, risk factors, proteinuria, Kidney Failure, Chronic, Renal Insufficiency, Chronic, Diabetes Complications, Dyslipidemias, Cerebrovascular Disorders, heart failure, Life StyleKidney Case ConferencesHow I TreatKidney Case ConferencesHow I Treatresearch-article20182018-02-07February 07, 201810.2215/CJN.046504171555-90411555-905X2017-10-18T06:20:27-07:002018-02-07Clinical Journal of the American Society of NephrologyKidney Case Conferences132335338
- The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA-Associated Vasculitis10.2215/CJN.04160417Thu, 25 Jan 2018 06:03:52 GMT-08:00The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA-Associated VasculitisRhee, Rennie L.Davis, John C.Ding, LinnaFervenza, Fernando C.Hoffman, Gary S.Kallenberg, Cees G.M.Langford, Carol A.McCune, W. JosephMonach, Paul A.Seo, PhilipSpiera, RobertSt. Clair, E. WilliamSpecks, UlrichStone, John H.Merkel, Peter A.2018-01-25T06:03:52-08:00doi:10.2215/CJN.04160417hwp:resource-id:clinjasn;13/2/251American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulonephritis, vasculitis, hematuria, relapse, proteinuria, Humans, Antibodies, Antineutrophil Cytoplasmic, Urinalysis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Granulomatosis with Polyangiitis, Recurrence, ErythrocytesOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-02-07February 07, 201810.2215/CJN.041604171555-90411555-905X2018-01-25T06:03:52-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1322251201257202
- Thrombotic Microangiopathy and the KidneyThrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and management.10.2215/CJN.00620117Tue, 17 Oct 2017 06:48:10 GMT-07:00Thrombotic Microangiopathy and the KidneyThrombotic microangiopathy can manifest in a diverse range of diseases and is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ injury, including AKI. It can be associated with significant morbidity and mortality, but a systematic approach to investigation and prompt initiation of supportive management and, in some cases, effective specific treatment can result in good outcomes. This review considers the classification, pathology, epidemiology, characteristics, and pathogenesis of the thrombotic microangiopathies, and outlines a pragmatic approach to diagnosis and management.Brocklebank, VickyWood, Katrina M.Kavanagh, David2017-10-17T06:48:10-07:00doi:10.2215/CJN.00620117hwp:resource-id:clinjasn;13/2/300American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyComplement, glomerular disease, atypical hemolytic uremic syndrome, Thrombotic Microangiopathies, Purpura, Thrombotic Thrombocytopenic, Acute Kidney Injury, kidney, Anemia, HemolyticGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20182018-02-07February 07, 201810.2215/CJN.006201171555-90411555-905X2017-10-17T06:48:10-07:002018-02-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician132300317
- Mesangial C4d Deposits in Early IgA Nephropathy10.2215/CJN.02530317Thu, 16 Nov 2017 06:49:11 GMT-08:00Mesangial C4d Deposits in Early IgA NephropathySegarra, AlfonsRomero, KatheryneAgraz, IreneRamos, NataliaMadrid, AlvaroCarnicer, ClaraJatem, EliasVilalta, RamónLara, Luis EnriqueOstos, ElenaValtierra, NaiaraJaramillo, JulianaArredondo, Karla V.Ariceta, GemaMartinez, Cristina2017-11-16T06:49:11-08:00doi:10.2215/CJN.02530317hwp:resource-id:clinjasn;13/2/258American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycomplement activation, C4d deposits, IgA nephropathy, lectin-pathway, prognosis, Humans, Glomerulonephritis, IGA, glomerular filtration rate, creatinine, Paraffin, Prevalence, Retrospective Studies, Follow-Up Studies, Glomerular Mesangium, Kidney Glomerulus, kidney, Renal Insufficiency, Chronic, Adrenal Cortex Hormones, BiopsyOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-02-07February 07, 201810.2215/CJN.025303171555-90411555-905X2017-11-16T06:49:11-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles132258264
- Correction10.2215/CJN.13831217Fri, 12 Jan 2018 07:46:38 GMT-08:00CorrectionAmerican Society of Nephrology2018-01-12T07:46:38-08:00doi:10.2215/CJN.13831217hwp:resource-id:clinjasn;13/2/299American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyerratum, correction, B-type Natriuretic Peptides, dialysis, mortalityErratumErratumcorrection20182018-02-07February 07, 201810.2215/CJN.138312171555-90411555-905X2018-01-12T07:46:38-08:002018-02-07Clinical Journal of the American Society of NephrologyErratum1332429910572991065
- Employment among Patients Starting Dialysis in the United States10.2215/CJN.06470617Thu, 18 Jan 2018 07:19:29 GMT-08:00Employment among Patients Starting Dialysis in the United StatesErickson, Kevin F.Zhao, BoHo, VivianWinkelmayer, Wolfgang C.2018-01-18T07:19:29-08:00doi:10.2215/CJN.06470617hwp:resource-id:clinjasn;13/2/265American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, clinical epidemiology, Economic Analysis, end-stage renal disease, Epidemiology and outcomes, United States Renal Data System, ethnicity, quality of life, Humans, United States, Unemployment, cyclo(Arg-Pro), Employment, Hispanic Americans, African Americans, Registries, Kidney Diseases, Kidney Failure, Chronic, Probability, renal dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-02-07February 07, 201810.2215/CJN.064706171555-90411555-905X2018-01-18T07:19:29-08:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1322265203273204
- Re-Evaluation of the Normal Range of Serum Total CO2 ConcentrationA reliable determination of blood pH, PCO2, and [HCO3−] is necessary for assessing the acid-base status of a patient. However, most acid-base disorders are first recognized through abnormalities in serum total CO2 concentration ([TCO2]) in venous blood, a surrogate for [HCO3−]. In screening patients on the basis of serum [TCO2], we have been concerned about the wide limits of normal for serum [TCO2], 10–13 mEq/L, reported by many clinical laboratories. Indeed, we have encountered patients with serum [TCO2] values within the lower or upper end of the normal range of the reporting laboratory, who subsequently were shown to have a cardinal acid-base disorder. Here, we present a patient who had a serum [TCO2] within the lower end of the normal range of the clinical laboratory, which resulted in delayed diagnosis of a clinically important “hidden” acid-base disorder. To better define the appropriate limits of normal for serum [TCO2], we derived the expected normal range in peripheral venous blood in adults at sea level from carefully conducted acid-base studies. We then compared this range, 23 to 30 mEq/L, to that reported by 64 clinical laboratories, 2 large commercial clinical laboratories, and the major textbook of clinical chemistry. For the most part, the range in the laboratories we queried was substantially different than that we derived and that published in the textbook, with some laboratories reporting values as low as 18–20 mEq/L and as high as 33–35 mEq/L. We conclude that the limits of values of serum [TCO2] reported by clinical laboratories are very often inordinately wide and not consistent with the range of normal expected in healthy individuals at sea level. We suggest that the limits of normal of serum [TCO2] at sea level be tightened to 23–30 mEq/L. Such correction will ensure recognition of the majority of “hidden” acid-base disorders.10.2215/CJN.11941017Tue, 16 Jan 2018 06:07:30 GMT-08:00Re-Evaluation of the Normal Range of Serum Total CO2 ConcentrationA reliable determination of blood pH, PCO2, and [HCO3−] is necessary for assessing the acid-base status of a patient. However, most acid-base disorders are first recognized through abnormalities in serum total CO2 concentration ([TCO2]) in venous blood, a surrogate for [HCO3−]. In screening patients on the basis of serum [TCO2], we have been concerned about the wide limits of normal for serum [TCO2], 10–13 mEq/L, reported by many clinical laboratories. Indeed, we have encountered patients with serum [TCO2] values within the lower or upper end of the normal range of the reporting laboratory, who subsequently were shown to have a cardinal acid-base disorder. Here, we present a patient who had a serum [TCO2] within the lower end of the normal range of the clinical laboratory, which resulted in delayed diagnosis of a clinically important “hidden” acid-base disorder. To better define the appropriate limits of normal for serum [TCO2], we derived the expected normal range in peripheral venous blood in adults at sea level from carefully conducted acid-base studies. We then compared this range, 23 to 30 mEq/L, to that reported by 64 clinical laboratories, 2 large commercial clinical laboratories, and the major textbook of clinical chemistry. For the most part, the range in the laboratories we queried was substantially different than that we derived and that published in the textbook, with some laboratories reporting values as low as 18–20 mEq/L and as high as 33–35 mEq/L. We conclude that the limits of values of serum [TCO2] reported by clinical laboratories are very often inordinately wide and not consistent with the range of normal expected in healthy individuals at sea level. We suggest that the limits of normal of serum [TCO2] at sea level be tightened to 23–30 mEq/L. Such correction will ensure recognition of the majority of “hidden” acid-base disorders.Kraut, Jeffrey A.Madias, Nicolaos E.2018-01-16T06:07:30-08:00doi:10.2215/CJN.11941017hwp:resource-id:clinjasn;13/2/343American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyReference Values, Chemistry, Clinical, Carbon Dioxide, Delayed Diagnosis, dioxotechnetium, Clinical Laboratory Services, Blood Gas Analysis, Laboratories, Research, Serum Total CO2 ConcentrationFeatureFeatureresearch-article20182018-02-07February 07, 201810.2215/CJN.119410171555-90411555-905X2018-01-16T06:07:30-08:002018-02-07Clinical Journal of the American Society of NephrologyFeature132343347
- The Urine Anion Gap in Context10.2215/CJN.13791217Mon, 08 Jan 2018 06:19:35 GMT-08:00The Urine Anion Gap in ContextBatlle, DanielBa Aqeel, Sheeba HabeebMarquez, Alonso2018-01-08T06:19:35-08:00doi:10.2215/CJN.13791217hwp:resource-id:clinjasn;13/2/195American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Acidosis, Renal Tubular, Ammonium Chloride, Acid-Base Equilibrium, Protons, Ammonium Compounds, glomerular filtration rate, acidosis, Hyperkalemia, Sodium, Body Fluids, Renal Insufficiency, ChronicEditorialsEditorialseditorial20182018-02-07February 07, 201810.2215/CJN.137912171555-90411555-905X2018-01-08T06:19:35-08:002018-02-07Clinical Journal of the American Society of NephrologyEditorials1322195205197212
- Urine Anion Gap to Predict Urine Ammonium and Related Outcomes in Kidney Disease10.2215/CJN.03770417Thu, 02 Nov 2017 07:40:19 GMT-07:00Urine Anion Gap to Predict Urine Ammonium and Related Outcomes in Kidney DiseaseRaphael, Kalani L.Gilligan, SarahIx, Joachim H.2017-11-02T07:40:19-07:00doi:10.2215/CJN.03770417hwp:resource-id:clinjasn;13/2/205American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic metabolic acidosis, chronic kidney disease, AASK (African American Study of Kidney Disease and Hypertension), urine anion gap, outcomes, ESRD, mortality, ammonium, Acid-Base Equilibrium, Ammonium Compounds, Body Fluids, Kidney DiseasesOriginal ArticlesAcid/Base and Electrolyte DisordersOriginal ArticlesAcid/Base and Electrolyte Disordersresearch-article20182018-02-07February 07, 201810.2215/CJN.037704171555-90411555-905X2017-11-02T07:40:19-07:002018-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1322205195212197
- Intragraft Molecular Pathways Associated with Tolerance Induction in Renal TransplantationThe modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell– and B cell–mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways.10.1681/ASN.2017030348Thu, 30 Nov 2017 06:22:04 GMT-08:00Intragraft Molecular Pathways Associated with Tolerance Induction in Renal TransplantationThe modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell– and B cell–mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways.Gallon, LorenzoMathew, James M.Bontha, Sai VineelaDumur, Catherine I.Dalal, PranavNadimpalli, LakshmiMaluf, Daniel G.Shetty, Aneesha A.Ildstad, Suzanne T.Leventhal, Joseph R.Mas, Valeria R.2017-11-30T06:22:04-08:00doi:10.1681/ASN.2017030348hwp:resource-id:jnephrol;29/2/423American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, tolerance, kidney biopsy, transcriptional profiling, Immunology and pathologyBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170303481046-66731533-34502017-11-30T06:22:04-08:002018-02Journal of the American Society of NephrologyBasic Research292423433
- A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant RejectionLate antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)–positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, −4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.10.1681/ASN.2017070818Thu, 14 Dec 2017 06:26:50 GMT-08:00A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant RejectionLate antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)–positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, −4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.Eskandary, FarsadRegele, HeinzBaumann, LukasBond, GregorKozakowski, NicolasWahrmann, MarkusHidalgo, Luis G.Haslacher, HelmuthKaltenecker, Christopher C.Aretin, Marie-BernadetteOberbauer, RainerPosch, MartinStaudenherz, AntonHandisurya, AmmonReeve, JeffHalloran, Philip F.Böhmig, Georg A.2017-12-14T06:26:50-08:00doi:10.1681/ASN.2017070818hwp:resource-id:jnephrol;29/2/591American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyantibody-mediated rejection, bortezomib, chronic allograft failure, kidney, transplantation, randomized controlled trialClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170708181046-66731533-34502017-12-14T06:26:50-08:002018-02Journal of the American Society of NephrologyClinical Research2922591350605352
- Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to TreatmentComplement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.10.1681/ASN.2017050589Tue, 17 Oct 2017 06:48:30 GMT-07:00Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to TreatmentComplement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.Lefaucheur, CarmenViglietti, DenisHidalgo, Luis G.Ratner, Lloyd E.Bagnasco, Serena M.Batal, IbrahimAubert, OlivierOrandi, Babak J.Oppenheimer, FedericoBestard, OriolRigotti, PaoloReisaeter, Anna V.Kamar, NassimLebranchu, YvonDuong Van Huyen, Jean-PaulBruneval, PatrickGlotz, DenisLegendre, ChristopheEmpana, Jean-PhilippeJouven, XavierSegev, Dorry L.Montgomery, Robert A.Zeevi, AdrianaHalloran, Philip F.Loupy, Alexandre2017-10-17T06:48:30-07:00doi:10.1681/ASN.2017050589hwp:resource-id:jnephrol;29/2/620American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, rejection, transcriptional profiling, complementClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170505891046-66731533-34502017-10-17T06:48:30-07:002018-02Journal of the American Society of NephrologyClinical Research292620635
- Editorial Note: From Both Sides Now10.1681/ASN.2017121322Thu, 25 Jan 2018 06:04:05 GMT-08:00Editorial Note: From Both Sides NowBriggs, Josephine P.Hostetter, Thomas H.2018-01-25T06:04:05-08:00doi:10.1681/ASN.2017121322hwp:resource-id:jnephrol;29/2/355American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAlport-s syndrome, Bardoxolone, GFRUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-02-01February 201810.1681/ASN.20171213221046-66731533-34502018-01-25T06:04:05-08:002018-02Journal of the American Society of NephrologyUp Front Matters29222355357360356359361
- Clinical Translation of Mesenchymal Stromal Cell Therapies in NephrologyMesenchymal stromal cells have emerged as potential candidates for cell-based therapies to modulate the immune response in organ transplantation and repair tissues after acute or chronic injury. Preclinical studies have shown convincingly in rodent models that mesenchymal stromal cells can prolong solid organ graft survival and that they can induce immune tolerance, accelerate recovery from AKI, and promote functional improvement in chronic nephropathies. Multiple complex properties of the cells, including immunomodulatory, anti-inflammatory, and proregenerative effects, seem to contribute. The promising preclinical studies have encouraged investigators to explore the safety, tolerability, and efficacy of mesenchymal stromal cell–based therapy in pilot clinical trials, including those for bone marrow and solid organ transplantation, autoimmune diseases, and tissue and organ repair. Here, we review the available data on culture-expanded mesenchymal stromal cells tested in renal transplantation, AKI, and CKD. We also briefly discuss the relevant issues that must be addressed to ensure rigorous assessment of the safety and efficacy of mesenchymal stromal cell therapies to allow the translation of this research into the practice of clinical nephrology.10.1681/ASN.2017070781Thu, 30 Nov 2017 06:22:03 GMT-08:00Clinical Translation of Mesenchymal Stromal Cell Therapies in NephrologyMesenchymal stromal cells have emerged as potential candidates for cell-based therapies to modulate the immune response in organ transplantation and repair tissues after acute or chronic injury. Preclinical studies have shown convincingly in rodent models that mesenchymal stromal cells can prolong solid organ graft survival and that they can induce immune tolerance, accelerate recovery from AKI, and promote functional improvement in chronic nephropathies. Multiple complex properties of the cells, including immunomodulatory, anti-inflammatory, and proregenerative effects, seem to contribute. The promising preclinical studies have encouraged investigators to explore the safety, tolerability, and efficacy of mesenchymal stromal cell–based therapy in pilot clinical trials, including those for bone marrow and solid organ transplantation, autoimmune diseases, and tissue and organ repair. Here, we review the available data on culture-expanded mesenchymal stromal cells tested in renal transplantation, AKI, and CKD. We also briefly discuss the relevant issues that must be addressed to ensure rigorous assessment of the safety and efficacy of mesenchymal stromal cell therapies to allow the translation of this research into the practice of clinical nephrology.Perico, NorbertoCasiraghi, FedericaRemuzzi, Giuseppe2017-11-30T06:22:03-08:00doi:10.1681/ASN.2017070781hwp:resource-id:jnephrol;29/2/362American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymesenchymal stromal cells, kidney disease, acute kidney injuryUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-02-01February 201810.1681/ASN.20170707811046-66731533-34502017-11-30T06:22:03-08:002018-02Journal of the American Society of NephrologyUp Front Matters292362375
- Suppression of microRNA Activity in Kidney Collecting Ducts Induces Partial Loss of Epithelial Phenotype and Renal FibrosismicroRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. The physiologic function of these noncoding RNAs in postnatal renal tubules still remains unclear. Surprisingly, they appear to be dispensable for mammalian proximal tubule (PT) function. Here, we examined the effects of miRNA suppression in collecting ducts (CDs). To conclusively evaluate the role of miRNAs, we generated three mouse models with CD-specific inactivation of key miRNA pathway genes Dicer, Dgcr8, and the entire Argonaute gene family (Ago1, 2, 3, and 4). Characterization of these three mouse models revealed that inhibition of miRNAs in CDs spontaneously evokes a renal tubule injury–like response, which culminates in progressive tubulointerstitial fibrosis (TIF) and renal failure. Global miRNA profiling of microdissected renal tubules showed that miRNAs exhibit segmental distribution along the nephron and CDs. In particular, the expression of miR-200c is nearly 70-fold higher in CDs compared with PTs. Accordingly, miR-200s are downregulated in Dicer-KO CDs, its direct target genes Zeb1, Zeb2, and Snail2 are upregulated, and miRNA-depleted CDs undergo partial epithelial-to-mesenchymal transition (EMT). Thus, miRNAs are essential for CD homeostasis. Downregulation of CD-enriched miRNAs and the subsequent induction of partial EMT may be a new mechanism for TIF progression.10.1681/ASN.2017030334Wed, 11 Oct 2017 08:23:23 GMT-07:00Suppression of microRNA Activity in Kidney Collecting Ducts Induces Partial Loss of Epithelial Phenotype and Renal FibrosismicroRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. The physiologic function of these noncoding RNAs in postnatal renal tubules still remains unclear. Surprisingly, they appear to be dispensable for mammalian proximal tubule (PT) function. Here, we examined the effects of miRNA suppression in collecting ducts (CDs). To conclusively evaluate the role of miRNAs, we generated three mouse models with CD-specific inactivation of key miRNA pathway genes Dicer, Dgcr8, and the entire Argonaute gene family (Ago1, 2, 3, and 4). Characterization of these three mouse models revealed that inhibition of miRNAs in CDs spontaneously evokes a renal tubule injury–like response, which culminates in progressive tubulointerstitial fibrosis (TIF) and renal failure. Global miRNA profiling of microdissected renal tubules showed that miRNAs exhibit segmental distribution along the nephron and CDs. In particular, the expression of miR-200c is nearly 70-fold higher in CDs compared with PTs. Accordingly, miR-200s are downregulated in Dicer-KO CDs, its direct target genes Zeb1, Zeb2, and Snail2 are upregulated, and miRNA-depleted CDs undergo partial epithelial-to-mesenchymal transition (EMT). Thus, miRNAs are essential for CD homeostasis. Downregulation of CD-enriched miRNAs and the subsequent induction of partial EMT may be a new mechanism for TIF progression.Hajarnis, SachinYheskel, MatanelWilliams, DarrenBrefort, ThomasGlaudemans, BobDebaix, HuguetteBaum, MichelDevuyst, OlivierPatel, Vishal2017-10-11T08:23:23-07:00doi:10.1681/ASN.2017030334hwp:resource-id:jnephrol;29/2/518American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologymicroRNAs, Dicer, collecting ducts, miR-200Basic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170303341046-66731533-34502017-10-11T08:23:23-07:002018-02Journal of the American Society of NephrologyBasic Research2922518349531350
- Making the Right Decision: Do Clinical Decision Support Systems for AKI Improve Patient Outcomes?10.1681/ASN.2017121284Mon, 15 Jan 2018 09:38:16 GMT-08:00Making the Right Decision: Do Clinical Decision Support Systems for AKI Improve Patient Outcomes?Selby, Nicholas M.Fluck, Richard J.2018-01-15T09:38:16-08:00doi:10.1681/ASN.2017121284hwp:resource-id:jnephrol;29/2/352American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, kidney disease, kidney dysfunctionUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-02-01February 201810.1681/ASN.20171212841046-66731533-34502018-01-15T09:38:16-08:002018-02Journal of the American Society of NephrologyUp Front Matters2922352654354660
- Reduced Expression of Glutathione S-Transferase α4 Promotes Vascular Neointimal Hyperplasia in CKDNeointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)–mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs. Compared with non-CKD controls, mice with CKD had downregulated expression of GSTA4 at the mRNA and protein levels, with concomitant increase in 4-HNE in arteries and veins. This effect was associated with upregulated phosphorylation of MAPK signaling pathway proteins in proliferating SMCs. Overexpressing GSTA4 blocked 4-HNE–induced SMC proliferation. Additionally, inhibitors of MAPK signaling inhibited the 4-HNE–induced responses. Compared with wild-type mice, mice lacking GSTA4 exhibited increased CKD-induced neointima formation in AVF. Transient expression of an activated form of GSTA4, achieved using a combined Tet-On/Cre induction system in mice, lowered levels of 4-HNE and reduced the proliferation of SMCs. Together, these results demonstrate the critical role of GSTA4 in blocking CKD-induced neointima formation and AVF failure.10.1681/ASN.2017030290Fri, 10 Nov 2017 10:49:37 GMT-08:00Reduced Expression of Glutathione S-Transferase α4 Promotes Vascular Neointimal Hyperplasia in CKDNeointima formation is the leading cause of arteriovenous fistula (AVF) failure. We have shown that CKD accelerates this process by transforming the vascular smooth muscle cells (SMCs) lining the AVF from a contractile to the synthetic phenotype. However, the underlying mechanisms affecting this transformation are not clear. Previous studies have shown that the α-class glutathione transferase isozymes have an important role in regulating 4-hydroxynonenal (4-HNE)–mediated proliferative signaling of cells. Here, using both the loss- and gain-of-function approaches, we investigated the role of glutathione S-transferase α4 (GSTA4) in modulating cellular 4-HNE levels for the transformation and proliferation of SMCs. Compared with non-CKD controls, mice with CKD had downregulated expression of GSTA4 at the mRNA and protein levels, with concomitant increase in 4-HNE in arteries and veins. This effect was associated with upregulated phosphorylation of MAPK signaling pathway proteins in proliferating SMCs. Overexpressing GSTA4 blocked 4-HNE–induced SMC proliferation. Additionally, inhibitors of MAPK signaling inhibited the 4-HNE–induced responses. Compared with wild-type mice, mice lacking GSTA4 exhibited increased CKD-induced neointima formation in AVF. Transient expression of an activated form of GSTA4, achieved using a combined Tet-On/Cre induction system in mice, lowered levels of 4-HNE and reduced the proliferation of SMCs. Together, these results demonstrate the critical role of GSTA4 in blocking CKD-induced neointima formation and AVF failure.Luo, JinlongChen, GuangLiang, MingXie, AiniLi, QingtianGuo, QunyingSharma, RajendraCheng, Jizhong2017-11-10T10:49:37-08:00doi:10.1681/ASN.2017030290hwp:resource-id:jnephrol;29/2/505American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, glutathione S-transferase A4, neointima, chronic kidney diseaseBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170302901046-66731533-34502017-11-10T10:49:37-08:002018-02Journal of the American Society of NephrologyBasic Research292505517
- Deletion Variants of CFHR1 and CFHR3 Associate with Mesangial Immune Deposits but Not with Progression of IgA NephropathyActivation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H–related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40.1 years; median follow-up, 132 months). We determined the number of CFHR3 and CFHR1 gene copies by quantitative PCR and collected clinical and biologic data by reviewing the patients’ medical records. In all, 30.5% of the patients were heterozygous and 4% were homozygous for CFHR3,1Δ. We did not detect an association between CFHR3,1Δ and age, eGFR, urinary protein excretion rate, or the presence of hypertension or hematuria at the time of diagnosis. The mean intensities of immune IgA, IgG, and C3 deposits were lower in the group with heterozygous or homozygous gene deletions than in those with no deletion. However, CFHR3,1Δ did not associate with progression to stage 3 CKD or renal death. In conclusion, the CFHR3,1Δ genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits.10.1681/ASN.2017010019Tue, 07 Nov 2017 08:42:45 GMT-08:00Deletion Variants of CFHR1 and CFHR3 Associate with Mesangial Immune Deposits but Not with Progression of IgA NephropathyActivation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H–related genes 1 and 3 (CFHR3,1Δ) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their CFHR3,1Δ genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40.1 years; median follow-up, 132 months). We determined the number of CFHR3 and CFHR1 gene copies by quantitative PCR and collected clinical and biologic data by reviewing the patients’ medical records. In all, 30.5% of the patients were heterozygous and 4% were homozygous for CFHR3,1Δ. We did not detect an association between CFHR3,1Δ and age, eGFR, urinary protein excretion rate, or the presence of hypertension or hematuria at the time of diagnosis. The mean intensities of immune IgA, IgG, and C3 deposits were lower in the group with heterozygous or homozygous gene deletions than in those with no deletion. However, CFHR3,1Δ did not associate with progression to stage 3 CKD or renal death. In conclusion, the CFHR3,1Δ genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits.Jullien, PerrineLaurent, BlandineClaisse, GuillaumeMasson, IngridDinic, MirianaThibaudin, DamienBerthoux, FrancoisAlamartine, EricMariat, ChristopheMaillard, Nicolas2017-11-07T08:42:45-08:00doi:10.1681/ASN.2017010019hwp:resource-id:jnephrol;29/2/661American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, histopathology, human genetics, IgA nephropathy, complementClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170100191046-66731533-34502017-11-07T08:42:45-08:002018-02Journal of the American Society of NephrologyClinical Research292661669
- Redirecting TGF-β Signaling through the β-Catenin/Foxo Complex Prevents Kidney FibrosisTGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β. In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity. Moreover, the level of β-catenin expression positively correlated with the level of Foxo1 binding to the Foxp3 promoter and Foxo transcriptional activity. T cell fate mapping in Foxp3gfp Ly5.1/5.2 mice revealed that coadministration of rhTGF-β1 and ICG-001 further enhanced the expansion of iTregs and natural Tregs observed with rhTGF-β1 treatment alone. Coadministration of rhTGF-β1 with ICG-001 also increased the number of Tregs and reduced inflammation and fibrosis in the kidney fibrosis models of unilateral ureteric obstruction and ischemia-reperfusion injury. Notably, ICG-001 prevented the fibrosis in distant organs (lung and liver) caused by rhTGF-β1. Together, our results show that diversion of β-catenin from TCF- to Foxo-mediated transcription inhibits the β-catenin/TCF–mediated profibrotic effects of TGF-β while enhancing the β-catenin/Foxo–mediated anti-inflammatory effects. Targeting β-catenin/Foxo may be a novel therapeutic strategy in the treatment of fibrotic diseases that lead to organ failure.10.1681/ASN.2016121362Mon, 27 Nov 2017 06:42:40 GMT-08:00Redirecting TGF-β Signaling through the β-Catenin/Foxo Complex Prevents Kidney FibrosisTGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β. In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity. Moreover, the level of β-catenin expression positively correlated with the level of Foxo1 binding to the Foxp3 promoter and Foxo transcriptional activity. T cell fate mapping in Foxp3gfp Ly5.1/5.2 mice revealed that coadministration of rhTGF-β1 and ICG-001 further enhanced the expansion of iTregs and natural Tregs observed with rhTGF-β1 treatment alone. Coadministration of rhTGF-β1 with ICG-001 also increased the number of Tregs and reduced inflammation and fibrosis in the kidney fibrosis models of unilateral ureteric obstruction and ischemia-reperfusion injury. Notably, ICG-001 prevented the fibrosis in distant organs (lung and liver) caused by rhTGF-β1. Together, our results show that diversion of β-catenin from TCF- to Foxo-mediated transcription inhibits the β-catenin/TCF–mediated profibrotic effects of TGF-β while enhancing the β-catenin/Foxo–mediated anti-inflammatory effects. Targeting β-catenin/Foxo may be a novel therapeutic strategy in the treatment of fibrotic diseases that lead to organ failure.Qiao, XiRao, PadmashreeZhang, YunLiu, LixinPang, MinWang, HailongHu, MinTian, XinruiZhang, JianlinZhao, YeWang, Xin MaggieWang, ChengshiYu, HongGuo, FeiCao, QiWang, YipingWang, Yuan MinZhang, Geoff YuLee, Vincent W.Alexander, Stephen I.Zheng, GuopingHarris, David C.H.2017-11-27T06:42:40-08:00doi:10.1681/ASN.2016121362hwp:resource-id:jnephrol;29/2/557American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, fibrosis, TGF-βBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20161213621046-66731533-34502017-11-27T06:42:40-08:002018-02Journal of the American Society of NephrologyBasic Research292557570
- LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody DiseasePrimary renal tubulointerstitial disease resulting from proximal tubule antigen–specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.10.1681/ASN.2017060664Thu, 26 Oct 2017 06:38:19 GMT-07:00LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody DiseasePrimary renal tubulointerstitial disease resulting from proximal tubule antigen–specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.Larsen, Christopher P.Trivin-Avillach, ClaireColes, PaigeCollins, A. BernardMerchant, MichaelMa, HongWilkey, Daniel W.Ambruzs, Josephine M.Messias, Nidia C.Cossey, L. NicholasRosales, Ivy A.Wooldridge, ThomasWalker, Patrick D.Colvin, Robert B.Klein, JonSalant, David J.Beck, Laurence H.2017-10-26T06:38:19-07:00doi:10.1681/ASN.2017060664hwp:resource-id:jnephrol;29/2/644American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyHeymann nephritis, immune complexes, kidney biopsy, kidney tubule, membranous nephropathy, Immunology and pathologyClinical ResearchClinical Researchresearch-article20182018-02-01February 201810.1681/ASN.20170606641046-66731533-34502017-10-26T06:38:19-07:002018-02Journal of the American Society of NephrologyClinical Research292644653
- Erratum10.1681/ASN.2017091022Wed, 31 Jan 2018 01:00:50 GMT-08:00ErratumAmerican Society of Nephrology2018-01-31T13:00:50-08:00doi:10.1681/ASN.2017091022hwp:resource-id:jnephrol;29/2/704American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20182018-02-01February 201810.1681/ASN.20170910221046-66731533-34502018-01-31T13:00:50-08:002018-02Journal of the American Society of NephrologyErratum292523704455704463
- This Month’s Highlights10.1681/ASN.2017121324Wed, 31 Jan 2018 01:00:50 GMT-08:00This Month’s HighlightsAmerican Society of Nephrology2018-01-31T13:00:50-08:00doi:10.1681/ASN.2017121324hwp:resource-id:jnephrol;29/2/iAmerican Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20182018-02-01February 201810.1681/ASN.20171213241046-66731533-34502018-01-31T13:00:50-08:002018-02Journal of the American Society of NephrologyThis Month’s Highlights292ii
- Tonicity-Responsive Enhancer-Binding Protein Mediates Hyperglycemia-Induced Inflammation and Vascular and Renal InjuryDiabetic nephropathy (DN) has become the single leading cause of ESRD in developed nations. Bearing in mind the paucity of effective treatment for DN and progressive CKD, novel targets for treatment are sorely needed. We previously reported that increased activity of tonicity-responsive enhancer-binding protein (TonEBP) in monocytes was associated with early DN in humans. We now extend these findings by testing the hypotheses that TonEBP in macrophages promotes hyperglycemia-mediated proinflammatory activation and chronic renal inflammation leading to DN and CKD, and TonEBP genetic variability in humans is associated with inflammatory, renal, and vascular function–related phenotypes. In a mouse model of DN, compared with the wild-type phenotype, TonEBP haplodeficiency associated with reduced activation of macrophages by hyperglycemia, fewer macrophages in the kidney, lower renal expression of proinflammatory genes, and attenuated DN. Furthermore, in a cohort of healthy humans, genetic variants within TonEBP associated with renal function, BP, and systemic inflammation. One of the genetic variants associated with renal function was replicated in a large population-based cohort. These findings suggest that TonEBP is a promising target for minimizing diabetes- and stress-induced inflammation and renovascular injury.10.1681/ASN.2017070718Mon, 20 Nov 2017 04:50:38 GMT-08:00Tonicity-Responsive Enhancer-Binding Protein Mediates Hyperglycemia-Induced Inflammation and Vascular and Renal InjuryDiabetic nephropathy (DN) has become the single leading cause of ESRD in developed nations. Bearing in mind the paucity of effective treatment for DN and progressive CKD, novel targets for treatment are sorely needed. We previously reported that increased activity of tonicity-responsive enhancer-binding protein (TonEBP) in monocytes was associated with early DN in humans. We now extend these findings by testing the hypotheses that TonEBP in macrophages promotes hyperglycemia-mediated proinflammatory activation and chronic renal inflammation leading to DN and CKD, and TonEBP genetic variability in humans is associated with inflammatory, renal, and vascular function–related phenotypes. In a mouse model of DN, compared with the wild-type phenotype, TonEBP haplodeficiency associated with reduced activation of macrophages by hyperglycemia, fewer macrophages in the kidney, lower renal expression of proinflammatory genes, and attenuated DN. Furthermore, in a cohort of healthy humans, genetic variants within TonEBP associated with renal function, BP, and systemic inflammation. One of the genetic variants associated with renal function was replicated in a large population-based cohort. These findings suggest that TonEBP is a promising target for minimizing diabetes- and stress-induced inflammation and renovascular injury.Choi, Soo YounLim, Sun WooSalimi, ShabnamYoo, Eun JinLee-Kwon, WhaseonLee, Hwan HeeLee, Jun HoMitchell, Braxton D.Sanada, SatoruParsa, AfshinKwon, Hyug Moo2017-11-20T04:50:38-08:00doi:10.1681/ASN.2017070718hwp:resource-id:jnephrol;29/2/492American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyDiabetic nephropathy, chronic kidney disease, blood pressure, macrophages, genetic variantsBasic ResearchBasic Researchresearch-article20182018-02-01February 201810.1681/ASN.20170707181046-66731533-34502017-11-20T04:50:38-08:002018-02Journal of the American Society of NephrologyBasic Research292492504
- Tissue-Resident Lymphocytes in the KidneyIt has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells. Additionally, a substantial proportion of the adaptive lymphocytes that are found in the kidney displays a surface phenotype suggestive of tissue residency, such as CD69+CD4+ T cells. In this review, we summarize recent advances in the understanding of tissue-resident lymphocyte populations, review the available evidence for the existence of these populations in the kidney, and discuss the potential physiologic and pathophysiologic roles thereof in kidney.10.1681/ASN.2017060599Wed, 01 Nov 2017 06:17:43 GMT-07:00Tissue-Resident Lymphocytes in the KidneyIt has become evident that nonlymphoid tissues are populated by distinct subsets of innate and adaptive lymphocytes that are characterized by minimal exchange with recirculating counterparts. Especially at barrier sites, such as the skin, gut, and lung, these tissue-resident lymphocyte populations are ideally positioned to quickly respond to pathogens and other environmental stimuli. The kidney harbors several classes of innate and innate-like lymphocytes that have been described to contribute to this tissue-resident population in other organs, including innate lymphoid cells, natural killer cells, natural killer T cells, mucosal-associated invariant T cells, and γδ T cells. Additionally, a substantial proportion of the adaptive lymphocytes that are found in the kidney displays a surface phenotype suggestive of tissue residency, such as CD69+CD4+ T cells. In this review, we summarize recent advances in the understanding of tissue-resident lymphocyte populations, review the available evidence for the existence of these populations in the kidney, and discuss the potential physiologic and pathophysiologic roles thereof in kidney.Turner, Jan-EricBecker, MartinaMittrücker, Hans-WilliPanzer, Ulf2017-11-01T06:17:43-07:00doi:10.1681/ASN.2017060599hwp:resource-id:jnephrol;29/2/389American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologylymphocytes, Immunology and pathology, cytokinesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-02-01February 201810.1681/ASN.20170605991046-66731533-34502017-11-01T06:17:43-07:002018-02Journal of the American Society of NephrologyUp Front Matters292389399
- Insights into the Regulation of Collecting Duct Homeostasis by Small Noncoding RNAs10.1681/ASN.2017101072Fri, 08 Dec 2017 08:43:45 GMT-08:00Insights into the Regulation of Collecting Duct Homeostasis by Small Noncoding RNAsPhua, Yu LengHo, Jacqueline2017-12-08T08:43:45-08:00doi:10.1681/ASN.2017101072hwp:resource-id:jnephrol;29/2/349American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyinterstitial fibrosis, non coding RNAs, collecting ductsUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-02-01February 201810.1681/ASN.20171010721046-66731533-34502017-12-08T08:43:45-08:002018-02Journal of the American Society of NephrologyUp Front Matters2922349518350531
- Serum Response Factor Is Essential for Maintenance of Podocyte Structure and FunctionPodocytes contain an intricate actin cytoskeleton that is essential for the specialized function of this cell type in renal filtration. Serum response factor (SRF) is a master transcription factor for the actin cytoskeleton, but the in vivo expression and function of SRF in podocytes are unknown. We found that SRF protein colocalizes with podocyte markers in human and mouse kidneys. Compared with littermate controls, mice in which the Srf gene was conditionally inactivated with NPHS2-Cre exhibited early postnatal proteinuria, hypoalbuminemia, and azotemia. Histologic changes in the mutant mice included glomerular capillary dilation and mild glomerulosclerosis, with reduced expression of multiple canonical podocyte markers. We also noted tubular dilation, cell proliferation, and protein casts as well as reactive changes in mesangial cells and interstitial inflammation. Ultrastructure analysis disclosed foot process effacement with loss of slit diaphragms. To ascertain the importance of SRF cofactors in podocyte function, we disabled the myocardin-related transcription factor A and B genes. Although loss of either SRF cofactor alone had no observable effect in the kidney, deficiency of both recapitulated the Srf-null phenotype. These results establish a vital role for SRF and two SRF cofactors in the maintenance of podocyte structure and function.10.1681/ASN.2017050473Tue, 07 Nov 2017 08:42:43 GMT-08:00Serum Response Factor Is Essential for Maintenance of Podocyte Structure and FunctionPodocytes contain an intricate actin cytoskeleton that is essential for the specialized function of this cell type in renal filtration. Serum response factor (SRF) is a master transcription factor for the actin cytoskeleton, but the in vivo expression and function of SRF in podocytes are unknown. We found that SRF protein colocalizes with podocyte markers in human and mouse kidneys. Compared with littermate controls, mice in which the Srf gene was conditionally inactivated with NPHS2-Cre exhibited early postnatal proteinuria, hypoalbuminemia, and azotemia. Histologic changes in the mutant mice included glomerular capillary dilation and mild glomerulosclerosis, with reduced expression of multiple canonical podocyte markers. We also noted tubular dilation, cell proliferation, and protein casts as well as reactive changes in mesangial cells and interstitial inflammation. Ultrastructure analysis disclosed foot process effacement with loss of slit diaphragms. To ascertain the importance of SRF cofactors in podocyte function, we disabled the myocardin-related transcription factor A and B genes. Although loss of either SRF cofactor alone had no observable effect in the kidney, deficiency of both recapitulated the Srf-null phenotype. These results establish a vital role for SRF and two SRF cofactors in the maintenance of podocyte structure and function.Guo, BingLyu, QingSlivano, Orazio J.Dirkx, RonaldChristie, Christine K.Czyzyk, JanHezel, Aram F.Gharavi, Ali G.Small, Eric M.Miano, Joseph M.2017-11-07T08:42:43-08:00doi:10.1681/ASN.2017050473hwp:resource-id:jnephrol;29/2/416American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyserum response factor, glomerulopathy, podocyte, renal failure, knockoutBrief CommunicationsBrief Communicationsbrief-report20182018-02-01February 201810.1681/ASN.20170504731046-66731533-34502017-11-07T08:42:43-08:002018-02Journal of the American Society of NephrologyBrief Communications292416422
- Any Progress in the Treatment of Antibody-Mediated Rejection?10.1681/ASN.2017121296Thu, 25 Jan 2018 06:04:05 GMT-08:00Any Progress in the Treatment of Antibody-Mediated Rejection?Budde, KlemensDürr, Michael2018-01-25T06:04:05-08:00doi:10.1681/ASN.2017121296hwp:resource-id:jnephrol;29/2/350American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, chronic allograft rejection, immunosuppression, kidney transplantation, transplant outcomes, antibody mediated rejectionUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-02-01February 201810.1681/ASN.20171212961046-66731533-34502018-01-25T06:04:05-08:002018-02Journal of the American Society of NephrologyUp Front Matters29222350606591352619605
- TRPC5 Does Not Cause or Aggravate Glomerular DiseaseTransient receptor potential channel 5 (TRPC5) is highly expressed in brain and kidney and mediates calcium influx and promotes cell migration. In the kidney, loss of TRPC5 function has been reported to benefit kidney filter dynamics by balancing podocyte cytoskeletal remodeling. However, in vivo gain-in-function studies of TRPC5 with respect to kidney function have not been reported. To address this gap, we developed two transgenic mouse models on the C57BL/6 background by overexpressing either wild-type TRPC5 or a TRPC5 ion-pore mutant. Compared with nontransgenic controls, neither transgenic model exhibited an increase in proteinuria at 8 months of age or a difference in LPS-induced albuminuria. Moreover, activation of TRPC5 by Englerin A did not stimulate proteinuria, and inhibition of TRPC5 by ML204 did not significantly lower the level of LPS-induced proteinuria in any group. Collectively, these data suggest that the overexpression or activation of the TRPC5 ion channel does not cause kidney barrier injury or aggravate such injury under pathologic conditions.10.1681/ASN.2017060682Mon, 23 Oct 2017 06:02:12 GMT-07:00TRPC5 Does Not Cause or Aggravate Glomerular DiseaseTransient receptor potential channel 5 (TRPC5) is highly expressed in brain and kidney and mediates calcium influx and promotes cell migration. In the kidney, loss of TRPC5 function has been reported to benefit kidney filter dynamics by balancing podocyte cytoskeletal remodeling. However, in vivo gain-in-function studies of TRPC5 with respect to kidney function have not been reported. To address this gap, we developed two transgenic mouse models on the C57BL/6 background by overexpressing either wild-type TRPC5 or a TRPC5 ion-pore mutant. Compared with nontransgenic controls, neither transgenic model exhibited an increase in proteinuria at 8 months of age or a difference in LPS-induced albuminuria. Moreover, activation of TRPC5 by Englerin A did not stimulate proteinuria, and inhibition of TRPC5 by ML204 did not significantly lower the level of LPS-induced proteinuria in any group. Collectively, these data suggest that the overexpression or activation of the TRPC5 ion channel does not cause kidney barrier injury or aggravate such injury under pathologic conditions.Wang, XuexiangDande, Ranadheer R.Yu, HaoSamelko, BeataMiller, Rachel E.Altintas, Mehmet M.Reiser, Jochen2017-10-23T06:02:12-07:00doi:10.1681/ASN.2017060682hwp:resource-id:jnephrol;29/2/409American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyTRPC5, podocyte, glomerular disease, glomerular filtration barrier, proteinuria, calcium channelsBrief CommunicationsBrief Communicationsbrief-report20182018-02-01February 201810.1681/ASN.20170606821046-66731533-34502017-10-23T06:02:12-07:002018-02Journal of the American Society of NephrologyBrief Communications292409415
- Banff Classification of Polyomavirus Nephropathy: A New Tool for Research and Clinical Practice10.1681/ASN.2017121328Thu, 25 Jan 2018 06:04:05 GMT-08:00Banff Classification of Polyomavirus Nephropathy: A New Tool for Research and Clinical PracticeB. Kopp, Jeffrey2018-01-25T06:04:05-08:00doi:10.1681/ASN.2017121328hwp:resource-id:jnephrol;29/2/354American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynephropathy, Renal pathology, transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-02-01February 201810.1681/ASN.20171213281046-66731533-34502018-01-25T06:04:05-08:002018-02Journal of the American Society of NephrologyUp Front Matters2922354680355693
- Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD10.2215/CJN.07300717Sat, 04 Nov 2017 02:30:09 GMT-07:00Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKDBushinsky, David A.Hostetter, ThomasKlaerner, GerritStasiv, YuriLockey, ClaireMcNulty, SarahLee, AngelaParsell, DawnMathur, VandanaLi, ElizabethBuysse, JerryAlpern, Robert2017-11-04T14:30:09-07:00doi:10.2215/CJN.07300717hwp:resource-id:clinjasn;13/1/26American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacidosis, bicarbonates, chronic kidney disease, comorbidity, Diabetes Mellitus, diet, Double-Blind Method, Heart Failure, humans, Hydrochloric Acid, hypertension, kidney, metabolic acidosis, chronic, Renal Insufficiency, Chronic, sodiumOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-01-06January 06, 201810.2215/CJN.073007171555-90411555-905X2017-11-04T14:30:09-07:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles13112264277355277
- FGF23 and Left Ventricular Hypertrophy in Children with CKD10.2215/CJN.02110217Thu, 12 Oct 2017 06:36:25 GMT-07:00FGF23 and Left Ventricular Hypertrophy in Children with CKDMitsnefes, Mark M.Betoko, AishaSchneider, Michael F.Salusky, Isidro B.Wolf, Myles SeligJüppner, HaraldWarady, Bradley A.Furth, Susan L.Portale, Anthony A.2017-10-12T06:36:25-07:00doi:10.2215/CJN.02110217hwp:resource-id:clinjasn;13/1/45American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFGF23, left ventricular hypertrophy, chronic kidney disease, children, cardiovascular disease, adult, child, humans, fibroblast growth factor 23, Odds Ratio, Hypertrophy, Left Ventricular, Logistic Models, risk factors, Prevalence, Body Mass Index, Confidence Intervals, Fibroblast Growth Factors, Renal Insufficiency, Chronic, echocardiography, EGFR protein, human, Receptor, Epidermal Growth FactorOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-01-06January 06, 201810.2215/CJN.021102171555-90411555-905X2017-10-12T06:36:25-07:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1314552
- The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD10.2215/CJN.05440517Tue, 05 Dec 2017 08:38:05 GMT-08:00The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKDMalhotra, RakeshKatz, RonitHoofnagle, AndrewBostom, AndrewRifkin, Dena E.Mcbride, RuthProbstfield, JeffreyBlock, GeoffreyIx, Joachim H.2017-12-05T08:38:05-08:00doi:10.2215/CJN.05440517hwp:resource-id:clinjasn;13/1/36American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymineral metabolism, chronic kidney disease, hyperphosphatemia, Humans, Niacin, fibroblast growth factor 23, parathyroid hormone, Metabolic Syndrome X, calcium, Sodium, Double-Blind Method, glomerular filtration rate, Global Health, Random Allocation, Phosphates, Renal Insufficiency, Chronic, Phosphorus, Minerals, Triglycerides, Cardiovascular Diseases, Kidney Failure, Chronic, Phosphate Transport Proteins, Vitamin D, Fibroblast Growth FactorsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20182018-01-06January 06, 201810.2215/CJN.054405171555-90411555-905X2017-12-05T08:38:05-08:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1311366448
- Donor-Specific Antibodies in Kidney Transplant RecipientsDonor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. De novo donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient’s immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.10.2215/CJN.00700117Wed, 26 Apr 2017 05:40:18 GMT-07:00Donor-Specific Antibodies in Kidney Transplant RecipientsDonor-specific antibodies have become an established biomarker predicting antibody-mediated rejection. Antibody-mediated rejection is the leading cause of graft loss after kidney transplant. There are several phenotypes of antibody-mediated rejection along post-transplant course that are determined by the timing and extent of humoral response and the various characteristics of donor-specific antibodies, such as antigen classes, specificity, antibody strength, IgG subclasses, and complement binding capacity. Preformed donor-specific antibodies in sensitized patients can trigger hyperacute rejection, accelerated acute rejection, and early acute antibody-mediated rejection. De novo donor-specific antibodies are associated with late acute antibody-mediated rejection, chronic antibody-mediated rejection, and transplant glomerulopathy. The pathogeneses of antibody-mediated rejection include not only complement-dependent cytotoxicity, but also complement-independent pathways of antibody-mediated cellular cytotoxicity and direct endothelial activation and proliferation. The novel assay for complement binding capacity has improved our ability to predict antibody-mediated rejection phenotypes. C1q binding donor-specific antibodies are closely associated with acute antibody-mediated rejection, more severe graft injuries, and early graft failure, whereas C1q nonbinding donor-specific antibodies correlate with subclinical or chronic antibody-mediated rejection and late graft loss. IgG subclasses have various abilities to activate complement and recruit effector cells through the Fc receptor. Complement binding IgG3 donor-specific antibodies are frequently associated with acute antibody-mediated rejection and severe graft injury, whereas noncomplement binding IgG4 donor-specific antibodies are more correlated with subclinical or chronic antibody-mediated rejection and transplant glomerulopathy. Our in-depth knowledge of complex characteristics of donor-specific antibodies can stratify the patient’s immunologic risk, can predict distinct phenotypes of antibody-mediated rejection, and hopefully, will guide our clinical practice to improve the transplant outcomes.Zhang, Rubin2017-04-26T05:40:18-07:00doi:10.2215/CJN.00700117hwp:resource-id:clinjasn;13/1/182American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydonor specific antibody, antibody-mediated rejection, C1q-binding DSA, IgG subclasses, Biomarkers, Complement System Proteins, Humans, Immunoglobulin G, kidney transplantation, Phenotype, Receptors, Fc, Tissue DonorsReviewReviewreview-article20182018-01-06January 06, 201810.2215/CJN.007001171555-90411555-905X2017-04-26T05:40:18-07:002018-01-06Clinical Journal of the American Society of NephrologyReview131182192
- Re-Establishing Brain Networks in Patients with ESRD after Successful Kidney Transplantation10.2215/CJN.00420117Wed, 18 Oct 2017 06:20:26 GMT-07:00Re-Establishing Brain Networks in Patients with ESRD after Successful Kidney TransplantationChen, Hui JuanWen, JiqiuQi, RongfengZhong, JianhuiSchoepf, U. JosephVarga-Szemes, AkosLesslie, Virginia W.Kong, XiangWang, Yun FeiXu, QiangZhang, ZheLi, XueLu, Guang MingZhang, Long Jiang2017-10-18T06:20:26-07:00doi:10.2215/CJN.00420117hwp:resource-id:clinjasn;13/1/109American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, kidney transplantation, Healthy Volunteers, Magnetic Resonance Imaging, Brain, Attention, Cognition, Kidney Failure, ChronicOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-01-06January 06, 201810.2215/CJN.004201171555-90411555-905X2017-10-18T06:20:26-07:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles13141171091107211721072
- Characteristics and Performance of Unilateral Kidney Transplants from Deceased Donors10.2215/CJN.06550617Thu, 07 Dec 2017 04:50:14 GMT-08:00Characteristics and Performance of Unilateral Kidney Transplants from Deceased DonorsHusain, Syed AliChiles, Mariana C.Lee, SamnangPastan, Stephen O.Patzer, Rachel E.Tanriover, BekirRatner, Lloyd E.Mohan, Sumit2017-12-07T04:50:14-08:00doi:10.2215/CJN.06550617hwp:resource-id:clinjasn;13/1/118American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycadaver organ transplantation, clinical epidemiology, transplant outcomes, United States, creatinine, Survival Rate, kidney transplantation, Life Tables, Retrospective Studies, Allografts, Tissue Donors, kidney, Death, Hepatitis C, hypertension, diabetes mellitus, Stroke, Biopsy, Centers for Disease Control and Prevention (U.S.)Original ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20182018-01-06January 06, 201810.2215/CJN.065506171555-90411555-905X2017-12-07T04:50:14-08:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles13111181312715
- Dysproteinemias and Glomerular DiseaseDysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein–related kidney diseases.10.2215/CJN.00560117Tue, 07 Nov 2017 08:42:20 GMT-08:00Dysproteinemias and Glomerular DiseaseDysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein–related kidney diseases.Leung, NelsonDrosou, Maria E.Nasr, Samih H.2017-11-07T08:42:20-08:00doi:10.2215/CJN.00560117hwp:resource-id:clinjasn;13/1/128American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydysproteinemia, MGRS, monoclonal gammopathy, glomerular disease, kidney, cytokines, Kidney Glomerulus, Kidney Diseases, Paraproteinemias, Thrombotic Microangiopathies, glomerulonephritis, Immunoglobulins, Amyloidosis, B-LymphocytesGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20182018-01-06January 06, 201810.2215/CJN.005601171555-90411555-905X2017-11-07T08:42:20-08:002018-01-06Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician131128139
- Predicting Outcome in Patients with Anti-GBM Glomerulonephritis10.2215/CJN.04290417Tue, 21 Nov 2017 06:12:49 GMT-08:00Predicting Outcome in Patients with Anti-GBM Glomerulonephritisvan Daalen, Emma E.Jennette, J. CharlesMcAdoo, Stephen P.Pusey, Charles D.Alba, Marco A.Poulton, Caroline J.Wolterbeek, RonNguyen, Tri Q.Goldschmeding, RoelAlchi, BassamGriffiths, Merylde Zoysa, Janak R.Vincent, BeulaBruijn, Jan A.Bajema, Ingeborg M.2017-11-21T06:12:49-08:00doi:10.2215/CJN.04290417hwp:resource-id:clinjasn;13/1/63American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanti-GBM disease, Goodpasture-s syndrome, kidney biopsy, ANCA, Antibodies, Antineutrophil Cytoplasmic, Retrospective Studies, Multivariate Analysis, Confidence Intervals, Survival Rate, Follow-Up Studies, Glomerular Basement Membrane, glomerulonephritis, antiglomerular basement membrane antibody, kidney, Autoantibodies, Biopsy, Regression Analysis, Kidney Failure, Chronic, renal dialysisOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20182018-01-06January 06, 201810.2215/CJN.042904171555-90411555-905X2017-11-21T06:12:49-08:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1311631722
- Hyperkalemia across the Continuum of Kidney Function10.2215/CJN.09340817Tue, 07 Nov 2017 08:42:21 GMT-08:00Hyperkalemia across the Continuum of Kidney FunctionPalmer, Biff F.Clegg, Deborah J.2017-11-07T08:42:21-08:00doi:10.2215/CJN.09340817hwp:resource-id:clinjasn;13/1/155American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, acute kidney injury, chronic kidney disease, transplant, hemodialysis, peritoneal dialysis, Male, Humans, renal dialysis, Renin, aldosterone, Angiotensins, Diabetes Mellitus, Type 2, kidney transplantation, Kidney Failure, Chronic, Renal Insufficiency, Chronic, hypertension, SepsisKidney Case Conference: Attending RoundsKidney Case Conference: Attending Roundsresearch-article20182018-01-06January 06, 201810.2215/CJN.093408171555-90411555-905X2017-11-07T08:42:21-08:002018-01-06Clinical Journal of the American Society of NephrologyKidney Case Conference: Attending Rounds131155157
- Prognosis of Patients with Cirrhosis and AKI Who Initiate RRT10.2215/CJN.03610417Thu, 09 Nov 2017 09:01:12 GMT-08:00Prognosis of Patients with Cirrhosis and AKI Who Initiate RRTAllegretti, Andrew S.Parada, Xavier VelaEneanya, Nwamaka D.Gilligan, HannahXu, DihuaZhao, SophiaDienstag, Jules L.Chung, Raymond T.Thadhani, Ravi I.2017-11-09T09:01:12-08:00doi:10.2215/CJN.03610417hwp:resource-id:clinjasn;13/1/16American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, hemodialysis, hepatorenal syndrome, continuous renal replacement therapy, acute tubular necrosis, transplant-free survival, futility, cirrhosis, liver transplantation, acute kidney injury, renal replacement therapy, Humans, Proportional Hazards Models, Retrospective Studies, Kidney Tubular Necrosis, Acute, Survival Analysis, Liver Cirrhosis, renal dialysis, PrognosisOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20182018-01-06January 06, 201810.2215/CJN.036104171555-90411555-905X2017-11-09T09:01:12-08:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1311625
- CJASN: What’s Behind and What’s Ahead10.2215/CJN.13321117Thu, 21 Dec 2017 10:04:42 GMT-08:00CJASN: What’s Behind and What’s AheadMehrotra, RajnishChonchol, Michelde Boer, Ian2017-12-21T10:04:42-08:00doi:10.2215/CJN.13321117hwp:resource-id:clinjasn;13/1/3American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTranslational Medical Research, nephrology, Peer Review, Publishing, Maintenance, VolunteersEditorialsEditorialseditorial20182018-01-06January 06, 201810.2215/CJN.133211171555-90411555-905X2017-12-21T10:04:42-08:002018-01-06Clinical Journal of the American Society of NephrologyEditorials13113132
- BP Reduction, Kidney Function Decline, and Cardiovascular Events in Patients without CKD10.2215/CJN.05510517Fri, 03 Nov 2017 02:30:09 GMT-07:00BP Reduction, Kidney Function Decline, and Cardiovascular Events in Patients without CKDMagriço, RitaBigotte Vieira, MiguelViegas Dias, CatarinaLeitão, LiaNeves, João Sérgio2017-11-03T14:30:09-07:00doi:10.2215/CJN.05510517hwp:resource-id:clinjasn;13/1/73American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, blood pressure, renal autoregulation, kidney dysfunction, Humans, Incidence, Propensity Score, Follow-Up Studies, Blood Pressure Determination, hypotension, Renal Insufficiency, ChronicOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20182018-01-06January 06, 201810.2215/CJN.055105171555-90411555-905X2017-11-03T14:30:09-07:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles13117398010
- Commentary on Lessons from CKD–Related Genetic Association Studies—Moving Forward10.2215/CJN.12421117Thu, 14 Dec 2017 06:26:35 GMT-08:00Commentary on Lessons from CKD–Related Genetic Association Studies—Moving ForwardKestenbaum, BryanSeliger, Stephen L.2017-12-14T06:26:35-08:00doi:10.2215/CJN.12421117hwp:resource-id:clinjasn;13/1/153American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal Insufficiency, Chronic, Genetic Association StudiesCommentaryCommentaryarticle-commentary20182018-01-06January 06, 201810.2215/CJN.124211171555-90411555-905X2017-12-14T06:26:35-08:002018-01-06Clinical Journal of the American Society of NephrologyCommentary1311153140154152
- Lowering Expectations with Niacin Treatment for CKD-MBD10.2215/CJN.12021017Tue, 05 Dec 2017 08:38:04 GMT-08:00Lowering Expectations with Niacin Treatment for CKD-MBDDrüeke, Tilman B.Massy, Ziad A.2017-12-05T08:38:04-08:00doi:10.2215/CJN.12021017hwp:resource-id:clinjasn;13/1/6American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, mineral metabolism, hyperphosphatemia, phosphate binders, phosphate transport inhibitors, nicotinic acid, niacin, Chronic Kidney Disease-Mineral and Bone Disorder, Probability, Bone Diseases, Metabolic, Renal Insufficiency, ChronicEditorialsEditorialseditorial20182018-01-06January 06, 201810.2215/CJN.120210171555-90411555-905X2017-12-05T08:38:04-08:002018-01-06Clinical Journal of the American Society of NephrologyEditorials1311636844
- Life Expectancy Gains for Patients with ESRD10.2215/CJN.12831117Thu, 14 Dec 2017 06:26:35 GMT-08:00Life Expectancy Gains for Patients with ESRDJohansen, Kirsten L.2017-12-14T06:26:35-08:00doi:10.2215/CJN.12831117hwp:resource-id:clinjasn;13/1/11American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhumans, United States, Nephrology, renal dialysis, life expectancy, allografts, drug labeling, glomerular filtration rate, survival analysis, renal replacement therapy, peritoneal dialysis, proportional hazards models, referral and consultation, Centers for Disease Control and Prevention (U.S.), fistula, kidney failure, chronic, hospitalization, neoplasms, hemoglobinsEditorialsEditorialseditorial20182018-01-06January 06, 201810.2215/CJN.128311171555-90411555-905X2017-12-14T06:26:35-08:002018-01-06Clinical Journal of the American Society of NephrologyEditorials131111911299
- Compelling Evidence of the Need for Policy Change to Decrease Deceased Donor Kidney Discard in the United States10.2215/CJN.12671117Thu, 07 Dec 2017 04:50:14 GMT-08:00Compelling Evidence of the Need for Policy Change to Decrease Deceased Donor Kidney Discard in the United StatesKadatz, MatthewGill, John S.2017-12-07T04:50:14-08:00doi:10.2215/CJN.12671117hwp:resource-id:clinjasn;13/1/13American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyorgan transplant, transplantation, kidney transplantationEditorialsEditorialseditorial20182018-01-06January 06, 201810.2215/CJN.126711171555-90411555-905X2017-12-07T04:50:14-08:002018-01-06Clinical Journal of the American Society of NephrologyEditorials13111311815127
- Changes in Excess Mortality from End Stage Renal Disease in the United States from 1995 to 201310.2215/CJN.04330417Thu, 14 Dec 2017 06:26:35 GMT-08:00Changes in Excess Mortality from End Stage Renal Disease in the United States from 1995 to 2013Foster, Bethany J.Mitsnefes, Mark M.Dahhou, MouradZhang, XunLaskin, Benjamin L.2017-12-14T06:26:35-08:00doi:10.2215/CJN.04330417hwp:resource-id:clinjasn;13/1/91American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Child, United States, Humans, kidney transplantation, Confidence Intervals, Renal Replacement Therapy, Kidney Failure, Chronic, Risk, kidney, Centers for Disease Control and Prevention (U.S.), renal dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-01-06January 06, 201810.2215/CJN.043304171555-90411555-905X2017-12-14T06:26:35-08:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles131191119912
- A Discrete Choice Study of Patient Preferences for Dialysis Modalities10.2215/CJN.06830617Thu, 19 Oct 2017 06:59:54 GMT-07:00A Discrete Choice Study of Patient Preferences for Dialysis ModalitiesWalker, Rachael C.Morton, Rachael L.Palmer, Suetonia C.Marshall, Mark R.Tong, AllisonHoward, Kirsten2017-10-19T06:59:54-07:00doi:10.2215/CJN.06830617hwp:resource-id:clinjasn;13/1/100American Society of NephrologyCopyright © 2018 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, chronic kidney disease, chronic kidney failure, dialysis, end stage kidney disease, hemodialysis, peritoneal dialysis, Adult, Humans, Patient Preference, renal dialysis, Life Expectancy, Odds Ratio, Confidence Intervals, Health Expenditures, Prospective Studies, Choice Behavior, Renal Insufficiency, Chronic, Surveys and QuestionnairesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20182018-01-06January 06, 201810.2215/CJN.068306171555-90411555-905X2017-10-19T06:59:54-07:002018-01-06Clinical Journal of the American Society of NephrologyOriginal Articles131110011082
- Precision Transplant Medicine: Biomarkers to the RescueThe concept that individuals with the same disease and a similar clinical presentation may have very different outcomes and need very different therapies is not novel. With the development of many innovative tools derived from the omics technologies, transplant medicine is slowly entering the era of precision medicine. Biomarkers are the cornerstone of precision medicine, which aims to integrate biomarkers with traditional clinical information and tailor medical care to achieve the best outcome for an individual patient. Here, we discuss the basic concepts of precision medicine and biomarkers, with a specific focus on progress in renal transplantation. We delineate the different types of biomarkers and provide a general assessment of the current applications and shortcomings of previously proposed biomarkers. We also outline the potential of precision medicine in transplantation. Moving toward precision medicine in the field of transplantation will require transplant physicians to embrace the increased complexity and expanded decision algorithms and therapeutic options that are associated with improved disease nosology.10.1681/ASN.2017010004Mon, 09 Oct 2017 10:43:42 GMT-07:00Precision Transplant Medicine: Biomarkers to the RescueThe concept that individuals with the same disease and a similar clinical presentation may have very different outcomes and need very different therapies is not novel. With the development of many innovative tools derived from the omics technologies, transplant medicine is slowly entering the era of precision medicine. Biomarkers are the cornerstone of precision medicine, which aims to integrate biomarkers with traditional clinical information and tailor medical care to achieve the best outcome for an individual patient. Here, we discuss the basic concepts of precision medicine and biomarkers, with a specific focus on progress in renal transplantation. We delineate the different types of biomarkers and provide a general assessment of the current applications and shortcomings of previously proposed biomarkers. We also outline the potential of precision medicine in transplantation. Moving toward precision medicine in the field of transplantation will require transplant physicians to embrace the increased complexity and expanded decision algorithms and therapeutic options that are associated with improved disease nosology.Naesens, MaartenAnglicheau, Dany2017-10-09T10:43:42-07:00doi:10.1681/ASN.2017010004hwp:resource-id:jnephrol;29/1/24American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant outcomes, acute rejection, chronic allograft failure, chronic graft deteriorationUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-01-01January 201810.1681/ASN.20170100041046-66731533-34502017-10-09T10:43:42-07:002018-01Journal of the American Society of NephrologyUp Front Matters2912434
- Aldosterone Is Essential for Angiotensin II-Induced Upregulation of PendrinThe renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl−/HCO3− exchanger pendrin in β-intercalated cells and the Na+-Cl− cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin and NCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and wild-type mice. A low-salt diet or AngII infusion upregulated NCC and pendrin levels, decreased the phosphorylation of mineralocorticoid receptor in β-intercalated cells, and increased plasma aldosterone levels. Notably, a low-salt diet did not alter BP in wild-type mice, but significantly decreased BP in pendrin-knockout mice. To dissect the roles of AngII and aldosterone, we performed adrenalectomies in mice to remove aldosterone from the circulation. In adrenalectomized mice, AngII infusion again upregulated NCC expression, but did not affect pendrin expression despite the decreased phosphorylation of mineralocorticoid receptor. By contrast, AngII and aldosterone coadministration markedly elevated pendrin levels in adrenalectomized mice. Our results indicate that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest that pendrin contributes to the maintenance of normal BP in cooperation with NCC during activation of the renin-angiotensin-aldosterone system by dietary salt restriction.10.1681/ASN.2017030243Wed, 11 Oct 2017 08:23:23 GMT-07:00Aldosterone Is Essential for Angiotensin II-Induced Upregulation of PendrinThe renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl−/HCO3− exchanger pendrin in β-intercalated cells and the Na+-Cl− cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin and NCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and wild-type mice. A low-salt diet or AngII infusion upregulated NCC and pendrin levels, decreased the phosphorylation of mineralocorticoid receptor in β-intercalated cells, and increased plasma aldosterone levels. Notably, a low-salt diet did not alter BP in wild-type mice, but significantly decreased BP in pendrin-knockout mice. To dissect the roles of AngII and aldosterone, we performed adrenalectomies in mice to remove aldosterone from the circulation. In adrenalectomized mice, AngII infusion again upregulated NCC expression, but did not affect pendrin expression despite the decreased phosphorylation of mineralocorticoid receptor. By contrast, AngII and aldosterone coadministration markedly elevated pendrin levels in adrenalectomized mice. Our results indicate that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest that pendrin contributes to the maintenance of normal BP in cooperation with NCC during activation of the renin-angiotensin-aldosterone system by dietary salt restriction.Hirohama, DaigoroAyuzawa, NobuhiroUeda, KoheiNishimoto, MitsuhiroKawarazaki, WakakoWatanabe, AtsushiShimosawa, TatsuoMarumo, TakeshiShibata, ShigeruFujita, Toshiro2017-10-11T08:23:23-07:00doi:10.1681/ASN.2017030243hwp:resource-id:jnephrol;29/1/57American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyaldosterone, angiotensin, Na transportBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170302431046-66731533-34502017-10-11T08:23:23-07:002018-01Journal of the American Society of NephrologyBasic Research2915768
- Impaired β-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKDStudies of lipids in CKD, including ESRD, have been limited to measures of conventional lipid profiles. We aimed to systematically identify 17 different lipid classes and associate the abundance thereof with alterations in acylcarnitines, a metric of β-oxidation, across stages of CKD. From the Clinical Phenotyping Resource and Biobank Core (CPROBE) cohort of 1235 adults, we selected a panel of 214 participants: 36 with stage 1 or 2 CKD, 99 with stage 3 CKD, 61 with stage 4 CKD, and 18 with stage 5 CKD. Among participants, 110 were men (51.4%), 64 were black (29.9%), and 150 were white (70.1%), and the mean (SD) age was 60 (16) years old. We measured plasma lipids and acylcarnitines using liquid chromatography-mass spectrometry. Overall, we identified 330 different lipids across 17 different classes. Compared with earlier stages, stage 5 CKD associated with a higher abundance of saturated C16–C20 free fatty acids (FFAs) and long polyunsaturated complex lipids. Long-chain–to–intermediate-chain acylcarnitine ratio, a marker of efficiency of β-oxidation, exhibited a graded decrease from stage 2 to 5 CKD (P<0.001). Additionally, multiple linear regression revealed that the long-chain–to–intermediate-chain acylcarnitine ratio inversely associated with polyunsaturated long complex lipid subclasses and the C16–C20 FFAs but directly associated with short complex lipids with fewer double bonds. We conclude that increased abundance of saturated C16–C20 FFAs coupled with impaired β-oxidation of FFAs and inverse partitioning into complex lipids may be mechanisms underpinning lipid metabolism changes that typify advancing CKD.10.1681/ASN.2017030350Wed, 11 Oct 2017 08:23:22 GMT-07:00Impaired β-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKDStudies of lipids in CKD, including ESRD, have been limited to measures of conventional lipid profiles. We aimed to systematically identify 17 different lipid classes and associate the abundance thereof with alterations in acylcarnitines, a metric of β-oxidation, across stages of CKD. From the Clinical Phenotyping Resource and Biobank Core (CPROBE) cohort of 1235 adults, we selected a panel of 214 participants: 36 with stage 1 or 2 CKD, 99 with stage 3 CKD, 61 with stage 4 CKD, and 18 with stage 5 CKD. Among participants, 110 were men (51.4%), 64 were black (29.9%), and 150 were white (70.1%), and the mean (SD) age was 60 (16) years old. We measured plasma lipids and acylcarnitines using liquid chromatography-mass spectrometry. Overall, we identified 330 different lipids across 17 different classes. Compared with earlier stages, stage 5 CKD associated with a higher abundance of saturated C16–C20 free fatty acids (FFAs) and long polyunsaturated complex lipids. Long-chain–to–intermediate-chain acylcarnitine ratio, a marker of efficiency of β-oxidation, exhibited a graded decrease from stage 2 to 5 CKD (P<0.001). Additionally, multiple linear regression revealed that the long-chain–to–intermediate-chain acylcarnitine ratio inversely associated with polyunsaturated long complex lipid subclasses and the C16–C20 FFAs but directly associated with short complex lipids with fewer double bonds. We conclude that increased abundance of saturated C16–C20 FFAs coupled with impaired β-oxidation of FFAs and inverse partitioning into complex lipids may be mechanisms underpinning lipid metabolism changes that typify advancing CKD.Afshinnia, FarsadRajendiran, Thekkelnaycke M.Soni, TanuByun, JaemanWernisch, StefanieSas, Kelli M.Hawkins, JenniferBellovich, KeithGipson, DebbieMichailidis, GeorgePennathur, Subramaniam,Kretzler, MatthiasBhat, ZeenatGadegbeku, CrystalMassengill, SusanPerumal, Kalyani2017-10-11T08:23:22-07:00doi:10.1681/ASN.2017030350hwp:resource-id:jnephrol;29/1/295American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologylipids, chronic kidney disease, Acylcarnitines, Free fatty acids, complex lipidsClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170303501046-66731533-34502017-10-11T08:23:22-07:002018-01Journal of the American Society of NephrologyClinical Research291295306
- Renal Dendritic Cells: The Long and Winding Road10.1681/ASN.2017101145Mon, 11 Dec 2017 05:06:45 GMT-08:00Renal Dendritic Cells: The Long and Winding RoadKitching, A. RichardOoi, Joshua D.2017-12-11T05:06:45-08:00doi:10.1681/ASN.2017101145hwp:resource-id:jnephrol;29/1/4American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, immunology, transgenic mouse, dendritic cells, macrophagesUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-01-01January 201810.1681/ASN.20171011451046-66731533-34502017-12-11T05:06:45-08:002018-01Journal of the American Society of NephrologyUp Front Matters291141387154
- Kidney Proximal Tubule Lipoapoptosis Is Regulated by Fatty Acid Transporter-2 (FATP2)Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface. Protein and mRNA expression analyses revealed that kidney proximal tubules express transmembrane fatty acid transporter-2 (FATP2), encoded by Slc27a2, but not the other candidate transporters CD36 and free fatty acid receptor 1. Kidney FATP2 localized exclusively to proximal tubule epithelial cells along the apical but not the basolateral membrane. Treatment of mice with lipidated albumin to induce proteinuria caused a decrease in the proportion of tubular epithelial cells and an increase in the proportion of interstitial space in kidneys from wild-type but not Slc27a2−/−mice. Ex vivo microperfusion and in vitro experiments with NEFA-bound albumin at concentrations that mimic apical proximal tubule exposure during glomerular injury revealed significantly reduced NEFA uptake and palmitate-induced apoptosis in microperfused Slc27a2−/− proximal tubules and Slc27a2−/− or FATP2 shRNA-treated proximal tubule cell lines compared with wild-type or scrambled oligonucleotide–treated cells, respectively. We conclude that FATP2 is a major apical proximal tubule NEFA transporter that regulates lipoapoptosis and may be an amenable target for the prevention of CKD progression.10.1681/ASN.2017030314Mon, 09 Oct 2017 10:43:43 GMT-07:00Kidney Proximal Tubule Lipoapoptosis Is Regulated by Fatty Acid Transporter-2 (FATP2)Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface. Protein and mRNA expression analyses revealed that kidney proximal tubules express transmembrane fatty acid transporter-2 (FATP2), encoded by Slc27a2, but not the other candidate transporters CD36 and free fatty acid receptor 1. Kidney FATP2 localized exclusively to proximal tubule epithelial cells along the apical but not the basolateral membrane. Treatment of mice with lipidated albumin to induce proteinuria caused a decrease in the proportion of tubular epithelial cells and an increase in the proportion of interstitial space in kidneys from wild-type but not Slc27a2−/−mice. Ex vivo microperfusion and in vitro experiments with NEFA-bound albumin at concentrations that mimic apical proximal tubule exposure during glomerular injury revealed significantly reduced NEFA uptake and palmitate-induced apoptosis in microperfused Slc27a2−/− proximal tubules and Slc27a2−/− or FATP2 shRNA-treated proximal tubule cell lines compared with wild-type or scrambled oligonucleotide–treated cells, respectively. We conclude that FATP2 is a major apical proximal tubule NEFA transporter that regulates lipoapoptosis and may be an amenable target for the prevention of CKD progression.Khan, ShenazCabral, Pablo D.Schilling, William P.Schmidt, Zachary W.Uddin, Asif N.Gingras, AmeliaMadhavan, Sethu M.Garvin, Jeffrey L.Schelling, Jeffrey R.2017-10-09T10:43:43-07:00doi:10.1681/ASN.2017030314hwp:resource-id:jnephrol;29/1/81American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyapoptosis, cell survival, epithelial, lipids, proximal tubule, albuminuriaBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170303141046-66731533-34502017-10-09T10:43:43-07:002018-01Journal of the American Society of NephrologyBasic Research2918191
- Effects of Two Immunosuppressive Treatment Protocols for IgA NephropathyThe role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2: 6-month corticosteroid monotherapy; GFR=30–59 ml/min per 1.73 m2: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m2 during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m2 did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.10.1681/ASN.2017060713Tue, 17 Oct 2017 06:48:31 GMT-07:00Effects of Two Immunosuppressive Treatment Protocols for IgA NephropathyThe role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2: 6-month corticosteroid monotherapy; GFR=30–59 ml/min per 1.73 m2: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m2 during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m2 did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.Rauen, ThomasFitzner, ChristinaEitner, FrankSommerer, ClaudiaZeier, MartinOtte, BrittaPanzer, UlfPeters, HarmBenck, UrsMertens, Peter R.Kuhlmann, UweWitzke, OliverGross, OliverVielhauer, VolkerMann, Johannes F.E.Hilgers, Ralf-DieterFloege, Jürgen2017-10-17T06:48:31-07:00doi:10.1681/ASN.2017060713hwp:resource-id:jnephrol;29/1/317American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, glomerular disease, glomerulonephritis, immunosuppressionClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170607131046-66731533-34502017-10-17T06:48:31-07:002018-01Journal of the American Society of NephrologyClinical Research291317325
- Glomerular Disease Pathology in the Era of Proteomics: From Pattern to Pathogenesis10.1681/ASN.2017080881Thu, 02 Nov 2017 02:30:09 GMT-07:00Glomerular Disease Pathology in the Era of Proteomics: From Pattern to PathogenesisHaas, Mark2017-11-02T14:30:09-07:00doi:10.1681/ASN.2017080881hwp:resource-id:jnephrol;29/1/2American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, Immunology and pathology, renal biopsyUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-01-01January 201810.1681/ASN.20170808811046-66731533-34502017-11-02T14:30:09-07:002018-01Journal of the American Society of NephrologyUp Front Matters29111251231456239
- Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver DiseasesData indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although genetics is only infrequently used for diagnosing these diseases and prognosing the associated outcomes, its value is beginning to be appreciated, and the genomics revolution promises more reliable and less expensive molecular diagnostic tools for these diseases. We therefore propose categorization of patients with a phenotypic and genotypic descriptor that will clarify etiology, provide prognostic information, and better describe atypical cases. In genetically defined cases, the designation would include the disease and gene names, with allelic (truncating/nontruncating) information included for PKD1. Recent data have shown that biallelic disease including at least one weak ADPKD allele is a significant cause of symptomatic, very early onset ADPKD. Including a genic (and allelic) descriptor with the disease name will provide outcome clues, guide treatment, and aid prevalence estimates.10.1681/ASN.2017050483Mon, 16 Oct 2017 07:40:31 GMT-07:00Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver DiseasesData indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although genetics is only infrequently used for diagnosing these diseases and prognosing the associated outcomes, its value is beginning to be appreciated, and the genomics revolution promises more reliable and less expensive molecular diagnostic tools for these diseases. We therefore propose categorization of patients with a phenotypic and genotypic descriptor that will clarify etiology, provide prognostic information, and better describe atypical cases. In genetically defined cases, the designation would include the disease and gene names, with allelic (truncating/nontruncating) information included for PKD1. Recent data have shown that biallelic disease including at least one weak ADPKD allele is a significant cause of symptomatic, very early onset ADPKD. Including a genic (and allelic) descriptor with the disease name will provide outcome clues, guide treatment, and aid prevalence estimates.Cornec-Le Gall, EmilieTorres, Vicente E.Harris, Peter C.2017-10-16T07:40:31-07:00doi:10.1681/ASN.2017050483hwp:resource-id:jnephrol;29/1/13American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, cystic kidney, liver cysts, polycystic kidney diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-01-01January 201810.1681/ASN.20170504831046-66731533-34502017-10-16T07:40:31-07:002018-01Journal of the American Society of NephrologyUp Front Matters2911323
- Opposing Roles of Dendritic Cell Subsets in Experimental GNDendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c+ cells forming a network throughout the renal interstitium expressed macrophage-specific markers. In contrast, DCs marked by Zbtb46-GFP or Snx22-GFP were less abundant, concentrated around blood vessels, and round in shape. We confirmed this pattern of localization using imaging mass cytometry. Motility measurements showed that resident macrophages were sessile, whereas DCs were motile before and after inflammation. Although uninflamed glomeruli rarely contained DCs, injury with nephrotoxic antibodies resulted in accumulation of ZBTB46+ cells in the periglomerular region. ZBTB46 identifies all classic DCs, which can be categorized into two functional subsets that express either CD103 or CD11b. Depletion of ZBTB46+ cells attenuated the antibody-induced kidney injury, whereas deficiency of the CD103+ subset accelerated injury through a mechanism that involved increased neutrophil infiltration. RNA sequencing 7 days after nephrotoxic antibody injection showed that CD11b+ DCs expressed the neutrophil-attracting cytokine CXCL2, whereas CD103+ DCs expressed high levels of several anti-inflammatory genes. These results provide new insights into the distinct functions of the two major DC subsets in glomerular inflammation.10.1681/ASN.2017030270Thu, 07 Dec 2017 04:50:48 GMT-08:00Opposing Roles of Dendritic Cell Subsets in Experimental GNDendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton microscopy of kidney sections confirmed that most of the dendritically shaped CD11c+ cells forming a network throughout the renal interstitium expressed macrophage-specific markers. In contrast, DCs marked by Zbtb46-GFP or Snx22-GFP were less abundant, concentrated around blood vessels, and round in shape. We confirmed this pattern of localization using imaging mass cytometry. Motility measurements showed that resident macrophages were sessile, whereas DCs were motile before and after inflammation. Although uninflamed glomeruli rarely contained DCs, injury with nephrotoxic antibodies resulted in accumulation of ZBTB46+ cells in the periglomerular region. ZBTB46 identifies all classic DCs, which can be categorized into two functional subsets that express either CD103 or CD11b. Depletion of ZBTB46+ cells attenuated the antibody-induced kidney injury, whereas deficiency of the CD103+ subset accelerated injury through a mechanism that involved increased neutrophil infiltration. RNA sequencing 7 days after nephrotoxic antibody injection showed that CD11b+ DCs expressed the neutrophil-attracting cytokine CXCL2, whereas CD103+ DCs expressed high levels of several anti-inflammatory genes. These results provide new insights into the distinct functions of the two major DC subsets in glomerular inflammation.Brähler, SebastianZinselmeyer, Bernd H.Raju, SaravananNitschke, MaximilianSuleiman, HaniSaunders, Brian T.Johnson, Michael W.Böhner, Alexander M.C.Viehmann, Susanne F.Theisen, Derek J.Kretzer, Nicole M.Briseño, Carlos G.Zaitsev, KonstantinOrnatsky, OlgaChang, QingCarrero, Javier A.Kopp, Jeffrey B.Artyomov, Maxim N.Kurts, ChristianMurphy, Kenneth M.Miner, Jeffrey H.Shaw, Andrey S.2017-12-07T04:50:48-08:00doi:10.1681/ASN.2017030270hwp:resource-id:jnephrol;29/1/138American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, glomerulonephritis, glomerular diseaseBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170302701046-66731533-34502017-12-07T04:50:48-08:002018-01Journal of the American Society of NephrologyBasic Research291113841547
- ShcA Adaptor Protein Promotes Nephrin Endocytosis and Is Upregulated in Proteinuric NephropathiesNephrin is a key structural component of the podocyte slit diaphragm, and proper expression of nephrin on the cell surface is critical to ensure integrity of the blood filtration barrier. Maintenance of nephrin within this unique cell junction has been proposed to require dynamic phosphorylation events and endocytic recycling, although the molecular mechanisms that control this interplay are poorly understood. Here, we investigated the possibility that the phosphotyrosine adaptor protein ShcA regulates nephrin turnover. Western blotting and immunostaining analysis confirmed that ShcA is expressed in podocytes. In immunoprecipitation and pulldown assays, ShcA, via its SH2 domain, was associated with several phosphorylated tyrosine residues on nephrin. Overexpression of ShcA promoted nephrin tyrosine phosphorylation and reduced nephrin signaling and cell surface expression in vitro. In a rat model of reversible podocyte injury and proteinuria, phosphorylated nephrin temporally colocalized with endocytic structures coincident with upregulation of ShcA expression. In vivo biotinylation assays confirmed that nephrin expression decreased at the cell surface and correspondingly increased in the cytosol during the injury time course. Finally, immunostaining in kidney biopsy specimens demonstrated overexpression of ShcA in several human proteinuric kidney diseases compared with normal conditions. Our results suggest that increases in ShcA perturb nephrin phosphosignaling dynamics, leading to aberrant nephrin turnover and slit diaphragm disassembly.10.1681/ASN.2017030285Tue, 10 Oct 2017 07:56:49 GMT-07:00ShcA Adaptor Protein Promotes Nephrin Endocytosis and Is Upregulated in Proteinuric NephropathiesNephrin is a key structural component of the podocyte slit diaphragm, and proper expression of nephrin on the cell surface is critical to ensure integrity of the blood filtration barrier. Maintenance of nephrin within this unique cell junction has been proposed to require dynamic phosphorylation events and endocytic recycling, although the molecular mechanisms that control this interplay are poorly understood. Here, we investigated the possibility that the phosphotyrosine adaptor protein ShcA regulates nephrin turnover. Western blotting and immunostaining analysis confirmed that ShcA is expressed in podocytes. In immunoprecipitation and pulldown assays, ShcA, via its SH2 domain, was associated with several phosphorylated tyrosine residues on nephrin. Overexpression of ShcA promoted nephrin tyrosine phosphorylation and reduced nephrin signaling and cell surface expression in vitro. In a rat model of reversible podocyte injury and proteinuria, phosphorylated nephrin temporally colocalized with endocytic structures coincident with upregulation of ShcA expression. In vivo biotinylation assays confirmed that nephrin expression decreased at the cell surface and correspondingly increased in the cytosol during the injury time course. Finally, immunostaining in kidney biopsy specimens demonstrated overexpression of ShcA in several human proteinuric kidney diseases compared with normal conditions. Our results suggest that increases in ShcA perturb nephrin phosphosignaling dynamics, leading to aberrant nephrin turnover and slit diaphragm disassembly.Martin, Claire E.Petersen, Kelly A.Aoudjit, LamineTilak, ManaliEremina, VeraHardy, W. RodQuaggin, Susan E.Takano, TomokoJones, Nina2017-10-10T07:56:49-07:00doi:10.1681/ASN.2017030285hwp:resource-id:jnephrol;29/1/92American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologynephrin, endocytosis, kidney disease, signaling, podocyteBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170302851046-66731533-34502017-10-10T07:56:49-07:002018-01Journal of the American Society of NephrologyBasic Research29192103
- Wnt/β-Catenin–Promoted Macrophage Alternative Activation Contributes to Kidney FibrosisThe Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4– or TGFβ1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro. Conversely, inhibition of Wnt/β-catenin signaling prevented these IL-4– or TGFβ1-induced processes. In a mouse model, induced deletion of β-catenin in macrophages attenuated the fibrosis, macrophage accumulation, and M2 polarization observed in the kidneys of wild-type littermates after unilateral ureter obstruction. This study shows that activation of Wnt/β-catenin signaling promotes kidney fibrosis by stimulating macrophage M2 polarization.10.1681/ASN.2017040391Wed, 11 Oct 2017 08:23:21 GMT-07:00Wnt/β-Catenin–Promoted Macrophage Alternative Activation Contributes to Kidney FibrosisThe Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4– or TGFβ1-induced macrophage alternative (M2) polarization and the phosphorylation and nuclear translocation of STAT3 in vitro. Conversely, inhibition of Wnt/β-catenin signaling prevented these IL-4– or TGFβ1-induced processes. In a mouse model, induced deletion of β-catenin in macrophages attenuated the fibrosis, macrophage accumulation, and M2 polarization observed in the kidneys of wild-type littermates after unilateral ureter obstruction. This study shows that activation of Wnt/β-catenin signaling promotes kidney fibrosis by stimulating macrophage M2 polarization.Feng, YeRen, JiafaGui, YuanWei, WeiShu, BingyanLu, QingmiaoXue, XianSun, XiaoliHe, WeichunYang, JunweiDai, Chunsun2017-10-11T08:23:21-07:00doi:10.1681/ASN.2017040391hwp:resource-id:jnephrol;29/1/182American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyWnt/β-catenin, kidney fibrosis, macrophagesBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170403911046-66731533-34502017-10-11T08:23:21-07:002018-01Journal of the American Society of NephrologyBasic Research291182193
- DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GNFibrillary GN (FGN) is a rare primary glomerular disease. Histologic and histochemical features of FGN overlap with those of other glomerular diseases, and no unique histologic biomarkers for diagnosing FGN have been identified. We analyzed the proteomic content of glomeruli in patient biopsy specimens and detected DnaJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. Compared with amyloidosis glomeruli, FGN glomeruli exhibited a >6-fold overexpression of DNAJB9 protein. Sanger sequencing and protein sequence coverage maps showed that the DNAJB9 protein deposited in FGN glomeruli did not have any major sequence or structural alterations. Notably, we detected DNAJB9 in all patients with FGN but not in healthy glomeruli or in 19 types of non-FGN glomerular diseases. We also observed the codeposition of DNAJB9 and Ig-γ. Overall, these findings indicate that DNAJB9 is an FGN marker with 100% sensitivity and 100% specificity. The magnitude and specificity of DNAJB9 overabundance in FGN also suggests that this protein has a role in FGN pathogenesis. With this evidence, we propose that DNAJB9 is a strong biomarker for rapid diagnosis of FGN in renal biopsy specimens.10.1681/ASN.2017030306Thu, 02 Nov 2017 02:30:09 GMT-07:00DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GNFibrillary GN (FGN) is a rare primary glomerular disease. Histologic and histochemical features of FGN overlap with those of other glomerular diseases, and no unique histologic biomarkers for diagnosing FGN have been identified. We analyzed the proteomic content of glomeruli in patient biopsy specimens and detected DnaJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. Compared with amyloidosis glomeruli, FGN glomeruli exhibited a >6-fold overexpression of DNAJB9 protein. Sanger sequencing and protein sequence coverage maps showed that the DNAJB9 protein deposited in FGN glomeruli did not have any major sequence or structural alterations. Notably, we detected DNAJB9 in all patients with FGN but not in healthy glomeruli or in 19 types of non-FGN glomerular diseases. We also observed the codeposition of DNAJB9 and Ig-γ. Overall, these findings indicate that DNAJB9 is an FGN marker with 100% sensitivity and 100% specificity. The magnitude and specificity of DNAJB9 overabundance in FGN also suggests that this protein has a role in FGN pathogenesis. With this evidence, we propose that DNAJB9 is a strong biomarker for rapid diagnosis of FGN in renal biopsy specimens.Dasari, SurendraAlexander, Mariam P.Vrana, Julie A.Theis, Jason D.Mills, John R.Negron, VivianSethi, SanjeevDispenzieri, AngelaHighsmith, W. EdwardNasr, Samih H.Kurtin, Paul J.2017-11-02T14:30:09-07:00doi:10.1681/ASN.2017030306hwp:resource-id:jnephrol;29/1/51American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyDNAJB9, biomarker, renal, fibrillary GN, proteomics, immunofluorescenceBrief CommunicationBrief Communicationbrief-report20182018-01-01January 201810.1681/ASN.20170303061046-66731533-34502017-11-02T14:30:09-07:002018-01Journal of the American Society of NephrologyBrief Communication2911512564
- Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac SurgeryAKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10–29 versus 6–21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.10.1681/ASN.2016101150Mon, 16 Oct 2017 07:40:30 GMT-07:00Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac SurgeryAKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68). The primary outcome was the time to recovery of kidney function defined as return of postintervention creatinine level to baseline. The median time to recovery of kidney function was 15 days with AC607 and 12 days with placebo (25th, 75th percentile range, 10–29 versus 6–21, respectively; hazard ratio, 0.81; 95% confidence interval, 0.53 to 1.24; P=0.32). We did not detect a significant difference between groups in 30-day all-cause mortality (16.7% with AC607; 11.8% with placebo) or dialysis (10.6% with AC607; 7.4% with placebo). At follow-up, 12 patients who received AC607 and six patients who received placebo had died. Rates of other adverse events did not differ between groups. In these patients with AKI after cardiac surgery, administration of allogeneic MSCs did not decrease the time to recovery of kidney function. Our results contrast with those in preclinical studies and provide important information regarding the potential effects of MSCs in this setting.Swaminathan, MadhavStafford-Smith, MarkChertow, Glenn M.Warnock, David G.Paragamian, VikenBrenner, Robert M.Lellouche, FrançoisFox-Robichaud, AlisonAtta, Mohamed G.Melby, SpencerMehta, Ravindra L.Wald, RonVerma, SubodhMazer, C. David,Swaminathan, MadhavStafford-Smith, MarkLombard, F. WillemSchroder, JacobKurtzberg, JoanneBisnar, TiffanyAtta, MohamedConte, JohnDodd-o, JeffreyRabb, HamidKatz, NevinShah, AshishHuyette-Arrizza, ElizabethMelby, SpencerBellot, ChrisKramer, RobertTolson, BetseySolomon, RichardBrooks, CharlesMora-Mangano, ChristinaWong, JimmyKashani, KianoushNaka, YoshifumiUmanath, KausikYee, JerryKilic, AhmetLecker, StewartFrendl, GyorgyMackensen, BurkhardChertow, Glenn M.Warnock, David G.Paragamian, VikenBrenner, Robert M.Mehta, Ravindra L.Lellouche, FrancoisSimon, MathieuDagenais, FrancoisFerland, Marie-ClaudeBouchard, Pierre-AlexandreFox-Robichaud, AlisonWhitlock, RichardAinsworth, CraigMcDonald, EllenMazer, C. DavidWald, RonVerma, SubodhCurley, GerardYagnik, SanjayCrescini, CharmagneFerland, AndreMaier, KarenDenault, AndreLy, HungBainbridge, DanielBentall, TraceyLegare, Jean-FrancoisGrocott, HilaryLevin, AdeeraUdelson, James E.Fleming, Thomas R.2017-10-16T07:40:30-07:00doi:10.1681/ASN.2016101150hwp:resource-id:jnephrol;29/1/260American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, stem cells, cardiac surgery, cardiopulmonary bypassClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20161011501046-66731533-34502017-10-16T07:40:30-07:002018-01Journal of the American Society of NephrologyClinical Research291126072679
- Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic SyndromeAtypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort (n=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (CFHR1) that originates by recurrent gene conversion events between the CFH and CFHR1 genes. The novel CFHR1 mutants encode an FHR-1 protein with two amino acid substitutions, L290S and A296V, converting the FHR-1 C terminus into that of factor H (FH). Next-generation massive-parallel DNA sequencing (NGS) analysis did not detect these genetic abnormalities. In addition to the CFHR1 mutant, six patients carried the previously uncharacterized CFH-411T variant. In functional analyses, the mutant FHR-1 protein strongly competed the binding of FH to cell surfaces, impairing complement regulation, whereas the CFH-411T polymorphism lacked functional consequences. Carriers of the CFHR1 mutation presented with severe aHUS during adulthood; 57% of affected women in this cohort presented during the postpartum period. Analyses in patients and unaffected carriers showed that FH plasma levels determined by the nonmutated chromosome modulate disease penetrance. Crucially, in the activated endothelial (HMEC-1) cell assay, reduced FH plasma levels produced by the nonmutated chromosome correlated inversely with impairment of complement regulation, measured as C5b-9 deposition. Our data advance understanding of the genetic complexities underlying aHUS, illustrate the importance of performing functional analysis, and support the use of complementary assays to disclose genetic abnormalities not revealed by current NGS analysis.10.1681/ASN.2017050518Mon, 09 Oct 2017 10:43:43 GMT-07:00Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic SyndromeAtypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort (n=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (CFHR1) that originates by recurrent gene conversion events between the CFH and CFHR1 genes. The novel CFHR1 mutants encode an FHR-1 protein with two amino acid substitutions, L290S and A296V, converting the FHR-1 C terminus into that of factor H (FH). Next-generation massive-parallel DNA sequencing (NGS) analysis did not detect these genetic abnormalities. In addition to the CFHR1 mutant, six patients carried the previously uncharacterized CFH-411T variant. In functional analyses, the mutant FHR-1 protein strongly competed the binding of FH to cell surfaces, impairing complement regulation, whereas the CFH-411T polymorphism lacked functional consequences. Carriers of the CFHR1 mutation presented with severe aHUS during adulthood; 57% of affected women in this cohort presented during the postpartum period. Analyses in patients and unaffected carriers showed that FH plasma levels determined by the nonmutated chromosome modulate disease penetrance. Crucially, in the activated endothelial (HMEC-1) cell assay, reduced FH plasma levels produced by the nonmutated chromosome correlated inversely with impairment of complement regulation, measured as C5b-9 deposition. Our data advance understanding of the genetic complexities underlying aHUS, illustrate the importance of performing functional analysis, and support the use of complementary assays to disclose genetic abnormalities not revealed by current NGS analysis.Goicoechea de Jorge, ElenaTortajada, AgustínGarcía, Sheila PintoGastoldi, SaraMerinero, Héctor MartínGarcía-Fernández, JesúsArjona, EmiliaCao, MercedesRemuzzi, GiuseppeNoris, MarinaRodríguez de Córdoba, Santiago2017-10-09T10:43:43-07:00doi:10.1681/ASN.2017050518hwp:resource-id:jnephrol;29/1/240American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, hemolytic uremic syndrome, gene conversion, CFHR1Clinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170505181046-66731533-34502017-10-09T10:43:43-07:002018-01Journal of the American Society of NephrologyClinical Research291240249
- Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A Randomized Clinical TrialCKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2×2 factorial design trial. Of 122 participants consented, 111 were randomized to receive caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Of those randomized, 42% were women, 25% were diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed the 4-month study. Primary outcomes were a change from baseline in absolute fat mass, body weight, plasma F2-isoprostane concentrations, and peak oxygen uptake (VO2 peak). Compared with usual care, the combined intervention led to statistically significant decreases in body weight and body fat percentage. Caloric restriction alone also led to significant decreases in these measures, but aerobic exercise alone did not. The combined intervention and each independent intervention also led to significant decreases in F2-isoprostane and IL-6 concentrations. No intervention produced significant changes in VO2 peak, kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month dietary calorie restriction and aerobic exercise had significant, albeit clinically modest, benefits on body weight, fat mass, and markers of oxidative stress and inflammatory response in patients with moderate to severe CKD. These results suggest healthy lifestyle interventions as a nonpharmacologic strategy to improve markers of metabolic health in these patients.10.1681/ASN.2017010020Mon, 16 Oct 2017 07:40:29 GMT-07:00Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A Randomized Clinical TrialCKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2×2 factorial design trial. Of 122 participants consented, 111 were randomized to receive caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Of those randomized, 42% were women, 25% were diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed the 4-month study. Primary outcomes were a change from baseline in absolute fat mass, body weight, plasma F2-isoprostane concentrations, and peak oxygen uptake (VO2 peak). Compared with usual care, the combined intervention led to statistically significant decreases in body weight and body fat percentage. Caloric restriction alone also led to significant decreases in these measures, but aerobic exercise alone did not. The combined intervention and each independent intervention also led to significant decreases in F2-isoprostane and IL-6 concentrations. No intervention produced significant changes in VO2 peak, kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month dietary calorie restriction and aerobic exercise had significant, albeit clinically modest, benefits on body weight, fat mass, and markers of oxidative stress and inflammatory response in patients with moderate to severe CKD. These results suggest healthy lifestyle interventions as a nonpharmacologic strategy to improve markers of metabolic health in these patients.Ikizler, T. AlpRobinson-Cohen, CassianneEllis, CharlesHeadley, Samuel A.E.Tuttle, KatherineWood, Richard J.Evans, Elizabeth ElspethMilch, Charles M.Moody, Kelsey AnneGermain, MichaelLimkunakul, ChutatipBian, AihuaStewart, Thomas G.Himmelfarb, Jonathan2017-10-16T07:40:29-07:00doi:10.1681/ASN.2017010020hwp:resource-id:jnephrol;29/1/250American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, exercise, metabolism, diet, Chronic inflammation, oxidative stressClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170100201046-66731533-34502017-10-16T07:40:29-07:002018-01Journal of the American Society of NephrologyClinical Research291250259
- Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the KidneyPreconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here, using the kidney as a model organ, we investigated cell type–specific responses to preconditioning. Compared with preadministration of vehicle, endotoxin preconditioning in the cecal ligation and puncture mouse model of sepsis led to significantly enhanced survival and reduced bacterial load in several organs. Furthermore, endotoxin preconditioning reduced serum levels of proinflammatory cytokines, upregulated molecular pathways involved in phagocytosis, and prevented the renal function decline and injury induced in mice by a toxic dose of endotoxin. The protective phenotype involved the clustering of macrophages around S1 segments of proximal tubules, and full renal protection required both macrophages and renal tubular cells. Using unbiased S1 transcriptomic and tissue metabolomic approaches, we identified multiple protective molecules that were operative in preconditioned animals, including molecules involved in antibacterial defense, redox balance, and tissue healing. We conclude that preconditioning reprograms macrophages and tubules to generate a protective environment, in which tissue health is preserved and immunity is controlled yet effective. Endotoxin preconditioning can thus be used as a discovery platform, and understanding the role and participation of both tissue and macrophages will help refine targeted therapies for sepsis.10.1681/ASN.2017060624Tue, 10 Oct 2017 07:56:48 GMT-07:00Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the KidneyPreconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here, using the kidney as a model organ, we investigated cell type–specific responses to preconditioning. Compared with preadministration of vehicle, endotoxin preconditioning in the cecal ligation and puncture mouse model of sepsis led to significantly enhanced survival and reduced bacterial load in several organs. Furthermore, endotoxin preconditioning reduced serum levels of proinflammatory cytokines, upregulated molecular pathways involved in phagocytosis, and prevented the renal function decline and injury induced in mice by a toxic dose of endotoxin. The protective phenotype involved the clustering of macrophages around S1 segments of proximal tubules, and full renal protection required both macrophages and renal tubular cells. Using unbiased S1 transcriptomic and tissue metabolomic approaches, we identified multiple protective molecules that were operative in preconditioned animals, including molecules involved in antibacterial defense, redox balance, and tissue healing. We conclude that preconditioning reprograms macrophages and tubules to generate a protective environment, in which tissue health is preserved and immunity is controlled yet effective. Endotoxin preconditioning can thus be used as a discovery platform, and understanding the role and participation of both tissue and macrophages will help refine targeted therapies for sepsis.Hato, TakashiZollman, AmyPlotkin, ZoyaEl-Achkar, Tarek M.Maier, Bernhard F.Pay, S. LouiseDube, ShataakshiCabral, PabloYoshimoto, MomokoMcClintick, JeanetteDagher, Pierre C.2017-10-10T07:56:48-07:00doi:10.1681/ASN.2017060624hwp:resource-id:jnephrol;29/1/104American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologysepsis, innate immunity, tlr4, metabolomics, transcriptomicsBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170606241046-66731533-34502017-10-10T07:56:48-07:002018-01Journal of the American Society of NephrologyBasic Research291104117
- Complement Activation in Peritoneal Dialysis–Induced ArteriolopathyCardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and is further aggravated by peritoneal dialysis (PD). Children are devoid of preexisting CVD and provide unique insight into specific uremia- and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children with established PD (PD group), and age-matched nonuremic controls (n=6/group). We microdissected omental arterioles from tissue layers not directly exposed to PD fluid and used adjacent sections of four arterioles per patient for transcriptomic and proteomic analyses. Findings were validated in omental and parietal arterioles from independent pediatric control (n=5), CKD5 (n=15), and PD (n=15) cohorts. Transcriptomic analysis revealed differential gene expression in control versus CKD5 arterioles and in CKD5 versus PD arterioles. Gene ontology analyses revealed activation of metabolic processes in CKD5 arterioles and of inflammatory, immunologic, and stress-response cascades in PD arterioles. PD arterioles exhibited particular upregulation of the complement system and respective regulatory pathways, with concordant findings at the proteomic level. In the validation cohorts, PD specimens had the highest abundance of omental and parietal arteriolar C1q, C3d, terminal complement complex, and phosphorylated SMAD2/3, a downstream effector of TGF-β. Furthermore, in the PD parietal arterioles, C1q and terminal complement complex abundance correlated with the level of dialytic glucose exposure, abundance of phosphorylated SMAD2/3, and degree of vasculopathy. We conclude that PD fluids activate arteriolar complement and TGF-β signaling, which quantitatively correlate with the severity of arteriolar vasculopathy.10.1681/ASN.2017040436Wed, 18 Oct 2017 06:23:21 GMT-07:00Complement Activation in Peritoneal Dialysis–Induced ArteriolopathyCardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and is further aggravated by peritoneal dialysis (PD). Children are devoid of preexisting CVD and provide unique insight into specific uremia- and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children with established PD (PD group), and age-matched nonuremic controls (n=6/group). We microdissected omental arterioles from tissue layers not directly exposed to PD fluid and used adjacent sections of four arterioles per patient for transcriptomic and proteomic analyses. Findings were validated in omental and parietal arterioles from independent pediatric control (n=5), CKD5 (n=15), and PD (n=15) cohorts. Transcriptomic analysis revealed differential gene expression in control versus CKD5 arterioles and in CKD5 versus PD arterioles. Gene ontology analyses revealed activation of metabolic processes in CKD5 arterioles and of inflammatory, immunologic, and stress-response cascades in PD arterioles. PD arterioles exhibited particular upregulation of the complement system and respective regulatory pathways, with concordant findings at the proteomic level. In the validation cohorts, PD specimens had the highest abundance of omental and parietal arteriolar C1q, C3d, terminal complement complex, and phosphorylated SMAD2/3, a downstream effector of TGF-β. Furthermore, in the PD parietal arterioles, C1q and terminal complement complex abundance correlated with the level of dialytic glucose exposure, abundance of phosphorylated SMAD2/3, and degree of vasculopathy. We conclude that PD fluids activate arteriolar complement and TGF-β signaling, which quantitatively correlate with the severity of arteriolar vasculopathy.Bartosova, MariaSchaefer, BettiBermejo, Justo LorenzoTarantino, SilviaLasitschka, FelixMacher-Goeppinger, StephanSinn, PeterWarady, Bradley A.Zaloszyc, ArianeParapatics, KatjaMájek, PeterBennett, Keiryn L.Oh, JunAufricht, ChristophSchaefer, FranzKratochwill, KlausSchmitt, Claus Peter2017-10-18T06:23:21-07:00doi:10.1681/ASN.2017040436hwp:resource-id:jnephrol;29/1/268American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, complement, TGF-beta, arteriosclerosis, children, vascular diseaseClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170404361046-66731533-34502017-10-18T06:23:21-07:002018-01Journal of the American Society of NephrologyClinical Research291268282
- Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKIThe proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β-hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.10.1681/ASN.2017060659Mon, 30 Oct 2017 06:34:13 GMT-07:00Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKIThe proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β-hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.Perry, Heather M.Huang, LipingWilson, Rebecca J.Bajwa, AmandeepSesaki, HiromiYan, ZhenRosin, Diane L.Kashatus, David F.Okusa, Mark D.2017-10-30T06:34:13-07:00doi:10.1681/ASN.2017060659hwp:resource-id:jnephrol;29/1/194American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymitochondria, ischemia-reperfusion, acute renal failure, chronic kidney disease, proximal tubule, fibrosisBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170606591046-66731533-34502017-10-30T06:34:13-07:002018-01Journal of the American Society of NephrologyBasic Research291194206
- Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRDElevated levels of fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5) are associated with increased risk of cardiovascular outcomes and death, but their association with risk of CKD and ESRD is unknown. We linked the Environmental Protection Agency and the Department of Veterans Affairs databases to build an observational cohort of 2,482,737 United States veterans, and used survival models to evaluate the association of PM2.5 concentrations and risk of incident eGFR <60 ml/min per 1.73 m2, incident CKD, eGFR decline ≥30%, and ESRD over a median follow-up of 8.52 years. County-level exposure was defined at baseline as the annual average PM2.5 concentrations in 2004, and separately as time-varying where it was updated annually and as cohort participants moved. In analyses of baseline exposure (median, 11.8 [interquartile range, 10.1–13.7] µg/m3), a 10-µg/m3 increase in PM2.5 concentration was associated with increased risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio [HR], 1.21; 95% confidence interval [95% CI], 1.14 to 1.29), CKD (HR, 1.27; 95% CI, 1.17 to 1.38), eGFR decline ≥30% (HR, 1.28; 95% CI, 1.18 to 1.39), and ESRD (HR, 1.26; 95% CI, 1.17 to 1.35). In time-varying analyses, a 10-µg/m3 increase in PM2.5 concentration was associated with similarly increased risk of eGFR<60 ml/min per 1.73 m2, CKD, eGFR decline ≥30%, and ESRD. Spline analyses showed a linear relationship between PM2.5 concentrations and risk of kidney outcomes. Exposure estimates derived from National Aeronautics and Space Administration satellite data yielded consistent results. Our findings demonstrate a significant association between exposure to PM2.5 and risk of incident CKD, eGFR decline, and ESRD.10.1681/ASN.2017030253Thu, 21 Sep 2017 05:39:14 GMT-07:00Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRDElevated levels of fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5) are associated with increased risk of cardiovascular outcomes and death, but their association with risk of CKD and ESRD is unknown. We linked the Environmental Protection Agency and the Department of Veterans Affairs databases to build an observational cohort of 2,482,737 United States veterans, and used survival models to evaluate the association of PM2.5 concentrations and risk of incident eGFR <60 ml/min per 1.73 m2, incident CKD, eGFR decline ≥30%, and ESRD over a median follow-up of 8.52 years. County-level exposure was defined at baseline as the annual average PM2.5 concentrations in 2004, and separately as time-varying where it was updated annually and as cohort participants moved. In analyses of baseline exposure (median, 11.8 [interquartile range, 10.1–13.7] µg/m3), a 10-µg/m3 increase in PM2.5 concentration was associated with increased risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio [HR], 1.21; 95% confidence interval [95% CI], 1.14 to 1.29), CKD (HR, 1.27; 95% CI, 1.17 to 1.38), eGFR decline ≥30% (HR, 1.28; 95% CI, 1.18 to 1.39), and ESRD (HR, 1.26; 95% CI, 1.17 to 1.35). In time-varying analyses, a 10-µg/m3 increase in PM2.5 concentration was associated with similarly increased risk of eGFR<60 ml/min per 1.73 m2, CKD, eGFR decline ≥30%, and ESRD. Spline analyses showed a linear relationship between PM2.5 concentrations and risk of kidney outcomes. Exposure estimates derived from National Aeronautics and Space Administration satellite data yielded consistent results. Our findings demonstrate a significant association between exposure to PM2.5 and risk of incident CKD, eGFR decline, and ESRD.Bowe, BenjaminXie, YanLi, TingtingYan, YanXian, HongAl-Aly, Ziyad2017-09-21T05:39:14-07:00doi:10.1681/ASN.2017030253hwp:resource-id:jnephrol;29/1/218American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, ESRD, glomerular filtration rateClinical EpidemiologyClinical Epidemiologyresearch-article20182018-01-01January 201810.1681/ASN.20170302531046-66731533-34502017-09-21T05:39:14-07:002018-01Journal of the American Society of NephrologyClinical Epidemiology291218230
- Collectin-11 Promotes the Development of Renal Tubulointerstitial FibrosisCollectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, Collec11 deficient (CL-11−/−) mice had significantly reduced renal functional impairment, tubular injury, renal leukocyte infiltration, renal tissue inflammation/fibrogenesis, and collagen deposition in the kidneys after renal ischemia-reperfusion injury. In vitro, recombinant collectin-11 potently promoted leukocyte migration and renal fibroblast proliferation in a carbohydrate-dependent manner. Additionally, compared with wild-type kidney grafts, CL-11−/− mice kidney grafts displayed significantly reduced tubular injury and collagen deposition after syngeneic kidney transplant. Our findings demonstrate a pathogenic role for collectin-11 in the development of tubulointerstitial fibrosis and suggest that local collectin-11 promotes this fibrosis through effects on leukocyte chemotaxis and renal fibroblast proliferation. This insight into the pathogenesis of tubulointerstitial fibrosis may have implications for CKD mediated by other causes as well.10.1681/ASN.2017050544Wed, 15 Nov 2017 12:04:11 GMT-08:00Collectin-11 Promotes the Development of Renal Tubulointerstitial FibrosisCollectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, Collec11 deficient (CL-11−/−) mice had significantly reduced renal functional impairment, tubular injury, renal leukocyte infiltration, renal tissue inflammation/fibrogenesis, and collagen deposition in the kidneys after renal ischemia-reperfusion injury. In vitro, recombinant collectin-11 potently promoted leukocyte migration and renal fibroblast proliferation in a carbohydrate-dependent manner. Additionally, compared with wild-type kidney grafts, CL-11−/− mice kidney grafts displayed significantly reduced tubular injury and collagen deposition after syngeneic kidney transplant. Our findings demonstrate a pathogenic role for collectin-11 in the development of tubulointerstitial fibrosis and suggest that local collectin-11 promotes this fibrosis through effects on leukocyte chemotaxis and renal fibroblast proliferation. This insight into the pathogenesis of tubulointerstitial fibrosis may have implications for CKD mediated by other causes as well.Wu, WeijuLiu, ChengfeiFarrar, Conrad A.Ma, LiangDong, XiaSacks, Steven H.Li, KeZhou, Wuding2017-11-15T12:04:11-08:00doi:10.1681/ASN.2017050544hwp:resource-id:jnephrol;29/1/168American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologycollectin 11, renal fibrosis, leukocyte migration, renal fibroblast proliferation, carbohydrate ligandsBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20170505441046-66731533-34502017-11-15T12:04:11-08:002018-01Journal of the American Society of NephrologyBasic Research291168181
- Mesenchymal Stromal Cells for AKI after Cardiac Surgery10.1681/ASN.2017111207Mon, 11 Dec 2017 05:06:45 GMT-08:00Mesenchymal Stromal Cells for AKI after Cardiac SurgeryPerico, NorbertoCasiraghi, FedericaRemuzzi, Giuseppe2017-12-11T05:06:45-08:00doi:10.1681/ASN.2017111207hwp:resource-id:jnephrol;29/1/7American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, Mesenchymal stromal cells, CKDUp Front MattersEditorialsUp Front MattersEditorialseditorial20182018-01-01January 201810.1681/ASN.20171112071046-66731533-34502017-12-11T05:06:45-08:002018-01Journal of the American Society of NephrologyUp Front Matters291172609267
- DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GNFibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12–24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. These studies identified DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein detected only in fibrillary GN cases. The glomerular proteome of fibrillary GN cases also contained IgG1 as the dominant Ig and proteins of the classic complement pathway. In fibrillary GN specimens only, immunofluorescence and immunohistochemistry with an anti-DNAJB9 antibody showed strong and specific staining of the glomerular tufts in a distribution that mimicked that of the immune deposits. Our results identify DNAJB9 as a putative autoantigen in fibrillary GN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease.10.1681/ASN.2017050566Thu, 02 Nov 2017 02:30:10 GMT-07:00DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GNFibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12–24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. These studies identified DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein detected only in fibrillary GN cases. The glomerular proteome of fibrillary GN cases also contained IgG1 as the dominant Ig and proteins of the classic complement pathway. In fibrillary GN specimens only, immunofluorescence and immunohistochemistry with an anti-DNAJB9 antibody showed strong and specific staining of the glomerular tufts in a distribution that mimicked that of the immune deposits. Our results identify DNAJB9 as a putative autoantigen in fibrillary GN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease.Andeen, Nicole K.Yang, Han-YinDai, Dao-FuMacCoss, Michael J.Smith, Kelly D.2017-11-02T14:30:10-07:00doi:10.1681/ASN.2017050566hwp:resource-id:jnephrol;29/1/231American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyFibrillary glomerulonephritis, renal biopsy, autoantigen, immunohistochemistry, mass spectrometryClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170505661046-66731533-34502017-11-02T14:30:10-07:002018-01Journal of the American Society of NephrologyClinical Research291123122394
- MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and MigrationIntronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease–associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense mutations and has been associated with nephropathy in some carriers. To determine the contribution of the E1841K mutation in kidney disease, we studied the effects of the E1841K mutation in mice subjected to high salt or angiotensin II (Ang II) as models of hypertension and in mice subjected to renal mass reduction as a model of CKD. Despite similar levels of BP among wild-type (MYH9+/+) mice and mice heterozygous (MYH9+/E1841K) and homozygous (MYH9E1841K/E1841K) for the mutation in each model, MYH9E1841K/E1841K mice exhibited mildly increased albuminuria in response to high salt; severe albuminuria, nephrinuria, FSGS, and podocyte foot effacement in Ang II–induced hypertension; and early mortality in the renal mass reduction model. Treatment with candesartan during Ang II–induced hypertension attenuated kidney disease development in MYH9E1841K/E1841K mice. In vitro, isolated primary podocytes from MYH9E1841K/E1841K mice exhibited increased lamellipodia formation and reorganization of F-actin stress fibers. Wound healing assays revealed that MYH9+/+ podocytes had the lowest migration rate, followed by MYH9+/E1841K then MYH9E1841K/E1841K podocytes. In conclusion, the MYH9 E1841K variant alters podocyte cytoskeletal structure and renders podocytes more susceptible to injury after a damaging stimulus.10.1681/ASN.2015060707Mon, 09 Oct 2017 10:43:42 GMT-07:00MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and MigrationIntronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease–associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense mutations and has been associated with nephropathy in some carriers. To determine the contribution of the E1841K mutation in kidney disease, we studied the effects of the E1841K mutation in mice subjected to high salt or angiotensin II (Ang II) as models of hypertension and in mice subjected to renal mass reduction as a model of CKD. Despite similar levels of BP among wild-type (MYH9+/+) mice and mice heterozygous (MYH9+/E1841K) and homozygous (MYH9E1841K/E1841K) for the mutation in each model, MYH9E1841K/E1841K mice exhibited mildly increased albuminuria in response to high salt; severe albuminuria, nephrinuria, FSGS, and podocyte foot effacement in Ang II–induced hypertension; and early mortality in the renal mass reduction model. Treatment with candesartan during Ang II–induced hypertension attenuated kidney disease development in MYH9E1841K/E1841K mice. In vitro, isolated primary podocytes from MYH9E1841K/E1841K mice exhibited increased lamellipodia formation and reorganization of F-actin stress fibers. Wound healing assays revealed that MYH9+/+ podocytes had the lowest migration rate, followed by MYH9+/E1841K then MYH9E1841K/E1841K podocytes. In conclusion, the MYH9 E1841K variant alters podocyte cytoskeletal structure and renders podocytes more susceptible to injury after a damaging stimulus.Cechova, SylviaDong, FanChan, FangKelley, Michael J.Ruiz, PhillipLe, Thu H.2017-10-09T10:43:42-07:00doi:10.1681/ASN.2015060707hwp:resource-id:jnephrol;29/1/155American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, glomerulosclerosis, hypertension, MYH9, genetics and development, kidney diseaseBasic ResearchBasic Researchresearch-article20182018-01-01January 201810.1681/ASN.20150607071046-66731533-34502017-10-09T10:43:42-07:002018-01Journal of the American Society of NephrologyBasic Research291155167
- Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary TractCongenital anomalies of the kidneys and urinary tract (CAKUT) comprise a large spectrum of congenital malformations ranging from severe manifestations, such as renal agenesis, to potentially milder conditions, such as vesicoureteral reflux. CAKUT causes approximately 40% of ESRD that manifests within the first three decades of life. Several lines of evidence indicate that CAKUT is often caused by recessive or dominant mutations in single (monogenic) genes. To date, approximately 40 monogenic genes are known to cause CAKUT if mutated, explaining 5%–20% of patients. However, hundreds of different monogenic CAKUT genes probably exist. The discovery of novel CAKUT-causing genes remains challenging because of this pronounced heterogeneity, variable expressivity, and incomplete penetrance. We here give an overview of known genetic causes for human CAKUT and shed light on distinct renal morphogenetic pathways that were identified as relevant for CAKUT in mice and humans.10.1681/ASN.2017050561Fri, 27 Oct 2017 06:06:36 GMT-07:00Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary TractCongenital anomalies of the kidneys and urinary tract (CAKUT) comprise a large spectrum of congenital malformations ranging from severe manifestations, such as renal agenesis, to potentially milder conditions, such as vesicoureteral reflux. CAKUT causes approximately 40% of ESRD that manifests within the first three decades of life. Several lines of evidence indicate that CAKUT is often caused by recessive or dominant mutations in single (monogenic) genes. To date, approximately 40 monogenic genes are known to cause CAKUT if mutated, explaining 5%–20% of patients. However, hundreds of different monogenic CAKUT genes probably exist. The discovery of novel CAKUT-causing genes remains challenging because of this pronounced heterogeneity, variable expressivity, and incomplete penetrance. We here give an overview of known genetic causes for human CAKUT and shed light on distinct renal morphogenetic pathways that were identified as relevant for CAKUT in mice and humans.van der Ven, Amelie T.Vivante, AsafHildebrandt, Friedhelm2017-10-27T06:06:36-07:00doi:10.1681/ASN.2017050561hwp:resource-id:jnephrol;29/1/36American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologymonogenic disease, genetic kidney disease, congenital anomalies of the kidneys and urinary tract, CAKUTUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20182018-01-01January 201810.1681/ASN.20170505611046-66731533-34502017-10-27T06:06:36-07:002018-01Journal of the American Society of NephrologyUp Front Matters2913650
- Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex–Mediated Membranoproliferative GNMembranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement–mediated C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1–3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment.10.1681/ASN.2017030258Fri, 13 Oct 2017 06:12:17 GMT-07:00Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex–Mediated Membranoproliferative GNMembranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement–mediated C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1–3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment.Iatropoulos, ParaskevasDaina, EricaCurreri, ManuelaPiras, RossellaValoti, ElisabettaMele, CaterinaBresin, ElenaGamba, SaraAlberti, MartaBreno, MatteoPerna, AnnalisaBettoni, SerenaSabadini, EttoreMurer, LuisaVivarelli, MarinaNoris, MarinaRemuzzi, Giuseppe,Remuzzi, G.Daina, E.Bresin, E.Curreri, M.Iatropoulos, P.Gamba, S.Bottanelli, L.Noris, M.Alberti, M.Bettoni, S.Breno, M.Donadelli, R.Mele, C.Piras, R.Valoti, E.Cuccarolo, P.Abbate, M.Carrara, C.Cannata, A.Ferrari, S.Gaspari, F.Stucchi, N.Bassani, C.Lena, M.Omati, G.,Taruscia, D.Bellantuono, R.Giordano, M.Messina, G.Caruso, M.Gotti, E.Mescia, F.Perticucci, E.,Sabadini, E.Schieppati, A.Verdoni, L.Berto, M.Baraldi, O.Montini, G.Pasini, A.Passler, W.Degasperi, T.Gaggiotti, M.Gregorini, G.Miglietti, N.Guarnieri, A.Cirami, L.Roperto, R.M.Di Giorgio, G.Barbano, G.Innocenti, M.L. DegliGhiggeri, G.M.Magnasco, A.Rolla, D.Casartelli, D.Lambertini, D.Maggio, M.Cosci, P.M.Conti, G.Amar, K.Ardissino, G.Marinosci, A.Sinico, R.A.Montoli, A.Bonucchi, D.Facchini, F.Furci, L.Ferretti, A.Nuzzi, F.Pecoraro, C.Visciano, B.Canavese, C.Radin, E.Stratta, P.Nordio, M.Benetti, E.Murer, L.Parolin, M.Alberici, F.Manenti, L.Brugnano, R.Manenti, F.Capitanini, A.Emma, F.,Massella, L.Vivarelli, M.Rosa, M.,Mazzon, M.Basso, E.Besso, L.Lavacca, A.Mella, A.Bertero, M.Coppo, R.Peruzzi, L.Porcellini, M.G.Piccoli, G.B.Clari, R.Pasi, A.Gangemi, C.Alfandary, H.Dagan, A.Conceiçao, M.Sameiro, F.M.Croze, L.Malvezzi, P.Tsygin, A.Zelan, B.2017-10-13T06:12:17-07:00doi:10.1681/ASN.2017030258hwp:resource-id:jnephrol;29/1/283American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of NephrologyC3 glomerulopathy, C3 glomerulonephritis, Dense Deposit Disease, membranoproliferative glomerulonephritis (MPGN), Complement system, Rare diseasesClinical ResearchClinical Researchresearch-article20182018-01-01January 201810.1681/ASN.20170302581046-66731533-34502017-10-13T06:12:17-07:002018-01Journal of the American Society of NephrologyClinical Research2911283929412
- Incident CKD after Radical or Partial NephrectomyThe comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001–2013). Among patients with preoperative eGFR≥30 ml/min per 1.73 m2, the incidence of CKD stage 4 or higher after radical (n=9759) or partial nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD after surgery was 5 months, after which few patients progressed. In propensity score–matched cohorts, partial nephrectomy associated with a significantly lower relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95% confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a parallel analysis of patients with normal or near-normal preoperative kidney function (eGFR≥60 ml/min per 1.73 m2), partial nephrectomy was also associated with a significantly lower relative risk of incident CKD stage 3b or higher (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in propensity score–matched cohorts. Competing risk regression models produced consistent results. Finally, patients treated with a partial nephrectomy had reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In conclusion, compared with radical nephrectomy, partial nephrectomy was associated with a marked reduction in the incidence of clinically significant CKD and with enhanced survival. Postoperative decline in kidney function occurred mainly in the first year after surgery and appeared stable over time.10.1681/ASN.2017020136Tue, 10 Oct 2017 07:56:50 GMT-07:00Incident CKD after Radical or Partial NephrectomyThe comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001–2013). Among patients with preoperative eGFR≥30 ml/min per 1.73 m2, the incidence of CKD stage 4 or higher after radical (n=9759) or partial nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD after surgery was 5 months, after which few patients progressed. In propensity score–matched cohorts, partial nephrectomy associated with a significantly lower relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95% confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a parallel analysis of patients with normal or near-normal preoperative kidney function (eGFR≥60 ml/min per 1.73 m2), partial nephrectomy was also associated with a significantly lower relative risk of incident CKD stage 3b or higher (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in propensity score–matched cohorts. Competing risk regression models produced consistent results. Finally, patients treated with a partial nephrectomy had reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In conclusion, compared with radical nephrectomy, partial nephrectomy was associated with a marked reduction in the incidence of clinically significant CKD and with enhanced survival. Postoperative decline in kidney function occurred mainly in the first year after surgery and appeared stable over time.Leppert, John T.Lamberts, Remy W.Thomas, I-ChunChung, Benjamin I.Sonn, Geoffrey A.Skinner, Eila C.Wagner, Todd H.Chertow, Glenn M.Brooks, James D.2017-10-10T07:56:50-07:00doi:10.1681/ASN.2017020136hwp:resource-id:jnephrol;29/1/207American Society of NephrologyCopyright © 2018 by the American Society of NephrologyJournal of the American Society of Nephrologykidney cancer, Nephrectomy, chronic kidney diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20182018-01-01January 201810.1681/ASN.20170201361046-66731533-34502017-10-10T07:56:50-07:002018-01Journal of the American Society of NephrologyClinical Epidemiology291207216
- Diabetic Kidney DiseaseDiabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Despite current therapies, there is large residual risk of diabetic kidney disease onset and progression. Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease. Achieving this goal will require characterization of new biomarkers, designing clinical trials that evaluate clinically pertinent end points, and development of therapeutic agents targeting kidney-specific disease mechanisms (e.g., glomerular hyperfiltration, inflammation, and fibrosis). Additionally, greater attention to dissemination and implementation of best practices is needed in both clinical and community settings.Introduction10.2215/CJN.11491116Thu, 18 May 2017 11:07:35 GMT-07:00Diabetic Kidney DiseaseDiabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Despite current therapies, there is large residual risk of diabetic kidney disease onset and progression. Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease. Achieving this goal will require characterization of new biomarkers, designing clinical trials that evaluate clinically pertinent end points, and development of therapeutic agents targeting kidney-specific disease mechanisms (e.g., glomerular hyperfiltration, inflammation, and fibrosis). Additionally, greater attention to dissemination and implementation of best practices is needed in both clinical and community settings.IntroductionAlicic, Radica Z.Rooney, Michele T.Tuttle, Katherine R.2017-05-18T11:07:35-07:00doi:10.2215/CJN.11491116hwp:resource-id:clinjasn;12/12/2032American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, structural changes, natural history, pathogenesis, altered renal hemodynamics, novel therapies, diagnosisGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-12-07December 07, 201710.2215/CJN.114911161555-90411555-905X2017-05-18T11:07:35-07:002017-12-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician121220322045
- Early Experience with the New Kidney Allocation System10.2215/CJN.07520717Tue, 21 Nov 2017 06:12:48 GMT-08:00Early Experience with the New Kidney Allocation SystemFriedewald, John J.Turgeon, Nicole2017-11-21T06:12:48-08:00doi:10.2215/CJN.07520717hwp:resource-id:clinjasn;12/12/2060American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Humans, Tissue and Organ Procurement, Tissue DonorsPerspectivesPerspectivesresearch-article20172017-12-07December 07, 201710.2215/CJN.075207171555-90411555-905X2017-11-21T06:12:48-08:002017-12-07Clinical Journal of the American Society of NephrologyPerspectives121220602062
- Association of Kidney Transplantation with Survival in Patients with Long Dialysis Exposure10.2215/CJN.06100617Thu, 26 Oct 2017 06:38:05 GMT-07:00Association of Kidney Transplantation with Survival in Patients with Long Dialysis ExposureRose, CarenGill, JagbirGill, John S.2017-10-26T06:38:05-07:00doi:10.2215/CJN.06100617hwp:resource-id:clinjasn;12/12/2024American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycadaver organ transplantation, survival, kidney transplantation, Risk, Transplant Recipients, Confidence Intervals, Follow-Up Studies, Graft Survival, Tissue Donors, kidney, Registries, diabetes mellitus, Humans, renal dialysisOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-12-07December 07, 201710.2215/CJN.061006171555-90411555-905X2017-10-26T06:38:05-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121220242031
- Drug-Induced Acute Interstitial Nephritis10.2215/CJN.07630717Mon, 11 Sep 2017 07:49:30 GMT-07:00Drug-Induced Acute Interstitial NephritisMoledina, Dennis G.Perazella, Mark A.2017-09-11T07:49:30-07:00doi:10.2215/CJN.07630717hwp:resource-id:clinjasn;12/12/2046American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute interstitial nephritis, acute kidney injury, corticosteroids, kidney biopsy, drugs, Nephritis, Interstitial, Kidney Tubular Necrosis, AcuteKidney Case Conference: How I TreatKidney Case Conference: How I Treatresearch-article20172017-12-07December 07, 201710.2215/CJN.076307171555-90411555-905X2017-09-11T07:49:30-07:002017-12-07Clinical Journal of the American Society of NephrologyKidney Case Conference: How I Treat121220462049
- Continued Search for Therapies to Favorably Modify Phosphate and FGF23 Levels in CKD10.2215/CJN.11011017Thu, 26 Oct 2017 06:38:05 GMT-07:00Continued Search for Therapies to Favorably Modify Phosphate and FGF23 Levels in CKDMehta, RupalIsakova, Tamara2017-10-26T06:38:05-07:00doi:10.2215/CJN.11011017hwp:resource-id:clinjasn;12/12/1911American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, phosphate binders, hyperphosphatemia, Humans, fibroblast growth factor 23, Hypertrophy, Left Ventricular, Atrial Fibrillation, risk factors, Myocytes, Cardiac, Fibroblast Growth Factors, Renal Insufficiency, Chronic, Phosphates, Cardiovascular Diseases, heart failure, Leukocytes, InflammationEditorialsEditorialseditorial20172017-12-07December 07, 201710.2215/CJN.110110171555-90411555-905X2017-10-26T06:38:05-07:002017-12-07Clinical Journal of the American Society of NephrologyEditorials1212121911193019131940
- Residual Kidney Function and Peritoneal Dialysis–Associated Peritonitis Treatment Outcomes10.2215/CJN.00630117Tue, 07 Nov 2017 08:42:20 GMT-08:00Residual Kidney Function and Peritoneal Dialysis–Associated Peritonitis Treatment OutcomesWhitty, RachelBargman, Joanne M.Kiss, AlexDresser, LindaLui, Philip2017-11-07T08:42:20-08:00doi:10.2215/CJN.00630117hwp:resource-id:clinjasn;12/12/2016American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitonitis, peritoneal dialysis, residual kidney function, antibiotic clearance, continuous cyclic peritoneal dialysis, continuous ambulatory peritoneal dialysis, Anti-Bacterial Agents, creatinine, Treatment Failure, Treatment Outcome, RecurrenceOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-12-07December 07, 201710.2215/CJN.006301171555-90411555-905X2017-11-07T08:42:20-08:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1212122016191920221921
- Brief Mindfulness Meditation for Depression and Anxiety Symptoms in Patients Undergoing Hemodialysis10.2215/CJN.03900417Thu, 12 Oct 2017 06:36:25 GMT-07:00Brief Mindfulness Meditation for Depression and Anxiety Symptoms in Patients Undergoing HemodialysisThomas, ZoëNovak, MartaPlatas, Susanna Gabriela TorresGautier, MaryseHolgin, Angela PotesFox, RebeccaSegal, MarilynLooper, Karl J.Lipman, MarkSelchen, StevenMucsi, IstvanHerrmann, NathanRej, Soham2017-10-12T06:36:25-07:00doi:10.2215/CJN.03900417hwp:resource-id:clinjasn;12/12/2008American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMeditation, Mindfulness, Anxiety, depression, dialysis, Depressive Disorder, Anxiety Disorders, renal dialysis, Surveys and QuestionnairesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-12-07December 07, 201710.2215/CJN.039004171555-90411555-905X2017-10-12T06:36:25-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121220082015
- Prospective Evaluation of Kidney Disease in Joubert Syndrome10.2215/CJN.05660517Thu, 16 Nov 2017 06:49:12 GMT-08:00Prospective Evaluation of Kidney Disease in Joubert SyndromeFleming, Leah R.Doherty, Daniel A.Parisi, Melissa A.Glass, Ian A.Bryant, JoyFischer, RoxanneTurkbey, BarisChoyke, PeterDaryanani, KailashVemulapalli, MeghanaMullikin, James C.Malicdan, May ChristineVilboux, ThierrySayer, John A.Gahl, William A.Gunay-Aygun, Meral2017-11-16T06:49:12-08:00doi:10.2215/CJN.05660517hwp:resource-id:clinjasn;12/12/1962American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, cystic kidney, ciliopathy, nephronophthisis, polycystic kidney disease, Joubert syndrome 1, Polycystic Kidney, Autosomal Recessive, Multicystic Dysplastic Kidney, Prospective Studies, Kidney Diseases, Cystic, Eye Abnormalities, kidney, Retina, Kidney Failure, Chronic, Mutation, Phenotype, Sequence Analysis, DNA, hypertension, Genetic Association Studies, Ultrasonography, Prenatal, Ciliopathies, Pregnancy, Abnormalities, Multiple, CerebellumOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20172017-12-07December 07, 201710.2215/CJN.056605171555-90411555-905X2017-11-16T06:49:12-08:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1212121962191419731916
- Multi-Disciplinary Vascular Access Care and Access Outcomes in People Starting Hemodialysis Therapy10.2215/CJN.03430317Thu, 14 Sep 2017 07:59:06 GMT-07:00Multi-Disciplinary Vascular Access Care and Access Outcomes in People Starting Hemodialysis TherapyGill, SimardeepQuinn, RobertOliver, MatthewKamar, FareedKabani, RameezDevoe, DanielMysore, PriyankaPannu, NeeshMacRae, JenniferManns, BradenHemmelgarn, BrendaJames, MatthewTonelli, MarcelloLewin, AdrianeLiu, PingRavani, Pietro2017-09-14T07:59:06-07:00doi:10.2215/CJN.03430317hwp:resource-id:clinjasn;12/12/1991American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, vascular access, Central Venous Catheters, hemodialysis, Aged, Odds Ratio, Logistic Models, Confidence Intervals, Comorbidity, renal dialysis, Probability, Surgeons, diabetes mellitus, Radiologists, Fistula, CanadaOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-12-07December 07, 201710.2215/CJN.034303171555-90411555-905X2017-09-14T07:59:06-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121219911999
- Effective Treatment of PD Peritonitis10.2215/CJN.11071017Tue, 07 Nov 2017 08:42:21 GMT-08:00Effective Treatment of PD PeritonitisPiraino, Beth2017-11-07T08:42:21-08:00doi:10.2215/CJN.11071017hwp:resource-id:clinjasn;12/12/1919American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitonitis, peritoneal dialysis, treatment, antibiotic, Humans, Anti-Bacterial Agents, Peritoneal Dialysis, Continuous Ambulatory, Dialysis Solutions, Staphylococcus, renal dialysisEditorialsEditorialseditorial20172017-12-07December 07, 201710.2215/CJN.110710171555-90411555-905X2017-11-07T08:42:21-08:002017-12-07Clinical Journal of the American Society of NephrologyEditorials1212121919201619212022
- Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies10.2215/CJN.01280217Thu, 16 Nov 2017 06:49:10 GMT-08:00Phenotypic Spectrum of Children with Nephronophthisis and Related CiliopathiesKönig, JensKranz, BirgittaKönig, SabineSchlingmann, Karl PeterTitieni, AndreaTönshoff, BurkhardHabbig, SandraPape, LarsHäffner, KarstenHansen, MatthiasBüscher, AnjaBald, MartinBilling, HeikoSchild, RaphaelWalden, UlrikeHampel, TobiasStaude, HagenRiedl, MagdalenaGretz, NorbertLablans, MartinBergmann, CarstenHildebrandt, FriedhelmOmran, HeymutKonrad, Martin,2017-11-16T06:49:10-08:00doi:10.2215/CJN.01280217hwp:resource-id:clinjasn;12/12/1974American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNephronophthisis (NPH), Nephronophthisis related ciliopathy, Joubert-like syndromes, Senior-Løken syndrome, Bardet-Biedl syndrome, Congenital oculomotor apraxia, COACH syndrome, Mainzer-Saldino syndrome, NEPHREG registry, Adolescent, Genetic Heterogeneity, Prevalence, Cross-Sectional Studies, Nephronophthisis, familial juvenile, Kidney Diseases, Cystic, Homozygote, Kidney Failure, Chronic, Mutation, Registries, CiliopathiesOriginal ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20172017-12-07December 07, 201710.2215/CJN.012802171555-90411555-905X2017-11-16T06:49:10-08:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1212121974191419831916
- Statistical Methods for Recurrent Event Analysis in Cohort Studies of CKDCardiovascular events, such as hospitalizations because of congestive heart failure, often occur repeatedly in patients with CKD. Many studies focus on analyses of the first occurrence of these events, and discard subsequent information. In this article, we review a number of statistical methods for analyzing ordered recurrent events of the same type, including Poisson regression and three commonly used survival models that are extensions of Cox proportional hazards regression. We illustrate the models by analyzing data from the Chronic Renal Insufficiency Cohort Study to identify risk factors for congestive heart failure hospitalizations in patients with CKD. We show that recurrent event analyses provide additional insights about the data compared with a standard survival analysis of time to the first event.10.2215/CJN.12841216Mon, 17 Jul 2017 08:58:16 GMT-07:00Statistical Methods for Recurrent Event Analysis in Cohort Studies of CKDCardiovascular events, such as hospitalizations because of congestive heart failure, often occur repeatedly in patients with CKD. Many studies focus on analyses of the first occurrence of these events, and discard subsequent information. In this article, we review a number of statistical methods for analyzing ordered recurrent events of the same type, including Poisson regression and three commonly used survival models that are extensions of Cox proportional hazards regression. We illustrate the models by analyzing data from the Chronic Renal Insufficiency Cohort Study to identify risk factors for congestive heart failure hospitalizations in patients with CKD. We show that recurrent event analyses provide additional insights about the data compared with a standard survival analysis of time to the first event.Yang, WeiJepson, ChristopherXie, DaweiRoy, Jason A.Shou, HaochangHsu, Jesse YenchihAnderson, Amanda HyreLandis, J. RichardHe, JiangFeldman, Harold I.,2017-07-17T08:58:16-07:00doi:10.2215/CJN.12841216hwp:resource-id:clinjasn;12/12/2066American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrecurrent event, chronic kidney disease, Poisson regression, Cox proportional hazards model, Cohort Studies, heart failure, hospitalization, Humans, Renal Insufficiency, Chronic, risk factors, Survival AnalysisFeatureFeatureresearch-article20172017-12-07December 07, 201710.2215/CJN.128412161555-90411555-905X2017-07-17T08:58:16-07:002017-12-07Clinical Journal of the American Society of NephrologyFeature121220662073
- Sociodemographic, Psychologic Health, and Lifestyle Outcomes in Young Adults on Renal Replacement Therapy10.2215/CJN.04760517Thu, 19 Oct 2017 06:59:53 GMT-07:00Sociodemographic, Psychologic Health, and Lifestyle Outcomes in Young Adults on Renal Replacement TherapyHamilton, Alexander J.Clissold, Rhian L.Inward, Carol D.Caskey, Fergus J.Ben-Shlomo, Yoav2017-10-19T06:59:53-07:00doi:10.2215/CJN.04760517hwp:resource-id:clinjasn;12/12/1951American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysystematic review, meta-analysis, young adult, renal replacement therapy, kidney transplantation, dialysis, education, employment, relationships, mental health, lifestyle, Cross-Sectional Studies, Risk, Confidence Intervals, Language, Alcohol Abstinence, quality of life, Smoking, RRT, Unemployment, Uncertainty, Demography, Renal Insufficiency, Life StyleOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-12-07December 07, 201710.2215/CJN.047605171555-90411555-905X2017-10-19T06:59:53-07:002017-12-07Clinical Journal of the American Society of NephrologyOriginal Articles121219511961
- Variations in MicroRNA-25 Expression Influence the Severity of Diabetic Kidney DiseaseDiabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and secondary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells. In db/db mice, systemic administration of an miR-25 agomir repressed glomerular fibrosis and reduced high BP. Notably, knockdown of miR-25 in normal mice by systemic administration of an miR-25 antagomir resulted in increased proteinuria, extracellular matrix accumulation, podocyte foot process effacement, and hypertension with renin-angiotensin system activation. However, excessive miR-25 did not cause kidney dysfunction in wild-type mice. RNA sequencing showed the alteration of miR-25 target genes in antagomir-treated mice, including the Ras-related gene CDC42. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the CDC42 3′ untranslated region. In conclusion, these results reveal a role for miR-25 in diabetic nephropathy and indicate a potential novel therapeutic target for this disease.10.1681/ASN.2015091017Mon, 18 Sep 2017 09:48:20 GMT-07:00Variations in MicroRNA-25 Expression Influence the Severity of Diabetic Kidney DiseaseDiabetic nephropathy is characterized by persistent albuminuria, progressive decline in GFR, and secondary hypertension. MicroRNAs are dysregulated in diabetic nephropathy, but identification of the specific microRNAs involved remains incomplete. Here, we show that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of microRNA-25 (miR-25) compared with those of their nondiabetic counterparts. Furthermore, treatment with high glucose decreased the expression of miR-25 in cultured kidney cells. In db/db mice, systemic administration of an miR-25 agomir repressed glomerular fibrosis and reduced high BP. Notably, knockdown of miR-25 in normal mice by systemic administration of an miR-25 antagomir resulted in increased proteinuria, extracellular matrix accumulation, podocyte foot process effacement, and hypertension with renin-angiotensin system activation. However, excessive miR-25 did not cause kidney dysfunction in wild-type mice. RNA sequencing showed the alteration of miR-25 target genes in antagomir-treated mice, including the Ras-related gene CDC42. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the CDC42 3′ untranslated region. In conclusion, these results reveal a role for miR-25 in diabetic nephropathy and indicate a potential novel therapeutic target for this disease.Liu, YunshuangLi, HongzhiLiu, JietingHan, PengfeiLi, XuefengBai, HeZhang, ChunleiSun, XuelianTeng, YanjieZhang, YufeiYuan, XiaohuanChu, YanhuiZhao, Binghai2017-09-18T09:48:20-07:00doi:10.1681/ASN.2015091017hwp:resource-id:jnephrol;28/12/3627American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, cardiovascular, diabetic nephropathy, fibrosis, focal segmental glomerulosclerosisBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20150910171046-66731533-34502017-09-18T09:48:20-07:002017-12Journal of the American Society of NephrologyBasic Research281236273638
- Developing Tools for Analysis of Renal Genomic Data: An Invitation to Participate10.1681/ASN.2017070811Thu, 05 Oct 2017 12:13:24 GMT-07:00Developing Tools for Analysis of Renal Genomic Data: An Invitation to ParticipateGonzalez-Vicente, AgustinHopfer, UlrichGarvin, Jeffrey L.2017-10-05T12:13:24-07:00doi:10.1681/ASN.2017070811hwp:resource-id:jnephrol;28/12/3438American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyRenal Genomics, Bioinformatics, Crowd Contributions, Pathway Analysis, Systems BiologyUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20172017-12-01December 201710.1681/ASN.20170708111046-66731533-34502017-10-05T12:13:24-07:002017-12Journal of the American Society of NephrologyUp Front Matters281234383440
- Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKDObesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β-oxidation. Collectively, these findings indicate that renal proximal tubule cell CB1R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway.10.1681/ASN.2016101085Thu, 31 Aug 2017 06:24:25 GMT-07:00Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKDObesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β-oxidation. Collectively, these findings indicate that renal proximal tubule cell CB1R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway.Udi, ShiranHinden, LiadEarley, BrianDrori, AdiReuveni, NoaHadar, RivkaCinar, ResatNemirovski, AlinaTam, Joseph2017-08-31T06:24:25-07:00doi:10.1681/ASN.2016101085hwp:resource-id:jnephrol;28/12/3518American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, chronic kidney disease, Endocannabinoids, CB1 receptor, AMPK, Renal Proximal Tubular CellBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20161010851046-66731533-34502017-08-31T06:24:25-07:002017-12Journal of the American Society of NephrologyBasic Research2812123518342935323432
- Serum Iron Protects from Renal Postischemic InjuryRenal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury–associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-κB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants.10.1681/ASN.2016080926Mon, 07 Aug 2017 06:45:23 GMT-07:00Serum Iron Protects from Renal Postischemic InjuryRenal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury–associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-κB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants.Vaugier, CélineAmano, Mariane T.Chemouny, Jonathan M.Dussiot, MichaelBerrou, ClaireMatignon, MarieBen Mkaddem, SanaeWang, Pamella H.M.Fricot, AurélieMaciel, Thiago T.Grapton, DamienMathieu, Jacques R.R.Beaumont, CarolePeraldi, Marie-NoëllePeyssonnaux, CaroleMesnard, LaurentDaugas, EricVrtovsnik, FrançoisMonteiro, Renato C.Hermine, OlivierGinzburg, Yelena Z.Benhamou, MarcCamara, Niels O.S.Flamant, MartinMoura, Ivan C.2017-08-07T06:45:23-07:00doi:10.1681/ASN.2016080926hwp:resource-id:jnephrol;28/12/3605American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyiron, transplantation, Chronic inflammation, macrophages, NRF2Basic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20160809261046-66731533-34502017-08-07T06:45:23-07:002017-12Journal of the American Society of NephrologyBasic Research281236053615
- Endothelial Epas1 Deficiency Is Sufficient To Promote Parietal Epithelial Cell Activation and FSGS in Experimental HypertensionFSGS, the most common primary glomerular disorder causing ESRD, is a complex disease that is only partially understood. Progressive sclerosis is a hallmark of FSGS, and genetic tracing studies have shown that parietal epithelial cells participate in the formation of sclerotic lesions. The loss of podocytes triggers a focal activation of parietal epithelial cells, which subsequently form cellular adhesions with the capillary tuft. However, in the absence of intrinsic podocyte alterations, the origin of the pathogenic signal that triggers parietal epithelial cell recruitment remains elusive. In this study, investigation of the role of the endothelial PAS domain-containing protein 1 (EPAS1), a regulatory α subunit of the hypoxia-inducible factor complex, during angiotensin II–induced hypertensive nephropathy provided novel insights into FSGS pathogenesis in the absence of a primary podocyte abnormality. We infused angiotensin II into endothelial-selective Epas1 knockout mice and their littermate controls. Although the groups presented with identical high BP, endothelial-specific Epas1 gene deletion accentuated albuminuria with severe podocyte lesions and recruitment of pathogenic parietal glomerular epithelial cells. These lesions and dysfunction of the glomerular filtration barrier were associated with FSGS in endothelial Epas1-deficient mice only. These results indicate that endothelial EPAS1 has a global protective role during glomerular hypertensive injuries without influencing the hypertensive effect of angiotensin II. Furthermore, these findings provide proof of principle that endothelial-derived signaling can trigger FSGS and illustrate the potential importance of the EPAS1 endothelial transcription factor in secondary FSGS.10.1681/ASN.2016090960Tue, 19 Sep 2017 07:06:03 GMT-07:00Endothelial Epas1 Deficiency Is Sufficient To Promote Parietal Epithelial Cell Activation and FSGS in Experimental HypertensionFSGS, the most common primary glomerular disorder causing ESRD, is a complex disease that is only partially understood. Progressive sclerosis is a hallmark of FSGS, and genetic tracing studies have shown that parietal epithelial cells participate in the formation of sclerotic lesions. The loss of podocytes triggers a focal activation of parietal epithelial cells, which subsequently form cellular adhesions with the capillary tuft. However, in the absence of intrinsic podocyte alterations, the origin of the pathogenic signal that triggers parietal epithelial cell recruitment remains elusive. In this study, investigation of the role of the endothelial PAS domain-containing protein 1 (EPAS1), a regulatory α subunit of the hypoxia-inducible factor complex, during angiotensin II–induced hypertensive nephropathy provided novel insights into FSGS pathogenesis in the absence of a primary podocyte abnormality. We infused angiotensin II into endothelial-selective Epas1 knockout mice and their littermate controls. Although the groups presented with identical high BP, endothelial-specific Epas1 gene deletion accentuated albuminuria with severe podocyte lesions and recruitment of pathogenic parietal glomerular epithelial cells. These lesions and dysfunction of the glomerular filtration barrier were associated with FSGS in endothelial Epas1-deficient mice only. These results indicate that endothelial EPAS1 has a global protective role during glomerular hypertensive injuries without influencing the hypertensive effect of angiotensin II. Furthermore, these findings provide proof of principle that endothelial-derived signaling can trigger FSGS and illustrate the potential importance of the EPAS1 endothelial transcription factor in secondary FSGS.Luque, YosuLenoir, OliviaBonnin, PhilippeHardy, LiseChipont, AnnaPlacier, SandrineVandermeersch, SophieXu-Dubois, Yi-ChunRobin, BlaiseLazareth, HélèneSouyri, MichèleGuyonnet, LéaBaudrie, VéroniqueCamerer, EricRondeau, EricMesnard, LaurentTharaux, Pierre-Louis2017-09-19T07:06:03-07:00doi:10.1681/ASN.2016090960hwp:resource-id:jnephrol;28/12/3563American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyendothelial cells, focal segmental glomerulosclerosis, glomerular endothelial cells, glomerular epithelial cells, hypertension, Pathophysiology of Renal Disease and ProgressionBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20160909601046-66731533-34502017-09-19T07:06:03-07:002017-12Journal of the American Society of NephrologyBasic Research281235633578
- C-Terminal Fibroblast Growth Factor 23, Iron Deficiency, and Mortality in Renal Transplant RecipientsIron deficiency (ID) is independently associated with an increased risk of death in renal transplant recipients (RTRs). ID promotes production and cleavage of intact fibroblast growth factor 23 (iFGF23) into C-terminal fibroblast growth factor 23 (cFGF23), elevated levels of which are also prospectively associated with adverse outcomes. We hypothesized that in RTRs, the relationship between ID and mortality is mediated by FGF23. We measured plasma iFGF23 and cFGF23 levels in 700 stable RTRs at a median of 5.4 years after transplant. RTRs with ID had median (interquartile range) cFGF23 concentrations higher than those of RTRs without ID (223 [131–361] versus 124 [88–180] RU/ml; P<0.001), whereas iFGF23 concentrations were similar between groups. In multivariable-adjusted Cox regression analyses, ID associated with increased mortality (81 events; hazard ratio, 1.95; 95% confidence interval, 1.22 to 3.10; P<0.01). However, this association lost significance after additional adjustment for cFGF23 levels (hazard ratio, 1.45; 95% confidence interval, 0.87 to 2.51; P=0.15). In further mediation analysis, cFGF23 explained 46% of the association between ID and mortality, whereas iFGF23 did not mediate this association. In conclusion, we found that cFGF23 levels are increased in iron-deficient RTRs and that the underlying biologic process driving production and cleavage of iFGF23, or alternatively the increased level of cFGF23 fragments, probably is an important mediator of the association between ID and mortality. Our results underline the strong relationship between iron and FGF23 physiology, and provide a potential mechanism explaining the relationship between ID and adverse outcome in RTRs.10.1681/ASN.2016121350Thu, 03 Aug 2017 07:02:28 GMT-07:00C-Terminal Fibroblast Growth Factor 23, Iron Deficiency, and Mortality in Renal Transplant RecipientsIron deficiency (ID) is independently associated with an increased risk of death in renal transplant recipients (RTRs). ID promotes production and cleavage of intact fibroblast growth factor 23 (iFGF23) into C-terminal fibroblast growth factor 23 (cFGF23), elevated levels of which are also prospectively associated with adverse outcomes. We hypothesized that in RTRs, the relationship between ID and mortality is mediated by FGF23. We measured plasma iFGF23 and cFGF23 levels in 700 stable RTRs at a median of 5.4 years after transplant. RTRs with ID had median (interquartile range) cFGF23 concentrations higher than those of RTRs without ID (223 [131–361] versus 124 [88–180] RU/ml; P<0.001), whereas iFGF23 concentrations were similar between groups. In multivariable-adjusted Cox regression analyses, ID associated with increased mortality (81 events; hazard ratio, 1.95; 95% confidence interval, 1.22 to 3.10; P<0.01). However, this association lost significance after additional adjustment for cFGF23 levels (hazard ratio, 1.45; 95% confidence interval, 0.87 to 2.51; P=0.15). In further mediation analysis, cFGF23 explained 46% of the association between ID and mortality, whereas iFGF23 did not mediate this association. In conclusion, we found that cFGF23 levels are increased in iron-deficient RTRs and that the underlying biologic process driving production and cleavage of iFGF23, or alternatively the increased level of cFGF23 fragments, probably is an important mediator of the association between ID and mortality. Our results underline the strong relationship between iron and FGF23 physiology, and provide a potential mechanism explaining the relationship between ID and adverse outcome in RTRs.Eisenga, Michele F.van Londen, MarcoLeaf, David E.Nolte, Ilja M.Navis, GerjanBakker, Stephan J.L.de Borst, Martin H.Gaillard, Carlo A.J.M.2017-08-03T07:02:28-07:00doi:10.1681/ASN.2016121350hwp:resource-id:jnephrol;28/12/3639American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfibroblast, kidney transplantation, mortality riskClinical EpidemiologyClinical Epidemiologyresearch-article20172017-12-01December 201710.1681/ASN.20161213501046-66731533-34502017-08-03T07:02:28-07:002017-12Journal of the American Society of NephrologyClinical Epidemiology281236393646
- The Clinical and Economic Effect of Vascular Access Selection in Patients Initiating Hemodialysis with a CatheterPatients in the United States frequently initiate hemodialysis with a central venous catheter (CVC) and subsequently undergo placement of a new arteriovenous fistula (AVF) or arteriovenous graft (AVG). Little is known about the clinical and economic effects of initial vascular access choice. We identified 479 patients starting hemodialysis with a CVC at a large medical center (during 2004–2012) who subsequently had an AVF (n=295) or AVG (n=105) placed or no arteriovenous access (CVC group, n=71). Compared with patients receiving an AVG, those receiving an AVF had more frequent surgical access procedures per year (1.01 [95% confidence interval, 0.95 to 1.08] versus 0.62 [95% confidence interval, 0.55 to 0.70]; P<0.001) but a similar frequency of percutaneous access procedures per year. Patients receiving an AVF had a higher median annual cost (interquartile range) of surgical access procedures than those receiving an AVG ($4857 [$2523–$8835] versus $2819 [$1411–$4274]; P<0.001), whereas the annual cost of percutaneous access procedures was similar in both groups. The AVF group had a higher median overall annual access-related cost than the AVG group ($10,642 [$5406–$19,878] versus $6810 [$3718–$13,651]; P=0.001) after controlling for patient age, sex, race, and diabetes. The CVC group had the highest median annual overall access-related cost ($28,709 [$11,793–$66,917]; P<0.001), largely attributable to the high frequency of hospitalizations due to catheter-related bacteremia. In conclusion, among patients initiating hemodialysis with a CVC, the annual cost of access-related procedures and complications is higher in patients who initially receive an AVF versus an AVG.10.1681/ASN.2016060707Fri, 14 Jul 2017 08:52:31 GMT-07:00The Clinical and Economic Effect of Vascular Access Selection in Patients Initiating Hemodialysis with a CatheterPatients in the United States frequently initiate hemodialysis with a central venous catheter (CVC) and subsequently undergo placement of a new arteriovenous fistula (AVF) or arteriovenous graft (AVG). Little is known about the clinical and economic effects of initial vascular access choice. We identified 479 patients starting hemodialysis with a CVC at a large medical center (during 2004–2012) who subsequently had an AVF (n=295) or AVG (n=105) placed or no arteriovenous access (CVC group, n=71). Compared with patients receiving an AVG, those receiving an AVF had more frequent surgical access procedures per year (1.01 [95% confidence interval, 0.95 to 1.08] versus 0.62 [95% confidence interval, 0.55 to 0.70]; P<0.001) but a similar frequency of percutaneous access procedures per year. Patients receiving an AVF had a higher median annual cost (interquartile range) of surgical access procedures than those receiving an AVG ($4857 [$2523–$8835] versus $2819 [$1411–$4274]; P<0.001), whereas the annual cost of percutaneous access procedures was similar in both groups. The AVF group had a higher median overall annual access-related cost than the AVG group ($10,642 [$5406–$19,878] versus $6810 [$3718–$13,651]; P=0.001) after controlling for patient age, sex, race, and diabetes. The CVC group had the highest median annual overall access-related cost ($28,709 [$11,793–$66,917]; P<0.001), largely attributable to the high frequency of hospitalizations due to catheter-related bacteremia. In conclusion, among patients initiating hemodialysis with a CVC, the annual cost of access-related procedures and complications is higher in patients who initially receive an AVF versus an AVG.Al-Balas, AlianLee, TimmyYoung, Carlton J.Kepes, Jeffrey A.Barker-Finkel, JillAllon, Michael2017-07-14T08:52:31-07:00doi:10.1681/ASN.2016060707hwp:resource-id:jnephrol;28/12/3679American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous access, arteriovenous fistula, arteriovenous graftClinical ResearchClinical Researchresearch-article20172017-12-01December 201710.1681/ASN.20160607071046-66731533-34502017-07-14T08:52:31-07:002017-12Journal of the American Society of NephrologyClinical Research281236793687
- Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac SurgeryClinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1–3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes.10.1681/ASN.2017010055Mon, 14 Aug 2017 07:12:17 GMT-07:00Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac SurgeryClinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1–3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB). The primary outcome was a composite of long-term CV events or death, which was assessed via national health care databases. During a median 3.8 years of follow-up, 219 (22.6%) patients experienced the primary outcome (136 CV events and 83 additional deaths). Compared with patients without postsurgical AKI, patients who experienced AKI Network stage 2 or 3 had an adjusted hazard ratio for the primary composite outcome of 3.52 (95% confidence interval, 2.17 to 5.71). However, none of the five urinary kidney injury biomarkers were significantly associated with the primary outcome. In contrast, four out of five postoperative cardiac injury biomarkers (NT-proBNP, H-FABP, hs-cTnT, and cTnI) strongly associated with the primary outcome. Mediation analyses demonstrated that cardiac biomarkers explained 49% (95% confidence interval, 1% to 97%) of the association between AKI and the primary outcome. These results suggest that clinical AKI at the time of cardiac surgery is indicative of concurrent CV stress rather than an independent renal pathway for long-term adverse CV outcomes.Parikh, Chirag R.Puthumana, JeremyShlipak, Michael G.Koyner, Jay L.Thiessen-Philbrook, HeatherMcArthur, EricKerr, KathleenKavsak, PeterWhitlock, Richard P.Garg, Amit X.Coca, Steven G.2017-08-14T07:12:17-07:00doi:10.1681/ASN.2017010055hwp:resource-id:jnephrol;28/12/3699American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cardiovascular disease, mortality riskClinical ResearchClinical Researchresearch-article20172017-12-01December 201710.1681/ASN.20170100551046-66731533-34502017-08-14T07:12:17-07:002017-12Journal of the American Society of NephrologyClinical Research281236993707
- The Association of Sleep Duration and Quality with CKD ProgressionEvidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m2, and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5–7 days of wrist actigraphy and self-report. Primary outcomes were incident ESRD, eGFR slope, log-transformed UPCR slope, and all-cause death. Participants slept an average of 6.5 hours per night; mean sleep fragmentation was 21%. Over a median follow-up of 5 years, we observed 70 ESRD events and 48 deaths. In adjusted analyses, greater sleep fragmentation associated with increased ESRD risk (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07 per 1% increase in fragmentation). In adjusted mixed effects regression models, shorter sleep duration (per hour less) and greater sleep fragmentation (per 1% more) each associated with greater eGFR decline (−1.12 and −0.18 ml/min per 1.73 m2 per year, respectively; P=0.02 and P<0.01, respectively) and greater log UPCR slope (0.06/yr and 0.01/yr, respectively; P=0.02 and P<0.001, respectively). Self-reported daytime sleepiness associated with increased risk for all-cause death (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20 per one-point increase in the Epworth Sleepiness Scale score). These findings suggest that short and poor-quality sleep are unrecognized risk factors for CKD progression.10.1681/ASN.2016121288Thu, 14 Sep 2017 08:01:33 GMT-07:00The Association of Sleep Duration and Quality with CKD ProgressionEvidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m2, and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5–7 days of wrist actigraphy and self-report. Primary outcomes were incident ESRD, eGFR slope, log-transformed UPCR slope, and all-cause death. Participants slept an average of 6.5 hours per night; mean sleep fragmentation was 21%. Over a median follow-up of 5 years, we observed 70 ESRD events and 48 deaths. In adjusted analyses, greater sleep fragmentation associated with increased ESRD risk (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07 per 1% increase in fragmentation). In adjusted mixed effects regression models, shorter sleep duration (per hour less) and greater sleep fragmentation (per 1% more) each associated with greater eGFR decline (−1.12 and −0.18 ml/min per 1.73 m2 per year, respectively; P=0.02 and P<0.01, respectively) and greater log UPCR slope (0.06/yr and 0.01/yr, respectively; P=0.02 and P<0.001, respectively). Self-reported daytime sleepiness associated with increased risk for all-cause death (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20 per one-point increase in the Epworth Sleepiness Scale score). These findings suggest that short and poor-quality sleep are unrecognized risk factors for CKD progression.Ricardo, Ana C.Knutson, KristenChen, JinsongAppel, Lawrence J.Bazzano, LydiaCarmona-Powell, EuniceCohan, JanetTamura, Manjula KurellaSteigerwalt, SusanThornton, John DarylWeir, MatthewTurek, Nicolas F.Rahman, MahboobVan Cauter, EveLash, James P.,Feldman, Harold I.Go, Alan S.He, JiangKusek, John W.Ojo, AkinloluTownsend, Raymond R.2017-09-14T08:01:33-07:00doi:10.1681/ASN.2016121288hwp:resource-id:jnephrol;28/12/3708American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Epidemiology and outcomes, mortality riskClinical ResearchClinical Researchresearch-article20172017-12-01December 201710.1681/ASN.20161212881046-66731533-34502017-09-14T08:01:33-07:002017-12Journal of the American Society of NephrologyClinical Research281237083715
- Tubulointerstitial Nephritis with IgM-Positive Plasma CellsInfiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3−-Cl− anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell–tubulointerstitial nephritis.10.1681/ASN.2016101074Wed, 09 Aug 2017 06:04:00 GMT-07:00Tubulointerstitial Nephritis with IgM-Positive Plasma CellsInfiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3−-Cl− anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell–tubulointerstitial nephritis.Takahashi, NaokiSaeki, TakakoKomatsuda, AtsushiMunemura, ChishioFukui, TakeakiImai, NaofumiHomma, NoriyukiHatta, TsuguruSamejima, Ken-ichiFujimoto, TakashiOmori, HirokiIto, YumiNishikawa, YudaiKobayashi, MamikoMorikawa, YukieFukushima, SachikoYokoi, SeijiMikami, DaisukeKasuno, KenjiKimura, HidekiNemoto, TomoyukiNakamoto, YasunariSada, KiyonaoSugai, ManabuNaiki, HironobuYoshida, HaruyoshiNarita, IchieiSaito, YoshihikoIwano, Masayuki2017-08-09T06:04:00-07:00doi:10.1681/ASN.2016101074hwp:resource-id:jnephrol;28/12/3688American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgM, plasma cell, tubulointerstitial nephritis (TIN), Fanconi syndrome, renal tubular acidosis (RTA)Clinical ResearchClinical Researchresearch-article20172017-12-01December 201710.1681/ASN.20161010741046-66731533-34502017-08-09T06:04:00-07:002017-12Journal of the American Society of NephrologyClinical Research281236883698
- Blocking TGF-β and β-Catenin Epithelial Crosstalk Exacerbates CKDThe TGF-β and Wnt/β-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-β has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-β signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-β type 2 receptor specifically in this epithelial segment. Compared with littermate controls, mice lacking the proximal tubular TGF-β receptor had significantly increased tubular injury and tubulointerstitial fibrosis in two different models of CKD. RNA sequencing indicated that deleting the TGF-β receptor in proximal tubule cells modulated many growth factor pathways, but Wnt/β-catenin signaling was the pathway most affected. We validated that deleting the proximal tubular TGF-β receptor impaired β-catenin activity in vitro and in vivo. Genetically restoring β-catenin activity in proximal tubules lacking the TGF-β receptor dramatically improved the tubular response to CKD in mice. Deleting the TGF-β receptor alters many growth factors, and therefore, this ameliorated response may be a direct effect of β-catenin activity or an indirect effect of β-catenin interacting with other growth factors. In conclusion, blocking TGF-β and β-catenin crosstalk in proximal tubules exacerbates tubular injury in two models of CKD.10.1681/ASN.2016121351Wed, 12 Jul 2017 06:10:46 GMT-07:00Blocking TGF-β and β-Catenin Epithelial Crosstalk Exacerbates CKDThe TGF-β and Wnt/β-catenin pathways have important roles in modulating CKD, but how these growth factors affect the epithelial response to CKD is not well studied. TGF-β has strong profibrotic effects, but this pleiotropic factor has many different cellular effects depending on the target cell type. To investigate how TGF-β signaling in the proximal tubule, a key target and mediator of CKD, alters the response to CKD, we injured mice lacking the TGF-β type 2 receptor specifically in this epithelial segment. Compared with littermate controls, mice lacking the proximal tubular TGF-β receptor had significantly increased tubular injury and tubulointerstitial fibrosis in two different models of CKD. RNA sequencing indicated that deleting the TGF-β receptor in proximal tubule cells modulated many growth factor pathways, but Wnt/β-catenin signaling was the pathway most affected. We validated that deleting the proximal tubular TGF-β receptor impaired β-catenin activity in vitro and in vivo. Genetically restoring β-catenin activity in proximal tubules lacking the TGF-β receptor dramatically improved the tubular response to CKD in mice. Deleting the TGF-β receptor alters many growth factors, and therefore, this ameliorated response may be a direct effect of β-catenin activity or an indirect effect of β-catenin interacting with other growth factors. In conclusion, blocking TGF-β and β-catenin crosstalk in proximal tubules exacerbates tubular injury in two models of CKD.Nlandu-Khodo, StellorNeelisetty, SurekhaPhillips, MelanieManolopoulou, MarikaBhave, GautamMay, LaurenClark, Peter E.Yang, HaichunFogo, Agnes B.Harris, Raymond C.Taketo, M. MarkLee, EthanGewin, Leslie S.2017-07-12T06:10:46-07:00doi:10.1681/ASN.2016121351hwp:resource-id:jnephrol;28/12/3490American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, proximal tubule, renal epithelial cell, fibrosisBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20161213511046-66731533-34502017-07-12T06:10:46-07:002017-12Journal of the American Society of NephrologyBasic Research2812123490342735033429
- Dialysate Potassium, Dialysate Magnesium, and Hemodialysis RiskOne of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams.10.1681/ASN.2017060640Mon, 09 Oct 2017 10:43:44 GMT-07:00Dialysate Potassium, Dialysate Magnesium, and Hemodialysis RiskOne of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams.Pun, Patrick H.Middleton, John P.2017-10-09T10:43:44-07:00doi:10.1681/ASN.2017060640hwp:resource-id:jnephrol;28/12/3441American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, end stage renal disease, clinical epidemiology, electrolytesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-12-01December 201710.1681/ASN.20170606401046-66731533-34502017-10-09T10:43:44-07:002017-12Journal of the American Society of NephrologyUp Front Matters281234413451
- Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial DamageIntracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gsα-deficient animals. Progressive albuminuria occurred in Gsα-deficient mice. Compared with controls expressing wild-type Gsα alleles, the Gsα-deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gsα-deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gsα knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gsα deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium.10.1681/ASN.2017020173Thu, 03 Aug 2017 07:02:31 GMT-07:00Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial DamageIntracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gsα-deficient animals. Progressive albuminuria occurred in Gsα-deficient mice. Compared with controls expressing wild-type Gsα alleles, the Gsα-deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gsα-deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gsα knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gsα deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium.Lachmann, PeterHickmann, LindaSteglich, AnneAl-Mekhlafi, MoathGerlach, MichaelJetschin, NielsJahn, SteffenHamann, BrigitteWnuk, MonikaMadsen, KirstenDjonov, ValentinChen, MinWeinstein, Lee S.Hohenstein, BerndHugo, Christian P.M.Todorov, Vladimir T.2017-08-03T07:02:31-07:00doi:10.1681/ASN.2017020173hwp:resource-id:jnephrol;28/12/3479American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCell Signaling, endothelium, glomerulopathy, Pathophysiology of Renal Disease and Progression, renin angiotensin system, VEGFBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20170201731046-66731533-34502017-08-03T07:02:31-07:002017-12Journal of the American Society of NephrologyBasic Research281234793489
- Assessing Microvascular Function in Humans from a Chronic Disease PerspectiveMicrovascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease.10.1681/ASN.2017020157Wed, 13 Sep 2017 06:51:36 GMT-07:00Assessing Microvascular Function in Humans from a Chronic Disease PerspectiveMicrovascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease.Houben, Alfons J.H.M.Martens, Remy J.H.Stehouwer, Coen D.A.2017-09-13T06:51:36-07:00doi:10.1681/ASN.2017020157hwp:resource-id:jnephrol;28/12/3461American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyMicrovascular dysfunction, endothelium, Cardiometabolic disease, Renal disease, PathophysiologyUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-12-01December 201710.1681/ASN.20170201571046-66731533-34502017-09-13T06:51:36-07:002017-12Journal of the American Society of NephrologyUp Front Matters281234613472
- Macrophage Migration Inhibitory Factor Limits Renal Inflammation and Fibrosis by Counteracting Tubular Cell Cycle ArrestRenal fibrosis is a common underlying process of progressive kidney diseases. We investigated the role of macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, in this process. In mice subjected to unilateral ureteral obstruction, genetic deletion or pharmacologic inhibition of MIF aggravated fibrosis and inflammation, whereas treatment with recombinant MIF was beneficial, even in established fibrosis. In two other models of progressive kidney disease, global Mif deletion or MIF inhibition also worsened fibrosis and inflammation and associated with worse kidney function. Renal MIF expression was reduced in tubular cells in fibrotic compared with healthy murine and human kidneys. Bone marrow chimeras showed that Mif expression in bone marrow-derived cells did not affect fibrosis and inflammation after UUO. However, Mif gene deletion restricted to renal tubular epithelial cells aggravated these effects. In LPS-stimulated tubular cell cultures, Mif deletion led to enhanced G2/M cell-cycle arrest and increased expression of the CDK inhibitor 1B (p27Kip1) and of proinflammatory and profibrotic mediators. Furthermore, MIF inhibition reduced tubular cell proliferation in vitro. In all three in vivo models, global Mif deletion or MIF inhibition caused similar effects and attenuated the expression of cyclin B1 in tubular cells. Mif deletion also resulted in reduced tubular cell apoptosis after UUO. Recombinant MIF exerted opposing effects on tubular cells in vitro and in vivo. Our data identify renal tubular MIF as an endogenous renoprotective factor in progressive kidney diseases, raising the possibility of pharmacologic intervention with MIF pathway agonists, which are in advanced preclinical development.10.1681/ASN.2017020190Fri, 11 Aug 2017 06:49:05 GMT-07:00Macrophage Migration Inhibitory Factor Limits Renal Inflammation and Fibrosis by Counteracting Tubular Cell Cycle ArrestRenal fibrosis is a common underlying process of progressive kidney diseases. We investigated the role of macrophage migration inhibitory factor (MIF), a pleiotropic proinflammatory cytokine, in this process. In mice subjected to unilateral ureteral obstruction, genetic deletion or pharmacologic inhibition of MIF aggravated fibrosis and inflammation, whereas treatment with recombinant MIF was beneficial, even in established fibrosis. In two other models of progressive kidney disease, global Mif deletion or MIF inhibition also worsened fibrosis and inflammation and associated with worse kidney function. Renal MIF expression was reduced in tubular cells in fibrotic compared with healthy murine and human kidneys. Bone marrow chimeras showed that Mif expression in bone marrow-derived cells did not affect fibrosis and inflammation after UUO. However, Mif gene deletion restricted to renal tubular epithelial cells aggravated these effects. In LPS-stimulated tubular cell cultures, Mif deletion led to enhanced G2/M cell-cycle arrest and increased expression of the CDK inhibitor 1B (p27Kip1) and of proinflammatory and profibrotic mediators. Furthermore, MIF inhibition reduced tubular cell proliferation in vitro. In all three in vivo models, global Mif deletion or MIF inhibition caused similar effects and attenuated the expression of cyclin B1 in tubular cells. Mif deletion also resulted in reduced tubular cell apoptosis after UUO. Recombinant MIF exerted opposing effects on tubular cells in vitro and in vivo. Our data identify renal tubular MIF as an endogenous renoprotective factor in progressive kidney diseases, raising the possibility of pharmacologic intervention with MIF pathway agonists, which are in advanced preclinical development.Djudjaj, SonjaMartin, Ina V.Buhl, Eva M.Nothofer, Nina J.Leng, LinPiecychna, MartaFloege, JürgenBernhagen, JürgenBucala, RichardBoor, Peter2017-08-11T06:49:05-07:00doi:10.1681/ASN.2017020190hwp:resource-id:jnephrol;28/12/3590American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, tubular epithelium, cell cycle arrestBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20170201901046-66731533-34502017-08-11T06:49:05-07:002017-12Journal of the American Society of NephrologyBasic Research281235903604
- Targeting Phospholipase D4 Attenuates Kidney FibrosisPhospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury. In vitro, treatment with NE attenuated TGF-β–induced accumulation of fibrotic markers. Furthermore, therapeutic targeting of PLD4 using specific siRNA protected mice from folic acid–induced kidney fibrosis and inhibited the increase in TGF-β signaling, decrease in NE expression, and upregulation of mitogen-activated protein kinase signaling. Immunoprecipitation/mass spectrometry and coimmunoprecipitation experiments confirmed that PLD4 binds three proteins that interact with neurotrophic receptor tyrosine kinase 1, a receptor also known as TrkA that upregulates mitogen-activated protein kinase. PLD4 inhibition also prevented the folic acid–induced upregulation of this receptor in mouse kidneys. These results suggest inhibition of PLD4 as a novel therapeutic strategy to activate protease-mediated degradation of extracellular matrix and reverse fibrosis.10.1681/ASN.2016111222Wed, 16 Aug 2017 08:19:55 GMT-07:00Targeting Phospholipase D4 Attenuates Kidney FibrosisPhospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury. In vitro, treatment with NE attenuated TGF-β–induced accumulation of fibrotic markers. Furthermore, therapeutic targeting of PLD4 using specific siRNA protected mice from folic acid–induced kidney fibrosis and inhibited the increase in TGF-β signaling, decrease in NE expression, and upregulation of mitogen-activated protein kinase signaling. Immunoprecipitation/mass spectrometry and coimmunoprecipitation experiments confirmed that PLD4 binds three proteins that interact with neurotrophic receptor tyrosine kinase 1, a receptor also known as TrkA that upregulates mitogen-activated protein kinase. PLD4 inhibition also prevented the folic acid–induced upregulation of this receptor in mouse kidneys. These results suggest inhibition of PLD4 as a novel therapeutic strategy to activate protease-mediated degradation of extracellular matrix and reverse fibrosis.Trivedi, PriyankaKumar, Ramya K.Iyer, AshwinBoswell, SarahGerarduzzi, CasimiroDadhania, Vivekkumar P.Herbert, ZachJoshi, NikitaLuyendyk, James P.Humphreys, Benjamin D.Vaidya, Vishal S.2017-08-16T08:19:55-07:00doi:10.1681/ASN.2016111222hwp:resource-id:jnephrol;28/12/3579American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, fibrosis, immunology, TGF-betaBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20161112221046-66731533-34502017-08-16T08:19:55-07:002017-12Journal of the American Society of NephrologyBasic Research281235793589
- Sexual Dimorphic Pattern of Renal Transporters and Electrolyte HomeostasisCompared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na+/H+ exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na+/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abundance of total and phosphorylated Na+/Cl− cotransporter (NCC), claudin-7, and cleaved forms of epithelial Na+ channel (ENaC) α and γ subunits, which associated with a lower baseline plasma K+ concentration. A K+-rich meal increased the urinary K+ concentration and decreased the level of renal phosphorylated NCC in females. Notably, we observed similar abundance profiles in female versus male C57BL/6 mice. These results define sexual dimorphic phenotypes along the nephron and suggest that lower proximal reabsorption in female rats expedites excretion of a saline load and enhances NCC and ENaC abundance and activation, which may facilitate K+ secretion and set plasma K+ at a lower level.10.1681/ASN.2017030295Thu, 03 Aug 2017 07:02:29 GMT-07:00Sexual Dimorphic Pattern of Renal Transporters and Electrolyte HomeostasisCompared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na+/H+ exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na+/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abundance of total and phosphorylated Na+/Cl− cotransporter (NCC), claudin-7, and cleaved forms of epithelial Na+ channel (ENaC) α and γ subunits, which associated with a lower baseline plasma K+ concentration. A K+-rich meal increased the urinary K+ concentration and decreased the level of renal phosphorylated NCC in females. Notably, we observed similar abundance profiles in female versus male C57BL/6 mice. These results define sexual dimorphic phenotypes along the nephron and suggest that lower proximal reabsorption in female rats expedites excretion of a saline load and enhances NCC and ENaC abundance and activation, which may facilitate K+ secretion and set plasma K+ at a lower level.Veiras, Luciana C.Girardi, Adriana C.C.Curry, JoshuaPei, LeiRalph, Donna L.Tran, AnCastelo-Branco, Regiane C.Pastor-Soler, NuriaArranz, Cristina T.Yu, Alan S.L.McDonough, Alicia A.2017-08-03T07:02:29-07:00doi:10.1681/ASN.2017030295hwp:resource-id:jnephrol;28/12/3504American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologygender difference, Na transport, proximal tubule, potassium, distal tubuleBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20170302951046-66731533-34502017-08-03T07:02:29-07:002017-12Journal of the American Society of NephrologyBasic Research281235043517
- Use and Outcomes of Kidneys from Donation after Circulatory Death Donors in the United StatesDonation after circulatory death (DCD) donors are an important source of kidneys for transplantation, but DCD donor transplantation is less common in the United States than in other countries. In this study of national data obtained between 2008 and 2015, recovery of DCD kidneys varied substantially among the country’s 58 donor service areas, and 25% of DCD kidneys were recovered in only four donor service areas. Overall, 20% of recovered DCD kidneys were discarded, varying from 3% to 33% among donor service areas. Compared with kidneys from neurologically brain dead (NBD) donors, DCD kidneys had a higher adjusted odds ratio of discard that varied from 1.25 (95% confidence interval [95% CI], 1.16 to 1.34) in kidneys with total donor warm ischemic time (WIT) of 10–26 minutes to 2.67 (95% CI, 2.34 to 3.04) in kidneys with total donor WIT >48 minutes. Among the 12,831 DCD kidneys transplanted, kidneys with WIT≤48 minutes had survival similar to that of NBD kidneys. DCD kidneys with WIT>48 minutes had a higher risk of allograft failure (hazard ratio, 1.23; 95% CI, 1.07 to 1.41), but this risk was limited to kidneys with cold ischemia time (CIT) >12 hours. We conclude that donor service area–level variation in the recovery and discard of DCD kidneys is large. Additional national data collection is needed to understand the potential to increase DCD donor transplantation in the United States. Strategies to minimize cold ischemic injury may safely allow increased use of DCD kidneys with WIT>48 minutes.10.1681/ASN.2017030238Thu, 05 Oct 2017 12:13:25 GMT-07:00Use and Outcomes of Kidneys from Donation after Circulatory Death Donors in the United StatesDonation after circulatory death (DCD) donors are an important source of kidneys for transplantation, but DCD donor transplantation is less common in the United States than in other countries. In this study of national data obtained between 2008 and 2015, recovery of DCD kidneys varied substantially among the country’s 58 donor service areas, and 25% of DCD kidneys were recovered in only four donor service areas. Overall, 20% of recovered DCD kidneys were discarded, varying from 3% to 33% among donor service areas. Compared with kidneys from neurologically brain dead (NBD) donors, DCD kidneys had a higher adjusted odds ratio of discard that varied from 1.25 (95% confidence interval [95% CI], 1.16 to 1.34) in kidneys with total donor warm ischemic time (WIT) of 10–26 minutes to 2.67 (95% CI, 2.34 to 3.04) in kidneys with total donor WIT >48 minutes. Among the 12,831 DCD kidneys transplanted, kidneys with WIT≤48 minutes had survival similar to that of NBD kidneys. DCD kidneys with WIT>48 minutes had a higher risk of allograft failure (hazard ratio, 1.23; 95% CI, 1.07 to 1.41), but this risk was limited to kidneys with cold ischemia time (CIT) >12 hours. We conclude that donor service area–level variation in the recovery and discard of DCD kidneys is large. Additional national data collection is needed to understand the potential to increase DCD donor transplantation in the United States. Strategies to minimize cold ischemic injury may safely allow increased use of DCD kidneys with WIT>48 minutes.Gill, JohnRose, CarenLesage, JulieJoffres, YayukGill, JagbirO’Connor, Kevin2017-10-05T12:13:25-07:00doi:10.1681/ASN.2017030238hwp:resource-id:jnephrol;28/12/3647American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycadaver organ transplantation, Epidemiology and outcomes, transplant outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-12-01December 201710.1681/ASN.20170302381046-66731533-34502017-10-05T12:13:25-07:002017-12Journal of the American Society of NephrologyClinical Epidemiology281236473657
- BPI Fold-Containing Family A Member 2/Parotid Secretory Protein Is an Early Biomarker of AKIAKI is a major cause of morbidity and mortality and an important contributor to the development and progression of CKD. Molecular biomarkers that improve the detection and prognostication of AKI are therefore required. We assessed the utility as such of BPI fold-containing family A member 2 (BPIFA2), also known as parotid secretory protein, which we identified via a multiplex quantitative proteomics screen of acutely injured murine kidneys. In physiologic conditions, BPIFA2 is expressed specifically in the parotid glands and is abundant in salivary secretions. In our study, AKI induced Bpifa2 expression in the kidneys of mice within 3 hours. Furthermore, we detected BPIFA2 protein in plasma and urine in these models as early as 6 hours after injury. However, renal injury did not induce the expression of Bpifa2 in mice lacking Nur77, an immediate early gene expressed in the kidneys during AKI. Notably, patients with AKI had higher blood and urine levels of BPIFA2 than did healthy individuals. Together, our results reveal that BPIFA2 is a potential early biomarker of AKI.10.1681/ASN.2016121265Thu, 03 Aug 2017 07:02:29 GMT-07:00BPI Fold-Containing Family A Member 2/Parotid Secretory Protein Is an Early Biomarker of AKIAKI is a major cause of morbidity and mortality and an important contributor to the development and progression of CKD. Molecular biomarkers that improve the detection and prognostication of AKI are therefore required. We assessed the utility as such of BPI fold-containing family A member 2 (BPIFA2), also known as parotid secretory protein, which we identified via a multiplex quantitative proteomics screen of acutely injured murine kidneys. In physiologic conditions, BPIFA2 is expressed specifically in the parotid glands and is abundant in salivary secretions. In our study, AKI induced Bpifa2 expression in the kidneys of mice within 3 hours. Furthermore, we detected BPIFA2 protein in plasma and urine in these models as early as 6 hours after injury. However, renal injury did not induce the expression of Bpifa2 in mice lacking Nur77, an immediate early gene expressed in the kidneys during AKI. Notably, patients with AKI had higher blood and urine levels of BPIFA2 than did healthy individuals. Together, our results reveal that BPIFA2 is a potential early biomarker of AKI.Kota, Satya K.Pernicone, ElizabethLeaf, David E.Stillman, Isaac E.Waikar, Sushrut S.Kota, Savithri Balasubramanian2017-08-03T07:02:29-07:00doi:10.1681/ASN.2016121265hwp:resource-id:jnephrol;28/12/3473American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, renal injury, renal ischemiaBrief CommunicationBrief Communicationbrief-report20172017-12-01December 201710.1681/ASN.20161212651046-66731533-34502017-08-03T07:02:29-07:002017-12Journal of the American Society of NephrologyBrief Communication281234733478
- Renal Tubular Cell-Derived Extracellular Vesicles Accelerate the Recovery of Established Renal Ischemia Reperfusion InjuryIschemic renal injury is a complex syndrome; multiple cellular abnormalities cause accelerating cycles of inflammation, cellular damage, and sustained local ischemia. There is no single therapy that effectively resolves the renal damage after ischemia. However, infusions of normal adult rat renal cells have been a successful therapy in several rat renal failure models. The sustained broad renal benefit achieved by relatively few donor cells led to the hypothesis that extracellular vesicles (EV, largely exosomes) derived from these cells are the therapeutic effector in situ. We now show that EV from adult rat renal tubular cells significantly improved renal function when administered intravenously 24 and 48 hours after renal ischemia in rats. Additionally, EV treatment significantly improved renal tubular damage, 4-hydroxynanoneal adduct formation, neutrophil infiltration, fibrosis, and microvascular pruning. EV therapy also markedly reduced the large renal transcriptome drift observed after ischemia. These data show the potential utility of EV to limit severe renal ischemic injury after the occurrence.10.1681/ASN.2016121278Wed, 26 Jul 2017 06:03:10 GMT-07:00Renal Tubular Cell-Derived Extracellular Vesicles Accelerate the Recovery of Established Renal Ischemia Reperfusion InjuryIschemic renal injury is a complex syndrome; multiple cellular abnormalities cause accelerating cycles of inflammation, cellular damage, and sustained local ischemia. There is no single therapy that effectively resolves the renal damage after ischemia. However, infusions of normal adult rat renal cells have been a successful therapy in several rat renal failure models. The sustained broad renal benefit achieved by relatively few donor cells led to the hypothesis that extracellular vesicles (EV, largely exosomes) derived from these cells are the therapeutic effector in situ. We now show that EV from adult rat renal tubular cells significantly improved renal function when administered intravenously 24 and 48 hours after renal ischemia in rats. Additionally, EV treatment significantly improved renal tubular damage, 4-hydroxynanoneal adduct formation, neutrophil infiltration, fibrosis, and microvascular pruning. EV therapy also markedly reduced the large renal transcriptome drift observed after ischemia. These data show the potential utility of EV to limit severe renal ischemic injury after the occurrence.Dominguez, Jesus H.Liu, YunlongGao, HongyuDominguez, James M.Xie, DanhuiKelly, K. J.2017-07-26T06:03:10-07:00doi:10.1681/ASN.2016121278hwp:resource-id:jnephrol;28/12/3533American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhypoxia, acute renal failure, cell survival, mRNA, exosomesBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20161212781046-66731533-34502017-07-26T06:03:10-07:002017-12Journal of the American Society of NephrologyBasic Research281235333544
- Opioid Prescription, Morbidity, and Mortality in United States Dialysis PatientsAggressive pain treatment was advocated for ESRD patients, but new Centers for Disease Control and Prevention guidelines recommend cautious opioid prescription. Little is known regarding outcomes associated with ESRD opioid prescription. We assessed opioid prescriptions and associations between opioid prescription and dose and patient outcomes using 2006–2010 US Renal Data System information in patients on maintenance dialysis with Medicare Part A, B, and D coverage in each study year (n=671,281, of whom 271,285 were unique patients). Opioid prescription was confirmed from Part D prescription claims. In the 2010 prevalent cohort (n=153,758), we examined associations of opioid prescription with subsequent all-cause death, dialysis discontinuation, and hospitalization controlled for demographics, comorbidity, modality, and residence. Overall, >60% of dialysis patients had at least one opioid prescription every year. Approximately 20% of patients had a chronic (≥90-day supply) opioid prescription each year, in 2010 usually for hydrocodone, oxycodone, or tramadol. In the 2010 cohort, compared with patients without an opioid prescription, patients with short-term (1–89 days) and chronic opioid prescriptions had increased mortality, dialysis discontinuation, and hospitalization. All opioid drugs associated with mortality; most associated with worsened morbidity. Higher opioid doses correlated with death in a monotonically increasing fashion. We conclude that opioid drug prescription is associated with increased risk of death, dialysis discontinuation, and hospitalization in dialysis patients. Causal relationships cannot be inferred, and opioid prescription may be an illness marker. Efforts to treat pain effectively in patients on dialysis yet decrease opioid prescriptions and dose deserve consideration.10.1681/ASN.2017010098Thu, 21 Sep 2017 05:39:13 GMT-07:00Opioid Prescription, Morbidity, and Mortality in United States Dialysis PatientsAggressive pain treatment was advocated for ESRD patients, but new Centers for Disease Control and Prevention guidelines recommend cautious opioid prescription. Little is known regarding outcomes associated with ESRD opioid prescription. We assessed opioid prescriptions and associations between opioid prescription and dose and patient outcomes using 2006–2010 US Renal Data System information in patients on maintenance dialysis with Medicare Part A, B, and D coverage in each study year (n=671,281, of whom 271,285 were unique patients). Opioid prescription was confirmed from Part D prescription claims. In the 2010 prevalent cohort (n=153,758), we examined associations of opioid prescription with subsequent all-cause death, dialysis discontinuation, and hospitalization controlled for demographics, comorbidity, modality, and residence. Overall, >60% of dialysis patients had at least one opioid prescription every year. Approximately 20% of patients had a chronic (≥90-day supply) opioid prescription each year, in 2010 usually for hydrocodone, oxycodone, or tramadol. In the 2010 cohort, compared with patients without an opioid prescription, patients with short-term (1–89 days) and chronic opioid prescriptions had increased mortality, dialysis discontinuation, and hospitalization. All opioid drugs associated with mortality; most associated with worsened morbidity. Higher opioid doses correlated with death in a monotonically increasing fashion. We conclude that opioid drug prescription is associated with increased risk of death, dialysis discontinuation, and hospitalization in dialysis patients. Causal relationships cannot be inferred, and opioid prescription may be an illness marker. Efforts to treat pain effectively in patients on dialysis yet decrease opioid prescriptions and dose deserve consideration.Kimmel, Paul L.Fwu, Chyng-WenAbbott, Kevin C.Eggers, Anne W.Kline, Prudence P.Eggers, Paul W.2017-09-21T05:39:13-07:00doi:10.1681/ASN.2017010098hwp:resource-id:jnephrol;28/12/3658American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, end stage kidney disease, Epidemiology and outcomes, mortality, United States Renal Data SystemClinical EpidemiologyClinical Epidemiologyresearch-article20172017-12-01December 201710.1681/ASN.20170100981046-66731533-34502017-09-21T05:39:13-07:002017-12Journal of the American Society of NephrologyClinical Epidemiology2812123658343236703434
- Kindlin-2 Association with Rho GDP-Dissociation Inhibitor α Suppresses Rac1 Activation and Podocyte InjuryAlteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo. Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure. Through proteomic analyses and in vitro coimmunoprecipitation experiments, we identified Rho GDP-dissociation inhibitor α (RhoGDIα) as a Kindlin-2–associated protein. Loss of Kindlin-2 in podocytes significantly reduced the expression of RhoGDIα and resulted in the dissociation of Rac1 from RhoGDIα, leading to Rac1 hyperactivation and increased motility of podocytes. Inhibition of Rac1 activation effectively suppressed podocyte motility and alleviated the podocyte defects and proteinuria induced by the loss of Kindlin-2 in vivo. Our results identify a novel Kindlin-2–RhoGDIα–Rac1 signaling axis that is critical for regulation of podocyte structure and function in vivo and provide evidence that it may serve as a useful target for therapeutic control of podocyte injury and associated glomerular diseases.10.1681/ASN.2016091021Thu, 03 Aug 2017 07:02:31 GMT-07:00Kindlin-2 Association with Rho GDP-Dissociation Inhibitor α Suppresses Rac1 Activation and Podocyte InjuryAlteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo. Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure. Through proteomic analyses and in vitro coimmunoprecipitation experiments, we identified Rho GDP-dissociation inhibitor α (RhoGDIα) as a Kindlin-2–associated protein. Loss of Kindlin-2 in podocytes significantly reduced the expression of RhoGDIα and resulted in the dissociation of Rac1 from RhoGDIα, leading to Rac1 hyperactivation and increased motility of podocytes. Inhibition of Rac1 activation effectively suppressed podocyte motility and alleviated the podocyte defects and proteinuria induced by the loss of Kindlin-2 in vivo. Our results identify a novel Kindlin-2–RhoGDIα–Rac1 signaling axis that is critical for regulation of podocyte structure and function in vivo and provide evidence that it may serve as a useful target for therapeutic control of podocyte injury and associated glomerular diseases.Sun, YingGuo, ChenMa, PingLai, YumeiYang, FanCai, JunCheng, ZhehaoZhang, KuoLiu, ZhongzhenTian, YetengSheng, YueTian, RuijunDeng, YiXiao, GuozhiWu, Chuanyue2017-08-03T07:02:31-07:00doi:10.1681/ASN.2016091021hwp:resource-id:jnephrol;28/12/3545American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyKindlin-2, RhoGDIα, Rac1, Slit diaphragms, podocyteBasic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20160910211046-66731533-34502017-08-03T07:02:31-07:002017-12Journal of the American Society of NephrologyBasic Research281235453562
- New Ultrasound Techniques Promise Further Advances in AKI and CKDAKI and CKD are important clinical problems because they affect many patients and the associated diagnostic and treatment paradigms are imperfect. Ultrasound is a cost-effective, noninvasive, and simple imaging modality that offers a multitude of means to improve the diagnosis, monitoring, and treatment of both AKI and CKD, especially considering recent advances in this technique. Ultrasound alone can attenuate AKI and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway. Additionally, microbubble contrast agents are improving the sensitivity and specificity of ultrasound for diagnosing kidney disease, especially when these agents are conjugated to ligand-specific mAbs or peptides, which make the dynamic assessment of disease progression and response to treatment possible. More recently, drug-loaded microbubbles have been developed and the load release by ultrasound exposure has been shown to be a highly specific treatment modality, making the potential applications of ultrasound even more promising. This review focuses on the multiple strategies for using ultrasound with and without microbubble technology for enhancing our understanding of the pathophysiology of AKI and CKD.10.1681/ASN.2017060647Mon, 18 Sep 2017 09:48:20 GMT-07:00New Ultrasound Techniques Promise Further Advances in AKI and CKDAKI and CKD are important clinical problems because they affect many patients and the associated diagnostic and treatment paradigms are imperfect. Ultrasound is a cost-effective, noninvasive, and simple imaging modality that offers a multitude of means to improve the diagnosis, monitoring, and treatment of both AKI and CKD, especially considering recent advances in this technique. Ultrasound alone can attenuate AKI and prevent CKD by stimulating the splenic cholinergic anti-inflammatory pathway. Additionally, microbubble contrast agents are improving the sensitivity and specificity of ultrasound for diagnosing kidney disease, especially when these agents are conjugated to ligand-specific mAbs or peptides, which make the dynamic assessment of disease progression and response to treatment possible. More recently, drug-loaded microbubbles have been developed and the load release by ultrasound exposure has been shown to be a highly specific treatment modality, making the potential applications of ultrasound even more promising. This review focuses on the multiple strategies for using ultrasound with and without microbubble technology for enhancing our understanding of the pathophysiology of AKI and CKD.Hull, Travis D.Agarwal, AnupamHoyt, Kenneth2017-09-18T09:48:20-07:00doi:10.1681/ASN.2017060647hwp:resource-id:jnephrol;28/12/3452American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, acute kidney injury, ultrasoundUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-12-01December 201710.1681/ASN.20170606471046-66731533-34502017-09-18T09:48:20-07:002017-12Journal of the American Society of NephrologyUp Front Matters281234523460
- Erratum10.1681/ASN.2017080916Thu, 30 Nov 2017 01:00:42 GMT-08:00ErratumAmerican Society of Nephrology2017-11-30T13:00:42-08:00doi:10.1681/ASN.2017080916hwp:resource-id:jnephrol;28/12/3716American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20172017-12-01December 201710.1681/ASN.20170809161046-66731533-34502017-11-30T13:00:42-08:002017-12Journal of the American Society of NephrologyErratum28281263716180237171813
- Multitarget Therapy for Maintenance Treatment of Lupus NephritisOur previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2–3 mg/d; mycophenolate mofetil, 0.50–0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P<0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; P=0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.10.1681/ASN.2017030263Mon, 31 Jul 2017 06:11:46 GMT-07:00Multitarget Therapy for Maintenance Treatment of Lupus NephritisOur previous studies showed that multitarget therapy is superior in efficacy to intravenous cyclophosphamide as an induction treatment for lupus nephritis in Asian populations. We conducted an open label, multicenter study for 18 months as an extension of the prior induction therapy trial in 19 renal centers in China to assess the efficacy and safety of multitarget maintenance therapy in patients who had responded at 24 weeks during the induction phase. Patients who had undergone multitarget induction therapy continued to receive multitarget therapy (tacrolimus, 2–3 mg/d; mycophenolate mofetil, 0.50–0.75 g/d; prednisone, 10 mg/d), and patients who had received intravenous cyclophosphamide induction treatment received azathioprine (2 mg/kg per day) plus prednisone (10 mg/d). We assessed the renal relapse rate during maintenance therapy as the primary outcome. We recruited 116 patients in the multitarget group and 90 patients in the azathioprine group. The multitarget and azathioprine groups had similar cumulative renal relapse rates (5.47% versus 7.62%, respectively; adjusted hazard ratio, 0.82; 95% confidence interval, 0.25 to 2.67; P=0.74), and serum creatinine levels and eGFR remained stable in both groups. The azathioprine group had more adverse events (44.4% versus 16.4% for multitarget therapy; P<0.01), and the multitarget group had a lower withdrawal rate due to adverse events (1.7% versus 8.9% for azathioprine; P=0.02). In conclusion, multitarget therapy as a maintenance treatment for lupus nephritis resulted in a low renal relapse rate and fewer adverse events, suggesting that multitarget therapy is an effective and safe maintenance treatment for patients with lupus nephritis.Zhang, HaitaoLiu, ZhengzhaoZhou, MinlinLiu, ZhangsuoChen, JianghuaXing, ChangyingLin, HongliNi, ZhaohuiFu, PingLiu, FuyouChen, NanHe, YongchengLiu, JiansheZeng, CaihongLiu, Zhihong2017-07-31T06:11:46-07:00doi:10.1681/ASN.2017030263hwp:resource-id:jnephrol;28/12/3671American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologylupus nephritis, multitarget therapy, maintenance treatment, renal relapse, adverse eventClinical ResearchClinical Researchresearch-article20172017-12-01December 201710.1681/ASN.20170302631046-66731533-34502017-07-31T06:11:46-07:002017-12Journal of the American Society of NephrologyClinical Research2812123671343536783437
- Targeting Anti–TGF-β Therapy to Fibrotic Kidneys with a Dual Specificity Antibody ApproachTargeted delivery of a therapeutic agent to a site of pathology to ameliorate disease while limiting exposure at undesired tissues is an aspirational treatment scenario. Targeting diseased kidneys for pharmacologic treatment has had limited success. We designed an approach to target an extracellular matrix protein, the fibronectin extra domain A isoform (FnEDA), which is relatively restricted in distribution to sites of tissue injury. In a mouse unilateral ureteral obstruction (UUO) model of renal fibrosis, injury induced significant upregulation of FnEDA in the obstructed kidney. Using dual variable domain Ig (DVD-Ig) technology, we constructed a molecule with a moiety to target FnEDA and a second moiety to neutralize TGF-β. After systemic injection of the bispecific TGF-β + FnEDA DVD-Ig or an FnEDA mAb, chemiluminescent detection and imaging with whole-body single-photon emission computed tomography (SPECT) revealed significantly higher levels of each molecule in the obstructed kidney than in the nonobstructed kidney, the ipsilateral kidney of sham animals, and other tissues. In comparison, a systemically administered TGF-β mAb accumulated at lower concentrations in the obstructed kidney and exhibited a more diffuse whole-body distribution. Systemic administration of the bispecific DVD-Ig or the TGF-β mAb (1–10 mg/kg) but not the FnEDA mAb attenuated the injury-induced collagen deposition detected by immunohistochemistry and elevation in Col1a1, FnEDA, and TIMP1 mRNA expression in the obstructed kidney. Overall, systemic delivery of a bispecific molecule targeting an extracellular matrix protein and delivering a TGF-β mAb resulted in a relatively focal uptake in the fibrotic kidney and reduced renal fibrosis.10.1681/ASN.2017010013Mon, 21 Aug 2017 05:12:43 GMT-07:00Targeting Anti–TGF-β Therapy to Fibrotic Kidneys with a Dual Specificity Antibody ApproachTargeted delivery of a therapeutic agent to a site of pathology to ameliorate disease while limiting exposure at undesired tissues is an aspirational treatment scenario. Targeting diseased kidneys for pharmacologic treatment has had limited success. We designed an approach to target an extracellular matrix protein, the fibronectin extra domain A isoform (FnEDA), which is relatively restricted in distribution to sites of tissue injury. In a mouse unilateral ureteral obstruction (UUO) model of renal fibrosis, injury induced significant upregulation of FnEDA in the obstructed kidney. Using dual variable domain Ig (DVD-Ig) technology, we constructed a molecule with a moiety to target FnEDA and a second moiety to neutralize TGF-β. After systemic injection of the bispecific TGF-β + FnEDA DVD-Ig or an FnEDA mAb, chemiluminescent detection and imaging with whole-body single-photon emission computed tomography (SPECT) revealed significantly higher levels of each molecule in the obstructed kidney than in the nonobstructed kidney, the ipsilateral kidney of sham animals, and other tissues. In comparison, a systemically administered TGF-β mAb accumulated at lower concentrations in the obstructed kidney and exhibited a more diffuse whole-body distribution. Systemic administration of the bispecific DVD-Ig or the TGF-β mAb (1–10 mg/kg) but not the FnEDA mAb attenuated the injury-induced collagen deposition detected by immunohistochemistry and elevation in Col1a1, FnEDA, and TIMP1 mRNA expression in the obstructed kidney. Overall, systemic delivery of a bispecific molecule targeting an extracellular matrix protein and delivering a TGF-β mAb resulted in a relatively focal uptake in the fibrotic kidney and reduced renal fibrosis.McGaraughty, SteveDavis-Taber, Rachel A.Zhu, Chang Z.Cole, Todd B.Nikkel, Arthur L.Chhaya, MehaDoyle, Kelly J.Olson, Lauren M.Preston, Gregory M.Grinnell, Christine M.Salte, Katherine M.Giamis, Anthony M.Luo, YanpingSun, VictorGoodearl, Andrew D.Gopalakrishnan, MuraliLacy, Susan E.2017-08-21T05:12:43-07:00doi:10.1681/ASN.2017010013hwp:resource-id:jnephrol;28/12/3616American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyTGF-β, FnEDA, interstitial fibrosis, Renal targeting, Dual variable domain Ig (DVD-Ig)Basic ResearchBasic Researchresearch-article20172017-12-01December 201710.1681/ASN.20170100131046-66731533-34502017-08-21T05:12:43-07:002017-12Journal of the American Society of NephrologyBasic Research281236163626
- Surprising Enhancement of Fibrosis by Tubule-Specific Deletion of the TGF-β Receptor: A New Twist on an Old Paradigm10.1681/ASN.2017080947Thu, 26 Oct 2017 06:38:19 GMT-07:00Surprising Enhancement of Fibrosis by Tubule-Specific Deletion of the TGF-β Receptor: A New Twist on an Old ParadigmBasile, David P.Mehrotra, Purvi2017-10-26T06:38:19-07:00doi:10.1681/ASN.2017080947hwp:resource-id:jnephrol;28/12/3427American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, epithelial, fibrosis, TGF-beta, signalingUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-12-01December 201710.1681/ASN.20170809471046-66731533-34502017-10-26T06:38:19-07:002017-12Journal of the American Society of NephrologyUp Front Matters2812123427349034293503
- Obesity-Related CKD: When Kidneys Get the Munchies10.1681/ASN.2017080850Fri, 20 Oct 2017 05:52:47 GMT-07:00Obesity-Related CKD: When Kidneys Get the MunchiesMount, Peter F.Juncos, Luis A.2017-10-20T05:52:47-07:00doi:10.1681/ASN.2017080850hwp:resource-id:jnephrol;28/12/3429American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycannabinoids, obesity-induced renal disease, renal fibrosis, lipotoxicityUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-12-01December 201710.1681/ASN.20170808501046-66731533-34502017-10-20T05:52:47-07:002017-12Journal of the American Society of NephrologyUp Front Matters2812123429351834323532
- Calcineurin Inhibitors in the Treatment of Lupus Nephritis: A Hare Versus Turtle Story?10.1681/ASN.2017080830Thu, 05 Oct 2017 12:13:25 GMT-07:00Calcineurin Inhibitors in the Treatment of Lupus Nephritis: A Hare Versus Turtle Story?Ayoub, IsabelleRovin, Brad H.2017-10-05T12:13:25-07:00doi:10.1681/ASN.2017080830hwp:resource-id:jnephrol;28/12/3435American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologysystemic lupus erythematosus, clinical trial, proteinuriaUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-12-01December 201710.1681/ASN.20170808301046-66731533-34502017-10-05T12:13:25-07:002017-12Journal of the American Society of NephrologyUp Front Matters2812123435367134373678
- This Month’s Highlights10.1681/ASN.2017090985Thu, 30 Nov 2017 01:00:41 GMT-08:00This Month’s HighlightsAmerican Society of Nephrology2017-11-30T13:00:41-08:00doi:10.1681/ASN.2017090985hwp:resource-id:jnephrol;28/12/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-12-01December 201710.1681/ASN.20170909851046-66731533-34502017-11-30T13:00:41-08:002017-12Journal of the American Society of NephrologyThis Month’s Highlights2812ii
- Prescription Opioids for Pain Management in Patients on Dialysis10.1681/ASN.2017091041Mon, 06 Nov 2017 06:04:24 GMT-08:00Prescription Opioids for Pain Management in Patients on DialysisHan, BethCompton, Wilson M.2017-11-06T06:04:24-08:00doi:10.1681/ASN.2017091041hwp:resource-id:jnephrol;28/12/3432American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, end-stage renal disease, quality of lifeUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-12-01December 201710.1681/ASN.20170910411046-66731533-34502017-11-06T06:04:24-08:002017-12Journal of the American Society of NephrologyUp Front Matters2812123432365834343670
- Perspectives from the Kidney Health Initiative on Advancing Technologies to Facilitate Remote Monitoring of Patient Self-Care in RRTTelehealth and remote monitoring of a patient’s health status has become more commonplace in the last decade and has been applied to conditions such as heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease. Conversely, uptake of these technologies to help engender and support home RRTs has lagged. Although studies have looked at the role of telehealth in RRT, they are small and single-centered, and both outcome and cost-effectiveness data are needed to inform future decision making. Furthermore, alignment of payer and government (federal and state) regulations with telehealth procedures is needed along with a better understanding of the viewpoints of the various stakeholders in this process (patients, caregivers, clinicians, payers, dialysis organizations, and government regulators). Despite these barriers, telehealth has great potential to increase the acceptance of home dialysis, and improve outcomes and patient satisfaction while potentially decreasing costs. The Kidney Health Initiative convened a multidisciplinary workgroup to examine the current state of telehealth use in home RRTs as well as outline potential benefits and drawbacks, impediments to implementation, and key unanswered questions.10.2215/CJN.12781216Fri, 14 Jul 2017 08:55:54 GMT-07:00Perspectives from the Kidney Health Initiative on Advancing Technologies to Facilitate Remote Monitoring of Patient Self-Care in RRTTelehealth and remote monitoring of a patient’s health status has become more commonplace in the last decade and has been applied to conditions such as heart failure, diabetes mellitus, hypertension, and chronic obstructive pulmonary disease. Conversely, uptake of these technologies to help engender and support home RRTs has lagged. Although studies have looked at the role of telehealth in RRT, they are small and single-centered, and both outcome and cost-effectiveness data are needed to inform future decision making. Furthermore, alignment of payer and government (federal and state) regulations with telehealth procedures is needed along with a better understanding of the viewpoints of the various stakeholders in this process (patients, caregivers, clinicians, payers, dialysis organizations, and government regulators). Despite these barriers, telehealth has great potential to increase the acceptance of home dialysis, and improve outcomes and patient satisfaction while potentially decreasing costs. The Kidney Health Initiative convened a multidisciplinary workgroup to examine the current state of telehealth use in home RRTs as well as outline potential benefits and drawbacks, impediments to implementation, and key unanswered questions.Rosner, Mitchell H.Lew, Susie Q.Conway, PaulEhrlich, JenniferJarrin, RobertPatel, Uptal D.Rheuban, KarenRobey, R. BrooksSikka, NealWallace, EricBrophy, PatrickSloand, James2017-07-14T08:55:54-07:00doi:10.2215/CJN.12781216hwp:resource-id:clinjasn;12/11/1900American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDialysis, monitoring, Caregivers, Cost-Benefit Analysis, diabetes mellitus, Government, Health Status, heart failure, Hemodialysis, Home, Humans, hypertension, Patient Satisfaction, Pulmonary Disease, Chronic Obstructive, renal dialysis, Self Care, TelemedicineReviewReviewreview-article20172017-11-07November 07, 201710.2215/CJN.127812161555-90411555-905X2017-07-14T08:55:54-07:002017-11-07Clinical Journal of the American Society of NephrologyReview121119001909
- APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD10.2215/CJN.01180117Thu, 19 Oct 2017 06:59:54 GMT-07:00APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKDChen, Teresa K.Tin, AdriennePeralta, Carmen A.Appel, Lawrence J.Choi, Michael J.Lipkowitz, Michael S.Winkler, Cheryl A.Estrella, Michelle M.2017-10-19T06:59:54-07:00doi:10.2215/CJN.01180117hwp:resource-id:clinjasn;12/11/1771American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAPOL1, Apo L1, CKD, AASK (African American Study of Kidney Disease and Hypertension), African Americans, Alleles, BP, creatinine, Follow-Up Studies, Genotype, GFR, Humans, hypertension, Kidney Failure, Chronic, Proportional Hazards Models, proteinuria, Renal Insufficiency, Chronic, United StatesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-11-07November 07, 201710.2215/CJN.011801171555-90411555-905X2017-10-19T06:59:54-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1211111771172317771725
- Metabolomic Alterations Associated with Cause of CKD10.2215/CJN.02560317Thu, 28 Sep 2017 09:24:53 GMT-07:00Metabolomic Alterations Associated with Cause of CKDGrams, Morgan E.Tin, AdrienneRebholz, Casey M.Shafi, TariqKöttgen, AnnaPerrone, Ronald D.Sarnak, Mark J.Inker, Lesley A.Levey, Andrew S.Coresh, Josef2017-09-28T09:24:53-07:00doi:10.2215/CJN.02560317hwp:resource-id:clinjasn;12/11/1787American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMDRD Study, Metabolomic profiling, metabolites, glomerular filtration rate, Kynurenic Acid, homocitrulline, blood pressure, Body Mass Index, Random Allocation, Tandem Mass Spectrometry, kidney, Renal Insufficiency, Chronic, proteinuria, Citrulline, Polycystic Kidney Diseases, Diet, Prognosis, Demography, Sulfates, Hippurates, Chromatography, Liquid, Dietary Proteins, MaleOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-11-07November 07, 201710.2215/CJN.025603171555-90411555-905X2017-09-28T09:24:53-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1211111787172617941727
- Patterns of NSAIDs Use and Their Association with Other Analgesic Use in CKD10.2215/CJN.12311216Tue, 15 Aug 2017 05:16:28 GMT-07:00Patterns of NSAIDs Use and Their Association with Other Analgesic Use in CKDZhan, MinSt. Peter, Wendy L.Doerfler, Rebecca M.Woods, Corinne M.Blumenthal, Jacob B.Diamantidis, Clarissa J.Hsu, Chi-yuanLash, James P.Lustigova, EvaMahone, Erin B.Ojo, Akinlolu O.Slaven, AnneStrauss, LouiseTaliercio, Jonathan J.Winkelmayer, Wolfgang C.Xie, DaweiFink, Jeffery C.,2017-08-15T05:16:28-07:00doi:10.2215/CJN.12311216hwp:resource-id:clinjasn;12/11/1778American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, safety, non-steroidal anti-inflammatory drugs, analgesics, opioidOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-11-07November 07, 201710.2215/CJN.123112161555-90411555-905X2017-08-15T05:16:28-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121117781786
- Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention10.2215/CJN.00390117Wed, 11 Oct 2017 07:42:40 GMT-07:00Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System InterventionPetrykiv, Sergei I.Laverman, Gozewijn DirkPersson, FrederikVogt, LiffertRossing, Peterde Borst, Martin H.Gansevoort, Ronald T.de Zeeuw, DickHeerspink, Hiddo J.L.2017-10-11T07:42:40-07:00doi:10.2215/CJN.00390117hwp:resource-id:clinjasn;12/11/1804American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, renin angiotensin system, ACE inhibitors, renal dysfunction, Angiotensin Receptor Antagonists, albuminuria, Potassium, blood pressure, Sodium, Peptidyl-Dipeptidase A, Prostaglandins, Anti-Inflammatory Agents, Non-Steroidal, Cross-Over Studies, Angiotensin-Converting Enzyme Inhibitors, Diet, Sodium-Restricted, Renal Insufficiency, Chronic, Psychotherapy, Drug Combinations, Sodium, DietaryOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-11-07November 07, 201710.2215/CJN.003901171555-90411555-905X2017-10-11T07:42:40-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121118041813
- Fibroblast Growth Factor 23 and Anemia in the Chronic Renal Insufficiency Cohort Study10.2215/CJN.03950417Mon, 07 Aug 2017 06:33:23 GMT-07:00Fibroblast Growth Factor 23 and Anemia in the Chronic Renal Insufficiency Cohort StudyMehta, RupalCai, XuanHodakowski, AlexanderLee, JungwhaLeonard, MaryRicardo, AnaChen, JingHamm, LeeSondheimer, JamesDobre, MirelaDavid, ValentinYang, WeiGo, AlanKusek, John W.Feldman, HaroldWolf, MylesIsakova, Tamara,2017-08-07T06:33:23-07:00doi:10.2215/CJN.03950417hwp:resource-id:clinjasn;12/11/1795American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, mineral metabolism, glomerular filtration rate, risk factors, Odds Ratio, erythropoietin, Confidence Intervals, Prospective Studies, Erythropoiesis, Fibroblast Growth Factors, Renal Insufficiency, Chronic, Hemoglobins, Demography, Cardiovascular Diseases, Minerals, Humans, Male, FemaleOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-11-07November 07, 201710.2215/CJN.039504171555-90411555-905X2017-08-07T06:33:23-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121117951803
- Nephrology Provider Prognostic Perceptions and Care Delivered to Older Adults with Advanced Kidney Disease10.2215/CJN.03830417Mon, 18 Sep 2017 12:49:23 GMT-07:00Nephrology Provider Prognostic Perceptions and Care Delivered to Older Adults with Advanced Kidney DiseaseSalat, HuzaifahJavier, AndreiSiew, Edward D.Figueroa, RocioLipworth, LorenKabagambe, EdmondBian, AihuaStewart, Thomas G.El-Sourady, Maie H.Karlekar, MohanaCardona, Cesar Y.Ikizler, T. AlpAbdel-Kader, Khaled2017-09-18T12:49:23-07:00doi:10.2215/CJN.03830417hwp:resource-id:clinjasn;12/11/1762American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, advance care planning, conservative management, surprise question, shared decision making, end of life care, living will, durable power of attorney, renal replacement therapy planning, medical order, Hospices, Prospective Studies, nephrology, Uncertainty, Nephrologists, Conservative Treatment, Follow-Up Studies, Advance Care Planning, Terminal Care, Hospice Care, kidney, Renal Insufficiency, Chronic, DocumentationOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-11-07November 07, 201710.2215/CJN.038304171555-90411555-905X2017-09-18T12:49:23-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121117621770
- Management of a Patient with Catheter-Related Bloodstream Infection10.2215/CJN.01210217Wed, 05 Jul 2017 06:34:13 GMT-07:00Management of a Patient with Catheter-Related Bloodstream InfectionLok, Charmaine E.2017-07-05T06:34:13-07:00doi:10.2215/CJN.01210217hwp:resource-id:clinjasn;12/11/1873American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis catheter, Bacteremia, Prophylaxis, Infection, Diagnosis, Catheter-Related Infections, Catheterization, Central Venous, HumansKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20172017-11-07November 07, 201710.2215/CJN.012102171555-90411555-905X2017-07-05T06:34:13-07:002017-11-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire121118731877
- Pregnancy and Glomerular DiseaseDuring pregnancy, CKD increases both maternal and fetal risk. Adverse maternal outcomes include progression of underlying renal dysfunction, worsening of urine protein, and hypertension, whereas adverse fetal outcomes include fetal loss, intrauterine growth restriction, and preterm delivery. As such, pregnancy in young women with CKD is anxiety provoking for both the patient and the clinician providing care, and because the heterogeneous group of glomerular diseases often affects young women, this is an area of heightened concern. In this invited review, we discuss pregnancy outcomes in young women with glomerular diseases. We have performed a systematic review in attempt to better understand these outcomes among young women with primary GN, we review the studies of pregnancy outcomes in lupus nephritis, and finally, we provide a potential construct for management. Although it is safe to say that the vast majority of young women with glomerular disease will have a live birth, the counseling that we can provide with respect to individualized risk remains imprecise in primary GN because the existing literature is extremely dated, and all management principles are extrapolated primarily from studies in lupus nephritis and diabetes. As such, the study of pregnancy outcomes and management strategies in these rare diseases requires a renewed interest and a dedicated collaborative effort.10.2215/CJN.00130117Thu, 18 May 2017 11:07:33 GMT-07:00Pregnancy and Glomerular DiseaseDuring pregnancy, CKD increases both maternal and fetal risk. Adverse maternal outcomes include progression of underlying renal dysfunction, worsening of urine protein, and hypertension, whereas adverse fetal outcomes include fetal loss, intrauterine growth restriction, and preterm delivery. As such, pregnancy in young women with CKD is anxiety provoking for both the patient and the clinician providing care, and because the heterogeneous group of glomerular diseases often affects young women, this is an area of heightened concern. In this invited review, we discuss pregnancy outcomes in young women with glomerular diseases. We have performed a systematic review in attempt to better understand these outcomes among young women with primary GN, we review the studies of pregnancy outcomes in lupus nephritis, and finally, we provide a potential construct for management. Although it is safe to say that the vast majority of young women with glomerular disease will have a live birth, the counseling that we can provide with respect to individualized risk remains imprecise in primary GN because the existing literature is extremely dated, and all management principles are extrapolated primarily from studies in lupus nephritis and diabetes. As such, the study of pregnancy outcomes and management strategies in these rare diseases requires a renewed interest and a dedicated collaborative effort.Blom, KimberlyOdutayo, AyodeleBramham, KateHladunewich, Michelle A.2017-05-18T11:07:33-07:00doi:10.2215/CJN.00130117hwp:resource-id:clinjasn;12/11/1862American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypregnancy, systematic review, glomerular disease, glomerulonephritisGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-11-07November 07, 201710.2215/CJN.001301171555-90411555-905X2017-05-18T11:07:33-07:002017-11-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician121118621872
- Disparity between Nephrologists’ Opinions and Contemporary Practices for Community Follow-Up after AKI Hospitalization10.2215/CJN.01450217Thu, 12 Oct 2017 06:36:23 GMT-07:00Disparity between Nephrologists’ Opinions and Contemporary Practices for Community Follow-Up after AKI HospitalizationKarsanji, Divya J.Pannu, NeeshManns, Braden J.Hemmelgarn, Brenda R.Tan, ZhiJindal, KailashScott-Douglas, NairneJames, Matthew T.2017-10-12T06:36:23-07:00doi:10.2215/CJN.01450217hwp:resource-id:clinjasn;12/11/1753American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, dialysis, clinical nephrology, nephrology, Nephrologists, Uncertainty, Alberta, Follow-Up Studies, Acute Kidney Injury, Renal Insufficiency, Chronic, Patient Discharge, hospitalization, Referral and Consultation, Surveys and Questionnaires, heart failureOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20172017-11-07November 07, 201710.2215/CJN.014502171555-90411555-905X2017-10-12T06:36:23-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121117531761
- Infrequent Provision of Palliative Care to Patients with Dialysis-Requiring AKI10.2215/CJN.00270117Tue, 17 Oct 2017 06:48:09 GMT-07:00Infrequent Provision of Palliative Care to Patients with Dialysis-Requiring AKIChong, KellySilver, Samuel A.Long, JinZheng, YuanchaoPankratz, V. ShaneUnruh, Mark L.Chertow, Glenn M.2017-10-17T06:48:09-07:00doi:10.2215/CJN.00270117hwp:resource-id:clinjasn;12/11/1744American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, clinical epidemiology, United States, Comorbidity, Logistic Models, Inpatients, Shock, Cardiogenic, International Classification of Diseases, Respiratory Distress Syndrome, Adult, Palliative Care, Acute Kidney Injury, Hispanic Americans, African Continental Ancestry Group, Fluid Therapy, Intracranial Hemorrhages, Prognosis, Demography, Humans, renal dialysisOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20172017-11-07November 07, 201710.2215/CJN.002701171555-90411555-905X2017-10-17T06:48:09-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1211111744172117521722
- Health Care Costs Associated with AKI10.2215/CJN.00950117Thu, 19 Oct 2017 06:59:53 GMT-07:00Health Care Costs Associated with AKICollister, DavidPannu, NeeshYe, FengJames, MatthewHemmelgarn, BrendaChui, BettyManns, BradenKlarenbach, Scott,2017-10-19T06:59:53-07:00doi:10.2215/CJN.00950117hwp:resource-id:clinjasn;12/11/1733American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, chronic kidney disease, dialysis, costs, resource utilization, creatinine, Cost-Benefit Analysis, Inpatients, Outpatients, Linear Models, Alberta, Investments, Length of Stay, Acute Kidney Injury, Kidney Function Tests, Renal Insufficiency, Chronic, hospitalization, Health Care Costs, Kidney Failure, Chronic, CanadaOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20172017-11-07November 07, 201710.2215/CJN.009501171555-90411555-905X2017-10-19T06:59:53-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121117331743
- The Lived Experience of “Being Evaluated” for Organ Donation10.2215/CJN.03550417Mon, 09 Oct 2017 07:00:35 GMT-07:00The Lived Experience of “Being Evaluated” for Organ DonationHanson, Camilla S.Ralph, Angelique F.Manera, Karine E.Gill, John S.Kanellis, JohnWong, GermaineCraig, Jonathan C.Chapman, Jeremy R.Tong, Allison2017-10-09T07:00:35-07:00doi:10.2215/CJN.03550417hwp:resource-id:clinjasn;12/11/1852American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, evaluation, assessment, focus groups, qualitative research, Panic, Shame, Uncertainty, Focus Groups, Investments, Emotions, Living Donors, Risk, Fear, Tissue and Organ Procurement, Anxiety, Life Style, Australia, CanadaOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-11-07November 07, 201710.2215/CJN.035504171555-90411555-905X2017-10-09T07:00:35-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121118521861
- Randomized Crossover Trial of Blood Volume Monitoring–Guided Ultrafiltration Biofeedback to Reduce Intradialytic Hypotensive Episodes with Hemodialysis10.2215/CJN.01030117Tue, 10 Oct 2017 07:48:57 GMT-07:00Randomized Crossover Trial of Blood Volume Monitoring–Guided Ultrafiltration Biofeedback to Reduce Intradialytic Hypotensive Episodes with HemodialysisLeung, Kelvin C.W.Quinn, Robert R.Ravani, PietroDuff, HenryMacRae, Jennifer M.2017-10-10T07:48:57-07:00doi:10.2215/CJN.01030117hwp:resource-id:clinjasn;12/11/1831American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, randomized controlled trials, intradialytic hypotension, biofeedback, Cross-Over Studies, renal dialysis, ultrafiltration, Natriuretic Peptide, Brain, Single-Blind Method, Alberta, Weight Gain, Confidence Intervals, Water, Random Allocation, Blood Volume, hypotension, Biofeedback, Psychology, Fluid Therapy, Troponin, CanadaOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-11-07November 07, 201710.2215/CJN.010301171555-90411555-905X2017-10-10T07:48:57-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1211111831173018401732
- Risk of Infective Endocarditis in Patients with End Stage Renal Disease10.2215/CJN.02320317Tue, 03 Oct 2017 08:54:15 GMT-07:00Risk of Infective Endocarditis in Patients with End Stage Renal DiseaseChaudry, Mavish S.Carlson, NicholasGislason, Gunnar H.Kamper, Anne-LiseRix, MarianneFowler, Vance G.Torp-Pedersen, ChristianBruun, Niels E.2017-10-03T08:54:15-07:00doi:10.2215/CJN.02320317hwp:resource-id:clinjasn;12/11/1814American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, peritoneal dialysis, kidney transplantation, vascular access, dialysis access, end stage kidney disease, Endocarditis, mortality, Middle Aged, renal dialysis, Central Venous Catheters, Incidence, risk factors, Aortic Valve, Kidney Failure, Chronic, RRT, kidney, Heart Defects, Congenital, Heart Valve Diseases, Registries, EndocarditisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-11-07November 07, 201710.2215/CJN.023203171555-90411555-905X2017-10-03T08:54:15-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1211111814172818221729
- Vascular Access Type and Clinical Outcomes among Elderly Patients on Hemodialysis10.2215/CJN.01410217Thu, 10 Aug 2017 06:07:20 GMT-07:00Vascular Access Type and Clinical Outcomes among Elderly Patients on HemodialysisLee, TimmyThamer, MaeZhang, QianZhang, YiAllon, Michael2017-08-10T06:07:20-07:00doi:10.2215/CJN.01410217hwp:resource-id:clinjasn;12/11/1823American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis access, dialysis, Aged, arteriovenous fistula, Arteriovenous Shunt, Surgical, Bacteremia, Central Venous Catheters, Confidence Intervals, hospitalization, Humans, Life Expectancy, Propensity Score, renal dialysis, Risk, SepsisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-11-07November 07, 201710.2215/CJN.014102171555-90411555-905X2017-08-10T06:07:20-07:002017-11-07Clinical Journal of the American Society of NephrologyOriginal Articles121118231830
- Feedback Control in Hemodialysis—Much Ado about Nothing?10.2215/CJN.09770917Tue, 10 Oct 2017 07:48:56 GMT-07:00Feedback Control in Hemodialysis—Much Ado about Nothing?Hecking, ManfredSchneditz, Daniel2017-10-10T07:48:56-07:00doi:10.2215/CJN.09770917hwp:resource-id:clinjasn;12/11/1730American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, ultrafiltration, renal dialysis, Blood Volume, hypotensionEditorialsEditorialseditorial20172017-11-07November 07, 201710.2215/CJN.097709171555-90411555-905X2017-10-10T07:48:56-07:002017-11-07Clinical Journal of the American Society of NephrologyEditorials1211111730183117321840
- Long Overdue Need to Reduce Infections with Hemodialysis10.2215/CJN.09280817Tue, 03 Oct 2017 08:54:14 GMT-07:00Long Overdue Need to Reduce Infections with HemodialysisKliger, Alan S.Collins, Allan J.2017-10-03T08:54:14-07:00doi:10.2215/CJN.09280817hwp:resource-id:clinjasn;12/11/1728American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, infections, renal dialysisEditorialsEditorialseditorial20172017-11-07November 07, 201710.2215/CJN.092808171555-90411555-905X2017-10-03T08:54:14-07:002017-11-07Clinical Journal of the American Society of NephrologyEditorials1211111728181417291822
- Statistical Methods for Modeling Time-Updated Exposures in Cohort Studies of Chronic Kidney DiseaseWhen estimating the effect of an exposure on a time-to-event type of outcome, one can focus on the baseline exposure or the time-updated exposures. Cox regression models can be used in both situations. When time-dependent confounding exists, the Cox model with time-updated covariates may produce biased effect estimates. Marginal structural models, estimated through inverse-probability weighting, were developed to appropriately adjust for time-dependent confounding. We review the concept of time-dependent confounding and illustrate the process of inverse-probability weighting. We fit a marginal structural model to estimate the effect of time-updated systolic BP on the time to renal events such as ESRD in the Chronic Renal Insufficiency Cohort. We compare the Cox regression model and the marginal structural model on several attributes (effects estimated, result interpretation, and assumptions) and give recommendations for when to use each method.10.2215/CJN.00650117Thu, 17 Aug 2017 10:24:17 GMT-07:00Statistical Methods for Modeling Time-Updated Exposures in Cohort Studies of Chronic Kidney DiseaseWhen estimating the effect of an exposure on a time-to-event type of outcome, one can focus on the baseline exposure or the time-updated exposures. Cox regression models can be used in both situations. When time-dependent confounding exists, the Cox model with time-updated covariates may produce biased effect estimates. Marginal structural models, estimated through inverse-probability weighting, were developed to appropriately adjust for time-dependent confounding. We review the concept of time-dependent confounding and illustrate the process of inverse-probability weighting. We fit a marginal structural model to estimate the effect of time-updated systolic BP on the time to renal events such as ESRD in the Chronic Renal Insufficiency Cohort. We compare the Cox regression model and the marginal structural model on several attributes (effects estimated, result interpretation, and assumptions) and give recommendations for when to use each method.Xie, DaweiYang, WeiJepson, ChristopherRoy, JasonHsu, Jesse Y.Shou, HaochangAnderson, Amanda H.Landis, J. RichardFeldman, Harold I.,2017-08-17T10:24:17-07:00doi:10.2215/CJN.00650117hwp:resource-id:clinjasn;12/11/1892American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCausal inference, marginal structural models, survival analysis, time-varying Cox model, time-dependent confounding, inverse-probability treatment weight, inverse-probability censoring weight, blood pressure, Cohort Studies, Kidney Failure, Chronic, Probability, Proportional Hazards Models, Renal Insufficiency, Chronic, chronic kidney diseaseFeatureFeatureresearch-article20172017-11-07November 07, 201710.2215/CJN.006501171555-90411555-905X2017-08-17T10:24:17-07:002017-11-07Clinical Journal of the American Society of NephrologyFeature121118921899
- Metabolomics and Kidney Precision Medicine10.2215/CJN.09480817Thu, 28 Sep 2017 09:24:53 GMT-07:00Metabolomics and Kidney Precision MedicineKalim, SahirRhee, Eugene P.2017-09-28T09:24:53-07:00doi:10.2215/CJN.09480817hwp:resource-id:clinjasn;12/11/1726American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMetabolomics, Metabolite profiling, Precision medicine, chronic kidney disease, kidneyEditorialsEditorialseditorial20172017-11-07November 07, 201710.2215/CJN.094808171555-90411555-905X2017-09-28T09:24:53-07:002017-11-07Clinical Journal of the American Society of NephrologyEditorials1211111726178717271794
- APOL1 and Proteinuria in the AASK10.2215/CJN.10680917Thu, 19 Oct 2017 06:59:52 GMT-07:00APOL1 and Proteinuria in the AASKO’Toole, John F.Bruggeman, Leslie A.Sedor, John R.2017-10-19T06:59:52-07:00doi:10.2215/CJN.10680917hwp:resource-id:clinjasn;12/11/1723American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAPOL1, proteinuria, AASK (African American Study of Kidney Disease and Hypertension), podocyte, Apolipoprotein L1, precision medicine, ApolipoproteinsEditorialsEditorialseditorial20172017-11-07November 07, 201710.2215/CJN.106809171555-90411555-905X2017-10-19T06:59:52-07:002017-11-07Clinical Journal of the American Society of NephrologyEditorials1211111723177117251777
- Recognizing the Elephant in the Room10.2215/CJN.09810917Tue, 17 Oct 2017 06:48:10 GMT-07:00Recognizing the Elephant in the RoomBansal, Amar D.Schell, Jane O.2017-10-17T06:48:10-07:00doi:10.2215/CJN.09810917hwp:resource-id:clinjasn;12/11/1721American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypalliative care, acute renal failure, Humans, nephrology, Outpatients, Acute Kidney Injury, Renal Insufficiency, Chronic, kidney, Chronic Disease, renal dialysisEditorialsEditorialseditorial20172017-11-07November 07, 201710.2215/CJN.098109171555-90411555-905X2017-10-17T06:48:10-07:002017-11-07Clinical Journal of the American Society of NephrologyEditorials1211111721174417221752
- Why Diuretics Fail Failing Hearts10.1681/ASN.2017070797Fri, 18 Aug 2017 06:57:11 GMT-07:00Why Diuretics Fail Failing HeartsRay, Evan C.Boyd-Shiwarski, Cary R.Kleyman, Thomas R.2017-08-18T06:57:11-07:00doi:10.1681/ASN.2017070797hwp:resource-id:jnephrol;28/11/3137American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydiuretics, heart failure, epithelial sodium transportUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-11-01November 201710.1681/ASN.20170707971046-66731533-34502017-08-18T06:57:11-07:002017-11Journal of the American Society of NephrologyUp Front Matters2811113137341431383424
- Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add-On Therapy for Diabetic NephropathyEstablished therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells. Indeed, TUDCA induced expression of FXR-dependent genes (SOCS3 and DDAH1) in tubular cells but not in other renal cells. In vivo, TUDCA reduced glomerular and tubular injury in db/db and diabetic endothelial nitric oxide synthase–deficient mice. FXR inhibition with Z-guggulsterone or vivo-morpholino targeting of FXR diminished the ER-stabilizing and renoprotective effects of TUDCA. Notably, these in vivo approaches abolished tubular but not glomerular protection by TUDCA. Combined intervention with TUDCA and the angiotensin-converting enzyme inhibitor enalapril in 16-week-old db/db mice reduced albuminuria more efficiently than did either treatment alone. Although both therapies reduced glomerular damage, only TUDCA ameliorated tubular damage. Thus, interventions that specifically protect the tubular compartment in dNP, such as FXR agonism, may provide renoprotective effects on top of those achieved by inhibiting angiotensin-converting enzyme.10.1681/ASN.2016101123Mon, 10 Jul 2017 11:39:50 GMT-07:00Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add-On Therapy for Diabetic NephropathyEstablished therapies for diabetic nephropathy (dNP) delay but do not prevent its progression. The shortage of established therapies may reflect the inability to target the tubular compartment. The chemical chaperone tauroursodeoxycholic acid (TUDCA) ameliorates maladaptive endoplasmic reticulum (ER) stress signaling and experimental dNP. Additionally, TUDCA activates the farnesoid X receptor (FXR), which is highly expressed in tubular cells. We hypothesized that TUDCA ameliorates maladaptive ER signaling via FXR agonism specifically in tubular cells. Indeed, TUDCA induced expression of FXR-dependent genes (SOCS3 and DDAH1) in tubular cells but not in other renal cells. In vivo, TUDCA reduced glomerular and tubular injury in db/db and diabetic endothelial nitric oxide synthase–deficient mice. FXR inhibition with Z-guggulsterone or vivo-morpholino targeting of FXR diminished the ER-stabilizing and renoprotective effects of TUDCA. Notably, these in vivo approaches abolished tubular but not glomerular protection by TUDCA. Combined intervention with TUDCA and the angiotensin-converting enzyme inhibitor enalapril in 16-week-old db/db mice reduced albuminuria more efficiently than did either treatment alone. Although both therapies reduced glomerular damage, only TUDCA ameliorated tubular damage. Thus, interventions that specifically protect the tubular compartment in dNP, such as FXR agonism, may provide renoprotective effects on top of those achieved by inhibiting angiotensin-converting enzyme.Marquardt, AndiAl-Dabet, Moh’d MohanadGhosh, SanchitaKohli, ShreyManoharan, JayakumarElWakiel, AhmedGadi, IhsanBock, FabianNazir, SumraWang, HongjieLindquist, Jonathan A.Nawroth, Peter PaulMadhusudhan, ThatiMertens, Peter R.Shahzad, KhurrumIsermann, Berend2017-07-10T11:39:50-07:00doi:10.1681/ASN.2016101123hwp:resource-id:jnephrol;28/11/3182American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytudca ER-stress diabetes, diabetic nephropathy, FXR, ACE inhibitorsBrief CommunicationsBrief Communicationsbrief-report20172017-11-01November 201710.1681/ASN.20161011231046-66731533-34502017-07-10T11:39:50-07:002017-11Journal of the American Society of NephrologyBrief Communications281131823189
- Lysophosphatidic Acid Receptor Antagonism Protects against Diabetic Nephropathy in a Type 2 Diabetic ModelLysophosphatidic acid (LPA) functions through activation of LPA receptors (LPARs). LPA–LPAR signaling has been implicated in development of fibrosis. However, the role of LPA–LPAR signaling in development of diabetic nephropathy (DN) has not been studied. We examined whether BMS002, a novel dual LPAR1 and LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase-knockout db/db mice. Treatment of these mice with BMS002 from 8 to 20 weeks of age led to a significant reduction in albuminuria, similar to that observed with renin-angiotensin system inhibition (losartan plus enalapril). LPAR inhibition also prevented the decline in GFR observed in vehicle-treated mice, such that GFR at week 20 differed significantly between vehicle and LPAR inhibitor groups (P<0.05). LPAR inhibition also reduced histologic glomerular injury; decreased the expression of profibrotic and fibrotic components, including fibronectin, α-smooth muscle actin, connective tissue growth factor, collagen I, and TGF-β; and reduced renal macrophage infiltration and oxidative stress. Notably, LPAR inhibition slowed podocyte loss (podocytes per glomerulus ±SEM at 8 weeks: 667±40, n=4; at 20 weeks: 364±18 with vehicle, n=7, and 536±12 with LPAR inhibition, n=7; P<0.001 versus vehicle). Finally, LPAR inhibition minimized the production of 4-hydroxynonenal (4-HNE), a marker of oxidative stress, in podocytes and increased the phosphorylation of AKT2, an indicator of AKT2 activity, in kidneys. Thus, the LPAR antagonist BMS002 protects against GFR decline and attenuates development of DN through multiple mechanisms. LPAR antagonism might provide complementary beneficial effects to renin-angiotensin system inhibition to slow progression of DN.10.1681/ASN.2017010107Mon, 24 Jul 2017 06:14:25 GMT-07:00Lysophosphatidic Acid Receptor Antagonism Protects against Diabetic Nephropathy in a Type 2 Diabetic ModelLysophosphatidic acid (LPA) functions through activation of LPA receptors (LPARs). LPA–LPAR signaling has been implicated in development of fibrosis. However, the role of LPA–LPAR signaling in development of diabetic nephropathy (DN) has not been studied. We examined whether BMS002, a novel dual LPAR1 and LPAR3 antagonist, affects development of DN in endothelial nitric oxide synthase-knockout db/db mice. Treatment of these mice with BMS002 from 8 to 20 weeks of age led to a significant reduction in albuminuria, similar to that observed with renin-angiotensin system inhibition (losartan plus enalapril). LPAR inhibition also prevented the decline in GFR observed in vehicle-treated mice, such that GFR at week 20 differed significantly between vehicle and LPAR inhibitor groups (P<0.05). LPAR inhibition also reduced histologic glomerular injury; decreased the expression of profibrotic and fibrotic components, including fibronectin, α-smooth muscle actin, connective tissue growth factor, collagen I, and TGF-β; and reduced renal macrophage infiltration and oxidative stress. Notably, LPAR inhibition slowed podocyte loss (podocytes per glomerulus ±SEM at 8 weeks: 667±40, n=4; at 20 weeks: 364±18 with vehicle, n=7, and 536±12 with LPAR inhibition, n=7; P<0.001 versus vehicle). Finally, LPAR inhibition minimized the production of 4-hydroxynonenal (4-HNE), a marker of oxidative stress, in podocytes and increased the phosphorylation of AKT2, an indicator of AKT2 activity, in kidneys. Thus, the LPAR antagonist BMS002 protects against GFR decline and attenuates development of DN through multiple mechanisms. LPAR antagonism might provide complementary beneficial effects to renin-angiotensin system inhibition to slow progression of DN.Zhang, Ming-ZhiWang, XinYang, HaichunFogo, Agnes B.Murphy, Brian J.Kaltenbach, RobertCheng, PeterZinker, BradleyHarris, Raymond C.2017-07-24T06:14:25-07:00doi:10.1681/ASN.2017010107hwp:resource-id:jnephrol;28/11/3300American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyLPA, autotoxin, macrophage, diabetic nephropathy, AKT2Basic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20170101071046-66731533-34502017-07-24T06:14:25-07:002017-11Journal of the American Society of NephrologyBasic Research281133003311
- The Evolving Complexity of the Podocyte CytoskeletonPodocytes exhibit a unique cytoskeletal architecture that is fundamentally linked to their function in maintaining the kidney filtration barrier. The cytoskeleton regulates podocyte shape, structure, stability, slit diaphragm insertion, adhesion, plasticity, and dynamic response to environmental stimuli. Genetic mutations demonstrate that even slight impairment of the podocyte cytoskeletal apparatus results in proteinuria and glomerular disease. Moreover, mechanisms underpinning all acquired glomerular pathologies converge on disruption of the cytoskeleton, suggesting that this subcellular structure could be targeted for therapeutic purposes. This review summarizes our current understanding of the function of the cytoskeleton in podocytes and the associated implications for pathophysiology.10.1681/ASN.2017020143Fri, 01 Sep 2017 06:49:06 GMT-07:00The Evolving Complexity of the Podocyte CytoskeletonPodocytes exhibit a unique cytoskeletal architecture that is fundamentally linked to their function in maintaining the kidney filtration barrier. The cytoskeleton regulates podocyte shape, structure, stability, slit diaphragm insertion, adhesion, plasticity, and dynamic response to environmental stimuli. Genetic mutations demonstrate that even slight impairment of the podocyte cytoskeletal apparatus results in proteinuria and glomerular disease. Moreover, mechanisms underpinning all acquired glomerular pathologies converge on disruption of the cytoskeleton, suggesting that this subcellular structure could be targeted for therapeutic purposes. This review summarizes our current understanding of the function of the cytoskeleton in podocytes and the associated implications for pathophysiology.Schell, ChristophHuber, Tobias B.2017-09-01T06:49:06-07:00doi:10.1681/ASN.2017020143hwp:resource-id:jnephrol;28/11/3166American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, glomerular disease, cytoskeleton, nephrotic syndromeUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-11-01November 201710.1681/ASN.20170201431046-66731533-34502017-09-01T06:49:06-07:002017-11Journal of the American Society of NephrologyUp Front Matters281131663174
- Haploinsufficiency of the Transcription Factor Ets-1 Is Renoprotective in Dahl Salt-Sensitive RatsStudies using Dahl salt-sensitive (SS) rats identified specific quantitative trait loci that predispose animals to hypertension-associated albuminuria and kidney injury. We explored the hypothesis that kidney-specific expression of the transcription factor Ets-1, located within one of these loci on chromosome 8, mediates glomerular injury in SS hypertension. During the first week on a high-salt diet, SS rats and SS rats with only one functioning Ets-1 gene (ES rats) demonstrated similar increases in BP. However, serum creatinine concentration, albuminuria, and glomerular expression of ETS-1 and two ETS-1 targets, MCP-1 and MMP2, did not increase as substantially in ES rats as in SS rats. Mean BP subsequently increased further in SS rats and remained higher than that of ES rats for the rest of the study. After 4 weeks of high-salt intake, ES rats still showed a lower mean serum creatinine concentration and less albuminuria, as well as less histologic evidence of glomerular injury and kidney fibrosis, than SS rats did. To investigate the specific contribution of renal Ets-1, we transplanted kidneys from ES or SS rats into salt-resistant SS-Chr 13BN/McwiCrl (SS-13BN) rats. Within 10 days on a high-salt diet, BP increased similarly in ES and SS allograft recipients, becoming significantly higher than the BP of control isograft recipients. However, mean serum creatinine concentration and albuminuria remained lower in ES allograft recipients than in SS allograft recipients at 2 weeks, and ES allografts showed less glomerular injury and interstitial fibrosis. In conclusion, reduced renal expression of ETS-1 prevented hypertension-associated kidney injury in SS rats.10.1681/ASN.2017010085Mon, 10 Jul 2017 11:39:52 GMT-07:00Haploinsufficiency of the Transcription Factor Ets-1 Is Renoprotective in Dahl Salt-Sensitive RatsStudies using Dahl salt-sensitive (SS) rats identified specific quantitative trait loci that predispose animals to hypertension-associated albuminuria and kidney injury. We explored the hypothesis that kidney-specific expression of the transcription factor Ets-1, located within one of these loci on chromosome 8, mediates glomerular injury in SS hypertension. During the first week on a high-salt diet, SS rats and SS rats with only one functioning Ets-1 gene (ES rats) demonstrated similar increases in BP. However, serum creatinine concentration, albuminuria, and glomerular expression of ETS-1 and two ETS-1 targets, MCP-1 and MMP2, did not increase as substantially in ES rats as in SS rats. Mean BP subsequently increased further in SS rats and remained higher than that of ES rats for the rest of the study. After 4 weeks of high-salt intake, ES rats still showed a lower mean serum creatinine concentration and less albuminuria, as well as less histologic evidence of glomerular injury and kidney fibrosis, than SS rats did. To investigate the specific contribution of renal Ets-1, we transplanted kidneys from ES or SS rats into salt-resistant SS-Chr 13BN/McwiCrl (SS-13BN) rats. Within 10 days on a high-salt diet, BP increased similarly in ES and SS allograft recipients, becoming significantly higher than the BP of control isograft recipients. However, mean serum creatinine concentration and albuminuria remained lower in ES allograft recipients than in SS allograft recipients at 2 weeks, and ES allografts showed less glomerular injury and interstitial fibrosis. In conclusion, reduced renal expression of ETS-1 prevented hypertension-associated kidney injury in SS rats.Feng, WenguangChen, BoXing, DongqiLi, XingshengFatima, HumaJaimes, Edgar A.Sanders, Paul W.2017-07-10T11:39:52-07:00doi:10.1681/ASN.2017010085hwp:resource-id:jnephrol;28/11/3239American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, Ets-1, albuminuria, kidney disease, kidney transplantationBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20170100851046-66731533-34502017-07-10T11:39:52-07:002017-11Journal of the American Society of NephrologyBasic Research2811113239313132503133
- Transplantation of Kidneys from HCV-Positive Donors: How to Best Use a Scarce Resource10.1681/ASN.2017060673Tue, 05 Sep 2017 06:44:23 GMT-07:00Transplantation of Kidneys from HCV-Positive Donors: How to Best Use a Scarce ResourceRoth, DavidLadino, Marco2017-09-05T06:44:23-07:00doi:10.1681/ASN.2017060673hwp:resource-id:jnephrol;28/11/3139American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, hepatitis, kidney donationUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20172017-11-01November 201710.1681/ASN.20170606731046-66731533-34502017-09-05T06:44:23-07:002017-11Journal of the American Society of NephrologyUp Front Matters281131393141
- Ets in the Kidney—Unraveling the Molecular Mechanism Underlying Renal Damage in Salt-Sensitive Hypertension10.1681/ASN.2017080917Mon, 16 Oct 2017 07:40:31 GMT-07:00Ets in the Kidney—Unraveling the Molecular Mechanism Underlying Renal Damage in Salt-Sensitive HypertensionGigliotti, Joseph C.Le, Thu H.2017-10-16T07:40:31-07:00doi:10.1681/ASN.2017080917hwp:resource-id:jnephrol;28/11/3131American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, kidney injury, salt-sensitivity, inflammationUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-11-01November 201710.1681/ASN.20170809171046-66731533-34502017-10-16T07:40:31-07:002017-11Journal of the American Society of NephrologyUp Front Matters2811113131323931333250
- Yap/Taz Deletion in Gli+ Cell-Derived Myofibroblasts Attenuates FibrosisIn damaged kidneys, increased extracellular matrix (ECM) and tissue stiffness stimulate kidney fibrosis through incompletely characterized molecular mechanisms. The transcriptional coactivators yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) function as mechanosensors in cancer cells and have been implicated in the regulation of myofibroblasts in the kidney. We hypothesized that the development of kidney fibrosis depends on Yap-induced activation and proliferation of kidney fibroblasts. In mice, Yap expression increased in renal fibroblasts after unilateral ureteral obstruction (UUO), in association with worsening of interstitial fibrosis. In cultured fibroblasts, inhibition of Yap/Taz signaling blocked TGF-β1–induced fibroblast-to-myofibroblast transformation and ECM production, whereas constitutive activation of Yap promoted fibroblast transformation and ECM production even in the absence of TGF-β1. Moreover, in the absence of TGF-β1, fibroblasts seeded on a stiffened ECM transformed into myofibroblasts in a process dependent on the activation of Yap. In mice with UUO, the Yap inhibitor verteporfin reduced interstitial fibrosis. Furthermore, Gli1+ cell-specific knockout of Yap/Taz in mice suppressed UUO-induced ECM deposition, myofibroblast accumulation, and interstitial fibrosis. In a UUO-release model, induction of Gli1+ cell-specific Yap/Taz knockout partially reversed the development of interstitial fibrosis. Thus, in the kidney, Yap is a tissue mechanosensor that can be activated by ECM and transforms fibroblasts into myofibroblasts; the interaction of Yap/Taz and ECM forms a feed-forward loop resulting in kidney fibrosis. Identifying mechanisms that interrupt this profibrotic cycle could lead to the development of anti-fibrosis therapy.10.1681/ASN.2015121354Wed, 02 Aug 2017 05:50:02 GMT-07:00Yap/Taz Deletion in Gli+ Cell-Derived Myofibroblasts Attenuates FibrosisIn damaged kidneys, increased extracellular matrix (ECM) and tissue stiffness stimulate kidney fibrosis through incompletely characterized molecular mechanisms. The transcriptional coactivators yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) function as mechanosensors in cancer cells and have been implicated in the regulation of myofibroblasts in the kidney. We hypothesized that the development of kidney fibrosis depends on Yap-induced activation and proliferation of kidney fibroblasts. In mice, Yap expression increased in renal fibroblasts after unilateral ureteral obstruction (UUO), in association with worsening of interstitial fibrosis. In cultured fibroblasts, inhibition of Yap/Taz signaling blocked TGF-β1–induced fibroblast-to-myofibroblast transformation and ECM production, whereas constitutive activation of Yap promoted fibroblast transformation and ECM production even in the absence of TGF-β1. Moreover, in the absence of TGF-β1, fibroblasts seeded on a stiffened ECM transformed into myofibroblasts in a process dependent on the activation of Yap. In mice with UUO, the Yap inhibitor verteporfin reduced interstitial fibrosis. Furthermore, Gli1+ cell-specific knockout of Yap/Taz in mice suppressed UUO-induced ECM deposition, myofibroblast accumulation, and interstitial fibrosis. In a UUO-release model, induction of Gli1+ cell-specific Yap/Taz knockout partially reversed the development of interstitial fibrosis. Thus, in the kidney, Yap is a tissue mechanosensor that can be activated by ECM and transforms fibroblasts into myofibroblasts; the interaction of Yap/Taz and ECM forms a feed-forward loop resulting in kidney fibrosis. Identifying mechanisms that interrupt this profibrotic cycle could lead to the development of anti-fibrosis therapy.Liang, MingYu, MichaelXia, RuohanSong, KeWang, JunLuo, JinlongChen, GuangCheng, Jizhong2017-08-02T05:50:02-07:00doi:10.1681/ASN.2015121354hwp:resource-id:jnephrol;28/11/3278American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, obstructive nephropathy, stiffness, YAPBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20151213541046-66731533-34502017-08-02T05:50:02-07:002017-11Journal of the American Society of NephrologyBasic Research281132783290
- Endothelial NF-κB Blockade Abrogates ANCA-Induced GNANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF-κB mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF-κB activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF-κB–dependent tumor necrosis factor α (TNF-α). NF-κB activation positively correlated with crescent formation, and nuclear phospho-p65 staining showed NF-κB activation within CD31-expressing endothelial cells (ECs) in affected glomeruli. Therefore, we studied the effect of ANCA on NF-κB activation in neutrophil/EC cocultures in vitro. ANCA did not activate NF-κB in primed human neutrophils, but ANCA-stimulated primed neutrophils activated NF-κB in ECs, at least in part via TNF-α release. This effect increased endothelial gene transcription and protein production of NF-κB–regulated interleukin-8. Moreover, upregulation of endothelial NF-κB promoted neutrophil adhesion to EC monolayers, an effect that was inhibited by a specific IKKβ inhibitor. In a murine NCGN model, prophylactic application of E-selectin–targeted immunoliposomes packed with p65 siRNA to downregulate endothelial NF-κB significantly reduced urine abnormalities, renal myeloid cell influx, and NCGN. Increased glomerular endothelial phospho-p65 staining in patients with AAV indicated that NF-κB is activated in human NCGN also. We suggest that ANCA-stimulated neutrophils activate endothelial NF-κB, which contributes to NCGN and provides a potential therapeutic target in AAV.10.1681/ASN.2016060690Fri, 07 Jul 2017 06:34:37 GMT-07:00Endothelial NF-κB Blockade Abrogates ANCA-Induced GNANCA-associated vasculitis (AAV) is a highly inflammatory condition in which ANCA-activated neutrophils interact with the endothelium, resulting in necrotizing vasculitis. We tested the hypothesis that endothelial NF-κB mediates necrotizing crescentic GN (NCGN) and provides a specific treatment target. Reanalysis of kidneys from previously examined murine NCGN disease models revealed NF-κB activation in affected kidneys, mostly as a p50/p65 heterodimer, and increased renal expression of NF-κB–dependent tumor necrosis factor α (TNF-α). NF-κB activation positively correlated with crescent formation, and nuclear phospho-p65 staining showed NF-κB activation within CD31-expressing endothelial cells (ECs) in affected glomeruli. Therefore, we studied the effect of ANCA on NF-κB activation in neutrophil/EC cocultures in vitro. ANCA did not activate NF-κB in primed human neutrophils, but ANCA-stimulated primed neutrophils activated NF-κB in ECs, at least in part via TNF-α release. This effect increased endothelial gene transcription and protein production of NF-κB–regulated interleukin-8. Moreover, upregulation of endothelial NF-κB promoted neutrophil adhesion to EC monolayers, an effect that was inhibited by a specific IKKβ inhibitor. In a murine NCGN model, prophylactic application of E-selectin–targeted immunoliposomes packed with p65 siRNA to downregulate endothelial NF-κB significantly reduced urine abnormalities, renal myeloid cell influx, and NCGN. Increased glomerular endothelial phospho-p65 staining in patients with AAV indicated that NF-κB is activated in human NCGN also. We suggest that ANCA-stimulated neutrophils activate endothelial NF-κB, which contributes to NCGN and provides a potential therapeutic target in AAV.Choi, MiraSchreiber, AdrianEulenberg-Gustavus, ClaudiaScheidereit, ClausKamps, JanKettritz, Ralph2017-07-07T06:34:37-07:00doi:10.1681/ASN.2016060690hwp:resource-id:jnephrol;28/11/3191American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, endothelium, transcription factors, vasculitis, glomerulonephritisBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20160606901046-66731533-34502017-07-07T06:34:37-07:002017-11Journal of the American Society of NephrologyBasic Research281131913204
- Kidney Disease in HIV: Moving beyond HIV-Associated NephropathyIn developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the APOL1 renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy. Concerns for nephrotoxicity also extend to HIV-negative individuals using tenofovir disoproxil fumarate–based pre-exposure prophylaxis for the prevention of HIV infection. Therefore, CKD remains an important comorbid condition in the HIV-positive population and an emerging concern among HIV-negative persons receiving pre-exposure prophylaxis. With the improved longevity of HIV-positive individuals, a kidney transplant has become a viable option for many who have progressed to ESRD. Herein, we review the growing knowledge regarding the APOL1 renal risk variants in the context of HIV infection, antiretroviral therapy–related nephrotoxicity, and developments in kidney transplantation among HIV-positive individuals.10.1681/ASN.2017040468Mon, 07 Aug 2017 06:45:22 GMT-07:00Kidney Disease in HIV: Moving beyond HIV-Associated NephropathyIn developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the APOL1 renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy. Concerns for nephrotoxicity also extend to HIV-negative individuals using tenofovir disoproxil fumarate–based pre-exposure prophylaxis for the prevention of HIV infection. Therefore, CKD remains an important comorbid condition in the HIV-positive population and an emerging concern among HIV-negative persons receiving pre-exposure prophylaxis. With the improved longevity of HIV-positive individuals, a kidney transplant has become a viable option for many who have progressed to ESRD. Herein, we review the growing knowledge regarding the APOL1 renal risk variants in the context of HIV infection, antiretroviral therapy–related nephrotoxicity, and developments in kidney transplantation among HIV-positive individuals.Jotwani, VasanthaAtta, Mohamed G.Estrella, Michelle M.2017-08-07T06:45:22-07:00doi:10.1681/ASN.2017040468hwp:resource-id:jnephrol;28/11/3142American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyHIV nephropathy, Apolipoprotein L1, chronic kidney diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-11-01November 201710.1681/ASN.20170404681046-66731533-34502017-08-07T06:45:22-07:002017-11Journal of the American Society of NephrologyUp Front Matters281131423154
- Hepatocyte Nuclear Factor-1β Controls Mitochondrial Respiration in Renal Tubular CellsAKI is a frequent condition that involves renal microcirculation impairment, infiltration of inflammatory cells with local production of proinflammatory cytokines, and subsequent epithelial disorders and mitochondrial dysfunction. Peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A), a coactivator of the transcription factor PPAR-γ that controls mitochondrial biogenesis and function, has a pivotal role in the early dysfunction of the proximal tubule and the subsequent renal repair. Here, we evaluated the potential role of hepatocyte nuclear factor–1β (HNF-1β) in regulating PPARGC1A expression in AKI. In mice, endotoxin injection to induce AKI also induced early and transient inflammation and PPARGC1A inhibition, which overlapped with downregulation of the HNF-1β transcriptional network. In vitro, exposure of proximal tubule cells to the inflammatory cytokines IFN-γ and TNF-α led to inhibition of HNF-1β transcriptional activity. Moreover, inhibition of HNF-1β significantly reduced PPARGC1A expression and altered mitochondrial morphology and respiration in proximal tubule cells. Chromatin immunoprecipitation assays and PCR analysis confirmed HNF-1β binding to the Ppargc1a promoter in mouse kidneys. We also demonstrated downregulation of renal PPARGC1A expression in a patient with an HNF1B germinal mutation. Thus, we propose that HNF-1β links extracellular inflammatory signals to mitochondrial dysfunction during AKI partly via PPARGC1A signaling. Our findings further strengthen the view of HNF1B-related nephropathy as a mitochondrial disorder in adulthood.10.1681/ASN.2016050508Mon, 24 Jul 2017 06:14:24 GMT-07:00Hepatocyte Nuclear Factor-1β Controls Mitochondrial Respiration in Renal Tubular CellsAKI is a frequent condition that involves renal microcirculation impairment, infiltration of inflammatory cells with local production of proinflammatory cytokines, and subsequent epithelial disorders and mitochondrial dysfunction. Peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A), a coactivator of the transcription factor PPAR-γ that controls mitochondrial biogenesis and function, has a pivotal role in the early dysfunction of the proximal tubule and the subsequent renal repair. Here, we evaluated the potential role of hepatocyte nuclear factor–1β (HNF-1β) in regulating PPARGC1A expression in AKI. In mice, endotoxin injection to induce AKI also induced early and transient inflammation and PPARGC1A inhibition, which overlapped with downregulation of the HNF-1β transcriptional network. In vitro, exposure of proximal tubule cells to the inflammatory cytokines IFN-γ and TNF-α led to inhibition of HNF-1β transcriptional activity. Moreover, inhibition of HNF-1β significantly reduced PPARGC1A expression and altered mitochondrial morphology and respiration in proximal tubule cells. Chromatin immunoprecipitation assays and PCR analysis confirmed HNF-1β binding to the Ppargc1a promoter in mouse kidneys. We also demonstrated downregulation of renal PPARGC1A expression in a patient with an HNF1B germinal mutation. Thus, we propose that HNF-1β links extracellular inflammatory signals to mitochondrial dysfunction during AKI partly via PPARGC1A signaling. Our findings further strengthen the view of HNF1B-related nephropathy as a mitochondrial disorder in adulthood.Casemayou, AudreyFournel, AudrenBagattin, AlessiaSchanstra, JoostBelliere, JulieDecramer, StéphaneMarsal, DimitriGillet, MarionChassaing, NicolasHuart, AntoinePontoglio, MarcoKnauf, ClaudeBascands, Jean-LoupChauveau, DominiqueFaguer, Stanislas2017-07-24T06:14:24-07:00doi:10.1681/ASN.2016050508hwp:resource-id:jnephrol;28/11/3205American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyHNF1B, acute kidney injury, mitochondria, PPARGC1ABasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20160505081046-66731533-34502017-07-24T06:14:24-07:002017-11Journal of the American Society of NephrologyBasic Research281132053217
- Extracellular Vesicles in Preeclampsia: Evolving Contributors to Proteinuria10.1681/ASN.2017070789Tue, 19 Sep 2017 07:06:02 GMT-07:00Extracellular Vesicles in Preeclampsia: Evolving Contributors to ProteinuriaPhipps, Elizabeth A.Khankin, Eliyahu V.2017-09-19T07:06:02-07:00doi:10.1681/ASN.2017070789hwp:resource-id:jnephrol;28/11/3135American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyextracellular vesicles, preeclampsia, nephrin, podocytes, nephrinuria, podocyturiaUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-11-01November 201710.1681/ASN.20170707891046-66731533-34502017-09-19T07:06:02-07:002017-11Journal of the American Society of NephrologyUp Front Matters2811113135336331373372
- Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody DevelopmentDespite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient’s individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch. HLA-DR/DQ eplet mismatch was a significant multivariate predictor of dnDSA development. Recipients treated with a cyclosporin regimen had a 2.7-fold higher incidence of dnDSA development than recipients on a tacrolimus regimen. Recipients treated with tacrolimus who developed HLA-DR/DQ dnDSA had a higher proportion of tacrolimus trough levels <5 ng/ml, which continued to be significant after adjustment for HLA-DR/DQ eplet mismatch. Mean tacrolimus trough levels in the 6 months before dnDSA development were significantly lower than the levels >6 months before dnDSA development in the same patients. Recipients with a high-risk HLA eplet mismatch score were less likely to tolerate low tacrolimus levels without developing dnDSA. We conclude that HLA-DR/DQ eplet mismatch and tacrolimus trough levels are independent predictors of dnDSA development. Recipients with high HLA alloimmune risk should not target tacrolimus levels <5 ng/ml unless essential, and monitoring for dnDSA may be advisable in this setting.10.1681/ASN.2017030287Thu, 20 Jul 2017 07:23:13 GMT-07:00Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody DevelopmentDespite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody (dnDSA) development correlates with tacrolimus trough levels and the recipient’s individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds <6 ng/ml and the mean tacrolimus levels before dnDSA development in the context of HLA-DR/DQ eplet mismatch. HLA-DR/DQ eplet mismatch was a significant multivariate predictor of dnDSA development. Recipients treated with a cyclosporin regimen had a 2.7-fold higher incidence of dnDSA development than recipients on a tacrolimus regimen. Recipients treated with tacrolimus who developed HLA-DR/DQ dnDSA had a higher proportion of tacrolimus trough levels <5 ng/ml, which continued to be significant after adjustment for HLA-DR/DQ eplet mismatch. Mean tacrolimus trough levels in the 6 months before dnDSA development were significantly lower than the levels >6 months before dnDSA development in the same patients. Recipients with a high-risk HLA eplet mismatch score were less likely to tolerate low tacrolimus levels without developing dnDSA. We conclude that HLA-DR/DQ eplet mismatch and tacrolimus trough levels are independent predictors of dnDSA development. Recipients with high HLA alloimmune risk should not target tacrolimus levels <5 ng/ml unless essential, and monitoring for dnDSA may be advisable in this setting.Wiebe, ChrisRush, David N.Nevins, Thomas E.Birk, Patricia E.Blydt-Hansen, TomGibson, Ian W.Goldberg, AvivaHo, JulieKarpinski, MartinPochinco, DeniseSharma, AtulStorsley, LeroyMatas, Arthur J.Nickerson, Peter W.2017-07-20T07:23:13-07:00doi:10.1681/ASN.2017030287hwp:resource-id:jnephrol;28/11/3353American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, acute allograft rejection, donor specific antibody, Human leukocyte antigen, tacrolimus, allograft survivalClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20170302871046-66731533-34502017-07-20T07:23:13-07:002017-11Journal of the American Society of NephrologyClinical Research281133533362
- Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in PreeclampsiaRenal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and α1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of HbF in podocyte injury was studied in pregnant rabbits. Compared with urine from women with normotensive pregnancies, urine from women with preeclamptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podocin+ EVs-to-nephrin+ EVs ratio) and increased nephrinuria, both of which correlated with proteinuria. Plasma levels of hemopexin, which were decreased in women with preeclampsia, negatively correlated with proteinuria, urinary podocin+ EVs-to-nephrin+ EVs ratio, and nephrinuria. Administration of HbF to pregnant rabbits increased the number of urinary EVs of podocyte origin. These findings provide evidence that urinary EVs are reflective of preeclampsia-related altered podocyte protein expression. Furthermore, renal injury in preeclampsia associated with an elevated urinary podocin+ EVs-to-nephrin+ EVs ratio and may be mediated by prolonged exposure to cellfree HbF.10.1681/ASN.2016111202Thu, 20 Jul 2017 07:23:13 GMT-07:00Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in PreeclampsiaRenal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and α1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of HbF in podocyte injury was studied in pregnant rabbits. Compared with urine from women with normotensive pregnancies, urine from women with preeclamptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podocin+ EVs-to-nephrin+ EVs ratio) and increased nephrinuria, both of which correlated with proteinuria. Plasma levels of hemopexin, which were decreased in women with preeclampsia, negatively correlated with proteinuria, urinary podocin+ EVs-to-nephrin+ EVs ratio, and nephrinuria. Administration of HbF to pregnant rabbits increased the number of urinary EVs of podocyte origin. These findings provide evidence that urinary EVs are reflective of preeclampsia-related altered podocyte protein expression. Furthermore, renal injury in preeclampsia associated with an elevated urinary podocin+ EVs-to-nephrin+ EVs ratio and may be mediated by prolonged exposure to cellfree HbF.Gilani, Sarwat I.Anderson, Ulrik DolbergJayachandran, MuthuvelWeissgerber, Tracey L.Zand, LadanWhite, Wendy M.Milic, NatasaSuarez, Maria Lourdes GonzalezVallapureddy, Rangit ReddyNääv, ÅsaErlandsson, LenaLieske, John C.Grande, Joseph P.Nath, Karl A.Hansson, Stefan R.Garovic, Vesna D.2017-07-20T07:23:13-07:00doi:10.1681/ASN.2016111202hwp:resource-id:jnephrol;28/11/3363American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, preeclampsia, extracellular vesiclesClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20161112021046-66731533-34502017-07-20T07:23:13-07:002017-11Journal of the American Society of NephrologyClinical Research2811113363313533723137
- Association Analysis of the MHC in Lupus NephritisLupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRβ1 amino acid 11 (Pomnibus<0.001), HLA-DQβ1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA-DPβ1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.10.1681/ASN.2016121331Fri, 28 Jul 2017 06:24:00 GMT-07:00Association Analysis of the MHC in Lupus NephritisLupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DRβ1 amino acid 11 (Pomnibus<0.001), HLA-DQβ1 amino acid 45 (P<0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (Pomnibus<0.001), HLA-DPβ1 amino acid 76 (Pomnibus<0.001), and a missense variant in PRRC2A (rs114580964; P<0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.Xu, RicongLi, QibinLiu, RongjunShen, JuanLi, MingZhao, MinghuiWang, MengLiao, QijunMao, HaipingLi, ZhijianZhou, NaYin, PeiranLi, YueTang, XueqingWu, TianZhong, ZhongWang, YanAi, ZhenWang, OuChen, NanYang, XiaoqinFang, JunbinFu, PingGu, JieruoYe, KunChen, JianDai, LieLiu, HuafengLiu, ZhangsuoLiao, YunhuaWan, JianxinDing, GuohuaZhao, JinghongZhang, HaoFu, ShuxiaSun, LiangdanZhang, XuejunYang, HuanmingWang, JianWang, JunLiu, JianjunLi, YingruiYu, Xueqing2017-07-28T06:24:00-07:00doi:10.1681/ASN.2016121331hwp:resource-id:jnephrol;28/11/3383American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyDeep Sequencing, Major Histocompatibility Complex, Multiple Risk Variants, lupus nephritisClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20161213311046-66731533-34502017-07-28T06:24:00-07:002017-11Journal of the American Society of NephrologyClinical Research281133833394
- The Loss of GSTM1 Associates with Kidney Failure and Heart FailureGlutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1, respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1: kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 (P>0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.10.1681/ASN.2017030228Tue, 18 Jul 2017 07:41:19 GMT-07:00The Loss of GSTM1 Associates with Kidney Failure and Heart FailureGlutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1, respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1: kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 (P>0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.Tin, AdrienneScharpf, RobertEstrella, Michelle M.Yu, BingGrove, Megan L.Chang, Patricia P.Matsushita, KunihiroKöttgen, AnnaArking, Dan E.Boerwinkle, EricLe, Thu H.Coresh, JosefGrams, Morgan E.2017-07-18T07:41:19-07:00doi:10.1681/ASN.2017030228hwp:resource-id:jnephrol;28/11/3345American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic heart failure, chronic renal failure, Epidemiology and outcomes, human geneticsClinical EpidemiologyClinical Epidemiologyresearch-article20172017-11-01November 201710.1681/ASN.20170302281046-66731533-34502017-07-18T07:41:19-07:002017-11Journal of the American Society of NephrologyClinical Epidemiology281133453352
- Breast Regression Protein–39/Chitinase 3–Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of MyofibroblastsThe normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein–39 (BRP-39), also known as chitinase 3–like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α2 (IL13Rα2)–mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI. In wild-type mice, failure to resolve tubular injury after unilateral ischemia-reperfusion injury (U-IRI) led to sustained low-level Chi3l1 mRNA expression by renal cells and promoted macrophage persistence and severe interstitial fibrosis. Analysis of macrophages isolated from wild-type kidneys 14 days after U-IRI revealed high-level expression of the profibrotic BRP-39 receptor Ptgdr2/Crth2 and expression of the profibrotic markers Lgals3, Pdgfb, Egf, and Tgfb. In comparison, injured kidneys from mice lacking BRP-39 had significantly fewer macrophages, reduced expression of profibrotic growth factors, and decreased accumulation of extracellular matrix. BRP-39 depletion did not affect myofibroblast accumulation but did attenuate myofibroblast expression of Col1a1, Col3a1, and Fn1. Together, these results identify BRP-39 as an important activator of macrophage-myofibroblast crosstalk and profibrotic signaling in the setting of maladaptive kidney repair.10.1681/ASN.2017010110Wed, 05 Jul 2017 06:37:27 GMT-07:00Breast Regression Protein–39/Chitinase 3–Like 1 Promotes Renal Fibrosis after Kidney Injury via Activation of MyofibroblastsThe normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein–39 (BRP-39), also known as chitinase 3–like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α2 (IL13Rα2)–mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI. In wild-type mice, failure to resolve tubular injury after unilateral ischemia-reperfusion injury (U-IRI) led to sustained low-level Chi3l1 mRNA expression by renal cells and promoted macrophage persistence and severe interstitial fibrosis. Analysis of macrophages isolated from wild-type kidneys 14 days after U-IRI revealed high-level expression of the profibrotic BRP-39 receptor Ptgdr2/Crth2 and expression of the profibrotic markers Lgals3, Pdgfb, Egf, and Tgfb. In comparison, injured kidneys from mice lacking BRP-39 had significantly fewer macrophages, reduced expression of profibrotic growth factors, and decreased accumulation of extracellular matrix. BRP-39 depletion did not affect myofibroblast accumulation but did attenuate myofibroblast expression of Col1a1, Col3a1, and Fn1. Together, these results identify BRP-39 as an important activator of macrophage-myofibroblast crosstalk and profibrotic signaling in the setting of maladaptive kidney repair.Montgomery, Tinika A.Xu, LeyuanMason, ShereneChinnadurai, AmirthaLee, Chun GeunElias, Jack A.Cantley, Lloyd G.2017-07-05T06:37:27-07:00doi:10.1681/ASN.2017010110hwp:resource-id:jnephrol;28/11/3218American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, extracellular matrix, interstitial fibrosis, ischemia-reperfusion, macrophages, myofibroblastBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20170101101046-66731533-34502017-07-05T06:37:27-07:002017-11Journal of the American Society of NephrologyBasic Research281132183226
- Mannose-Binding Lectin Levels Could Predict Prognosis in IgA NephropathyIgA nephropathy (IgAN) is characterized by infections followed by episodic gross hematuria. Deficiency of mannose-binding lectin (MBL) is associated with recurrent infection in many diseases, but controversy exists regarding the role of MBL in IgAN. Here, we measured MBL2 variants and MBL levels in 749 patients with IgAN and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with IgAN had MBL deficiency (MBL levels <100 ng/ml), among whom LYPB/LYPB and LXPA/LYPB were the predominant MBL2 haplotypes (82%; 32 of 39). We found a nonlinear association between MBL levels and renal outcome in IgAN. Patients with IgAN and MBL deficiency had a higher incidence of prodromic infections and gross hematuria than those with sufficient MBL levels (100–3540 ng/ml). Moreover, MBL deficiency independently associated with poor renal outcome in IgAN after multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72; P<0.001). Patients with high MBL levels (>3540 ng/ml) had more severe proteinuria and a higher proportion of crescents, although the association with IgAN progression did not reach statistical significance after adjustments. In conclusion, MBL deficiency and MBL excess may both have deleterious effects on IgAN progression, which suggests that MBL contributes to IgAN pathogenesis through multiple mechanisms.10.1681/ASN.2017010076Tue, 11 Jul 2017 07:47:36 GMT-07:00Mannose-Binding Lectin Levels Could Predict Prognosis in IgA NephropathyIgA nephropathy (IgAN) is characterized by infections followed by episodic gross hematuria. Deficiency of mannose-binding lectin (MBL) is associated with recurrent infection in many diseases, but controversy exists regarding the role of MBL in IgAN. Here, we measured MBL2 variants and MBL levels in 749 patients with IgAN and 489 healthy controls. Overall, 5.2% (39 of 749) of patients with IgAN had MBL deficiency (MBL levels <100 ng/ml), among whom LYPB/LYPB and LXPA/LYPB were the predominant MBL2 haplotypes (82%; 32 of 39). We found a nonlinear association between MBL levels and renal outcome in IgAN. Patients with IgAN and MBL deficiency had a higher incidence of prodromic infections and gross hematuria than those with sufficient MBL levels (100–3540 ng/ml). Moreover, MBL deficiency independently associated with poor renal outcome in IgAN after multiple adjustments (hazard ratio, 5.18; 95% confidence interval, 2.50 to 10.72; P<0.001). Patients with high MBL levels (>3540 ng/ml) had more severe proteinuria and a higher proportion of crescents, although the association with IgAN progression did not reach statistical significance after adjustments. In conclusion, MBL deficiency and MBL excess may both have deleterious effects on IgAN progression, which suggests that MBL contributes to IgAN pathogenesis through multiple mechanisms.Guo, Wei-yiZhu, LiMeng, Si-junShi, Su-fangLiu, Li-junLv, Ji-chengZhang, Hong2017-07-11T07:47:36-07:00doi:10.1681/ASN.2017010076hwp:resource-id:jnephrol;28/11/3175American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, MBL, renal outcomeBrief CommunicationsBrief Communicationsbrief-report20172017-11-01November 201710.1681/ASN.20170100761046-66731533-34502017-07-11T07:47:36-07:002017-11Journal of the American Society of NephrologyBrief Communications281131753181
- How Dangerous Is Hyperkalemia?Hyperkalemia is a potentially life-threatening electrolyte disorder appreciated with greater frequency in patients with renal disease, heart failure, and with use of certain medications such as renin angiotensin aldosterone inhibitors. The traditional views that hyperkalemia can be reliably diagnosed by electrocardiogram and that particular levels of hyperkalemia confer cardiotoxic risk have been challenged by several reports of patients with atypic presentations. Epidemiologic data demonstrate strong associations of morbidity and mortality in patients with hyperkalemia but these associations appear disconnected in certain patient populations and in differing clinical presentations. Physiologic adaptation, structural cardiac disease, medication use, and degree of concurrent illness might predispose certain patients presenting with hyperkalemia to a lower or higher threshold for toxicity. These factors are often overlooked; yet data suggest that the clinical context in which hyperkalemia develops is at least as important as the degree of hyperkalemia is in determining patient outcome. This review summarizes the clinical data linking hyperkalemia with poor outcomes and discusses how the efficacy of certain treatments might depend on the clinical presentation.10.1681/ASN.2016121344Fri, 04 Aug 2017 12:03:21 GMT-07:00How Dangerous Is Hyperkalemia?Hyperkalemia is a potentially life-threatening electrolyte disorder appreciated with greater frequency in patients with renal disease, heart failure, and with use of certain medications such as renin angiotensin aldosterone inhibitors. The traditional views that hyperkalemia can be reliably diagnosed by electrocardiogram and that particular levels of hyperkalemia confer cardiotoxic risk have been challenged by several reports of patients with atypic presentations. Epidemiologic data demonstrate strong associations of morbidity and mortality in patients with hyperkalemia but these associations appear disconnected in certain patient populations and in differing clinical presentations. Physiologic adaptation, structural cardiac disease, medication use, and degree of concurrent illness might predispose certain patients presenting with hyperkalemia to a lower or higher threshold for toxicity. These factors are often overlooked; yet data suggest that the clinical context in which hyperkalemia develops is at least as important as the degree of hyperkalemia is in determining patient outcome. This review summarizes the clinical data linking hyperkalemia with poor outcomes and discusses how the efficacy of certain treatments might depend on the clinical presentation.Montford, John R.Linas, Stuart2017-08-04T12:03:21-07:00doi:10.1681/ASN.2016121344hwp:resource-id:jnephrol;28/11/3155American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperkalemia, chronic kidney disease, electrolytesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-11-01November 201710.1681/ASN.20161213441046-66731533-34502017-08-04T12:03:21-07:002017-11Journal of the American Society of NephrologyUp Front Matters281131553165
- PGC-1α Protects from Notch-Induced Kidney Fibrosis DevelopmentKidney fibrosis is the histologic manifestation of CKD. Sustained activation of developmental pathways, such as Notch, in tubule epithelial cells has been shown to have a key role in fibrosis development. The molecular mechanism of Notch-induced fibrosis, however, remains poorly understood. Here, we show that, that expression of peroxisomal proliferation g-coactivator (PGC-1α) and fatty acid oxidation-related genes are lower in mice expressing active Notch1 in tubular epithelial cells (Pax8-rtTA/ICN1) compared to littermate controls. Chromatin immunoprecipitation assays revealed that the Notch target gene Hes1 directly binds to the regulatory region of PGC-1α. Compared with Pax8-rtTA/ICN1 transgenic animals, Pax8-rtTA/ICN1/Ppargc1a transgenic mice showed improvement of renal structural alterations (on histology) and molecular defect (expression of profibrotic genes). Overexpression of PGC-1α restored mitochondrial content and reversed the fatty acid oxidation defect induced by Notch overexpression in vitro in tubule cells. Furthermore, compared with Pax8-rtTA/ICN1 mice, Pax8-rtTA/ICN1/Ppargc1a mice exhibited improvement in renal fatty acid oxidation gene expression and apoptosis. Our results show that metabolic dysregulation has a key role in kidney fibrosis induced by sustained activation of the Notch developmental pathway and can be ameliorated by PGC-1α.10.1681/ASN.2017020130Thu, 27 Jul 2017 09:44:38 GMT-07:00PGC-1α Protects from Notch-Induced Kidney Fibrosis DevelopmentKidney fibrosis is the histologic manifestation of CKD. Sustained activation of developmental pathways, such as Notch, in tubule epithelial cells has been shown to have a key role in fibrosis development. The molecular mechanism of Notch-induced fibrosis, however, remains poorly understood. Here, we show that, that expression of peroxisomal proliferation g-coactivator (PGC-1α) and fatty acid oxidation-related genes are lower in mice expressing active Notch1 in tubular epithelial cells (Pax8-rtTA/ICN1) compared to littermate controls. Chromatin immunoprecipitation assays revealed that the Notch target gene Hes1 directly binds to the regulatory region of PGC-1α. Compared with Pax8-rtTA/ICN1 transgenic animals, Pax8-rtTA/ICN1/Ppargc1a transgenic mice showed improvement of renal structural alterations (on histology) and molecular defect (expression of profibrotic genes). Overexpression of PGC-1α restored mitochondrial content and reversed the fatty acid oxidation defect induced by Notch overexpression in vitro in tubule cells. Furthermore, compared with Pax8-rtTA/ICN1 mice, Pax8-rtTA/ICN1/Ppargc1a mice exhibited improvement in renal fatty acid oxidation gene expression and apoptosis. Our results show that metabolic dysregulation has a key role in kidney fibrosis induced by sustained activation of the Notch developmental pathway and can be ameliorated by PGC-1α.Han, Seung HyeokWu, Mei-yanNam, Bo YoungPark, Jung TakYoo, Tae-HyunKang, Shin-WookPark, JihwanChinga, FrankLi, Szu-YuanSusztak, Katalin2017-07-27T09:44:38-07:00doi:10.1681/ASN.2017020130hwp:resource-id:jnephrol;28/11/3312American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyPGC-1α, Notch, kidney fibrosis, fatty acid oxidation, mitochondriaBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20170201301046-66731533-34502017-07-27T09:44:38-07:002017-11Journal of the American Society of NephrologyBasic Research281133123322
- MicroRNA-92a Mediates Endothelial Dysfunction in CKDCKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress–responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant N-acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144+ endothelial microparticles. Furthermore, CD144+ microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.10.1681/ASN.2016111215Mon, 10 Jul 2017 11:39:50 GMT-07:00MicroRNA-92a Mediates Endothelial Dysfunction in CKDCKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress–responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant N-acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144+ endothelial microparticles. Furthermore, CD144+ microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.Shang, FenqingWang, Shen-ChihHsu, Chien-YiMiao, YifeiMartin, MarcyYin, YanjunWu, Chih-ChengWang, Yun-TingWu, GaihongChien, ShuHuang, Hsien-DaTarng, Der-CherngShiu, Yan-TingCheung, Alfred K.Huang, Po-HsunChen, ZhenShyy, John Y.-J.2017-07-10T11:39:50-07:00doi:10.1681/ASN.2016111215hwp:resource-id:jnephrol;28/11/3251American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, endothelial cells, oxidative stress, microRNA-92Basic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20161112151046-66731533-34502017-07-10T11:39:50-07:002017-11Journal of the American Society of NephrologyBasic Research281132513261
- A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous NephropathyThrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures. Therefore, we generated antibodies against the human and mouse orthologs of THSD7A in rabbits by coimmunization with the respective cDNAs. Injection of these anti-THSD7A antibodies into mice induced a severe nephrotic syndrome with proteinuria, weight gain, and hyperlipidemia. Immunofluorescence analyses revealed granular antigen-antibody complexes in a subepithelial location along the glomerular filtration barrier 14 days after antibody injection, and immunohistochemistry for rabbit IgG and THSD7A as well as ultrastructural analyses showed the typical characteristics of human MN. Mice injected with purified IgG from rabbit serum that was taken before immunization failed to develop any of these changes. Notably, MN developed in the absence of detectable complement activation, and disease was strain dependent. In vitro, anti-THSD7A antibodies caused cytoskeletal rearrangement and activation of focal adhesion signaling. Knockdown of the THSD7A ortholog, thsd7aa, in zebrafish larvae resulted in altered podocyte differentiation and impaired glomerular filtration barrier function, with development of pericardial edema, suggesting an important role of THSD7A in glomerular filtration barrier integrity. In summary, our study introduces a heterologous mouse model that allows further investigation of the molecular events that underlie MN.10.1681/ASN.2017010030Wed, 16 Aug 2017 08:19:55 GMT-07:00A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous NephropathyThrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures. Therefore, we generated antibodies against the human and mouse orthologs of THSD7A in rabbits by coimmunization with the respective cDNAs. Injection of these anti-THSD7A antibodies into mice induced a severe nephrotic syndrome with proteinuria, weight gain, and hyperlipidemia. Immunofluorescence analyses revealed granular antigen-antibody complexes in a subepithelial location along the glomerular filtration barrier 14 days after antibody injection, and immunohistochemistry for rabbit IgG and THSD7A as well as ultrastructural analyses showed the typical characteristics of human MN. Mice injected with purified IgG from rabbit serum that was taken before immunization failed to develop any of these changes. Notably, MN developed in the absence of detectable complement activation, and disease was strain dependent. In vitro, anti-THSD7A antibodies caused cytoskeletal rearrangement and activation of focal adhesion signaling. Knockdown of the THSD7A ortholog, thsd7aa, in zebrafish larvae resulted in altered podocyte differentiation and impaired glomerular filtration barrier function, with development of pericardial edema, suggesting an important role of THSD7A in glomerular filtration barrier integrity. In summary, our study introduces a heterologous mouse model that allows further investigation of the molecular events that underlie MN.Tomas, Nicola M.Meyer-Schwesinger, Catherinevon Spiegel, HanningKotb, Ahmed M.Zahner, GuntherHoxha, ElionHelmchen, UdoEndlich, NicoleKoch-Nolte, FriedrichStahl, Rolf A.K.2017-08-16T08:19:55-07:00doi:10.1681/ASN.2017010030hwp:resource-id:jnephrol;28/11/3262American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, podocyte, glomerular diseaseBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20170100301046-66731533-34502017-08-16T08:19:55-07:002017-11Journal of the American Society of NephrologyBasic Research281132623277
- Association between Endothelin-1 Levels and Kidney Disease among BlacksEndothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000–2004; n=3538). We defined incident CKD as eGFR<60 ml/min per 1.73 m2 and ≥30% eGFR decline at the third visit (2009–2013) relative to baseline among those participants with baseline eGFR ≥60 ml/min per 1.73 m2. At baseline, mean age was 55 years old, 37% of participants were men, and mean eGFR was 94 ml/min per 1.73 m2. Over a median follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants. Participants with baseline endothelin-1 levels in higher quartiles had a greater incidence of CKD in the fully adjusted model (odds ratio for fourth versus first quartile, 1.81; 95% confidence interval, 1.11 to 2.96; Ptrend=0.04). Endothelin-1 positively associated with all-cause mortality (hazard ratio for fourth versus first quartile, 1.64; 95% confidence interval, 1.24 to 2.16; Ptrend<0.001). In conclusion, higher baseline serum endothelin-1 levels associated with incident CKD and all-cause mortality during follow-up in this general population sample of blacks.10.1681/ASN.2016111236Tue, 11 Jul 2017 07:47:35 GMT-07:00Association between Endothelin-1 Levels and Kidney Disease among BlacksEndothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000–2004; n=3538). We defined incident CKD as eGFR<60 ml/min per 1.73 m2 and ≥30% eGFR decline at the third visit (2009–2013) relative to baseline among those participants with baseline eGFR ≥60 ml/min per 1.73 m2. At baseline, mean age was 55 years old, 37% of participants were men, and mean eGFR was 94 ml/min per 1.73 m2. Over a median follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants. Participants with baseline endothelin-1 levels in higher quartiles had a greater incidence of CKD in the fully adjusted model (odds ratio for fourth versus first quartile, 1.81; 95% confidence interval, 1.11 to 2.96; Ptrend=0.04). Endothelin-1 positively associated with all-cause mortality (hazard ratio for fourth versus first quartile, 1.64; 95% confidence interval, 1.24 to 2.16; Ptrend<0.001). In conclusion, higher baseline serum endothelin-1 levels associated with incident CKD and all-cause mortality during follow-up in this general population sample of blacks.Rebholz, Casey M.Harman, Jane L.Grams, Morgan E.Correa, AdolfoShimbo, DaichiCoresh, JosefYoung, Bessie A.2017-07-11T07:47:35-07:00doi:10.1681/ASN.2016111236hwp:resource-id:jnephrol;28/11/3337American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyChronic kidney disease, endothelin-1, Epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-11-01November 201710.1681/ASN.20161112361046-66731533-34502017-07-11T07:47:35-07:002017-11Journal of the American Society of NephrologyClinical Epidemiology281133373344
- Intracellular APOL1 Risk Variants Cause Cytotoxicity Accompanied by Energy DepletionPopulation genetic approaches have uncovered a strong association between kidney diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism whereby these variants lead to disease manifestation and, in particular, whether this involves an intracellular or extracellular pool of APOL1 remains unclear. Herein, we show a predominantly intracellular localization of APOL1 G0 and the renal risk variants, which localized to membranes of the endoplasmic reticulum in podocyte cell lines. This localization did not depend on the N-terminal signal peptide that mediates APOL1 secretion into the circulation. Additionally, a fraction of these proteins localized to structures surrounding mitochondria. In vitro overexpression of G1 or G2 lacking the signal peptide inhibited cell viability, triggered phosphorylation of stress-induced kinases, increased the phosphorylation of AMP-activated protein kinase, reduced intracellular potassium levels, and reduced mitochondrial respiration rates. These findings indicate that functions at intracellular membranes, specifically those of the endoplasmic reticulum and mitochondria, are crucial factors in APOL1 renal risk variant–mediated cell injury.10.1681/ASN.2016111220Mon, 10 Jul 2017 11:39:51 GMT-07:00Intracellular APOL1 Risk Variants Cause Cytotoxicity Accompanied by Energy DepletionPopulation genetic approaches have uncovered a strong association between kidney diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism whereby these variants lead to disease manifestation and, in particular, whether this involves an intracellular or extracellular pool of APOL1 remains unclear. Herein, we show a predominantly intracellular localization of APOL1 G0 and the renal risk variants, which localized to membranes of the endoplasmic reticulum in podocyte cell lines. This localization did not depend on the N-terminal signal peptide that mediates APOL1 secretion into the circulation. Additionally, a fraction of these proteins localized to structures surrounding mitochondria. In vitro overexpression of G1 or G2 lacking the signal peptide inhibited cell viability, triggered phosphorylation of stress-induced kinases, increased the phosphorylation of AMP-activated protein kinase, reduced intracellular potassium levels, and reduced mitochondrial respiration rates. These findings indicate that functions at intracellular membranes, specifically those of the endoplasmic reticulum and mitochondria, are crucial factors in APOL1 renal risk variant–mediated cell injury.Granado, DanielMüller, DariaKrausel, VanessaKruzel-Davila, EttySchuberth, ChristianEschborn, MelanieWedlich-Söldner, RolandSkorecki, KarlPavenstädt, HermannMichgehl, UlfWeide, Thomas2017-07-10T11:39:51-07:00doi:10.1681/ASN.2016111220hwp:resource-id:jnephrol;28/11/3227American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAPOL1, renal risk variant, podocyte, endoplasmic reticulum, mitochondria, energy depletionBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20161112201046-66731533-34502017-07-10T11:39:51-07:002017-11Journal of the American Society of NephrologyBasic Research281132273238
- Regulation of Nephron Progenitor Cell Self-Renewal by Intermediary MetabolismNephron progenitor cells (NPCs) show an age-dependent capacity to balance self-renewal with differentiation. Older NPCs (postnatal day 0) exit the progenitor niche at a higher rate than younger (embryonic day 13.5) NPCs do. This behavior is reflected in the transcript profiles of young and old NPCs. Bioenergetic pathways have emerged as important regulators of stem cell fate. Here, we investigated the mechanisms underlying this regulation in murine NPCs. Upon isolation and culture in NPC renewal medium, younger NPCs displayed a higher glycolysis rate than older NPCs. Inhibition of glycolysis enhanced nephrogenesis in cultured embryonic kidneys, without increasing ureteric tree branching, and promoted mesenchymal-to-epithelial transition in cultured isolated metanephric mesenchyme. Cotreatment with a canonical Wnt signaling inhibitor attenuated but did not entirely block the increase in nephrogenesis observed after glycolysis inhibition. Furthermore, inhibition of the phosphatidylinositol 3-kinase/Akt self-renewal signaling pathway or stimulation of differentiation pathways in the NPC decreased glycolytic flux. Our findings suggest that glycolysis is a pivotal, cell-intrinsic determinant of NPC fate, with a high glycolytic flux supporting self-renewal and inhibition of glycolysis stimulating differentiation.10.1681/ASN.2016111246Fri, 28 Jul 2017 06:24:00 GMT-07:00Regulation of Nephron Progenitor Cell Self-Renewal by Intermediary MetabolismNephron progenitor cells (NPCs) show an age-dependent capacity to balance self-renewal with differentiation. Older NPCs (postnatal day 0) exit the progenitor niche at a higher rate than younger (embryonic day 13.5) NPCs do. This behavior is reflected in the transcript profiles of young and old NPCs. Bioenergetic pathways have emerged as important regulators of stem cell fate. Here, we investigated the mechanisms underlying this regulation in murine NPCs. Upon isolation and culture in NPC renewal medium, younger NPCs displayed a higher glycolysis rate than older NPCs. Inhibition of glycolysis enhanced nephrogenesis in cultured embryonic kidneys, without increasing ureteric tree branching, and promoted mesenchymal-to-epithelial transition in cultured isolated metanephric mesenchyme. Cotreatment with a canonical Wnt signaling inhibitor attenuated but did not entirely block the increase in nephrogenesis observed after glycolysis inhibition. Furthermore, inhibition of the phosphatidylinositol 3-kinase/Akt self-renewal signaling pathway or stimulation of differentiation pathways in the NPC decreased glycolytic flux. Our findings suggest that glycolysis is a pivotal, cell-intrinsic determinant of NPC fate, with a high glycolytic flux supporting self-renewal and inhibition of glycolysis stimulating differentiation.Liu, JiaoEdgington-Giordano, FrancescaDugas, CourtneyAbrams, AnnaKatakam, PrasadSatou, RyousukeSaifudeen, Zubaida2017-07-28T06:24:00-07:00doi:10.1681/ASN.2016111246hwp:resource-id:jnephrol;28/11/3323American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCell Signaling, kidney development, Stem Cell Renewal, Glycolysis, Differentiation, PI3K/AktBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20161112461046-66731533-34502017-07-28T06:24:00-07:002017-11Journal of the American Society of NephrologyBasic Research2811113323313333353135
- A Missense Mutation in the Extracellular Domain of αENaC Causes Liddle SyndromeLiddle syndrome is an autosomal dominant form of hypokalemic hypertension due to mutations in the β- or γ-subunit of the epithelial sodium channel (ENaC). Here, we describe a family with Liddle syndrome due to a mutation in αENaC. The proband was referred because of resistant hypokalemic hypertension, suppressed renin and aldosterone, and no mutations in the genes encoding β- or γENaC. Exome sequencing revealed a heterozygous, nonconservative T>C single-nucleotide mutation in αENaC that substituted Cys479 with Arg (C479R). C479 is a highly conserved residue in the extracellular domain of ENaC and likely involved in a disulfide bridge with the partner cysteine C394. In oocytes, the C479R and C394S mutations resulted in similar twofold increases in amiloride-sensitive ENaC current. Quantification of mature cleaved αENaC in membrane fractions showed that the number of channels did not increase with these mutations. Trypsin, which increases open probability of the channel by proteolytic cleavage, resulted in significantly higher currents in the wild type than in C479R or C394S mutants. In summary, a mutation in the extracellular domain of αENaC causes Liddle syndrome by increasing intrinsic channel activity. This mechanism differs from that of the β- and γ-mutations, which result in an increase in channel density at the cell surface. This mutation may explain other cases of patients with resistant hypertension and also provides novel insight into ENaC activation, which is relevant for kidney sodium reabsorption and salt-sensitive hypertension.10.1681/ASN.2016111163Fri, 14 Jul 2017 08:52:32 GMT-07:00A Missense Mutation in the Extracellular Domain of αENaC Causes Liddle SyndromeLiddle syndrome is an autosomal dominant form of hypokalemic hypertension due to mutations in the β- or γ-subunit of the epithelial sodium channel (ENaC). Here, we describe a family with Liddle syndrome due to a mutation in αENaC. The proband was referred because of resistant hypokalemic hypertension, suppressed renin and aldosterone, and no mutations in the genes encoding β- or γENaC. Exome sequencing revealed a heterozygous, nonconservative T>C single-nucleotide mutation in αENaC that substituted Cys479 with Arg (C479R). C479 is a highly conserved residue in the extracellular domain of ENaC and likely involved in a disulfide bridge with the partner cysteine C394. In oocytes, the C479R and C394S mutations resulted in similar twofold increases in amiloride-sensitive ENaC current. Quantification of mature cleaved αENaC in membrane fractions showed that the number of channels did not increase with these mutations. Trypsin, which increases open probability of the channel by proteolytic cleavage, resulted in significantly higher currents in the wild type than in C479R or C394S mutants. In summary, a mutation in the extracellular domain of αENaC causes Liddle syndrome by increasing intrinsic channel activity. This mechanism differs from that of the β- and γ-mutations, which result in an increase in channel density at the cell surface. This mutation may explain other cases of patients with resistant hypertension and also provides novel insight into ENaC activation, which is relevant for kidney sodium reabsorption and salt-sensitive hypertension.Salih, MahdiGautschi, Ivanvan Bemmelen, Miguel X.Di Benedetto, MichaelBrooks, Alice S.Lugtenberg, DorienSchild, LaurentHoorn, Ewout J.2017-07-14T08:52:32-07:00doi:10.1681/ASN.2016111163hwp:resource-id:jnephrol;28/11/3291American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyENaC, hypertension, hypokalemia, genetic renal disease, electrophysiologyBasic ResearchBasic Researchresearch-article20172017-11-01November 201710.1681/ASN.20161111631046-66731533-34502017-07-14T08:52:32-07:002017-11Journal of the American Society of NephrologyBasic Research281132913299
- Erratum10.1681/ASN.2017091018Tue, 31 Oct 2017 01:00:38 GMT-07:00ErratumAmerican Society of Nephrology2017-10-31T13:00:38-07:00doi:10.1681/ASN.2017091018hwp:resource-id:jnephrol;28/11/3425American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErratum, DGKE, nephropathyErratumErratumcorrection20172017-11-01November 201710.1681/ASN.20170910181046-66731533-34502017-10-31T13:00:38-07:002017-11Journal of the American Society of NephrologyErratum28282811610342518023066342518133075
- Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney DiseaseOveractivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.73 m2, and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg/d were later reduced to 200 mg/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg/d versus placebo (1.63% versus 4.74%, respectively; P=0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively; P<0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified. (ClinicalTrials.gov: NCT01233869).10.1681/ASN.2016111232Thu, 24 Aug 2017 07:01:36 GMT-07:00Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney DiseaseOveractivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.73 m2, and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg/d were later reduced to 200 mg/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg/d versus placebo (1.63% versus 4.74%, respectively; P=0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively; P<0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified. (ClinicalTrials.gov: NCT01233869).Tesar, VladimirCiechanowski, KazimierzPei, YorkBarash, IrinaShannon, MeganLi, RayWilliams, Jason H.Levisetti, MatteoArkin, StevenSerra, Andreas2017-08-24T07:01:36-07:00doi:10.1681/ASN.2016111232hwp:resource-id:jnephrol;28/11/3404American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologybosutinib, ADPKD, total kidney volume, clinical trial, SrcClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20161112321046-66731533-34502017-08-24T07:01:36-07:002017-11Journal of the American Society of NephrologyClinical Research281134043413
- Urinary Matrix Metalloproteinase-7 Predicts Severe AKI and Poor Outcomes after Cardiac SurgeryUrinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/β-catenin, which is activated in AKI models. To test the hypothesis that uMMP-7 is a predictor for severe AKI in patients after cardiac surgery, we performed a prospective, multicenter, two-stage cohort study in 721 patients undergoing cardiac surgery. In stage 1, we enrolled 323 children from three academic medical centers. In stage 2, we enrolled 398 adults at six centers. We analyzed levels of uMMP-7 and other injury biomarkers during the perioperative period. Severe AKI was defined as Kidney Disease Improving Global Outcomes stage 2 or 3. uMMP-7 level peaked within 6 hours after surgery in patients who subsequently developed severe AKI. After multivariate adjustment, the highest quintile of postoperative uMMP-7 level, compared with the lowest quintile, associated with 17-fold (in adults) and 36-fold (in children) higher odds of severe AKI. Elevated uMMP-7 level associated with increased risk of composite events (severe AKI, acute dialysis, and in-hospital death) and longer stay in the intensive care unit and hospital. For predicting severe AKI, uMMP-7 had an area under the receiver operating characteristic curve of 0.81 (in children) and 0.76 (in adults), outperforming urinary IL-18, angiotensinogen, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, and tissue inhibitor of metalloproteinase-2·IGF-binding protein-7 and the clinical model. uMMP-7 significantly improved risk reclassification over the clinical model alone, as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, uMMP-7 is a promising predictor for severe AKI and poor in-hospital outcomes in patients after cardiac surgery.10.1681/ASN.2017020142Tue, 11 Jul 2017 07:47:35 GMT-07:00Urinary Matrix Metalloproteinase-7 Predicts Severe AKI and Poor Outcomes after Cardiac SurgeryUrinary matrix metalloproteinase-7 (uMMP-7) levels consistently reflect the activity of intrarenal Wnt/β-catenin, which is activated in AKI models. To test the hypothesis that uMMP-7 is a predictor for severe AKI in patients after cardiac surgery, we performed a prospective, multicenter, two-stage cohort study in 721 patients undergoing cardiac surgery. In stage 1, we enrolled 323 children from three academic medical centers. In stage 2, we enrolled 398 adults at six centers. We analyzed levels of uMMP-7 and other injury biomarkers during the perioperative period. Severe AKI was defined as Kidney Disease Improving Global Outcomes stage 2 or 3. uMMP-7 level peaked within 6 hours after surgery in patients who subsequently developed severe AKI. After multivariate adjustment, the highest quintile of postoperative uMMP-7 level, compared with the lowest quintile, associated with 17-fold (in adults) and 36-fold (in children) higher odds of severe AKI. Elevated uMMP-7 level associated with increased risk of composite events (severe AKI, acute dialysis, and in-hospital death) and longer stay in the intensive care unit and hospital. For predicting severe AKI, uMMP-7 had an area under the receiver operating characteristic curve of 0.81 (in children) and 0.76 (in adults), outperforming urinary IL-18, angiotensinogen, neutrophil gelatinase-associated lipocalin, albumin-to-creatinine ratio, and tissue inhibitor of metalloproteinase-2·IGF-binding protein-7 and the clinical model. uMMP-7 significantly improved risk reclassification over the clinical model alone, as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, uMMP-7 is a promising predictor for severe AKI and poor in-hospital outcomes in patients after cardiac surgery.Yang, XiaobingChen, ChunboTeng, SiyuanFu, XiaoruiZha, YanLiu, HuafengWang, LiTian, JianweiZhang, XiangyanLiu, YouhuaNie, JingHou, Fan Fan2017-07-11T07:47:35-07:00doi:10.1681/ASN.2017020142hwp:resource-id:jnephrol;28/11/3373American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyMatrix Metalloproteinase-7, Acute Kidney Injury, Biomarker, Cardiac SurgeryClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20170201421046-66731533-34502017-07-11T07:47:35-07:002017-11Journal of the American Society of NephrologyClinical Research281133733382
- Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart FailureUnderstanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (n=128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine. The mean±SD prediuretic FELi was 16.2%±9.5%, similar to that in a control cohort without HF not receiving diuretics (n=52; 16.6%±9.2%; P=0.82). Administration of a median of 160 (interquartile range, 40–270) mg intravenous furosemide equivalents increased FELi by 12.6%±10.8% (P<0.001) but increased FENa by only 4.8%±3.3%. Thus, only 34% (interquartile range, 15.6%–75.7%) of the estimated diuretic-induced sodium release did not undergo distal reabsorption. After controlling for urine diuretic levels, the increase in FELi explained only 6.4% of the increase in FENa (P=0.002). These data suggest that administration of high-dose loop diuretics to patients with HF yields meaningful increases in sodium exit from the proximal tubule/loop of Henle. However, little of this sodium seems to reach the urine, consistent with findings from animal models that indicate that distal tubular compensatory sodium reabsorption is a primary driver of DR.10.1681/ASN.2016111178Mon, 24 Jul 2017 06:14:24 GMT-07:00Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart FailureUnderstanding the tubular location of diuretic resistance (DR) in heart failure (HF) is critical to developing targeted treatment strategies. Rodents chronically administered loop diuretics develop DR due to compensatory distal tubular sodium reabsorption, but whether this translates to human DR is unknown. We studied consecutive patients with HF (n=128) receiving treatment with loop diuretics at the Yale Transitional Care Center. We measured the fractional excretion of lithium (FELi), the gold standard for in vivo assessment of proximal tubular and loop of Henle sodium handling, to assess sodium exit after loop diuretic administration and FENa to assess the net sodium excreted into the urine. The mean±SD prediuretic FELi was 16.2%±9.5%, similar to that in a control cohort without HF not receiving diuretics (n=52; 16.6%±9.2%; P=0.82). Administration of a median of 160 (interquartile range, 40–270) mg intravenous furosemide equivalents increased FELi by 12.6%±10.8% (P<0.001) but increased FENa by only 4.8%±3.3%. Thus, only 34% (interquartile range, 15.6%–75.7%) of the estimated diuretic-induced sodium release did not undergo distal reabsorption. After controlling for urine diuretic levels, the increase in FELi explained only 6.4% of the increase in FENa (P=0.002). These data suggest that administration of high-dose loop diuretics to patients with HF yields meaningful increases in sodium exit from the proximal tubule/loop of Henle. However, little of this sodium seems to reach the urine, consistent with findings from animal models that indicate that distal tubular compensatory sodium reabsorption is a primary driver of DR.Rao, Veena S.Planavsky, NoahHanberg, Jennifer S.Ahmad, TariqBrisco-Bacik, Meredith A.Wilson, Francis P.Jacoby, DanielChen, MichaelTang, W.H. WilsonCherney, David Z.I.Ellison, David H.Testani, Jeffrey M.2017-07-24T06:14:24-07:00doi:10.1681/ASN.2016111178hwp:resource-id:jnephrol;28/11/3414American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyloop diuretic, heart failure, lithium, proximal tubular sodiumClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20161111781046-66731533-34502017-07-24T06:14:24-07:002017-11Journal of the American Society of NephrologyClinical Research2811113414313734243138
- Characterization and Correction of Olfactory Deficits in Kidney DiseasePatients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort (n=161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P=0.02) and ESRD (66.8%±15.1%; P<0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial.10.1681/ASN.2016121308Thu, 03 Aug 2017 07:02:30 GMT-07:00Characterization and Correction of Olfactory Deficits in Kidney DiseasePatients with CKD suffer from food aversion, anorexia, and malnutrition. Although olfaction has a significant role in determining food flavor, our understanding of olfactory impairment and of the olfaction-nutrition axis in patients with kidney disease is limited. We quantified odor identification, odor threshold, and subjective odor perception in a cohort (n=161) comprising 36 participants with CKD, 100 participants with ESRD, and 25 controls. We investigated olfaction-nutrition associations in these participants and examined a novel intervention to improve olfaction in ESRD. The mean odor identification score was lower in patients with CKD (75.6%±13.1%; P=0.02) and ESRD (66.8%±15.1%; P<0.001) than in controls (83.6%±11.4%). Patients with ESRD exhibited higher odor threshold than the remaining participants exhibited. All groups had similar scores for subjective smell assessment. In multivariable adjusted analyses, kidney disease associated with increased odds of odor identification deficits (odds ratio, 4.80; 95% confidence interval, 1.94 to 11.89). A reduction in odor identification score was associated with higher subjective global assessment score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. We found no associations between odor threshold and nutritional parameters. In a proof of concept, 6-week, open-label clinical trial, intranasal theophylline (an epithelial membrane transport and proton secretion activator) increased odor identification score in five out of seven (71%) patients with ESRD. In conclusion, patients with kidney disease have olfactory deficits that may influence their nutritional status. Our preliminary results regarding olfactory improvement using intranasal theophylline warrant confirmation in a randomized controlled trial.Nigwekar, Sagar U.Weiser, Jeremy M.Kalim, SahirXu, DihuaWibecan, Joshua L.Dougherty, Sarah M.Mercier-Lafond, LaurenceCorapi, Kristin M.Eneanya, Nwamaka D.Holbrook, Eric H.Brown, DennisThadhani, Ravi I.Păunescu, Teodor G.2017-08-03T07:02:30-07:00doi:10.1681/ASN.2016121308hwp:resource-id:jnephrol;28/11/3395American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, end-stage renal disease, olfaction, malnutrition, theophyllineClinical ResearchClinical Researchresearch-article20172017-11-01November 201710.1681/ASN.20161213081046-66731533-34502017-08-03T07:02:30-07:002017-11Journal of the American Society of NephrologyClinical Research281133953403
- New Insights into Fuel Choices of Nephron Progenitor Cells10.1681/ASN.2017070795Tue, 05 Sep 2017 06:44:24 GMT-07:00New Insights into Fuel Choices of Nephron Progenitor CellsOxburgh, LeifRosen, Clifford J.2017-09-05T06:44:24-07:00doi:10.1681/ASN.2017070795hwp:resource-id:jnephrol;28/11/3133American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolism, fuel source, glycolysis, kidney development, nephrogenesis, cessation of nephrogenesisUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-11-01November 201710.1681/ASN.20170707951046-66731533-34502017-09-05T06:44:24-07:002017-11Journal of the American Society of NephrologyUp Front Matters2811113133332331353335
- This Month’s Highlights10.1681/ASN.2017090987Tue, 31 Oct 2017 01:00:37 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-10-31T13:00:37-07:00doi:10.1681/ASN.2017090987hwp:resource-id:jnephrol;28/11/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20172017-11-01November 201710.1681/ASN.20170909871046-66731533-34502017-10-31T13:00:37-07:002017-11Journal of the American Society of NephrologyThis Month's Highlights2811ii
- Current Uses of Dietary Therapy for Patients with Far-Advanced CKDFor several decades, inquiry concerning dietary therapy for nondialyzed patients with CKD has focused mainly on its capability to retard progression of CKD. However, several studies published in recent years indicate that, independent of whether diet can delay progression of CKD, well designed low-protein diets may provide a number of benefits for people with advanced CKD who are close to requiring or actually in need of RRT. Dietary therapy may both maintain good nutritional status and safely delay the need for chronic dialysis in such patients, offering the possibility of improving quality of life and reducing health care costs. With the growing interest in incremental dialysis, dietary therapy may enable lower doses of dialysis to be safely and effectively used, even as GFR continues to decrease. Such combinations of dietary and incremental dialysis therapy might slow the rate of loss of residual GFR, possibly reduce mortality in patients with advanced CKD, improve quality of life, and also, reduce health care costs. The amount of evidence that supports these possibilities is limited, and more well designed, randomized clinical trials are clearly indicated.10.2215/CJN.09340916Wed, 22 Feb 2017 04:50:59 GMT-08:00Current Uses of Dietary Therapy for Patients with Far-Advanced CKDFor several decades, inquiry concerning dietary therapy for nondialyzed patients with CKD has focused mainly on its capability to retard progression of CKD. However, several studies published in recent years indicate that, independent of whether diet can delay progression of CKD, well designed low-protein diets may provide a number of benefits for people with advanced CKD who are close to requiring or actually in need of RRT. Dietary therapy may both maintain good nutritional status and safely delay the need for chronic dialysis in such patients, offering the possibility of improving quality of life and reducing health care costs. With the growing interest in incremental dialysis, dietary therapy may enable lower doses of dialysis to be safely and effectively used, even as GFR continues to decrease. Such combinations of dietary and incremental dialysis therapy might slow the rate of loss of residual GFR, possibly reduce mortality in patients with advanced CKD, improve quality of life, and also, reduce health care costs. The amount of evidence that supports these possibilities is limited, and more well designed, randomized clinical trials are clearly indicated.Hanafusa, NorioLodebo, Bereket TessemaKopple, Joel D.2017-02-22T04:50:59-08:00doi:10.2215/CJN.09340916hwp:resource-id:clinjasn;12/7/1190American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, uremia, dialysis, incremental dialysis, low protein diet, ketoacids, essential amino acids, Diet, Protein-Restricted, glomerular filtration rate, Health Care Costs, humans, Nutritional Status, quality of life, renal dialysis, Renal Insufficiency, Chronic, Renal Replacement TherapyReviewsReviewsreview-article20172017-07-07July 07, 201710.2215/CJN.093409161555-90411555-905X2017-02-22T04:50:59-08:002017-07-07Clinical Journal of the American Society of NephrologyReviews12711901195
- Treatment of Renal Angiomyolipoma and Other Hamartomas in Patients with Tuberous Sclerosis ComplexTuberous sclerosis complex is an autosomal dominant genetic disease characterized by growth of benign tumors (hamartomas) in multiple organs, especially the kidneys, brain, heart, lungs, and skin. Tuberous sclerosis complex is usually caused by a mutation in either the tuberous sclerosis complex 1 or tuberous sclerosis complex 2 gene, resulting in constitutive activation of mammalian target of rapamycin signaling. Currently, mammalian target of rapamycin inhibitors are recommended in adult patients with tuberous sclerosis complex for the treatment of asymptomatic, growing renal angiomyolipoma that are >3 cm in diameter and pediatric or adult patients with brain lesions (subependymal giant cell astrocytoma) that either are growing or are not amenable to surgical resection. Clinical evidence suggests that systemic administration of a mammalian target of rapamycin inhibitor may provide concurrent improvements in multiple lesions and symptoms of tuberous sclerosis complex. With the major paradigm shift in consensus guidelines toward screening at diagnosis and ongoing monitoring and with the recent availability of an effective oral treatment, it is important that nephrologists have a thorough understanding of our role in the management of patients with tuberous sclerosis complex. Because the various manifestations of tuberous sclerosis complex typically emerge at different periods during patients’ lifetimes, patients will need to be followed throughout their lives. Unlike brain and cardiac lesions, renal lesions are more likely to emerge as patients age and can grow at any time. Considerations regarding long-term medication administration for the potential control of multiple tuberous sclerosis complex manifestations will need to be addressed; these include the most appropriate starting dose, appropriate doses for tumor shrinkage versus prevention of regrowth, and management of adverse events. Best practices and potential obstacles for nephrologists treating patients with tuberous sclerosis complex who have multiple manifestations are considered.10.2215/CJN.08150816Thu, 16 Mar 2017 07:37:31 GMT-07:00Treatment of Renal Angiomyolipoma and Other Hamartomas in Patients with Tuberous Sclerosis ComplexTuberous sclerosis complex is an autosomal dominant genetic disease characterized by growth of benign tumors (hamartomas) in multiple organs, especially the kidneys, brain, heart, lungs, and skin. Tuberous sclerosis complex is usually caused by a mutation in either the tuberous sclerosis complex 1 or tuberous sclerosis complex 2 gene, resulting in constitutive activation of mammalian target of rapamycin signaling. Currently, mammalian target of rapamycin inhibitors are recommended in adult patients with tuberous sclerosis complex for the treatment of asymptomatic, growing renal angiomyolipoma that are >3 cm in diameter and pediatric or adult patients with brain lesions (subependymal giant cell astrocytoma) that either are growing or are not amenable to surgical resection. Clinical evidence suggests that systemic administration of a mammalian target of rapamycin inhibitor may provide concurrent improvements in multiple lesions and symptoms of tuberous sclerosis complex. With the major paradigm shift in consensus guidelines toward screening at diagnosis and ongoing monitoring and with the recent availability of an effective oral treatment, it is important that nephrologists have a thorough understanding of our role in the management of patients with tuberous sclerosis complex. Because the various manifestations of tuberous sclerosis complex typically emerge at different periods during patients’ lifetimes, patients will need to be followed throughout their lives. Unlike brain and cardiac lesions, renal lesions are more likely to emerge as patients age and can grow at any time. Considerations regarding long-term medication administration for the potential control of multiple tuberous sclerosis complex manifestations will need to be addressed; these include the most appropriate starting dose, appropriate doses for tumor shrinkage versus prevention of regrowth, and management of adverse events. Best practices and potential obstacles for nephrologists treating patients with tuberous sclerosis complex who have multiple manifestations are considered.Samuels, Joshua A.2017-03-16T07:37:31-07:00doi:10.2215/CJN.08150816hwp:resource-id:clinjasn;12/7/1196American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal angiomyolipoma, tuberous sclerosis, mTOR, multidisciplinary approachReviewsReviewsreview-article20172017-07-07July 07, 201710.2215/CJN.081508161555-90411555-905X2017-03-16T07:37:31-07:002017-07-07Clinical Journal of the American Society of NephrologyReviews12711961202
- The 3-Year Incidence of Gout in Elderly Patients with CKD10.2215/CJN.06790616Thu, 02 Feb 2017 07:36:26 GMT-08:00The 3-Year Incidence of Gout in Elderly Patients with CKDTan, Vivian S.Garg, Amit X.McArthur, EricLam, Ngan N.Sood, Manish M.Naylor, Kyla L.2017-02-02T07:36:26-08:00doi:10.2215/CJN.06790616hwp:resource-id:clinjasn;12/4/577American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, dialysis, gout, incidence, estimated glomerular filtration rate, adult, aged, albuminuria, allopurinol, colchicine, female, glomerular filtration rate, gout, humans, incidence, male, Ontario, renal dialysis, renal insufficiency, chronic, retrospective studies, riskOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-04-03April 03, 201710.2215/CJN.067906161555-90411555-905X2017-02-02T07:36:26-08:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124577584
- Beliefs and Attitudes to Bowel Cancer Screening in Patients with CKD: A Semistructured Interview Study10.2215/CJN.10090916Thu, 02 Feb 2017 07:36:27 GMT-08:00Beliefs and Attitudes to Bowel Cancer Screening in Patients with CKD: A Semistructured Interview StudyJames, Laura J.Wong, GermaineCraig, Jonathan C.Ju, AngelaWilliams, NarelleLim, Wai H.Cross, NicholasTong, Allison2017-02-02T07:36:27-08:00doi:10.2215/CJN.10090916hwp:resource-id:clinjasn;12/4/568American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybowel cancer screening, chronic kidney disease, kidney transplant recipient, shared-decision making, qualitative research, interview, Anxiety, Attention, Attitude, Australia, Cognition, Early Detection of Cancer, Graft Survival, Humans, kidney, Neoplasms, New Zealand, Patient Satisfaction, renal dialysis, Renal Insufficiency, Chronic, Risk, Transplant RecipientsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-04-03April 03, 201710.2215/CJN.100909161555-90411555-905X2017-02-02T07:36:27-08:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124568576
- Biomarkers for Diagnosis and Prognosis of AKI in Children: One Size Does Not Fit AllPediatric AKI has become a significant health concern due to its rising incidence and association with adverse outcomes. Because of the limitations of serum creatinine, ongoing research has evaluated multiple novel biomarkers for the early detection of AKI. Identifying biomarkers that precede changes in serum creatinine is vital, because these biomarkers provide opportunities to improve outcomes through early diagnosis and timely disease management. In this review, we discuss salient findings on 16 candidate biomarkers and their association with AKI. We explore the differences in biomarker distribution by age and discuss why adult biomarker research findings cannot be directly extrapolated to children. With future research, more consideration needs to be given to how the maturing kidney affects biomarker levels and how we interpret biomarker performance in children. A comprehensive approach using age-specific biomarker reference ranges is required to develop pediatric biomarkers and improve outcomes for children with kidney disease.10.2215/CJN.12851216Fri, 30 Jun 2017 06:52:06 GMT-07:00Biomarkers for Diagnosis and Prognosis of AKI in Children: One Size Does Not Fit AllPediatric AKI has become a significant health concern due to its rising incidence and association with adverse outcomes. Because of the limitations of serum creatinine, ongoing research has evaluated multiple novel biomarkers for the early detection of AKI. Identifying biomarkers that precede changes in serum creatinine is vital, because these biomarkers provide opportunities to improve outcomes through early diagnosis and timely disease management. In this review, we discuss salient findings on 16 candidate biomarkers and their association with AKI. We explore the differences in biomarker distribution by age and discuss why adult biomarker research findings cannot be directly extrapolated to children. With future research, more consideration needs to be given to how the maturing kidney affects biomarker levels and how we interpret biomarker performance in children. A comprehensive approach using age-specific biomarker reference ranges is required to develop pediatric biomarkers and improve outcomes for children with kidney disease.Greenberg, Jason H.Parikh, Chirag R.2017-06-30T06:52:06-07:00doi:10.2215/CJN.12851216hwp:resource-id:clinjasn;12/9/1551American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, pediatric nephrology, pediatric intensive care medicine, Epidemiology and outcomes, kidney development, albuminuriaReviewReviewreview-article20172017-09-07September 07, 201710.2215/CJN.128512161555-90411555-905X2017-06-30T06:52:06-07:002017-09-07Clinical Journal of the American Society of NephrologyReview12915511557
- Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD10.2215/CJN.00530117Wed, 02 Aug 2017 05:49:35 GMT-07:00Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKDBatacchi, ZonaRobinson-Cohen, CassianneHoofnagle, Andrew N.Isakova, TamaraKestenbaum, BryanMartin, Kevin J.Wolf, Myles S.de Boer, Ian H.2017-08-02T05:49:35-07:00doi:10.2215/CJN.00530117hwp:resource-id:clinjasn;12/9/1498American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyVitamin D, metabolism, chronic kidney diseaseOriginal ArticlesMineral MetabolismOriginal ArticlesMineral Metabolismresearch-article20172017-09-07September 07, 201710.2215/CJN.005301171555-90411555-905X2017-08-02T05:49:35-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914981506
- eGFR and the Risk of Community-Acquired Infections10.2215/CJN.00250117Thu, 17 Aug 2017 10:24:19 GMT-07:00eGFR and the Risk of Community-Acquired InfectionsXu, HongGasparini, AlessandroIshigami, JunichiMzayen, KhaledSu, GuobinBarany, PeterÄrnlöv, JohanLindholm, BengtElinder, Carl GustafMatsushita, KunihiroCarrero, Juan Jesús2017-08-17T10:24:19-07:00doi:10.2215/CJN.00250117hwp:resource-id:clinjasn;12/9/1399American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Epidemiology and outcomes, renal function, risk factors, urinary tract infections, lower respiratory tract infection, sepsis, community, Adult, Aged, Communicable Diseases, Community-Acquired Infections, creatinine, Female, glomerular filtration rate, Health Care Costs, Humans, Incidence, Middle Aged, Nervous System, Renal Insufficiency, Chronic, Respiratory Tract Infections, Urinary Tract InfectionsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.002501171555-90411555-905X2017-08-17T10:24:19-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12913991408
- Pre-ESRD Depression and Post-ESRD Mortality in Patients with Advanced CKD Transitioning to Dialysis10.2215/CJN.00570117Wed, 05 Jul 2017 06:34:13 GMT-07:00Pre-ESRD Depression and Post-ESRD Mortality in Patients with Advanced CKD Transitioning to DialysisMolnar, Miklos Z.Streja, ElaniSumida, KeiichiSoohoo, MelissaRavel, Vanessa A.Gaipov, AbduzhapparPotukuchi, Praveen K.Thomas, FridtjofRhee, Connie M.Lu, Jun LingKalantar-Zadeh, KamyarKovesdy, Csaba P.2017-07-05T06:34:13-07:00doi:10.2215/CJN.00570117hwp:resource-id:clinjasn;12/9/1428American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymortality, chronic kidney disease, end stage kidney disease, transition, African Americans, Comorbidity, Confidence Intervals, depression, diabetes mellitus, Disease Progression, hospitalization, Humans, Kidney Failure, Chronic, Male, Proportional Hazards Models, quality of life, renal dialysis, Renal Insufficiency, Chronic, Risk, VeteransOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.005701171555-90411555-905X2017-07-05T06:34:13-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914281437
- Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD10.2215/CJN.10791016Fri, 26 May 2017 08:29:41 GMT-07:00Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKDLevin, AdeeraTang, MilaPerry, TaylorZalunardo, NadiaBeaulieu, MonicaDubland, Joshua A.Zerr, KellyDjurdjev, Ognjenka2017-05-26T08:29:41-07:00doi:10.2215/CJN.10791016hwp:resource-id:clinjasn;12/9/1447American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyVitamin D, vascular calcification, vascular disease, mineral metabolism, Aged, Arm, blood pressure, C-Reactive Protein, Calcifediol, Calcitriol, calcium, Canada, diabetes mellitus, Fibroblast Growth Factors, Humans, Male, Minerals, Outpatients, parathyroid hormone, proteinuria, Pulse Wave Analysis, Renal Insufficiency, Chronic, Vascular Stiffness, Vitamins, fibroblast growth factor 23Original ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.107910161555-90411555-905X2017-05-26T08:29:41-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12991447137714601379
- eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health Study10.2215/CJN.01860217Thu, 10 Aug 2017 06:07:21 GMT-07:00eGFR and Albuminuria in Relation to Risk of Incident Atrial Fibrillation: A Meta-Analysis of the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Cardiovascular Health StudyBansal, NishaZelnick, Leila R.Alonso, AlvaroBenjamin, Emelia J.de Boer, Ian H.Deo, RajatKatz, RonitKestenbaum, BryanMathew, JehuRobinson-Cohen, CassianneSarnak, Mark J.Shlipak, Michael G.Sotoodehnia, NonaYoung, BessieHeckbert, Susan R.2017-08-10T06:07:21-07:00doi:10.2215/CJN.01860217hwp:resource-id:clinjasn;12/9/1386American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, albuminuriaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.018602171555-90411555-905X2017-08-10T06:07:21-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12913861398
- Association of QT-Prolonging Medication Use in CKD with Electrocardiographic Manifestations10.2215/CJN.12991216Wed, 09 Aug 2017 08:31:27 GMT-07:00Association of QT-Prolonging Medication Use in CKD with Electrocardiographic ManifestationsSnitker, SorenDoerfler, Rebecca M.Soliman, Elsayed Z.Deo, RajatSt. Peter, Wendy L.Kramlik, SusanFischer, Michael J.Navaneethan, SankarDelafontaine, PatriceJaar, Bernard G.Ojo, AkinloluMakos, Gail K.Slaven, AnneWeir, Matthew R.Zhan, MinFink, Jeffrey C.,2017-08-09T08:31:27-07:00doi:10.2215/CJN.12991216hwp:resource-id:clinjasn;12/9/1409American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAmiodarone, Arrhythmias, Cardiac, Brugada Syndrome, Citalopram, Diuretics, Electrocardiography, Electrolytes, Fluoxetine, Furosemide, Heart Conduction System, Humans, Hydroxyzine, Metolazone, Potassium, Proton Pump Inhibitors, Renal Dialysis, Renal Insufficiency, Chronic, Sodium Chloride Symporter Inhibitors, Spironolactone, Venlafaxine Hydrochloride, Cardiac Conduction DefectOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.129912161555-90411555-905X2017-08-09T08:31:27-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914091417
- Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial10.2215/CJN.01870217Mon, 07 Aug 2017 06:33:23 GMT-07:00Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind TrialKendrick, JessicaAndrews, EmilyYou, ZhiyingMoreau, KerrieNowak, Kristen L.Farmer-Bailey, HeatherSeals, Douglas R.Chonchol, Michel2017-08-07T06:33:23-07:00doi:10.2215/CJN.01870217hwp:resource-id:clinjasn;12/9/1438American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Vitamin D, vascular disease, clinical trial, Adult, Brachial Artery, Calcifediol, Calcitriol, Cholecalciferol, Dilatation, Double-Blind Method, glomerular filtration rate, Humans, Inflammation, Minerals, parathyroid hormone, Prospective Studies, Renal Insufficiency, Chronic, Vitamins, 25-hydroxyvitamin DOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.018702171555-90411555-905X2017-08-07T06:33:23-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12991438137714461379
- Pragmatic Randomized, Controlled Trial of Patient Navigators and Enhanced Personal Health Records in CKD10.2215/CJN.02100217Fri, 04 Aug 2017 12:04:26 GMT-07:00Pragmatic Randomized, Controlled Trial of Patient Navigators and Enhanced Personal Health Records in CKDNavaneethan, Sankar D.Jolly, Stacey E.Schold, Jesse D.Arrigain, SusanaNakhoul, GeorgesKonig, VictoriaHyland, JenniferBurrucker, Yvette K.Dann, Priscilla DavisTucky, Barbara H.Sharp, JohnNally, Joseph V.2017-08-04T12:04:26-07:00doi:10.2215/CJN.02100217hwp:resource-id:clinjasn;12/9/1418American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, navigator, personal health record, Aged, Ambulatory Care Facilities, Cost-Benefit Analysis, Electronic Health Records, Emergency Service, Hospital, Follow-Up Studies, Health Records, Personal, hospitalization, Humans, Nephrologists, nephrology, Outcome Assessment (Health Care), Patient Care Planning, Patient Navigation, Primary Health Care, Referral and Consultation, renal dialysis, Renal Insufficiency, Chronic, Renin-Angiotensin SystemOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.021002171555-90411555-905X2017-08-04T12:04:26-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12991418137514271376
- Diagnosis and Management of Type 2 Diabetic Kidney DiseaseType 2 diabetic kidney disease (DKD) is the most common cause of CKD and ESRD worldwide, and carries with it enormous human and societal costs. The goal of this review is to provide an update on the diagnosis and management of DKD based on a comprehensive review of the medical literature. Topics addressed include the evolving presentation of DKD, clinical differentiation of DKD from non-DKD, a state-of-the-art evaluation of current treatment strategies, and promising emerging treatments. It is expected that the review will help clinicians to diagnose and manage patients with DKD.10.2215/CJN.11111016Thu, 09 Mar 2017 06:04:22 GMT-08:00Diagnosis and Management of Type 2 Diabetic Kidney DiseaseType 2 diabetic kidney disease (DKD) is the most common cause of CKD and ESRD worldwide, and carries with it enormous human and societal costs. The goal of this review is to provide an update on the diagnosis and management of DKD based on a comprehensive review of the medical literature. Topics addressed include the evolving presentation of DKD, clinical differentiation of DKD from non-DKD, a state-of-the-art evaluation of current treatment strategies, and promising emerging treatments. It is expected that the review will help clinicians to diagnose and manage patients with DKD.Doshi, Simit M.Friedman, Allon N.2017-03-09T06:04:22-08:00doi:10.2215/CJN.11111016hwp:resource-id:clinjasn;12/8/1366American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCosts and Cost Analysis, Diabetic Nephropathies, Disease Management Disease Management, Goals, Humans, Kidney Failure, Chronic, Publications, Renal Insufficiency, ChronicReviewReviewreview-article20172017-08-07August 07, 201710.2215/CJN.111110161555-90411555-905X2017-03-09T06:04:22-08:002017-08-07Clinical Journal of the American Society of NephrologyReview12813661373
- Use of Proteomics To Investigate Kidney Function Decline over 5 Years10.2215/CJN.08780816Fri, 21 Jul 2017 06:03:09 GMT-07:00Use of Proteomics To Investigate Kidney Function Decline over 5 YearsCarlsson, Axel C.Ingelsson, ErikSundström, JohanJesus Carrero, JuanGustafsson, StefanFeldreich, TobiasStenemo, MarkusLarsson, AndersLind, LarsÄrnlöv, Johan2017-07-21T06:03:09-07:00doi:10.2215/CJN.08780816hwp:resource-id:clinjasn;12/8/1226American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Aged, Albumins, apoptosis, Cardiovascular Diseases, creatinine, extracellular matrix, Fatty Acid-Binding Proteins, Fibroblast Growth Factors, Follow-Up Studies, glomerular filtration rate, Homeostasis, Longitudinal Studies, Phosphates, Plasminogen, Prospective Studies, Proteomics, risk factors, Urokinase-Type Plasminogen ActivatorOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-08-07August 07, 201710.2215/CJN.087808161555-90411555-905X2017-07-21T06:03:09-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12881226120612351208
- Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining BarriersA key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)–based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar.10.2215/CJN.07900716Wed, 15 Mar 2017 06:02:16 GMT-07:00Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining BarriersA key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)–based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar.Leung, GeneralKirpalani, AnishSzeto, Stephen G.Deeb, MayaFoltz, WarrenSimmons, Craig A.Yuen, Darren A.2017-03-15T06:02:16-07:00doi:10.2215/CJN.07900716hwp:resource-id:clinjasn;12/6/1019American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, MRI, microvascular injury, stiffness, elastography, biopsy, cicatrix, fibrosis, kidney, magnetic resonance imaging, renal insufficiency, chronic, selection biasReviewReviewreview-article20172017-06-07June 07, 201710.2215/CJN.079007161555-90411555-905X2017-03-15T06:02:16-07:002017-06-07Clinical Journal of the American Society of NephrologyReview12610191028
- Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKD10.2215/CJN.07010716Thu, 18 May 2017 11:07:36 GMT-07:00Comparison between Different Measures of Body Fat with Kidney Function Decline and Incident CKDMadero, MagdalenaKatz, RonitMurphy, RachelNewman, AnnePatel, KushangIx, JoachimPeralta, CarmenSatterfield, SuzanneFried, LindaShlipak, MichaelSarnak, Mark2017-05-18T11:07:36-07:00doi:10.2215/CJN.07010716hwp:resource-id:clinjasn;12/6/893American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, renal function decline, Aged, Body Composition, Body Mass Index, diabetes mellitus, Follow-Up Studies, Humans, Intra-Abdominal Fat, Logistic Models, Male, obesity, Renal Insufficiency, Chronic, risk factors, Subcutaneous Fat, Subcutaneous Fat, Abdominal, Tomography, Tomography, X-Ray Computed, Waist CircumferenceOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-06-07June 07, 201710.2215/CJN.070107161555-90411555-905X2017-05-18T11:07:36-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126893903
- Sleep and CKD in Chinese Adults: A Cross-Sectional Study10.2215/CJN.09270816Fri, 07 Apr 2017 06:05:36 GMT-07:00Sleep and CKD in Chinese Adults: A Cross-Sectional StudyLi, JunjuanHuang, ZheHou, JinhongSawyer, Amy M.Wu, ZhijunCai, JianfangCurhan, GaryWu, ShoulingGao, Xiang2017-04-07T06:05:36-07:00doi:10.2215/CJN.09270816hwp:resource-id:clinjasn;12/6/885American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologySleep, chronic kidney disease, cross-sectional study, Adult, creatinine, Cross-Sectional Studies, Fasting, glomerular filtration rate, Humans, Kidney Function Tests, Logistic Models, Prospective Studies, proteinuria, Renal Insufficiency, Chronic, Self Report, Sleep Initiation and Maintenance Disorders, Snoring, Surveys and QuestionnairesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-06-07June 07, 201710.2215/CJN.092708161555-90411555-905X2017-04-07T06:05:36-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126885892
- Time-Varying Association of Individual BP Components with eGFR in Late-Stage CKD10.2215/CJN.05640516Wed, 29 Mar 2017 05:48:06 GMT-07:00Time-Varying Association of Individual BP Components with eGFR in Late-Stage CKDSood, Manish M.Akbari, AyubManuel, DougRuzicka, MarcelHiremath, SwapnilZimmerman, DeborahMcCormick, BrendenTaljaard, Monica2017-03-29T05:48:06-07:00doi:10.2215/CJN.05640516hwp:resource-id:clinjasn;12/6/904American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyeGFR, CKD, systolic blood pressure, diastolic blood pressure, pulse pressure, linear mixed model, repeat measures, time-varying Cox proportional hazards model, blood pressure, Blood Pressure Determination, glomerular filtration rate, Humans, Proportional Hazards Models, Renal Insufficiency, Chronic, Retrospective Studies, Risk, SystoleOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-06-07June 07, 201710.2215/CJN.056405161555-90411555-905X2017-03-29T05:48:06-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126904911
- Albuminuria, Proteinuria, and Renal Disease Progression in Children with CKD10.2215/CJN.11971116Thu, 25 May 2017 07:13:49 GMT-07:00Albuminuria, Proteinuria, and Renal Disease Progression in Children with CKDFuhrman, Dana Y.Schneider, Michael F.Dell, Katherine M.Blydt-Hansen, Tom D.Mak, RobertSaland, Jeffrey M.Furth, Susan L.Warady, Bradley A.Moxey-Mims, Marva M.Schwartz, George J.2017-05-25T07:13:49-07:00doi:10.2215/CJN.11971116hwp:resource-id:clinjasn;12/6/912American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, pediatrics, progression of chronic renal failure, renal function decline, creatinine, Cross-Sectional Studies, diabetes mellitus, Disease Progression, Follow-Up Studies, glomerular filtration rate, Humans, kidney, Linear Models, proteinuria, Renal Insufficiency, Chronic, Renal Replacement Therapy, Sample SizeOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-06-07June 07, 201710.2215/CJN.119711161555-90411555-905X2017-05-25T07:13:49-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126912920
- A Population-Based Analysis of Quality Indicators in CKD10.2215/CJN.08720816Tue, 04 Apr 2017 05:44:18 GMT-07:00A Population-Based Analysis of Quality Indicators in CKDManns, LiamScott-Douglas, NairneTonelli, MarcelloWeaver, RobertTam-Tham, HelenChong, ChristyHemmelgarn, Brenda2017-04-04T05:44:18-07:00doi:10.2215/CJN.08720816hwp:resource-id:clinjasn;12/5/727American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal Insufficiency, Chronic, Quality Indicators, Health Care, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Health Care Quality, Access, and Evaluation, Adult, Albumins, albuminuria, Angiotensin Receptor, Antagonists, Chronic Disease, creatinine, diabetes mellitus, Humans, Kidney Function Tests, Quality ImprovementOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-05-08May 08, 201710.2215/CJN.087208161555-90411555-905X2017-04-04T05:44:18-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125727733
- Association of CKD with Outcomes Among Patients Undergoing Transcatheter Aortic Valve Implantation10.2215/CJN.10471016Mon, 13 Mar 2017 07:21:33 GMT-07:00Association of CKD with Outcomes Among Patients Undergoing Transcatheter Aortic Valve ImplantationLüders, FlorianKaier, KlausKaleschke, GerritGebauer, KatrinMeyborg, MatthiasMalyar, Nasser M.Freisinger, EvaBaumgartner, HelmutReinecke, HolgerReinöhl, Jochen2017-03-13T07:21:33-07:00doi:10.2215/CJN.10471016hwp:resource-id:clinjasn;12/5/718American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTranscatheter Aortic Valve Replacement, Aortic Valve Stenosis, chronic renal insufficiency, Treatment Outcome, Economics, Acute Kidney Injury, Comorbidity, Confidence Intervals, coronary artery disease, diabetes mellitus, Female, Germany, heart failure, Hospital Mortality, Humans, Length of Stay, Peripheral Arterial Disease, Prognosis, Renal Insufficiency, Chronic, Risk Assessment, StrokeOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-05-08May 08, 201710.2215/CJN.104710161555-90411555-905X2017-03-13T07:21:33-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125718726
- Randomized, Controlled Trial of the Effect of Dietary Potassium Restriction on Nerve Function in CKD10.2215/CJN.00670117Mon, 11 Sep 2017 07:49:30 GMT-07:00Randomized, Controlled Trial of the Effect of Dietary Potassium Restriction on Nerve Function in CKDArnold, RiaPianta, Timothy J.Pussell, Bruce A.Kirby, AdrienneO’Brien, KateSullivan, KarenHolyday, MargaretCormack, ChristineKiernan, Matthew C.Krishnan, Arun V.2017-09-11T07:49:30-07:00doi:10.2215/CJN.00670117hwp:resource-id:clinjasn;12/10/1569American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical trial, electrophysiology, Arm, Control Groups, Diet, electrolytes, Humans, Hyperkalemia, Neuroprotection, Nutritional Status, Polystyrenes, Potassium, Potassium, Dietary, Prospective Studies, quality of life, renal dialysis, Renal Insufficiency, Chronic, Single-Blind Method, Walking Speed, polystyrene sulfonic acidOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-10-06October 06, 201710.2215/CJN.006701171555-90411555-905X2017-09-11T07:49:30-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles1210101569155915771560
- Endothelium-Dependent and -Independent Vascular Function in Advanced Chronic Kidney Disease10.2215/CJN.12811216Mon, 07 Aug 2017 06:33:22 GMT-07:00Endothelium-Dependent and -Independent Vascular Function in Advanced Chronic Kidney DiseaseKopel, TalKaufman, James S.Hamburg, NaomiSampalis, John S.Vita, Joseph A.Dember, Laura M.2017-08-07T06:33:22-07:00doi:10.2215/CJN.12811216hwp:resource-id:clinjasn;12/10/1588American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteries, cardiovascular disease, chronic kidney disease, chronic renal disease, chronic renal insufficiency, end-stage renal disease, endothelium, vascular disease, nitric oxide, Accidental Falls, Brachial Artery, Cohort Studies, coronary artery disease, Dilatation, Endothelium, Vascular, Humans, hypertension, Nitroglycerin, Renal Insufficiency, Chronic, risk factorsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-10-06October 06, 201710.2215/CJN.128112161555-90411555-905X2017-08-07T06:33:22-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121015881594
- Marijuana Use and Estimated Glomerular Filtration Rate in Young Adults10.2215/CJN.01530217Thu, 24 Aug 2017 06:58:16 GMT-07:00Marijuana Use and Estimated Glomerular Filtration Rate in Young AdultsIshida, Julie H.Auer, RetoVittinghoff, EricPletcher, Mark J.Reis, Jared P.Sidney, StephenJohansen, Kirsten L.Bibbins-Domingo, KirstenPeralta, Carmen A.Shlipak, Michael G.2017-08-24T06:58:16-07:00doi:10.2215/CJN.01530217hwp:resource-id:clinjasn;12/10/1578American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMarijuana, kidney disease, clinical epidemiology, Adult, Albumins, albuminuria, Cannabis, Cohort Studies, Coronary Vessels, creatinine, Cross-Sectional Studies, Cystatin C, glomerular filtration rate, Humans, Kidney Function Tests, Marijuana Abuse, Marijuana Smoking, Receptor, Epidermal Growth Factor, United States, Young Adult, EGFR protein, humanOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-10-06October 06, 201710.2215/CJN.015302171555-90411555-905X2017-08-24T06:58:16-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121015781587
- Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKD10.2215/CJN.02510317Thu, 07 Sep 2017 08:28:55 GMT-07:00Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKDSise, Meghan E.Backman, ElkeOrtiz, Guillermo A.Hundemer, Gregory L.Ufere, Nneka N.Chute, Donald F.Brancale, JosephXu, DihuaWisocky, JessicaLin, Ming V.Kim, Arthur Y.Thadhani, RaviChung, Raymond T.2017-09-07T08:28:55-07:00doi:10.2215/CJN.02510317hwp:resource-id:clinjasn;12/10/1615American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, virology, chronic kidney disease, drug nephrotoxicity, progression of renal failure, albuminuria, Antiviral Agents, creatinine, diabetes mellitus, Disease Progression, Follow-Up Studies, Genotype, glomerular filtration rate, Hepacivirus, Hepatitis C, Humans, Kidney Failure, Chronic, Liver, Cirrhosis, Male, Middle Aged, proteinuria, Renal Insufficiency, Chronic, Retrospective Studies, Sofosbuvir, Sustained Virologic ResponseOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-10-06October 06, 201710.2215/CJN.025103171555-90411555-905X2017-09-07T08:28:55-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles1210101615156316231565
- Is Chronic Dialysis the Right Hard Renal End Point To Evaluate Renoprotective Drug Effects?10.2215/CJN.09590916Mon, 18 Sep 2017 12:49:23 GMT-07:00Is Chronic Dialysis the Right Hard Renal End Point To Evaluate Renoprotective Drug Effects?Weldegiorgis, Misghinade Zeeuw, DickDwyer, Jamie P.Mol, PeterHeerspink, Hiddo J.L.2017-09-18T12:49:23-07:00doi:10.2215/CJN.09590916hwp:resource-id:clinjasn;12/10/1595American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAngiotensin II, Biphenyl Compounds, creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, glomerular filtration rate, Humans, kidney, Linear Models, Losartan, nephrology, renal dialysis, Renal Replacement Therapy, Tetrazoles, irbesartanOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-10-06October XX, 201710.2215/CJN.095909161555-90411555-905X2017-09-18T12:49:23-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles1210101595156116001562
- Effectiveness of Quality Improvement Strategies for the Management of CKD10.2215/CJN.02490317Wed, 06 Sep 2017 05:54:04 GMT-07:00Effectiveness of Quality Improvement Strategies for the Management of CKDSilver, Samuel A.Bell, Chaim M.Chertow, Glenn M.Shah, Prakesh S.Shojania, KavehWald, RonHarel, Ziv2017-09-06T05:54:04-07:00doi:10.2215/CJN.02490317hwp:resource-id:clinjasn;12/10/1601American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, quality improvement, chronic kidney failure, Adult, blood pressure, Cholesterol, LDL, Chronic Disease, Confidence Intervals, Disease Management, glomerular filtration rate, Hemoglobin A, Glycosylated, Humans, Incidence, Odds Ratio, Probability, Quality Improvement, Randomized Controlled Trials as Topic, renal dialysis, Renal Insufficiency, Chronic, Renin-Angiotensin System, RiskOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20172017-10-06October 06, 201710.2215/CJN.024903171555-90411555-905X2017-09-06T05:54:04-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121016011614
- A French Cohort Study of Kidney Retransplantation after Post-Transplant Lymphoproliferative Disorders10.2215/CJN.03790417Thu, 17 Aug 2017 10:24:18 GMT-07:00A French Cohort Study of Kidney Retransplantation after Post-Transplant Lymphoproliferative DisordersCaillard, SophieCellot, EtienneDantal, JacquesThaunat, OlivierProvot, FrançoisJanbon, BénédicteBuchler, MatthiasAnglicheau, DanyMerville, PierreLang, PhilippeFrimat, LucColosio, CharlotteAlamartine, EricKamar, NassimHeng, Anne ElisabethDurrbach, AntoineMoal, ValérieRivalan, JosephEtienne, IsabellePeraldi, Marie NoelleMoreau, AnneMoulin, Bruno,2017-08-17T10:24:18-07:00doi:10.2215/CJN.03790417hwp:resource-id:clinjasn;12/10/1663American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdult, Antilymphocyte Serum, Antiviral Agents, Calcineurin, Calcineurin Inhibitors, Cohort Studies, Epstein-Barr Virus Infections, France, Herpesvirus 4, Human, Humans, immunosuppression, kidney, kidney transplantation, Lymphoproliferative Disorders, Mycophenolic Acid, Neoplasm Recurrence, Local, Receptors, Interleukin-2, Reoperation, Rituximab, thymoglobulinOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-10-06October 06, 201710.2215/CJN.037904171555-90411555-905X2017-08-17T10:24:18-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121016631670
- Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous Nephropathy10.2215/CJN.01460217Fri, 11 Aug 2017 06:44:56 GMT-07:00Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous NephropathyWang, JiaCui, ZhaoLu, JieProbst, ChristianZhang, Yi-miaoWang, XinQu, ZhenWang, FangMeng, Li-qiangCheng, Xu-yangLiu, GangDebiec, HannaRonco, PierreZhao, Ming-hui2017-08-11T06:44:56-07:00doi:10.2215/CJN.01460217hwp:resource-id:clinjasn;12/10/1642American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, Immunology and pathology, membranous nephropathy, Antibodies, Antibodies, Anti-Idiotypic, Autoimmunity, Biopsy, Fluorescent Antibody Technique, Follow-Up Studies, GN, Membranous, Humans, immunohistochemistry, Kidney Glomerulus, Neoplasms, Prevalence, proteinuria, Receptors, Phospholipase A2, Recurrence, Thrombospondins, United States, PLA2R1 protein, humanOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20172017-10-06October 06, 201710.2215/CJN.014602171555-90411555-905X2017-08-11T06:44:56-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121016421651
- The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis10.2215/CJN.00180117Wed, 09 Aug 2017 08:31:26 GMT-07:00The Clinical and Mutational Spectrum of Turkish Patients with CystinosisTopaloglu, RezanGulhan, Boraİnözü, MihribanCanpolat, NurYilmaz, AlevNoyan, AytülDursun, İsmailGökçe, İbrahimGürgöze, Metin KayaAkinci, NurverBaskin, EsraSerdaroğlu, ErkinDemircioğlu Kiliç, BeltingeYüksel, SelçukÖvünç Hacihamdioğlu, DuyguKorkmaz, EmineHayran, MutluOzaltin, Fatih,2017-08-09T08:31:26-07:00doi:10.2215/CJN.00180117hwp:resource-id:clinjasn;12/10/1634American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCystinosis, CTNS gene, Alleles, Appetite, Child, Female, Follow-Up Studies, glomerular filtration rate, Humans, kidney, Kidney Failure, Chronic, Male, Mutation, Mutation, Missense, Polyuria, Sequence Deletion, Turkey, Cystinosis, Infantile NephropathicOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20172017-10-06October 06, 201710.2215/CJN.001801171555-90411555-905X2017-08-09T08:31:26-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121016341641
- ANCA Glomerulonephritis and VasculitisANCA vasculitis has an associated autoimmune response that produces ANCAs that induce distinct pathologic lesions. Pauci-immune necrotizing and crescentic GN is a frequent component of ANCA vasculitis. ANCA vasculitis is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). A diagnosis of ANCA vasculitis should always specify the serotype as MPO-ANCA positive, PR3-ANCA positive, or ANCA-negative. To fully characterize a patient, the serotype also should be accompanied by the clinicopathologic variant if this can be determined: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener), eosinophilic granulomatosis with polyangiitis (Churg–Strauss), or renal-limited vasculitis. ANCA vasculitis is most prevalent in individuals >50 years old. There are racial/ethnic and geographic influences on the prevalence, serotype frequencies, and clinicopathologic phenotypes. There is clinical, in vitro, and animal model evidence that ANCAs cause disease by activating neutrophils to attack small vessels. Immunomodulatory and immunosuppressive therapies are used to induce remission, maintain remission, and treat relapses. Over recent years, there have been major advances in optimizing treatment by minimizing toxic therapy and utilizing more targeted therapy.10.2215/CJN.02500317Fri, 25 Aug 2017 06:30:49 GMT-07:00ANCA Glomerulonephritis and VasculitisANCA vasculitis has an associated autoimmune response that produces ANCAs that induce distinct pathologic lesions. Pauci-immune necrotizing and crescentic GN is a frequent component of ANCA vasculitis. ANCA vasculitis is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). A diagnosis of ANCA vasculitis should always specify the serotype as MPO-ANCA positive, PR3-ANCA positive, or ANCA-negative. To fully characterize a patient, the serotype also should be accompanied by the clinicopathologic variant if this can be determined: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener), eosinophilic granulomatosis with polyangiitis (Churg–Strauss), or renal-limited vasculitis. ANCA vasculitis is most prevalent in individuals >50 years old. There are racial/ethnic and geographic influences on the prevalence, serotype frequencies, and clinicopathologic phenotypes. There is clinical, in vitro, and animal model evidence that ANCAs cause disease by activating neutrophils to attack small vessels. Immunomodulatory and immunosuppressive therapies are used to induce remission, maintain remission, and treat relapses. Over recent years, there have been major advances in optimizing treatment by minimizing toxic therapy and utilizing more targeted therapy.Jennette, J. CharlesNachman, Patrick H.2017-08-25T06:30:49-07:00doi:10.2215/CJN.02500317hwp:resource-id:clinjasn;12/10/1680American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, Myeloblastin, Antibodies, Antineutrophil Cytoplasmic, Granulomatosis with Polyangiitis, Peroxidase, Neutrophils, Autoantibodies, Autoimmunity, Prevalence, Microscopic Polyangiitis, Serogroup, Churg-Strauss Syndrome, glomerulonephritis, Neutrophil Activation, Models, Animal, RecurrenceGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-10-06October 06, 201710.2215/CJN.025003171555-90411555-905X2017-08-25T06:30:49-07:002017-10-06Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician121016801691
- A Patient with a Novel Gene Mutation Leading to Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.02830317Mon, 07 Aug 2017 06:33:22 GMT-07:00A Patient with a Novel Gene Mutation Leading to Autosomal Dominant Polycystic Kidney DiseaseReddy, Bharathi V.Chapman, Arlene B.2017-08-07T06:33:22-07:00doi:10.2215/CJN.02830317hwp:resource-id:clinjasn;12/10/1695American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, kidney, Mutation, Polycystic Kidney, Autosomal DominantKidney Case ConferencesAttending RoundsKidney Case ConferencesAttending Roundsresearch-article20172017-10-06October 06, 201710.2215/CJN.028303171555-90411555-905X2017-08-07T06:33:22-07:002017-10-06Clinical Journal of the American Society of NephrologyKidney Case Conferences121016951698
- Slow Rise in Serum Creatinine Level in a Kidney Transplant Recipient 3 Years Post-Transplant10.2215/CJN.12691216Thu, 23 Mar 2017 07:14:54 GMT-07:00Slow Rise in Serum Creatinine Level in a Kidney Transplant Recipient 3 Years Post-TransplantBia, Margaret J.2017-03-23T07:14:54-07:00doi:10.2215/CJN.12691216hwp:resource-id:clinjasn;12/10/1692American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycreatinine, kidney, kidney transplantation, Transplant Recipients, TransplantsKidney Case ConferencesNephrology Quiz and QuestionnaireKidney Case ConferencesNephrology Quiz and Questionnaireresearch-article20172017-10-06October 06, 201710.2215/CJN.126912161555-90411555-905X2017-03-23T07:14:54-07:002017-10-06Clinical Journal of the American Society of NephrologyKidney Case Conferences121016921694
- Thirty-Day Hospital Readmissions in the Hemodialysis Population10.2215/CJN.08810817Thu, 28 Sep 2017 09:24:53 GMT-07:00Thirty-Day Hospital Readmissions in the Hemodialysis PopulationAssimon, Magdalene M.Flythe, Jennifer E.2017-09-28T09:24:53-07:00doi:10.2215/CJN.08810817hwp:resource-id:clinjasn;12/10/1566American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, hospitalization, Epidemiology and outcomes, Patient Readmission, renal dialysisEditorialsEditorialseditorial20172017-10-06October 06, 201710.2215/CJN.088108171555-90411555-905X2017-09-28T09:24:53-07:002017-10-06Clinical Journal of the American Society of NephrologyEditorials1210101566165215681662
- Approaches to and Clinical Benefits of Reducing Dietary K in CKD10.2215/CJN.08470817Mon, 11 Sep 2017 07:49:29 GMT-07:00Approaches to and Clinical Benefits of Reducing Dietary K in CKDKendrick, JessicaLinas, Stuart2017-09-11T07:49:29-07:00doi:10.2215/CJN.08470817hwp:resource-id:clinjasn;12/10/1559American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, electrolytes, Diet, Potassium, Renal Insufficiency, ChronicEditorialsEditorialseditorial20172017-10-06October 06, 201710.2215/CJN.084708171555-90411555-905X2017-09-11T07:49:29-07:002017-10-06Clinical Journal of the American Society of NephrologyEditorials1210101559156915601577
- Rethinking End Points in Clinical Trials of Renoprotective Medication10.2215/CJN.09040817Mon, 18 Sep 2017 12:49:22 GMT-07:00Rethinking End Points in Clinical Trials of Renoprotective MedicationThompson, Aliza2017-09-18T12:49:22-07:00doi:10.2215/CJN.09040817hwp:resource-id:clinjasn;12/10/1561American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEndpoint Determination, Renoprotective Medication, Clinical TrialsEditorialsEditorialseditorial20172017-10-06October 06, 201710.2215/CJN.090408171555-90411555-905X2017-09-18T12:49:22-07:002017-10-06Clinical Journal of the American Society of NephrologyEditorials1210101561159515621600
- Magnetic Resonance Elastography to Assess Fibrosis in Kidney Allografts10.2215/CJN.01830217Wed, 30 Aug 2017 05:48:49 GMT-07:00Magnetic Resonance Elastography to Assess Fibrosis in Kidney AllograftsKirpalani, AnishHashim, EyeshaLeung, GeneralKim, Jin K.Krizova, AdrianaJothy, SergeDeeb, MayaJiang, Nan N.Glick, LaurenMnatzakanian, GevorkYuen, Darren A.2017-08-30T05:48:49-07:00doi:10.2215/CJN.01830217hwp:resource-id:clinjasn;12/10/1671American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-10-06October 06, 201710.2215/CJN.018302171555-90411555-905X2017-08-30T05:48:49-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121016711679
- Commentary on “Effectiveness of Treatment Modalities on Kidney Stone Recurrence”10.2215/CJN.07780717Tue, 22 Aug 2017 06:23:24 GMT-07:00Commentary on “Effectiveness of Treatment Modalities on Kidney Stone Recurrence”Seliger, Stephen L.Kestenbaum, Bryan R.2017-08-22T06:23:24-07:00doi:10.2215/CJN.07780717hwp:resource-id:clinjasn;12/10/1709American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, Kidney Calculi, RecurrenceCommentaryCommentaryarticle-commentary20172017-10-06October 06, 201710.2215/CJN.077807171555-90411555-905X2017-08-22T06:23:24-07:002017-10-06Clinical Journal of the American Society of NephrologyCommentary121017091710
- National Estimates of 30-Day Unplanned Readmissions of Patients on Maintenance Hemodialysis10.2215/CJN.02600317Thu, 28 Sep 2017 09:24:54 GMT-07:00National Estimates of 30-Day Unplanned Readmissions of Patients on Maintenance HemodialysisChan, LiliChauhan, KinsukPoojary, PritiSaha, AparnaHammer, ElizabethVassalotti, Joseph A.Jubelt, LindsayFerket, BartCoca, Steven G.Nadkarni, Girish N.2017-09-28T09:24:54-07:00doi:10.2215/CJN.02600317hwp:resource-id:clinjasn;12/10/1652American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end stage kidney disease, mortality, Readmission, Comorbidity, depression, Depressive Disorder, hospitalization, Humans, hypertension, Kidney Failure, Chronic, Logistic Models, Myocardial Infarction, Odds Ratio, Patient Discharge, Patient Readmission, renal dialysis, Retrospective Studies, Software, Substance-Related Disorders, Surveys and QuestionnairesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-10-06October 06, 201710.2215/CJN.026003171555-90411555-905X2017-09-28T09:24:54-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121410109165215661383166215681383
- Contemporary Management of Hepatitis C in Patients with CKD10.2215/CJN.07620717Thu, 07 Sep 2017 08:28:55 GMT-07:00Contemporary Management of Hepatitis C in Patients with CKDJohnson, Richard J.Shimada, Michiko2017-09-07T08:28:55-07:00doi:10.2215/CJN.07620717hwp:resource-id:clinjasn;12/10/1563American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHepatitis C, Hepacivirus, Disease Management, Renal Insufficiency, Chronic, HumansEditorialsEditorialseditorial20172017-10-06October 06, 201710.2215/CJN.076207171555-90411555-905X2017-09-07T08:28:55-07:002017-10-06Clinical Journal of the American Society of NephrologyEditorials1210101563161515651623
- Epidemiology and Natural History of the Cardiorenal Syndromes in a Cohort with Echocardiography10.2215/CJN.04020417Fri, 11 Aug 2017 06:44:57 GMT-07:00Epidemiology and Natural History of the Cardiorenal Syndromes in a Cohort with EchocardiographyMavrakanas, Thomas A.Khattak, AishaSingh, KarandeepCharytan, David M.2017-08-11T06:44:57-07:00doi:10.2215/CJN.04020417hwp:resource-id:clinjasn;12/10/1624American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and outcomes, mortality, myocardial infarction, Cardio-Renal Syndrome, Comorbidity, Confidence Intervals, echocardiography, heart failure, Humans, Incidence, Prognosis, Pulmonary Artery, Renal Insufficiency, Chronic, Retrospective Studies, Stroke, Stroke VolumeOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-10-06October 06, 201710.2215/CJN.040204171555-90411555-905X2017-08-11T06:44:57-07:002017-10-06Clinical Journal of the American Society of NephrologyOriginal Articles121016241633
- Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA NephropathyIgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell–positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell–positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.10.1681/ASN.2016101103Fri, 23 Jun 2017 05:41:13 GMT-07:00Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA NephropathyIgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type–specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell–positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell–positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell–positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell–positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.Liu, PeidiLassén, EmelieNair, VijiBerthier, Celine C.Suguro, MiyukiSihlbom, CarinaKretzler, MatthiasBetsholtz, ChristerHaraldsson, BörjeJu, WenjunEbefors, KerstinNyström, Jenny2017-06-23T05:41:13-07:00doi:10.1681/ASN.2016101103hwp:resource-id:jnephrol;28/10/2961American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, mesangial cells, transcriptional profilingBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20161011031046-66731533-34502017-06-23T05:41:13-07:002017-10Journal of the American Society of NephrologyBasic Research281029612972
- The Trauma of Dialysis Initiation10.1681/ASN.2017020212Mon, 28 Aug 2017 05:37:12 GMT-07:00The Trauma of Dialysis InitiationHercz, Gavril2017-08-28T05:37:12-07:00doi:10.1681/ASN.2017020212hwp:resource-id:jnephrol;28/10/2835American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis initiation, psychosocial, quality of lifeUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20172017-10-01October 201710.1681/ASN.20170202121046-66731533-34502017-08-28T05:37:12-07:002017-10Journal of the American Society of NephrologyUp Front Matters281028352837
- N-Degradomic Analysis Reveals a Proteolytic Network Processing the Podocyte CytoskeletonRegulated intracellular proteostasis, controlled in part by proteolysis, is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, and quantification of protein N-termini to comprehensively characterize cleaved podocyte proteins in the glomerulus in vivo. We found evidence that defined proteolytic cleavage results in various proteoforms of important podocyte proteins, including those of podocin, nephrin, neph1, α-actinin-4, and vimentin. Quantitative mapping of N-termini demonstrated perturbation of protease action during podocyte injury in vitro, including diminished proteolysis of α-actinin-4. Differentially regulated protease substrates comprised cytoskeletal proteins as well as intermediate filaments. Determination of preferential protease motifs during podocyte damage indicated activation of caspase proteases and inhibition of arginine-specific proteases. Several proteolytic processes were clearly site-specific, were conserved across species, and could be confirmed by differential migration behavior of protein fragments in gel electrophoresis. Some of the proteolytic changes discovered in vitro also occurred in two in vivo models of podocyte damage (WT1 heterozygous knockout mice and puromycin aminonucleoside–treated rats). Thus, we provide direct and systems-level evidence that the slit diaphragm and podocyte cytoskeleton are regulated targets of proteolytic modification, which is altered upon podocyte damage.10.1681/ASN.2016101119Wed, 19 Jul 2017 12:02:03 GMT-07:00N-Degradomic Analysis Reveals a Proteolytic Network Processing the Podocyte CytoskeletonRegulated intracellular proteostasis, controlled in part by proteolysis, is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, and quantification of protein N-termini to comprehensively characterize cleaved podocyte proteins in the glomerulus in vivo. We found evidence that defined proteolytic cleavage results in various proteoforms of important podocyte proteins, including those of podocin, nephrin, neph1, α-actinin-4, and vimentin. Quantitative mapping of N-termini demonstrated perturbation of protease action during podocyte injury in vitro, including diminished proteolysis of α-actinin-4. Differentially regulated protease substrates comprised cytoskeletal proteins as well as intermediate filaments. Determination of preferential protease motifs during podocyte damage indicated activation of caspase proteases and inhibition of arginine-specific proteases. Several proteolytic processes were clearly site-specific, were conserved across species, and could be confirmed by differential migration behavior of protein fragments in gel electrophoresis. Some of the proteolytic changes discovered in vitro also occurred in two in vivo models of podocyte damage (WT1 heterozygous knockout mice and puromycin aminonucleoside–treated rats). Thus, we provide direct and systems-level evidence that the slit diaphragm and podocyte cytoskeleton are regulated targets of proteolytic modification, which is altered upon podocyte damage.Rinschen, Markus M.Hoppe, Ann-KathrinGrahammer, FlorianKann, MartinVölker, Linus A.Schurek, Eva-MariaBinz, JulieHöhne, MartinDemir, FatihMalisic, MilenaHuber, Tobias B.Kurschat, ChristineKizhakkedathu, Jayachandran N.Schermer, BernhardHuesgen, Pitter F.Benzing, Thomas2017-07-19T12:02:03-07:00doi:10.1681/ASN.2016101119hwp:resource-id:jnephrol;28/10/2867American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, cell biology and structure, signaling, Cell Signaling, intracellular signal, Pathophysiology of Renal Disease and ProgressionBrief CommunicationsBrief Communicationsbrief-report20172017-10-01October 201710.1681/ASN.20161011191046-66731533-34502017-07-19T12:02:03-07:002017-10Journal of the American Society of NephrologyBrief Communications281028672878
- A Novel Hypokalemic-Alkalotic Salt-Losing Tubulopathy in Patients with CLDN10 MutationsMice lacking distal tubular expression of CLDN10, the gene encoding the tight junction protein Claudin-10, show enhanced paracellular magnesium and calcium permeability and reduced sodium permeability in the thick ascending limb (TAL), leading to a urine concentrating defect. However, the function of renal Claudin-10 in humans remains undetermined. We identified and characterized CLDN10 mutations in two patients with a hypokalemic-alkalotic salt-losing nephropathy. The first patient was diagnosed with Bartter syndrome (BS) >30 years ago. At re-evaluation, we observed hypocalciuria and hypercalcemia, suggesting Gitelman syndrome (GS). However, serum magnesium was in the upper normal to hypermagnesemic range, thiazide responsiveness was not blunted, and genetic analyses did not show mutations in genes associated with GS or BS. Whole-exome sequencing revealed compound heterozygous CLDN10 sequence variants [c.446C>G (p.Pro149Arg) and c.465–1G>A (p.Glu157_Tyr192del)]. The patient had reduced urinary concentrating ability, with a preserved aquaporin-2 response to desmopressin and an intact response to furosemide. These findings were not in line with any other known salt-losing nephropathy. Subsequently, we identified a second unrelated patient showing a similar phenotype, in whom we detected compound heterozygous CLDN10 sequence variants [c.446C>G (p.(Pro149Arg) and c.217G>A (p.Asp73Asn)]. Cell surface biotinylation and immunofluorescence experiments in cells expressing the encoded mutants showed that only one mutation caused significant differences in Claudin-10 membrane localization and tight junction strand formation, indicating that these alterations do not fully explain the phenotype. These data suggest that pathogenic CLDN10 mutations affect TAL paracellular ion transport and cause a novel tight junction disease characterized by a non-BS, non-GS autosomal recessive hypokalemic-alkalotic salt-losing phenotype.10.1681/ASN.2016080881Mon, 03 Jul 2017 07:30:32 GMT-07:00A Novel Hypokalemic-Alkalotic Salt-Losing Tubulopathy in Patients with CLDN10 MutationsMice lacking distal tubular expression of CLDN10, the gene encoding the tight junction protein Claudin-10, show enhanced paracellular magnesium and calcium permeability and reduced sodium permeability in the thick ascending limb (TAL), leading to a urine concentrating defect. However, the function of renal Claudin-10 in humans remains undetermined. We identified and characterized CLDN10 mutations in two patients with a hypokalemic-alkalotic salt-losing nephropathy. The first patient was diagnosed with Bartter syndrome (BS) >30 years ago. At re-evaluation, we observed hypocalciuria and hypercalcemia, suggesting Gitelman syndrome (GS). However, serum magnesium was in the upper normal to hypermagnesemic range, thiazide responsiveness was not blunted, and genetic analyses did not show mutations in genes associated with GS or BS. Whole-exome sequencing revealed compound heterozygous CLDN10 sequence variants [c.446C>G (p.Pro149Arg) and c.465–1G>A (p.Glu157_Tyr192del)]. The patient had reduced urinary concentrating ability, with a preserved aquaporin-2 response to desmopressin and an intact response to furosemide. These findings were not in line with any other known salt-losing nephropathy. Subsequently, we identified a second unrelated patient showing a similar phenotype, in whom we detected compound heterozygous CLDN10 sequence variants [c.446C>G (p.(Pro149Arg) and c.217G>A (p.Asp73Asn)]. Cell surface biotinylation and immunofluorescence experiments in cells expressing the encoded mutants showed that only one mutation caused significant differences in Claudin-10 membrane localization and tight junction strand formation, indicating that these alterations do not fully explain the phenotype. These data suggest that pathogenic CLDN10 mutations affect TAL paracellular ion transport and cause a novel tight junction disease characterized by a non-BS, non-GS autosomal recessive hypokalemic-alkalotic salt-losing phenotype.Bongers, Ernie M.H.F.Shelton, Luke M.Milatz, SusanneVerkaart, SjoerdBech, Anneke P.Schoots, JeroenCornelissen, Elisabeth A.M.Bleich, MarkusHoenderop, Joost G.J.Wetzels, Jack F.M.Lugtenberg, DorienNijenhuis, Tom2017-07-03T07:30:32-07:00doi:10.1681/ASN.2016080881hwp:resource-id:jnephrol;28/10/3118American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfamilial nephropathy, kidney tubule, hypokalemia, Cell & Transport Physiology, ion transport, salt-losing nephropathyClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20160808811046-66731533-34502017-07-03T07:30:32-07:002017-10Journal of the American Society of NephrologyClinical Research281031183128
- Pregnancy-Induced Sensitization Promotes Sex Disparity in Living Donor Kidney TransplantationThe presence of sex disparity in living donor kidney transplantation (LDKT) remains controversial. To determine if women fall behind men in LDKT evaluation, we performed an intention to treat study of 2587 candidates listed for kidney transplant at a single transplant center over 7 years. We found that women and men kidney transplant candidates engaged an equivalent type and number of prospective living donors. However, sex-specific differences in sensitization history and histocompatibility reduced the rate of LDKT for women by 30%. Pregnancy-induced incompatibility with spouse donors was limiting given that spouses were among the individuals most likely to complete donation. Notably, participation in a kidney paired exchange program eliminated sex-based differences in LDKT. Collectively, these data suggest that pregnancy is a formidable biologic barrier for women and contributes uniquely to sex disparity in LDKT. Targeted efforts to improve transplant center participation in paired kidney exchanges may increase sex equity in LDKT.10.1681/ASN.2016101059Mon, 08 May 2017 07:21:55 GMT-07:00Pregnancy-Induced Sensitization Promotes Sex Disparity in Living Donor Kidney TransplantationThe presence of sex disparity in living donor kidney transplantation (LDKT) remains controversial. To determine if women fall behind men in LDKT evaluation, we performed an intention to treat study of 2587 candidates listed for kidney transplant at a single transplant center over 7 years. We found that women and men kidney transplant candidates engaged an equivalent type and number of prospective living donors. However, sex-specific differences in sensitization history and histocompatibility reduced the rate of LDKT for women by 30%. Pregnancy-induced incompatibility with spouse donors was limiting given that spouses were among the individuals most likely to complete donation. Notably, participation in a kidney paired exchange program eliminated sex-based differences in LDKT. Collectively, these data suggest that pregnancy is a formidable biologic barrier for women and contributes uniquely to sex disparity in LDKT. Targeted efforts to improve transplant center participation in paired kidney exchanges may increase sex equity in LDKT.Bromberger, BiancaSpragan, DanielleHashmi, SohaibMorrison, AlexanderThomasson, ArwinNazarian, SusannaSawinski, DeirdrePorrett, Paige2017-05-08T07:21:55-07:00doi:10.1681/ASN.2016101059hwp:resource-id:jnephrol;28/10/3025American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologygender difference, kidney donation, kidney transplantation, pregnancy, disparityClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20161010591046-66731533-34502017-05-08T07:21:55-07:002017-10Journal of the American Society of NephrologyClinical Research2810103025282930332831
- Sex and Kidney Transplantation: Why Can’t a Woman Be More Like a Man?10.1681/ASN.2017060657Fri, 28 Jul 2017 06:23:59 GMT-07:00Sex and Kidney Transplantation: Why Can’t a Woman Be More Like a Man?August, PhyllisSuthanthiran, Manikkam2017-07-28T06:23:59-07:00doi:10.1681/ASN.2017060657hwp:resource-id:jnephrol;28/10/2829American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, gender, transplant outcomesUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-10-01October 201710.1681/ASN.20170606571046-66731533-34502017-07-28T06:23:59-07:002017-10Journal of the American Society of NephrologyUp Front Matters28101010282930253014283130333023
- Association between Reperfusion Renal Allograft Biopsy Findings and Transplant OutcomesBiopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0–3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation–related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.10.1681/ASN.2016121330Thu, 06 Jul 2017 06:51:31 GMT-07:00Association between Reperfusion Renal Allograft Biopsy Findings and Transplant OutcomesBiopsy findings at the time of procurement of deceased donor kidneys remain the most common reason cited for kidney discard. To determine the value of renal allograft histology in predicting outcomes, we evaluated the significance of histologic findings, read by experienced renal pathologists, in 975 postreperfusion biopsy specimens collected from 2005 to 2009 after living donor (n=427) or deceased donor (n=548) renal transplant. We evaluated specimens for the degree of glomerulosclerosis, interstitial fibrosis and tubular atrophy, and vascular disease; specimens with a score of 0 or 1 (scale, 0–3) for each parameter were considered optimal. Overall, 66.3% of living donor kidneys and 50.7% of deceased donor kidneys received an optimal histology score (P<0.001). Irrespective of donor status, suboptimal kidneys came from older donors with a higher incidence of diabetes mellitus, hypertension, and obesity and a higher mean kidney donor risk index (all P<0.001). Death-censored outcomes after transplant differed significantly between optimal and suboptimal kidneys only in the deceased donor transplants (P=0.02). Regardless of histologic classification, outcomes with deceased donor kidneys were inferior to outcomes with living donor kidneys. However, 73.2% of deceased donor kidneys with suboptimal histology remained functional at 5 years. Our findings suggest that histologic findings on postreperfusion biopsy associate with outcomes after deceased donor but not living donor renal transplants, thus donor death and organ preservation–related factors may be of greater prognostic importance. Discarding donated kidneys on the basis of histologic factors may be inappropriate and merits further study.Mohan, SumitCampenot, EricChiles, Mariana C.Santoriello, DominickBland, EricCrew, R. JohnRosenstiel, PaulDube, GeoffreyBatal, IbrahimRadhakrishnan, JaiSandoval, P. RodrigoGuarrera, JamesStokes, M. BarryD’Agati, VivetteCohen, David J.Ratner, Lloyd E.Markowitz, Glen2017-07-06T06:51:31-07:00doi:10.1681/ASN.2016121330hwp:resource-id:jnephrol;28/10/3109American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant pathology, transplant outcomes, renal transplantation, kidney histology, post-reperfusion biopsyClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20161213301046-66731533-34502017-07-06T06:51:31-07:002017-10Journal of the American Society of NephrologyClinical Research281031093117
- Autoantibodies against C-Reactive Protein Influence Complement Activation and Clinical Course in Lupus NephritisAutoantibodies against the major acute-phase reactant C-reactive protein (CRP) are frequently found in patients with lupus nephritis. Further defining the autoimmune epitopes on CRP may not only improve patient stratification but also, hint at mechanisms of CRP action. Herein, we show that amino acids 35–47 constitute the major epitope recognized by anti-CRP autoantibodies in patients with lupus nephritis. Notably, the presence of autoantibodies against amino acids 35–47 associated with more severe renal damage and predicted worse outcome. This epitope is exposed on CRP only after irreversible structure changes, yielding a conformationally altered form termed modified or monomeric CRP (mCRP). ELISA and surface plasmon resonance assays showed that amino acids 35–47 mediate the interaction of mCRP with complement factor H, an inhibitor of alternative pathway activation, and this interaction greatly enhanced the in vitro cofactor activity of complement factor H. In contrast, autoantibodies against amino acids 35–47 inhibited these actions of mCRP. Our results thus provide evidence for the in vivo generation of mCRP in a human disease and suggest that mCRP actively controls the pathogenesis of lupus nephritis by regulating complement activation. Therefore, amino acids 35–47 constitute a functional autoimmune epitope on CRP that can be targeted therapeutically and diagnostically.10.1681/ASN.2016070735Wed, 31 May 2017 10:57:18 GMT-07:00Autoantibodies against C-Reactive Protein Influence Complement Activation and Clinical Course in Lupus NephritisAutoantibodies against the major acute-phase reactant C-reactive protein (CRP) are frequently found in patients with lupus nephritis. Further defining the autoimmune epitopes on CRP may not only improve patient stratification but also, hint at mechanisms of CRP action. Herein, we show that amino acids 35–47 constitute the major epitope recognized by anti-CRP autoantibodies in patients with lupus nephritis. Notably, the presence of autoantibodies against amino acids 35–47 associated with more severe renal damage and predicted worse outcome. This epitope is exposed on CRP only after irreversible structure changes, yielding a conformationally altered form termed modified or monomeric CRP (mCRP). ELISA and surface plasmon resonance assays showed that amino acids 35–47 mediate the interaction of mCRP with complement factor H, an inhibitor of alternative pathway activation, and this interaction greatly enhanced the in vitro cofactor activity of complement factor H. In contrast, autoantibodies against amino acids 35–47 inhibited these actions of mCRP. Our results thus provide evidence for the in vivo generation of mCRP in a human disease and suggest that mCRP actively controls the pathogenesis of lupus nephritis by regulating complement activation. Therefore, amino acids 35–47 constitute a functional autoimmune epitope on CRP that can be targeted therapeutically and diagnostically.Li, Qiu-yuLi, Hai-yunFu, GeYu, FengWu, YiZhao, Ming-hui2017-05-31T10:57:18-07:00doi:10.1681/ASN.2016070735hwp:resource-id:jnephrol;28/10/3044American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologylupus nephritis, C-reactive protein, Autoantibody, Complement factor HClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20160707351046-66731533-34502017-05-31T10:57:18-07:002017-10Journal of the American Society of NephrologyClinical Research281030443054
- The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase εThe recent discovery of mutations in the gene encoding diacylglycerol kinase ε (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.10.1681/ASN.2017010031Fri, 19 May 2017 08:59:51 GMT-07:00The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase εThe recent discovery of mutations in the gene encoding diacylglycerol kinase ε (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.Azukaitis, KarolisSimkova, EvaMajid, Mohammad AbdulGaliano, MatthiasBenz, KerstinAmann, KerstinBockmeyer, ClemensGajjar, RadhaMeyers, Kevin E.Cheong, Hae IlLange-Sperandio, BärbelJungraithmayr, ThereseFrémeaux-Bacchi, VéroniqueBergmann, CarstenBereczki, CsabaMiklaszewska, MonikaCsuka, DorottyaProhászka, ZoltánGipson, PatrickSampson, Matthew G.Lemaire, MathieuSchaefer, Franz2017-05-19T08:59:51-07:00doi:10.1681/ASN.2017010031hwp:resource-id:jnephrol;28/10/3066American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyDGKE, diacylglycerol kinase epsilon, atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, thrombotic microangiopathyClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20170100311046-66731533-34502017-05-19T08:59:51-07:002017-10Journal of the American Society of NephrologyClinical Research282810113066342530753425
- Structural and Functional Changes in Human Kidneys with Healthy AgingAging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m2) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.10.1681/ASN.2017040421Tue, 08 Aug 2017 05:43:50 GMT-07:00Structural and Functional Changes in Human Kidneys with Healthy AgingAging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m2) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.Hommos, Musab S.Glassock, Richard J.Rule, Andrew D.2017-08-08T05:43:50-07:00doi:10.1681/ASN.2017040421hwp:resource-id:jnephrol;28/10/2838American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyaging, glomerulosclerosis, nephrosclerosis, glomerular filtration rate, nephron number, kidney volumeUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-10-01October 201710.1681/ASN.20170404211046-66731533-34502017-08-08T05:43:50-07:002017-10Journal of the American Society of NephrologyUp Front Matters281028382844
- Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary TractCongenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT. Here, we report the targeted exome sequencing of 330 genes, including genes known to be involved in CAKUT and candidate genes, in a cohort of 204 unrelated patients with CAKUT; 45% of the patients were severe fetal cases. We identified pathogenic mutations in 36 of 204 (17.6%) patients. These mutations included five de novo heterozygous loss of function mutations/deletions in the PBX homeobox 1 gene (PBX1), a gene known to have a crucial role in kidney development. In contrast, the frequency of SOX17 and DSTYK variants recently reported as pathogenic in CAKUT did not indicate causality. These findings suggest that PBX1 is involved in monogenic CAKUT in humans and call into question the role of some gene variants recently reported as pathogenic in CAKUT. Targeted exome sequencing also proved to be an efficient and cost-effective strategy to identify pathogenic mutations and deletions in known CAKUT genes.10.1681/ASN.2017010043Wed, 31 May 2017 10:57:17 GMT-07:00Targeted Exome Sequencing Identifies PBX1 as Involved in Monogenic Congenital Anomalies of the Kidney and Urinary TractCongenital anomalies of the kidney and urinary tract (CAKUT) occur in three to six of 1000 live births, represent about 20% of the prenatally detected anomalies, and constitute the main cause of CKD in children. These disorders are phenotypically and genetically heterogeneous. Monogenic causes of CAKUT in humans and mice have been identified. However, despite high-throughput sequencing studies, the cause of the disease remains unknown in most patients, and several studies support more complex inheritance and the role of environmental factors and/or epigenetics in the pathophysiology of CAKUT. Here, we report the targeted exome sequencing of 330 genes, including genes known to be involved in CAKUT and candidate genes, in a cohort of 204 unrelated patients with CAKUT; 45% of the patients were severe fetal cases. We identified pathogenic mutations in 36 of 204 (17.6%) patients. These mutations included five de novo heterozygous loss of function mutations/deletions in the PBX homeobox 1 gene (PBX1), a gene known to have a crucial role in kidney development. In contrast, the frequency of SOX17 and DSTYK variants recently reported as pathogenic in CAKUT did not indicate causality. These findings suggest that PBX1 is involved in monogenic CAKUT in humans and call into question the role of some gene variants recently reported as pathogenic in CAKUT. Targeted exome sequencing also proved to be an efficient and cost-effective strategy to identify pathogenic mutations and deletions in known CAKUT genes.Heidet, LaurenceMorinière, VincentHenry, CharlineDe Tomasi, LaraReilly, Madeline LouiseHumbert, CamilleAlibeu, OlivierFourrage, CécileBole-Feysot, ChristineNitschké, PatrickTores, FrédéricBras, MarcJeanpierre, MarcPietrement, ChristineGaillard, DominiqueGonzales, MarieNovo, RobertSchaefer, EliseRoume, JoëlleMartinovic, JelenaMalan, ValérieSalomon, RémiSaunier, SophieAntignac, CorinneJeanpierre, Cécile2017-05-31T10:57:17-07:00doi:10.1681/ASN.2017010043hwp:resource-id:jnephrol;28/10/2901American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, genetics and development, genetic renal diseaseBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20170100431046-66731533-34502017-05-31T10:57:17-07:002017-10Journal of the American Society of NephrologyBasic Research281029012914
- Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin NephropathyMultilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow–derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively). In FSGS-SCID mice, human Muse cells preferentially integrated into the damaged glomeruli and spontaneously differentiated into cells expressing markers of podocytes (podocin; 31%), mesangial cells (megsin; 13%), and endothelial cells (CD31; 41%) without fusing to the host cells; attenuated glomerular sclerosis and interstitial fibrosis; and induced the recovery of creatinine clearance at 7 weeks. Human Muse cells induced similar effects in FSGS-BALB/c mice at 5 weeks, despite xenotransplant without concurrent immunosuppressant administration, and led to improvement in urine protein, creatinine clearance, and plasma creatinine levels more impressive than that in the FSGS-SCID mice at 5 weeks. However, functional recovery in FSGS-BALB/c mice was impaired at 7 weeks due to immunorejection, suggesting the importance of Muse cell survival as glomerular cells in the FSGS kidney for tissue repair and functional recovery. In conclusion, Muse cells are unique reparative stem cells that preferentially home to damaged glomeruli and spontaneously differentiate into glomerular cells after systemic administration. Introduction of genes to induce differentiation is not required before Muse cell administration; thus, Muse cells may be a feasible therapeutic strategy in FSGS.10.1681/ASN.2016070775Mon, 03 Jul 2017 07:30:32 GMT-07:00Beneficial Effects of Systemically Administered Human Muse Cells in Adriamycin NephropathyMultilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow–derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively). In FSGS-SCID mice, human Muse cells preferentially integrated into the damaged glomeruli and spontaneously differentiated into cells expressing markers of podocytes (podocin; 31%), mesangial cells (megsin; 13%), and endothelial cells (CD31; 41%) without fusing to the host cells; attenuated glomerular sclerosis and interstitial fibrosis; and induced the recovery of creatinine clearance at 7 weeks. Human Muse cells induced similar effects in FSGS-BALB/c mice at 5 weeks, despite xenotransplant without concurrent immunosuppressant administration, and led to improvement in urine protein, creatinine clearance, and plasma creatinine levels more impressive than that in the FSGS-SCID mice at 5 weeks. However, functional recovery in FSGS-BALB/c mice was impaired at 7 weeks due to immunorejection, suggesting the importance of Muse cell survival as glomerular cells in the FSGS kidney for tissue repair and functional recovery. In conclusion, Muse cells are unique reparative stem cells that preferentially home to damaged glomeruli and spontaneously differentiate into glomerular cells after systemic administration. Introduction of genes to induce differentiation is not required before Muse cell administration; thus, Muse cells may be a feasible therapeutic strategy in FSGS.Uchida, NaoKushida, YoshihiroKitada, MasaakiWakao, ShoheiKumagai, NaonoriKuroda, YasumasaKondo, YoshiakiHirohara, YukariKure, ShigeoChazenbalk, GregorioDezawa, Mari2017-07-03T07:30:32-07:00doi:10.1681/ASN.2016070775hwp:resource-id:jnephrol;28/10/2946American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, adult stem cells, cell survival, glomerulosclerosis, podocyteBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20160707751046-66731533-34502017-07-03T07:30:32-07:002017-10Journal of the American Society of NephrologyBasic Research281029462960
- A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKDVitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18–70 years, with nondiabetic CKD stage 3–4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P<0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3–4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648).10.1681/ASN.2017010003Fri, 30 Jun 2017 07:08:31 GMT-07:00A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKDVitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18–70 years, with nondiabetic CKD stage 3–4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P<0.001). Intervention also led to significant favorable changes in pulse wave velocity and circulating IL-6 levels. Thus, in nondiabetic patients with stage 3–4 CKD and vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648).Kumar, VivekYadav, Ashok KumarLal, AnupamKumar, VinodSinghal, ManphoolBillot, LaurentGupta, Krishan LalBanerjee, DebasishJha, Vivekanand2017-06-30T07:08:31-07:00doi:10.1681/ASN.2017010003hwp:resource-id:jnephrol;28/10/3100American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, Vitamin DClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20170100031046-66731533-34502017-06-30T07:08:31-07:002017-10Journal of the American Society of NephrologyClinical Research281031003108
- Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney FunctionEfficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2. Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30–60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.10.1681/ASN.2016090957Mon, 15 May 2017 05:34:39 GMT-07:00Benefit of Ezetimibe Added to Simvastatin in Reduced Kidney FunctionEfficacy of statin-based therapies in reducing cardiovascular mortality in individuals with CKD seems to diminish as eGFR declines. The strongest evidence supporting the cardiovascular benefit of statins in individuals with CKD was shown with ezetimibe plus simvastatin versus placebo. However, whether combination therapy or statin alone resulted in cardiovascular benefit is uncertain. Therefore, we estimated GFR in 18,015 individuals from the IMPROVE-IT (ezetimibe plus simvastatin versus simvastatin alone in individuals with cardiovascular disease and creatinine clearance >30 ml/min) and examined post hoc the relationship of eGFR with end points across treatment arms. For the primary end point of cardiovascular death, major coronary event, or nonfatal stroke, the relative risk reduction of combination therapy compared with monotherapy differed by eGFR (P=0.04). The difference in treatment effect was observed at eGFR≤75 ml/min per 1.73 m2 and most apparent at levels ≤60 ml/min per 1.73 m2. Compared with individuals receiving monotherapy, individuals receiving combination therapy with a baseline eGFR of 60 ml/min per 1.73 m2 experienced a 12% risk reduction (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.82 to 0.95); those with a baseline eGFR of 45 ml/min per 1.73 m2 had a 13% risk reduction (HR, 0.87; 95% CI, 0.78 to 0.98). In stabilized individuals within 10 days of acute coronary syndrome, combination therapy seemed to be more effective than monotherapy in individuals with moderately reduced eGFR (30–60 ml/min per 1.73 m2). Further studies examining potential benefits of combination lipid-lowering therapy in individuals with CKD are needed.Stanifer, John W.Charytan, David M.White, JenniferLokhnygina, YuliyaCannon, Christopher P.Roe, Matthew T.Blazing, Michael A.2017-05-15T05:34:39-07:00doi:10.1681/ASN.2016090957hwp:resource-id:jnephrol;28/10/3034American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologylipids, statins, chronic kidney disease, cardiovascularClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20160909571046-66731533-34502017-05-15T05:34:39-07:002017-10Journal of the American Society of NephrologyClinical Research281030343043
- Persistent Microscopic Hematuria as a Risk Factor for Progression of IgA Nephropathy: New Floodlight on a Nearly Forgotten Biomarker10.1681/ASN.2017060639Mon, 24 Jul 2017 06:14:25 GMT-07:00Persistent Microscopic Hematuria as a Risk Factor for Progression of IgA Nephropathy: New Floodlight on a Nearly Forgotten BiomarkerCoppo, RosannaFervenza, Fernando C.2017-07-24T06:14:25-07:00doi:10.1681/ASN.2017060639hwp:resource-id:jnephrol;28/10/2831American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, hematuria, proteinuriaUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-10-01October 201710.1681/ASN.20170606391046-66731533-34502017-07-24T06:14:25-07:002017-10Journal of the American Society of NephrologyUp Front Matters2810102831308928343099
- Decreased Expression of Connexin 43 Blunts the Progression of Experimental GNGN refers to a variety of renal pathologies that often progress to ESRD, but the molecular mechanisms underlying this progression remain incompletely characterized. Here, we determined whether dysregulated expression of the gap junction protein connexin 43, which has been observed in the progression of renal disease, contributes to GN progression. Immunostaining revealed de novo expression of connexin 43 in damaged glomeruli in patients with glomerular diseases as well as in mice after induction of experimental GN. Notably, 2 weeks after the induction of GN with nephrotoxic serum, mice with a heterozygous deletion of the connexin 43 gene (connexin 43+/−) had proteinuria, BUN, and serum creatinine levels significantly lower than those of wild-type animals. Additionally, the connexin 43+/− mice showed less crescent formation, tubular dilation, monocyte infiltration, and interstitial renal fibrosis. Treatment of cultured podocytes with connexin 43–specific blocking peptides attenuated TGF-β–induced cytoskeletal and morphologic changes and apoptosis as did treatment with the purinergic blocker suramin. Finally, therapeutic treatment of GN mice with connexin 43–specific antisense oligodeoxynucleotide improved functional and structural renal parameters. These findings suggest that crosstalk between connexin 43 and purinergic signaling contributes to podocyte damage in GN. Given that this protein is highly induced in individuals with glomerular diseases, connexin 43 may be a novel target for therapeutic treatment of GN.10.1681/ASN.2016111211Fri, 30 Jun 2017 07:08:30 GMT-07:00Decreased Expression of Connexin 43 Blunts the Progression of Experimental GNGN refers to a variety of renal pathologies that often progress to ESRD, but the molecular mechanisms underlying this progression remain incompletely characterized. Here, we determined whether dysregulated expression of the gap junction protein connexin 43, which has been observed in the progression of renal disease, contributes to GN progression. Immunostaining revealed de novo expression of connexin 43 in damaged glomeruli in patients with glomerular diseases as well as in mice after induction of experimental GN. Notably, 2 weeks after the induction of GN with nephrotoxic serum, mice with a heterozygous deletion of the connexin 43 gene (connexin 43+/−) had proteinuria, BUN, and serum creatinine levels significantly lower than those of wild-type animals. Additionally, the connexin 43+/− mice showed less crescent formation, tubular dilation, monocyte infiltration, and interstitial renal fibrosis. Treatment of cultured podocytes with connexin 43–specific blocking peptides attenuated TGF-β–induced cytoskeletal and morphologic changes and apoptosis as did treatment with the purinergic blocker suramin. Finally, therapeutic treatment of GN mice with connexin 43–specific antisense oligodeoxynucleotide improved functional and structural renal parameters. These findings suggest that crosstalk between connexin 43 and purinergic signaling contributes to podocyte damage in GN. Given that this protein is highly induced in individuals with glomerular diseases, connexin 43 may be a novel target for therapeutic treatment of GN.Kavvadas, PanagiotisAbed, AhmedPoulain, CoralieAuthier, FlorenceLabéjof, Lise-PauleCalmont, AmelieAfieri, CarloPrakoura, NikiDussaule, Jean-ClaudeChatziantoniou, ChristosChadjichristos, Christos E.2017-06-30T07:08:30-07:00doi:10.1681/ASN.2016111211hwp:resource-id:jnephrol;28/10/2915American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, connexins, podocyte, renal fibrosisBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20161112111046-66731533-34502017-06-30T07:08:30-07:002017-10Journal of the American Society of NephrologyBasic Research281029152930
- FSGS as an Adaptive Response to Growth-Induced Podocyte StressGlomerular sclerotic lesions develop when the glomerular filtration surface area exceeds the availability of podocyte foot process coverage, but the mechanisms involved are incompletely characterized. We evaluated potential mechanisms using a transgenic (podocin promoter-AA-4E-BP1) rat in which podocyte capacity for hypertrophy in response to growth factor/nutrient signaling is impaired. FSGS lesions resembling human FSGS developed spontaneously by 7 months of age, and could be induced earlier by accelerating kidney hypertrophy by nephrectomy. Early segmental glomerular lesions occurred in the absence of a detectable reduction in average podocyte number per glomerulus and resulted from the loss of podocytes in individual glomerular capillary loops. Parietal epithelial cell division, accumulation on Bowman’s capsule, and tuft invasion occurred at these sites. Three different interventions that prevented kidney growth and glomerular enlargement (calorie intake reduction, inhibition of mammalian target of rapamycin complex, and inhibition of angiotensin-converting enzyme) protected against FSGS lesion development, even when initiated late in the process. Ki67 nuclear staining and unbiased transcriptomic analysis identified increased glomerular (but not podocyte) cell cycling as necessary for FSGS lesion development. The rat FSGS-associated transcriptomic signature correlated with human glomerular transcriptomes associated with disease progression, compatible with similar processes occurring in man. We conclude that FSGS lesion development resulted from glomerular growth that exceeded the capacity of podocytes to adapt and adequately cover some parts of the filtration surface. Modest modulation of the growth side of this equation significantly ameliorated FSGS progression, suggesting that glomerular growth is an underappreciated therapeutic target for preservation of renal function.10.1681/ASN.2017020174Tue, 18 Jul 2017 07:41:19 GMT-07:00FSGS as an Adaptive Response to Growth-Induced Podocyte StressGlomerular sclerotic lesions develop when the glomerular filtration surface area exceeds the availability of podocyte foot process coverage, but the mechanisms involved are incompletely characterized. We evaluated potential mechanisms using a transgenic (podocin promoter-AA-4E-BP1) rat in which podocyte capacity for hypertrophy in response to growth factor/nutrient signaling is impaired. FSGS lesions resembling human FSGS developed spontaneously by 7 months of age, and could be induced earlier by accelerating kidney hypertrophy by nephrectomy. Early segmental glomerular lesions occurred in the absence of a detectable reduction in average podocyte number per glomerulus and resulted from the loss of podocytes in individual glomerular capillary loops. Parietal epithelial cell division, accumulation on Bowman’s capsule, and tuft invasion occurred at these sites. Three different interventions that prevented kidney growth and glomerular enlargement (calorie intake reduction, inhibition of mammalian target of rapamycin complex, and inhibition of angiotensin-converting enzyme) protected against FSGS lesion development, even when initiated late in the process. Ki67 nuclear staining and unbiased transcriptomic analysis identified increased glomerular (but not podocyte) cell cycling as necessary for FSGS lesion development. The rat FSGS-associated transcriptomic signature correlated with human glomerular transcriptomes associated with disease progression, compatible with similar processes occurring in man. We conclude that FSGS lesion development resulted from glomerular growth that exceeded the capacity of podocytes to adapt and adequately cover some parts of the filtration surface. Modest modulation of the growth side of this equation significantly ameliorated FSGS progression, suggesting that glomerular growth is an underappreciated therapeutic target for preservation of renal function.Nishizono, RyuzohKikuchi, MasaoWang, Su Q.Chowdhury, MahboobNair, VijiHartman, JohnFukuda, AkihiroWickman, LarysaHodgin, Jeffrey B.Bitzer, MarkusNaik, AbhijitWiggins, JocelynKretzler, MatthiasWiggins, Roger C.2017-07-18T07:41:19-07:00doi:10.1681/ASN.2017020174hwp:resource-id:jnephrol;28/10/2931American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, podocyte, progression of renal failure, hypertrophic stress, growthBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20170201741046-66731533-34502017-07-18T07:41:19-07:002017-10Journal of the American Society of NephrologyBasic Research2810102931282529452827
- Podocyte Growing Pains in Adaptive FSGS10.1681/ASN.2017060612Mon, 17 Jul 2017 08:43:17 GMT-07:00Podocyte Growing Pains in Adaptive FSGSD’Agati, Vivette D.2017-07-17T08:43:17-07:00doi:10.1681/ASN.2017060612hwp:resource-id:jnephrol;28/10/2825American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyFSGS, podocyte, glomerular sizeUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-10-01October 201710.1681/ASN.20170606121046-66731533-34502017-07-17T08:43:17-07:002017-10Journal of the American Society of NephrologyUp Front Matters2810102825293128272945
- Association of Sex with Risk of Kidney Graft Failure Differs by AgePrior studies of sex differences in kidney graft survival showed conflicting results. We hypothesized that the association between recipient sex and kidney graft failure risk differs by recipient age and donor sex. We evaluated 159,417 patients recorded in the Scientific Registry of Transplant Recipients database who received a first deceased-donor kidney transplant (1995–2013). We used time-varying Cox models to estimate the association between recipient sex and death-censored graft failure. Models, stratified on donor sex and adjusted for potential confounders, included a recipient sex by current age interaction term. Among recipients of male donors, females of all ages had significantly higher graft failure risks than males (adjusted hazard ratios 0–14 years: 1.51 [95% confidence intervals 1.19 to 1.90]; 15–24 years: 1.37 [1.18 to 1.59]; 25–44 years: 1.14 [1.03 to 1.26]; 45 years: 1.05 [1.01 to 1.09]). Among recipients of female-donor grafts, only female recipients aged 15–24 years had a significantly higher graft failure risk than their male counterparts had (1.28 [1.06 to 1.53]). Indeed, female recipients aged ≥45 years had a significantly lower graft failure risk than their male counterparts had (0.95 [0.91 to 0.99]). These observations might be explained by the combined influence of several factors, including recognition of sex-determined minor histocompatibility antigens, influence of sex hormones on immune activation, sex- and age-related differences in medication adherence, and sex-related differences in body size. Additional studies should determine whether sex- and age-specific immunosuppression strategies are warranted for kidney graft recipients.10.1681/ASN.2016121380Wed, 07 Jun 2017 10:41:59 GMT-07:00Association of Sex with Risk of Kidney Graft Failure Differs by AgePrior studies of sex differences in kidney graft survival showed conflicting results. We hypothesized that the association between recipient sex and kidney graft failure risk differs by recipient age and donor sex. We evaluated 159,417 patients recorded in the Scientific Registry of Transplant Recipients database who received a first deceased-donor kidney transplant (1995–2013). We used time-varying Cox models to estimate the association between recipient sex and death-censored graft failure. Models, stratified on donor sex and adjusted for potential confounders, included a recipient sex by current age interaction term. Among recipients of male donors, females of all ages had significantly higher graft failure risks than males (adjusted hazard ratios 0–14 years: 1.51 [95% confidence intervals 1.19 to 1.90]; 15–24 years: 1.37 [1.18 to 1.59]; 25–44 years: 1.14 [1.03 to 1.26]; 45 years: 1.05 [1.01 to 1.09]). Among recipients of female-donor grafts, only female recipients aged 15–24 years had a significantly higher graft failure risk than their male counterparts had (1.28 [1.06 to 1.53]). Indeed, female recipients aged ≥45 years had a significantly lower graft failure risk than their male counterparts had (0.95 [0.91 to 0.99]). These observations might be explained by the combined influence of several factors, including recognition of sex-determined minor histocompatibility antigens, influence of sex hormones on immune activation, sex- and age-related differences in medication adherence, and sex-related differences in body size. Additional studies should determine whether sex- and age-specific immunosuppression strategies are warranted for kidney graft recipients.Lepeytre, FannyDahhou, MouradZhang, XunBoucquemont, JulieSapir-Pichhadze, RuthCardinal, HeloiseFoster, Bethany J.2017-06-07T10:41:59-07:00doi:10.1681/ASN.2016121380hwp:resource-id:jnephrol;28/10/3014American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant outcomes, Epidemiology and outcomes, kidney transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20172017-10-01October 201710.1681/ASN.20161213801046-66731533-34502017-06-07T10:41:59-07:002017-10Journal of the American Society of NephrologyClinical Epidemiology2810103014282930232831
- Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial ExpansionHuman glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)–S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and α–smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.10.1681/ASN.2016111196Wed, 12 Jul 2017 06:10:46 GMT-07:00Mesangial Cell Mammalian Target of Rapamycin Complex 1 Activation Results in Mesangial ExpansionHuman glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)–S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]. Foxd1ER(+) TSC1 mice showed mesangial expansion with increased production of collagen IV, collagen I, and α–smooth muscle actin in glomeruli, but did not exhibit significant mesangial proliferation or albuminuria. Furthermore, rapamycin treatment of Foxd1ER(+) TSC1 mice suppressed mesangial expansion. Among biopsy specimens from patients with glomerular diseases, analysis of phosphorylated ribosomal protein S6 revealed mesangial cell mTORC1 activation in IgA nephropathy and in lupus mesangial proliferative nephritis but not in the early phase of diabetic nephropathy. In summary, mesangial cell mTORC1 activation can cause mesangial expansion and has clinical relevance for human glomerular diseases. This report also confirms that the tamoxifen-induced mesangium-specific Cre-loxP system is useful for studies designed to clarify the role of the mesangium in glomerular diseases in adults.Nagai, KojiroTominaga, TatsuyaUeda, SayoShibata, ErikoTamaki, MasanoriMatsuura, MotokazuKishi, SeijiMurakami, TaichiMoriya, TatsumiAbe, HideharuDoi, Toshio2017-07-12T06:10:46-07:00doi:10.1681/ASN.2016111196hwp:resource-id:jnephrol;28/10/2879American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymesangial cells, proteinuria, Cell Signaling, glomerular diseaseBrief CommunicationsBrief Communicationsbrief-report20172017-10-01October 201710.1681/ASN.20161111961046-66731533-34502017-07-12T06:10:46-07:002017-10Journal of the American Society of NephrologyBrief Communications281028792885
- The Sorting Nexin 3 Retromer Pathway Regulates the Cell Surface Localization and Activity of a Wnt-Activated Polycystin Channel ComplexAutosomal dominant polycystic kidney disease (ADPKD) is caused by inactivating mutations in PKD1 (85%) or PKD2 (15%). The ADPKD proteins encoded by these genes, polycystin-1 (PC1) and polycystin-2 (PC2), form a plasma membrane receptor–ion channel complex. However, the mechanisms controlling the subcellular localization of PC1 and PC2 are poorly understood. Here, we investigated the involvement of the retromer complex, an ancient protein module initially discovered in yeast that regulates the retrieval, sorting, and retrograde transport of membrane receptors. Using yeast two-hybrid, biochemical, and cellular assays, we determined that PC2 binds two isoforms of the retromer-associated protein sorting nexin 3 (SNX3), including a novel isoform that binds PC2 in a direct manner. Knockdown of SNX3 or the core retromer protein VPS35 increased the surface expression of endogenous PC1 and PC2 in vitro and in vivo and increased Wnt-activated PC2-dependent whole-cell currents. These findings indicate that an SNX3-retromer complex regulates the surface expression and function of PC1 and PC2. Molecular targeting of proteins involved in the endosomal sorting of PC1 and PC2 could lead to new therapeutic approaches in ADPKD.10.1681/ASN.2016121349Thu, 15 Jun 2017 06:12:52 GMT-07:00The Sorting Nexin 3 Retromer Pathway Regulates the Cell Surface Localization and Activity of a Wnt-Activated Polycystin Channel ComplexAutosomal dominant polycystic kidney disease (ADPKD) is caused by inactivating mutations in PKD1 (85%) or PKD2 (15%). The ADPKD proteins encoded by these genes, polycystin-1 (PC1) and polycystin-2 (PC2), form a plasma membrane receptor–ion channel complex. However, the mechanisms controlling the subcellular localization of PC1 and PC2 are poorly understood. Here, we investigated the involvement of the retromer complex, an ancient protein module initially discovered in yeast that regulates the retrieval, sorting, and retrograde transport of membrane receptors. Using yeast two-hybrid, biochemical, and cellular assays, we determined that PC2 binds two isoforms of the retromer-associated protein sorting nexin 3 (SNX3), including a novel isoform that binds PC2 in a direct manner. Knockdown of SNX3 or the core retromer protein VPS35 increased the surface expression of endogenous PC1 and PC2 in vitro and in vivo and increased Wnt-activated PC2-dependent whole-cell currents. These findings indicate that an SNX3-retromer complex regulates the surface expression and function of PC1 and PC2. Molecular targeting of proteins involved in the endosomal sorting of PC1 and PC2 could lead to new therapeutic approaches in ADPKD.Feng, ShuangStreets, Andrew J.Nesin, VasylTran, UyenNie, HongguangOnopiuk, MartaWessely, OliverTsiokas, LeonidasOng, Albert C.M.2017-06-15T06:12:52-07:00doi:10.1681/ASN.2016121349hwp:resource-id:jnephrol;28/10/2973American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, polycystic kidney disease, retromer, PKD1, PKD2Basic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20161213491046-66731533-34502017-06-15T06:12:52-07:002017-10Journal of the American Society of NephrologyBasic Research281029732984
- Pharmacologic Approaches to Improve Mitochondrial Function in AKI and CKDAKI is associated with high morbidity and mortality, and it predisposes to the development and progression of CKD. Novel strategies that minimize AKI and halt the progression of CKD are urgently needed. Normal kidney function involves numerous different cell types, such as tubular epithelial cells, endothelial cells, and podocytes, working in concert. This delicate balance involves many energy-intensive processes. Fatty acids are the preferred energy substrates for the kidney, and defects in fatty acid oxidation and mitochondrial dysfunction are universally involved in diverse causes of AKI and CKD. This review provides an overview of ATP production and energy demands in the kidney and summarizes preclinical and clinical evidence of mitochondrial dysfunction in AKI and CKD. New therapeutic strategies targeting mitochondria protection and cellular bioenergetics are presented, with emphasis on those that have been evaluated in animal models of AKI and CKD. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer advantages compared with targeting downstream inflammatory and fibrosis processes.10.1681/ASN.2017030247Fri, 04 Aug 2017 12:03:21 GMT-07:00Pharmacologic Approaches to Improve Mitochondrial Function in AKI and CKDAKI is associated with high morbidity and mortality, and it predisposes to the development and progression of CKD. Novel strategies that minimize AKI and halt the progression of CKD are urgently needed. Normal kidney function involves numerous different cell types, such as tubular epithelial cells, endothelial cells, and podocytes, working in concert. This delicate balance involves many energy-intensive processes. Fatty acids are the preferred energy substrates for the kidney, and defects in fatty acid oxidation and mitochondrial dysfunction are universally involved in diverse causes of AKI and CKD. This review provides an overview of ATP production and energy demands in the kidney and summarizes preclinical and clinical evidence of mitochondrial dysfunction in AKI and CKD. New therapeutic strategies targeting mitochondria protection and cellular bioenergetics are presented, with emphasis on those that have been evaluated in animal models of AKI and CKD. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer advantages compared with targeting downstream inflammatory and fibrosis processes.Szeto, Hazel H.2017-08-04T12:03:21-07:00doi:10.1681/ASN.2017030247hwp:resource-id:jnephrol;28/10/2856American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, fibrosis, mitochondria, reactive oxygen species, metabolism, ischemia-reperfusionUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-10-01October 201710.1681/ASN.20170302471046-66731533-34502017-08-04T12:03:21-07:002017-10Journal of the American Society of NephrologyUp Front Matters281028562865
- Intimal Hyperplasia, Stenosis, and Arteriovenous Fistula Maturation Failure in the Hemodialysis Fistula Maturation StudyIntimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination. On ultrasounds performed 1 day and 2 and 6 weeks after fistula creation, we assessed fistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flow velocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%–100%), modestly associated with lower fistula blood flow rate (relative change, −2.5%; 95% confidence interval [95% CI], −4.6% to −0.4%; P=0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio [OR], 1.07; 95% CI, 1.00 to 1.16; P=0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15; P=0.07). Fistula venous stenosis at 6 weeks associated with maturation failure (OR, 1.98; 95% CI, 1.25 to 3.12; P=0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly.10.1681/ASN.2016121355Fri, 14 Jul 2017 08:52:32 GMT-07:00Intimal Hyperplasia, Stenosis, and Arteriovenous Fistula Maturation Failure in the Hemodialysis Fistula Maturation StudyIntimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination. On ultrasounds performed 1 day and 2 and 6 weeks after fistula creation, we assessed fistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flow velocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%–100%), modestly associated with lower fistula blood flow rate (relative change, −2.5%; 95% confidence interval [95% CI], −4.6% to −0.4%; P=0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio [OR], 1.07; 95% CI, 1.00 to 1.16; P=0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15; P=0.07). Fistula venous stenosis at 6 weeks associated with maturation failure (OR, 1.98; 95% CI, 1.25 to 3.12; P=0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly.Cheung, Alfred K.Imrey, Peter B.Alpers, Charles E.Robbin, Michelle L.Radeva, MilenaLarive, BrettShiu, Yan-TingAllon, MichaelDember, Laura M.Greene, TomHimmelfarb, JonathanRoy-Chaudhury, PrabirTerry, Christi M.Vazquez, Miguel A.Kusek, John W.Feldman, Harold I.,Feldman, H.I.Dember, L.M.Farber, A.Kaufman, J.Stern, L.LeSage, P.Kivork, C.Soares, D.Malikova, M.Young, C.Taylor, M.Woodard, L.Mangadi, K.Roy-Chaudhury, P.Munda, R.Lee, T.Alloway, R.El-Khatib, M.Canaan, T.Pflum, A.Thieken, L.Campos-Naciff, B.Huber, T.Berceli, S.Jansen, M.McCaslin, G.Trahan, Y.Vazquez, M.A.Vongpatanasin, W.Davidson, I.Hwang, C.Lightfoot, T.Livingston, C.Valencia, A.Dolmatch, B.Fenves, A.Hawkins, N.Cheung, A.K.Kraiss, L.Kinikini, D.Treiman, G.Ihnat, D.Sarfati, M.Shiu, Y.-TTerry, C.M.Lavasani, I.Maloney, M.Schlotfeldt, L.Himmelfarm, J.Buchanan, C.Clark, C.Crawford, C.Hamlett, J.Kundzins, J.Manahan, L.Wise, J.Beck, G.Gassman, J.Greene, T.Imrey, P.B.Li, L.Alster, J.Li, M.MacKrell, J.Radeva, M.Weiss, B.Wiggins, K.Alpers, C.E.Hudkins, K.Wietecha, T.Robbin, M.L.Umphrey, H.Alexander, L.Abts, C.Belt, L.Vita, J.Hamburg, N.Duess, M.Levit, A.Higgins, H.Ke, S.Mandaci, O.Snell, C.Gravley, J.Behnken, S.Mortensen, R.Chertow, G.Besarab, A.Brayman, K.Diener-West, M.Harrison, D.Inker, L.Louis, T.McClellan, W.Rubin, J.Kusek, J.W.Star, R.2017-07-14T08:52:32-07:00doi:10.1681/ASN.2016121355hwp:resource-id:jnephrol;28/10/3005American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyClinical EpidemiologyClinical Epidemiologyresearch-article20172017-10-01October 201710.1681/ASN.20161213551046-66731533-34502017-07-14T08:52:32-07:002017-10Journal of the American Society of NephrologyClinical Epidemiology2810103005282730132829
- Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in ChildrenWe investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor–based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.10.1681/ASN.2016101121Wed, 31 May 2017 04:48:29 GMT-07:00Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in ChildrenWe investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor–based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.Trautmann, AgnesSchnaidt, SvenLipska-Ziętkiewicz, Beata S.Bodria, MonicaOzaltin, FatihEmma, FrancescoAnarat, AliMelk, AnetteAzocar, MartaOh, JunSaeed, BassamGheisari, AlalehCaliskan, SalimGellermann, JuttaHiguita, Lina Maria SernaJankauskiene, AugustinaDrozdz, DorotaMir, SevgiBalat, AyseSzczepanska, MariaParipovic, DusanZurowska, AlexandraBogdanovic, RadovanYilmaz, AlevRanchin, BrunoBaskin, EsraErdogan, OzlemRemuzzi, GiuseppeFirszt-Adamczyk, AgnieszkaKuzma-Mroczkowska, ElzbietaLitwin, MieczyslawMurer, LuisaTkaczyk, MarcinJardim, HelenaWasilewska, AnnaPrintza, NikoletaFidan, KibriyaSimkova, EvaBorzecka, HalinaStaude, HagenHees, KatharinaSchaefer, Franz,Azocar, MQuiroz, LilyHiguita, LM SernaDušek, JiříRanchin, BFischbach, MichelDavitaia, TinatinGellerman, JOh, JMelk, ASchaefer, FWigger, MariannePrintza, NSallay, PeterGheissari, AlalehNoris, MarinaPasini, AndreaGhiggeri, Gian MarcoArdissino, GianluigiBenetti, ElisaEmma, FAoun, BilalAbou-Jaoudé, PaulineJankauskiene, AWasilewska, AGacka, EwaZurowska, ADrozdz, DTkaczyk, MLodz, Małgorzata StańczykBorzecka, HSilska, MagdalenaJarmolinski, TomaszFirszt-Adamczyk, AKsiazek, JoannaKuzma-Mroczkowska, EMedynska, AnnaSzczepanska, MAfonso, Alberto CaldasJardim, HBelgrade, Amira Peco-AnticBogdanovic, RKrmar, Rafael TSimonetti, Giacomo DSaeed, BAnarat, ABalat, ABaskin, ECakar, NilgunErdogan, OÖzcakar, BirsinOzaltin, FSakallioglu, OnurSoylemezoglu, OguzAkman, SemaGok, FaysalCaliskan, SCandan, CengizYilmaz, AMir, SAkil, IpekErtan, PelinÖzkaya, OzanKalyoncu, MukaddesSimkova, EAlhammadi, EntesarSobko, Roman2017-05-31T04:48:29-07:00doi:10.1681/ASN.2016101121hwp:resource-id:jnephrol;28/10/3055American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, children, podocytopathies, immunosuppression, steroid resistance, outcomesClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20161011211046-66731533-34502017-05-31T04:48:29-07:002017-10Journal of the American Society of NephrologyClinical Research281030553065
- Histopathology of Veins Obtained at Hemodialysis Arteriovenous Fistula Creation SurgeryStenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α–smooth muscle actin–expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort.10.1681/ASN.2016050598Wed, 19 Jul 2017 12:02:02 GMT-07:00Histopathology of Veins Obtained at Hemodialysis Arteriovenous Fistula Creation SurgeryStenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α–smooth muscle actin–expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort.Alpers, Charles E.Imrey, Peter B.Hudkins, Kelly L.Wietecha, Tomasz A.Radeva, MilenaAllon, MichaelCheung, Alfred K.Dember, Laura M.Roy-Chaudhury, PrabirShiu, Yan-TingTerry, Christi M.Farber, AlikBeck, Gerald J.Feldman, Harold I.Kusek, John W.Himmelfarb, Jonathan,Dember, LMImrey, PBBeck, GJCheung, AKHimmelfarb, JHuber, TSKusek, JWRoy-Chaudhury, PVazquez, MAAlpers, CERobbin, MLVita, JAGreene, TGassman, JJFeldman, HI2017-07-19T12:02:02-07:00doi:10.1681/ASN.2016050598hwp:resource-id:jnephrol;28/10/3076American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous access, arteriovenous fistula, pathology, dialysis accessClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20160505981046-66731533-34502017-07-19T12:02:02-07:002017-10Journal of the American Society of NephrologyClinical Research2810103076282730882829
- Effect of Cytochrome P450 Metabolites of Arachidonic Acid in NephrologyThirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing. Studies in animal models suggest that changes in the production of cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are vasodilators with anti-inflammatory properties that oppose the development of hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after renal ischemia and may protect against injury. Levels of this eicosanoid are also elevated in polycystic kidney disease and may contribute to cyst formation. Our review summarizes the emerging evidence that cytochrome P450 eicosanoids have a role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and CKD.10.1681/ASN.2017030252Wed, 12 Jul 2017 06:10:47 GMT-07:00Effect of Cytochrome P450 Metabolites of Arachidonic Acid in NephrologyThirty-five years ago, a third pathway for the metabolism of arachidonic acid by cytochrome P450 enzymes emerged. Subsequent work revealed that 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids formed by these pathways have essential roles in the regulation of renal tubular and vascular function. Sequence variants in the genes that produce 20-hydroxyeicosatetraenoic acid are associated with hypertension in humans, whereas the evidence supporting a role for variants in the genes that alter levels of epoxyeicosatrienoic acids is less convincing. Studies in animal models suggest that changes in the production of cytochrome P450 eicosanoids alter BP. However, the mechanisms involved remain controversial, especially for 20-hydroxyeicosatetraenoic acid, which has both vasoconstrictive and natriuretic actions. Epoxyeicosatrienoic acids are vasodilators with anti-inflammatory properties that oppose the development of hypertension and CKD; 20-hydroxyeicosatetraenoic acid levels are elevated after renal ischemia and may protect against injury. Levels of this eicosanoid are also elevated in polycystic kidney disease and may contribute to cyst formation. Our review summarizes the emerging evidence that cytochrome P450 eicosanoids have a role in the pathogenesis of hypertension, polycystic kidney disease, AKI, and CKD.Fan, FanRoman, Richard J.2017-07-12T06:10:47-07:00doi:10.1681/ASN.2017030252hwp:resource-id:jnephrol;28/10/2845American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, hypertension, polycystic kidney disease, acute renal failure, chronic kidney diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-10-01October 201710.1681/ASN.20170302521046-66731533-34502017-07-12T06:10:47-07:002017-10Journal of the American Society of NephrologyUp Front Matters281028452855
- Home Dialysis in the Prospective Payment System EraThe ESRD Prospective Payment System introduced two incentives to increase home dialysis use: bundling injectable medications into a single payment for treatment and paying for home dialysis training. We evaluated the effects of the ESRD Prospective Payment System on home dialysis use by patients starting dialysis in the United States from January 1, 2006 to August 31, 2013. We analyzed data on dialysis modality, insurance type, and comorbidities from the United States Renal Data System. We estimated the effect of the policy on home dialysis use with multivariable logistic regression and compared the effect on Medicare Parts A/B beneficiaries with the effect on patients with other types of insurance. The ESRD Prospective Payment System associated with a 5.0% (95% confidence interval [95% CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period. Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other forms of health insurance. The difference between these groups was not statistically significant (1.8%; 95% CI, −0.2% to 3.8%). Conversely, in both populations, the training add-on did not associate with increases in home dialysis use beyond the effect of the policy. The ESRD Prospective Payment System bundling, but not the training add-on, associated with substantial increases in home dialysis, which were identical for both Medicare and non-Medicare patients. These spill-over effects suggest that major payment changes in Medicare can affect all patients with ESRD.10.1681/ASN.2017010041Wed, 10 May 2017 06:03:26 GMT-07:00Home Dialysis in the Prospective Payment System EraThe ESRD Prospective Payment System introduced two incentives to increase home dialysis use: bundling injectable medications into a single payment for treatment and paying for home dialysis training. We evaluated the effects of the ESRD Prospective Payment System on home dialysis use by patients starting dialysis in the United States from January 1, 2006 to August 31, 2013. We analyzed data on dialysis modality, insurance type, and comorbidities from the United States Renal Data System. We estimated the effect of the policy on home dialysis use with multivariable logistic regression and compared the effect on Medicare Parts A/B beneficiaries with the effect on patients with other types of insurance. The ESRD Prospective Payment System associated with a 5.0% (95% confidence interval [95% CI], 4.0% to 6.0%) increase in home dialysis use by the end of the study period. Home dialysis use increased by 5.8% (95% CI, 4.3% to 6.9%) among Medicare beneficiaries and 4.1% (95% CI, 2.3% to 5.4%) among patients covered by other forms of health insurance. The difference between these groups was not statistically significant (1.8%; 95% CI, −0.2% to 3.8%). Conversely, in both populations, the training add-on did not associate with increases in home dialysis use beyond the effect of the policy. The ESRD Prospective Payment System bundling, but not the training add-on, associated with substantial increases in home dialysis, which were identical for both Medicare and non-Medicare patients. These spill-over effects suggest that major payment changes in Medicare can affect all patients with ESRD.Lin, EugeneCheng, Xingxing S.Chin, Kuo-KaiZubair, TalhahChertow, Glenn M.Bendavid, EranBhattacharya, Jayanta2017-05-10T06:03:26-07:00doi:10.1681/ASN.2017010041hwp:resource-id:jnephrol;28/10/2993American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, Economic Analysis, end-stage renal disease, peritoneal dialysis, United States Renal Data SystemClinical EpidemiologyClinical Epidemiologyresearch-article20172017-10-01October 201710.1681/ASN.20170100411046-66731533-34502017-05-10T06:03:26-07:002017-10Journal of the American Society of NephrologyClinical Epidemiology281029933004
- Moving Beyond the Assumed: Improving Fistula Success Rates10.1681/ASN.2017060663Fri, 21 Jul 2017 06:04:40 GMT-07:00Moving Beyond the Assumed: Improving Fistula Success RatesWish, Jay B.Moe, Sharon M.2017-07-21T06:04:40-07:00doi:10.1681/ASN.2017060663hwp:resource-id:jnephrol;28/10/2827American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, hemodialysis access, arteriovenous fistulaUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-10-01October 201710.1681/ASN.20170606631046-66731533-34502017-07-21T06:04:40-07:002017-10Journal of the American Society of NephrologyUp Front Matters28101010282730763005282930883013
- Hepatocyte Nuclear Factor–1β Regulates Urinary Concentration and Response to HypertonicityThe transcription factor hepatocyte nuclear factor–1β (HNF-1β) is essential for normal kidney development and function. Inactivation of HNF-1β in mouse kidney tubules leads to early-onset cyst formation and postnatal lethality. Here, we used Pkhd1/Cre mice to delete HNF-1β specifically in renal collecting ducts (CDs). CD-specific HNF-1β mutant mice survived long term and developed slowly progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared with wild-type littermates, HNF-1β mutant mice exhibited polyuria and polydipsia. Before the development of significant renal structural abnormalities, mutant mice exhibited low urine osmolality at baseline and after water restriction and administration of desmopressin. However, mutant and wild-type mice had similar plasma vasopressin and solute excretion levels. HNF-1β mutant kidneys showed increased expression of aquaporin-2 mRNA but mislocalized expression of aquaporin-2 protein in the cytoplasm of CD cells. Mutant kidneys also had decreased expression of the UT-A urea transporter and collectrin, which is involved in apical membrane vesicle trafficking. Treatment of HNF-1β mutant mIMCD3 cells with hypertonic NaCl inhibited the induction of osmoregulated genes, including Nr1h4, which encodes the transcription factor FXR that is required for maximal urinary concentration. Chromatin immunoprecipitation and sequencing experiments revealed HNF-1β binding to the Nr1h4 promoter in wild-type kidneys, and immunoblot analysis revealed downregulated expression of FXR in HNF-1β mutant kidneys. These findings reveal a novel role of HNF-1β in osmoregulation and identify multiple mechanisms, whereby mutations of HNF-1β produce defects in urinary concentration.10.1681/ASN.2016101095Mon, 15 May 2017 05:34:40 GMT-07:00Hepatocyte Nuclear Factor–1β Regulates Urinary Concentration and Response to HypertonicityThe transcription factor hepatocyte nuclear factor–1β (HNF-1β) is essential for normal kidney development and function. Inactivation of HNF-1β in mouse kidney tubules leads to early-onset cyst formation and postnatal lethality. Here, we used Pkhd1/Cre mice to delete HNF-1β specifically in renal collecting ducts (CDs). CD-specific HNF-1β mutant mice survived long term and developed slowly progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared with wild-type littermates, HNF-1β mutant mice exhibited polyuria and polydipsia. Before the development of significant renal structural abnormalities, mutant mice exhibited low urine osmolality at baseline and after water restriction and administration of desmopressin. However, mutant and wild-type mice had similar plasma vasopressin and solute excretion levels. HNF-1β mutant kidneys showed increased expression of aquaporin-2 mRNA but mislocalized expression of aquaporin-2 protein in the cytoplasm of CD cells. Mutant kidneys also had decreased expression of the UT-A urea transporter and collectrin, which is involved in apical membrane vesicle trafficking. Treatment of HNF-1β mutant mIMCD3 cells with hypertonic NaCl inhibited the induction of osmoregulated genes, including Nr1h4, which encodes the transcription factor FXR that is required for maximal urinary concentration. Chromatin immunoprecipitation and sequencing experiments revealed HNF-1β binding to the Nr1h4 promoter in wild-type kidneys, and immunoblot analysis revealed downregulated expression of FXR in HNF-1β mutant kidneys. These findings reveal a novel role of HNF-1β in osmoregulation and identify multiple mechanisms, whereby mutations of HNF-1β produce defects in urinary concentration.Aboudehen, KaramNoureddine, LamaCobo-Stark, PatriciaAvdulov, SvetlanaFarahani, ShayanGearhart, Micah D.Bichet, Daniel G.Pontoglio, MarcoPatel, VishalIgarashi, Peter2017-05-15T05:34:40-07:00doi:10.1681/ASN.2016101095hwp:resource-id:jnephrol;28/10/2887American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytranscription factors, collecting ducts, urea, cystic kidney, water-electrolyte balance, osmolalityBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20161010951046-66731533-34502017-05-15T05:34:40-07:002017-10Journal of the American Society of NephrologyBasic Research281028872900
- Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney DiseaseMicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19–23 for each disease), and a control group (n=14). Compared with control glomeruli, DN, FSGS, IgAN, and MPGN glomeruli exhibited differential expression of 18, 12, two, and 17 known microRNAs, respectively. The expression of several microRNAs also differed between disease conditions. Specifically, compared with control or FSGS glomeruli, IgAN glomeruli exhibited downregulated expression of hsa-miR-3182. Furthermore, in combination, the expression levels of hsa-miR-146a-5p and hsa-miR-30a-5p distinguished DN from all other conditions except IgAN. Compared with control proximal tubules, DN, FSGS, IgAN, and MPGN proximal tubules had differential expression of 13, 14, eight, and eight microRNAs, respectively, but expression of microRNAs did not differ significantly between the disease conditions. The abundance of several microRNAs correlated with indexes of renal function. Finally, we validated the differential glomerular expression of select microRNAs in a second cohort of patients with DN (n=19) and FSGS (n=21). In conclusion, we identified tissue-specific microRNA expression patterns associated with several kidney pathologies. The identified microRNAs could be developed as biomarkers of kidney diseases and might be involved in disease mechanisms.10.1681/ASN.2016121280Thu, 29 Jun 2017 06:34:33 GMT-07:00Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney DiseaseMicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19–23 for each disease), and a control group (n=14). Compared with control glomeruli, DN, FSGS, IgAN, and MPGN glomeruli exhibited differential expression of 18, 12, two, and 17 known microRNAs, respectively. The expression of several microRNAs also differed between disease conditions. Specifically, compared with control or FSGS glomeruli, IgAN glomeruli exhibited downregulated expression of hsa-miR-3182. Furthermore, in combination, the expression levels of hsa-miR-146a-5p and hsa-miR-30a-5p distinguished DN from all other conditions except IgAN. Compared with control proximal tubules, DN, FSGS, IgAN, and MPGN proximal tubules had differential expression of 13, 14, eight, and eight microRNAs, respectively, but expression of microRNAs did not differ significantly between the disease conditions. The abundance of several microRNAs correlated with indexes of renal function. Finally, we validated the differential glomerular expression of select microRNAs in a second cohort of patients with DN (n=19) and FSGS (n=21). In conclusion, we identified tissue-specific microRNA expression patterns associated with several kidney pathologies. The identified microRNAs could be developed as biomarkers of kidney diseases and might be involved in disease mechanisms.Baker, Maria AngelesDavis, Seth J.Liu, PengyuanPan, XiaoqingWilliams, Anna MarieIczkowski, Kenneth A.Gallagher, Sean T.Bishop, KayleeRegner, Kevin R.Liu, YongLiang, Mingyu2017-06-29T06:34:33-07:00doi:10.1681/ASN.2016121280hwp:resource-id:jnephrol;28/10/2985American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologymicroRNA, glomerulus, proximal tubule, chronic kidney disease, kidney, biopsyBasic ResearchBasic Researchresearch-article20172017-10-01October 201710.1681/ASN.20161212801046-66731533-34502017-06-29T06:34:33-07:002017-10Journal of the American Society of NephrologyBasic Research281029852992
- Remission of Hematuria Improves Renal Survival in IgA NephropathyHematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from −6.45±14.66 to −0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.10.1681/ASN.2017010108Wed, 07 Jun 2017 10:41:59 GMT-07:00Remission of Hematuria Improves Renal Survival in IgA NephropathyHematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from −6.45±14.66 to −0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.Sevillano, Angel M.Gutiérrez, EduardoYuste, ClaudiaCavero, TeresaMérida, EvangelinaRodríguez, PaolaGarcía, AnaMorales, EnriqueFernández, CristinaMartínez, Miguel AngelMoreno, Juan AntonioPraga, Manuel2017-06-07T10:41:59-07:00doi:10.1681/ASN.2017010108hwp:resource-id:jnephrol;28/10/3089American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, progression of renal failure, proteinuria, hematuriaClinical ResearchClinical Researchresearch-article20172017-10-01October 201710.1681/ASN.20170101081046-66731533-34502017-06-07T10:41:59-07:002017-10Journal of the American Society of NephrologyClinical Research2810103089283130992834
- Erratum10.1681/ASN.2017080862Fri, 29 Sep 2017 01:00:41 GMT-07:00ErratumAmerican Society of Nephrology2017-09-29T13:00:41-07:00doi:10.1681/ASN.2017080862hwp:resource-id:jnephrol;28/10/3129American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20172017-10-01October 201710.1681/ASN.20170808621046-66731533-34502017-09-29T13:00:41-07:002017-10Journal of the American Society of NephrologyErratum28281083129227531292289
- This Month’s Highlights10.1681/ASN.2017070736Fri, 29 Sep 2017 01:00:41 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-09-29T13:00:41-07:00doi:10.1681/ASN.2017070736hwp:resource-id:jnephrol;28/10/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-10-01October 201710.1681/ASN.20170707361046-66731533-34502017-09-29T13:00:41-07:002017-10Journal of the American Society of NephrologyThis Month’s Highlights2810ii
- Outcomes of In–Hospital Cardiopulmonary Resuscitation in Patients with CKD10.2215/CJN.07530715Thu, 21 Jul 2016 06:25:38 GMT-07:00Outcomes of In–Hospital Cardiopulmonary Resuscitation in Patients with CKDSaeed, FahadAdil, Malik M.Kaleem, Umar M.Zafar, Taqi T.Khan, Abdus SalamHolley, Jean L.Nally, Joseph V.2016-07-21T06:25:38-07:00doi:10.2215/CJN.07530715hwp:resource-id:clinjasn;11/10/1744American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular, chronic kidney disease, outcomes, Advance Care Planning, Cardiopulmonary Resuscitation, Hospital Mortality, Humans, Inpatients, Length of Stay, Nursing Homes, Patient Discharge, Renal Insufficiency, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-10-07October 07, 201610.2215/CJN.075307151555-90411555-905X2016-07-21T06:25:38-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111017441751
- Moving from Intuition to Data: Building the Evidence to Support and Increase Living Donor Kidney Transplantation10.2215/CJN.07150717Thu, 17 Aug 2017 10:24:18 GMT-07:00Moving from Intuition to Data: Building the Evidence to Support and Increase Living Donor Kidney TransplantationLentine, Krista L.Mandelbrot, Didier2017-08-17T10:24:18-07:00doi:10.2215/CJN.07150717hwp:resource-id:clinjasn;12/9/1383American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, living donation, systematic review, disparities, Living Donors, Intuition, kidneyEditorialsEditorialseditorial20172017-09-07September 07, 201710.2215/CJN.071507171555-90411555-905X2017-08-17T10:24:18-07:002017-09-07Clinical Journal of the American Society of NephrologyEditorials12991383151813851527
- Viral-Associated GN: Hepatitis B and Other Viral InfectionsBy definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in sharp contrast to the semantic label and pathophysiologic foundation behind postinfectious GN that uniquely develops only during a period of resolved and absent active infection. The primary example of postinfectious GN are the glomerular lesions described after a pharyngeal or cutaneous streptococcal infection and do not represent the clinical or immunologic pattern seen with viral-associated GN. Hepatitis B (HBV) is the most common chronic viral infection in the world affecting >400 million people which is more than double the prevalence of chronic HIV and hepatitis C carriers combined. In addition, 10%–20% of HBV patients may be coinfected with hepatitis C and 5%–10% will have coinfection with HIV. Being able to distinguish the different types of GN seen with each viral infection is essential for the practicing clinician as each virus requires its own specific antiviral therapy. HBV-induced immune complex disease with renal injury lies on one end of the spectrum of disorders that occurs after a prolonged chronic carrier state. On the opposite end of the spectrum are renal diseases that develop from acute or subacute viral infections. One important glomerular lesion in this category is the association of collapsing FSGS with acute active cytomegalovirus, Epstein–Barr virus, and parvovirus B19 infection. The data supporting or disproving this relationship for each of these viruses will be discussed. A second renal manifestation of acute viral infections often occurs with many different sporadic or epidemic infections such as dengue and hantavirus and can lead to a transient proliferative GN that resolves upon viral clearance. The complex interplay of HBV and all viruses with the immune system provides conceptual lessons on the pathophysiology of immune complex GN that can be applied to all infection-related renal disease and plays an integral role in developing an approach to therapeutic intervention.10.2215/CJN.09180816Tue, 18 Oct 2016 05:20:33 GMT-07:00Viral-Associated GN: Hepatitis B and Other Viral InfectionsBy definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in sharp contrast to the semantic label and pathophysiologic foundation behind postinfectious GN that uniquely develops only during a period of resolved and absent active infection. The primary example of postinfectious GN are the glomerular lesions described after a pharyngeal or cutaneous streptococcal infection and do not represent the clinical or immunologic pattern seen with viral-associated GN. Hepatitis B (HBV) is the most common chronic viral infection in the world affecting >400 million people which is more than double the prevalence of chronic HIV and hepatitis C carriers combined. In addition, 10%–20% of HBV patients may be coinfected with hepatitis C and 5%–10% will have coinfection with HIV. Being able to distinguish the different types of GN seen with each viral infection is essential for the practicing clinician as each virus requires its own specific antiviral therapy. HBV-induced immune complex disease with renal injury lies on one end of the spectrum of disorders that occurs after a prolonged chronic carrier state. On the opposite end of the spectrum are renal diseases that develop from acute or subacute viral infections. One important glomerular lesion in this category is the association of collapsing FSGS with acute active cytomegalovirus, Epstein–Barr virus, and parvovirus B19 infection. The data supporting or disproving this relationship for each of these viruses will be discussed. A second renal manifestation of acute viral infections often occurs with many different sporadic or epidemic infections such as dengue and hantavirus and can lead to a transient proliferative GN that resolves upon viral clearance. The complex interplay of HBV and all viruses with the immune system provides conceptual lessons on the pathophysiology of immune complex GN that can be applied to all infection-related renal disease and plays an integral role in developing an approach to therapeutic intervention.Kupin, Warren L.2016-10-18T05:20:33-07:00doi:10.2215/CJN.09180816hwp:resource-id:clinjasn;12/9/1529American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyViral-Associated Glomerulonephritis, Hepatitis B virus, glomerular disease, Antigen-Antibody Complex, Antiviral Agents, Carrier State, Coinfection, cytomegalovirus, Dengue, glomerulonephritis, HIV Infections, Hantavirus, Hepatitis C, Herpesvirus 4, Human, Humans, Immune Complex Diseases, Immune System, Parvovirus, Prevalence, Semantics, Streptococcal InfectionsGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-09-07September 07, 201710.2215/CJN.091808161555-90411555-905X2016-10-18T05:20:33-07:002017-09-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician12915291533
- A Pregnant Woman with Lupus and Nephrotic-Range Proteinuria10.2215/CJN.13251216Tue, 04 Apr 2017 05:44:17 GMT-07:00A Pregnant Woman with Lupus and Nephrotic-Range ProteinuriaBomback, Andrew S.2017-04-04T05:44:17-07:00doi:10.2215/CJN.13251216hwp:resource-id:clinjasn;12/9/1534American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, renal biopsy, podocyteKidney Case ConferencesNephrology Quiz and QuestionnaireKidney Case ConferencesNephrology Quiz and Questionnaireresearch-article20172017-09-07September 07, 201710.2215/CJN.132512161555-90411555-905X2017-04-04T05:44:17-07:002017-09-07Clinical Journal of the American Society of NephrologyKidney Case Conferences12915341537
- Managing Issues in Dialysis for the Patient with AKI10.2215/CJN.02270217Wed, 21 Jun 2017 07:24:13 GMT-07:00Managing Issues in Dialysis for the Patient with AKIJudd, EricTolwani, Ashita2017-06-21T07:24:13-07:00doi:10.2215/CJN.02270217hwp:resource-id:clinjasn;12/9/1538American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, dialysis, Acute Kidney Injury, Fluid Therapy, Humans, renal dialysisKidney Case ConferencesHow I TreatKidney Case ConferencesHow I Treatreview20172017-09-07September 07, 201710.2215/CJN.022702171555-90411555-905X2017-06-21T07:24:13-07:002017-09-07Clinical Journal of the American Society of NephrologyKidney Case Conferences12915381542
- The Times, They Are A-Changin: Innovations in Health Care Delivery To Reduce CKD Progression10.2215/CJN.07410717Fri, 04 Aug 2017 12:04:26 GMT-07:00The Times, They Are A-Changin: Innovations in Health Care Delivery To Reduce CKD ProgressionAbdel-Kader, Khaled2017-08-04T12:04:26-07:00doi:10.2215/CJN.07410717hwp:resource-id:clinjasn;12/9/1375American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, patient navigator, personal health records, health care delivery, Disease Progression, Renal Insufficiency, ChronicEditorialsEditorialseditorial20172017-09-07September 07, 201710.2215/CJN.074107171555-90411555-905X2017-08-04T12:04:26-07:002017-09-07Clinical Journal of the American Society of NephrologyEditorials12991375141813761427
- Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.12821216Thu, 13 Jul 2017 06:25:55 GMT-07:00Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney DiseaseChonchol, MichelGitomer, BereniceIsakova, TamaraCai, XuanSalusky, IsidroPereira, RenataAbebe, KaleabTorres, VicenteSteinman, Theodor I.Grantham, Jared J.Chapman, Arlene B.Schrier, Robert W.Wolf, Myles2017-07-13T06:25:55-07:00doi:10.2215/CJN.12821216hwp:resource-id:clinjasn;12/9/1461American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, chronic kidney disease, Epidemiology and outcomes, ESRD, renal progression, Disease Progression, Fibroblast Growth Factors, glomerular filtration rate, Humans, kidney, Kidney Failure, Chronic, Polycystic Kidney, Autosomal Dominant, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk, fibroblast growth factor 23Original ArticlesCystic Kidney DiseaseOriginal ArticlesCystic Kidney Diseaseresearch-article20172017-09-07September 07, 201710.2215/CJN.128212161555-90411555-905X2017-07-13T06:25:55-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914611469
- Frailty Screening Tools for Elderly Patients Incident to Dialysis10.2215/CJN.11801116Mon, 17 Jul 2017 08:58:15 GMT-07:00Frailty Screening Tools for Elderly Patients Incident to Dialysisvan Loon, Ismay N.Goto, Namiko A.Boereboom, Franciscus T.J.Bots, Michiel L.Verhaar, Marianne C.Hamaker, Marije E.2017-07-17T08:58:15-07:00doi:10.2215/CJN.11801116hwp:resource-id:clinjasn;12/9/1480American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, elderly, frailty, geriatric assessment, screening, Aged, Frail Elderly, Geriatric Assessment, Humans, Judgment, Nephrologists, Outcome Assessment (Health Care), renal dialysis, Renal Insufficiency, Chronic, Risk, Safety, SensitivityOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20172017-09-07September 07, 201710.2215/CJN.118011161555-90411555-905X2017-07-17T08:58:15-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914801488
- Correction10.2215/CJN.07190717Thu, 03 Aug 2017 06:43:46 GMT-07:00CorrectionAmerican Society of Nephrology2017-08-03T06:43:46-07:00doi:10.2215/CJN.07190717hwp:resource-id:clinjasn;12/9/1528American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20172017-09-07September 07, 201710.2215/CJN.071907171555-90411555-905X2017-08-03T06:43:46-07:002017-09-07Clinical Journal of the American Society of NephrologyErratum12129615289831528997
- Refining Diagnostic Approaches in Nephrolithiasis: Incomplete Distal Renal Tubular Acidosis10.2215/CJN.07160717Thu, 03 Aug 2017 06:43:46 GMT-07:00Refining Diagnostic Approaches in Nephrolithiasis: Incomplete Distal Renal Tubular AcidosisGoldfarb, David S.2017-08-03T06:43:46-07:00doi:10.2215/CJN.07160717hwp:resource-id:clinjasn;12/9/1380American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcidosis, Renal Tubular, Kidney Calculi, NephrolithiasisEditorialsEditorialseditorial20172017-09-07September 07, 201710.2215/CJN.071607171555-90411555-905X2017-08-03T06:43:46-07:002017-09-07Clinical Journal of the American Society of NephrologyEditorials12991380150713821517
- A Scoping Review for Strategies to Increase Living Kidney Donation10.2215/CJN.01470217Thu, 17 Aug 2017 10:24:17 GMT-07:00A Scoping Review for Strategies to Increase Living Kidney DonationBarnieh, LianneCollister, DavidManns, BradenLam, Ngan N.Shojai, SoroushLorenzetti, DianeGill, John S.Klarenbach, Scott2017-08-17T10:24:17-07:00doi:10.2215/CJN.01470217hwp:resource-id:clinjasn;12/9/1518American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, kidney donation, kidney transplantation, kidney, Living Donors, Nephrectomy, Outcome Assessment (Health Care), Randomized Controlled Trials as Topic, Social Support, Tissue and Organ HarvestingOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-09-07September 07, 201710.2215/CJN.014702171555-90411555-905X2017-08-17T10:24:17-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12991518138315271385
- Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers10.2215/CJN.01320217Thu, 03 Aug 2017 06:43:46 GMT-07:00Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone FormersDhayat, Nasser A.Gradwell, Michael W.Pathare, GaneshAnderegg, ManuelSchneider, LisaLuethi, DavidMattmann, CedricMoe, Orson W.Vogt, BrunoFuster, Daniel G.2017-08-03T06:43:46-07:00doi:10.2215/CJN.01320217hwp:resource-id:clinjasn;12/9/1507American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical nephrology, mineral metabolism, renal tubular acidosis, kidney stones, Acidosis, Renal Tubular, Ammonium Chloride, Ammonium Compounds, Diagnostic Tests, Routine, Fasting, Fludrocortisone, Furosemide, Kidney Calculi, Potassium, Prevalence, Prospective Studies, Sensitivity and SpecificityOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20172017-09-07September 07, 201710.2215/CJN.013202171555-90411555-905X2017-08-03T06:43:46-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12991507138015171382
- Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease10.2215/CJN.01820217Fri, 16 Jun 2017 06:34:53 GMT-07:00Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry DiseaseSkrunes, RannveigTøndel, CamillaLeh, SabineLarsen, Kristin KampevoldHouge, GunnarDavidsen, Einar SkulstadHollak, Carlavan Kuilenburg, André B.P.Vaz, Frédéric M.Svarstad, Einar2017-06-16T06:34:53-07:00doi:10.2215/CJN.01820217hwp:resource-id:clinjasn;12/9/1470American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, chronic kidney disease, podocyte, Adolescent, Adult, albuminuria, Biomarkers, Biopsy, Child, Disease Progression, Enzyme Replacement Therapy, Fabry Disease, Follow-Up Studies, glomerular filtration rate, Humans, Isoenzymes, Male, Middle Aged, Podocytes, Trihexosylceramides, Young Adult, alpha-GalactosidasOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20172017-09-07September 07, 201710.2215/CJN.018202171555-90411555-905X2017-06-16T06:34:53-07:002017-09-07Clinical Journal of the American Society of NephrologyOriginal Articles12914701479
- What Is the Role of Vitamin D Supplementation on Vascular Health in CKD?10.2215/CJN.07170717Mon, 07 Aug 2017 06:33:23 GMT-07:00What Is the Role of Vitamin D Supplementation on Vascular Health in CKD?Toussaint, Nigel D.Ruderman, Irene2017-08-07T06:33:23-07:00doi:10.2215/CJN.07170717hwp:resource-id:clinjasn;12/9/1377American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDietary Supplements, Nutrition Therapy, Vitamin D, Renal Insufficiency, Chronic, Vitamin D DeficiencyEditorialsEditorialseditorial20172017-09-07September 07, 201710.2215/CJN.071707171555-90411555-905X2017-08-07T06:33:23-07:002017-09-07Clinical Journal of the American Society of NephrologyEditorials12999137714471438137914601446
- PLA2R and THSD7A: Disparate Paths to the Same Disease?The phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major autoantigens in primary membranous nephropathy (MN), and define two molecular subclasses of this disease. Both proteins are large transmembrane glycoproteins expressed by the podocyte, and both induce IgG4-predominant humoral immune responses that produce circulating autoantibodies that can be used clinically for diagnostic and monitoring purposes. The biologic roles of these proteins remain speculative, although several features of THSD7A suggest a role in adhesion. PLA2R-associated MN was initially found to associate with risk alleles within HLA-DQA1, but subsequent studies have shifted the focus to the HLA-DRB locus. Three distinct humoral epitope-containing regions have been defined within the extracellular portion of PLA2R, and it appears that the number of targeted epitopes may determine disease severity. Although similar information is not yet available for THSD7A-associated MN, this form of MN may have a unique association with malignancy. Finally, it appears likely that other autoantigens in primary MN exist. Although protocols similar to those that identified PLA2R and THSD7A may be successful in the identification of novel antigenic targets in MN, newer techniques such as laser-capture mass spectrometry or protein arrays may be helpful as well.10.1681/ASN.2017020178Mon, 03 Jul 2017 07:30:33 GMT-07:00PLA2R and THSD7A: Disparate Paths to the Same Disease?The phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major autoantigens in primary membranous nephropathy (MN), and define two molecular subclasses of this disease. Both proteins are large transmembrane glycoproteins expressed by the podocyte, and both induce IgG4-predominant humoral immune responses that produce circulating autoantibodies that can be used clinically for diagnostic and monitoring purposes. The biologic roles of these proteins remain speculative, although several features of THSD7A suggest a role in adhesion. PLA2R-associated MN was initially found to associate with risk alleles within HLA-DQA1, but subsequent studies have shifted the focus to the HLA-DRB locus. Three distinct humoral epitope-containing regions have been defined within the extracellular portion of PLA2R, and it appears that the number of targeted epitopes may determine disease severity. Although similar information is not yet available for THSD7A-associated MN, this form of MN may have a unique association with malignancy. Finally, it appears likely that other autoantigens in primary MN exist. Although protocols similar to those that identified PLA2R and THSD7A may be successful in the identification of novel antigenic targets in MN, newer techniques such as laser-capture mass spectrometry or protein arrays may be helpful as well.Beck, Laurence H.2017-07-03T07:30:33-07:00doi:10.1681/ASN.2017020178hwp:resource-id:jnephrol;28/9/2579American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, Phospholipase A2 receptor, thrombospondin, type-1 domain-containing 7A, autoantibody, podocyte, human geneticsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-09-01September 201710.1681/ASN.20170201781046-66731533-34502017-07-03T07:30:33-07:002017-09Journal of the American Society of NephrologyUp Front Matters28925792589
- Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney DiseaseBiomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor–1 (TNFR-1), TNFR-2, and kidney injury molecule–1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome.10.1681/ASN.2016101101Fri, 05 May 2017 06:28:24 GMT-07:00Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney DiseaseBiomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor–1 (TNFR-1), TNFR-2, and kidney injury molecule–1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome.Coca, Steven G.Nadkarni, Girish N.Huang, YuanMoledina, Dennis G.Rao, VeenaZhang, JaneFerket, BartCrowley, Susan T.Fried, Linda F.Parikh, Chirag R.2017-05-05T06:28:24-07:00doi:10.1681/ASN.2016101101hwp:resource-id:jnephrol;28/9/2786American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20161011011046-66731533-34502017-05-05T06:28:24-07:002017-09Journal of the American Society of NephrologyClinical Research28927862793
- Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated VasculitisAlternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, −4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, −11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.10.1681/ASN.2016111179Tue, 11 Apr 2017 06:01:00 GMT-07:00Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated VasculitisAlternative C activation is involved in the pathogenesis of ANCA-associated vasculitis. However, glucocorticoids used as treatment contribute to the morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), an orally administered, selective C5a receptor inhibitor, could replace oral glucocorticoids without compromising efficacy. In this randomized, placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis received placebo plus prednisone starting at 60 mg daily (control group), avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or avacopan (30 mg, twice daily) without prednisone. All patients received cyclophosphamide or rituximab. The primary efficacy measure was the proportion of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in the control and 22 in each of the avacopan groups. Clinical response at week 12 was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in the avacopan plus reduced-dose prednisone group (difference from control 16.4%; two-sided 90% confidence limit, −4.3% to 37.1%; P=0.002 for noninferiority), and 17 of 21 (81.0%) patients in the avacopan without prednisone group (difference from control 11.0%; two-sided 90% confidence limit, −11.0% to 32.9%; P=0.01 for noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 of 22 (96%) patients in the avacopan without prednisone group. In conclusion, C5a receptor inhibition with avacopan was effective in replacing high-dose glucocorticoids in treating vasculitis.Jayne, David R.W.Bruchfeld, Annette N.Harper, LorraineSchaier, MatthiasVenning, Michael C.Hamilton, PatrickBurst, VolkerGrundmann, FranziskaJadoul, MichelSzombati, IstvánTesař, VladimírSegelmark, MårtenPotarca, AntoniaSchall, Thomas J.Bekker, Pirow,Jayne, David R.W.Bruchfeld, Annette N.Harper, LorraineSchaier, MatthiasVenning, Michael C.Hamilton, PatrickBurst, VolkerGrundmann, FranziskaJadoul, MichelSzombati, IstvánTesař, VladimírSegelmark, MårtenPotarca, AntoniaSchall, Thomas J.Bekker, Pirow2017-04-11T06:01:00-07:00doi:10.1681/ASN.2016111179hwp:resource-id:jnephrol;28/9/2756American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyavacopan, complement, complement 5a, complement 5a receptor, ANCA, ANCA-associated vasculitisClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20161111791046-66731533-34502017-04-11T06:01:00-07:002017-09Journal of the American Society of NephrologyClinical Research28927562767
- The Medicare Access and CHIP Reauthorization Act: Implications for NephrologyIn response to rising Medicare costs, Congress passed the Medicare Access and Children’s Health Insurance Program Reauthorization Act in 2015. The law fundamentally changes the way that health care providers are reimbursed by implementing a pay for performance system that rewards providers for high-value health care. As of the beginning of 2017, providers will be evaluated on quality and in later years, cost as well. High-quality, cost-efficient providers will receive bonuses in reimbursement, and low-quality, expensive providers will be penalized financially. The Centers for Medicare and Medicaid Services will evaluate provider costs through episodes of care, which are currently in development, and alternative payment models. Although dialysis-specific alternative payment models have already been implemented, current models do not address the transition of patients from CKD to ESRD, a particularly vulnerable time for patients. Nephrology providers have an opportunity to develop cost-efficient ways to care for patients during these transitions. Efforts like these, if successful, will help ensure that Medicare remains solvent in coming years.10.1681/ASN.2017040407Fri, 28 Jul 2017 06:23:59 GMT-07:00The Medicare Access and CHIP Reauthorization Act: Implications for NephrologyIn response to rising Medicare costs, Congress passed the Medicare Access and Children’s Health Insurance Program Reauthorization Act in 2015. The law fundamentally changes the way that health care providers are reimbursed by implementing a pay for performance system that rewards providers for high-value health care. As of the beginning of 2017, providers will be evaluated on quality and in later years, cost as well. High-quality, cost-efficient providers will receive bonuses in reimbursement, and low-quality, expensive providers will be penalized financially. The Centers for Medicare and Medicaid Services will evaluate provider costs through episodes of care, which are currently in development, and alternative payment models. Although dialysis-specific alternative payment models have already been implemented, current models do not address the transition of patients from CKD to ESRD, a particularly vulnerable time for patients. Nephrology providers have an opportunity to develop cost-efficient ways to care for patients during these transitions. Efforts like these, if successful, will help ensure that Medicare remains solvent in coming years.Lin, EugeneMaCurdy, ThomasBhattacharya, Jay2017-07-28T06:23:59-07:00doi:10.1681/ASN.2017040407hwp:resource-id:jnephrol;28/9/2590American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, dialysis, Economic Impact, nephrologyUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20172017-09-01September 201710.1681/ASN.20170404071046-66731533-34502017-07-28T06:23:59-07:002017-09Journal of the American Society of NephrologyUp Front Matters28925902596
- Complement Recognition Pathways in Renal TransplantationThe complement system, consisting of soluble and cell membrane–bound components of the innate immune system, has defined roles in the pathophysiology of renal allograft rejection. Notably, the unavoidable ischemia-reperfusion injury inherent to transplantation is mediated through the terminal complement activation products C5a and C5b-9. Furthermore, biologically active fragments C3a and C5a, produced during complement activation, can modulate both antigen presentation and T cell priming, ultimately leading to allograft rejection. Earlier work identified renal tubule cell synthesis of C3, rather than hepatic synthesis of C3, as the primary source of C3 driving these effects. Recent efforts have focused on identifying the local triggers of complement activation. Collectin-11, a soluble C-type lectin expressed in renal tissue, has been implicated as an important trigger of complement activation in renal tissue. In particular, collectin-11 has been shown to engage L-fucose at sites of ischemic stress, activating the lectin complement pathway and directing the innate immune response to the distressed renal tubule. The interface between collectin-11 and L-fucose, in both the recipient and the allograft, is an attractive target for therapies intended to curtail renal inflammation in the acute phase.10.1681/ASN.2017010079Thu, 29 Jun 2017 06:34:33 GMT-07:00Complement Recognition Pathways in Renal TransplantationThe complement system, consisting of soluble and cell membrane–bound components of the innate immune system, has defined roles in the pathophysiology of renal allograft rejection. Notably, the unavoidable ischemia-reperfusion injury inherent to transplantation is mediated through the terminal complement activation products C5a and C5b-9. Furthermore, biologically active fragments C3a and C5a, produced during complement activation, can modulate both antigen presentation and T cell priming, ultimately leading to allograft rejection. Earlier work identified renal tubule cell synthesis of C3, rather than hepatic synthesis of C3, as the primary source of C3 driving these effects. Recent efforts have focused on identifying the local triggers of complement activation. Collectin-11, a soluble C-type lectin expressed in renal tissue, has been implicated as an important trigger of complement activation in renal tissue. In particular, collectin-11 has been shown to engage L-fucose at sites of ischemic stress, activating the lectin complement pathway and directing the innate immune response to the distressed renal tubule. The interface between collectin-11 and L-fucose, in both the recipient and the allograft, is an attractive target for therapies intended to curtail renal inflammation in the acute phase.Nauser, Christopher L.Farrar, Conrad A.Sacks, Steven H.2017-06-29T06:34:33-07:00doi:10.1681/ASN.2017010079hwp:resource-id:jnephrol;28/9/2571American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, lectin pathway, collectin-11, renal transplantationUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-09-01September 201710.1681/ASN.20170100791046-66731533-34502017-06-29T06:34:33-07:002017-09Journal of the American Society of NephrologyUp Front Matters28925712578
- Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular DiseaseAtherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (n=14) received a single infusion of MSC (1.0 × 105 or 2.5 × 105 cells/kg; n=7 each) plus standardized medical treatment; the medical treatment only group (n=14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level–dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8–185.5 ml/min, P=0.01); contralateral kidney RBF increased (212.7–271.8 ml/min, P=0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%–17.8%] to 6.8% [interquartile range, 1.8%–12.9%], P=0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (−3% versus −24%, P=0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.10.1681/ASN.2017020151Mon, 01 May 2017 05:14:11 GMT-07:00Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular DiseaseAtherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (n=14) received a single infusion of MSC (1.0 × 105 or 2.5 × 105 cells/kg; n=7 each) plus standardized medical treatment; the medical treatment only group (n=14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level–dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8–185.5 ml/min, P=0.01); contralateral kidney RBF increased (212.7–271.8 ml/min, P=0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%–17.8%] to 6.8% [interquartile range, 1.8%–12.9%], P=0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (−3% versus −24%, P=0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.Saad, AhmedDietz, Allan B.Herrmann, Sandra M.S.Hickson, LaTonya J.Glockner, James F.McKusick, Michael A.Misra, SanjayBjarnason, HaraldurArmstrong, Adam S.Gastineau, Dennis A.Lerman, Lilach O.Textor, Stephen C.2017-05-01T05:14:11-07:00doi:10.1681/ASN.2017020151hwp:resource-id:jnephrol;28/9/2777American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal artery stenosis, ischemia, stem cell, Renovascular diseaseClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20170201511046-66731533-34502017-05-01T05:14:11-07:002017-09Journal of the American Society of NephrologyClinical Research28927772785
- Sleep-Time Ambulatory BP Is an Independent Prognostic Marker of CKDThe prognostic value of clinic and ambulatory BP in predicting incident CKD and whether CKD risk reduction associates with progressive treatment–induced decrease of clinic, awake, or asleep BP are unknown. We prospectively evaluated 2763 individuals without CKD, 1343 men and 1420 women (mean±SD age: 51.5±14.3 years old), with baseline ambulatory BP ranging from normotension to hypertension. On recruitment and annually thereafter (more frequently if hypertension treatment was adjusted on the basis of ambulatory BP), we simultaneously monitored BP and physical activity (wrist actigraphy) for 48 hours to accurately derive individualized mean awake and asleep BP. During a median 5.9-year follow-up, 404 participants developed CKD. Mean asleep systolic BP was the most significant predictor of CKD in a Cox proportional hazard model adjusted for age, diabetes, serum creatinine concentration, urinary albumin concentration, previous cardiovascular event, and hypertension treatment time (on awakening versus at bedtime; per 1-SD elevation: hazard ratio, 1.44; 95% confidence interval, 1.31 to 1.56; P<0.001). The predictive values of mean clinic BP and mean awake or 48-hour ambulatory BP was not significant when corrected by mean asleep BP. Analyses of BP changes during follow-up revealed 27% reduction in the risk of CKD per 1-SD decrease in mean asleep systolic BP, independent of changes in mean clinic BP or awake ambulatory BP. In conclusion, sleep-time BP is a highly significant independent prognostic marker for CKD. Furthermore, progressive treatment–induced decrease of asleep BP, a potential therapeutic target requiring ambulatory BP evaluation, might be a significant method for reducing CKD risk.10.1681/ASN.2016111186Fri, 28 Apr 2017 05:47:12 GMT-07:00Sleep-Time Ambulatory BP Is an Independent Prognostic Marker of CKDThe prognostic value of clinic and ambulatory BP in predicting incident CKD and whether CKD risk reduction associates with progressive treatment–induced decrease of clinic, awake, or asleep BP are unknown. We prospectively evaluated 2763 individuals without CKD, 1343 men and 1420 women (mean±SD age: 51.5±14.3 years old), with baseline ambulatory BP ranging from normotension to hypertension. On recruitment and annually thereafter (more frequently if hypertension treatment was adjusted on the basis of ambulatory BP), we simultaneously monitored BP and physical activity (wrist actigraphy) for 48 hours to accurately derive individualized mean awake and asleep BP. During a median 5.9-year follow-up, 404 participants developed CKD. Mean asleep systolic BP was the most significant predictor of CKD in a Cox proportional hazard model adjusted for age, diabetes, serum creatinine concentration, urinary albumin concentration, previous cardiovascular event, and hypertension treatment time (on awakening versus at bedtime; per 1-SD elevation: hazard ratio, 1.44; 95% confidence interval, 1.31 to 1.56; P<0.001). The predictive values of mean clinic BP and mean awake or 48-hour ambulatory BP was not significant when corrected by mean asleep BP. Analyses of BP changes during follow-up revealed 27% reduction in the risk of CKD per 1-SD decrease in mean asleep systolic BP, independent of changes in mean clinic BP or awake ambulatory BP. In conclusion, sleep-time BP is a highly significant independent prognostic marker for CKD. Furthermore, progressive treatment–induced decrease of asleep BP, a potential therapeutic target requiring ambulatory BP evaluation, might be a significant method for reducing CKD risk.Hermida, Ramón C.Ayala, Diana E.Mojón, ArtemioFernández, José R.2017-04-28T05:47:12-07:00doi:10.1681/ASN.2016111186hwp:resource-id:jnephrol;28/9/2802American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAmbulatory blood pressure, Incident chronic kidney disease, sleep-time blood pressure, hypertension chronotherapyClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20161111861046-66731533-34502017-04-28T05:47:12-07:002017-09Journal of the American Society of NephrologyClinical Research28928022811
- Quantifying Postdonation Risk of ESRD in Living Kidney DonorsStudies have estimated the average risk of postdonation ESRD for living kidney donors in the United States, but personalized estimation on the basis of donor characteristics remains unavailable. We studied 133,824 living kidney donors from 1987 to 2015, as reported to the Organ Procurement and Transplantation Network, with ESRD ascertainment via Centers for Medicare and Medicaid Services linkage, using Cox regression with late entries. Black race (hazard ratio [HR], 2.96; 95% confidence interval [95% CI], 2.25 to 3.89; P<0.001) and male sex (HR, 1.88; 95% CI, 1.50 to 2.35; P<0.001) was associated with higher risk of ESRD in donors. Among nonblack donors, older age was associated with greater risk (HR per 10 years, 1.40; 95% CI, 1.23 to 1.59; P<0.001). Among black donors, older age was not significantly associated with risk (HR, 0.88; 95% CI, 0.72 to 1.09; P=0.3). Greater body mass index was associated with higher risk (HR per 5 kg/m2, 1.61; 95% CI, 1.29 to 2.00; P<0.001). Donors who had a first-degree biological relationship to the recipient had increased risk (HR, 1.70; 95% CI, 1.24 to 2.34; P<0.01). C-statistic of the model was 0.71. Predicted 20-year risk of ESRD for the median donor was only 34 cases per 10,000 donors, but 1% of donors had predicted risk exceeding 256 cases per 10,000 donors. Risk estimation is critical for appropriate informed consent and varies substantially across living kidney donors. Greater permissiveness may be warranted in older black candidate donors; young black candidates should be evaluated carefully.10.1681/ASN.2016101084Thu, 27 Apr 2017 06:30:57 GMT-07:00Quantifying Postdonation Risk of ESRD in Living Kidney DonorsStudies have estimated the average risk of postdonation ESRD for living kidney donors in the United States, but personalized estimation on the basis of donor characteristics remains unavailable. We studied 133,824 living kidney donors from 1987 to 2015, as reported to the Organ Procurement and Transplantation Network, with ESRD ascertainment via Centers for Medicare and Medicaid Services linkage, using Cox regression with late entries. Black race (hazard ratio [HR], 2.96; 95% confidence interval [95% CI], 2.25 to 3.89; P<0.001) and male sex (HR, 1.88; 95% CI, 1.50 to 2.35; P<0.001) was associated with higher risk of ESRD in donors. Among nonblack donors, older age was associated with greater risk (HR per 10 years, 1.40; 95% CI, 1.23 to 1.59; P<0.001). Among black donors, older age was not significantly associated with risk (HR, 0.88; 95% CI, 0.72 to 1.09; P=0.3). Greater body mass index was associated with higher risk (HR per 5 kg/m2, 1.61; 95% CI, 1.29 to 2.00; P<0.001). Donors who had a first-degree biological relationship to the recipient had increased risk (HR, 1.70; 95% CI, 1.24 to 2.34; P<0.01). C-statistic of the model was 0.71. Predicted 20-year risk of ESRD for the median donor was only 34 cases per 10,000 donors, but 1% of donors had predicted risk exceeding 256 cases per 10,000 donors. Risk estimation is critical for appropriate informed consent and varies substantially across living kidney donors. Greater permissiveness may be warranted in older black candidate donors; young black candidates should be evaluated carefully.Massie, Allan B.Muzaale, Abimereki D.Luo, XunChow, Eric K.H.Locke, Jayme E.Nguyen, Anh Q.Henderson, Macey L.Snyder, Jon J.Segev, Dorry L.2017-04-27T06:30:57-07:00doi:10.1681/ASN.2016101084hwp:resource-id:jnephrol;28/9/2749American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney donation, ESRD, risk factorsClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20161010841046-66731533-34502017-04-27T06:30:57-07:002017-09Journal of the American Society of NephrologyClinical Research289991227492559256129682755256125632969
- Erratum10.1681/ASN.2017070806Thu, 31 Aug 2017 01:04:40 GMT-07:00ErratumAmerican Society of Nephrology2017-08-31T13:04:40-07:00doi:10.1681/ASN.2017070806hwp:resource-id:jnephrol;28/9/2824American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20172017-09-01September 201710.1681/ASN.20170708061046-66731533-34502017-08-31T13:04:40-07:002017-09Journal of the American Society of NephrologyErratum282828988282422552472282422582481
- Safety of Rituximab Compared with Steroids and Cyclophosphamide for Idiopathic Membranous NephropathyGuidelines recommend steroid plus cyclical cyclophosphamide (St-Cp) therapy for patients with idiopathic membranous nephropathy at high risk of progression to ESRD. Rituximab (Rtx) may be a safer alternative. In this retrospective, observational cohort study, we compared time to any adverse event (primary outcome); serious or nonserious events; partial and complete remission of the nephrotic syndrome; and a composite of doubling of serum creatinine, ESRD, or death between 100 Rtx-treated patients and 103 patients who received daily St-Cp. We monitored patients with standardized protocols and adjusted for baseline characteristics by Cox regression. Over a median follow-up of 40 months, the Rtx group had significantly fewer adverse events than the St-Cp group (63 versus 173; P<0.001), both serious (11 versus 46; P<0.001) and nonserious (52 versus 127; P<0.001). Cumulative incidence of any first (35.5% versus 69.0%; P<0.001), serious (16.4% versus 30.2%; P=0.002), or nonserious (23.6% versus 60.8%; P<0.001) event was significantly lower with Rtx. Adjusted hazard ratios (95% confidence intervals) between Rtx and St-Cp groups were 0.27 (0.16 to 0.44) for any first adverse event, 0.32 (0.15 to 0.68) for serious adverse events, and 0.23 (0.13 to 0.41) for nonserious adverse events. Although the cumulative incidence of partial remission was lower in the Rtx group, rates of complete remission and the composite renal end point did not differ significantly between groups. Because of its superior safety profile, we suggest that Rtx might replace St-Cp as first-line immunosuppressive therapy in patients with idiopathic membranous nephropathy and nephrotic syndrome.10.1681/ASN.2016091022Tue, 09 May 2017 06:07:30 GMT-07:00Safety of Rituximab Compared with Steroids and Cyclophosphamide for Idiopathic Membranous NephropathyGuidelines recommend steroid plus cyclical cyclophosphamide (St-Cp) therapy for patients with idiopathic membranous nephropathy at high risk of progression to ESRD. Rituximab (Rtx) may be a safer alternative. In this retrospective, observational cohort study, we compared time to any adverse event (primary outcome); serious or nonserious events; partial and complete remission of the nephrotic syndrome; and a composite of doubling of serum creatinine, ESRD, or death between 100 Rtx-treated patients and 103 patients who received daily St-Cp. We monitored patients with standardized protocols and adjusted for baseline characteristics by Cox regression. Over a median follow-up of 40 months, the Rtx group had significantly fewer adverse events than the St-Cp group (63 versus 173; P<0.001), both serious (11 versus 46; P<0.001) and nonserious (52 versus 127; P<0.001). Cumulative incidence of any first (35.5% versus 69.0%; P<0.001), serious (16.4% versus 30.2%; P=0.002), or nonserious (23.6% versus 60.8%; P<0.001) event was significantly lower with Rtx. Adjusted hazard ratios (95% confidence intervals) between Rtx and St-Cp groups were 0.27 (0.16 to 0.44) for any first adverse event, 0.32 (0.15 to 0.68) for serious adverse events, and 0.23 (0.13 to 0.41) for nonserious adverse events. Although the cumulative incidence of partial remission was lower in the Rtx group, rates of complete remission and the composite renal end point did not differ significantly between groups. Because of its superior safety profile, we suggest that Rtx might replace St-Cp as first-line immunosuppressive therapy in patients with idiopathic membranous nephropathy and nephrotic syndrome.van den Brand, Jan A.J.G.Ruggenenti, PieroChianca, AntoniettaHofstra, Julia M.Perna, AnnalisaRuggiero, BarbaraWetzels, Jack F.M.Remuzzi, Giuseppe2017-05-09T06:07:30-07:00doi:10.1681/ASN.2016091022hwp:resource-id:jnephrol;28/9/2729American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, adverse events, drug safety, clinical epidemiology, rituximab, cyclophosphamideClinical EpidemiologyClinical Epidemiologyresearch-article20172017-09-01September 201710.1681/ASN.20160910221046-66731533-34502017-05-09T06:07:30-07:002017-09Journal of the American Society of NephrologyClinical Epidemiology28927292737
- Polycystic Kidney Disease without an Apparent Family HistoryThe absence of a positive family history (PFH) in 10%–25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with de novo disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with de novo cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified PKD1 or PKD2 mutation (15 of 34), asymmetric and de novo PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable PKD1 or PKD2 mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to de novo disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic PKD1 and PKD2 mutations. Furthermore, mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.10.1681/ASN.2016090938Thu, 18 May 2017 07:52:41 GMT-07:00Polycystic Kidney Disease without an Apparent Family HistoryThe absence of a positive family history (PFH) in 10%–25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with de novo disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with de novo cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified PKD1 or PKD2 mutation (15 of 34), asymmetric and de novo PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable PKD1 or PKD2 mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to de novo disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic PKD1 and PKD2 mutations. Furthermore, mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.Iliuta, Ioan-AndreiKalatharan, VinushaWang, KairongCornec-Le Gall, EmilieConklin, JohnPourafkari, MarinaTing, RyanChen, ChenBorgo, Alessia C.He, NingSong, XuewenHeyer, Christina M.Senum, Sarah R.Hwang, Young-HwanPaterson, Andrew D.Harris, Peter C.Khalili, KoroshPei, York2017-05-18T07:52:41-07:00doi:10.1681/ASN.2016090938hwp:resource-id:jnephrol;28/9/2768American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, family history, human geneticsClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20160909381046-66731533-34502017-05-18T07:52:41-07:002017-09Journal of the American Society of NephrologyClinical Research28927682776
- Biliary Tract and Liver Complications in Polycystic Kidney DiseasePolycystic liver disease is a well described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well recognized. We report a 50-year single-center experience of 1007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease. We tested this hypothesis using all England Hospital Episode Statistics data (1998–2012), within which we identified 23,454 people with ADPKD and 6,412,754 hospital controls. Hospitalization rates for biliary tract disease, serious liver complications, and a range of other known ADPKD manifestations were adjusted for potential confounders. Compared with non-ADPKD hospital controls, those with ADPKD had higher rates of admission for biliary tract disease (rate ratio [RR], 2.24; 95% confidence interval [95% CI], 2.16 to 2.33) and serious liver complications (RR, 4.67; 95% CI, 4.35 to 5.02). In analyses restricted to those on maintenance dialysis or with a kidney transplant, RRs attenuated substantially, but ADPKD remained associated with biliary tract disease (RR, 1.19; 95% CI, 1.08 to 1.31) and perhaps with serious liver complications (RR, 1.15; 95% CI, 0.98 to 1.33). The ADPKD versus non-ADPKD RRs for biliary tract disease were larger for men than women (heterogeneity P<0.001), but RRs for serious liver complications appeared higher in women (heterogeneity P<0.001). Absolute excess risk of biliary tract disease associated with ADPKD was larger than that for serious liver disease, cerebral aneurysms, and inguinal hernias but less than that for urinary tract infections. Overall, biliary tract disease seems to be a distinct and important extrarenal complication of ADPKD.10.1681/ASN.2017010084Tue, 02 May 2017 07:10:33 GMT-07:00Biliary Tract and Liver Complications in Polycystic Kidney DiseasePolycystic liver disease is a well described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well recognized. We report a 50-year single-center experience of 1007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease. We tested this hypothesis using all England Hospital Episode Statistics data (1998–2012), within which we identified 23,454 people with ADPKD and 6,412,754 hospital controls. Hospitalization rates for biliary tract disease, serious liver complications, and a range of other known ADPKD manifestations were adjusted for potential confounders. Compared with non-ADPKD hospital controls, those with ADPKD had higher rates of admission for biliary tract disease (rate ratio [RR], 2.24; 95% confidence interval [95% CI], 2.16 to 2.33) and serious liver complications (RR, 4.67; 95% CI, 4.35 to 5.02). In analyses restricted to those on maintenance dialysis or with a kidney transplant, RRs attenuated substantially, but ADPKD remained associated with biliary tract disease (RR, 1.19; 95% CI, 1.08 to 1.31) and perhaps with serious liver complications (RR, 1.15; 95% CI, 0.98 to 1.33). The ADPKD versus non-ADPKD RRs for biliary tract disease were larger for men than women (heterogeneity P<0.001), but RRs for serious liver complications appeared higher in women (heterogeneity P<0.001). Absolute excess risk of biliary tract disease associated with ADPKD was larger than that for serious liver disease, cerebral aneurysms, and inguinal hernias but less than that for urinary tract infections. Overall, biliary tract disease seems to be a distinct and important extrarenal complication of ADPKD.Judge, Parminder K.Harper, Charlie H.S.Storey, Benjamin C.Haynes, RichardWilcock, Martin J.Staplin, NatalieGoldacre, RaphBaigent, ColinCollier, JaneGoldacre, MichaelLandray, Martin J.Winearls, Christopher G.Herrington, William G.2017-05-02T07:10:33-07:00doi:10.1681/ASN.2017010084hwp:resource-id:jnephrol;28/9/2738American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, liver, infections, biliary tract, complications, outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-09-01September 201710.1681/ASN.20170100841046-66731533-34502017-05-02T07:10:33-07:002017-09Journal of the American Society of NephrologyClinical Epidemiology28927382748
- Acute Declines in Renal Function during Intensive BP Lowering: Implications for Future ESRD RiskThe magnitude of decline in renal function that should be tolerated during intensive BP lowering and its association with risk of ESRD are unclear. To determine whether the acute declines in kidney function in the intensive BP lowering arm of two trials in CKD associated with higher risk of ESRD, we performed a retrospective study of 899 African American Study of Kidney Disease and Hypertension (AASK) and 761 Modification of Diet in Renal Disease (MDRD) Trial participants previously randomized to strict versus usual BP control. The predictor was the percentage decline in eGFR (<5%, 5% to <20%, or ≥20%) between randomization and months 3 and 4 of the trial (time to achieve BP goals). ESRD was the outcome of interest. Compared with a <5% eGFR decline in the usual BP arm, a 5% to <20% eGFR decline during intensive BP lowering did not associate with a higher risk of ESRD in the AASK (adjusted hazard ratio [aHR], 1.19; 95% confidence interval [95% CI], 0.84 to 1.68) or the MDRD Trial (aHR, 1.08; 95% CI, 0.84 to 1.40). However, a 5% to <20% eGFR decline in the usual BP arm associated with higher risk of ESRD in AASK (aHR, 1.83; 95% CI, 1.30 to 2.57) and MDRD Trial (aHR, 1.62; 95% CI, 1.25 to 2.11). A ≥20% eGFR decline associated with higher risk of ESRD in both strict and usual BP arms. Thus, acute eGFR declines ≥20% during intensive BP lowering identified a subset of patients at higher risk for adverse outcomes.10.1681/ASN.2017010040Thu, 04 May 2017 06:04:53 GMT-07:00Acute Declines in Renal Function during Intensive BP Lowering: Implications for Future ESRD RiskThe magnitude of decline in renal function that should be tolerated during intensive BP lowering and its association with risk of ESRD are unclear. To determine whether the acute declines in kidney function in the intensive BP lowering arm of two trials in CKD associated with higher risk of ESRD, we performed a retrospective study of 899 African American Study of Kidney Disease and Hypertension (AASK) and 761 Modification of Diet in Renal Disease (MDRD) Trial participants previously randomized to strict versus usual BP control. The predictor was the percentage decline in eGFR (<5%, 5% to <20%, or ≥20%) between randomization and months 3 and 4 of the trial (time to achieve BP goals). ESRD was the outcome of interest. Compared with a <5% eGFR decline in the usual BP arm, a 5% to <20% eGFR decline during intensive BP lowering did not associate with a higher risk of ESRD in the AASK (adjusted hazard ratio [aHR], 1.19; 95% confidence interval [95% CI], 0.84 to 1.68) or the MDRD Trial (aHR, 1.08; 95% CI, 0.84 to 1.40). However, a 5% to <20% eGFR decline in the usual BP arm associated with higher risk of ESRD in AASK (aHR, 1.83; 95% CI, 1.30 to 2.57) and MDRD Trial (aHR, 1.62; 95% CI, 1.25 to 2.11). A ≥20% eGFR decline associated with higher risk of ESRD in both strict and usual BP arms. Thus, acute eGFR declines ≥20% during intensive BP lowering identified a subset of patients at higher risk for adverse outcomes.Ku, ElaineBakris, GeorgeJohansen, Kirsten L.Lin, FengSarnak, Mark J.Campese, Vito M.Jamerson, KennethGassman, Jennifer J.Smogorzewski, MiroslawHsu, Chi-yuan2017-05-04T06:04:53-07:00doi:10.1681/ASN.2017010040hwp:resource-id:jnephrol;28/9/2794American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, chronic kidney disease, ESRDClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20170100401046-66731533-34502017-05-04T06:04:53-07:002017-09Journal of the American Society of NephrologyClinical Research28927942801
- Sex Differences in Hospitalizations with Maintenance HemodialysisHospitalization is a major source of morbidity among patients with ESRD undergoing maintenance hemodialysis and is a significant contributor to health care costs. To identify subgroups at the highest risk of hospitalization, we analyzed by sex, age, and race, adjusting for demographic and clinical characteristics, the hospitalization rates, and 30-day readmissions for 333,756 hospitalizations among 111,653 patients undergoing maintenance hemodialysis in facilities operated by a large dialysis organization in the United States (2007–2011). The overall hospitalization rate was 1.85 hospitalizations per person-year and was much higher among women than among men (2.08 versus 1.68 hospitalizations per year for women versus men, P<0.001). Age group–specific hospitalization rates were consistently higher for women than for men of the same race, and the differences were greatest in younger age groups (for example, women aged 18–34 years and ≥75 years had 54% [95% confidence interval, 42% to 67%] and 14% [95% confidence interval, 11% to 18%] higher hospitalization rates, respectively, than did men of respective ages). Women also had substantially higher risk for 30-day readmission, with the largest differences at younger ages. Women had a significantly lower serum albumin level than men, and stratification by serum albumin level attenuated sex differences in the age group–specific hospitalization and 30-day readmission rates. These findings suggest that women undergoing maintenance hemodialysis have substantially higher risks for hospitalization and 30-day readmission than men. In this cohort, the sex differences were greatest in the younger age groups and were attenuated by accounting for differences in health status reflected by serum albumin level.10.1681/ASN.2016090986Fri, 21 Apr 2017 06:54:07 GMT-07:00Sex Differences in Hospitalizations with Maintenance HemodialysisHospitalization is a major source of morbidity among patients with ESRD undergoing maintenance hemodialysis and is a significant contributor to health care costs. To identify subgroups at the highest risk of hospitalization, we analyzed by sex, age, and race, adjusting for demographic and clinical characteristics, the hospitalization rates, and 30-day readmissions for 333,756 hospitalizations among 111,653 patients undergoing maintenance hemodialysis in facilities operated by a large dialysis organization in the United States (2007–2011). The overall hospitalization rate was 1.85 hospitalizations per person-year and was much higher among women than among men (2.08 versus 1.68 hospitalizations per year for women versus men, P<0.001). Age group–specific hospitalization rates were consistently higher for women than for men of the same race, and the differences were greatest in younger age groups (for example, women aged 18–34 years and ≥75 years had 54% [95% confidence interval, 42% to 67%] and 14% [95% confidence interval, 11% to 18%] higher hospitalization rates, respectively, than did men of respective ages). Women also had substantially higher risk for 30-day readmission, with the largest differences at younger ages. Women had a significantly lower serum albumin level than men, and stratification by serum albumin level attenuated sex differences in the age group–specific hospitalization and 30-day readmission rates. These findings suggest that women undergoing maintenance hemodialysis have substantially higher risks for hospitalization and 30-day readmission than men. In this cohort, the sex differences were greatest in the younger age groups and were attenuated by accounting for differences in health status reflected by serum albumin level.Adams, Scott V.Rivara, MatthewStreja, ElaniCheung, Alfred K.Arah, Onyebuchi A.Kalantar-Zadeh, KamyarMehrotra, Rajnish2017-04-21T06:54:07-07:00doi:10.1681/ASN.2016090986hwp:resource-id:jnephrol;28/9/2721American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, hemodialysis, hospitalizationClinical EpidemiologyClinical Epidemiologyresearch-article20172017-09-01September 201710.1681/ASN.20160909861046-66731533-34502017-04-21T06:54:07-07:002017-09Journal of the American Society of NephrologyClinical Epidemiology28927212728
- Effects of Intensive BP Control in CKDThe appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (−0.47 versus −0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.10.1681/ASN.2017020148Thu, 22 Jun 2017 06:57:50 GMT-07:00Effects of Intensive BP Control in CKDThe appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n=1330) or <140 mm Hg (standard group; n=1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD (P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (−0.47 versus −0.32 ml/min per 1.73 m2 per year; P<0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.Cheung, Alfred K.Rahman, MahboobReboussin, David M.Craven, Timothy E.Greene, TomKimmel, Paul L.Cushman, William C.Hawfield, Amret T.Johnson, Karen C.Lewis, Cora E.Oparil, SuzanneRocco, Michael V.Sink, Kaycee M.Whelton, Paul K.Wright, Jackson T.Basile, JanBeddhu, SrinivasanBhatt, UdayanChang, Tara I.Chertow, Glenn M.Chonchol, MichelFreedman, Barry I.Haley, WilliamIx, Joachim H.Katz, Lois A.Killeen, Anthony A.Papademetriou, VasiliosRicardo, Ana C.Servilla, KarenWall, BarryWolfgram, DawnYee, Jerry,Cheung, Alfred K.Rahman, MahboobReboussin, David M.Craven, Timothy E.Greene, TomKimmel, Paul L.Cushman, William C.Hawfield, Amret T.Johnson, Karen C.Lewis, Cora E.Oparil, SuzanneRocco, Michael V.Sink, Kaycee M.Whelton, Paul K.Wright, Jackson T.Basile, JanBeddhu, SrinivasanBhatt, UdayanChang, Tara I.Chertow, Glenn M.Chonchol, MichelFreedman, Barry I.Haley, WilliamIx, Joachim H.Katz, Lois A.Killeen, Anthony A.Papademetriou, VasiliosRicardo, Ana C.Servilla, KarenWall, BarryWolfgram, DawnYee, Jerry2017-06-22T06:57:50-07:00doi:10.1681/ASN.2017020148hwp:resource-id:jnephrol;28/9/2812American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, chronic kidney disease, cardiovascular disease, glomerular filtration rate, hypertension, mortalityClinical ResearchClinical Researchresearch-article20172017-09-01September 201710.1681/ASN.20170201481046-66731533-34502017-06-22T06:57:50-07:002017-09Journal of the American Society of NephrologyClinical Research28992812256128232563
- A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or Dietary Coenzyme Q10 SupplementationClinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function. Nephrocyte-specific silencing of Coq2, Coq6, and Coq8, which are genes involved in the CoQ10 pathway that have been associated with genetic nephrotic syndrome in humans, induced dramatic adverse changes in these cells. In particular, silencing of Coq2 led to an abnormal localization of slit diaphragms, collapse of lacunar channels, and more dysmorphic mitochondria. In addition, Coq2-deficient nephrocytes showed elevated levels of autophagy and mitophagy, increased levels of reactive oxygen species, and increased sensitivity to oxidative stress. Dietary supplementation with CoQ10 at least partially rescued these defects. Furthermore, expressing the wild-type human COQ2 gene specifically in nephrocytes rescued the defective protein uptake, but expressing the mutant allele derived from a patient with COQ2 nephropathy did not. We conclude that transgenic Drosophila lines carrying mutations in the CoQ10 pathway genes are clinically relevant models with which to explore the pathogenesis of podocyte injury and could serve as a new platform to test novel therapeutic approaches.10.1681/ASN.2016060626Thu, 20 Apr 2017 06:08:57 GMT-07:00A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or Dietary Coenzyme Q10 SupplementationClinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function. Nephrocyte-specific silencing of Coq2, Coq6, and Coq8, which are genes involved in the CoQ10 pathway that have been associated with genetic nephrotic syndrome in humans, induced dramatic adverse changes in these cells. In particular, silencing of Coq2 led to an abnormal localization of slit diaphragms, collapse of lacunar channels, and more dysmorphic mitochondria. In addition, Coq2-deficient nephrocytes showed elevated levels of autophagy and mitophagy, increased levels of reactive oxygen species, and increased sensitivity to oxidative stress. Dietary supplementation with CoQ10 at least partially rescued these defects. Furthermore, expressing the wild-type human COQ2 gene specifically in nephrocytes rescued the defective protein uptake, but expressing the mutant allele derived from a patient with COQ2 nephropathy did not. We conclude that transgenic Drosophila lines carrying mutations in the CoQ10 pathway genes are clinically relevant models with which to explore the pathogenesis of podocyte injury and could serve as a new platform to test novel therapeutic approaches.Zhu, Jun-yiFu, YulongRichman, AdamZhao, ZhanzhengRay, Patricio E.Han, Zhe2017-04-20T06:08:57-07:00doi:10.1681/ASN.2016060626hwp:resource-id:jnephrol;28/9/2607American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, pediatric nephrology, podocyte, reactive oxygen species, renal cell biology, mitochondriaBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20160606261046-66731533-34502017-04-20T06:08:57-07:002017-09Journal of the American Society of NephrologyBasic Research28926072617
- ELABELA and an ELABELA Fragment Protect against AKIRenal ischemia-reperfusion (I/R) injury is the most common cause of AKI, which associates with high mortality and has no effective therapy. ELABELA (ELA) is a newly identified 32-residue hormone peptide highly expressed in adult kidney. To investigate whether ELA has protective effects on renal I/R injury, we administered the mature peptide (ELA32) or the 11-residue furin-cleaved fragment (ELA11) to hypoxia-reperfusion (H/R)–injured or adriamycin-treated renal tubular cells in vitro. ELA32 and ELA11 significantly inhibited the elevation of the DNA damage response, apoptosis, and inflammation in H/R-injured renal tubular cells and suppressed adriamycin-induced DNA damage response. Similarly, overexpression of ELA32 or ELA11 significantly inhibited H/R-induced cell death, DNA damage response, and inflammation. Notably, treatment of mice with ELA32 or ELA11 but not an ELA11 mutant with a cysteine to alanine substitution at the N terminus (AE11C) inhibited I/R injury-induced renal fibrosis, inflammation, apoptosis, and the DNA damage response and markedly reduced the renal tubular lesions and renal dysfunction. Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI.10.1681/ASN.2016111210Mon, 05 Jun 2017 05:15:30 GMT-07:00ELABELA and an ELABELA Fragment Protect against AKIRenal ischemia-reperfusion (I/R) injury is the most common cause of AKI, which associates with high mortality and has no effective therapy. ELABELA (ELA) is a newly identified 32-residue hormone peptide highly expressed in adult kidney. To investigate whether ELA has protective effects on renal I/R injury, we administered the mature peptide (ELA32) or the 11-residue furin-cleaved fragment (ELA11) to hypoxia-reperfusion (H/R)–injured or adriamycin-treated renal tubular cells in vitro. ELA32 and ELA11 significantly inhibited the elevation of the DNA damage response, apoptosis, and inflammation in H/R-injured renal tubular cells and suppressed adriamycin-induced DNA damage response. Similarly, overexpression of ELA32 or ELA11 significantly inhibited H/R-induced cell death, DNA damage response, and inflammation. Notably, treatment of mice with ELA32 or ELA11 but not an ELA11 mutant with a cysteine to alanine substitution at the N terminus (AE11C) inhibited I/R injury-induced renal fibrosis, inflammation, apoptosis, and the DNA damage response and markedly reduced the renal tubular lesions and renal dysfunction. Together, our results suggest that ELA32 and ELA11 may be therapeutic candidates for treating AKI.Chen, HongWang, LinWang, WenjunCheng, ChengZhang, YuZhou, YuWang, CongyiMiao, XiaopingWang, JiaoWang, ChaoLi, JianshuangZheng, LingHuang, Kun2017-06-05T05:15:30-07:00doi:10.1681/ASN.2016111210hwp:resource-id:jnephrol;28/9/2694American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyELABELA, acute kidney injury, DNA damage response, inflammationBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161112101046-66731533-34502017-06-05T05:15:30-07:002017-09Journal of the American Society of NephrologyBasic Research28926942707
- MicroRNA as Novel Exercise Mimetic for Muscle Wasting in CKD10.1681/ASN.2017060631Tue, 18 Jul 2017 07:41:18 GMT-07:00MicroRNA as Novel Exercise Mimetic for Muscle Wasting in CKDMak, Robert H.Cheung, Wai W.2017-07-18T07:41:18-07:00doi:10.1681/ASN.2017060631hwp:resource-id:jnephrol;28/9/2557American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, nutrition, signalingUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-09-01September 201710.1681/ASN.20170606311046-66731533-34502017-07-18T07:41:18-07:002017-09Journal of the American Society of NephrologyUp Front Matters28992557263125592640
- Glomerulosclerosis Induced by Deficiency of Membrane-Associated Guanylate Kinase Inverted 2 in Kidney PodocytesMembrane-associated guanylate kinase inverted 2 (MAGI-2) is a component of the slit diaphragm (SD) of glomerular podocytes. Here, we investigated the podocyte-specific function of MAGI-2 using newly generated podocyte-specific MAGI-2–knockout (MAGI-2–KO) mice. Compared with podocytes from wild-type mice, podocytes from MAGI-2–KO mice exhibited SD disruption, morphologic abnormalities of foot processes, and podocyte apoptosis leading to podocyte loss. These pathologic changes manifested as massive albuminuria by 8 weeks of age and glomerulosclerosis and significantly higher plasma creatinine levels at 12 weeks of age; all MAGI-2–KO mice died by 20 weeks of age. Loss of MAGI-2 in podocytes associated with decreased expression and nuclear translocation of dendrin, which is also a component of the SD complex. Dendrin translocates from the SD to the nucleus of injured podocytes, promoting apoptosis. Our coimmunoprecipitation and in vitro reconstitution studies showed that dendrin is phosphorylated by Fyn and dephosphorylated by PTP1B, and that Fyn-induced phosphorylation prevents Nedd4–2–mediated ubiquitination of dendrin. Under physiologic conditions in vivo, phosphorylated dendrin localized at the SDs; in the absence of MAGI-2, dephosphorylated dendrin accumulated in the nucleus. Furthermore, induction of experimental GN in rats led to the downregulation of MAGI-2 expression and the nuclear accumulation of dendrin in podocytes. In summary, MAGI-2 and Fyn protect dendrin from Nedd4–2–mediated ubiquitination and from nuclear translocation, thereby maintaining the physiologic homeostasis of podocytes, and the lack of MAGI-2 in podocytes results in FSGS.10.1681/ASN.2016121356Wed, 24 May 2017 05:54:42 GMT-07:00Glomerulosclerosis Induced by Deficiency of Membrane-Associated Guanylate Kinase Inverted 2 in Kidney PodocytesMembrane-associated guanylate kinase inverted 2 (MAGI-2) is a component of the slit diaphragm (SD) of glomerular podocytes. Here, we investigated the podocyte-specific function of MAGI-2 using newly generated podocyte-specific MAGI-2–knockout (MAGI-2–KO) mice. Compared with podocytes from wild-type mice, podocytes from MAGI-2–KO mice exhibited SD disruption, morphologic abnormalities of foot processes, and podocyte apoptosis leading to podocyte loss. These pathologic changes manifested as massive albuminuria by 8 weeks of age and glomerulosclerosis and significantly higher plasma creatinine levels at 12 weeks of age; all MAGI-2–KO mice died by 20 weeks of age. Loss of MAGI-2 in podocytes associated with decreased expression and nuclear translocation of dendrin, which is also a component of the SD complex. Dendrin translocates from the SD to the nucleus of injured podocytes, promoting apoptosis. Our coimmunoprecipitation and in vitro reconstitution studies showed that dendrin is phosphorylated by Fyn and dephosphorylated by PTP1B, and that Fyn-induced phosphorylation prevents Nedd4–2–mediated ubiquitination of dendrin. Under physiologic conditions in vivo, phosphorylated dendrin localized at the SDs; in the absence of MAGI-2, dephosphorylated dendrin accumulated in the nucleus. Furthermore, induction of experimental GN in rats led to the downregulation of MAGI-2 expression and the nuclear accumulation of dendrin in podocytes. In summary, MAGI-2 and Fyn protect dendrin from Nedd4–2–mediated ubiquitination and from nuclear translocation, thereby maintaining the physiologic homeostasis of podocytes, and the lack of MAGI-2 in podocytes results in FSGS.Shirata, NaritoshiIhara, Kan-ichiroYamamoto-Nonaka, KanaeSeki, TakutoMakino, Shin-ichiOliva Trejo, Juan AlejandroMiyake, TakafumiYamada, HiroyukiCampbell, Kirk NicholasNakagawa, TakahikoMori, KiyoshiYanagita, MotokoMundel, PeterNishimori, KatsuhikoAsanuma, Katsuhiko2017-05-24T05:54:42-07:00doi:10.1681/ASN.2016121356hwp:resource-id:jnephrol;28/9/2654American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, MAGI-2, Dendrin, FSGSBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161213561046-66731533-34502017-05-24T05:54:42-07:002017-09Journal of the American Society of NephrologyBasic Research28926542669
- Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal TubulesAberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine–rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt.10.1681/ASN.2016090948Tue, 25 Apr 2017 10:51:18 GMT-07:00Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal TubulesAberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced kinase-activating mutations after Lox-P sites in the mouse Stk39 gene, which encodes the terminal kinase in the WNK signaling pathway, Ste20-related proline-alanine–rich kinase (SPAK). Renal expression of the constitutively active (CA)-SPAK mutant was specifically targeted to the early DCT using a DCT-driven Cre recombinase. CA-SPAK mice displayed thiazide-treatable hypertension and hyperkalemia, concurrent with NCC hyperphosphorylation. However, thiazide-mediated inhibition of NCC and consequent restoration of sodium excretion did not immediately restore urinary potassium excretion in CA-SPAK mice. Notably, CA-SPAK mice exhibited ASDN remodeling, involving a reduction in connecting tubule mass and attenuation of epithelial sodium channel (ENaC) and ROMK expression and apical localization. Blocking hyperactive NCC in the DCT gradually restored ASDN structure and ENaC and ROMK expression, concurrent with the restoration of urinary potassium excretion. These findings verify that NCC hyperactivity underlies FHHt but also reveal that NCC-dependent changes in the driving force for potassium secretion are not sufficient to explain hyperkalemia. Instead, a DCT-ASDN coupling process controls potassium balance in health and becomes aberrantly activated in FHHt.Grimm, P. RichardColeman, RichardDelpire, EricWelling, Paul A.2017-04-25T10:51:18-07:00doi:10.1681/ASN.2016090948hwp:resource-id:jnephrol;28/9/2597American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyParvalbumin-Cre, Ste20 kinase, NCC, Na Reabsorption, FHHtBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20160909481046-66731533-34502017-04-25T10:51:18-07:002017-09Journal of the American Society of NephrologyBasic Research28992597255526062557
- This Month’s Highlights10.1681/ASN.2017060610Thu, 31 Aug 2017 01:04:39 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-08-31T13:04:39-07:00doi:10.1681/ASN.2017060610hwp:resource-id:jnephrol;28/9/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-09-01September 201710.1681/ASN.20170606101046-66731533-34502017-08-31T13:04:39-07:002017-09Journal of the American Society of NephrologyThis Month’s Highlights289ii
- MicroRNA-23a and MicroRNA-27a Mimic Exercise by Ameliorating CKD-Induced Muscle AtrophyMuscle atrophy is a frequent complication of CKD, and exercise can attenuate the process. This study investigated the role of microRNA-23a (miR-23a) and miR-27a in the regulation of muscle mass in mice with CKD. These miRs are located in a gene cluster that is regulated by the transcription factor NFAT. CKD mice expressed less miR-23a in muscle than controls, and resistance exercise (muscle overload) increased the levels of miR-23a and miR-27a in CKD mice. Injection of an adeno-associated virus encoding the miR-23a/27a/24–2 precursor RNA into the tibialis anterior muscles of normal and CKD mice led to increases in mature miR-23a and miR-27a but not miR-24–2 in the muscles of both cohorts. Overexpression of miR-23a/miR-27a in CKD mice attenuated muscle loss, improved grip strength, increased the phosphorylation of Akt and FoxO1, and decreased the activation of phosphatase and tensin homolog (PTEN) and FoxO1 and the expression of TRIM63/MuRF1 and FBXO32/atrogin-1 proteins. Provision of miR-23a/miR-27a also reduced myostatin expression and downstream SMAD-2/3 signaling, decreased activation of caspase-3 and -7, and increased the expression of markers of muscle regeneration. Lastly, in silico miR target analysis and luciferase reporter assays in primary satellite cells identified PTEN and caspase-7 as targets of miR-23a and FoxO1 as a target of miR-27a in muscle. These findings provide new insights about the roles of the miR-23a/27a-24–2 cluster in CKD-induced muscle atrophy in mice and suggest a mechanism by which exercise helps to maintain muscle mass.10.1681/ASN.2016111213Tue, 11 Apr 2017 06:01:00 GMT-07:00MicroRNA-23a and MicroRNA-27a Mimic Exercise by Ameliorating CKD-Induced Muscle AtrophyMuscle atrophy is a frequent complication of CKD, and exercise can attenuate the process. This study investigated the role of microRNA-23a (miR-23a) and miR-27a in the regulation of muscle mass in mice with CKD. These miRs are located in a gene cluster that is regulated by the transcription factor NFAT. CKD mice expressed less miR-23a in muscle than controls, and resistance exercise (muscle overload) increased the levels of miR-23a and miR-27a in CKD mice. Injection of an adeno-associated virus encoding the miR-23a/27a/24–2 precursor RNA into the tibialis anterior muscles of normal and CKD mice led to increases in mature miR-23a and miR-27a but not miR-24–2 in the muscles of both cohorts. Overexpression of miR-23a/miR-27a in CKD mice attenuated muscle loss, improved grip strength, increased the phosphorylation of Akt and FoxO1, and decreased the activation of phosphatase and tensin homolog (PTEN) and FoxO1 and the expression of TRIM63/MuRF1 and FBXO32/atrogin-1 proteins. Provision of miR-23a/miR-27a also reduced myostatin expression and downstream SMAD-2/3 signaling, decreased activation of caspase-3 and -7, and increased the expression of markers of muscle regeneration. Lastly, in silico miR target analysis and luciferase reporter assays in primary satellite cells identified PTEN and caspase-7 as targets of miR-23a and FoxO1 as a target of miR-27a in muscle. These findings provide new insights about the roles of the miR-23a/27a-24–2 cluster in CKD-induced muscle atrophy in mice and suggest a mechanism by which exercise helps to maintain muscle mass.Wang, BinZhang, CongZhang, AiqingCai, HuiPrice, S. RussWang, Xiaonan H.2017-04-11T06:01:00-07:00doi:10.1681/ASN.2016111213hwp:resource-id:jnephrol;28/9/2631American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyuremia, microRNA, exosome, TRIM63/MuRF1, FBXO32/atroginBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161112131046-66731533-34502017-04-11T06:01:00-07:002017-09Journal of the American Society of NephrologyBasic Research28992631255726402559
- BP Targets in CKD, Mortality, and SPRINT: What Have We Learned?10.1681/ASN.2017060652Thu, 20 Jul 2017 07:23:12 GMT-07:00BP Targets in CKD, Mortality, and SPRINT: What Have We Learned?Textor, Stephen C.Schwartz, Gary L.2017-07-20T07:23:12-07:00doi:10.1681/ASN.2017060652hwp:resource-id:jnephrol;28/9/2561American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, CKD, mortality, targetsUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-09-01September 201710.1681/ASN.20170606521046-66731533-34502017-07-20T07:23:12-07:002017-09Journal of the American Society of NephrologyUp Front Matters28999256127492812256327552823
- IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal InjuryCD4+Foxp3+ regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4+ T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI. In vitro, splenic Tregs from IL233-treated mice suppressed CD4+ T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential.10.1681/ASN.2016121272Wed, 24 May 2017 05:54:41 GMT-07:00IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal InjuryCD4+Foxp3+ regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4+ T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI. In vitro, splenic Tregs from IL233-treated mice suppressed CD4+ T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential.Stremska, Marta E.Jose, SheethalSabapathy, VikramHuang, LipingBajwa, AmandeepKinsey, Gilbert R.Sharma, Poonam R.Mohammad, SalehRosin, Diane L.Okusa, Mark D.Sharma, Rahul2017-05-24T05:54:41-07:00doi:10.1681/ASN.2016121272hwp:resource-id:jnephrol;28/9/2681American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyTregs, AKI, IRI, nephrotoxicity, Inflammation, ILC2Basic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161212721046-66731533-34502017-05-24T05:54:41-07:002017-09Journal of the American Society of NephrologyBasic Research28926812693
- Synthesizing Absolute and Relative Risks and the Many Unknowns to Inform Living Kidney Donors10.1681/ASN.2017040375Tue, 02 May 2017 07:10:33 GMT-07:00Synthesizing Absolute and Relative Risks and the Many Unknowns to Inform Living Kidney DonorsPoggio, Emilio D.Schold, Jesse D.2017-05-02T07:10:33-07:00doi:10.1681/ASN.2017040375hwp:resource-id:jnephrol;28/9/2559American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyliving kidney donor, outcomes, ESRDUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-09-01September 201710.1681/ASN.20170403751046-66731533-34502017-05-02T07:10:33-07:002017-09Journal of the American Society of NephrologyUp Front Matters28992559274925612755
- Magnetic Resonance Imaging of the Fibrotic KidneyMagnetic resonance imaging (MRI) has been used for many years for anatomic evaluation of the kidney. Recently developed methods attempt to go beyond anatomy to give information about the health and function of the kidneys. Several methods, including diffusion-weighted MRI, renal blood oxygen level–dependent MRI, renal MR elastography, and renal susceptibility imaging, show promise for providing unique insight into kidney function and severity of fibrosis. However, substantial limitations in accuracy and practicality limit the immediate clinical application of each method. Further development and improvement are necessary to achieve the ideal of a noninvasive image-based measure of renal fibrosis. Our brief review provides a short explanation of these emerging MRI methods and outlines the promising initial results obtained with each as well as current limitations and barriers to clinical implementation.10.1681/ASN.2016101089Mon, 07 Aug 2017 06:45:23 GMT-07:00Magnetic Resonance Imaging of the Fibrotic KidneyMagnetic resonance imaging (MRI) has been used for many years for anatomic evaluation of the kidney. Recently developed methods attempt to go beyond anatomy to give information about the health and function of the kidneys. Several methods, including diffusion-weighted MRI, renal blood oxygen level–dependent MRI, renal MR elastography, and renal susceptibility imaging, show promise for providing unique insight into kidney function and severity of fibrosis. However, substantial limitations in accuracy and practicality limit the immediate clinical application of each method. Further development and improvement are necessary to achieve the ideal of a noninvasive image-based measure of renal fibrosis. Our brief review provides a short explanation of these emerging MRI methods and outlines the promising initial results obtained with each as well as current limitations and barriers to clinical implementation.Morrell, Glen R.Zhang, Jeff L.Lee, Vivian S.2017-08-07T06:45:23-07:00doi:10.1681/ASN.2016101089hwp:resource-id:jnephrol;28/9/2564American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, kidney imaging, MRIUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-09-01September 201710.1681/ASN.20161010891046-66731533-34502017-08-07T06:45:23-07:002017-09Journal of the American Society of NephrologyUp Front Matters28925642570
- Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor DependentNephrotic syndrome is characterized by massive proteinuria and injury of specialized glomerular epithelial cells called podocytes. Studies have shown that, whereas low-concentration thrombin may be cytoprotective, higher thrombin concentrations may contribute to podocyte injury. We and others have demonstrated that ex vivo plasma thrombin generation is enhanced during nephrosis, suggesting that thrombin may contribute to nephrotic progression. Moreover, nonspecific thrombin inhibition has been shown to decrease proteinuria in nephrotic animal models. We thus hypothesized that thrombin contributes to podocyte injury in a protease-activated receptor-specific manner during nephrosis. Here, we show that specific inhibition of thrombin with hirudin reduced proteinuria in two rat nephrosis models, and thrombin colocalized with a podocyte-specific marker in rat glomeruli. Furthermore, flow cytometry immunophenotyping revealed that rat podocytes express the protease-activated receptor family of coagulation receptors in vivo. High-concentration thrombin directly injured conditionally immortalized human and rat podocytes. Using receptor-blocking antibodies and activation peptides, we determined that thrombin-mediated injury depended upon interactions between protease-activated receptor 3 and protease-activated receptor 4 in human podocytes, and between protease-activated receptor 1 and protease-activated receptor 4 in rat podocytes. Proximity ligation and coimmunoprecipitation assays confirmed thrombin-dependent interactions between human protease-activated receptor 3 and protease-activated receptor 4, and between rat protease-activated receptor 1 and protease-activated receptor 4 in cultured podocytes. Collectively, these data implicate thrombinuria as a contributor to podocyte injury during nephrosis, and suggest that thrombin and/or podocyte-expressed thrombin receptors may be novel therapeutic targets for nephrotic syndrome.10.1681/ASN.2016070789Wed, 19 Apr 2017 06:08:41 GMT-07:00Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor DependentNephrotic syndrome is characterized by massive proteinuria and injury of specialized glomerular epithelial cells called podocytes. Studies have shown that, whereas low-concentration thrombin may be cytoprotective, higher thrombin concentrations may contribute to podocyte injury. We and others have demonstrated that ex vivo plasma thrombin generation is enhanced during nephrosis, suggesting that thrombin may contribute to nephrotic progression. Moreover, nonspecific thrombin inhibition has been shown to decrease proteinuria in nephrotic animal models. We thus hypothesized that thrombin contributes to podocyte injury in a protease-activated receptor-specific manner during nephrosis. Here, we show that specific inhibition of thrombin with hirudin reduced proteinuria in two rat nephrosis models, and thrombin colocalized with a podocyte-specific marker in rat glomeruli. Furthermore, flow cytometry immunophenotyping revealed that rat podocytes express the protease-activated receptor family of coagulation receptors in vivo. High-concentration thrombin directly injured conditionally immortalized human and rat podocytes. Using receptor-blocking antibodies and activation peptides, we determined that thrombin-mediated injury depended upon interactions between protease-activated receptor 3 and protease-activated receptor 4 in human podocytes, and between protease-activated receptor 1 and protease-activated receptor 4 in rat podocytes. Proximity ligation and coimmunoprecipitation assays confirmed thrombin-dependent interactions between human protease-activated receptor 3 and protease-activated receptor 4, and between rat protease-activated receptor 1 and protease-activated receptor 4 in cultured podocytes. Collectively, these data implicate thrombinuria as a contributor to podocyte injury during nephrosis, and suggest that thrombin and/or podocyte-expressed thrombin receptors may be novel therapeutic targets for nephrotic syndrome.Sharma, RuchikaWaller, Amanda P.Agrawal, ShipraWolfgang, Katelyn J.Luu, HiepShahzad, KhurrumIsermann, BerendSmoyer, William E.Nieman, Marvin T.Kerlin, Bryce A.2017-04-19T06:08:41-07:00doi:10.1681/ASN.2016070789hwp:resource-id:jnephrol;28/9/2618American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, proteinuria, nephrotic syndrome, thrombin, protease activated receptorBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20160707891046-66731533-34502017-04-19T06:08:41-07:002017-09Journal of the American Society of NephrologyBasic Research28926182630
- Asymmetric Dimethylarginine Contributes to the Impaired Response to Erythropoietin in CKD-AnemiaErythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers. Furthermore, erythrocyte ADMA level associated with the erythropoietin resistance index in patients receiving a weekly injected dose of erythropoiesis-stimulating agents standardized for hemoglobin levels and body weight, whereas it correlated with the erythropoietin demand index (plasma erythropoietin units divided by the hemoglobin value) in patients not receiving erythropoiesis-stimulating agents. Compared with sham-operated controls, wild-type mice with 5/6 subtotal nephrectomy (Nx), a remnant kidney model with advanced CKD, had decreased hemoglobin, hematocrit, and mean corpuscular volume values but increased erythrocyte and plasma ADMA and plasma erythropoietin levels. In comparison, dimethylarginine dimethlaminohydrolase-1 transgenic (DDAH-1 Tg) mice, which efficiently metabolized ADMA, had significant improvements in all of the values except those for erythropoietin after 5/6 Nx. Additionally, wild-type Nx mice, but not DDAH-1 Tg Nx mice, had reduced splenic gene expression of erythropoietin receptor and erythroferrone, which regulates iron metabolism in response to erythropoietin. This study suggests that erythrocyte ADMA accumulation contributes to impaired response to erythropoietin in predialysis patients and advanced CKD mice via suppression of erythropoietin receptor expression.10.1681/ASN.2016111184Fri, 09 Jun 2017 05:46:53 GMT-07:00Asymmetric Dimethylarginine Contributes to the Impaired Response to Erythropoietin in CKD-AnemiaErythropoietin-resistant anemia is associated with adverse cardiovascular events in patients with ESRD, but the underlying mechanism remains unclear. Here, we evaluated the role of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In 54 patients with advanced CKD, erythrocyte but not plasma ADMA levels independently associated with low hemoglobin values, although levels of both types of ADMA were elevated compared with those in healthy volunteers. Furthermore, erythrocyte ADMA level associated with the erythropoietin resistance index in patients receiving a weekly injected dose of erythropoiesis-stimulating agents standardized for hemoglobin levels and body weight, whereas it correlated with the erythropoietin demand index (plasma erythropoietin units divided by the hemoglobin value) in patients not receiving erythropoiesis-stimulating agents. Compared with sham-operated controls, wild-type mice with 5/6 subtotal nephrectomy (Nx), a remnant kidney model with advanced CKD, had decreased hemoglobin, hematocrit, and mean corpuscular volume values but increased erythrocyte and plasma ADMA and plasma erythropoietin levels. In comparison, dimethylarginine dimethlaminohydrolase-1 transgenic (DDAH-1 Tg) mice, which efficiently metabolized ADMA, had significant improvements in all of the values except those for erythropoietin after 5/6 Nx. Additionally, wild-type Nx mice, but not DDAH-1 Tg Nx mice, had reduced splenic gene expression of erythropoietin receptor and erythroferrone, which regulates iron metabolism in response to erythropoietin. This study suggests that erythrocyte ADMA accumulation contributes to impaired response to erythropoietin in predialysis patients and advanced CKD mice via suppression of erythropoietin receptor expression.Yokoro, MiyukiNakayama, YosukeYamagishi, Sho-ichiAndo, RyotaroSugiyama, MikiIto, SakuyaYano, JunkoTaguchi, KenseiKaida, YusukeSaigusa, DaisukeKimoto, MasumiAbe, TakaakiUeda, SeijiFukami, Kei2017-06-09T05:46:53-07:00doi:10.1681/ASN.2016111184hwp:resource-id:jnephrol;28/9/2670American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, erythropoietin, chronic kidney disease, nitric oxide, erythropoietin receptor, ADMABasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161111841046-66731533-34502017-06-09T05:46:53-07:002017-09Journal of the American Society of NephrologyBasic Research28926702680
- Janus Kinase 2 Regulates Transcription Factor EB Expression and Autophagy Completion in Glomerular PodocytesThe nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion. In cultured podocytes, knockdown of JAK2 similarly impaired autophagy and led to downregulation in the expression of lysosomal genes and decreased activity of the lysosomal enzyme, cathepsin D. Because transcription factor EB (TFEB) has recently emerged as a master regulator of autophagosome-lysosome function, controlling the expression of several of the genes downregulated by JAK2 knockdown, we questioned whether TFEB is regulated by JAK2. In immortalized mouse podocytes, JAK2 knockdown decreased TFEB promoter activity, expression, and nuclear localization. In silico analysis and chromatin immunoprecipitation assays revealed that the downstream mediator of JAK2 signaling STAT1 binds to the TFEB promoter. Finally, overexpression of TFEB in JAK2-deficient podocytes reversed lysosomal dysfunction and restored albumin permselectivity. Collectively, these observations highlight the homeostatic actions of JAK2 in podocytes and the importance of TFEB to autophagosome-lysosome function in these cells. These results also raise the possibility that therapeutically modulating TFEB activity may improve podocyte health in glomerular disease.10.1681/ASN.2016111208Wed, 19 Apr 2017 06:08:41 GMT-07:00Janus Kinase 2 Regulates Transcription Factor EB Expression and Autophagy Completion in Glomerular PodocytesThe nonreceptor kinase Janus kinase 2 (JAK2) has garnered attention as a promising therapeutic target for the treatment of CKD. However, being ubiquitously expressed in the adult, JAK2 is also likely to be necessary for normal organ function. Here, we investigated the phenotypic effects of JAK2 deficiency. Mice in which JAK2 had been deleted from podocytes exhibited an elevation in urine albumin excretion that was accompanied by increased podocyte autophagosome fractional volume and p62 aggregation, which are indicative of impaired autophagy completion. In cultured podocytes, knockdown of JAK2 similarly impaired autophagy and led to downregulation in the expression of lysosomal genes and decreased activity of the lysosomal enzyme, cathepsin D. Because transcription factor EB (TFEB) has recently emerged as a master regulator of autophagosome-lysosome function, controlling the expression of several of the genes downregulated by JAK2 knockdown, we questioned whether TFEB is regulated by JAK2. In immortalized mouse podocytes, JAK2 knockdown decreased TFEB promoter activity, expression, and nuclear localization. In silico analysis and chromatin immunoprecipitation assays revealed that the downstream mediator of JAK2 signaling STAT1 binds to the TFEB promoter. Finally, overexpression of TFEB in JAK2-deficient podocytes reversed lysosomal dysfunction and restored albumin permselectivity. Collectively, these observations highlight the homeostatic actions of JAK2 in podocytes and the importance of TFEB to autophagosome-lysosome function in these cells. These results also raise the possibility that therapeutically modulating TFEB activity may improve podocyte health in glomerular disease.Alghamdi, Tamadher A.Majumder, SyamantakThieme, KarinaBatchu, Sri N.White, Kathryn E.Liu, YouanBrijmohan, Angela S.Bowskill, Bridgit B.Advani, Suzanne L.Woo, MinnaAdvani, Andrew2017-04-19T06:08:41-07:00doi:10.1681/ASN.2016111208hwp:resource-id:jnephrol;28/9/2641American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, autophagy, JAK2, lysosomeBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161112081046-66731533-34502017-04-19T06:08:41-07:002017-09Journal of the American Society of NephrologyBasic Research28926412653
- Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin. Pharmacologic inhibition or shRNA knockdown of ILK prevented periostin-induced Akt/mammalian target of rapamycin (mTOR) signaling and ADPKD cell proliferation in vitro. Homozygous deletion of ILK in renal collecting ducts (CD) of Ilkfl/fl;Pkhd1-Cre mice caused tubule dilations, apoptosis, fibrosis, and organ failure by 10 weeks of age. By contrast, Ilkfl/+;Pkhd1-Cre mice had normal renal morphology and function and survived >1 year. Reduced expression of ILK in Pkd1fl/fl;Pkhd1-Cre mice, a rapidly progressive model of ADPKD, decreased renal Akt/mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis, and significantly improved renal function and animal survival. Additionally, CD-specific knockdown of ILK strikingly reduced renal cystic disease and fibrosis and extended the life of pcy/pcy mice, a slowly progressive PKD model. We conclude that ILK is critical for maintaining the CD epithelium and renal function and is a key intermediate for periostin activation of signaling pathways involved in cyst growth and fibrosis in PKD.10.1681/ASN.2016111235Thu, 18 May 2017 07:52:41 GMT-07:00Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin. Pharmacologic inhibition or shRNA knockdown of ILK prevented periostin-induced Akt/mammalian target of rapamycin (mTOR) signaling and ADPKD cell proliferation in vitro. Homozygous deletion of ILK in renal collecting ducts (CD) of Ilkfl/fl;Pkhd1-Cre mice caused tubule dilations, apoptosis, fibrosis, and organ failure by 10 weeks of age. By contrast, Ilkfl/+;Pkhd1-Cre mice had normal renal morphology and function and survived >1 year. Reduced expression of ILK in Pkd1fl/fl;Pkhd1-Cre mice, a rapidly progressive model of ADPKD, decreased renal Akt/mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis, and significantly improved renal function and animal survival. Additionally, CD-specific knockdown of ILK strikingly reduced renal cystic disease and fibrosis and extended the life of pcy/pcy mice, a slowly progressive PKD model. We conclude that ILK is critical for maintaining the CD epithelium and renal function and is a key intermediate for periostin activation of signaling pathways involved in cyst growth and fibrosis in PKD.Raman, ArchanaReif, Gail A.Dai, YuqiaoKhanna, AditiLi, XiaogangAstleford, LindsayParnell, Stephen C.Calvet, James P.Wallace, Darren P.2017-05-18T07:52:41-07:00doi:10.1681/ASN.2016111235hwp:resource-id:jnephrol;28/9/2708American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyILK, matricellular proteins, periostin, PKDBasic ResearchBasic Researchresearch-article20172017-09-01September 201710.1681/ASN.20161112351046-66731533-34502017-05-18T07:52:41-07:002017-09Journal of the American Society of NephrologyBasic Research28927082719
- Nephron Remodeling Underlies Hyperkalemia in Familial Hyperkalemic Hypertension10.1681/ASN.2017060660Thu, 13 Jul 2017 06:28:32 GMT-07:00Nephron Remodeling Underlies Hyperkalemia in Familial Hyperkalemic HypertensionMcCormick, James A.Ellison, David H.2017-07-13T06:28:32-07:00doi:10.1681/ASN.2017060660hwp:resource-id:jnephrol;28/9/2555American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperkalemia, sodium, chloride, thiazide, Gordon SyndromeUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-09-01September 201710.1681/ASN.20170606601046-66731533-34502017-07-13T06:28:32-07:002017-09Journal of the American Society of NephrologyUp Front Matters28992555259725572606
- CMV and BKPyV Infections in Renal Transplant Recipients Receiving an mTOR Inhibitor–Based Regimen Versus a CNI-Based Regimen: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials10.2215/CJN.13221216Fri, 02 Jun 2017 08:37:26 GMT-07:00CMV and BKPyV Infections in Renal Transplant Recipients Receiving an mTOR Inhibitor–Based Regimen Versus a CNI-Based Regimen: A Systematic Review and Meta-Analysis of Randomized, Controlled TrialsMallat, Samir G.Tanios, Bassem Y.Itani, Houssam S.Lotfi, TamaraMcMullan, CiaranGabardi, StevenAkl, Elie A.Azzi, Jamil R.2017-06-02T08:37:26-07:00doi:10.2215/CJN.13221216hwp:resource-id:clinjasn;12/8/1321American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyimmunosuppression, cytomegalovirus, Meta-analysis, Calcineurin inhibitor, BK virus, cyclosporine, tacrolimus, sirolimus, everolimus, Calcineurin, Calcineurin Inhibitors, Confidence Intervals, Cytomegalovirus Infections, glomerular filtration rate, Incidence, kidney transplantation, Odds Ratio, Polyomavirus, proteinuria, Randomized Controlled Trials as Topic, Risk, Assessment, Sirolimus, Wound HealingOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-08-07August 07, 201710.2215/CJN.132212161555-90411555-905X2017-06-02T08:37:26-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12813211336
- Post-Transplant Hypophosphatemia and the Risk of Death-Censored Graft Failure and Mortality after Kidney Transplantation10.2215/CJN.10270916Thu, 25 May 2017 07:13:50 GMT-07:00Post-Transplant Hypophosphatemia and the Risk of Death-Censored Graft Failure and Mortality after Kidney Transplantationvan Londen, MarcoAarts, Brigitte M.Deetman, Petronella E.van der Weijden, JessicaEisenga, Michele F.Navis, GerjanBakker, Stephan J. L.de Borst, Martin H.,2017-05-25T07:13:50-07:00doi:10.2215/CJN.10270916hwp:resource-id:clinjasn;12/8/1301American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypophosphatemia, graft survival, mortality, transplantation, chronic kidney disease-mineral and bone disorder, phosphate, Cardiovascular Diseases, Confidence Intervals, Follow-Up Studies, Humans, Hypophosphatemia, kidney transplantation, Longitudinal Studies, Phosphates, Proportional Hazards Models, Regression Analysis, Renal Insufficiency, Chronic, RiskOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-08-07August 07, 201710.2215/CJN.102709161555-90411555-905X2017-05-25T07:13:50-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12813011310
- Renal Toxicities of Novel Agents Used for Treatment of Multiple MyelomaSurvival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma.10.2215/CJN.06100616Wed, 21 Sep 2016 10:03:53 GMT-07:00Renal Toxicities of Novel Agents Used for Treatment of Multiple MyelomaSurvival for patients with multiple myeloma has significantly improved in the last decade in large part due to the development of proteasome inhibitors and immunomodulatory drugs. These next generation agents with novel mechanisms of action as well as targeted therapies are being used both in the preclinical and clinical settings for patients with myeloma. These agents include monoclonal antibodies, deacetylase inhibitors, kinase inhibitors, agents affecting various signaling pathways, immune check point inhibitors, and other targeted therapies. In some cases, off target effects of these therapies can lead to unanticipated effects on the kidney that can range from electrolyte disorders to AKI. In this review, we discuss the nephrotoxicities of novel agents currently in practice as well as in development for the treatment of myeloma.Wanchoo, RimdaAbudayyeh, AlaDoshi, MonaEdeani, AmakaGlezerman, Ilya G.Monga, DivyaRosner, MitchellJhaveri, Kenar D.2016-09-21T10:03:53-07:00doi:10.2215/CJN.06100616hwp:resource-id:clinjasn;12/1/176American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, cancer, chronic kidney disease, drug nephrotoxicity, Acute Kidney Injury, Antibodies, Monoclonal, Coal Tar, electrolytes, humans, kidney, multiple myeloma, Proteasome Inhibitors, Water-Electrolyte ImbalanceMini-ReviewMini-Reviewreview-article20162017-01-06January 06, 201710.2215/CJN.061006161555-90411555-905X2016-09-21T10:03:53-07:002017-01-06Clinical Journal of the American Society of NephrologyMini-Review121176189
- Blood Calcification Propensity, Cardiovascular Events, and Survival in Patients Receiving Hemodialysis in the EVOLVE Trial10.2215/CJN.04720416Fri, 09 Dec 2016 06:58:12 GMT-08:00Blood Calcification Propensity, Cardiovascular Events, and Survival in Patients Receiving Hemodialysis in the EVOLVE TrialPasch, AndreasBlock, Geoffrey A.Bachtler, MatthiasSmith, Edward R.Jahnen-Dechent, WilhelmArampatzis, SpyridonChertow, Glenn M.Parfrey, PatrickMa, XiaoyeFloege, Juergen2016-12-09T06:58:12-08:00doi:10.2215/CJN.04720416hwp:resource-id:clinjasn;12/2/315American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycalcification propensity, T50, calciprotein particles, CPP, hemodialysis, EVOLVE, angina, unstable, bicarbonates, cholesterol, HDL, cinacalcet hydrochloride, creatinine, follow-up studies, heart failure, hematologic tests, hospitalization, humans, myocardial infarction, phosphates, prospective studies, renal dialysis, serum albuminOriginal ArticlesMineral Metabolism/Bone DiseaseOriginal ArticlesMineral Metabolism/Bone Diseaseresearch-article20172017-02-07February 07, 201710.2215/CJN.047204161555-90411555-905X2016-12-09T06:58:12-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122315322
- Cardiovascular Phenotypes in Children with CKD: The 4C Study10.2215/CJN.01090216Tue, 08 Nov 2016 11:03:47 GMT-08:00Cardiovascular Phenotypes in Children with CKD: The 4C StudySchaefer, FranzDoyon, AnkeAzukaitis, KarolisBayazit, AysunCanpolat, NurDuzova, AliNiemirska, AnaSözeri, BetulThurn, DanielaAnarat, AliRanchin, BrunoLitwin, MieczyslavCaliskan, SalimCandan, CengizBaskin, EsraYilmaz, EbruMir, SevgiKirchner, MariettaSander, AnjaHaffner, DieterMelk, AnetteWühl, ElkeShroff, RukshanaQuerfeld, Uwe2016-11-08T11:03:47-08:00doi:10.2215/CJN.01090216hwp:resource-id:clinjasn;12/1/19American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyleft ventricular hypertrophy, arteriosclerosis, pulse wave velocity, Biomarkers, blood pressure, Blood Pressure Monitoring, Ambulatory, Body Mass Index, Carotid Intima-Media Thickness, Child, Comorbidity, Europe, glomerular filtration rate, Hemoglobins, Humans, hypertension, Hypertrophy, Left Ventricular, Phenotype, Phosphorus, Phosphorus, Dietary, Prevalence, Prospective Studies, Pulse Wave Analysis, Renal Insufficiency, Chronic, vesico-ureteral refluxOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162017-01-06January 06, 201710.2215/CJN.010902161555-90411555-905X2016-11-08T11:03:47-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1211928
- Interlaboratory Variability in Plasma Creatinine Measurement and the Relation with Estimated Glomerular Filtration Rate and Chronic Kidney Disease Diagnosis10.2215/CJN.05400516Tue, 08 Nov 2016 11:03:49 GMT-08:00Interlaboratory Variability in Plasma Creatinine Measurement and the Relation with Estimated Glomerular Filtration Rate and Chronic Kidney Disease DiagnosisLee, ElizabethCollier, Christine P.White, Christine A.2016-11-08T11:03:49-08:00doi:10.2215/CJN.05400516hwp:resource-id:clinjasn;12/1/29American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical laboratory techniques, African Americans, creatinine, enzyme assays, female, glomerular filtration rate, humans, intensive care units, kidney function tests, renal insufficiency, chronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162017-01-06January 06, 201710.2215/CJN.054005161555-90411555-905X2016-11-08T11:03:49-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1212937
- Viral-Associated GN: Hepatitis C and HIVViruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%–30% of all HIV patients are coinfected with HCV and 5%–10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under “postinfectious” GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage.10.2215/CJN.04320416Mon, 24 Oct 2016 08:02:50 GMT-07:00Viral-Associated GN: Hepatitis C and HIVViruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%–30% of all HIV patients are coinfected with HCV and 5%–10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under “postinfectious” GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage.Kupin, Warren L.2016-10-24T08:02:50-07:00doi:10.2215/CJN.04320416hwp:resource-id:clinjasn;12/8/1337American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGlomerulonephritis, hantavirus kidney, polyarteritis nodosa HCV, focal segmental glomerulosclerosis, APOL1, Antigen-Antibody Complex, Antigens, Viral, Antiviral Agents, Carrier State, Coinfection, Diagnosis, Differential, Glomerular Basement Membrane, HIV Infections, Hepacivirus, Hepatitis C, Humans, Immune System, ViremiaGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-08-07August 07, 201710.2215/CJN.043204161555-90411555-905X2016-10-24T08:02:50-07:002017-08-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician12813371342
- Nephrotic Syndrome Post–Kidney Transplant10.2215/CJN.01200117Thu, 08 Jun 2017 06:52:21 GMT-07:00Nephrotic Syndrome Post–Kidney TransplantHennigar, Randolph A.Klein, Christina L.2017-06-08T06:52:21-07:00doi:10.2215/CJN.01200117hwp:resource-id:clinjasn;12/8/1347American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulopathy, collapsing FSGS, transplantation, kidney, nephrotic syndrome, Transplants, collapsing focal segmental, glomerulosclerosisKidney Case ConferencesClinicopathologic ConferenceKidney Case ConferencesClinicopathologic Conferenceresearch-article20172017-08-07August 07, 201710.2215/CJN.012001171555-90411555-905X2017-06-08T06:52:21-07:002017-08-07Clinical Journal of the American Society of NephrologyKidney Case Conferences12813471350
- Polyuria in a Patient with Aspergillus Infection10.2215/CJN.12791216Mon, 13 Mar 2017 07:21:33 GMT-07:00Polyuria in a Patient with Aspergillus InfectionRosner, Mitchell H.2017-03-13T07:21:33-07:00doi:10.2215/CJN.12791216hwp:resource-id:clinjasn;12/8/1343American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyamphotericin, polyuria, diabetes insipidus, hypokalemia, electrolytes, nephrology, Surveys and QuestionnairesKidney Case ConferencesNephrology Quiz and QuestionnaireKidney Case ConferencesNephrology Quiz and Questionnaireresearch-article20172017-08-07August 07, 201710.2215/CJN.127912161555-90411555-905X2017-03-13T07:21:33-07:002017-08-07Clinical Journal of the American Society of NephrologyKidney Case Conferences12813431346
- Characteristics and Outcomes of Patients Discharged Home from an Emergency Department with AKI10.2215/CJN.10431016Thu, 20 Jul 2017 01:51:38 GMT-07:00Characteristics and Outcomes of Patients Discharged Home from an Emergency Department with AKIAcedillo, Rey R.Wald, RonMcArthur, EricNash, Danielle MarieSilver, Samuel A.James, Matthew T.Schull, Michael J.Siew, Edward D.Matheny, Michael E.House, Andrew A.Garg, Amit X.2017-07-20T13:51:38-07:00doi:10.2215/CJN.10431016hwp:resource-id:clinjasn;12/8/1215American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Aged, Canada, Confidence Intervals, creatinine, Emergency Service, Hospital, hospitalization, Humans, Kidney Function Tests, Ontario, Patient Discharge, Propensity Score, renal dialysis, Retrospective Studies, RiskOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20172017-08-07August 07, 201710.2215/CJN.104310161555-90411555-905X2017-07-20T13:51:38-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12881215120312251205
- Temporal Trends and Factors Associated with Home Hemodialysis Technique Survival in Canada10.2215/CJN.13271216Mon, 24 Jul 2017 06:07:48 GMT-07:00Temporal Trends and Factors Associated with Home Hemodialysis Technique Survival in CanadaPerl, JeffreyNa, YingboTennankore, Karthik K.Chan, Christopher T.2017-07-24T06:07:48-07:00doi:10.2215/CJN.13271216hwp:resource-id:clinjasn;12/8/1248American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, survival, technique survival, home hemodialysis, short daily hemodialysis, slow nocturnal hemodialysis, Canadian Organ Replacement Register, Technique Failure, Dialysis Modality Discontinuation, Home Dialysis Discontinuation, Canada, Comorbidity, Death, diabetes mellitus, Hemodialysis, Home, Humans, kidney transplantation, Proportional Hazards Models, risk factors, SmokingOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-08-07August 07, 201710.2215/CJN.132712161555-90411555-905X2017-07-24T06:07:48-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12881248120912581211
- The Possibilities to Improve Kidney Health with Proteomics10.2215/CJN.06200617Fri, 21 Jul 2017 06:03:08 GMT-07:00The Possibilities to Improve Kidney Health with ProteomicsHallan, Stein Ivar2017-07-21T06:03:08-07:00doi:10.2215/CJN.06200617hwp:resource-id:clinjasn;12/8/1206American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyElectrophoresis, Gel, Two-Dimensional, kidney, ProteomicsEditorialsEditorialseditorial20172017-08-07August 07, 201710.2215/CJN.062006171555-90411555-905X2017-07-21T06:03:08-07:002017-08-07Clinical Journal of the American Society of NephrologyEditorials12881206122612081235
- Quality Assurance Audit of Technique Failure and 90-Day Mortality after Program Discharge in a Canadian Home Hemodialysis Program10.2215/CJN.00140117Mon, 24 Jul 2017 06:07:46 GMT-07:00Quality Assurance Audit of Technique Failure and 90-Day Mortality after Program Discharge in a Canadian Home Hemodialysis ProgramShah, NikhilReintjes, FrancesCourtney, MarkKlarenbach, Scott W.Ye, FengSchick-Makaroff, KaraJindal, KailashPauly, Robert P.2017-07-24T06:07:46-07:00doi:10.2215/CJN.00140117hwp:resource-id:clinjasn;12/8/1259American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymortality, intensive hemodialysis, modality conversion, transplantation, program exits, technique failure, technique survival, Home hemodialysis, training failure, therapy cessation, treatment discontinuation, Burnout, Professional, Canada, Caregivers, Hemodialysis, Home, hospitalization, Humans, Patient Care Team, Patient Discharge, Prevalence, renal dialysis, Vital StatisticsOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-08-07August 07, 201710.2215/CJN.001401171555-90411555-905X2017-07-24T06:07:46-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12881259120912641211
- Thyroid Status, Quality of Life, and Mental Health in Patients on Hemodialysis10.2215/CJN.13211216Thu, 13 Jul 2017 06:25:56 GMT-07:00Thyroid Status, Quality of Life, and Mental Health in Patients on HemodialysisRhee, Connie M.Chen, YanjunYou, Amy S.Brunelli, Steven M.Kovesdy, Csaba P.Budoff, Matthew J.Brent, Gregory A.Kalantar-Zadeh, KamyarNguyen, Danh V.2017-07-13T06:25:56-07:00doi:10.2215/CJN.13211216hwp:resource-id:clinjasn;12/8/1274American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyThyroid function, Thyrotropin, Mental health, hemodialysis, depression, Depressive Disorder, Fatigue, Humans, Hypothyroidism, Mental Health, Outpatients, Pain, Prospective Studies, quality of life, renal dialysis, risk factors, Surveys and QuestionnairesOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-08-07August 07, 201710.2215/CJN.132112161555-90411555-905X2017-07-13T06:25:56-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12812741283
- Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft Nephropathy10.2215/CJN.05300516Tue, 23 May 2017 06:39:01 GMT-07:00Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft NephropathyMedeiros, MaraVelásquez-Jones, LuisHernández, Ana M.Ramón-García, GuillermoValverde, SaúlFuentes, YolandaVargas, ArindalPatiño, MauricioPérez-Villalva, RosalbaOrtega-Trejo, Juan AntonioBarrera-Chimal, JonatanBobadilla, Norma A.2017-05-23T06:39:01-07:00doi:10.2215/CJN.05300516hwp:resource-id:clinjasn;12/8/1291American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-08-07August 07, 201710.2215/CJN.053005161555-90411555-905X2017-05-23T06:39:01-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12812911300
- Analytic Considerations for Repeated Measures of eGFR in Cohort Studies of CKDRepeated measures of various biomarkers provide opportunities for us to enhance understanding of many important clinical aspects of CKD, including patterns of disease progression, rates of kidney function decline under different risk factors, and the degree of heterogeneity in disease manifestations across patients. However, because of unique features, such as correlations across visits and time dependency, these data must be appropriately handled using longitudinal data analysis methods. We provide a general overview of the characteristics of data collected in cohort studies and compare appropriate statistical methods for the analysis of longitudinal exposures and outcomes. We use examples from the Chronic Renal Insufficiency Cohort Study to illustrate these methods. More specifically, we model longitudinal kidney outcomes over annual clinical visits and assess the association with both baseline and longitudinal risk factors.10.2215/CJN.11311116Thu, 27 Jul 2017 09:44:22 GMT-07:00Analytic Considerations for Repeated Measures of eGFR in Cohort Studies of CKDRepeated measures of various biomarkers provide opportunities for us to enhance understanding of many important clinical aspects of CKD, including patterns of disease progression, rates of kidney function decline under different risk factors, and the degree of heterogeneity in disease manifestations across patients. However, because of unique features, such as correlations across visits and time dependency, these data must be appropriately handled using longitudinal data analysis methods. We provide a general overview of the characteristics of data collected in cohort studies and compare appropriate statistical methods for the analysis of longitudinal exposures and outcomes. We use examples from the Chronic Renal Insufficiency Cohort Study to illustrate these methods. More specifically, we model longitudinal kidney outcomes over annual clinical visits and assess the association with both baseline and longitudinal risk factors.Shou, HaochangHsu, Jesse Y.Xie, DaweiYang, WeiRoy, JasonAnderson, Amanda H.Landis, J. RichardFeldman, Harold I.Parsa, AfshinJepson, Christopher,2017-07-27T09:44:22-07:00doi:10.2215/CJN.11311116hwp:resource-id:clinjasn;12/8/1357American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, longitudinal data, repeated measures, GEE, mixed effects model, correlation structures, Biomarkers, Cohort Studies, Disease Progression, GFR, Humans, kidney, Renal Insufficiency, Chronic, risk factorsFeatureFeatureresearch-article20172017-08-07August 07, 201710.2215/CJN.113111161555-90411555-905X2017-07-27T09:44:22-07:002017-08-07Clinical Journal of the American Society of NephrologyFeature12813571365
- Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones10.2215/CJN.01420217Fri, 02 Jun 2017 08:37:27 GMT-07:00Low Bone Density and Bisphosphonate Use and the Risk of Kidney StonesProchaska, MeganTaylor, EricVaidya, AnandCurhan, Gary2017-06-02T08:37:27-07:00doi:10.2215/CJN.01420217hwp:resource-id:clinjasn;12/8/1284American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBody Mass Index, Bone Density, Calcium, Dietary, Cross-Sectional Studies, Diphosphonates, Epidemiologic Studies, Female, Follow-Up Studies, Humans, Kidney Calculi, Linear Models, Proportional Hazards Models, Prospective Studies, Risk Assessment, risk factors, ThiazidesOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20172017-08-07August 07, 201710.2215/CJN.014202171555-90411555-905X2017-06-02T08:37:27-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12812841290
- Reconfiguring Health Care Delivery to Improve AKI Outcomes10.2215/CJN.05940617Thu, 20 Jul 2017 01:51:36 GMT-07:00Reconfiguring Health Care Delivery to Improve AKI OutcomesKoyner, Jay L.2017-07-20T13:51:36-07:00doi:10.2215/CJN.05940617hwp:resource-id:clinjasn;12/8/1203American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, Epidemiology and outcomes, dialysis, Acute Kidney Injury, Delivery of Health CareEditorialsEditorialseditorial20172017-08-07August 07, 201710.2215/CJN.059406171555-90411555-905X2017-07-20T13:51:36-07:002017-08-07Clinical Journal of the American Society of NephrologyEditorials12881203121512051225
- Building an Ideal Quality Metric for ESRD Health Care Delivery10.2215/CJN.01020117Wed, 17 May 2017 05:38:17 GMT-07:00Building an Ideal Quality Metric for ESRD Health Care DeliverySchold, Jesse D.Buccini, Laura D.Phelan, Michael P.Jay, Colleen L.Goldfarb, David A.Poggio, Emilio D.Sedor, John R.2017-05-17T05:38:17-07:00doi:10.2215/CJN.01020117hwp:resource-id:clinjasn;12/8/1351American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyquality, performance evaluations, report cards, ESRD, transplantation, survival, Delivery of Health Care, Kidney Failure, ChronicCommentaryCommentaryarticle-commentary20172017-08-07August 07, 201710.2215/CJN.010201171555-90411555-905X2017-05-17T05:38:17-07:002017-08-07Clinical Journal of the American Society of NephrologyCommentary12813511356
- Outcomes of Deceased Donor Kidney Offers to Patients at the Top of the Waiting List10.2215/CJN.10130916Thu, 27 Jul 2017 09:44:23 GMT-07:00Outcomes of Deceased Donor Kidney Offers to Patients at the Top of the Waiting ListHuml, Anne M.Albert, Jeffrey M.Thornton, J. DarylSehgal, Ashwini R.2017-07-27T09:44:23-07:00doi:10.2215/CJN.10130916hwp:resource-id:clinjasn;12/8/1311American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologywaiting list, deceased donor offer, kidney transplantationOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-08-07August 07, 201710.2215/CJN.101309161555-90411555-905X2017-07-27T09:44:23-07:002017-08-07Clinical Journal of the American Society of NephrologyOriginal Articles12881311121213201214
- Maintaining Patients on Home Hemodialysis: The Journey Matters as Does the Destination10.2215/CJN.06890617Mon, 24 Jul 2017 06:07:46 GMT-07:00Maintaining Patients on Home Hemodialysis: The Journey Matters as Does the DestinationShafi, TariqJaar, Bernard G.2017-07-24T06:07:46-07:00doi:10.2215/CJN.06890617hwp:resource-id:clinjasn;12/8/1209American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhome dialysis, patient-centered care, nocturnal hemodialysis, frequent hemodialysis, Technique failure, training, survival, Hemodialysis, Home, Maintenance, Humans, Kidney Failure, ChronicEditorialsEditorialseditorial20172017-08-07August 07, 201710.2215/CJN.068906171555-90411555-905X2017-07-24T06:07:46-07:002017-08-07Clinical Journal of the American Society of NephrologyEditorials12888120912481259121112581264
- Chronic Fluid Overload and Mortality in ESRDSustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status. Analyses were applied across three discrete systolic BP (syst-BP) categories (<130, 130–160, and >160 mmHg), with nonoverhydrated patients with syst-BP=130–160 mmHg as the reference category; >200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (<130 mmHg: hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.38 to 1.65; 130–160 mmHg: HR, 1.25; 95% CI, 1.16 to 1.36; >160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all P<0.001). However, cumulative 1-year FO exposure predicted a higher death risk (P<0.001) across all syst-BP categories (<130 mmHg: HR, 1.94; 95% CI, 1.68 to 2.23; 130–160 mmHg: HR, 1.51; 95% CI, 1.35 to 1.69; >160 mmHg: HR, 1.62; 95% CI, 1.39 to 1.90). In conclusion, chronic exposure to FO in ESRD is a strong risk factor for death across discrete BP categories. Whether treatment policies that account for fluid status monitoring are preferable to policies that account solely for predialysis BP measurements remains to be tested in a clinical trial.10.1681/ASN.2016121341Thu, 04 May 2017 06:04:53 GMT-07:00Chronic Fluid Overload and Mortality in ESRDSustained fluid overload (FO) is considered a major cause of hypertension, heart failure, and mortality in patients with ESRD on maintenance hemodialysis. However, there has not been a cohort study investigating the relationship between chronic exposure to FO and mortality in this population. We studied the relationship of baseline and cumulative FO exposure over 1 year with mortality in 39,566 patients with incident ESRD in a large dialysis network in 26 countries using whole-body bioimpedance spectroscopy to assess fluid status. Analyses were applied across three discrete systolic BP (syst-BP) categories (<130, 130–160, and >160 mmHg), with nonoverhydrated patients with syst-BP=130–160 mmHg as the reference category; >200,000 FO measurements were performed over follow-up. Baseline FO value predicted excess risk of mortality across syst-BP categories (<130 mmHg: hazard ratio [HR], 1.51; 95% confidence interval [95% CI], 1.38 to 1.65; 130–160 mmHg: HR, 1.25; 95% CI, 1.16 to 1.36; >160 mmHg: HR, 1.30; 95% CI, 1.19 to 1.42; all P<0.001). However, cumulative 1-year FO exposure predicted a higher death risk (P<0.001) across all syst-BP categories (<130 mmHg: HR, 1.94; 95% CI, 1.68 to 2.23; 130–160 mmHg: HR, 1.51; 95% CI, 1.35 to 1.69; >160 mmHg: HR, 1.62; 95% CI, 1.39 to 1.90). In conclusion, chronic exposure to FO in ESRD is a strong risk factor for death across discrete BP categories. Whether treatment policies that account for fluid status monitoring are preferable to policies that account solely for predialysis BP measurements remains to be tested in a clinical trial.Zoccali, CarmineMoissl, UlrichChazot, CharlesMallamaci, FrancescaTripepi, GiovanniArkossy, OttoWabel, PeterStuard, Stefano2017-05-04T06:04:53-07:00doi:10.1681/ASN.2016121341hwp:resource-id:jnephrol;28/8/2491American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyEpidemiology and outcomes, blood pressure, VOLUME EXPANSION, ESRD, hemodialysis, mortality riskClinical EpidemiologyClinical Epidemiologyresearch-article20172017-08-01August 201710.1681/ASN.20161213411046-66731533-34502017-05-04T06:04:53-07:002017-08Journal of the American Society of NephrologyClinical Epidemiology28882491226024972262
- Urine Ammonium and Preclinical Acidosis in CKD10.1681/ASN.2017040470Mon, 19 Jun 2017 06:25:10 GMT-07:00Urine Ammonium and Preclinical Acidosis in CKDDuBose, Thomas D.2017-06-19T06:25:10-07:00doi:10.1681/ASN.2017040470hwp:resource-id:jnephrol;28/8/2258American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis, Cell Signaling, chronic kidney disease, chronic metabolic acidosis, complementUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-08-01August 201710.1681/ASN.20170404701046-66731533-34502017-06-19T06:25:10-07:002017-08Journal of the American Society of NephrologyUp Front Matters28882258248322602490
- Therapeutic Considerations for Antihyperglycemic Agents in Diabetic Kidney DiseaseDiabetic kidney disease is among the most frequent complications of diabetes, with approximately 50% of patients with ESRD attributed to diabetes in developed countries. Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced GFR in patients with diabetes, conservative dose selection and adjustment of antihyperglycemic medications are necessary to balance glycemic control with safety. A growing body of literature is providing valuable insight into the cardiovascular and renal safety and efficacy of newer antihyperglycemic medications in the dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, and sodium-glucose cotransporter 2 inhibitor classes of medications. Ongoing studies will continue to inform future use of these agents in patients with diabetic kidney disease.10.1681/ASN.2016121372Tue, 02 May 2017 07:10:33 GMT-07:00Therapeutic Considerations for Antihyperglycemic Agents in Diabetic Kidney DiseaseDiabetic kidney disease is among the most frequent complications of diabetes, with approximately 50% of patients with ESRD attributed to diabetes in developed countries. Although intensive glycemic management has been shown to delay the onset and progression of increased urinary albumin excretion and reduced GFR in patients with diabetes, conservative dose selection and adjustment of antihyperglycemic medications are necessary to balance glycemic control with safety. A growing body of literature is providing valuable insight into the cardiovascular and renal safety and efficacy of newer antihyperglycemic medications in the dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, and sodium-glucose cotransporter 2 inhibitor classes of medications. Ongoing studies will continue to inform future use of these agents in patients with diabetic kidney disease.Neumiller, Joshua J.Alicic, Radica Z.Tuttle, Katherine R.2017-05-02T07:10:33-07:00doi:10.1681/ASN.2016121372hwp:resource-id:jnephrol;28/8/2263American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes mellitus, renal protection, diabetesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-08-01August 201710.1681/ASN.20161213721046-66731533-34502017-05-02T07:10:33-07:002017-08Journal of the American Society of NephrologyUp Front Matters28822632274
- Endothelium-Neutrophil Communication via B1-Kinin Receptor–Bearing Microvesicles in Vasculitis10.1681/ASN.2017030300Fri, 14 Jul 2017 08:52:31 GMT-07:00Endothelium-Neutrophil Communication via B1-Kinin Receptor–Bearing Microvesicles in VasculitisTharaux, Pierre-LouisDhaun, Neeraj2017-07-14T08:52:31-07:00doi:10.1681/ASN.2017030300hwp:resource-id:jnephrol;28/8/2255American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyendothelium, Henoch-Schonlein Purpura, Immunology and pathology, vasculitis, bradykinin, microvesiclesUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-08-01August 201710.1681/ASN.20170303001046-66731533-34502017-07-14T08:52:31-07:002017-08Journal of the American Society of NephrologyUp Front Matters2828889225524722824225824812824
- Clinical and Genetic Spectrum of Bartter Syndrome Type 3Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1–41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.10.1681/ASN.2016101057Wed, 05 Apr 2017 06:47:12 GMT-07:00Clinical and Genetic Spectrum of Bartter Syndrome Type 3Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1–41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.Seys, ElsaAndrini, OlgaKeck, MathildeMansour-Hendili, LamisseCourand, Pierre-YvesSimian, ChristopheDeschenes, GeorgesKwon, TheresaBertholet-Thomas, AuréliaBobrie, GuillaumeBorde, Jean SébastienBourdat-Michel, GuylhèneDecramer, StéphaneCailliez, MathildeKrug, PaulineCozette, PaulDelbet, Jean DanielDubourg, LaurenceChaveau, DominiqueFila, MarcJourde-Chiche, NoémieKnebelmann, BertrandLavocat, Marie-PierreLemoine, SandrineDjeddi, DjamalLlanas, BrigitteLouillet, FerielleMerieau, ElodieMileva, MariaMota-Vieira, LuisaMousson, ChristianeNobili, FrançoisNovo, RobertRoussey-Kesler, GwenaëlleVrillon, IsabelleWalsh, Stephen B.Teulon, JacquesBlanchard, AnneVargas-Poussou, Rosa2017-04-05T06:47:12-07:00doi:10.1681/ASN.2016101057hwp:resource-id:jnephrol;28/8/2540American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyBartter-s syndrome, chronic kidney disease, human genetics, proteinuriaClinical ResearchClinical Researchresearch-article20172017-08-01August 201710.1681/ASN.20161010571046-66731533-34502017-04-05T06:47:12-07:002017-08Journal of the American Society of NephrologyClinical Research28825402552
- Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene (PMM2), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic β cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy.10.1681/ASN.2016121312Mon, 03 Apr 2017 06:18:22 GMT-07:00Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene (PMM2), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic β cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2. We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy.Cabezas, Oscar RubioFlanagan, Sarah E.Stanescu, HoriaGarcía-Martínez, ElenaCaswell, RichardLango-Allen, HanaAntón-Gamero, MontserratArgente, JesúsBussell, Anna-MarieBrandli, AndreCheshire, ChrisCrowne, ElizabethDumitriu, SimonaDrynda, RobertHamilton-Shield, Julian PHayes, WesleyHofherr, AlexisIancu, DanielaIssler, NaomiJefferies, CraigJones, PeterJohnson, MatthewKesselheim, AnneKlootwijk, EnrikoKoettgen, MichaelLewis, WendyMartos, José MaríaMozere, MonikaNorman, JillPatel, VakshaParrish, AndrewPérez-Cerdá, CeliaPozo, JesúsRahman, Sofia ASebire, NeilTekman, MehmetTurnpenny, Peter D.Hoff, William van’tViering, Daan H.H.M.Weedon, Michael N.Wilson, PatriciaGuay-Woodford, LisaKleta, RobertHussain, KhalidEllard, SianBockenhauer, Detlef2017-04-03T06:18:22-07:00doi:10.1681/ASN.2016121312hwp:resource-id:jnephrol;28/8/2529American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, hyperinsulinemic hypoglycemia, glycosylation, promoter, PMM2, ZNF143Clinical ResearchClinical Researchresearch-article20172017-08-01August 201710.1681/ASN.20161213121046-66731533-34502017-04-03T06:18:22-07:002017-08Journal of the American Society of NephrologyClinical Research28825292539
- Understanding Medication Nonadherence after Kidney TransplantAlloimmunity remains a barrier to long-term graft survival that necessitates lifelong immunosuppressive therapy after renal transplant. Medication nonadherence has been increasingly recognized as a major impediment to achieving effective immunosuppression. Electronic medication monitoring further reveals that nonadherence manifests early after transplant, although the effect is delayed. The etiology of nonadherence is multifactorial, with the strongest risk factors including past nonadherence and being an adolescent or young adult. Other risk factors with smaller but consistently important effects include minority race/ethnicity, poor social supports, and poor perceived health. In children, risk factors related to parental and child psychologic and behavioral functioning and parental distress and burden are also important. Qualitative systematic reviews highlight the need to tailor interventions to each transplant recipient’s unique needs, motivations, and barriers rather than offer a one size fits all approach. To date, relatively few interventions have been studied, and most studies conducted were underpowered to allow definitive conclusions. If the kidney transplant community’s goal of “one transplant for life” is to become a reality, then solutions for medication nonadherence must be found and implemented.10.1681/ASN.2017020216Mon, 19 Jun 2017 06:25:11 GMT-07:00Understanding Medication Nonadherence after Kidney TransplantAlloimmunity remains a barrier to long-term graft survival that necessitates lifelong immunosuppressive therapy after renal transplant. Medication nonadherence has been increasingly recognized as a major impediment to achieving effective immunosuppression. Electronic medication monitoring further reveals that nonadherence manifests early after transplant, although the effect is delayed. The etiology of nonadherence is multifactorial, with the strongest risk factors including past nonadherence and being an adolescent or young adult. Other risk factors with smaller but consistently important effects include minority race/ethnicity, poor social supports, and poor perceived health. In children, risk factors related to parental and child psychologic and behavioral functioning and parental distress and burden are also important. Qualitative systematic reviews highlight the need to tailor interventions to each transplant recipient’s unique needs, motivations, and barriers rather than offer a one size fits all approach. To date, relatively few interventions have been studied, and most studies conducted were underpowered to allow definitive conclusions. If the kidney transplant community’s goal of “one transplant for life” is to become a reality, then solutions for medication nonadherence must be found and implemented.Nevins, Thomas E.Nickerson, Peter W.Dew, Mary Amanda2017-06-19T06:25:11-07:00doi:10.1681/ASN.2017020216hwp:resource-id:jnephrol;28/8/2290American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, transplant outcomes, rejectionUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-08-01August 201710.1681/ASN.20170202161046-66731533-34502017-06-19T06:25:11-07:002017-08Journal of the American Society of NephrologyUp Front Matters28822902301
- Erythropoietin Receptor-Mediated Molecular Crosstalk Promotes T Cell Immunoregulation and Transplant SurvivalAlthough spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4+ T cells into functional Foxp3+ regulatory T cells (Treg). In murine transplant models, pharmacologic downregulation of kidney-derived EPO prevented spontaneous Treg generation. In a controlled, prospective cohort clinical study, EPO administration at doses used to correct anemia augmented the frequency of peripheral CD4+CD25+CD127lo T cells in humans with CKD. Furthermore, EPO directly inhibited conventional T cell proliferation in vitro via tyrosine phosphatase SHP-1–dependent uncoupling of IL-2Rβ signaling. Conversely, EPO-initiated signals facilitated Treg proliferation by augmenting IL-2Rγ signaling and maintaining constitutively quenched IL-2Rβ signaling. In additional murine transplant models, recombinant EPO administration prolonged heart allograft survival, whereas pharmacologic downregulation of kidney-derived EPO reduced the expression of TGFβ mRNA and abrogated kidney allograft acceptance. Together, our findings delineate the protolerogenic properties of EPO in inhibiting conventional T cells while simultaneously promoting Treg induction, and suggest that manipulating the EPO/EPO receptor signaling axis could be exploited to prevent and/or treat T cell-mediated pathologies, including transplant rejection.10.1681/ASN.2016101100Thu, 16 Mar 2017 07:18:00 GMT-07:00Erythropoietin Receptor-Mediated Molecular Crosstalk Promotes T Cell Immunoregulation and Transplant SurvivalAlthough spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally in humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by the adult kidney, has immunomodulating properties that are required for spontaneous kidney graft acceptance. In vitro, in a manner dependent on the EPO receptor and CD131 on antigen-presenting cells, EPO induced the secretion of active TGFβ by antigen-presenting cells, which in turn converted naïve CD4+ T cells into functional Foxp3+ regulatory T cells (Treg). In murine transplant models, pharmacologic downregulation of kidney-derived EPO prevented spontaneous Treg generation. In a controlled, prospective cohort clinical study, EPO administration at doses used to correct anemia augmented the frequency of peripheral CD4+CD25+CD127lo T cells in humans with CKD. Furthermore, EPO directly inhibited conventional T cell proliferation in vitro via tyrosine phosphatase SHP-1–dependent uncoupling of IL-2Rβ signaling. Conversely, EPO-initiated signals facilitated Treg proliferation by augmenting IL-2Rγ signaling and maintaining constitutively quenched IL-2Rβ signaling. In additional murine transplant models, recombinant EPO administration prolonged heart allograft survival, whereas pharmacologic downregulation of kidney-derived EPO reduced the expression of TGFβ mRNA and abrogated kidney allograft acceptance. Together, our findings delineate the protolerogenic properties of EPO in inhibiting conventional T cells while simultaneously promoting Treg induction, and suggest that manipulating the EPO/EPO receptor signaling axis could be exploited to prevent and/or treat T cell-mediated pathologies, including transplant rejection.Purroy, CarolinaFairchild, Robert L.Tanaka, ToshiakiBaldwin, William M.Manrique, JoaquinMadsen, Joren C.Colvin, Robert B.Alessandrini, AlessandroBlazar, Bruce R.Fribourg, MiguelDonadei, ChiaraMaggiore, UmbertoHeeger, Peter S.Cravedi, Paolo2017-03-16T07:18:00-07:00doi:10.1681/ASN.2016101100hwp:resource-id:jnephrol;28/8/2377American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyerythropoietin, transplantation, acute allograft rejection, Regulatory T cellBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20161011001046-66731533-34502017-03-16T07:18:00-07:002017-08Journal of the American Society of NephrologyBasic Research28823772392
- Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United StatesLower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001–2005 period and the 2011–2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.10.1681/ASN.2016050543Tue, 07 Mar 2017 06:25:48 GMT-08:00Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United StatesLower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001–2005 period and the 2011–2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.Huang, YihungTilea, AncaGillespie, BrendaShahinian, VahaknBanerjee, TanushreeGrubbs, VanessaPowe, NeilRios-Burrows, NilkaPavkov, MedaSaran, Rajiv2017-03-07T06:25:48-08:00doi:10.1681/ASN.2016050543hwp:resource-id:jnephrol;28/8/2498American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, transplantation, glomerular filtration rateClinical EpidemiologyClinical Epidemiologyresearch-article20172017-08-01August 201710.1681/ASN.20160505431046-66731533-34502017-03-07T06:25:48-08:002017-08Journal of the American Society of NephrologyClinical Epidemiology28824982510
- C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial MicrovesiclesThe kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor–depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.10.1681/ASN.2016060637Mon, 13 Mar 2017 07:26:32 GMT-07:00C1-Inhibitor Decreases the Release of Vasculitis-Like Chemotactic Endothelial MicrovesiclesThe kinin system is activated during vasculitis and may contribute to chronic inflammation. C1-inhibitor is the main inhibitor of the kinin system. In this study, we investigated the presence of the kinin B1 receptor on endothelial microvesicles and its contribution to the inflammatory process. Compared with controls (n=15), patients with acute vasculitis (n=12) had markedly higher levels of circulating endothelial microvesicles, identified by flow cytometry analysis, and significantly more microvesicles that were positive for the kinin B1 receptor (P<0.001). Compared with microvesicles from wild-type cells, B1 receptor-positive microvesicles derived from transfected human embryonic kidney cells induced a significant neutrophil chemotactic effect, and a B1 receptor antagonist blocked this effect. Likewise, patient plasma induced neutrophil chemotaxis, an effect decreased by reduction of microvesicle levels and by blocking the B1 receptor. We used a perfusion system to study the effect of patient plasma (n=6) and control plasma (n=6) on the release of microvesicles from glomerular endothelial cells. Patient samples induced the release of significantly more B1 receptor-positive endothelial microvesicles than control samples, an effect abrogated by reduction of the microvesicles in the perfused samples. Perfusion of C1-inhibitor–depleted plasma over glomerular endothelial cells promoted excessive release of B1 receptor-positive endothelial microvesicles compared with normal plasma, an effect significantly decreased by addition of C1-inhibitor or B1 receptor-antagonist. Thus, B1 receptor-positive endothelial microvesicles may contribute to chronic inflammation by inducing neutrophil chemotaxis, and the reduction of these microvesicles by C1-inhibitor should be explored as a potential treatment for neutrophil-induced inflammation.Mossberg, MariaStåhl, Anne-lieKahn, RobinKristoffersson, Ann-CharlotteTati, RameshHeijl, CarolineSegelmark, MårtenLeeb-Lundberg, L.M. FredrikKarpman, Diana2017-03-13T07:26:32-07:00doi:10.1681/ASN.2016060637hwp:resource-id:jnephrol;28/8/2472American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyvasculitis, complement, Chronic inflammation, glomerular endothelial cells, neutrophils, kininBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160606371046-66731533-34502017-03-13T07:26:32-07:002017-08Journal of the American Society of NephrologyBasic Research2828889247222552824248122582824
- Colon Cancer Screening among Patients Receiving Dialysis in the United States: Are We Choosing Wisely?The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.10.1681/ASN.2016091019Thu, 23 Mar 2017 07:24:44 GMT-07:00Colon Cancer Screening among Patients Receiving Dialysis in the United States: Are We Choosing Wisely?The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.Carlos, Christopher A.McCulloch, Charles E.Hsu, Chi-yuanGrimes, BarbaraPavkov, Meda E.Burrows, Nilka R.Shahinian, Vahakn B.Saran, RajivPowe, Neil R.Johansen, Kirsten L.,Carlos, Christopher A.McCulloch, Charles E.Hsu, Chi-yuanGrimes, BarbaraPavkov, Meda E.Burrows, Nilka R.Shahinian, Vahakn B.Saran, RajivPowe, Neil R.Johansen, Kirsten L.2017-03-23T07:24:44-07:00doi:10.1681/ASN.2016091019hwp:resource-id:jnephrol;28/8/2521American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, colon cancer screening, hemodialysisClinical ResearchClinical Researchresearch-article20172017-08-01August 201710.1681/ASN.20160910191046-66731533-34502017-03-23T07:24:44-07:002017-08Journal of the American Society of NephrologyClinical Research28825212528
- Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium DepletionAdaptation of the organism to potassium (K+) deficiency requires precise coordination among organs involved in K+ homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K+ retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na+/Cl− cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K+ restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4LPax8/LC1) mice exhibited severe hypokalemia and urinary K+ wasting. Notably, expression of the ROMK K+ channel did not change in the distal convoluted tubule and decreased slightly in the cortical/medullary collecting duct, whereas BK channel abundance increased in principal cells of the connecting tubule/collecting ducts. However, K+ restriction also enhanced ENaC expression in Nedd4LPax8/LC1 mice, and treatment with the ENaC inhibitor, benzamil, reversed excessive K+ wasting. Moreover, K+ restriction increased WNK1 and WNK4 expression and enhanced SPAK-mediated NCC phosphorylation in Nedd4LPax8/LC1 mice, with no change in total NCC. We propose a mechanism in which NEDD4-2 deficiency exacerbates hypokalemia during dietary K+ restriction primarily through direct upregulation of ENaC, whereas increased BK channel expression has a less significant role. These changes outweigh the compensatory antikaliuretic effects of diminished ROMK expression, increased NCC phosphorylation, and enhanced WNK pathway activity in the distal convoluted tubule. Thus, NEDD4-2 has a crucial role in K+ conservation through direct and indirect effects on ENaC, distal nephron K+ channels, and WNK signaling.10.1681/ASN.2016070732Mon, 13 Mar 2017 07:26:32 GMT-07:00Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium DepletionAdaptation of the organism to potassium (K+) deficiency requires precise coordination among organs involved in K+ homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K+ retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na+/Cl− cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K+ restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4LPax8/LC1) mice exhibited severe hypokalemia and urinary K+ wasting. Notably, expression of the ROMK K+ channel did not change in the distal convoluted tubule and decreased slightly in the cortical/medullary collecting duct, whereas BK channel abundance increased in principal cells of the connecting tubule/collecting ducts. However, K+ restriction also enhanced ENaC expression in Nedd4LPax8/LC1 mice, and treatment with the ENaC inhibitor, benzamil, reversed excessive K+ wasting. Moreover, K+ restriction increased WNK1 and WNK4 expression and enhanced SPAK-mediated NCC phosphorylation in Nedd4LPax8/LC1 mice, with no change in total NCC. We propose a mechanism in which NEDD4-2 deficiency exacerbates hypokalemia during dietary K+ restriction primarily through direct upregulation of ENaC, whereas increased BK channel expression has a less significant role. These changes outweigh the compensatory antikaliuretic effects of diminished ROMK expression, increased NCC phosphorylation, and enhanced WNK pathway activity in the distal convoluted tubule. Thus, NEDD4-2 has a crucial role in K+ conservation through direct and indirect effects on ENaC, distal nephron K+ channels, and WNK signaling.Al-Qusairi, LamaBasquin, DenisRoy, AnkitaRajaram, Renuga DeviMaillard, Marc P.Subramanya, Arohan R.Staub, Olivier2017-03-13T07:26:32-07:00doi:10.1681/ASN.2016070732hwp:resource-id:jnephrol;28/8/2431American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyENaC, ion transport, K channels, signalingBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160707321046-66731533-34502017-03-13T07:26:32-07:002017-08Journal of the American Society of NephrologyBasic Research28824312442
- CORRIGENDUM10.1681/ASN.2017030275Fri, 14 Apr 2017 05:52:28 GMT-07:00CORRIGENDUMAmerican Society of Nephrology2017-04-14T05:52:28-07:00doi:10.1681/ASN.2017030275hwp:resource-id:jnephrol;28/8/2553American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCorrigendumCorrigendumcorrection20172017-08-01August 201710.1681/ASN.20170302751046-66731533-34502017-04-14T05:52:28-07:002017-08Journal of the American Society of NephrologyCorrigendum2828882553233725532352
- Na+/HCO3– Cotransporter NBCn2 Mediates HCO3− Reclamation in the Apical Membrane of Renal Proximal TubulesThe kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO3− filtered in glomeruli and by secreting additional H+ to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO3− reclamation depends solely on H+ secretion, mediated by the apical Na+/H+ exchanger NHE3 and the vacuolar proton pump. However, NHE3 and the proton pump cannot account for all HCO3− reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na+/HCO3– cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NH4Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE3. Conversely, NaHCO3-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE3. We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO3− reclamation: the conventional indirect pathway, in which NHE3 and the proton pump secrete H+ to titrate luminal HCO3−, and the novel direct pathway, in which NBCn2 removes HCO3− from the lumen. The reciprocal regulation of NBCn2 and NHE3 under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO3− uptake and H+ secretion have reciprocal efficiencies for HCO3− reclamation versus titration of luminal buffers.10.1681/ASN.2016080930Thu, 09 Mar 2017 06:00:46 GMT-08:00Na+/HCO3– Cotransporter NBCn2 Mediates HCO3− Reclamation in the Apical Membrane of Renal Proximal TubulesThe kidney maintains systemic acid-base balance by reclaiming from the renal tubule lumen virtually all HCO3− filtered in glomeruli and by secreting additional H+ to titrate luminal buffers. For proximal tubules, which are responsible for about 80% of this activity, it is believed that HCO3− reclamation depends solely on H+ secretion, mediated by the apical Na+/H+ exchanger NHE3 and the vacuolar proton pump. However, NHE3 and the proton pump cannot account for all HCO3− reclamation. Here, we investigated the potential contribution of two variants of the electroneutral Na+/HCO3– cotransporter NBCn2, the amino termini of which start with the amino acids MCDL (MCDL-NBCn2) and MEIK (MEIK-NBCn2). Western blot analysis and immunocytochemistry revealed that MEIK-NBCn2 predominantly localizes at the basolateral membrane of medullary thick ascending limbs in the rat kidney, whereas MCDL-NBCn2 localizes at the apical membrane of proximal tubules. Notably, NH4Cl-induced systemic metabolic acidosis or hypokalemic alkalosis downregulated the abundance of MCDL-NBCn2 and reciprocally upregulated NHE3. Conversely, NaHCO3-induced metabolic alkalosis upregulated MCDL-NBCn2 and reciprocally downregulated NHE3. We propose that the apical membrane of the proximal tubules has two distinct strategies for HCO3− reclamation: the conventional indirect pathway, in which NHE3 and the proton pump secrete H+ to titrate luminal HCO3−, and the novel direct pathway, in which NBCn2 removes HCO3− from the lumen. The reciprocal regulation of NBCn2 and NHE3 under different physiologic conditions is consistent with our mathematical simulations, which suggest that HCO3− uptake and H+ secretion have reciprocal efficiencies for HCO3− reclamation versus titration of luminal buffers.Guo, Yi-MinLiu, YingLiu, MeiWang, Jin-LinXie, Zhang-DongChen, Kang-JingWang, Deng-KeOcchipinti, RossanaBoron, Walter F.Chen, Li-Ming2017-03-09T06:00:46-08:00doi:10.1681/ASN.2016080930hwp:resource-id:jnephrol;28/8/2409American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, bicarbonate reabsorption, acid-base balance, metabolic, acidosis, metabolic alkalosis, mathematical simulationBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160809301046-66731533-34502017-03-09T06:00:46-08:002017-08Journal of the American Society of NephrologyBasic Research28824092419
- Two-Photon Intravital Fluorescence Lifetime Imaging of the Kidney Reveals Cell-Type Specific Metabolic SignaturesIn the live animal, tissue autofluorescence arises from a number of biologically important metabolites, such as the reduced form of nicotinamide adenine dinucleotide. Because autofluorescence changes with metabolic state, it can be harnessed as a label-free imaging tool with which to study metabolism in vivo. Here, we used the combination of intravital two-photon microscopy and frequency-domain fluorescence lifetime imaging microscopy (FLIM) to map cell-specific metabolic signatures in the kidneys of live animals. The FLIM images are analyzed using the phasor approach, which requires no prior knowledge of metabolite species and can provide unbiased metabolic fingerprints for each pixel of the lifetime image. Intravital FLIM revealed the metabolic signatures of S1 and S2 proximal tubules to be distinct and resolvable at the subcellular level. Notably, S1 and distal tubules exhibited similar metabolic profiles despite apparent differences in morphology and autofluorescence emission with traditional two-photon microscopy. Time-lapse imaging revealed dynamic changes in the metabolic profiles of the interstitium, urinary lumen, and glomerulus—areas that are not resolved by traditional intensity-based two-photon microscopy. Finally, using a model of endotoxemia, we present examples of the way in which intravital FLIM can be applied to study kidney diseases and metabolism. In conclusion, intravital FLIM of intrinsic metabolites is a bias-free approach with which to characterize and monitor metabolism in vivo, and offers the unique opportunity to uncover dynamic metabolic changes in living animals with subcellular resolution.10.1681/ASN.2016101153Wed, 01 Mar 2017 08:45:56 GMT-08:00Two-Photon Intravital Fluorescence Lifetime Imaging of the Kidney Reveals Cell-Type Specific Metabolic SignaturesIn the live animal, tissue autofluorescence arises from a number of biologically important metabolites, such as the reduced form of nicotinamide adenine dinucleotide. Because autofluorescence changes with metabolic state, it can be harnessed as a label-free imaging tool with which to study metabolism in vivo. Here, we used the combination of intravital two-photon microscopy and frequency-domain fluorescence lifetime imaging microscopy (FLIM) to map cell-specific metabolic signatures in the kidneys of live animals. The FLIM images are analyzed using the phasor approach, which requires no prior knowledge of metabolite species and can provide unbiased metabolic fingerprints for each pixel of the lifetime image. Intravital FLIM revealed the metabolic signatures of S1 and S2 proximal tubules to be distinct and resolvable at the subcellular level. Notably, S1 and distal tubules exhibited similar metabolic profiles despite apparent differences in morphology and autofluorescence emission with traditional two-photon microscopy. Time-lapse imaging revealed dynamic changes in the metabolic profiles of the interstitium, urinary lumen, and glomerulus—areas that are not resolved by traditional intensity-based two-photon microscopy. Finally, using a model of endotoxemia, we present examples of the way in which intravital FLIM can be applied to study kidney diseases and metabolism. In conclusion, intravital FLIM of intrinsic metabolites is a bias-free approach with which to characterize and monitor metabolism in vivo, and offers the unique opportunity to uncover dynamic metabolic changes in living animals with subcellular resolution.Hato, TakashiWinfree, SethDay, RichardSandoval, Ruben M.Molitoris, Bruce A.Yoder, Mervin C.Wiggins, Roger C.Zheng, YiDunn, Kenneth W.Dagher, Pierre C.2017-03-01T08:45:56-08:00doi:10.1681/ASN.2016101153hwp:resource-id:jnephrol;28/8/2420American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolism, podocyte, tubules, endotheliumBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20161011531046-66731533-34502017-03-01T08:45:56-08:002017-08Journal of the American Society of NephrologyBasic Research28824202430
- Urine Ammonium Predicts Clinical Outcomes in Hypertensive Kidney DiseaseMetabolic acidosis is associated with poor outcomes in CKD. Because impaired renal ammonium excretion is important in the pathogenesis of acidosis, urine ammonium excretion might be a better and perhaps earlier acid–base indicator of risk than serum bicarbonate, particularly in patients without acidosis. We evaluated the association between baseline ammonium excretion and clinical outcomes in African American Study of Kidney Disease and Hypertension participants (n=1044). Median daily ammonium excretion was 19.5 (95% confidence interval [95% CI], 6.5 to 43.2) mEq. In Cox regression models (adjusted for demographics, measured GFR, proteinuria, body mass index, net endogenous acid production, and serum potassium and bicarbonate), hazard ratios of the composite outcome of death or dialysis were 1.46 (95% CI, 1.13 to 1.87) in the low tertile and 1.14 (95% CI, 0.89 to 1.46) in the middle tertile of daily ammonium excretion compared with the high tertile. Among participants without acidosis at baseline, the adjusted hazard ratio for those with ammonium excretion <20 mEq/d was 1.36 (95% CI, 1.09 to 1.71) compared with those with ammonium excretion ≥20 mEq/d. Additionally, compared with participants in the high ammonium tertile, those in the low ammonium tertile had higher adjusted odds of incident acidosis at 1 year (adjusted odds ratio, 2.56; 95% CI, 1.04 to 6.27). In conclusion, low ammonium excretion is associated with death and renal failure in hypertensive kidney disease, even among those without acidosis. Low ammonium excretion could identify patients with CKD and normal bicarbonate levels who might benefit from alkali before acidosis develops.10.1681/ASN.2016101151Thu, 06 Apr 2017 06:42:48 GMT-07:00Urine Ammonium Predicts Clinical Outcomes in Hypertensive Kidney DiseaseMetabolic acidosis is associated with poor outcomes in CKD. Because impaired renal ammonium excretion is important in the pathogenesis of acidosis, urine ammonium excretion might be a better and perhaps earlier acid–base indicator of risk than serum bicarbonate, particularly in patients without acidosis. We evaluated the association between baseline ammonium excretion and clinical outcomes in African American Study of Kidney Disease and Hypertension participants (n=1044). Median daily ammonium excretion was 19.5 (95% confidence interval [95% CI], 6.5 to 43.2) mEq. In Cox regression models (adjusted for demographics, measured GFR, proteinuria, body mass index, net endogenous acid production, and serum potassium and bicarbonate), hazard ratios of the composite outcome of death or dialysis were 1.46 (95% CI, 1.13 to 1.87) in the low tertile and 1.14 (95% CI, 0.89 to 1.46) in the middle tertile of daily ammonium excretion compared with the high tertile. Among participants without acidosis at baseline, the adjusted hazard ratio for those with ammonium excretion <20 mEq/d was 1.36 (95% CI, 1.09 to 1.71) compared with those with ammonium excretion ≥20 mEq/d. Additionally, compared with participants in the high ammonium tertile, those in the low ammonium tertile had higher adjusted odds of incident acidosis at 1 year (adjusted odds ratio, 2.56; 95% CI, 1.04 to 6.27). In conclusion, low ammonium excretion is associated with death and renal failure in hypertensive kidney disease, even among those without acidosis. Low ammonium excretion could identify patients with CKD and normal bicarbonate levels who might benefit from alkali before acidosis develops.Raphael, Kalani L.Carroll, David J.Murray, JenniferGreene, TomBeddhu, Srinivasan2017-04-06T06:42:48-07:00doi:10.1681/ASN.2016101151hwp:resource-id:jnephrol;28/8/2483American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis., chronic kidney disease, dialysis, mortality, AASK (African American Study of Kidney Disease and Hypertension)Clinical EpidemiologyClinical Epidemiologyresearch-article20172017-08-01August 201710.1681/ASN.20161011511046-66731533-34502017-04-06T06:42:48-07:002017-08Journal of the American Society of NephrologyClinical Epidemiology28882483225824902260
- Relationship between Hypotension and Cerebral Ischemia during HemodialysisThe relationship between BP and downstream ischemia during hemodialysis has not been characterized. We studied the dynamic relationship between BP, real-time symptoms, and cerebral oxygenation during hemodialysis, using continuous BP and cerebral oxygenation measurements prospectively gathered from 635 real-world hemodialysis sessions in 58 prevalent patients. We examined the relationship between BP and cerebral ischemia (relative drop in cerebral saturation >15%) and explored the lower limit of cerebral autoregulation at patient and population levels. Furthermore, we estimated intradialytic exposure to cerebral ischemia and hypotension for each patient, and entered these values into multivariate models predicting change in cognitive function. In all, 23.5% of hemodialysis sessions featured cerebral ischemia; 31.9% of these events were symptomatic. Episodes of hypotension were common, with mean arterial pressure falling by a median of 22 mmHg (interquartile range, 14.3–31.9 mmHg) and dropping below 60 mmHg in 24% of sessions. Every 10 mmHg drop from baseline in mean arterial pressure associated with a 3% increase in ischemic events (P<0.001), and the incidence of ischemic events rose rapidly below an absolute mean arterial pressure of 60 mmHg. Overall, however, BP poorly predicted downstream ischemia. The lower limit of cerebral autoregulation varied substantially (mean 74.1 mmHg, SD 17.6 mmHg). Intradialytic cerebral ischemia, but not hypotension, correlated with decreased executive cognitive function at 12 months (P=0.03). This pilot study demonstrates that intradialytic cerebral ischemia occurs frequently, is not easily predicted from BP, and may be clinically significant.10.1681/ASN.2016060704Tue, 07 Mar 2017 06:25:47 GMT-08:00Relationship between Hypotension and Cerebral Ischemia during HemodialysisThe relationship between BP and downstream ischemia during hemodialysis has not been characterized. We studied the dynamic relationship between BP, real-time symptoms, and cerebral oxygenation during hemodialysis, using continuous BP and cerebral oxygenation measurements prospectively gathered from 635 real-world hemodialysis sessions in 58 prevalent patients. We examined the relationship between BP and cerebral ischemia (relative drop in cerebral saturation >15%) and explored the lower limit of cerebral autoregulation at patient and population levels. Furthermore, we estimated intradialytic exposure to cerebral ischemia and hypotension for each patient, and entered these values into multivariate models predicting change in cognitive function. In all, 23.5% of hemodialysis sessions featured cerebral ischemia; 31.9% of these events were symptomatic. Episodes of hypotension were common, with mean arterial pressure falling by a median of 22 mmHg (interquartile range, 14.3–31.9 mmHg) and dropping below 60 mmHg in 24% of sessions. Every 10 mmHg drop from baseline in mean arterial pressure associated with a 3% increase in ischemic events (P<0.001), and the incidence of ischemic events rose rapidly below an absolute mean arterial pressure of 60 mmHg. Overall, however, BP poorly predicted downstream ischemia. The lower limit of cerebral autoregulation varied substantially (mean 74.1 mmHg, SD 17.6 mmHg). Intradialytic cerebral ischemia, but not hypotension, correlated with decreased executive cognitive function at 12 months (P=0.03). This pilot study demonstrates that intradialytic cerebral ischemia occurs frequently, is not easily predicted from BP, and may be clinically significant.MacEwen, ClareSutherland, SheeraDaly, JonathanPugh, ChristopherTarassenko, Lionel2017-03-07T06:25:47-08:00doi:10.1681/ASN.2016060704hwp:resource-id:jnephrol;28/8/2511American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyintra-dialytic hypotension, hemodialysis, ischemia, cognitive decline, cardiovascular physiologyClinical ResearchClinical Researchresearch-article20172017-08-01August 201710.1681/ASN.20160607041046-66731533-34502017-03-07T06:25:47-08:002017-08Journal of the American Society of NephrologyClinical Research28825112520
- (Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and FibrosisThe (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/β-catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β-catenin induced PRR mRNA and protein expression in vitro. Notably, forced expression of PRR potentiated Wnt1-mediated β-catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α–smooth muscle actin (α-SMA). Conversely, knockdown of PRR by siRNA abolished β-catenin activation. PRR potentiation of Wnt/β-catenin signaling did not require renin, but required vacuolar H+ ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β-catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/β-catenin signaling.10.1681/ASN.2016070811Tue, 07 Mar 2017 06:25:47 GMT-08:00(Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and FibrosisThe (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/β-catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β-catenin induced PRR mRNA and protein expression in vitro. Notably, forced expression of PRR potentiated Wnt1-mediated β-catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α–smooth muscle actin (α-SMA). Conversely, knockdown of PRR by siRNA abolished β-catenin activation. PRR potentiation of Wnt/β-catenin signaling did not require renin, but required vacuolar H+ ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β-catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/β-catenin signaling.Li, ZhenZhou, LiliWang, YongpingMiao, JinhuaHong, XueHou, Fan FanLiu, Youhua2017-03-07T06:25:47-08:00doi:10.1681/ASN.2016070811hwp:resource-id:jnephrol;28/8/2393American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, renal fibrosis, (pro)renin receptor, Wnt, betacatenin, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160708111046-66731533-34502017-03-07T06:25:47-08:002017-08Journal of the American Society of NephrologyBasic Research28823932408
- Long-Term Endothelin-A Receptor Antagonism Provides Robust Renal Protection in Humanized Sickle Cell Disease MiceSickle cell disease (SCD)–associated nephropathy is a major source of morbidity and mortality in patients because of the lack of efficacious treatments targeting renal manifestations of the disease. Here, we describe a long-term treatment strategy with the selective endothelin-A receptor (ETA) antagonist, ambrisentan, designed to interfere with the development of nephropathy in a humanized mouse model of SCD. Ambrisentan preserved GFR at the level of nondisease controls and prevented the development of proteinuria, albuminuria, and nephrinuria. Microscopy studies demonstrated prevention of podocyte loss and structural alterations, the absence of vascular congestion, and attenuation of glomerulosclerosis in treated mice. Studies in isolated glomeruli showed that treatment reduced inflammation and oxidative stress. At the level of renal tubules, ambrisentan treatment prevented the increased excretion of urinary tubular injury biomarkers. Additionally, the treatment strategy prevented tubular brush border loss, diminished tubular iron deposition, blocked the development of interstitial fibrosis, and prevented immune cell infiltration. Furthermore, the prevention of albuminuria in treated mice was associated with preservation of cortical megalin expression. In a separate series of identical experiments, combined ETA and ETB receptor antagonism provided only some of the protection observed with ambrisentan, highlighting the importance of exclusively targeting the ETA receptor in SCD. Our results demonstrate that ambrisentan treatment provides robust protection from diverse renal pathologies in SCD mice, and suggest that long-term ETA receptor antagonism may provide a strategy for the prevention of renal complications of SCD.10.1681/ASN.2016070711Mon, 27 Mar 2017 06:47:49 GMT-07:00Long-Term Endothelin-A Receptor Antagonism Provides Robust Renal Protection in Humanized Sickle Cell Disease MiceSickle cell disease (SCD)–associated nephropathy is a major source of morbidity and mortality in patients because of the lack of efficacious treatments targeting renal manifestations of the disease. Here, we describe a long-term treatment strategy with the selective endothelin-A receptor (ETA) antagonist, ambrisentan, designed to interfere with the development of nephropathy in a humanized mouse model of SCD. Ambrisentan preserved GFR at the level of nondisease controls and prevented the development of proteinuria, albuminuria, and nephrinuria. Microscopy studies demonstrated prevention of podocyte loss and structural alterations, the absence of vascular congestion, and attenuation of glomerulosclerosis in treated mice. Studies in isolated glomeruli showed that treatment reduced inflammation and oxidative stress. At the level of renal tubules, ambrisentan treatment prevented the increased excretion of urinary tubular injury biomarkers. Additionally, the treatment strategy prevented tubular brush border loss, diminished tubular iron deposition, blocked the development of interstitial fibrosis, and prevented immune cell infiltration. Furthermore, the prevention of albuminuria in treated mice was associated with preservation of cortical megalin expression. In a separate series of identical experiments, combined ETA and ETB receptor antagonism provided only some of the protection observed with ambrisentan, highlighting the importance of exclusively targeting the ETA receptor in SCD. Our results demonstrate that ambrisentan treatment provides robust protection from diverse renal pathologies in SCD mice, and suggest that long-term ETA receptor antagonism may provide a strategy for the prevention of renal complications of SCD.Kasztan, MalgorzataFox, Brandon M.Speed, Joshua S.De Miguel, CarmenGohar, Eman Y.Townes, Tim M.Kutlar, AbdullahPollock, Jennifer S.Pollock, David M.2017-03-27T06:47:49-07:00doi:10.1681/ASN.2016070711hwp:resource-id:jnephrol;28/8/2443American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologysickle nephropathy, endothelin, proteinuria, renal injury, glomerular filtration barrierBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160707111046-66731533-34502017-03-27T06:47:49-07:002017-08Journal of the American Society of NephrologyBasic Research28882443225324582255
- The MicroRNA-199a/214 Cluster Targets E-Cadherin and Claudin-2 and Promotes High Glucose-Induced Peritoneal FibrosisSerum response factor (SRF) was found to be involved in the phenotypic transition and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs) that contain the SRF-binding consensus (CArG) element in the promoter region. Therefore, we investigated whether the miR-199a/214 gene cluster, which contains a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG) treatment significantly unregulated the expression of the miR-199a-5p/214–3p gene cluster in human peritoneal mesothelial cells (HPMCs). By chromatin immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a-5p/214–3p gene cluster promoter after HG stimulation. In vitro, in HPMCs, silencing of miR-199a-5p or miR-214–3p inhibited the HG-induced phenotypic transition and cell migration but enhanced cell adhesion, whereas ectopic expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p and miR-214–3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model, treatment with an SRF inhibitor silenced miR-199a-5p and miR-214–3p and alleviated HG-PD fluid–induced damage and fibrosis. Overall, this study reveals a novel SRF–miR-199a/miR-214–E-cadherin/claudin-2 axis that mediates damage and fibrosis in PD.10.1681/ASN.2016060663Thu, 20 Apr 2017 06:08:58 GMT-07:00The MicroRNA-199a/214 Cluster Targets E-Cadherin and Claudin-2 and Promotes High Glucose-Induced Peritoneal FibrosisSerum response factor (SRF) was found to be involved in the phenotypic transition and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs) that contain the SRF-binding consensus (CArG) element in the promoter region. Therefore, we investigated whether the miR-199a/214 gene cluster, which contains a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG) treatment significantly unregulated the expression of the miR-199a-5p/214–3p gene cluster in human peritoneal mesothelial cells (HPMCs). By chromatin immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a-5p/214–3p gene cluster promoter after HG stimulation. In vitro, in HPMCs, silencing of miR-199a-5p or miR-214–3p inhibited the HG-induced phenotypic transition and cell migration but enhanced cell adhesion, whereas ectopic expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p and miR-214–3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model, treatment with an SRF inhibitor silenced miR-199a-5p and miR-214–3p and alleviated HG-PD fluid–induced damage and fibrosis. Overall, this study reveals a novel SRF–miR-199a/miR-214–E-cadherin/claudin-2 axis that mediates damage and fibrosis in PD.Che, MingwenShi, TiantianFeng, ShidongLi, HuanZhang, XiaominFeng, NingLou, WeijuanDou, JianhuaTang, GuangboHuang, ChenXu, GuoshuangQian, QiSun, ShirenHe, LijieWang, Hanmin2017-04-20T06:08:58-07:00doi:10.1681/ASN.2016060663hwp:resource-id:jnephrol;28/8/2459American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, fibrosis, claudins, miR-199a/214 gene clusterBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160606631046-66731533-34502017-04-20T06:08:58-07:002017-08Journal of the American Society of NephrologyBasic Research28824592471
- Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1–Dependent MannerThe rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD+. Supplementation with nicotinamide mononucleotide (NMN), an NAD+ precursor, restored renal SIRT1 activity and NAD+ content in 20-month-old mice and further increased both in 3-month-old mice. Moreover, supplementation with NMN significantly protected mice in both age groups from cisplatin-induced AKI. SIRT1 deficiency blunted the protective effect of NMN, and microarray data revealed that c-Jun N-terminal kinase (JNK) signaling activation associated with renal injury in SIRT1 heterozygotes. In vitro, SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably via the deacetylation of a JNK phosphatase, DUSP16. Taken together, our findings reveal SIRT1 as a crucial mediator in the renal aging process. Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI.10.1681/ASN.2016040385Tue, 28 Feb 2017 07:21:57 GMT-08:00Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1–Dependent MannerThe rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD+. Supplementation with nicotinamide mononucleotide (NMN), an NAD+ precursor, restored renal SIRT1 activity and NAD+ content in 20-month-old mice and further increased both in 3-month-old mice. Moreover, supplementation with NMN significantly protected mice in both age groups from cisplatin-induced AKI. SIRT1 deficiency blunted the protective effect of NMN, and microarray data revealed that c-Jun N-terminal kinase (JNK) signaling activation associated with renal injury in SIRT1 heterozygotes. In vitro, SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably via the deacetylation of a JNK phosphatase, DUSP16. Taken together, our findings reveal SIRT1 as a crucial mediator in the renal aging process. Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI.Guan, YiWang, Su-RongHuang, Xin-ZhongXie, Qiong-hongXu, Yun-YuShang, DaHao, Chuan-Ming2017-02-28T07:21:57-08:00doi:10.1681/ASN.2016040385hwp:resource-id:jnephrol;28/8/2337American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologySIRT1, NAD+, NMN, AKI, Aging, cisplatin nephrotoxicityBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160403851046-66731533-34502017-02-28T07:21:57-08:002017-08Journal of the American Society of NephrologyBasic Research2828882337255323522553
- Endothelin-A Receptor Antagonism Retards the Progression of Murine Sickle Cell Nephropathy10.1681/ASN.2017030320Tue, 25 Apr 2017 10:51:19 GMT-07:00Endothelin-A Receptor Antagonism Retards the Progression of Murine Sickle Cell NephropathyNath, Karl A.Katusic, Zvonimir S.2017-04-25T10:51:19-07:00doi:10.1681/ASN.2017030320hwp:resource-id:jnephrol;28/8/2253American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologysickle cell disease, endothelin, kidney, hemolysis, heme, hemoglobin SUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-08-01August 201710.1681/ASN.20170303201046-66731533-34502017-04-25T10:51:19-07:002017-08Journal of the American Society of NephrologyUp Front Matters28882253244322552458
- Re-Examining Neutrophil Participation in GNSignificant advances in understanding the pathogenesis of GN have occurred in recent decades. Among those advances is the finding that both innate and adaptive immune cells contribute to the development of GN. Neutrophils were recognized as key contributors in early animal models of GN, at a time when the prevailing view considered neutrophils to function as nonspecific effector cells that die quickly after performing antimicrobial functions. However, advances over the past two decades have shown that neutrophil functions are more complex and sophisticated. Specifically, research has revealed that neutrophil survival is regulated by the inflammatory milieu and that neutrophils demonstrate plasticity, mediate microbial killing through previously unrecognized mechanisms, demonstrate transcriptional activity leading to the release of cytokines and chemokines, interact with and regulate cells of the innate and adaptive immune systems, and contribute to the resolution of inflammation. Therefore, neutrophil participation in glomerular diseases deserves re-evaluation. In this review, we describe advances in understanding classic neutrophil functions, review the expanded roles of neutrophils in innate and adaptive immune responses, and summarize current knowledge of neutrophil contributions to GN.10.1681/ASN.2016121271Thu, 15 Jun 2017 06:12:53 GMT-07:00Re-Examining Neutrophil Participation in GNSignificant advances in understanding the pathogenesis of GN have occurred in recent decades. Among those advances is the finding that both innate and adaptive immune cells contribute to the development of GN. Neutrophils were recognized as key contributors in early animal models of GN, at a time when the prevailing view considered neutrophils to function as nonspecific effector cells that die quickly after performing antimicrobial functions. However, advances over the past two decades have shown that neutrophil functions are more complex and sophisticated. Specifically, research has revealed that neutrophil survival is regulated by the inflammatory milieu and that neutrophils demonstrate plasticity, mediate microbial killing through previously unrecognized mechanisms, demonstrate transcriptional activity leading to the release of cytokines and chemokines, interact with and regulate cells of the innate and adaptive immune systems, and contribute to the resolution of inflammation. Therefore, neutrophil participation in glomerular diseases deserves re-evaluation. In this review, we describe advances in understanding classic neutrophil functions, review the expanded roles of neutrophils in innate and adaptive immune responses, and summarize current knowledge of neutrophil contributions to GN.Caster, Dawn J.Powell, David W.Miralda, IrinaWard, Richard A.McLeish, Kenneth R.2017-06-15T06:12:53-07:00doi:10.1681/ASN.2016121271hwp:resource-id:jnephrol;28/8/2275American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, immunology, glomerular disease, neutrophilUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-08-01August 201710.1681/ASN.20161212711046-66731533-34502017-06-15T06:12:53-07:002017-08Journal of the American Society of NephrologyUp Front Matters28288102275312922893129
- NFAT5 and SLC4A10 Loci Associate with Plasma OsmolalityDisorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P<5.0 × 10−6. Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 × 10−5), with combined stages 1 and 2 genome-wide significance of P=5.6 × 10−10. Transethnic meta-analysis further supported the association at rs9980 (P=5.9 × 10−12). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 × 10−8). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous system and relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance.10.1681/ASN.2016080892Thu, 30 Mar 2017 06:09:02 GMT-07:00NFAT5 and SLC4A10 Loci Associate with Plasma OsmolalityDisorders of water balance, an excess or deficit of total body water relative to body electrolyte content, are common and ascertained by plasma hypo- or hypernatremia, respectively. We performed a two-stage genome-wide association study meta-analysis on plasma sodium concentration in 45,889 individuals of European descent (stage 1 discovery) and 17,637 additional individuals of European descent (stage 2 replication), and a transethnic meta-analysis of replicated single-nucleotide polymorphisms in 79,506 individuals (63,526 individuals of European descent, 8765 individuals of Asian Indian descent, and 7215 individuals of African descent). In stage 1, we identified eight loci associated with plasma sodium concentration at P<5.0 × 10−6. Of these, rs9980 at NFAT5 replicated in stage 2 meta-analysis (P=3.1 × 10−5), with combined stages 1 and 2 genome-wide significance of P=5.6 × 10−10. Transethnic meta-analysis further supported the association at rs9980 (P=5.9 × 10−12). Additionally, rs16846053 at SLC4A10 showed nominally, but not genome-wide, significant association in combined stages 1 and 2 meta-analysis (P=6.7 × 10−8). NFAT5 encodes a ubiquitously expressed transcription factor that coordinates the intracellular response to hypertonic stress but was not previously implicated in the regulation of systemic water balance. SLC4A10 encodes a sodium bicarbonate transporter with a brain-restricted expression pattern, and variant rs16846053 affects a putative intronic NFAT5 DNA binding motif. The lead variants for NFAT5 and SLC4A10 are cis expression quantitative trait loci in tissues of the central nervous system and relevant to transcriptional regulation. Thus, genetic variation in NFAT5 and SLC4A10 expression and function in the central nervous system may affect the regulation of systemic water balance.Böger, Carsten A.Gorski, MathiasMcMahon, Gearoid M.Xu, HuichunChang, Yen-Pei C.van der Most, Peter J.Navis, GerjanNolte, Ilja M.de Borst, Martin H.Zhang, WeihuaLehne, BenjaminLoh, MarieTan, Sian-TsungBoerwinkle, EricGrams, Morgan E.Sekula, PeggyLi, ManWilmot, BethMoon, James G.Scheet, PaulCucca, FrancescoXiao, XiangjunLyytikäinen, Leo-PekkaDelgado, GracielaGrammer, Tanja B.Kleber, Marcus E.Sedaghat, SanazRivadeneira, FernandoCorre, TanguyKutalik, ZoltanBergmann, SvenNielson, Carrie M.Srikanth, PriyaTeumer, AlexanderMüller-Nurasyid, MartinaBrockhaus, Anne CatharinaPfeufer, ArneRathmann, WolfgangPeters, AnnetteMatsumoto, Marthade Andrade, MarizaAtkinson, Elizabeth J.Robinson-Cohen, Cassiannede Boer, Ian H.Hwang, Shih-JenHeid, Iris M.Gögele, MartinConcas, Maria PinaTanaka, ToshikoBandinelli, StefaniaNalls, Mike A.Singleton, AndrewTajuddin, Salman M.Adeyemo, AdebowaleZhou, JieDoumatey, AyoMcWeeney, ShannonMurabito, JoanneFranceschini, NoraFlessner, MichaelShlipak, MichaelWilson, James G.Chen, GuanjieRotimi, Charles N.Zonderman, Alan B.Evans, Michele K.Ferrucci, LuigiDevuyst, OlivierPirastu, MarioShuldiner, AlanHicks, Andrew A.Pramstaller, Peter PaulKestenbaum, BryanKardia, Sharon L.R.Turner, Stephen T.Study, LifeLines CohortBriske, Tamara EllefsonGieger, ChristianStrauch, KonstantinMeisinger, ChristaMeitinger, ThomasVölker, UweNauck, MatthiasVölzke, HenryVollenweider, PeterBochud, MurielleWaeber, GerardKähönen, MikaLehtimäki, TerhoMärz, WinfriedDehghan, AbbasFranco, Oscar H.Uitterlinden, Andre G.Hofman, AlbertTaylor, Herman A.Chambers, John C.Kooner, Jaspal S.Fox, Caroline S.Hitzemann, RobertOrwoll, Eric S.Pattaro, CristianSchlessinger, DavidKöttgen, AnnaSnieder, HaroldParsa, AfshinCohen, David M.Alizadeh, Behrooz Z.Boezen, H. MarikeFranke, Ludevan der Harst, PimN., G.Rots, Marianne G.S., H.Swertz, MorrisWolffenbuttel, Bruce H.R.Wijmenga, Cisca2017-03-30T06:09:02-07:00doi:10.1681/ASN.2016080892hwp:resource-id:jnephrol;28/8/2311American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhyponatremia, water-electrolyte balance, human genetics, hypernatremiaBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160808921046-66731533-34502017-03-30T06:09:02-07:002017-08Journal of the American Society of NephrologyBasic Research28823112321
- A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid SignalingCongenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene (NRIP1) in all seven affected members. NRIP1 encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity. Unlike wild-type NRIP1, the altered NRIP1 protein did not translocate to the nucleus, did not interact with RARα, and failed to inhibit retinoic acid–dependent transcriptional activity upon expression in HEK293 cells. Notably, we also showed that treatment with retinoic acid enhanced NRIP1 binding to RARα. RNA in situ hybridization confirmed Nrip1 expression in the developing urogenital system of the mouse. In explant cultures of embryonic kidney rudiments, retinoic acid stimulated Nrip1 expression, whereas a pan-RAR antagonist strongly reduced it. Furthermore, mice heterozygous for a null allele of Nrip1 showed a CAKUT-spectrum phenotype. Finally, expression and knockdown experiments in Xenopus laevis confirmed an evolutionarily conserved role for NRIP1 in renal development. These data indicate that dominant NRIP1 mutations can cause CAKUT by interference with retinoic acid transcriptional signaling, shedding light on the well documented association between abnormal vitamin A levels and renal malformations in humans, and suggest a possible gene-environment pathomechanism in this disease.10.1681/ASN.2016060694Wed, 05 Apr 2017 06:47:11 GMT-07:00A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid SignalingCongenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene (NRIP1) in all seven affected members. NRIP1 encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity. Unlike wild-type NRIP1, the altered NRIP1 protein did not translocate to the nucleus, did not interact with RARα, and failed to inhibit retinoic acid–dependent transcriptional activity upon expression in HEK293 cells. Notably, we also showed that treatment with retinoic acid enhanced NRIP1 binding to RARα. RNA in situ hybridization confirmed Nrip1 expression in the developing urogenital system of the mouse. In explant cultures of embryonic kidney rudiments, retinoic acid stimulated Nrip1 expression, whereas a pan-RAR antagonist strongly reduced it. Furthermore, mice heterozygous for a null allele of Nrip1 showed a CAKUT-spectrum phenotype. Finally, expression and knockdown experiments in Xenopus laevis confirmed an evolutionarily conserved role for NRIP1 in renal development. These data indicate that dominant NRIP1 mutations can cause CAKUT by interference with retinoic acid transcriptional signaling, shedding light on the well documented association between abnormal vitamin A levels and renal malformations in humans, and suggest a possible gene-environment pathomechanism in this disease.Vivante, AsafMann, NinaYonath, HagithWeiss, Anna-CarinaGetwan, MaikeKaminski, Michael M.Bohnenpoll, TobiasTeyssier, CatherineChen, JingShril, Shirleevan der Ven, Amelie T.Ityel, HadasSchmidt, Johanna MagdalenaWidmeier, EugenBauer, Stuart B.Sanna-Cherchi, SimoneGharavi, Ali G.Lu, WeiningMagen, DaniellaShukrun, RachelLifton, Richard P.Tasic, VeliborStanescu, Horia C.Cavaillès, VincentKleta, RobertAnikster, YairDekel, BenjaminKispert, AndreasLienkamp, Soeren S.Hildebrandt, Friedhelm2017-04-05T06:47:11-07:00doi:10.1681/ASN.2016060694hwp:resource-id:jnephrol;28/8/2364American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCAKUT, NRIP1, retinoic acidBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160606941046-66731533-34502017-04-05T06:47:11-07:002017-08Journal of the American Society of NephrologyBasic Research28823642376
- This Month’s Highlights10.1681/ASN.2017060710Mon, 31 Jul 2017 01:03:45 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-07-31T13:03:45-07:00doi:10.1681/ASN.2017060710hwp:resource-id:jnephrol;28/8/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-08-01August 201710.1681/ASN.20170607101046-66731533-34502017-07-31T13:03:45-07:002017-08Journal of the American Society of NephrologyThis Month’s Highlights288ii
- Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary HyperparathyroidismSecondary hyperparathyroidism commonly complicates CKD and associates with morbidity and mortality. We profiled microRNA (miRNA) in parathyroid glands from experimental hyperparathyroidism models and patients receiving dialysis and studied the function of specific miRNAs. miRNA deep-sequencing showed that human and rodent parathyroids share similar profiles. Parathyroids from uremic and normal rats segregated on the basis of their miRNA expression profiles, and a similar finding was observed in humans. We identified parathyroid miRNAs that were dysregulated in experimental hyperparathyroidism, including miR-29, miR-21, miR-148, miR-30, and miR-141 (upregulated); and miR-10, miR-125, and miR-25 (downregulated). Inhibition of the abundant let-7 family increased parathyroid hormone (PTH) secretion in normal and uremic rats, as well as in mouse parathyroid organ cultures. Conversely, inhibition of the upregulated miR-148 family prevented the increase in serum PTH level in uremic rats and decreased levels of secreted PTH in parathyroid cultures. The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism indicates their importance for parathyroid function and the development of hyperparathyroidism. Specifically, let-7 and miR-148 antagonism modified PTH secretion in vivo and in vitro, implying roles for these specific miRNAs. These findings may be utilized for therapeutic interventions aimed at altering PTH expression in diseases such as osteoporosis and secondary hyperparathyroidism.10.1681/ASN.2016050585Wed, 15 Mar 2017 05:56:08 GMT-07:00Let-7 and MicroRNA-148 Regulate Parathyroid Hormone Levels in Secondary HyperparathyroidismSecondary hyperparathyroidism commonly complicates CKD and associates with morbidity and mortality. We profiled microRNA (miRNA) in parathyroid glands from experimental hyperparathyroidism models and patients receiving dialysis and studied the function of specific miRNAs. miRNA deep-sequencing showed that human and rodent parathyroids share similar profiles. Parathyroids from uremic and normal rats segregated on the basis of their miRNA expression profiles, and a similar finding was observed in humans. We identified parathyroid miRNAs that were dysregulated in experimental hyperparathyroidism, including miR-29, miR-21, miR-148, miR-30, and miR-141 (upregulated); and miR-10, miR-125, and miR-25 (downregulated). Inhibition of the abundant let-7 family increased parathyroid hormone (PTH) secretion in normal and uremic rats, as well as in mouse parathyroid organ cultures. Conversely, inhibition of the upregulated miR-148 family prevented the increase in serum PTH level in uremic rats and decreased levels of secreted PTH in parathyroid cultures. The evolutionary conservation of abundant miRNAs in normal parathyroid glands and the regulation of these miRNAs in secondary hyperparathyroidism indicates their importance for parathyroid function and the development of hyperparathyroidism. Specifically, let-7 and miR-148 antagonism modified PTH secretion in vivo and in vitro, implying roles for these specific miRNAs. These findings may be utilized for therapeutic interventions aimed at altering PTH expression in diseases such as osteoporosis and secondary hyperparathyroidism.Shilo, VitaliMor-Yosef Levi, IritAbel, RoyMihailović, AleksandraWasserman, GiladNaveh-Many, TallyBen-Dov, Iddo Z.2017-03-15T05:56:08-07:00doi:10.1681/ASN.2016050585hwp:resource-id:jnephrol;28/8/2353American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperparathyroidism, chronic kidney disease, mineral metabolism, gene expression, microRNABasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160505851046-66731533-34502017-03-15T05:56:08-07:002017-08Journal of the American Society of NephrologyBasic Research28823532363
- Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney FibrosisCell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β-catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro, incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication.10.1681/ASN.2016080902Thu, 23 Mar 2017 07:24:44 GMT-07:00Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney FibrosisCell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β-catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro, incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication.Zhou, DongFu, HaiyanZhang, LuZhang, KeMin, YaliXiao, LiangxiangLin, LinBastacky, Sheldon I.Liu, Youhua2017-03-23T07:24:44-07:00doi:10.1681/ASN.2016080902hwp:resource-id:jnephrol;28/8/2322American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, fibroblast, Wnt signaling, chronic kidney disease, WntlessBasic ResearchBasic Researchresearch-article20172017-08-01August 201710.1681/ASN.20160809021046-66731533-34502017-03-23T07:24:44-07:002017-08Journal of the American Society of NephrologyBasic Research28823222336
- Turning the Tide: Improving Fluid Management in Dialysis through Technology10.1681/ASN.2017050491Thu, 15 Jun 2017 06:12:53 GMT-07:00Turning the Tide: Improving Fluid Management in Dialysis through TechnologyFlythe, Jennifer E.2017-06-15T06:12:53-07:00doi:10.1681/ASN.2017050491hwp:resource-id:jnephrol;28/8/2260American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, Life-threatening dialysis complications, fluid overloadUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-08-01August 201710.1681/ASN.20170504911046-66731533-34502017-06-15T06:12:53-07:002017-08Journal of the American Society of NephrologyUp Front Matters28882260249122622497
- Genomic Disorders and Neurocognitive Impairment in Pediatric CKDChildren with CKD are at increased risk for neurocognitive impairment, but whether neurocognitive dysfunction is solely attributable to impaired renal function is unclear. Data from the CKD in Children Study Chronic Kidney Disease in Children (CKiD) Study indicate that a subset of children with CKD have unsuspected genomic disorders that predispose them to organ malformations and neurocognitive impairment. We therefore tested whether the CKiD Study participants with genomic disorders had impaired neurocognitive performance at enrollment. Compared with noncarriers (n=389), children with genomic disorders (n=31) scored significantly poorer on all measures of intelligence, anxiety/depressive symptoms, and executive function (differences of 0.6–0.7 SD; P=1.2×10−3–2.4×10−4). These differences persisted after controlling for known modifiers, including low birth weight, maternal education, seizure disorder, kidney disease duration, and genetically defined ancestry. The deleterious effect of genomic disorders on neurocognitive function was significantly attenuated in offspring of mothers with higher education, indicating the potential for modification by genetic and/or environmental factors. These data indicate that impaired neurocognitive function in some children with CKD may be attributable to genetic lesions that affect both kidney and neurocognitive development. Early identification of genomic disorders may provide opportunity for early diagnosis and personalized interventions to mitigate the effect on neurocognitive function.10.1681/ASN.2016101108Mon, 27 Mar 2017 06:47:49 GMT-07:00Genomic Disorders and Neurocognitive Impairment in Pediatric CKDChildren with CKD are at increased risk for neurocognitive impairment, but whether neurocognitive dysfunction is solely attributable to impaired renal function is unclear. Data from the CKD in Children Study Chronic Kidney Disease in Children (CKiD) Study indicate that a subset of children with CKD have unsuspected genomic disorders that predispose them to organ malformations and neurocognitive impairment. We therefore tested whether the CKiD Study participants with genomic disorders had impaired neurocognitive performance at enrollment. Compared with noncarriers (n=389), children with genomic disorders (n=31) scored significantly poorer on all measures of intelligence, anxiety/depressive symptoms, and executive function (differences of 0.6–0.7 SD; P=1.2×10−3–2.4×10−4). These differences persisted after controlling for known modifiers, including low birth weight, maternal education, seizure disorder, kidney disease duration, and genetically defined ancestry. The deleterious effect of genomic disorders on neurocognitive function was significantly attenuated in offspring of mothers with higher education, indicating the potential for modification by genetic and/or environmental factors. These data indicate that impaired neurocognitive function in some children with CKD may be attributable to genetic lesions that affect both kidney and neurocognitive development. Early identification of genomic disorders may provide opportunity for early diagnosis and personalized interventions to mitigate the effect on neurocognitive function.Verbitsky, MiguelKogon, Amy J.Matheson, MatthewHooper, Stephen R.Wong, Craig S.Warady, Bradley A.Furth, Susan L.Gharavi, Ali G.2017-03-27T06:47:49-07:00doi:10.1681/ASN.2016101108hwp:resource-id:jnephrol;28/8/2303American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, pediatric nephrology, human genetics, Epidemiology and outcomesBrief CommunicationBrief Communicationbrief-report20172017-08-01August 201710.1681/ASN.20161011081046-66731533-34502017-03-27T06:47:49-07:002017-08Journal of the American Society of NephrologyBrief Communication28823032309
- Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the NephronTight control of extracellular and intracellular inorganic phosphate (Pi) levels is critical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the molecular identity of the protein(s) participating in the basolateral Pi efflux remains unknown. Evidence has suggested that xenotropic and polytropic retroviral receptor 1 (XPR1) might be involved in this process. Here, we show that conditional inactivation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi reabsorption. Analysis of Pi transport in primary cultures of proximal tubular cells or in freshly isolated renal tubules revealed that this Xpr1 deficiency significantly affected Pi efflux. Further, mice with conditional inactivation of Xpr1 in the renal tubule exhibited generalized proximal tubular dysfunction indicative of Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria, and albuminuria. Dramatic alterations in the renal transcriptome, including a significant reduction in NaPi-IIa/NaPi-IIc expression, accompanied these functional changes. Additionally, Xpr1-deficient mice developed hypophosphatemic rickets secondary to renal dysfunction. These results identify XPR1 as a major regulator of Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.10.1681/ASN.2016070726Mon, 31 Oct 2016 09:16:37 GMT-07:00Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the NephronTight control of extracellular and intracellular inorganic phosphate (Pi) levels is critical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the molecular identity of the protein(s) participating in the basolateral Pi efflux remains unknown. Evidence has suggested that xenotropic and polytropic retroviral receptor 1 (XPR1) might be involved in this process. Here, we show that conditional inactivation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi reabsorption. Analysis of Pi transport in primary cultures of proximal tubular cells or in freshly isolated renal tubules revealed that this Xpr1 deficiency significantly affected Pi efflux. Further, mice with conditional inactivation of Xpr1 in the renal tubule exhibited generalized proximal tubular dysfunction indicative of Fanconi syndrome, characterized by glycosuria, aminoaciduria, calciuria, and albuminuria. Dramatic alterations in the renal transcriptome, including a significant reduction in NaPi-IIa/NaPi-IIc expression, accompanied these functional changes. Additionally, Xpr1-deficient mice developed hypophosphatemic rickets secondary to renal dysfunction. These results identify XPR1 as a major regulator of Pi homeostasis and as a potential therapeutic target in bone and kidney disorders.Ansermet, CamilleMoor, Matthias B.Centeno, GabrielAuberson, MurielHu, Dorothy ZhangBaron, RolandNikolaeva, SvetlanaHaenzi, BarbaraKatanaeva, NatalyaGautschi, IvanKatanaev, VladimirRotman, SamuelKoesters, RobertSchild, LaurentPradervand, SylvainBonny, OlivierFirsov, Dmitri2016-10-31T09:16:37-07:00doi:10.1681/ASN.2016070726hwp:resource-id:jnephrol;28/4/1073American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate homeostasis, kidney, retroviral receptor XPR1, Fanconi syndrome, hypophosphatemic ricketsBrief CommunicationsBrief Communicationsbrief-report20172017-04-01April 201710.1681/ASN.20160707261046-66731533-34502016-10-31T09:16:37-07:002017-04Journal of the American Society of NephrologyBrief Communications28410731078
- Update on the Burden of CKD10.1681/ASN.2016121374Thu, 16 Mar 2017 07:18:01 GMT-07:00Update on the Burden of CKDCoresh, Josef2017-03-16T07:18:01-07:00doi:10.1681/ASN.2016121374hwp:resource-id:jnephrol;28/4/1020American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, burden, renal replacement therapyUp Front MattersPerspectivesUp Front MattersPerspectivesresearch-article20172017-04-01April 201710.1681/ASN.20161213741046-66731533-34502017-03-16T07:18:01-07:002017-04Journal of the American Society of NephrologyUp Front Matters28410201022
- Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD TrialReduction of residual albuminuria during single–agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)–controlled, crossover trial, 45 patients with nondiabetic CKD stages 1–3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na+ per day in the combined RS groups and 108±61 mmol Na+ per day in the LS groups (P<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin–converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.10.1681/ASN.2016040407Thu, 17 Nov 2016 07:23:27 GMT-08:00Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD TrialReduction of residual albuminuria during single–agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)–controlled, crossover trial, 45 patients with nondiabetic CKD stages 1–3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na+ per day in the combined RS groups and 108±61 mmol Na+ per day in the LS groups (P<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin–converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.Keyzer, Charlotte A.van Breda, G. FennaVervloet, Marc G.de Jong, Maarten A.Laverman, Gozewijn D.Hemmelder, Marc H.Janssen, Wilbert M.T.Lambers Heerspink, Hiddo J.Kwakernaak, Arjan J.Bakker, Stephan J.L.Navis, Gerjande Borst, Martin H.Keyzer, Charlotte A.van Breda, G. FennaVervloet, Marc G.de Jong, Maarten A.Laverman, Gozewijn D.Hemmelder, Marc H.Janssen, Wilbert M.T.Lambers Heerspink, Hiddo J.Kwakernaak, Arjan J.Bakker, Stephan J.L.Navis, Gerjande Borst, Martin H.2016-11-17T07:23:27-08:00doi:10.1681/ASN.2016040407hwp:resource-id:jnephrol;28/4/1296American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrandomized-controlled trial, paricalcitol, VDRA, dietary sodium restriction, albuminuria, chronic kidney diseaseClinical ResearchClinical Researchresearch-article20172017-04-01April 201710.1681/ASN.20160404071046-66731533-34502016-11-17T07:23:27-08:002017-04Journal of the American Society of NephrologyClinical Research28441296101613051019
- Thrombotic Microangiopathy in Inverted Formin 2–Mediated Renal DiseaseThe demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab. Her mother had previously presented with a post–renal transplant TMA. Both the proposita and her mother also had Charcot–Marie–Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionally-significant mutation in INF2. In this family, renal transplantation was associated with post-transplant TMA. All individuals with INF2 mutations presenting with a TMA also had aHUS risk haplotypes, potentially accounting for the genetic pleiotropy. Identifying individuals with TMAs who may not respond to eculizumab will avoid prolonged exposure of such individuals to the infectious complications of terminal pathway C blockade.10.1681/ASN.2015101189Wed, 14 Dec 2016 05:05:25 GMT-08:00Thrombotic Microangiopathy in Inverted Formin 2–Mediated Renal DiseaseThe demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab. Her mother had previously presented with a post–renal transplant TMA. Both the proposita and her mother also had Charcot–Marie–Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionally-significant mutation in INF2. In this family, renal transplantation was associated with post-transplant TMA. All individuals with INF2 mutations presenting with a TMA also had aHUS risk haplotypes, potentially accounting for the genetic pleiotropy. Identifying individuals with TMAs who may not respond to eculizumab will avoid prolonged exposure of such individuals to the infectious complications of terminal pathway C blockade.Challis, Rachel C.Ring, TroelsXu, YaoboWong, Edwin K.S.Flossmann, OliverRoberts, Ian S.D.Ahmed, SaeedWetherall, MichaelSalkus, GiedriusBrocklebank, VickyFester, JulianStrain, LisaWilson, ValerieWood, Katrina M.Marchbank, Kevin J.Santibanez-Koref, MauroGoodship, Timothy H.J.Kavanagh, David2016-12-14T05:05:25-08:00doi:10.1681/ASN.2015101189hwp:resource-id:jnephrol;28/4/1084American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, hemolytic uremic syndrome, focal segmental glomerulosclerosisBrief CommunicationsBrief Communicationsbrief-report20172017-04-01April 201710.1681/ASN.20151011891046-66731533-34502016-12-14T05:05:25-08:002017-04Journal of the American Society of NephrologyBrief Communications28410841091
- GFR Evaluation in Living Kidney Donor CandidatesEvaluation of GFR, required in the evaluation of living kidney donor candidates, is now receiving increasing emphasis because recent data demonstrate increased risk of kidney disease after donation, including a small increase in the risk of kidney failure. The international guideline development group, Kidney Disease Improving Global Outcomes, recently published a comprehensive set of recommendations for living donor evaluation, with three recommendations regarding GFR. (1) Donor candidacy is evaluated in light of long-term risk, in which GFR is one of many factors. ESRD is considered a central outcome, and a method for estimating long-term risk of ESRD in donor candidates is described. (2) Two GFR thresholds are used for decision-making: a high threshold (≥90 ml/min per 1.73 m2) to accept and a low threshold (<60 ml/min per 1.73 m2) to decline, with 60–89 ml/min per 1.73 m2 as an intermediate range in which the decision to accept or decline is made on the basis of factors in addition to GFR. (3) GFR is evaluated using several methods available at the transplant center, including estimating equations and clearance measurements. We review the rationale for the guideline recommendations, principles of GFR measurement and estimation, and our suggestions for implementation.10.1681/ASN.2016070790Wed, 15 Mar 2017 05:56:07 GMT-07:00GFR Evaluation in Living Kidney Donor CandidatesEvaluation of GFR, required in the evaluation of living kidney donor candidates, is now receiving increasing emphasis because recent data demonstrate increased risk of kidney disease after donation, including a small increase in the risk of kidney failure. The international guideline development group, Kidney Disease Improving Global Outcomes, recently published a comprehensive set of recommendations for living donor evaluation, with three recommendations regarding GFR. (1) Donor candidacy is evaluated in light of long-term risk, in which GFR is one of many factors. ESRD is considered a central outcome, and a method for estimating long-term risk of ESRD in donor candidates is described. (2) Two GFR thresholds are used for decision-making: a high threshold (≥90 ml/min per 1.73 m2) to accept and a low threshold (<60 ml/min per 1.73 m2) to decline, with 60–89 ml/min per 1.73 m2 as an intermediate range in which the decision to accept or decline is made on the basis of factors in addition to GFR. (3) GFR is evaluated using several methods available at the transplant center, including estimating equations and clearance measurements. We review the rationale for the guideline recommendations, principles of GFR measurement and estimation, and our suggestions for implementation.Levey, Andrew S.Inker, Lesley A.2017-03-15T05:56:07-07:00doi:10.1681/ASN.2016070790hwp:resource-id:jnephrol;28/4/1062American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rate, kidney donation, living donor evaluation, ESRD, riskUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20172017-04-01April 201710.1681/ASN.20160707901046-66731533-34502017-03-15T05:56:07-07:002017-04Journal of the American Society of NephrologyUp Front Matters28410621071
- Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United StatesIncreased urine albumin excretion is highly prevalent in Hispanics/Latinos. Previous studies have found an association between urine albumin excretion and Amerindian ancestry in Hispanic/Latino populations. Admixture between racial/ethnic groups creates long-range linkage disequilibrium between variants with different allelic frequencies in the founding populations and it can be used to localize genes. Hispanic/Latino genomes are an admixture of European, African, and Amerindian ancestries. We leveraged this admixture to identify associations between urine albumin excretion (urine albumin-to-creatinine ratio [UACR]) and genomic regions harboring variants with highly differentiated allele frequencies among the ancestral populations. Admixture mapping analysis of 12,212 Hispanic Community Health Study/Study of Latinos participants, using a linear mixed model, identified three novel genome-wide significant signals on chromosomes 2, 11, and 16. The admixture mapping signal identified on chromosome 2, spanning q11.2–14.1 and not previously reported for UACR, is driven by a difference between Amerindian ancestry and the other two ancestries (P<5.7 × 10−5). Within this locus, two common variants located at the proapoptotic BCL2L11 gene associated with UACR: rs116907128 (allele frequency =0.14; P=1.5 × 10−7) and rs586283 (C allele frequency =0.35; P=4.2 × 10−7). In a secondary analysis, rs116907128 accounted for most of the admixture mapping signal observed in the region. The rs116907128 variant is common among full-heritage Pima Indians (A allele frequency =0.54) but is monomorphic in the 1000 Genomes European and African populations. In a replication analysis using a sample of full-heritage Pima Indians, rs116907128 significantly associated with UACR (P=0.01; n=1568). Our findings provide evidence for the presence of Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.10.1681/ASN.2016091010Mon, 30 Jan 2017 06:48:05 GMT-08:00Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United StatesIncreased urine albumin excretion is highly prevalent in Hispanics/Latinos. Previous studies have found an association between urine albumin excretion and Amerindian ancestry in Hispanic/Latino populations. Admixture between racial/ethnic groups creates long-range linkage disequilibrium between variants with different allelic frequencies in the founding populations and it can be used to localize genes. Hispanic/Latino genomes are an admixture of European, African, and Amerindian ancestries. We leveraged this admixture to identify associations between urine albumin excretion (urine albumin-to-creatinine ratio [UACR]) and genomic regions harboring variants with highly differentiated allele frequencies among the ancestral populations. Admixture mapping analysis of 12,212 Hispanic Community Health Study/Study of Latinos participants, using a linear mixed model, identified three novel genome-wide significant signals on chromosomes 2, 11, and 16. The admixture mapping signal identified on chromosome 2, spanning q11.2–14.1 and not previously reported for UACR, is driven by a difference between Amerindian ancestry and the other two ancestries (P<5.7 × 10−5). Within this locus, two common variants located at the proapoptotic BCL2L11 gene associated with UACR: rs116907128 (allele frequency =0.14; P=1.5 × 10−7) and rs586283 (C allele frequency =0.35; P=4.2 × 10−7). In a secondary analysis, rs116907128 accounted for most of the admixture mapping signal observed in the region. The rs116907128 variant is common among full-heritage Pima Indians (A allele frequency =0.54) but is monomorphic in the 1000 Genomes European and African populations. In a replication analysis using a sample of full-heritage Pima Indians, rs116907128 significantly associated with UACR (P=0.01; n=1568). Our findings provide evidence for the presence of Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.Brown, Lisa A.Sofer, TamarStilp, Adrienne M.Baier, Leslie J.Kramer, Holly J.Masindova, IvicaLevy, DanielHanson, Robert L.Moncrieft, Ashley E.Redline, SusanRosas, Sylvia E.Lash, James P.Cai, JianwenLaurie, Cathy C.Browning, SharonThornton, TimothyFranceschini, Nora2017-01-30T06:48:05-08:00doi:10.1681/ASN.2016091010hwp:resource-id:jnephrol;28/7/2211American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhuman genetics, albuminuria, ethnic minority, genomics, ethnic groups, albuminsClinical ResearchClinical Researchresearch-article20172017-07-01July 201710.1681/ASN.20160910101046-66731533-34502017-01-30T06:48:05-08:002017-07Journal of the American Society of NephrologyClinical Research28722112220
- Targeting mTOR Signaling Can Prevent the Progression of FSGSMammalian target of rapamycin (mTOR) signaling is involved in a variety of kidney diseases. Clinical trials administering mTOR inhibitors to patients with FSGS, a prototypic podocyte disease, led to conflicting results, ranging from remission to deterioration of kidney function. Here, we combined complex genetic titration of mTOR complex 1 (mTORC1) levels in murine glomerular disease models, pharmacologic studies, and human studies to precisely delineate the role of mTOR in FSGS. mTORC1 target genes were significantly induced in microdissected glomeruli from both patients with FSGS and a murine FSGS model. Furthermore, a mouse model with constitutive mTORC1 activation closely recapitulated human FSGS. Notably, the complete knockout of mTORC1 by induced deletion of both Raptor alleles accelerated the progression of murine FSGS models. However, lowering mTORC1 signaling by deleting just one Raptor allele ameliorated the progression of glomerulosclerosis. Similarly, low-dose treatment with the mTORC1 inhibitor rapamycin efficiently diminished disease progression. Mechanistically, complete pharmacologic inhibition of mTOR in immortalized podocytes shifted the cellular energy metabolism toward reduced rates of oxidative phosphorylation and anaerobic glycolysis, which correlated with increased production of reactive oxygen species. Together, these data suggest that podocyte injury and loss is commonly followed by adaptive mTOR activation. Prolonged mTOR activation, however, results in a metabolic podocyte reprogramming leading to increased cellular stress and dedifferentiation, thus offering a treatment rationale for incomplete mTOR inhibition.10.1681/ASN.2016050519Tue, 07 Mar 2017 06:25:48 GMT-08:00Targeting mTOR Signaling Can Prevent the Progression of FSGSMammalian target of rapamycin (mTOR) signaling is involved in a variety of kidney diseases. Clinical trials administering mTOR inhibitors to patients with FSGS, a prototypic podocyte disease, led to conflicting results, ranging from remission to deterioration of kidney function. Here, we combined complex genetic titration of mTOR complex 1 (mTORC1) levels in murine glomerular disease models, pharmacologic studies, and human studies to precisely delineate the role of mTOR in FSGS. mTORC1 target genes were significantly induced in microdissected glomeruli from both patients with FSGS and a murine FSGS model. Furthermore, a mouse model with constitutive mTORC1 activation closely recapitulated human FSGS. Notably, the complete knockout of mTORC1 by induced deletion of both Raptor alleles accelerated the progression of murine FSGS models. However, lowering mTORC1 signaling by deleting just one Raptor allele ameliorated the progression of glomerulosclerosis. Similarly, low-dose treatment with the mTORC1 inhibitor rapamycin efficiently diminished disease progression. Mechanistically, complete pharmacologic inhibition of mTOR in immortalized podocytes shifted the cellular energy metabolism toward reduced rates of oxidative phosphorylation and anaerobic glycolysis, which correlated with increased production of reactive oxygen species. Together, these data suggest that podocyte injury and loss is commonly followed by adaptive mTOR activation. Prolonged mTOR activation, however, results in a metabolic podocyte reprogramming leading to increased cellular stress and dedifferentiation, thus offering a treatment rationale for incomplete mTOR inhibition.Zschiedrich, StefanBork, TillmannLiang, WeiWanner, NicolaEulenbruch, KristinaMunder, StefanHartleben, BjörnKretz, OliverGerber, SimonSimons, MatiasViau, AmandineBurtin, MartineWei, ChangliReiser, JochenHerbach, NadjaRastaldi, Maria-PiaCohen, Clemens DTharaux, Pierre-LouisTerzi, FabiolaWalz, GerdGödel, MarkusHuber, Tobias B2017-03-07T06:25:48-08:00doi:10.1681/ASN.2016050519hwp:resource-id:jnephrol;28/7/2144American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, mTOR, Pathophysiology of Renal Disease and Progression, mitochondrial function, rapamycin, raptorBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160505191046-66731533-34502017-03-07T06:25:48-08:002017-07Journal of the American Society of NephrologyBasic Research28721442157
- Global Cardiovascular and Renal Outcomes of Reduced GFRThe burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.10.1681/ASN.2016050562Thu, 13 Apr 2017 06:19:33 GMT-07:00Global Cardiovascular and Renal Outcomes of Reduced GFRThe burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.Thomas, BernadetteMatsushita, KunihiroAbate, Kalkidan HassenAl-Aly, ZiyadÄrnlöv, JohanAsayama, KeiAtkins, RobertBadawi, AlaaBallew, Shoshana H.Banerjee, AmitavaBarregård, LarsBarrett-Connor, ElizabethBasu, SanjayBello, Aminu K.Bensenor, IsabelaBergstrom, JaclynBikbov, BorisBlosser, ChristopherBrenner, HermannCarrero, Juan-JesusChadban, SteveCirillo, MassimoCortinovis, MonicaCourville, KarenDandona, LalitDandona, RakhiEstep, KaraFernandes, JoãoFischer, FlorianFox, CarolineGansevoort, Ron T.Gona, Philimon N.Gutierrez, Orlando M.Hamidi, SamerHanson, Sarah WulfHimmelfarb, JonathanJassal, Simerjot K.Jee, Sun HaJha, VivekanandJimenez-Corona, AidaJonas, Jost B.Kengne, Andre PascalKhader, YousefKhang, Young-HoKim, Yun JinKlein, BarbaraKlein, RonaldKokubo, YoshihiroKolte, DhavalLee, KristineLevey, Andrew S.Li, YongmeiLotufo, PauloEl Razek, Hassan Magdy AbdMendoza, WalterMetoki, HirohitoMok, YejinMuraki, IsaoMuntner, Paul M.Noda, HiroyukiOhkubo, TakayoshiOrtiz, AlbertoPerico, NorbertoPolkinghorne, KevanAl-Radaddi, RajaaRemuzzi, GiuseppeRoth, GregoryRothenbacher, DietrichSatoh, MichihiroSaum, Kai-UweSawhney, MonikaSchöttker, BenShankar, AnoopShlipak, MichaelSilva, Diego Augusto SantosToyoshima, HideakiUkwaja, KingsleyUmesawa, MitsumasaVollset, Stein EmilWarnock, David G.Werdecker, AndreaYamagishi, KazumasaYano, YuichiroYonemoto, NaohiroZaki, Maysaa El SayedNaghavi, MohsenForouzanfar, Mohammad H.Murray, Christopher J.L.Coresh, JosefVos, Theo,,,Thomas, BernadetteMatsushita, KunihiroAbate, Kalkidan HassenAl-Aly, ZiyadÄrnlöv, JohanAsayama, KeiAtkins, RobertBadawi, AlaaBallew, Shoshana H.Banerjee, AmitavaBarregård, LarsBarrett-Connor, ElizabethBello, AminuBensenor, IsabelaBergstrom, JaclynBikbov, BorisBlosser, ChristopherBrenner, HermannCarrero, Juan-JesusChadban, SteveCirillo, MassimoCortinovis, MonicaCourville, KarenDandona, LalitDandona, RakhiEstep, KaraFernandes, JoãoFischer, FlorianFox, CarolineGansevoort, Ron T.Gutierrez, Orlando M.Hamidi, SamerHanson, SarahHimmelfarb, JonathanJassal, Simerjot K.Jee, Sun HaJha, VivekanandJimenez-Corona, AidaJonas, Jost B.Kengne, Andre PascalKhader, YousefKhang, Young-HoKim, Yun JinKlein, BarbaraKlein, RonaldKokubo, YoshihiroKolte, DhavalLee, KristineLevey, Andrew S.Li, YongmeiLotufo, PauloEl Razek, Hassan Magdy AbdMendoza, WalterMetoki, HirohitoMok, YejinMuraki, IsaoMuntner, Paul M.Noda, HiroyukiOhkubo, TakayoshiOrtiz, AlbertoPerico, NorbertoPolkinghorne, KevanAl-Radaddi, RajaaRemuzzi, GiuseppiRoth, GregoryRothenbacher, DietrichSatoh, MichihiroSaum, Kai-UweSawhney, MonikaSchöttker, BenShankar, AnoopShlipak, MichaelSilva, Diego Augusto SantosToyoshima, HideakiUkwaja, KingsleyUmesawa, MitsumasaVollset, Stein EmilWarnock, David G.Werdecker, AndreaYamagishi, KazumasaYano, YuichiroYonemoto, NaohiroZaki, Maysaa El SayedNaghavi, MohsenForouzanfar, Mohammad H.Murray, Christopher J. L.Coresh, JosefVos, Theo2017-04-13T06:19:33-07:00doi:10.1681/ASN.2016050562hwp:resource-id:jnephrol;28/7/2167American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, cardiovascular disease, chronic kidney disease, Epidemiology and outcomes, chronic dialysisClinical EpidemiologyClinical Epidemiologyresearch-article20172017-07-01July 201710.1681/ASN.20160505621046-66731533-34502017-04-13T06:19:33-07:002017-07Journal of the American Society of NephrologyClinical Epidemiology28721672179
- Education in Nephrology Fellowship: A Survey-Based Needs AssessmentEducational needs assessments for nephrology fellowship training are limited. This study assessed fellows’ perceptions of current educational needs and interest in novel modalities that may improve their educational experience and quantified educational resources used by programs and fellows. We distributed a seven-question electronic survey to all United States–based fellows receiving complimentary American Society of Nephrology (ASN) membership at the end of the 2015–2016 academic year in conjunction with the ASN Nephrology Fellows Survey. One third (320 of 863; 37%) of fellows in Accreditation Council for Graduate Medical Education–accredited positions responded. Most respondents rated overall quality of teaching in fellowship as either “good” (37%) or “excellent” (44%), and most (55%) second-year fellows felt “fully prepared” for independent practice. Common educational resources used by fellows included UpToDate, Journal of the American Society of Nephrology/Clinical Journal of the American Society of Nephrology, and Nephrology Self-Assessment Program; others—including ASN’s online curricula—were used less often. Fellows indicated interest in additional instruction in several core topics, including home dialysis modalities, ultrasonography, and pathology. Respondents strongly supported interventions to improve pathology instruction and increase time for physiology and clinical review. In conclusion, current nephrology fellows perceive several gaps in training. Innovation in education and training is needed to better prepare future nephrologists for the growing challenges of kidney care.10.1681/ASN.2016101061Thu, 20 Apr 2017 06:08:57 GMT-07:00Education in Nephrology Fellowship: A Survey-Based Needs AssessmentEducational needs assessments for nephrology fellowship training are limited. This study assessed fellows’ perceptions of current educational needs and interest in novel modalities that may improve their educational experience and quantified educational resources used by programs and fellows. We distributed a seven-question electronic survey to all United States–based fellows receiving complimentary American Society of Nephrology (ASN) membership at the end of the 2015–2016 academic year in conjunction with the ASN Nephrology Fellows Survey. One third (320 of 863; 37%) of fellows in Accreditation Council for Graduate Medical Education–accredited positions responded. Most respondents rated overall quality of teaching in fellowship as either “good” (37%) or “excellent” (44%), and most (55%) second-year fellows felt “fully prepared” for independent practice. Common educational resources used by fellows included UpToDate, Journal of the American Society of Nephrology/Clinical Journal of the American Society of Nephrology, and Nephrology Self-Assessment Program; others—including ASN’s online curricula—were used less often. Fellows indicated interest in additional instruction in several core topics, including home dialysis modalities, ultrasonography, and pathology. Respondents strongly supported interventions to improve pathology instruction and increase time for physiology and clinical review. In conclusion, current nephrology fellows perceive several gaps in training. Innovation in education and training is needed to better prepare future nephrologists for the growing challenges of kidney care.Rope, Robert W.Pivert, Kurtis A.Parker, Mark G.Sozio, Stephen M.Merell, Sylvia Bereknyei2017-04-20T06:08:57-07:00doi:10.1681/ASN.2016101061hwp:resource-id:jnephrol;28/7/1983American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyeducation, fellowship, needs-assessmentUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20172017-07-01July 201710.1681/ASN.20161010611046-66731533-34502017-04-20T06:08:57-07:002017-07Journal of the American Society of NephrologyUp Front Matters28719831990
- The Angiopoietin-Tie2 Signaling Axis in Systemic InflammationSystemic inflammation is a hallmark of commonly encountered diseases ranging from bacterial sepsis to sterile syndromes such as major trauma. Derangements in the host vasculature contribute to the cardinal manifestations of sepsis in profound ways. Recent studies of control pathways regulating the vascular endothelium have illuminated how this single cell layer toggles between quiescence and activation to affect the development of shock and multiorgan dysfunction. This article focuses on one such control pathway, the Tie2 receptor and its ligands the angiopoietins, to describe a growing body of genetic, biochemical, mechanistic, and human studies that implicate Tie2 as a critical switch. In health, activated Tie2 maintains the endothelium in a quiescent state characterized by dynamic barrier function and antiadhesion against circulating leukocytes. In sepsis and related diseases, expression of the angiopoietins becomes markedly imbalanced and Tie2 signaling is greatly attenuated. These rapid molecular changes potentiate pathophysiologic responses throughout the body, resulting in injurious vascular leakage and organ inflammation. The Tie2 axis, therefore, may be a promising avenue for future translational studies.10.1681/ASN.2017010069Tue, 02 May 2017 07:10:34 GMT-07:00The Angiopoietin-Tie2 Signaling Axis in Systemic InflammationSystemic inflammation is a hallmark of commonly encountered diseases ranging from bacterial sepsis to sterile syndromes such as major trauma. Derangements in the host vasculature contribute to the cardinal manifestations of sepsis in profound ways. Recent studies of control pathways regulating the vascular endothelium have illuminated how this single cell layer toggles between quiescence and activation to affect the development of shock and multiorgan dysfunction. This article focuses on one such control pathway, the Tie2 receptor and its ligands the angiopoietins, to describe a growing body of genetic, biochemical, mechanistic, and human studies that implicate Tie2 as a critical switch. In health, activated Tie2 maintains the endothelium in a quiescent state characterized by dynamic barrier function and antiadhesion against circulating leukocytes. In sepsis and related diseases, expression of the angiopoietins becomes markedly imbalanced and Tie2 signaling is greatly attenuated. These rapid molecular changes potentiate pathophysiologic responses throughout the body, resulting in injurious vascular leakage and organ inflammation. The Tie2 axis, therefore, may be a promising avenue for future translational studies.Parikh, Samir M.2017-05-02T07:10:34-07:00doi:10.1681/ASN.2017010069hwp:resource-id:jnephrol;28/7/1973American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cardiovascular, chronic kidney disease, vascular, endothelial cells, kidney stonesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-07-01July 201710.1681/ASN.20170100691046-66731533-34502017-05-02T07:10:34-07:002017-07Journal of the American Society of NephrologyUp Front Matters28719731982
- Anti-Glomerular Basement Membrane DiseaseAnti–glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals. The majority of patients develop widespread glomerular crescent formation, presenting with features of rapidly progressive GN, and 40%–60% will have concurrent alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody, typically with the use of plasma exchange, along with steroids and cytotoxic therapy to prevent ongoing autoantibody production and tissue inflammation. Retrospective cohort studies suggest that when this combination of treatment is started early, the majority of patients will have good renal outcome, although presentation with oligoanuria, a high proportion of glomerular crescents, or kidney failure requiring dialysis augur badly for renal prognosis. Relapse and recurrent disease after kidney transplantation are both uncommon, although de novo anti-GBM disease after transplantation for Alport syndrome is a recognized phenomenon. Copresentation with other kidney diseases such as ANCA-associated vasculitis and membranous nephropathy seems to occur at a higher frequency than would be expected by chance alone, and in addition atypical presentations of anti-GBM disease are increasingly reported. These observations highlight the need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, particularly for patients presenting with adverse prognostic factors.10.2215/CJN.01380217Wed, 17 May 2017 05:38:18 GMT-07:00Anti-Glomerular Basement Membrane DiseaseAnti–glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals. The majority of patients develop widespread glomerular crescent formation, presenting with features of rapidly progressive GN, and 40%–60% will have concurrent alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody, typically with the use of plasma exchange, along with steroids and cytotoxic therapy to prevent ongoing autoantibody production and tissue inflammation. Retrospective cohort studies suggest that when this combination of treatment is started early, the majority of patients will have good renal outcome, although presentation with oligoanuria, a high proportion of glomerular crescents, or kidney failure requiring dialysis augur badly for renal prognosis. Relapse and recurrent disease after kidney transplantation are both uncommon, although de novo anti-GBM disease after transplantation for Alport syndrome is a recognized phenomenon. Copresentation with other kidney diseases such as ANCA-associated vasculitis and membranous nephropathy seems to occur at a higher frequency than would be expected by chance alone, and in addition atypical presentations of anti-GBM disease are increasingly reported. These observations highlight the need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, particularly for patients presenting with adverse prognostic factors.McAdoo, Stephen P.Pusey, Charles D.2017-05-17T05:38:18-07:00doi:10.2215/CJN.01380217hwp:resource-id:clinjasn;12/7/1162American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyImmunology and pathology, vasculitis, Anti-Glomerular Basement Membrane Disease, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Autoantibodies, Autoantigens, Autoimmunity, Capillaries, Glomerular Basement Membrane, glomerulonephritis, Glomerulonephritis, Membranous, Humans, Inflammation, kidney, kidney transplantation, Nephritis, Hereditary, Plasma Exchange, Plasmapheresis, Prognosis, Recurrence, renal dialysis, Renal Insufficiency, Retrospective StudiesGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-07-07July 07, 201710.2215/CJN.013802171555-90411555-905X2017-05-17T05:38:18-07:002017-07-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician12711621172
- A Woman with ESRD with Increasing Need for Erythropoietin to Maintain Hemoglobin10.2215/CJN.01160117Thu, 18 May 2017 11:07:34 GMT-07:00A Woman with ESRD with Increasing Need for Erythropoietin to Maintain HemoglobinKoncicki, Holly M.Fishbane, Steven2017-05-18T11:07:34-07:00doi:10.2215/CJN.01160117hwp:resource-id:clinjasn;12/7/1173American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, erythropoietin, hyperparathyroidismKidney Case ConferencesAttending RoundsKidney Case ConferencesAttending Roundsresearch-article20172017-07-07July 07, 201710.2215/CJN.011601171555-90411555-905X2017-05-18T11:07:34-07:002017-07-07Clinical Journal of the American Society of NephrologyKidney Case Conferences12711731175
- Paroxysmal Atrial Fibrillation in a Patient on Hemodialysis10.2215/CJN.00790117Fri, 09 Jun 2017 05:45:20 GMT-07:00Paroxysmal Atrial Fibrillation in a Patient on HemodialysisLok, Charmaine E.2017-06-09T05:45:20-07:00doi:10.2215/CJN.00790117hwp:resource-id:clinjasn;12/7/1176American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAtrial Fibrillation, Humans, renal dialysisKidney Case ConferencesNephrology Quiz and QuestionnaireKidney Case ConferencesNephrology Quiz and Questionnaireresearch-article20172017-07-07July 07, 201710.2215/CJN.007901171555-90411555-905X2017-06-09T05:45:20-07:002017-07-07Clinical Journal of the American Society of NephrologyKidney Case Conferences12711761180
- A Systematic Review of the Prevalence and Associations of Limited Health Literacy in CKD10.2215/CJN.12921216Tue, 09 May 2017 06:37:07 GMT-07:00A Systematic Review of the Prevalence and Associations of Limited Health Literacy in CKDTaylor, Dominic M.Fraser, Simon D.S.Bradley, J. AndrewBradley, ClareDraper, HeatherMetcalfe, WendyOniscu, Gabriel C.Tomson, Charles R.V.Ravanan, RommelRoderick, Paul J.,2017-05-09T06:37:07-07:00doi:10.2215/CJN.12921216hwp:resource-id:clinjasn;12/7/1070American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, chronic kidney disease, ethnicity, Cohort Studies, Cross-Sectional Studies, Disease Management, Ethnic Groups, Health Literacy, Humans, Patient Selection, Prevalence, renal dialysis, Renal Insufficiency, Chronic, Self Care, Social Class, Surveys and QuestionnairesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-07-07July 07, 201710.2215/CJN.129212161555-90411555-905X2017-05-09T06:37:07-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12710701084
- Renal Functional Outcomes after Surgery, Ablation, and Active Surveillance of Localized Renal Tumors: A Systematic Review and Meta-Analysis10.2215/CJN.11941116Mon, 08 May 2017 08:02:26 GMT-07:00Renal Functional Outcomes after Surgery, Ablation, and Active Surveillance of Localized Renal Tumors: A Systematic Review and Meta-AnalysisPatel, Hiten D.Pierorazio, Phillip M.Johnson, Michael H.Sharma, RituIyoha, EmmanuelAllaf, Mohamad E.Bass, Eric B.Sozio, Stephen M.2017-05-08T08:02:26-07:00doi:10.2215/CJN.11941116hwp:resource-id:clinjasn;12/7/1057American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, kidney neoplasms, acute kidney injury, outcome studies, Acute Kidney Injury, Attention, Carcinoma, Renal Cell, Clinical Decision-Making, Confidence Intervals, glomerular filtration rate, Humans, Incidence, kidney, Kidney Failure, Chronic, MEDLINE, Nephrectomy, Nephrons, Renal Insufficiency, Chronic, RiskOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-07-07July 07, 201710.2215/CJN.119411161555-90411555-905X2017-05-08T08:02:26-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12710571069
- Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing Hemodialysis10.2215/CJN.11141016Mon, 19 Jun 2017 06:13:11 GMT-07:00Calcium-Sensing Receptor Genotype and Response to Cinacalcet in Patients Undergoing HemodialysisMoe, Sharon M.Wetherill, LeahDecker, Brian ScottLai, DongbingAbdalla, SafaLong, JinVatta, MatteoForoud, Tatiana M.Chertow, Glenn M.2017-06-19T06:13:11-07:00doi:10.2215/CJN.11141016hwp:resource-id:clinjasn;12/7/1128American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhuman genetics, calcium sensing receptor, fracture, FGF23, single nucleotide polymorphisms, Alkaline Phosphatase, Alleles, calcium, Chronic Kidney Disease-Mineral and Bone Disorder, Cinacalcet Hydrochloride, DNA, Genotype, Humans, Linkage Disequilibrium, Minerals, parathyroid hormone, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing, renal dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-07-07July 07, 201710.2215/CJN.111410161555-90411555-905X2017-06-19T06:13:11-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12771128103511381037
- Infection Monitoring in Dialysis Units: A Plea for “Cleaner” Data10.2215/CJN.05220517Thu, 29 Jun 2017 06:17:45 GMT-07:00Infection Monitoring in Dialysis Units: A Plea for “Cleaner” DataMiskulin, Dana C.Gul, Ambreen2017-06-29T06:17:45-07:00doi:10.2215/CJN.05220517hwp:resource-id:clinjasn;12/7/1038American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis access, bacteremia, quality improvement, Animals, Hemodialysis Units, Hospital, Hepatitis C, Heteroptera, renal dialysisEditorialsEditorialseditorial20172017-07-07July 07, 201710.2215/CJN.052205171555-90411555-905X2017-06-29T06:17:45-07:002017-07-07Clinical Journal of the American Society of NephrologyEditorials12771038113910391146
- Longitudinal Associations among Renal Urea Clearance–Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis10.2215/CJN.13141216Wed, 10 May 2017 06:17:27 GMT-07:00Longitudinal Associations among Renal Urea Clearance–Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on HemodialysisEriguchi, RiekoObi, YoshitsuguStreja, ElaniTortorici, Amanda R.Rhee, Connie M.Soohoo, MelissaKim, TaeheeKovesdy, Csaba P.Kalantar-Zadeh, Kamyar2017-05-10T06:17:27-07:00doi:10.2215/CJN.13141216hwp:resource-id:clinjasn;12/7/1109American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDietary protein intake (DPI), residual kidney function, mortality, hemodialysis, albumin, protein catabolic rate (PCR), Dietary Proteins, Fluid Therapy, Follow-Up Studies, Humans, Odds Ratio, Proportional Hazards Models, renal dialysis, Serum Albumin, urea, Urinary Tract Physiological PhenomenaOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-07-07July 07, 201710.2215/CJN.131412161555-90411555-905X2017-05-10T06:17:27-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12711091117
- Characteristics and Outcomes of In-Hospital Palliative Care Consultation among Patients with Renal Disease Versus Other Serious Illnesses10.2215/CJN.12231116Tue, 27 Jun 2017 07:25:27 GMT-07:00Characteristics and Outcomes of In-Hospital Palliative Care Consultation among Patients with Renal Disease Versus Other Serious IllnessesGrubbs, VanessaO’Riordan, DavidPantilat, Steve2017-06-27T07:25:27-07:00doi:10.2215/CJN.12231116hwp:resource-id:clinjasn;12/7/1085American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypalliative care, end-stage renal disease, advance care planning, Adolescent, Anxiety, Demography, Hospice Care, Hospices, Humans, Kidney Diseases, Kidney Failure, Chronic, Nausea, Palliative Care, Patient Care Planning, Quality Improvement, Quality of Health Care, Referral and Consultation, Retrospective Studies, United StatesOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20172017-07-07July 07, 201710.2215/CJN.122311161555-90411555-905X2017-06-27T07:25:27-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12710851089
- A Kidney Graft Survival Calculator that Accounts for Mismatches in Age, Sex, HLA, and Body Size10.2215/CJN.09330916Thu, 08 Jun 2017 06:52:21 GMT-07:00A Kidney Graft Survival Calculator that Accounts for Mismatches in Age, Sex, HLA, and Body SizeAshby, Valarie B.Leichtman, Alan B.Rees, Michael A.Song, Peter X.-K.Bray, MathieuWang, WenKalbfleisch, John D.2017-06-08T06:52:21-07:00doi:10.2215/CJN.09330916hwp:resource-id:clinjasn;12/7/1148American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, kidney transplantation, renal failure, transplantation, transplant outcomes, donor exchange, age, body size, gender, graft survival, HLA Antigens, kidney donation, Living Donors, obesity, Organ Procurement, Proportional Hazards Models, Registries, risk factors, Survival Rate, Transplant Recipients, Unrelated Donors, Attention, FemaleOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-07-07July 07, 201710.2215/CJN.093309161555-90411555-905X2017-06-08T06:52:21-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12711481160
- Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function10.2215/CJN.00100117Wed, 26 Apr 2017 05:40:18 GMT-07:00Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney FunctionIkeme, Jesse C.Pergola, Pablo E.Scherzer, RebeccaShlipak, Michael G.Benavente, Oscar R.Peralta, Carmen A.2017-04-26T05:40:18-07:00doi:10.2215/CJN.00100117hwp:resource-id:clinjasn;12/7/1040American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyantiplatelet, decline, creatinine, eGFR, Animals, Aspirin, blood pressure, Confidence Intervals, diabetes mellitus, Disease Progression, glomerular filtration rate, Humans, hypertension, Incidence, Models, Animal, Random Allocation, Renal Insufficiency, Chronic, Secondary Prevention, Stroke, Stroke, Lacunar, Ticlopidine, clopidogrelOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-07-07July 07, 201710.2215/CJN.001001171555-90411555-905X2017-04-26T05:40:18-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12710401047
- Statistical Methods for Cohort Studies of CKD: Survival Analysis in the Setting of Competing RisksSurvival analysis is commonly used to evaluate factors associated with time to an event of interest (e.g., ESRD, cardiovascular disease, and mortality) among CKD populations. Time to the event of interest is typically observed only for some participants. Other participants have their event time censored because of the end of the study, death, withdrawal from the study, or some other competing event. Classic survival analysis methods, such as Cox proportional hazards regression, rely on the assumption that any censoring is independent of the event of interest. However, in most clinical settings, such as in CKD populations, this assumption is unlikely to be true. For example, participants whose follow-up time is censored because of health-related death likely would have had a shorter time to ESRD, had they not died. These types of competing events that cause dependent censoring are referred to as competing risks. Here, we first describe common circumstances in clinical renal research where competing risks operate and then review statistical approaches for dealing with competing risks. We compare two of the most popular analytical methods used in settings of competing risks: cause-specific hazards models and the Fine and Gray approach (subdistribution hazards models). We also discuss practical recommendations for analysis and interpretation of survival data that incorporate competing risks. To demonstrate each of the analytical tools, we use a study of fibroblast growth factor 23 and risks of mortality and ESRD in participants with CKD from the Chronic Renal Insufficiency Cohort Study.10.2215/CJN.10301016Mon, 27 Feb 2017 07:22:09 GMT-08:00Statistical Methods for Cohort Studies of CKD: Survival Analysis in the Setting of Competing RisksSurvival analysis is commonly used to evaluate factors associated with time to an event of interest (e.g., ESRD, cardiovascular disease, and mortality) among CKD populations. Time to the event of interest is typically observed only for some participants. Other participants have their event time censored because of the end of the study, death, withdrawal from the study, or some other competing event. Classic survival analysis methods, such as Cox proportional hazards regression, rely on the assumption that any censoring is independent of the event of interest. However, in most clinical settings, such as in CKD populations, this assumption is unlikely to be true. For example, participants whose follow-up time is censored because of health-related death likely would have had a shorter time to ESRD, had they not died. These types of competing events that cause dependent censoring are referred to as competing risks. Here, we first describe common circumstances in clinical renal research where competing risks operate and then review statistical approaches for dealing with competing risks. We compare two of the most popular analytical methods used in settings of competing risks: cause-specific hazards models and the Fine and Gray approach (subdistribution hazards models). We also discuss practical recommendations for analysis and interpretation of survival data that incorporate competing risks. To demonstrate each of the analytical tools, we use a study of fibroblast growth factor 23 and risks of mortality and ESRD in participants with CKD from the Chronic Renal Insufficiency Cohort Study.Hsu, Jesse YenchihRoy, Jason A.Xie, DaweiYang, WeiShou, HaochangAnderson, Amanda HyreLandis, J. RichardJepson, ChristopherWolf, MylesIsakova, TamaraRahman, MahboobFeldman, Harold I.,2017-02-27T07:22:09-08:00doi:10.2215/CJN.10301016hwp:resource-id:clinjasn;12/7/1181American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCumulative incidence function, Cause-specific, Cox proportional hazards models, FGF-23, Cardiovascular Diseases, Fibroblast Growth Factors, Follow-Up Studies, Kidney Failure, Chronic, Proportional Hazards Models, Renal Insufficiency, Chronic, Risk, Survival Analysis, Fibroblast growth factor 23FeatureFeatureresearch-article20172017-07-07July 07, 201710.2215/CJN.103010161555-90411555-905X2017-02-27T07:22:09-08:002017-07-07Clinical Journal of the American Society of NephrologyFeature12711811189
- Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal Dialysis10.2215/CJN.12321216Wed, 21 Jun 2017 07:24:13 GMT-07:00Multicenter Registry Analysis of Center Characteristics Associated with Technique Failure in Patients on Incident Peritoneal DialysisHtay, HtayCho, YeoungjeePascoe, Elaine M.Darssan, DarsyNadeau-Fredette, Annie-ClaireHawley, CarmelClayton, Philip A.Borlace, MoniqueBadve, Sunil V.Sud, KamalBoudville, NeilMcDonald, Stephen P.Johnson, David W.2017-06-21T07:24:13-07:00doi:10.2215/CJN.12321216hwp:resource-id:clinjasn;12/7/1090American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnti-Bacterial Agents, Australia, Glucans, Glucose, Hemoglobins, hospitalization, Humans, New Zealand, peritoneal dialysis, Peritonitis, Phosphates, Registries, renal dialysis, icodextrinOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-07-07July 07, 201710.2215/CJN.123212161555-90411555-905X2017-06-21T07:24:13-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12771090103210991034
- Correction10.2215/CJN.04890517Wed, 14 Jun 2017 05:48:52 GMT-07:00CorrectionAmerican Society of Nephrology2017-06-14T05:48:52-07:00doi:10.2215/CJN.04890517hwp:resource-id:clinjasn;12/7/1161American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratumErratumcorrection20172017-07-07July 07, 201710.2215/CJN.048905171555-90411555-905X2017-06-14T05:48:52-07:002017-07-07Clinical Journal of the American Society of NephrologyErratum12971111611911911161200200
- Are Peritoneal Dialysis Center Characteristics a Modifiable Risk Factor to Improve Peritoneal Dialysis Outcomes?10.2215/CJN.05260517Wed, 21 Jun 2017 07:24:14 GMT-07:00Are Peritoneal Dialysis Center Characteristics a Modifiable Risk Factor to Improve Peritoneal Dialysis Outcomes?Lambie, MarkDavies, Simon J.2017-06-21T07:24:14-07:00doi:10.2215/CJN.05260517hwp:resource-id:clinjasn;12/7/1032American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, survival, outcomes, mortality risk, Peritoneum, risk factorsEditorialsEditorialseditorial20172017-07-07July 07, 201710.2215/CJN.052605171555-90411555-905X2017-06-21T07:24:14-07:002017-07-07Clinical Journal of the American Society of NephrologyEditorials12771032109010341099
- Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function10.2215/CJN.11931116Tue, 09 May 2017 06:37:07 GMT-07:00Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney FunctionWang, MengjingObi, YoshitsuguStreja, ElaniRhee, Connie M.Lau, Wei LingChen, JingHao, ChuanmingHamano, TakayukiKovesdy, Csaba P.Kalantar-Zadeh, Kamyar2017-05-09T06:37:07-07:00doi:10.2215/CJN.11931116hwp:resource-id:clinjasn;12/7/1118American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMortality, chronic kidney failure, hemodialysis, end stage kidney disease, mineral metabolism, renal function, Albumins, Alkaline Phosphatase, calcium, Follow-Up Studies, Humans, Minerals, parathyroid hormone, Phosphorus, Phosphorus, Dietary, Proportional Hazards Models, renal dialysis, Risk, urea, Urinary Tract Physiological PhenomenaOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-07-07July 07, 201710.2215/CJN.119311161555-90411555-905X2017-05-09T06:37:07-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12711181127
- National Healthcare Safety Network (NHSN) Dialysis Event Surveillance Report for 201410.2215/CJN.11411116Thu, 29 Jun 2017 06:17:45 GMT-07:00National Healthcare Safety Network (NHSN) Dialysis Event Surveillance Report for 2014Nguyen, Duc B.Shugart, AliciaLines, ChristiShah, Ami B.Edwards, JonathanPollock, DanielSievert, DawnPatel, Priti R.2017-06-29T06:17:45-07:00doi:10.2215/CJN.11411116hwp:resource-id:clinjasn;12/7/1139American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, infection, surveillanceOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-07-07July 07, 201710.2215/CJN.114111161555-90411555-905X2017-06-29T06:17:45-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12771139103811461039
- The Potential of Pharmacogenomics to Advance Kidney Disease Treatment10.2215/CJN.05170517Mon, 19 Jun 2017 06:13:10 GMT-07:00The Potential of Pharmacogenomics to Advance Kidney Disease TreatmentBirdwell, Kelly A.Chung, Cecilia P.2017-06-19T06:13:10-07:00doi:10.2215/CJN.05170517hwp:resource-id:clinjasn;12/7/1035American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhuman genetics, mineral metabolismEditorialsEditorialseditorial20172017-07-07July 07, 201710.2215/CJN.051705171555-90411555-905X2017-06-19T06:13:10-07:002017-07-07Clinical Journal of the American Society of NephrologyEditorials12771035112810371138
- Factors Associated with Frailty and Its Trajectory among Patients on Hemodialysis10.2215/CJN.12131116Fri, 02 Jun 2017 08:37:26 GMT-07:00Factors Associated with Frailty and Its Trajectory among Patients on HemodialysisJohansen, Kirsten L.Dalrymple, Lorien S.Delgado, CynthiaChertow, Glenn M.Segal, Mark R.Chiang, JanetGrimes, BarbaraKaysen, George A.2017-06-02T08:37:26-07:00doi:10.2215/CJN.12131116hwp:resource-id:clinjasn;12/7/1100American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, frailty, end-stage renal disease, physical function, functional status, chronic kidney disease, Adiposity, diabetes mellitus, Follow-Up Studies, Hispanic Americans, hospitalization, Humans, Inflammation, Interleukin-6, obesity, renal dialysis, Serum Albumin, IL6 protein, humanOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-07-07July 07, 201710.2215/CJN.121311161555-90411555-905X2017-06-02T08:37:26-07:002017-07-07Clinical Journal of the American Society of NephrologyOriginal Articles12711001108
- Cell Therapy in Kidney Transplantation: Focus on Regulatory T CellsRenal transplantation is the renal replacement modality of choice for suitable candidates with advanced CKD or ESRD. Prevention of rejection, however, requires treatment with nonspecific pharmacologic immunosuppressants that carry both systemic and nephrologic toxicities. Use of a patient’s own suppressive regulatory T cells (Tregs) is an attractive biologic approach to reduce this burden. Here, we review the immunologic underpinnings of Treg therapy and technical challenges to developing successful cell therapy. These issues include the selection of appropriate Treg subsets, ex vivo Treg expansion approaches, how many Tregs to administer and when, and how to care for patients after Treg administration.10.1681/ASN.2016111206Tue, 02 May 2017 07:10:33 GMT-07:00Cell Therapy in Kidney Transplantation: Focus on Regulatory T CellsRenal transplantation is the renal replacement modality of choice for suitable candidates with advanced CKD or ESRD. Prevention of rejection, however, requires treatment with nonspecific pharmacologic immunosuppressants that carry both systemic and nephrologic toxicities. Use of a patient’s own suppressive regulatory T cells (Tregs) is an attractive biologic approach to reduce this burden. Here, we review the immunologic underpinnings of Treg therapy and technical challenges to developing successful cell therapy. These issues include the selection of appropriate Treg subsets, ex vivo Treg expansion approaches, how many Tregs to administer and when, and how to care for patients after Treg administration.Zwang, Nicholas A.Leventhal, Joseph R.2017-05-02T07:10:33-07:00doi:10.1681/ASN.2016111206hwp:resource-id:jnephrol;28/7/1960American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCell transfer, immunology, kidney transplantation, toleranceUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-07-01July 201710.1681/ASN.20161112061046-66731533-34502017-05-02T07:10:33-07:002017-07Journal of the American Society of NephrologyUp Front Matters28719601972
- Comparing Outcomes between Antibody Induction Therapies in Kidney TransplantationKidney transplant recipients often receive antibody induction. Previous studies of induction therapy were often limited by short follow-up and/or absence of information about complications. After linking Organ Procurement and Transplantation Network data with Medicare claims, we compared outcomes between three induction therapies for kidney recipients. Using novel matching techniques developed on the basis of 15 clinical and demographic characteristics, we generated 1:1 pairs of alemtuzumab–rabbit antithymocyte globulin (rATG) (5330 pairs) and basiliximab-rATG (9378 pairs) recipients. We used paired Cox regression to analyze the primary outcomes of death and death or allograft failure. Secondary outcomes included death or sepsis, death or lymphoma, death or melanoma, and healthcare resource utilization within 1 year. Compared with rATG recipients, alemtuzumab recipients had higher risk of death (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 1.03 to 1.26; P<0.01) and death or allograft failure (HR, 1.18; 95% CI, 1.09 to 1.28; P<0.001). Results for death as well as death or allograft failure were generally consistent among elderly and nonelderly subgroups and among pairs receiving oral prednisone. Compared with rATG recipients, basiliximab recipients had higher risk of death (HR, 1.08; 95% CI, 1.01 to 1.16; P=0.03) and death or lymphoma (HR, 1.12; 95% CI, 1.01 to 1.23; P=0.03), although these differences were not confirmed in subgroup analyses. One-year resource utilization was slightly lower among alemtuzumab recipients than among rATG recipients, but did not differ between basiliximab and rATG recipients. This observational evidence indicates that, compared with alemtuzumab and basiliximab, rATG associates with lower risk of adverse outcomes, including mortality.10.1681/ASN.2016070768Mon, 20 Mar 2017 07:16:45 GMT-07:00Comparing Outcomes between Antibody Induction Therapies in Kidney TransplantationKidney transplant recipients often receive antibody induction. Previous studies of induction therapy were often limited by short follow-up and/or absence of information about complications. After linking Organ Procurement and Transplantation Network data with Medicare claims, we compared outcomes between three induction therapies for kidney recipients. Using novel matching techniques developed on the basis of 15 clinical and demographic characteristics, we generated 1:1 pairs of alemtuzumab–rabbit antithymocyte globulin (rATG) (5330 pairs) and basiliximab-rATG (9378 pairs) recipients. We used paired Cox regression to analyze the primary outcomes of death and death or allograft failure. Secondary outcomes included death or sepsis, death or lymphoma, death or melanoma, and healthcare resource utilization within 1 year. Compared with rATG recipients, alemtuzumab recipients had higher risk of death (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 1.03 to 1.26; P<0.01) and death or allograft failure (HR, 1.18; 95% CI, 1.09 to 1.28; P<0.001). Results for death as well as death or allograft failure were generally consistent among elderly and nonelderly subgroups and among pairs receiving oral prednisone. Compared with rATG recipients, basiliximab recipients had higher risk of death (HR, 1.08; 95% CI, 1.01 to 1.16; P=0.03) and death or lymphoma (HR, 1.12; 95% CI, 1.01 to 1.23; P=0.03), although these differences were not confirmed in subgroup analyses. One-year resource utilization was slightly lower among alemtuzumab recipients than among rATG recipients, but did not differ between basiliximab and rATG recipients. This observational evidence indicates that, compared with alemtuzumab and basiliximab, rATG associates with lower risk of adverse outcomes, including mortality.Koyawala, NeelSilber, Jeffrey H.Rosenbaum, Paul R.Wang, WeiHill, Alexander S.Reiter, Joseph G.Niknam, Bijan A.Even-Shoshan, OritBloom, Roy D.Sawinski, DeirdreNazarian, SusannaTrofe-Clark, JenniferLim, Mary AnnSchold, Jesse D.Reese, Peter P.2017-03-20T07:16:45-07:00doi:10.1681/ASN.2016070768hwp:resource-id:jnephrol;28/7/2188American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycancer, acute rejection, transplant outcomes, immunosuppression, survivalClinical EpidemiologyClinical Epidemiologyresearch-article20172017-07-01July 201710.1681/ASN.20160707681046-66731533-34502017-03-20T07:16:45-07:002017-07Journal of the American Society of NephrologyClinical Epidemiology28721882200
- Apixaban Pharmacokinetics at Steady State in Hemodialysis PatientsIt is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.10.1681/ASN.2016090980Thu, 16 Mar 2017 07:18:00 GMT-07:00Apixaban Pharmacokinetics at Steady State in Hemodialysis PatientsIt is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.Mavrakanas, Thomas A.Samer, Caroline F.Nessim, Sharon J.Frisch, GershonLipman, Mark L.2017-03-16T07:18:00-07:00doi:10.1681/ASN.2016090980hwp:resource-id:jnephrol;28/7/2241American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyapixaban, hemodialysis, atrial fibrillation, pharmacokineticsClinical ResearchClinical Researchresearch-article20172017-07-01July 201710.1681/ASN.20160909801046-66731533-34502017-03-16T07:18:00-07:002017-07Journal of the American Society of NephrologyClinical Research28772241195722481959
- Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft InjuryInterstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α–smooth muscle actin [α-SMA]) markers. CD68+/α-SMA+ cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α-SMA+ myofibroblasts in renal allografts originated from recipient bone marrow–derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow–derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism.10.1681/ASN.2016050573Thu, 16 Feb 2017 05:53:08 GMT-08:00Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft InjuryInterstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α–smooth muscle actin [α-SMA]) markers. CD68+/α-SMA+ cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α-SMA+ myofibroblasts in renal allografts originated from recipient bone marrow–derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow–derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism.Wang, Ying-YingJiang, HongPan, JunHuang, Xiao-RuWang, Yu-ChengHuang, Hong-FengTo, Ka-FaiNikolic-Paterson, David J.Lan, Hui-YaoChen, Jiang-Hua2017-02-16T05:53:08-08:00doi:10.1681/ASN.2016050573hwp:resource-id:jnephrol;28/7/2053American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymacrophage myofibroblast transition, chronic allograft rejection, interstitial fibrosis, lineage tracing, Smad3, M2 macrophageBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160505731046-66731533-34502017-02-16T05:53:08-08:002017-07Journal of the American Society of NephrologyBasic Research28720532067
- IL-33–Mediated Expansion of Type 2 Innate Lymphoid Cells Protects from Progressive GlomerulosclerosisInnate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5– and IL-13–producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor–positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor–positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.10.1681/ASN.2016080877Thu, 02 Feb 2017 07:53:15 GMT-08:00IL-33–Mediated Expansion of Type 2 Innate Lymphoid Cells Protects from Progressive GlomerulosclerosisInnate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5– and IL-13–producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor–positive ILC2s are a major ILC subtype in the kidney of humans and mice. Short-term IL-33 treatment in mice led to sustained expansion of IL-33 receptor–positive kidney ILC2s and ameliorated adriamycin-induced glomerulosclerosis. Furthermore, the expansion of ILC2s modulated the inflammatory response in the diseased kidney in favor of an anti-inflammatory milieu with a reduction of pathogenic myeloid cell infiltration and a marked accumulation of eosinophils that was required for tissue protection. In summary, kidney-residing ILC2s can be effectively expanded in the mouse kidney by IL-33 treatment and are central regulators of renal repair mechanisms. The presence of ILC2s in the human kidney tissue identifies these cells as attractive therapeutic targets for CKD in humans.Riedel, Jan-HendrikBecker, MartinaKopp, KerstinDüster, MathisBrix, Silke R.Meyer-Schwesinger, CatherineKluth, Luis A.Gnirck, Ann-ChristinAttar, MadenaKrohn, SonjaFehse, BorisStahl, Rolf A.K.Panzer, UlfTurner, Jan-Eric2017-02-02T07:53:15-08:00doi:10.1681/ASN.2016080877hwp:resource-id:jnephrol;28/7/2068American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyinnate lymphoid cells, IL-33, glomerulosclerosisBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160808771046-66731533-34502017-02-02T07:53:15-08:002017-07Journal of the American Society of NephrologyBasic Research28772068195320801955
- Balancing Anticoagulation Decisions in Patients on Dialysis with Atrial Fibrillation10.1681/ASN.2017040451Mon, 05 Jun 2017 05:15:30 GMT-07:00Balancing Anticoagulation Decisions in Patients on Dialysis with Atrial FibrillationDeal, Eli N.Shuster, Jerrica E.2017-06-05T05:15:30-07:00doi:10.1681/ASN.2017040451hwp:resource-id:jnephrol;28/7/1957American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, anticoagulation, apixaban, rivaroxaban, atrial fibrillationUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-07-01July 201710.1681/ASN.20170404511046-66731533-34502017-06-05T05:15:30-07:002017-07Journal of the American Society of NephrologyUp Front Matters28771957224119592248
- Sickle Cell Trait and the Risk of ESRD in BlacksBlacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to APOL1 high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown. In a large population-based cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated 9909 self-reported blacks (739 with SCT and 243 with hemoglobin C trait). Incident ESRD occurred in 40 of 739 (5.4%) individuals with SCT, six of 243 (2.5%) individuals with hemoglobin C trait, and 234 of 8927 (2.6%) noncarriers. The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT and 4.0 per 1000 person-years for noncarriers. Compared with individuals without SCT, individuals with SCT had a hazard ratio for ESRD of 2.03 (95% confidence interval, 1.44 to 2.84). Hemoglobin C trait did not associate with prevalent CKD or ESRD. The incidence rate for ESRD among participants with APOL1 high-risk genotypes was 6.6 per 1000 person-years, with a hazard ratio for ESRD of 1.77 (95% confidence interval, 1.31 to 2.38) for participants with, compared with those without, APOL1 high-risk genotypes. In this cohort, SCT strongly associated with risk of progression to ESRD in blacks, and this degree of risk for ESRD was similar to that conferred by APOL1 high-risk genotypes. These results may have important public policy implications for genetic counseling of SCT carriers.10.1681/ASN.2016101086Thu, 09 Mar 2017 06:00:45 GMT-08:00Sickle Cell Trait and the Risk of ESRD in BlacksBlacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to APOL1 high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown. In a large population-based cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated 9909 self-reported blacks (739 with SCT and 243 with hemoglobin C trait). Incident ESRD occurred in 40 of 739 (5.4%) individuals with SCT, six of 243 (2.5%) individuals with hemoglobin C trait, and 234 of 8927 (2.6%) noncarriers. The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT and 4.0 per 1000 person-years for noncarriers. Compared with individuals without SCT, individuals with SCT had a hazard ratio for ESRD of 2.03 (95% confidence interval, 1.44 to 2.84). Hemoglobin C trait did not associate with prevalent CKD or ESRD. The incidence rate for ESRD among participants with APOL1 high-risk genotypes was 6.6 per 1000 person-years, with a hazard ratio for ESRD of 1.77 (95% confidence interval, 1.31 to 2.38) for participants with, compared with those without, APOL1 high-risk genotypes. In this cohort, SCT strongly associated with risk of progression to ESRD in blacks, and this degree of risk for ESRD was similar to that conferred by APOL1 high-risk genotypes. These results may have important public policy implications for genetic counseling of SCT carriers.Naik, Rakhi P.Irvin, Marguerite R.Judd, SuzanneGutiérrez, Orlando M.Zakai, Neil A.Derebail, Vimal K.Peralta, CarmenLewis, Michael R.Zhi, DeguiArnett, DonnaMcClellan, WilliamWilson, James G.Reiner, Alexander P.Kopp, Jeffrey B.Winkler, Cheryl A.Cushman, Mary2017-03-09T06:00:45-08:00doi:10.1681/ASN.2016101086hwp:resource-id:jnephrol;28/7/2180American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, genetic renal disease, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-07-01July 201710.1681/ASN.20161010861046-66731533-34502017-03-09T06:00:45-08:002017-07Journal of the American Society of NephrologyClinical Epidemiology28721802187
- Targeting Plasma Cells with Proteasome Inhibitors: Principles from Primates10.1681/ASN.2017040443Wed, 07 Jun 2017 10:42:00 GMT-07:00Targeting Plasma Cells with Proteasome Inhibitors: Principles from PrimatesWoodle, E. SteveTremblay, SimonDriscoll, James2017-06-07T10:42:00-07:00doi:10.1681/ASN.2017040443hwp:resource-id:jnephrol;28/7/1951American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyplasma cell, proteasome inhibitor, desensitization, B cell, HLA antibodyUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-07-01July 201710.1681/ASN.20170404431046-66731533-34502017-06-07T10:42:00-07:002017-07Journal of the American Society of NephrologyUp Front Matters28771951199119531996
- Pals1 Haploinsufficiency Results in Proteinuria and Cyst FormationThe nephron is the basic physiologic subunit of the mammalian kidney and is made up of several apicobasally polarized epithelial cell types. The process of apicobasal polarization in animal cells is controlled by the evolutionarily conserved Crumbs (CRB), Partitioning-defective, and Scribble protein complexes. Here, we investigated the role of protein associated with LIN-7 1 (Pals1, also known as Mpp5), a core component of the apical membrane–determining CRB complex in the nephron. Pals1 interacting proteins, including Crb3 and Wwtr1/Taz, have been linked to renal cyst formation in mice before. Immunohistologic analysis revealed Pals1 expression in renal tubular cells and podocytes of human kidneys. Mice lacking one Pals1 allele (functionally haploid for Pals1) in nephrons developed a fully penetrant phenotype, characterized by cyst formation and severe defects in renal barrier function, which led to death within 6–8 weeks. In Drosophila nephrocytes, deficiency of the Pals1 ortholog caused alterations in slit-diaphragm–like structures. Additional studies in epithelial cell culture models revealed that Pals1 functions as a dose-dependent upstream regulator of the crosstalk between Hippo- and TGF-β–mediated signaling. Furthermore, Pals1 haploinsufficiency in mouse kidneys associated with the upregulation of Hippo pathway target genes and marker genes of TGF-β signaling, including biomarkers of renal diseases. These findings support a link between apical polarity proteins and renal diseases, especially renal cyst diseases. Further investigation of the Pals1-linked networks is required to decipher the mechanisms underlying the pathogenesis of these diseases.10.1681/ASN.2016040474Thu, 02 Feb 2017 07:53:16 GMT-08:00Pals1 Haploinsufficiency Results in Proteinuria and Cyst FormationThe nephron is the basic physiologic subunit of the mammalian kidney and is made up of several apicobasally polarized epithelial cell types. The process of apicobasal polarization in animal cells is controlled by the evolutionarily conserved Crumbs (CRB), Partitioning-defective, and Scribble protein complexes. Here, we investigated the role of protein associated with LIN-7 1 (Pals1, also known as Mpp5), a core component of the apical membrane–determining CRB complex in the nephron. Pals1 interacting proteins, including Crb3 and Wwtr1/Taz, have been linked to renal cyst formation in mice before. Immunohistologic analysis revealed Pals1 expression in renal tubular cells and podocytes of human kidneys. Mice lacking one Pals1 allele (functionally haploid for Pals1) in nephrons developed a fully penetrant phenotype, characterized by cyst formation and severe defects in renal barrier function, which led to death within 6–8 weeks. In Drosophila nephrocytes, deficiency of the Pals1 ortholog caused alterations in slit-diaphragm–like structures. Additional studies in epithelial cell culture models revealed that Pals1 functions as a dose-dependent upstream regulator of the crosstalk between Hippo- and TGF-β–mediated signaling. Furthermore, Pals1 haploinsufficiency in mouse kidneys associated with the upregulation of Hippo pathway target genes and marker genes of TGF-β signaling, including biomarkers of renal diseases. These findings support a link between apical polarity proteins and renal diseases, especially renal cyst diseases. Further investigation of the Pals1-linked networks is required to decipher the mechanisms underlying the pathogenesis of these diseases.Weide, ThomasVollenbröker, BeateSchulze, UlfDjuric, IvonaEdeling, MariaBonse, JakobHochapfel, FlorianPanichkina, OlgaWennmann, Dirk-OliverGeorge, BrittaKim, SeonheeDaniel, ChristophSeggewiß, JochenAmann, KerstinKriz, WilhelmKrahn, Michael P.Pavenstädt, Hermann2017-02-02T07:53:16-08:00doi:10.1681/ASN.2016040474hwp:resource-id:jnephrol;28/7/2093American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyPals1, Mpp5, cell signaling, cell polarity, proteinuria, cystic kidneyBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160404741046-66731533-34502017-02-02T07:53:16-08:002017-07Journal of the American Society of NephrologyBasic Research28720932107
- ILC2: There’s a New Cell in Town10.1681/ASN.2017040398Wed, 31 May 2017 10:57:17 GMT-07:00ILC2: There’s a New Cell in TownWang, Yuan MinBakhtiar, MahnoorAlexander, Stephen I.2017-05-31T10:57:17-07:00doi:10.1681/ASN.2017040398hwp:resource-id:jnephrol;28/7/1953American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyILC2, IL-33, chronic kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-07-01July 201710.1681/ASN.20170403981046-66731533-34502017-05-31T10:57:17-07:002017-07Journal of the American Society of NephrologyUp Front Matters28771953206819552080
- Uromodulin in the Bloodstream: Old Wine in a New Wineskin10.1681/ASN.2017040447Wed, 07 Jun 2017 10:41:59 GMT-07:00Uromodulin in the Bloodstream: Old Wine in a New WineskinKraus, DanielWanner, Christoph2017-06-07T10:41:59-07:00doi:10.1681/ASN.2017040447hwp:resource-id:jnephrol;28/7/1955American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, mortality, Epidemiology and outcomesUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-07-01July 201710.1681/ASN.20170404471046-66731533-34502017-06-07T10:41:59-07:002017-07Journal of the American Society of NephrologyUp Front Matters28771955220119572210
- IL-36 Signaling Facilitates Activation of the NLRP3 Inflammasome and IL-23/IL-17 Axis in Renal Inflammation and FibrosisIL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1. In contrast, the kidneys of IL-36 receptor (IL-36R) knockout mice exhibit attenuated TILs after UUO. Compared with UUO-treated wild-type mice, UUO-treated IL-36 knockout mice exhibited markedly reduced NLRP3 inflammasome activation and macrophage/T cell infiltration in the kidney and T cell activation in the renal draining lymph nodes. In vitro, recombinant IL-36α facilitated NLRP3 inflammasome activation in renal tubular epithelial cells, macrophages, and dendritic cells and enhanced dendritic cell–induced T cell proliferation and Th17 differentiation. Furthermore, deficiency of IL-23, which was diminished in IL-36R knockout UUO mice, also reduced renal TIL formation in UUO mice. In wild-type mice, administration of an IL-36R antagonist after UUO reproduced the results obtained in UUO-treated IL-36R knockout mice. We propose that IL-36 signaling contributes to the pathogenesis of renal TILs through the activation of the NLRP3 inflammasome and IL-23/IL-17 axis.10.1681/ASN.2016080840Wed, 08 Feb 2017 04:49:34 GMT-08:00IL-36 Signaling Facilitates Activation of the NLRP3 Inflammasome and IL-23/IL-17 Axis in Renal Inflammation and FibrosisIL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1. In contrast, the kidneys of IL-36 receptor (IL-36R) knockout mice exhibit attenuated TILs after UUO. Compared with UUO-treated wild-type mice, UUO-treated IL-36 knockout mice exhibited markedly reduced NLRP3 inflammasome activation and macrophage/T cell infiltration in the kidney and T cell activation in the renal draining lymph nodes. In vitro, recombinant IL-36α facilitated NLRP3 inflammasome activation in renal tubular epithelial cells, macrophages, and dendritic cells and enhanced dendritic cell–induced T cell proliferation and Th17 differentiation. Furthermore, deficiency of IL-23, which was diminished in IL-36R knockout UUO mice, also reduced renal TIL formation in UUO mice. In wild-type mice, administration of an IL-36R antagonist after UUO reproduced the results obtained in UUO-treated IL-36R knockout mice. We propose that IL-36 signaling contributes to the pathogenesis of renal TILs through the activation of the NLRP3 inflammasome and IL-23/IL-17 axis.Chi, Hsi-HuaHua, Kuo-FengLin, Yu-ChuanChu, Ching-LiangHsieh, Chih-YuHsu, Yu-JueiKa, Shuk-ManTsai, Yu-LingLiu, Feng-ChengChen, Ann2017-02-08T04:49:34-08:00doi:10.1681/ASN.2016080840hwp:resource-id:jnephrol;28/7/2022American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIL-36α, IL-36 receptor, IL-36 receptor antagonist, knockout mice, patients’ samples, unilateral ureteral obstructionBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160808401046-66731533-34502017-02-08T04:49:34-08:002017-07Journal of the American Society of NephrologyBasic Research28720222037
- Cell-Free DNA and Active Rejection in Kidney AllograftsHistologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell–mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell–mediated types ≥IB), 0.2% (T cell–mediated type IA), and 0.3% in controls (P=0.05 for T cell–mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell–mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.10.1681/ASN.2016091034Thu, 09 Mar 2017 06:00:47 GMT-08:00Cell-Free DNA and Active Rejection in Kidney AllograftsHistologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell–mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell–mediated types ≥IB), 0.2% (T cell–mediated type IA), and 0.3% in controls (P=0.05 for T cell–mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell–mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.Bloom, Roy D.Bromberg, Jonathan S.Poggio, Emilio D.Bunnapradist, SuphamaiLangone, Anthony J.Sood, PuneetMatas, Arthur J.Mehta, ShikhaMannon, Roslyn B.Sharfuddin, AsifFischbach, BernardNarayanan, MohanramJordan, Stanley C.Cohen, DavidWeir, Matthew R.Hiller, DavidPrasad, PreethiWoodward, Robert N.Grskovic, MaricaSninsky, John J.Yee, James P.Brennan, Daniel C.Bloom, Roy D.Bromberg, Jonathan S.Poggio, EmilioBunnapradist, SuphamaiLangone, AnthonySood, PuneetMatas, ArthurMehta, ShikhaMannon, Roslyn B.Sharfuddin, AsifFischbach, BernardNarayanan, MohanramJordan, StanleyCohen, DavidWeir, MatthewHiller, DavidPrasad, PreethiWoodward, Robert N.Grskovic, MaricaSninsky, JohnYee, James P.Brennan, Daniel C.2017-03-09T06:00:47-08:00doi:10.1681/ASN.2016091034hwp:resource-id:jnephrol;28/7/2221American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycell-free DNA, kidney, transplant, rejection, biomarker, DARTClinical ResearchClinical Researchresearch-article20172017-07-01July 201710.1681/ASN.20160910341046-66731533-34502017-03-09T06:00:47-08:002017-07Journal of the American Society of NephrologyClinical Research287112221297222322973
- Serum Uromodulin and Mortality Risk in Patients Undergoing Coronary AngiographyThe mucoprotein uromodulin is the most abundant protein in mammalian urine and has important roles in ion transport, maintenance of water and electrolyte balance, and clearance of bacteria from the urinary tract. Low urinary uromodulin concentrations have been associated with increased mortality risk. However, measuring uromodulin in urine has several preanalytic drawbacks, and sensitive assays for the detection of uromodulin in blood have become available. In this study, we investigated the association of serum uromodulin concentration with cardiovascular biomarkers and mortality risk in a large cohort of patients referred for coronary angiography. Uromodulin concentrations were available in 3057 of 3316 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Higher serum uromodulin concentration associated with a favorable metabolic profile, lower prevalence rates of comorbidities (arterial hypertension, diabetes mellitus, and heart failure), and a lower risk for 10-year mortality, with hazard ratios (95% confidence intervals) of 0.65 (0.54 to 0.78), 0.71 (0.58 to 0.88), and 0.57 (0.45 to 0.73) in the second, third, and fourth quartiles, respectively, compared with the first quartile. The association with reduced mortality was independent of other cardiovascular risk factors, including eGFR, and stronger after adjustment for the genotype of the rs12917707 polymorphism at the UMOD locus. Adding serum uromodulin concentration to established cardiovascular risk prediction scores improved risk prediction. Uromodulin may, therefore, be a useful marker for cardiovascular and renal health.10.1681/ASN.2016111162Mon, 27 Feb 2017 07:09:50 GMT-08:00Serum Uromodulin and Mortality Risk in Patients Undergoing Coronary AngiographyThe mucoprotein uromodulin is the most abundant protein in mammalian urine and has important roles in ion transport, maintenance of water and electrolyte balance, and clearance of bacteria from the urinary tract. Low urinary uromodulin concentrations have been associated with increased mortality risk. However, measuring uromodulin in urine has several preanalytic drawbacks, and sensitive assays for the detection of uromodulin in blood have become available. In this study, we investigated the association of serum uromodulin concentration with cardiovascular biomarkers and mortality risk in a large cohort of patients referred for coronary angiography. Uromodulin concentrations were available in 3057 of 3316 participants of the Ludwigshafen Risk and Cardiovascular Health Study. Higher serum uromodulin concentration associated with a favorable metabolic profile, lower prevalence rates of comorbidities (arterial hypertension, diabetes mellitus, and heart failure), and a lower risk for 10-year mortality, with hazard ratios (95% confidence intervals) of 0.65 (0.54 to 0.78), 0.71 (0.58 to 0.88), and 0.57 (0.45 to 0.73) in the second, third, and fourth quartiles, respectively, compared with the first quartile. The association with reduced mortality was independent of other cardiovascular risk factors, including eGFR, and stronger after adjustment for the genotype of the rs12917707 polymorphism at the UMOD locus. Adding serum uromodulin concentration to established cardiovascular risk prediction scores improved risk prediction. Uromodulin may, therefore, be a useful marker for cardiovascular and renal health.Delgado, Graciela E.Kleber, Marcus E.Scharnagl, HubertKrämer, Bernhard K.März, WinfriedScherberich, Jürgen E.2017-02-27T07:09:50-08:00doi:10.1681/ASN.2016111162hwp:resource-id:jnephrol;28/7/2201American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular events, cardiovascular disease, clinical epidemiology, glomerular disease, mortality risk, renal tubular epithelial cellsClinical EpidemiologyClinical Epidemiologyresearch-article20172017-07-01July 201710.1681/ASN.20161111621046-66731533-34502017-02-27T07:09:50-08:002017-07Journal of the American Society of NephrologyClinical Epidemiology28772201195522101957
- Growth Differentiation Factor–15 and Risk of CKD ProgressionGrowth differentiation factor–15 (GDF-15) is a member of the TGF-β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal GDF15 transcript levels (r=0.54, P=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45; P=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; P=0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of GDF15 and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal GDF15-related signaling pathways associated with CKD and CKD progression.10.1681/ASN.2016080919Fri, 03 Feb 2017 08:05:16 GMT-08:00Growth Differentiation Factor–15 and Risk of CKD ProgressionGrowth differentiation factor–15 (GDF-15) is a member of the TGF-β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal GDF15 transcript levels (r=0.54, P=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45; P=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; P=0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of GDF15 and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal GDF15-related signaling pathways associated with CKD and CKD progression.Nair, VijiRobinson-Cohen, CassianneSmith, Michelle R.Bellovich, Keith A.Bhat, Zeenat YousufBobadilla, MariaBrosius, Frankde Boer, Ian H.Essioux, LaurentFormentini, IvanGadegbeku, Crystal A.Gipson, DebbieHawkins, JenniferHimmelfarb, JonathanKestenbaum, BryanKretzler, MatthiasMagnone, Maria ChiaraPerumal, KalyaniSteigerwalt, SusanJu, WenjunBansal, Nisha2017-02-03T08:05:16-08:00doi:10.1681/ASN.2016080919hwp:resource-id:jnephrol;28/7/2233American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, end-stage renal disease, gene expression, glomerular filtration rate, kidney biopsyClinical ResearchClinical Researchresearch-article20172017-07-01July 201710.1681/ASN.20160809191046-66731533-34502017-02-03T08:05:16-08:002017-07Journal of the American Society of NephrologyClinical Research28722332240
- Erratum10.1681/ASN.2017040415Fri, 30 Jun 2017 01:03:38 GMT-07:00ErratumAmerican Society of Nephrology2017-06-30T13:03:38-07:00doi:10.1681/ASN.2017040415hwp:resource-id:jnephrol;28/7/2249American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20172017-07-01July 201710.1681/ASN.20170404151046-66731533-34502017-06-30T13:03:38-07:002017-07Journal of the American Society of NephrologyErrata2827792249263122512644
- Erratum10.1681/ASN.2017040437Fri, 30 Jun 2017 01:03:38 GMT-07:00ErratumAmerican Society of Nephrology2017-06-30T13:03:38-07:00doi:10.1681/ASN.2017040437hwp:resource-id:jnephrol;28/7/2252American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20172017-07-01July 201710.1681/ASN.20170404371046-66731533-34502017-06-30T13:03:38-07:002017-07Journal of the American Society of NephrologyErrata2827772252209222522108
- This Month’s Highlights10.1681/ASN.2017040370Fri, 30 Jun 2017 01:03:38 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-06-30T13:03:38-07:00doi:10.1681/ASN.2017040370hwp:resource-id:jnephrol;28/7/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-07-01July 201710.1681/ASN.20170403701046-66731533-34502017-06-30T13:03:38-07:002017-07Journal of the American Society of NephrologyThis Month’s Highlights287ii
- The NLRP3 Inflammasome Has a Critical Role in Peritoneal Dialysis-Related PeritonitisBacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1β. The NLRP3 inflammasome is a caspase-1–activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1β. The potential roles of the NLRP3 inflammasome and IL-1β in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1β in the dialysate. In mice, lipopolysaccharide- or Escherichia coli-induced peritonitis led to IL-1β release in the peritoneal membrane. The genetic deletion of Nalp3, which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1β treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1β receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1β release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1β axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis.10.1681/ASN.2016070729Mon, 13 Feb 2017 05:19:30 GMT-08:00The NLRP3 Inflammasome Has a Critical Role in Peritoneal Dialysis-Related PeritonitisBacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1β. The NLRP3 inflammasome is a caspase-1–activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1β. The potential roles of the NLRP3 inflammasome and IL-1β in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1β in the dialysate. In mice, lipopolysaccharide- or Escherichia coli-induced peritonitis led to IL-1β release in the peritoneal membrane. The genetic deletion of Nalp3, which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1β treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1β receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1β release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1β axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis.Hautem, NicolasMorelle, JohannSow, AmadouCorbet, CyrilFeron, OlivierGoffin, EricHuaux, FrançoisDevuyst, Olivier2017-02-13T05:19:30-08:00doi:10.1681/ASN.2016070729hwp:resource-id:jnephrol;28/7/2038American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyInterleukin-1, vascular permeability, anakinra, ultrafiltration, peritoneal membrane, cytokinesBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160707291046-66731533-34502017-02-13T05:19:30-08:002017-07Journal of the American Society of NephrologyBasic Research28720382052
- Pharmacologic Blockade of αvβ1 Integrin Ameliorates Renal Failure and Fibrosis In VivoActivated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells in vivo is poorly understood. PDGF receptor β (PDGFRβ) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFRβ promoter–driven Cre system to delete αv integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFRβ-Cre line to isolate and study renal fibroblasts ex vivo. We found that renal fibroblasts express three αv integrins, namely αvβ1, αvβ3, and αvβ5. Blockade of αvβ1 prevented direct binding of fibroblasts to the latency-associated peptide of TGF-β1 and prevented activation of the latent TGF-β complex. Continuous administration of a recently described potent small molecule inhibitor of αvβ1, compound 8, starting the day of unilateral ureteral obstruction operation, inhibited collagen deposition in the kidneys of mice 14 days later. Compound 8 also effectively attenuated renal failure, as measured by BUN levels in mice fed an adenine diet known to cause renal injury followed by fibrosis. Inhibition of αvβ1 integrin could thus hold promise as a therapeutic intervention in CKD characterized by renal fibrosis.10.1681/ASN.2015050585Mon, 20 Feb 2017 05:25:57 GMT-08:00Pharmacologic Blockade of αvβ1 Integrin Ameliorates Renal Failure and Fibrosis In VivoActivated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells in vivo is poorly understood. PDGF receptor β (PDGFRβ) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFRβ promoter–driven Cre system to delete αv integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFRβ-Cre line to isolate and study renal fibroblasts ex vivo. We found that renal fibroblasts express three αv integrins, namely αvβ1, αvβ3, and αvβ5. Blockade of αvβ1 prevented direct binding of fibroblasts to the latency-associated peptide of TGF-β1 and prevented activation of the latent TGF-β complex. Continuous administration of a recently described potent small molecule inhibitor of αvβ1, compound 8, starting the day of unilateral ureteral obstruction operation, inhibited collagen deposition in the kidneys of mice 14 days later. Compound 8 also effectively attenuated renal failure, as measured by BUN levels in mice fed an adenine diet known to cause renal injury followed by fibrosis. Inhibition of αvβ1 integrin could thus hold promise as a therapeutic intervention in CKD characterized by renal fibrosis.Chang, YongenLau, Wei LingJo, HyunilTsujino, KazuyukiGewin, LeslieReed, Nilgun IsikAtakilit, AmhaNunes, Ane Claudia FernandesDeGrado, William F.Sheppard, Dean2017-02-20T05:25:57-08:00doi:10.1681/ASN.2015050585hwp:resource-id:jnephrol;28/7/1998American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIntegrin, TGFβ, renal fibrosis, CKD, UUO, AdenineBrief CommunicationsBrief Communicationsbrief-report20172017-07-01July 201710.1681/ASN.20150505851046-66731533-34502017-02-20T05:25:57-08:002017-07Journal of the American Society of NephrologyBrief Communications28719982005
- Hydrodynamic Isotonic Fluid Delivery Ameliorates Moderate-to-Severe Ischemia-Reperfusion Injury in Rat KidneysHighly aerobic organs like the kidney are innately susceptible to ischemia-reperfusion (I/R) injury, which can originate from sources including myocardial infarction, renal trauma, and transplant. Therapy is mainly supportive and depends on the cause(s) of damage. In the absence of hypervolemia, intravenous fluid delivery is frequently the first course of treatment but does not reverse established AKI. Evidence suggests that disrupting leukocyte adhesion may prevent the impairment of renal microvascular perfusion and the heightened inflammatory response that exacerbate ischemic renal injury. We investigated the therapeutic potential of hydrodynamic isotonic fluid delivery (HIFD) to the left renal vein 24 hours after inducing moderate-to-severe unilateral IRI in rats. HIFD significantly increased hydrostatic pressure within the renal vein. When conducted after established AKI, 24 hours after I/R injury, HIFD produced substantial and statistically significant decreases in serum creatinine levels compared with levels in animals given an equivalent volume of saline via peripheral infusion (P<0.05). Intravital confocal microscopy performed immediately after HIFD showed improved microvascular perfusion. Notably, HIFD also resulted in immediate enhancement of parenchymal labeling with the fluorescent dye Hoechst 33342. HIFD also associated with a significant reduction in the accumulation of renal leukocytes, including proinflammatory T cells. Additionally, HIFD significantly reduced peritubular capillary erythrocyte congestion and improved histologic scores of tubular injury 4 days after IRI. Taken together, these results indicate that HIFD performed after establishment of AKI rapidly restores microvascular perfusion and small molecule accessibility, with improvement in overall renal function.10.1681/ASN.2016040404Wed, 25 Jan 2017 05:34:06 GMT-08:00Hydrodynamic Isotonic Fluid Delivery Ameliorates Moderate-to-Severe Ischemia-Reperfusion Injury in Rat KidneysHighly aerobic organs like the kidney are innately susceptible to ischemia-reperfusion (I/R) injury, which can originate from sources including myocardial infarction, renal trauma, and transplant. Therapy is mainly supportive and depends on the cause(s) of damage. In the absence of hypervolemia, intravenous fluid delivery is frequently the first course of treatment but does not reverse established AKI. Evidence suggests that disrupting leukocyte adhesion may prevent the impairment of renal microvascular perfusion and the heightened inflammatory response that exacerbate ischemic renal injury. We investigated the therapeutic potential of hydrodynamic isotonic fluid delivery (HIFD) to the left renal vein 24 hours after inducing moderate-to-severe unilateral IRI in rats. HIFD significantly increased hydrostatic pressure within the renal vein. When conducted after established AKI, 24 hours after I/R injury, HIFD produced substantial and statistically significant decreases in serum creatinine levels compared with levels in animals given an equivalent volume of saline via peripheral infusion (P<0.05). Intravital confocal microscopy performed immediately after HIFD showed improved microvascular perfusion. Notably, HIFD also resulted in immediate enhancement of parenchymal labeling with the fluorescent dye Hoechst 33342. HIFD also associated with a significant reduction in the accumulation of renal leukocytes, including proinflammatory T cells. Additionally, HIFD significantly reduced peritubular capillary erythrocyte congestion and improved histologic scores of tubular injury 4 days after IRI. Taken together, these results indicate that HIFD performed after establishment of AKI rapidly restores microvascular perfusion and small molecule accessibility, with improvement in overall renal function.Collett, Jason A.Corridon, Peter R.Mehrotra, PurviKolb, Alexander L.Rhodes, George J.Miller, Caroline A.Molitoris, Bruce A.Pennington, Janice G.Sandoval, Ruben M.Atkinson, Simon J.Campos-Bilderback, Silvia B.Basile, David P.Bacallao, Robert L.2017-01-25T05:34:06-08:00doi:10.1681/ASN.2016040404hwp:resource-id:jnephrol;28/7/2081American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, retrograde saline delivery, peritubular capillariesBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160404041046-66731533-34502017-01-25T05:34:06-08:002017-07Journal of the American Society of NephrologyBasic Research28720812092
- A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF-β1/Smad3 PathwayHomeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2. Among these compounds, we identified one, BT173, that strongly inhibited the ability of HIPK2 to potentiate the downstream transcriptional activity of Smad3 in kidney tubular cells. Notably, binding of BT173 to HIPK2 did not inhibit HIPK2 kinase activity but rather, interfered allosterically with the ability of HIPK2 to associate with Smad3. In vitro, treatment with BT173 inhibited TGF-β1–induced Smad3 phosphorylation and Smad3 target gene expression in human renal tubular epithelial cells. In vivo, administration of BT173 decreased Smad3 phosphorylation and mitigated renal fibrosis and deposition of extracellular matrix in unilateral ureteral obstruction and Tg26 mouse models of renal fibrosis. Our data indicate that BT173 is a novel HIPK2 inhibitor that attenuates renal fibrosis through suppression of the TGF-β1/Smad3 pathway and may be developed as an antifibrotic therapy in patients with kidney disease.10.1681/ASN.2016080841Mon, 20 Feb 2017 05:25:56 GMT-08:00A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF-β1/Smad3 PathwayHomeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2. Among these compounds, we identified one, BT173, that strongly inhibited the ability of HIPK2 to potentiate the downstream transcriptional activity of Smad3 in kidney tubular cells. Notably, binding of BT173 to HIPK2 did not inhibit HIPK2 kinase activity but rather, interfered allosterically with the ability of HIPK2 to associate with Smad3. In vitro, treatment with BT173 inhibited TGF-β1–induced Smad3 phosphorylation and Smad3 target gene expression in human renal tubular epithelial cells. In vivo, administration of BT173 decreased Smad3 phosphorylation and mitigated renal fibrosis and deposition of extracellular matrix in unilateral ureteral obstruction and Tg26 mouse models of renal fibrosis. Our data indicate that BT173 is a novel HIPK2 inhibitor that attenuates renal fibrosis through suppression of the TGF-β1/Smad3 pathway and may be developed as an antifibrotic therapy in patients with kidney disease.Liu, RuijieDas, BhaskarXiao, WenzhenLi, ZhengzheLi, HuilinLee, KyungHe, John Cijiang2017-02-20T05:25:56-08:00doi:10.1681/ASN.2016080841hwp:resource-id:jnephrol;28/7/2133American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyHIPK2, renal fibrosis, TGF-beta, Smad3, tubular cellsBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160808411046-66731533-34502017-02-20T05:25:56-08:002017-07Journal of the American Society of NephrologyBasic Research28721332143
- Inhibition of Reticulon-1A–Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis DevelopmentSeveral animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD. In a retrospective study of 51 patients with AKI, increased expression of RTN1A and other ER stress markers were associated with the severity of kidney injury and with progression to CKD. In an inducible tubular cell–specific RTN1A-knockdown mouse model subjected to folic acid nephropathy (FAN) or aristolochic acid nephropathy, reduction of RTN1A expression during the initial stage of AKI attenuated ER stress and kidney cell injury in early stages and renal fibrosis development in later stages. Treatment of wild-type mice with tauroursodeoxycholic acid, an inhibitor of ER stress, after the induction of kidney injury with FA facilitated renoprotection similar to that observed in RTN1A-knockdown mice. Conversely, in transgenic mice with inducible tubular cell–specific overexpression of RTN1A subjected to FAN, induction of RTN1A overexpression aggravated ER stress and renal injury at the early stage and renal fibrosis at the late stage of FAN. Together, our human and mouse data suggest that the RTN1A-mediated ER stress response may be an important determinant in the severity of AKI and maladaptive repair that may promote progression to CKD.10.1681/ASN.2016091001Mon, 30 Jan 2017 06:48:05 GMT-08:00Inhibition of Reticulon-1A–Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis DevelopmentSeveral animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD. In a retrospective study of 51 patients with AKI, increased expression of RTN1A and other ER stress markers were associated with the severity of kidney injury and with progression to CKD. In an inducible tubular cell–specific RTN1A-knockdown mouse model subjected to folic acid nephropathy (FAN) or aristolochic acid nephropathy, reduction of RTN1A expression during the initial stage of AKI attenuated ER stress and kidney cell injury in early stages and renal fibrosis development in later stages. Treatment of wild-type mice with tauroursodeoxycholic acid, an inhibitor of ER stress, after the induction of kidney injury with FA facilitated renoprotection similar to that observed in RTN1A-knockdown mice. Conversely, in transgenic mice with inducible tubular cell–specific overexpression of RTN1A subjected to FAN, induction of RTN1A overexpression aggravated ER stress and renal injury at the early stage and renal fibrosis at the late stage of FAN. Together, our human and mouse data suggest that the RTN1A-mediated ER stress response may be an important determinant in the severity of AKI and maladaptive repair that may promote progression to CKD.Fan, YingXiao, WenzhenLee, KyungSalem, FadiWen, JiejunHe, LiZhang, JingFei, YangCheng, DongshengBao, HongdaLiu, YumeiLin, FujunJiang, GengruGuo, ZhiyongWang, NiansongHe, John Cijiang2017-01-30T06:48:05-08:00doi:10.1681/ASN.2016091001hwp:resource-id:jnephrol;28/7/2007American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, reticulon-1, renal fibrosis, renal tubular epithelial cells, ER stressBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160910011046-66731533-34502017-01-30T06:48:05-08:002017-07Journal of the American Society of NephrologyBasic Research28720072021
- Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune CellsAnalysis of the immune system in the kidney relies predominantly on flow cytometry. Although powerful, the process of tissue homogenization necessary for flow cytometry analysis introduces bias and results in the loss of morphologic landmarks needed to determine the spatial distribution of immune cells. An ideal approach would support three-dimensional (3D) tissue cytometry: an automated quantitation of immune cells and associated spatial parameters in 3D image volumes collected from intact kidney tissue. However, widespread application of this approach is limited by the lack of accessible software tools for digital analysis of large 3D microscopy data. Here, we describe Volumetric Tissue Exploration and Analysis (VTEA) image analysis software designed for efficient exploration and quantitative analysis of large, complex 3D microscopy datasets. In analyses of images collected from fixed kidney tissue, VTEA replicated the results of flow cytometry while providing detailed analysis of the spatial distribution of immune cells in different regions of the kidney and in relation to specific renal structures. Unbiased exploration with VTEA enabled us to discover a population of tubular epithelial cells that expresses CD11C, a marker typically expressed on dendritic cells. Finally, we show the use of VTEA for large-scale quantitation of immune cells in entire human kidney biopsies. In summary, we show that VTEA is a simple and effective tool that supports unique digital interrogation and analysis of kidney tissue from animal models or biobanked human kidney biopsies. We have made VTEA freely available to interested investigators via electronic download.10.1681/ASN.2016091027Thu, 02 Feb 2017 07:53:17 GMT-08:00Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune CellsAnalysis of the immune system in the kidney relies predominantly on flow cytometry. Although powerful, the process of tissue homogenization necessary for flow cytometry analysis introduces bias and results in the loss of morphologic landmarks needed to determine the spatial distribution of immune cells. An ideal approach would support three-dimensional (3D) tissue cytometry: an automated quantitation of immune cells and associated spatial parameters in 3D image volumes collected from intact kidney tissue. However, widespread application of this approach is limited by the lack of accessible software tools for digital analysis of large 3D microscopy data. Here, we describe Volumetric Tissue Exploration and Analysis (VTEA) image analysis software designed for efficient exploration and quantitative analysis of large, complex 3D microscopy datasets. In analyses of images collected from fixed kidney tissue, VTEA replicated the results of flow cytometry while providing detailed analysis of the spatial distribution of immune cells in different regions of the kidney and in relation to specific renal structures. Unbiased exploration with VTEA enabled us to discover a population of tubular epithelial cells that expresses CD11C, a marker typically expressed on dendritic cells. Finally, we show the use of VTEA for large-scale quantitation of immune cells in entire human kidney biopsies. In summary, we show that VTEA is a simple and effective tool that supports unique digital interrogation and analysis of kidney tissue from animal models or biobanked human kidney biopsies. We have made VTEA freely available to interested investigators via electronic download.Winfree, SethKhan, ShehnazMicanovic, RadmilaEadon, Michael T.Kelly, Katherine J.Sutton, Timothy A.Phillips, Carrie L.Dunn, Kenneth W.El-Achkar, Tarek M.2017-02-02T07:53:17-08:00doi:10.1681/ASN.2016091027hwp:resource-id:jnephrol;28/7/2108American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, Renal imaging, kidney biopsy, microscopy, softwareBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160910271046-66731533-34502017-02-02T07:53:17-08:002017-07Journal of the American Society of NephrologyBasic Research28721082118
- Humoral Compensation after Bortezomib Treatment of Allosensitized RecipientsThe efficacy of bortezomib monotherapy in desensitizing kidney transplant candidates with preformed donor-specific antibodies remains unclear. We evaluated the effect of bortezomib on preformed antibodies and upstream components of the B cell response in a primate model sensitized by fully mismatched allogeneic skin transplants to provide mechanistic insights regarding the use of bortezomib as a means of desensitization. Bortezomib treatment given intravenously twice weekly for 1 month (1.3 mg/m2 per dose) clearly reduced the numbers of antibody-producing cells and CD38+CD19+CD20− plasma cells in the bone marrow (P<0.05), but donor-specific alloantibody levels did not decrease. We observed a rapid but transient induction of circulating IgG+ B cells and an increased number of proliferating B cells in the lymph nodes after 1 month of treatment. Notably, bortezomib treatment induced germinal center B cell and follicular helper T cell expansion in the lymph nodes. These data suggest that bortezomib-induced plasma cell depletion triggers humoral compensation.10.1681/ASN.2016070727Thu, 23 Feb 2017 06:34:25 GMT-08:00Humoral Compensation after Bortezomib Treatment of Allosensitized RecipientsThe efficacy of bortezomib monotherapy in desensitizing kidney transplant candidates with preformed donor-specific antibodies remains unclear. We evaluated the effect of bortezomib on preformed antibodies and upstream components of the B cell response in a primate model sensitized by fully mismatched allogeneic skin transplants to provide mechanistic insights regarding the use of bortezomib as a means of desensitization. Bortezomib treatment given intravenously twice weekly for 1 month (1.3 mg/m2 per dose) clearly reduced the numbers of antibody-producing cells and CD38+CD19+CD20− plasma cells in the bone marrow (P<0.05), but donor-specific alloantibody levels did not decrease. We observed a rapid but transient induction of circulating IgG+ B cells and an increased number of proliferating B cells in the lymph nodes after 1 month of treatment. Notably, bortezomib treatment induced germinal center B cell and follicular helper T cell expansion in the lymph nodes. These data suggest that bortezomib-induced plasma cell depletion triggers humoral compensation.Kwun, JeanBurghuber, ChristopherManook, MiriamIwakoshi, NealGibby, AdrianaHong, Jung JooKnechtle, Stuart2017-02-23T06:34:25-08:00doi:10.1681/ASN.2016070727hwp:resource-id:jnephrol;28/7/1991American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyBortezomib, Desensitization, alloantibody, nonhuman primate, antibody mediated rejectionBrief CommunicationsBrief Communicationsbrief-report20172017-07-01July 201710.1681/ASN.20160707271046-66731533-34502017-02-23T06:34:25-08:002017-07Journal of the American Society of NephrologyBrief Communications28771991195119961953
- Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in O-glycosylation of the IgA1 molecule. Here, we sought to identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in white and Chinese populations. Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. White patients with IgAN exhibited significantly higher Gd-IgA1 levels than did Chinese patients. Among individuals without IgAN, Gd-IgA1 levels did not correlate with kidney function. Gd-IgA1 level heritability (h2), estimated by comparing midparental and offspring Gd-IgA1 levels, was 0.39. Genome-wide association analysis by linear regression identified alleles at a single locus spanning the C1GALT1 gene that strongly associated with Gd-IgA1 level (β=0.26; P=2.35×10−9). This association was replicated in a genome-wide association study of separate cohorts comprising 308 patients with membranous GN from the UK (P<1.00×10−6) and 622 controls with normal kidney function from the UK (P<1.00×10−10), and in a candidate gene study of 704 Chinese patients with IgAN (P<1.00×10−5). The same extended haplotype associated with elevated Gd-IgA1 levels in all cohorts studied. C1GALT1 encodes a galactosyltransferase enzyme that is important in O-galactosylation of glycoproteins. These findings demonstrate that common variation at C1GALT1 influences Gd-IgA1 level in the population, which independently associates with risk of progressive IgAN, and that the pathogenic importance of changes in IgA1 O-glycosylation may vary between white and Chinese patients with IgAN.10.1681/ASN.2016091043Thu, 16 Feb 2017 05:53:07 GMT-08:00Galactosylation of IgA1 Is Associated with Common Variation in C1GALT1IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in O-glycosylation of the IgA1 molecule. Here, we sought to identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in white and Chinese populations. Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. White patients with IgAN exhibited significantly higher Gd-IgA1 levels than did Chinese patients. Among individuals without IgAN, Gd-IgA1 levels did not correlate with kidney function. Gd-IgA1 level heritability (h2), estimated by comparing midparental and offspring Gd-IgA1 levels, was 0.39. Genome-wide association analysis by linear regression identified alleles at a single locus spanning the C1GALT1 gene that strongly associated with Gd-IgA1 level (β=0.26; P=2.35×10−9). This association was replicated in a genome-wide association study of separate cohorts comprising 308 patients with membranous GN from the UK (P<1.00×10−6) and 622 controls with normal kidney function from the UK (P<1.00×10−10), and in a candidate gene study of 704 Chinese patients with IgAN (P<1.00×10−5). The same extended haplotype associated with elevated Gd-IgA1 levels in all cohorts studied. C1GALT1 encodes a galactosyltransferase enzyme that is important in O-galactosylation of glycoproteins. These findings demonstrate that common variation at C1GALT1 influences Gd-IgA1 level in the population, which independently associates with risk of progressive IgAN, and that the pathogenic importance of changes in IgA1 O-glycosylation may vary between white and Chinese patients with IgAN.Gale, Daniel P.Molyneux, KarenWimbury, DavidHiggins, PatriciaLevine, Adam P.Caplin, BenFerlin, AnnaYin, PeiranNelson, Christopher P.Stanescu, HoriaSamani, Nilesh J.Kleta, RobertYu, XueqingBarratt, Jonathan2017-02-16T05:53:07-08:00doi:10.1681/ASN.2016091043hwp:resource-id:jnephrol;28/7/2158American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, glomerulonephritis, human genetics, IgA, SNP, Genome Wide Association StudyBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20160910431046-66731533-34502017-02-16T05:53:07-08:002017-07Journal of the American Society of NephrologyBasic Research28721582166
- Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular InjuryAminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases.10.1681/ASN.2016111166Wed, 15 Feb 2017 06:09:58 GMT-08:00Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular InjuryAminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases.Velez, Juan Carlos Q.Arif, EhteshamRodgers, JessalynHicks, Megan P.Arthur, John M.Nihalani, DeepakBruner, Evelyn T.Budisavljevic, Milos N.Atkinson, CarlFitzgibbon, Wayne R.Janech, Michael G.2017-02-15T06:09:58-08:00doi:10.1681/ASN.2016111166hwp:resource-id:jnephrol;28/7/2119American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyangiotensin II, intrarenal, podocyte, glomerulosclerosis, murine, albuminuriaBasic ResearchBasic Researchresearch-article20172017-07-01July 201710.1681/ASN.20161111661046-66731533-34502017-02-15T06:09:58-08:002017-07Journal of the American Society of NephrologyBasic Research28721192132
- Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist10.2215/CJN.10280916Thu, 25 May 2017 07:13:48 GMT-07:00Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the WaitlistCohen, Jordana B.Eddinger, Kevin C.Locke, Jayme E.Forde, Kimberly A.Reese, Peter P.Sawinski, Deirdre L.2017-05-25T07:13:48-07:00doi:10.2215/CJN.10280916hwp:resource-id:clinjasn;12/6/974American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, transplant recipients, mortality, transplant donors, Confidence Intervals, Death, Follow-Up Studies, Humans, kidney transplantation, Tissue Donors, Tissue and Organ Procurement, Transplant Recipients, Waiting ListsOriginal ArticlesTransplantationOriginal ArticlesTransplantationresearch-article20172017-06-07June 07, 201710.2215/CJN.102809161555-90411555-905X2017-05-25T07:13:48-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles1266974871982873
- Diarrhea in a Long-Term Kidney-Pancreas Recipient10.2215/CJN.12671216Fri, 24 Mar 2017 05:51:56 GMT-07:00Diarrhea in a Long-Term Kidney-Pancreas RecipientBia, Margaret J.2017-03-24T05:51:56-07:00doi:10.2215/CJN.12671216hwp:resource-id:clinjasn;12/6/998American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiarrhea, kidney transplant, mycophenolate mofetil, mycophenolic acid colitisKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20172017-06-07June 07, 201710.2215/CJN.126712161555-90411555-905X2017-03-24T05:51:56-07:002017-06-07Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire1269981000
- Primary Membranous NephropathyMembranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%–5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.10.2215/CJN.11761116Fri, 26 May 2017 08:29:41 GMT-07:00Primary Membranous NephropathyMembranous nephropathy (MN) is a unique glomerular lesion that is the most common cause of idiopathic nephrotic syndrome in nondiabetic white adults. About 80% of cases are renal limited (primary MN, PMN) and 20% are associated with other systemic diseases or exposures (secondary MN). This review focuses only on PMN. Most cases of PMN have circulating IgG4 autoantibody to the podocyte membrane antigen PLA2R (70%), biopsy evidence PLA2R staining indicating recent immunologic disease activity despite negative serum antibody levels (15%), or serum anti-THSD7A (3%–5%). The remaining 10% without demonstrable anti-PLA2R/THSd7A antibody or antigen likely have PMN probably secondary to a different, still unidentified, anti-podocyte antibody. Considerable clinical and experimental data now suggests these antibodies are pathogenic. Clinically, 80% of patients with PMN present with nephrotic syndrome and 20% with non-nephrotic proteinuria. Untreated, about one third undergo spontaneous remission, especially those with absent or low anti-PLA2R levels, one-third progress to ESRD over 10 years, and the remainder develop nonprogressive CKD. Proteinuria can persist for months after circulating anti-PLA2R/THSD7A antibody is no longer detectable (immunologic remission). All patients with PMN should be treated with supportive care from the time of diagnosis to minimize protein excretion. Patients with elevated anti-PLA2R/THSD7A levels and proteinuria >3.5 g/d at diagnosis, and those who fail to reduce proteinuria to <3.5 g after 6 months of supportive care or have complications of nephrotic syndrome, should be considered for immunosuppressive therapy. Accepted regimens include steroids/cyclophosphamide, calcineurin inhibitors, and B cell depletion. With proper management, only 10% or less will develop ESRD over the subsequent 10 years.Couser, William G.2017-05-26T08:29:41-07:00doi:10.2215/CJN.11761116hwp:resource-id:clinjasn;12/6/983American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymembranous nephropathy, PLA2R, THSD7A, Adult, B-Lymphocytes, Biopsy, Calcineurin Inhibitors, Cyclophosphamide, Glomerulonephritis, Membranous, Humans, Immunoglobulin G, Kidney Failure, Chronic, Kidney Glomerulus, Nephrosis, Lipoid, nephrotic syndrome, Podocytes, proteinuria, Receptors, Phospholipase A2, Remission, Spontaneous, Renal Insufficiency, Chronic, Staining and Labeling, Nephrosis, congenital, PLA2R1 protein, humanGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-06-07June 07, 201710.2215/CJN.117611161555-90411555-905X2017-05-26T08:29:41-07:002017-06-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician12126998315289971528
- Kidney Outcomes and Risk Factors for Nephritis (Flare/De Novo) in a Multiethnic Cohort of Pregnant Patients with Lupus10.2215/CJN.11431116Tue, 11 Apr 2017 05:52:49 GMT-07:00Kidney Outcomes and Risk Factors for Nephritis (Flare/De Novo) in a Multiethnic Cohort of Pregnant Patients with LupusBuyon, Jill P.Kim, Mimi Y.Guerra, Marta M.Lu, SifanReeves, EmilyPetri, MichelleLaskin, Carl A.Lockshin, Michael D.Sammaritano, Lisa R.Branch, D. WarePorter, T. FlintSawitzke, AllenMerrill, Joan T.Stephenson, Mary D.Cohn, ElisabethSalmon, Jane E.2017-04-11T05:52:49-07:00doi:10.2215/CJN.11431116hwp:resource-id:clinjasn;12/6/940American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysystemic lupus erythematosus, Pregnancy Outcome, Antihypertensive Agents, Antiphospholipid Syndrome, Biomarkers, blood pressure, Counseling, creatinine, Erythrocytes, Female, Humans, Kidney Diseases, Logistic Models, Lupus Erythematosus, Systemic, lupus nephritis, Pregnancy, proteinuria, risk factorsOriginal ArticlesGlomerular and Tubulointerstitial DiseasesOriginal ArticlesGlomerular and Tubulointerstitial Diseasesresearch-article20172017-06-07June 07, 201710.2215/CJN.114311161555-90411555-905X2017-04-11T05:52:49-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126940946
- The Diagnosis-Wide Landscape of Hospital-Acquired AKI10.2215/CJN.10981016Thu, 11 May 2017 07:12:36 GMT-07:00The Diagnosis-Wide Landscape of Hospital-Acquired AKIJannot, Anne-SophieBurgun, AnitaThervet, EricPallet, Nicolas2017-05-11T07:12:36-07:00doi:10.2215/CJN.10981016hwp:resource-id:clinjasn;12/6/874American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, clinical nephrology, hospitalization, Acute Kidney Injury, creatinine, Heart Diseases, Hemodynamics, Hospital Records, Humans, Influenza, Human, International Classification of Diseases, Length of Stay, Liver Diseases, Multiple Trauma, Neoplasms, Nephritis, Interstitial, Prevalence, Retrospective Studies, Sepsis, Urogenital System, vasculitisOriginal ArticlesAcute Kidney Injury and ICU NephrologyOriginal ArticlesAcute Kidney Injury and ICU Nephrologyresearch-article20172017-06-07June 07, 201710.2215/CJN.109810161555-90411555-905X2017-05-11T07:12:36-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126874884
- Statistical Methods for Cohort Studies of CKD: Prediction ModelingPrediction models are often developed in and applied to CKD populations. These models can be used to inform patients and clinicians about the potential risks of disease development or progression. With increasing availability of large datasets from CKD cohorts, there is opportunity to develop better prediction models that will lead to more informed treatment decisions. It is important that prediction modeling be done using appropriate statistical methods to achieve the highest accuracy, while avoiding overfitting and poor calibration. In this paper, we review prediction modeling methods in general from model building to assessing model performance as well as the application to new patient populations. Throughout, the methods are illustrated using data from the Chronic Renal Insufficiency Cohort Study.10.2215/CJN.06210616Thu, 22 Sep 2016 06:35:07 GMT-07:00Statistical Methods for Cohort Studies of CKD: Prediction ModelingPrediction models are often developed in and applied to CKD populations. These models can be used to inform patients and clinicians about the potential risks of disease development or progression. With increasing availability of large datasets from CKD cohorts, there is opportunity to develop better prediction models that will lead to more informed treatment decisions. It is important that prediction modeling be done using appropriate statistical methods to achieve the highest accuracy, while avoiding overfitting and poor calibration. In this paper, we review prediction modeling methods in general from model building to assessing model performance as well as the application to new patient populations. Throughout, the methods are illustrated using data from the Chronic Renal Insufficiency Cohort Study.Roy, JasonShou, HaochangXie, DaweiHsu, Jesse Y.Yang, WeiAnderson, Amanda H.Landis, J. RichardJepson, ChristopherHe, JiangLiu, Kathleen D.Hsu, Chi-yuanFeldman, Harold I.2016-09-22T06:35:07-07:00doi:10.2215/CJN.06210616hwp:resource-id:clinjasn;12/6/1010American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCalibration, C-statistic, ROC curve, Sensitivity, Specificity, Cohort Studies, Disease Progression, Humans, Risk, Renal Insufficiency, ChronicFeatureFeatureresearch-article20172017-06-07June 07, 201710.2215/CJN.062106161555-90411555-905X2016-09-22T06:35:07-07:002017-06-07Clinical Journal of the American Society of NephrologyFeature12610101017
- Time to Improve Informed Consent for Dialysis: An International PerspectiveThe literature reveals that current nephrology practice in obtaining informed consent for dialysis falls short of ethical and legal requirements. Meeting these requirements represents a significant challenge, especially because the benefits and risks of dialysis have shifted significantly with the growing number of older, comorbid patients. The importance of informed consent for dialysis is heightened by several concerns, including: (1) the proportion of predialysis patients and patients on dialysis who lack capacity in decision making and (2) whether older, comorbid, and frail patients understand their poor prognosis and the full implications to their independence and functional status of being on dialysis. This article outlines the ethical and legal requirements for a valid informed consent to dialysis: (1) the patient was competent, (2) the consent was made voluntarily, and (3) the patient was given sufficient information in an understandable manner to make the decision. It then considers the application of these requirements to practice across different countries. In the process of informed consent, the law requires a discussion by the physician of the material risks associated with dialysis and alternative options. We argue that, legally and ethically, this discussion should include both the anticipated trajectory of the illness and the effect on the life of the patient with particular regard to the outcomes most important to the individual. In addition, a discussion should occur about the option of a conservative, nondialysis pathway. These requirements ensure that the ethical principle of respect for patient autonomy is honored in the context of dialysis. Nephrologists need to be open to, comfortable with, and skillful in communicating this information. From these clear, open, ethically, and legally valid consent discussions, a significant dividend will hopefully flow for patients, families, and nephrologists alike.10.2215/CJN.09740916Tue, 04 Apr 2017 05:44:18 GMT-07:00Time to Improve Informed Consent for Dialysis: An International PerspectiveThe literature reveals that current nephrology practice in obtaining informed consent for dialysis falls short of ethical and legal requirements. Meeting these requirements represents a significant challenge, especially because the benefits and risks of dialysis have shifted significantly with the growing number of older, comorbid patients. The importance of informed consent for dialysis is heightened by several concerns, including: (1) the proportion of predialysis patients and patients on dialysis who lack capacity in decision making and (2) whether older, comorbid, and frail patients understand their poor prognosis and the full implications to their independence and functional status of being on dialysis. This article outlines the ethical and legal requirements for a valid informed consent to dialysis: (1) the patient was competent, (2) the consent was made voluntarily, and (3) the patient was given sufficient information in an understandable manner to make the decision. It then considers the application of these requirements to practice across different countries. In the process of informed consent, the law requires a discussion by the physician of the material risks associated with dialysis and alternative options. We argue that, legally and ethically, this discussion should include both the anticipated trajectory of the illness and the effect on the life of the patient with particular regard to the outcomes most important to the individual. In addition, a discussion should occur about the option of a conservative, nondialysis pathway. These requirements ensure that the ethical principle of respect for patient autonomy is honored in the context of dialysis. Nephrologists need to be open to, comfortable with, and skillful in communicating this information. From these clear, open, ethically, and legally valid consent discussions, a significant dividend will hopefully flow for patients, families, and nephrologists alike.Brennan, FrankStewart, CameronBurgess, HannahDavison, Sara N.Moss, Alvin H.Murtagh, Fliss E.M.Germain, MichaelTranter, ShelleyBrown, Mark2017-04-04T05:44:18-07:00doi:10.2215/CJN.09740916hwp:resource-id:clinjasn;12/6/1001American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyconsent, dialysis, ethics, autonomy, decision making, survival, quality of life, Comprehension, Decision Making, Dissent and Disputes, Humans, Informed Consent, Internationality, Nephrologists, nephrology, Prognosis, renal dialysis, Risk AssessmentEthics SeriesEthics Seriesresearch-article20172017-06-07June 07, 201710.2215/CJN.097409161555-90411555-905X2017-04-04T05:44:18-07:002017-06-07Clinical Journal of the American Society of NephrologyEthics Series12610011009
- Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial10.2215/CJN.10941016Fri, 26 May 2017 08:29:40 GMT-07:00Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled TrialWald, RonRabbat, Christian G.Girard, LouisGarg, Amit X.Tennankore, KarthikTyrwhitt, JessicaSmyth, AndrewRathe-Skafel, AndreaGao, PeggyMazzetti, AndreaBosch, JackieYan, Andrew T.Parfrey, PatrickManns, Braden J.Walsh, Michael2017-05-26T08:29:40-07:00doi:10.2215/CJN.10941016hwp:resource-id:clinjasn;12/6/965American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, phosphate binders, randomized controlled trials, Calcium Carbonate, Calcium, Dietary, Canada, Goals, Humans, Hypercalcemia, hyperphosphatemia, Hypocalcemia, Kidney Failure, Chronic, Nomograms, Parathyroidectomy, Phosphates, Pilots, Prevalence, Random Allocation, renal dialysis, renal insufficiency, chronicOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-06-07June 07, 201710.2215/CJN.109410161555-90411555-905X2017-05-26T08:29:40-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles1266965868973870
- Choice of Hemodialysis Access in Older Adults: A Cost-Effectiveness Analysis10.2215/CJN.11631116Thu, 18 May 2017 11:07:35 GMT-07:00Choice of Hemodialysis Access in Older Adults: A Cost-Effectiveness AnalysisHall, Rasheeda K.Myers, Evan R.Rosas, Sylvia E.O’Hare, Ann M.Colón-Emeric, Cathleen S.2017-05-18T11:07:35-07:00doi:10.2215/CJN.11631116hwp:resource-id:clinjasn;12/6/947American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfrail elderly, vascular access, health care costs, geriatric nephrology, Medicare, dialysis, arteriovenous fistula, arteriovenous graft, life-expectancy, Arteriovenous Shunt, Surgical, Central Venous Catheters, Cost-Benefit Analysis, Humans, Probability, renal dialysisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-06-07June 07, 201710.2215/CJN.116311161555-90411555-905X2017-05-18T11:07:35-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles1266947865954867
- Opportunities to Increase Availability of Deceased Donor Kidneys10.2215/CJN.04490417Thu, 25 May 2017 07:13:49 GMT-07:00Opportunities to Increase Availability of Deceased Donor KidneysFormica, Richard N.2017-05-25T07:13:49-07:00doi:10.2215/CJN.04490417hwp:resource-id:clinjasn;12/6/871American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, cadaver organ transplantation, kidney donation, health care crisis, Death, Tissue DonorsEditorialsEditorialseditorial20172017-06-07June 07, 201710.2215/CJN.044904171555-90411555-905X2017-05-25T07:13:49-07:002017-06-07Clinical Journal of the American Society of NephrologyEditorials1266871974873982
- Getting Out of the Phosphate Bind: Trials to Guide Treatment Targets10.2215/CJN.04380417Fri, 26 May 2017 08:29:40 GMT-07:00Getting Out of the Phosphate Bind: Trials to Guide Treatment TargetsOlivo, Robert E.Scialla, Julia J.2017-05-26T08:29:40-07:00doi:10.2215/CJN.04380417hwp:resource-id:clinjasn;12/6/868American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiophysical Phenomena, PhosphatesEditorialsEditorialseditorial20172017-06-07June 07, 201710.2215/CJN.043804171555-90411555-905X2017-05-26T08:29:40-07:002017-06-07Clinical Journal of the American Society of NephrologyEditorials1266868965870973
- Reassessing Recommendations for Choice of Vascular Access10.2215/CJN.04070417Thu, 18 May 2017 11:07:34 GMT-07:00Reassessing Recommendations for Choice of Vascular AccessLee, TimmyAllon, Michael2017-05-18T11:07:34-07:00doi:10.2215/CJN.04070417hwp:resource-id:clinjasn;12/6/865American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, arteriovenous graft, Arteriovenous Shunt, Surgical, Catheters, Indwelling, Choice BehaviorEditorialsEditorialseditorial20172017-06-07June 07, 201710.2215/CJN.040704171555-90411555-905X2017-05-18T11:07:34-07:002017-06-07Clinical Journal of the American Society of NephrologyEditorials12666865947955867954964
- Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patients10.2215/CJN.08990816Tue, 09 May 2017 06:37:06 GMT-07:00Relation between Kidney Length and Cardiovascular and Renal Risk in High-Risk Patientsvan der Sande, Nicolette G.C.Visseren, Frank L.J.van der Graaf, YolandaNathoe, Hendrik M.de Borst, Gert JanLeiner, TimBlankestijn, Peter J.2017-05-09T06:37:06-07:00doi:10.2215/CJN.08990816hwp:resource-id:clinjasn;12/6/921American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, end-stage renal disease, kidney, Biomarkers, Body Surface Area, Cardiovascular Diseases, Cause of Death, Follow-Up Studies, Humans, Kidney Failure, Chronic, Linear Models, Myocardial Infarction, Reference Values, Renal Insufficiency, Chronic, risk factors, StrokeOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-06-07June 07, 201710.2215/CJN.089908161555-90411555-905X2017-05-09T06:37:06-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126921928
- “Maybe They Don't Even Know That I Exist”: Challenges Faced by Family Members and Friends of Patients with Advanced Kidney Disease10.2215/CJN.12721216Wed, 29 Mar 2017 05:48:05 GMT-07:00“Maybe They Don't Even Know That I Exist”: Challenges Faced by Family Members and Friends of Patients with Advanced Kidney DiseaseO’Hare, Ann M.Szarka, JackieMcFarland, Lynne V.Vig, Elizabeth K.Sudore, Rebecca L.Crowley, SusanReinke, Lynn F.Trivedi, RanakTaylor, Janelle S.2017-03-29T05:48:05-07:00doi:10.2215/CJN.12721216hwp:resource-id:clinjasn;12/6/930American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyadvanced kidney disease, qualitative, family, Advance Care Planning, Chronic Disease, Friends, Goals, Grounded Theory, Humans, kidney, Kidney Diseases, Patient CareOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-06-07June 07, 201710.2215/CJN.127212161555-90411555-905X2017-03-29T05:48:05-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles126930938
- Examining the Association between Hemodialysis Access Type and Mortality: The Role of Access Complications10.2215/CJN.12181116Thu, 18 May 2017 11:07:33 GMT-07:00Examining the Association between Hemodialysis Access Type and Mortality: The Role of Access ComplicationsRavani, PietroQuinn, RobertOliver, MatthewRobinson, BrucePisoni, RonaldPannu, NeeshMacRae, JenniferManns, BradenHemmelgarn, BrendaJames, MatthewTonelli, MarcelloGillespie, Brenda2017-05-18T11:07:33-07:00doi:10.2215/CJN.12181116hwp:resource-id:clinjasn;12/6/955American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyArteriovenous Shunt, Surgical, Australasia, Central Venous Catheters, diabetes mellitus, Europe, Fistula, Follow-Up Studies, Humans, Male, North America, renal dialysis, Renal Insufficiency, thrombosisOriginal ArticlesMaintenance DialysisOriginal ArticlesMaintenance Dialysisresearch-article20172017-06-07June 07, 201710.2215/CJN.121811161555-90411555-905X2017-05-18T11:07:33-07:002017-06-07Clinical Journal of the American Society of NephrologyOriginal Articles1266955865964867
- Diversification of Cell Lineages in Ureter DevelopmentThe mammalian ureter consists of a mesenchymal wall composed of smooth muscle cells and surrounding fibrocytes of the tunica adventitia and the lamina propria and an inner epithelial lining composed of layers of basal, intermediate, and superficial cells. How these cell types arise from multipotent progenitors is poorly understood. Here, we performed marker analysis, cell proliferation assays, and genetic lineage tracing to define the lineage relations and restrictions of the mesenchymal and epithelial cell types in the developing and mature mouse ureter. At embryonic day (E) 12.5, the mesenchymal precursor pool began to subdivide into an inner and outer compartment that began to express markers of smooth muscle precursors and adventitial fibrocytes, respectively, by E13.5. Smooth muscle precursors further diversified into lamina propria cells directly adjacent to the ureteric epithelium and differentiated smooth muscle cells from E16.5 onwards. Uncommitted epithelial progenitors of the ureter differentiated into intermediate cells at E14.5. After stratification into two layers at E15.5 and three cell layers at E18.5, intermediate cells differentiated into basal cells and superficial cells. In homeostasis, proliferation of all epithelial and mesenchymal cell types remained low but intermediate cells still gave rise to basal cells, whereas basal cells divided only into basal cells. These studies provide a framework to further determine the molecular mechanisms of cell differentiation in the tissues of the developing ureter.10.1681/ASN.2016080849Tue, 27 Dec 2016 05:03:29 GMT-08:00Diversification of Cell Lineages in Ureter DevelopmentThe mammalian ureter consists of a mesenchymal wall composed of smooth muscle cells and surrounding fibrocytes of the tunica adventitia and the lamina propria and an inner epithelial lining composed of layers of basal, intermediate, and superficial cells. How these cell types arise from multipotent progenitors is poorly understood. Here, we performed marker analysis, cell proliferation assays, and genetic lineage tracing to define the lineage relations and restrictions of the mesenchymal and epithelial cell types in the developing and mature mouse ureter. At embryonic day (E) 12.5, the mesenchymal precursor pool began to subdivide into an inner and outer compartment that began to express markers of smooth muscle precursors and adventitial fibrocytes, respectively, by E13.5. Smooth muscle precursors further diversified into lamina propria cells directly adjacent to the ureteric epithelium and differentiated smooth muscle cells from E16.5 onwards. Uncommitted epithelial progenitors of the ureter differentiated into intermediate cells at E14.5. After stratification into two layers at E15.5 and three cell layers at E18.5, intermediate cells differentiated into basal cells and superficial cells. In homeostasis, proliferation of all epithelial and mesenchymal cell types remained low but intermediate cells still gave rise to basal cells, whereas basal cells divided only into basal cells. These studies provide a framework to further determine the molecular mechanisms of cell differentiation in the tissues of the developing ureter.Bohnenpoll, TobiasFeraric, SarahNattkemper, MarvinWeiss, Anna-CarinaRudat, CarstenMeuser, MaxTrowe, Mark-OliverKispert, Andreas2016-12-27T05:03:29-08:00doi:10.1681/ASN.2016080849hwp:resource-id:jnephrol;28/6/1792American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyureteric bud, renal development, renal cell biology, genetics and development, kidney development, molecular geneticsBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160808491046-66731533-34502016-12-27T05:03:29-08:002017-06Journal of the American Society of NephrologyBasic Research28617921801
- Should Statins Be Banned from Dialysis?10.1681/ASN.2017020201Wed, 03 May 2017 05:32:29 GMT-07:00Should Statins Be Banned from Dialysis?De Vriese, An S.2017-05-03T05:32:29-07:00doi:10.1681/ASN.2017020201hwp:resource-id:jnephrol;28/6/1675American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, coronary calcification, dialysis, statinsUp Front MattersPerspectiveUp Front MattersPerspectiveresearch-article20172017-06-01June 201710.1681/ASN.20170202011046-66731533-34502017-05-03T05:32:29-07:002017-06Journal of the American Society of NephrologyUp Front Matters28616751676
- New Insights into Podocyte Biology in Glomerular Health and DiseasePodocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3–6, 2016, the 11th International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.10.1681/ASN.2017010027Wed, 12 Apr 2017 12:47:47 GMT-07:00New Insights into Podocyte Biology in Glomerular Health and DiseasePodocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3–6, 2016, the 11th International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.Assady, SuheirWanner, NicolaSkorecki, Karl L.Huber, Tobias B.2017-04-12T12:47:47-07:00doi:10.1681/ASN.2017010027hwp:resource-id:jnephrol;28/6/1707American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, slit diaphragm, glomerular basement membrane, glomerular diseaseUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20172017-06-01June 201710.1681/ASN.20170100271046-66731533-34502017-04-12T12:47:47-07:002017-06Journal of the American Society of NephrologyUp Front Matters28617071715
- The ESRD Quality Incentive Program—Can We Bridge the Chasm?The ESRD Quality Incentive Program (QIP) is the first mandatory federal pay for performance program launched on January 1, 2012. The QIP is tied to the ESRD prospective payment system and mandated by the Medicare Improvements for Patients and Providers Act of 2008, which directed the Centers for Medicare and Medicaid Services to expand the payment bundle for renal dialysis services and legislated that payment be tied to quality measures. The QIP links 2% of the payment that a dialysis facility receives for Medicare patients on dialysis to the facility’s performance on quality of care measures. Quality measures are evaluated annually for inclusion on the basis of importance, validity, and performance gap. Other quality assessment programs overlap with the QIP; all have substantial effects on provision of care as clinicians, patients, regulators, and dialysis organizations scramble to keep up with the frequent release of wide-ranging regulations. In this review, we provide an overview of quality assessment and quality measures, focusing on the ESRD QIP, its effect on care, and its potential future directions. We conclude that a patient-centered, individualized, and parsimonious approach to quality assessment needs to be maintained to allow the nephrology community to further bridge the quality chasm in dialysis care.10.1681/ASN.2016101079Wed, 15 Mar 2017 05:56:06 GMT-07:00The ESRD Quality Incentive Program—Can We Bridge the Chasm?The ESRD Quality Incentive Program (QIP) is the first mandatory federal pay for performance program launched on January 1, 2012. The QIP is tied to the ESRD prospective payment system and mandated by the Medicare Improvements for Patients and Providers Act of 2008, which directed the Centers for Medicare and Medicaid Services to expand the payment bundle for renal dialysis services and legislated that payment be tied to quality measures. The QIP links 2% of the payment that a dialysis facility receives for Medicare patients on dialysis to the facility’s performance on quality of care measures. Quality measures are evaluated annually for inclusion on the basis of importance, validity, and performance gap. Other quality assessment programs overlap with the QIP; all have substantial effects on provision of care as clinicians, patients, regulators, and dialysis organizations scramble to keep up with the frequent release of wide-ranging regulations. In this review, we provide an overview of quality assessment and quality measures, focusing on the ESRD QIP, its effect on care, and its potential future directions. We conclude that a patient-centered, individualized, and parsimonious approach to quality assessment needs to be maintained to allow the nephrology community to further bridge the quality chasm in dialysis care.Weiner, DanielWatnick, Suzanne2017-03-15T05:56:06-07:00doi:10.1681/ASN.2016101079hwp:resource-id:jnephrol;28/6/1697American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyQuality incentive program, end-stage renal disease, Centers for Medicare and Medicaid Services, prospective payment systemUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-06-01June 201710.1681/ASN.20161010791046-66731533-34502017-03-15T05:56:06-07:002017-06Journal of the American Society of NephrologyUp Front Matters28616971706
- Perspective on Clinical Application of Biomarkers in AKISeveral biomarkers of renal injury have been identified but the utility of these biomarkers is largely confined to research studies, whereas widespread clinical applicability is limited. This is partly because the use of serum creatinine as the comparator has several limitations and restricts the full interpretation of biomarker performance. To highlight the potential for clinical application of biomarkers, the most pertinent biomarker data are summarized here, using clinically relevant scenarios in which biomarkers could assist with diagnostic and management dilemmas. The paradigms proposed in this review aim to enhance the clinical diagnosis, management, and prognosis of AKI through the combined use of available clinical markers and novel inflammatory, injury, and repair biomarkers.10.1681/ASN.2016101127Mon, 20 Feb 2017 05:25:55 GMT-08:00Perspective on Clinical Application of Biomarkers in AKISeveral biomarkers of renal injury have been identified but the utility of these biomarkers is largely confined to research studies, whereas widespread clinical applicability is limited. This is partly because the use of serum creatinine as the comparator has several limitations and restricts the full interpretation of biomarker performance. To highlight the potential for clinical application of biomarkers, the most pertinent biomarker data are summarized here, using clinically relevant scenarios in which biomarkers could assist with diagnostic and management dilemmas. The paradigms proposed in this review aim to enhance the clinical diagnosis, management, and prognosis of AKI through the combined use of available clinical markers and novel inflammatory, injury, and repair biomarkers.Parikh, Chirag R.Mansour, Sherry G.2017-02-20T05:25:55-08:00doi:10.1681/ASN.2016101127hwp:resource-id:jnephrol;28/6/1677American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, injury biomarkers, clinical applicationUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-06-01June 201710.1681/ASN.20161011271046-66731533-34502017-02-20T05:25:55-08:002017-06Journal of the American Society of NephrologyUp Front Matters28616771685
- MicroRNAs as Master Regulators of Glomerular Function in Health and DiseaseMicroRNAs (miRNAs) are important regulators of gene expression, and the dysregulation of miRNAs is a common feature of several diseases. More miRNAs are identified almost daily, revealing the complexity of these transcripts in eukaryotic cellular networks. The study of renal miRNAs, using genetically modified mice or by perturbing endogenous miRNA levels, has revealed the important biologic roles miRNAs have in the major cell lineages that compose the glomerulus. Here, we provide an overview of miRNA biogenesis and function in regulating key genes and cellular pathways in glomerular cells during development and homeostasis. Moreover, we focus on the emerging mechanisms through which miRNAs contribute to different diseases affecting the glomerulus, such as FSGS, IgA nephropathy, lupus nephritis, and diabetic nephropathy. In-depth knowledge of miRNA-based gene regulation has made it possible to unravel pathomechanisms, enabling the design of new therapeutic strategies for glomerular diseases for which available therapies are not fully efficacious.10.1681/ASN.2016101117Thu, 23 Feb 2017 06:34:26 GMT-08:00MicroRNAs as Master Regulators of Glomerular Function in Health and DiseaseMicroRNAs (miRNAs) are important regulators of gene expression, and the dysregulation of miRNAs is a common feature of several diseases. More miRNAs are identified almost daily, revealing the complexity of these transcripts in eukaryotic cellular networks. The study of renal miRNAs, using genetically modified mice or by perturbing endogenous miRNA levels, has revealed the important biologic roles miRNAs have in the major cell lineages that compose the glomerulus. Here, we provide an overview of miRNA biogenesis and function in regulating key genes and cellular pathways in glomerular cells during development and homeostasis. Moreover, we focus on the emerging mechanisms through which miRNAs contribute to different diseases affecting the glomerulus, such as FSGS, IgA nephropathy, lupus nephritis, and diabetic nephropathy. In-depth knowledge of miRNA-based gene regulation has made it possible to unravel pathomechanisms, enabling the design of new therapeutic strategies for glomerular diseases for which available therapies are not fully efficacious.Trionfini, PieraBenigni, Ariela2017-02-23T06:34:26-08:00doi:10.1681/ASN.2016101117hwp:resource-id:jnephrol;28/6/1686American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, miRNA, podocyte, mesangial cells, parietal epithelial cellsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-06-01June 201710.1681/ASN.20161011171046-66731533-34502017-02-23T06:34:26-08:002017-06Journal of the American Society of NephrologyUp Front Matters28616861696
- Prognostic Value of Serum Biomarkers of Autoimmunity for Recurrence of IgA Nephropathy after Kidney TransplantationA prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years) on calcineurin inhibitor–based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy-proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1–specific IgG and IgA autoantibodies in serum obtained at time of transplant or native-kidney IgAN diagnosis (30 patients only). Overall, 13 patients died, 34 kidneys failed (17 due to CPR), and 34 patients developed CPR after a mean interval of 5.8 years. Compared with healthy controls (n=30), patients had significantly elevated serum Gd-IgA1 levels at diagnosis and transplant, but levels did not associate with any outcome. Patients also had significantly elevated levels of normalized (but not total) serum Gd-IgA1–specific IgG autoantibodies at diagnosis and transplant, and the level at transplant associated with higher risk of CPR (relative risk, 2.68; 95% confidence interval, 1.26 to 5.71; P=0.01; area under the receiver operating characteristic curve, 0.62; 95% confidence interval, 0.51 to 0.74; P=0.05). Normalized Gd-IgA1–specific IgG autoantibody level remained an independent risk factor for CPR in multivariate analysis. Serum Gd-IgA1–specific IgA autoantibody level did not change between diagnosis and transplant or predict outcome. This study emphasizes post-transplant prognostic value of normalized serum IgG antiglycan autoantibody level in patients with IgAN.10.1681/ASN.2016060670Thu, 02 Mar 2017 06:54:40 GMT-08:00Prognostic Value of Serum Biomarkers of Autoimmunity for Recurrence of IgA Nephropathy after Kidney TransplantationA prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years) on calcineurin inhibitor–based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy-proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1–specific IgG and IgA autoantibodies in serum obtained at time of transplant or native-kidney IgAN diagnosis (30 patients only). Overall, 13 patients died, 34 kidneys failed (17 due to CPR), and 34 patients developed CPR after a mean interval of 5.8 years. Compared with healthy controls (n=30), patients had significantly elevated serum Gd-IgA1 levels at diagnosis and transplant, but levels did not associate with any outcome. Patients also had significantly elevated levels of normalized (but not total) serum Gd-IgA1–specific IgG autoantibodies at diagnosis and transplant, and the level at transplant associated with higher risk of CPR (relative risk, 2.68; 95% confidence interval, 1.26 to 5.71; P=0.01; area under the receiver operating characteristic curve, 0.62; 95% confidence interval, 0.51 to 0.74; P=0.05). Normalized Gd-IgA1–specific IgG autoantibody level remained an independent risk factor for CPR in multivariate analysis. Serum Gd-IgA1–specific IgA autoantibody level did not change between diagnosis and transplant or predict outcome. This study emphasizes post-transplant prognostic value of normalized serum IgG antiglycan autoantibody level in patients with IgAN.Berthoux, FrancoisSuzuki, HitoshiMohey, HeshamMaillard, NicolasMariat, ChristopheNovak, JanJulian, Bruce A.2017-03-02T06:54:40-08:00doi:10.1681/ASN.2016060670hwp:resource-id:jnephrol;28/6/1943American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, renal transplantation, IgA deposition, transplant outcomes, recurrent diseaseClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160606701046-66731533-34502017-03-02T06:54:40-08:002017-06Journal of the American Society of NephrologyClinical Research28619431950
- Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant RecipientsMetabolic acidosis (MA), indicated by low serum total CO2 (TCO2) concentration, is a risk factor for mortality and progressive renal dysfunction in CKD. However, the long-term effects of MA on kidney transplant recipients (KTRs) are unclear. We conducted a multicenter retrospective cohort study of 2318 adult KTRs, from January 1, 1997 to March 31, 2015, to evaluate the prevalence of MA and the relationships between TCO2 concentration and clinical outcomes. The prevalence of low TCO2 concentration (<22 mmol/L) began to increase in KTRs with eGFR<60 ml/min per 1.73 m2 and ranged from approximately 30% to 70% in KTRs with eGFR<30 ml/min per 1.73 m2. Multivariable Cox proportional hazards models revealed that low TCO2 concentration 3 months after transplant associated with increased risk of graft loss (hazard ratio [HR], 1.74%; 95% confidence interval [95% CI], 1.26 to 2.42) and death-censored graft failure (DCGF) (HR, 1.66; 95% CI, 1.14 to 2.42). Cox regression models using time-varying TCO2 concentration additionally demonstrated significant associations between low TCO2 concentration and graft loss (HR, 3.48; 95% CI, 2.47 to 4.90), mortality (HR, 3.16; 95% CI, 1.77 to 5.62), and DCGF (HR, 3.17; 95% CI, 2.12 to 4.73). Marginal structural Cox models adjusted for time-varying eGFR further verified significant hazards of low TCO2 concentration for graft loss, mortality, and DCGF. In conclusion, MA was frequent in KTRs despite relatively preserved renal function and may be a significant risk factor for graft failure and patient mortality, even after adjusting for eGFR.10.1681/ASN.2016070793Wed, 28 Dec 2016 04:52:04 GMT-08:00Metabolic Acidosis and Long-Term Clinical Outcomes in Kidney Transplant RecipientsMetabolic acidosis (MA), indicated by low serum total CO2 (TCO2) concentration, is a risk factor for mortality and progressive renal dysfunction in CKD. However, the long-term effects of MA on kidney transplant recipients (KTRs) are unclear. We conducted a multicenter retrospective cohort study of 2318 adult KTRs, from January 1, 1997 to March 31, 2015, to evaluate the prevalence of MA and the relationships between TCO2 concentration and clinical outcomes. The prevalence of low TCO2 concentration (<22 mmol/L) began to increase in KTRs with eGFR<60 ml/min per 1.73 m2 and ranged from approximately 30% to 70% in KTRs with eGFR<30 ml/min per 1.73 m2. Multivariable Cox proportional hazards models revealed that low TCO2 concentration 3 months after transplant associated with increased risk of graft loss (hazard ratio [HR], 1.74%; 95% confidence interval [95% CI], 1.26 to 2.42) and death-censored graft failure (DCGF) (HR, 1.66; 95% CI, 1.14 to 2.42). Cox regression models using time-varying TCO2 concentration additionally demonstrated significant associations between low TCO2 concentration and graft loss (HR, 3.48; 95% CI, 2.47 to 4.90), mortality (HR, 3.16; 95% CI, 1.77 to 5.62), and DCGF (HR, 3.17; 95% CI, 2.12 to 4.73). Marginal structural Cox models adjusted for time-varying eGFR further verified significant hazards of low TCO2 concentration for graft loss, mortality, and DCGF. In conclusion, MA was frequent in KTRs despite relatively preserved renal function and may be a significant risk factor for graft failure and patient mortality, even after adjusting for eGFR.Park, SeokwooKang, EunjeongPark, SehoonKim, Yong ChulHan, Seung SeokHa, JongwonKim, Dong KiKim, SejoongPark, Su-KilHan, Duck JongLim, Chun SooKim, Yon SuLee, Jung PyoKim, Young Hoon2016-12-28T04:52:04-08:00doi:10.1681/ASN.2016070793hwp:resource-id:jnephrol;28/6/1886American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacidosis, kidney transplantation, chronic graft deterioration, mortality, transplant recipients, glomerular filtration rateClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160707931046-66731533-34502016-12-28T04:52:04-08:002017-06Journal of the American Society of NephrologyClinical Research28661886167218971674
- Megalin Blockade with Cilastatin Suppresses Drug-Induced NephrotoxicityNephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I–mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney-specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.10.1681/ASN.2016060606Wed, 04 Jan 2017 07:45:11 GMT-08:00Megalin Blockade with Cilastatin Suppresses Drug-Induced NephrotoxicityNephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I–mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney-specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.Hori, YoshihisaAoki, NobumasaKuwahara, ShojiHosojima, MichihiroKaseda, RyoheiGoto, SawakoIida, TomomichiDe, ShankhajitKabasawa, HideyukiKaneko, ReikaAoki, HiroyukiTanabe, YoshinariKagamu, HiroshiNarita, IchieiKikuchi, ToshiakiSaito, Akihiko2017-01-04T07:45:11-08:00doi:10.1681/ASN.2016060606hwp:resource-id:jnephrol;28/6/1783American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, Colistin, gentamicin, nephrotoxicity, VancomycinBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160606061046-66731533-34502017-01-04T07:45:11-08:002017-06Journal of the American Society of NephrologyBasic Research283364417838728721791872872
- Unique Transcriptional Programs Identify Subtypes of AKITwo metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to the injury of the kidney tubule and the epithelial cells thereof (AKI). Yet neither criterion emphasizes the etiology or the pathogenetic heterogeneity of acute decreases in kidney excretory function. In fact, whether decreased excretory function due to contraction of the extracellular fluid volume (vAKI) or due to intrinsic kidney injury (iAKI) actually share pathogenesis and should be aggregated in the same diagnostic group remains an open question. To examine this possibility, we created mouse models of iAKI and vAKI that induced a similar increase in serum creatinine concentration. Using laser microdissection to isolate specific domains of the kidney, followed by RNA sequencing, we found that thousands of genes responded specifically to iAKI or to vAKI, but very few responded to both stimuli. In fact, the activated gene sets comprised different, functionally unrelated signal transduction pathways and were expressed in different regions of the kidney. Moreover, we identified distinctive gene expression patterns in human urine as potential biomarkers of either iAKI or vAKI, but not both. Hence, iAKI and vAKI are biologically unrelated, suggesting that molecular analysis should clarify our current definitions of acute changes in kidney excretory function.10.1681/ASN.2016090974Tue, 27 Dec 2016 05:03:28 GMT-08:00Unique Transcriptional Programs Identify Subtypes of AKITwo metrics, a rise in serum creatinine concentration and a decrease in urine output, are considered tantamount to the injury of the kidney tubule and the epithelial cells thereof (AKI). Yet neither criterion emphasizes the etiology or the pathogenetic heterogeneity of acute decreases in kidney excretory function. In fact, whether decreased excretory function due to contraction of the extracellular fluid volume (vAKI) or due to intrinsic kidney injury (iAKI) actually share pathogenesis and should be aggregated in the same diagnostic group remains an open question. To examine this possibility, we created mouse models of iAKI and vAKI that induced a similar increase in serum creatinine concentration. Using laser microdissection to isolate specific domains of the kidney, followed by RNA sequencing, we found that thousands of genes responded specifically to iAKI or to vAKI, but very few responded to both stimuli. In fact, the activated gene sets comprised different, functionally unrelated signal transduction pathways and were expressed in different regions of the kidney. Moreover, we identified distinctive gene expression patterns in human urine as potential biomarkers of either iAKI or vAKI, but not both. Hence, iAKI and vAKI are biologically unrelated, suggesting that molecular analysis should clarify our current definitions of acute changes in kidney excretory function.Xu, KatherineRosenstiel, PaulParagas, NealHinze, ChristianGao, XiaoboHuai Shen, TianWerth, MaxForster, CatherineDeng, RongBruck, EfratBoles, Roger W.Tornato, AlexandraGopal, TejashreeJones, MadisonKonig, JustinStauber, JacobD’Agati, VivetteErdjument-Bromage, HediyeSaggi, SubodhWagener, GebhardSchmidt-Ott, Kai M.Tatonetti, NicholasTempst, PaulOliver, Juan A.Guarnieri, PaoloBarasch, Jonathan2016-12-27T05:03:28-08:00doi:10.1681/ASN.2016090974hwp:resource-id:jnephrol;28/6/1729American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytranscriptional profiling, acute kidney injury, volume depletion, renal ischemia, biomarkersBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160909741046-66731533-34502016-12-27T05:03:28-08:002017-06Journal of the American Society of NephrologyBasic Research28617291740
- Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition StudyCKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble α-klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m2 and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism.10.1681/ASN.2016080828Thu, 19 Jan 2017 06:14:46 GMT-08:00Association between Soluble Klotho and Change in Kidney Function: The Health Aging and Body Composition StudyCKD appears to be a condition of soluble klotho deficiency. Despite known associations between low soluble klotho levels and conditions that promote kidney damage, such as oxidative stress and fibrosis, little information exists regarding the longitudinal association between soluble klotho levels and change in kidney function. We assayed serum soluble α-klotho in 2496 participants within the Health Aging and Body Composition study, a cohort of older adults. The associations between soluble klotho levels and decline in kidney function (relative decline: eGFR decline ≥30%; absolute decline: eGFR decline >3 ml/min per year) and incident CKD (incident eGFR <60 ml/min per 1.73 m2 and >1 ml/min per year decline) were evaluated. We adjusted models for demographics, baseline eGFR, urine albumin-to-creatinine ratio, comorbidity, and measures of mineral metabolism. Among participants, the mean (SD) age was 75 (3) years, 52% were women, and 38% were black. Median (25th, 75th percentiles) klotho level was 630 (477, 817) pg/ml. In fully adjusted models, each two-fold higher level of klotho associated with lower odds of decline in kidney function (odds ratio, 0.78 [95% confidence interval, 0.66 to 0.93] for 30% decline in eGFR, and 0.85 [95% confidence interval, 0.73 to 0.98] for >3 ml/min per year decline in eGFR), but not of incident CKD (incident rate ratio, 0.90 [95% confidence interval, 0.78 to 1.04]). Overall, a higher soluble klotho level independently associated with a lower risk of decline in kidney function. Future studies should attempt to replicate these results in other cohorts and evaluate the underlying mechanism.Drew, David A.Katz, RonitKritchevsky, StephenIx, JoachimShlipak, MichaelGutiérrez, Orlando M.Newman, AnneHoofnagle, AndyFried, LindaSemba, Richard D.Sarnak, Mark2017-01-19T06:14:46-08:00doi:10.1681/ASN.2016080828hwp:resource-id:jnephrol;28/6/1859American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyklotho, kidney dysfunction, chronic kidney disease, risk factorsClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160808281046-66731533-34502017-01-19T06:14:46-08:002017-06Journal of the American Society of NephrologyClinical Research28618591866
- Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency AnemiaIron deficiency anemia is common and consequential in nondialysis-dependent CKD (NDD-CKD). Efficacy and tolerability of conventional oral iron supplements are mixed; intravenous iron administration associates with finite but important risks. We conducted a randomized double-blind clinical trial in adults with NDD-CKD and iron deficiency anemia to compare the safety and efficacy of oral ferric citrate (n=117) and placebo (n=115). The primary end point was the proportion of patients who achieved a ≥1.0 g/dl increase in hemoglobin at any time during a 16-week randomized period. Patients who completed the 16-week period could also participate in an 8-week open-label extension period. Significantly more patients randomized to ferric citrate achieved the primary end point (61 [52.1%] versus 22 [19.1%] with placebo; P<0.001). All secondary end points reached statistical significance in the ferric citrate group, including the mean relative change in hemoglobin (0.84 g/dl; 95% confidence interval, 0.58 to 1.10 g/dl; P<0.001) and the proportion of patients who achieved a sustained increase in hemoglobin (≥0.75 g/dl over any 4-week period during the randomized trial; 57 [48.7%] versus 17 [14.8%] with placebo; P<0.001). Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders were the most common adverse events, with diarrhea reported in 24 (20.5%) and 19 (16.4%) and constipation in 22 (18.8%) and 15 (12.9%) patients treated with ferric citrate and placebo, respectively. Overall, in patients with NDD-CKD, we found oral ferric citrate to be a safe and efficacious treatment for iron deficiency anemia.10.1681/ASN.2016101053Thu, 12 Jan 2017 05:15:04 GMT-08:00Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency AnemiaIron deficiency anemia is common and consequential in nondialysis-dependent CKD (NDD-CKD). Efficacy and tolerability of conventional oral iron supplements are mixed; intravenous iron administration associates with finite but important risks. We conducted a randomized double-blind clinical trial in adults with NDD-CKD and iron deficiency anemia to compare the safety and efficacy of oral ferric citrate (n=117) and placebo (n=115). The primary end point was the proportion of patients who achieved a ≥1.0 g/dl increase in hemoglobin at any time during a 16-week randomized period. Patients who completed the 16-week period could also participate in an 8-week open-label extension period. Significantly more patients randomized to ferric citrate achieved the primary end point (61 [52.1%] versus 22 [19.1%] with placebo; P<0.001). All secondary end points reached statistical significance in the ferric citrate group, including the mean relative change in hemoglobin (0.84 g/dl; 95% confidence interval, 0.58 to 1.10 g/dl; P<0.001) and the proportion of patients who achieved a sustained increase in hemoglobin (≥0.75 g/dl over any 4-week period during the randomized trial; 57 [48.7%] versus 17 [14.8%] with placebo; P<0.001). Rates of serious adverse events were similar in the ferric citrate (12.0%) and placebo groups (11.2%). Gastrointestinal disorders were the most common adverse events, with diarrhea reported in 24 (20.5%) and 19 (16.4%) and constipation in 22 (18.8%) and 15 (12.9%) patients treated with ferric citrate and placebo, respectively. Overall, in patients with NDD-CKD, we found oral ferric citrate to be a safe and efficacious treatment for iron deficiency anemia.Fishbane, StevenBlock, Geoffrey A.Loram, LisaNeylan, JohnPergola, Pablo E.Uhlig, KatrinChertow, Glenn M.2017-01-12T05:15:04-08:00doi:10.1681/ASN.2016101053hwp:resource-id:jnephrol;28/6/1851American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, iron deficiency, clinical trial, blood transfusion, hemoglobin, renal dialysisClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20161010531046-66731533-34502017-01-12T05:15:04-08:002017-06Journal of the American Society of NephrologyClinical Research28618511858
- Vancomycin-Associated Cast NephropathyVancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.10.1681/ASN.2016080867Thu, 12 Jan 2017 05:15:04 GMT-08:00Vancomycin-Associated Cast NephropathyVancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.Luque, YosuLouis, KevinJouanneau, ChantalPlacier, SandrineEsteve, EmmanuelBazin, DominiqueRondeau, EricLetavernier, EmmanuelWolfromm, AliceGosset, ClémentBoueilh, AnnaBurbach, MarenFrère, PerrineVerpont, Marie-ChristineVandermeersch, SophieLangui, DominiqueDaudon, MichelFrochot, VincentMesnard, Laurent2017-01-12T05:15:04-08:00doi:10.1681/ASN.2016080867hwp:resource-id:jnephrol;28/6/1723American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyvancomycin, acute renal failure, tubular epithelium, acute tubular necrosis, tubular castBrief CommunicationsBrief Communicationsbrief-report20172017-06-01June 201710.1681/ASN.20160808671046-66731533-34502017-01-12T05:15:04-08:002017-06Journal of the American Society of NephrologyBrief Communications28661723166917281670
- Vitamin K–Dependent Carboxylation of Matrix Gla Protein Influences the Risk of CalciphylaxisMatrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K–dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; P=0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses (β=−8.99; P=0.04). In conclusion, vitamin K deficiency–mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study.10.1681/ASN.2016060651Tue, 03 Jan 2017 06:06:01 GMT-08:00Vitamin K–Dependent Carboxylation of Matrix Gla Protein Influences the Risk of CalciphylaxisMatrix Gla protein (MGP) is a potent inhibitor of vascular calcification. The ability of MGP to inhibit calcification requires the activity of a vitamin K–dependent enzyme, which mediates MGP carboxylation. We investigated how MGP carboxylation influences the risk of calciphylaxis in adult patients receiving dialysis and examined the effects of vitamin K deficiency on MGP carboxylation. Our study included 20 patients receiving hemodialysis with calciphylaxis (cases) and 20 patients receiving hemodialysis without calciphylaxis (controls) matched for age, sex, race, and warfarin use. Cases had higher plasma levels of uncarboxylated MGP (ucMGP) and carboxylated MGP (cMGP) than controls. However, the fraction of total MGP that was carboxylated (relative cMGP concentration = cMGP/[cMGP + uncarboxylated MGP]) was lower in cases than in controls (0.58±0.02 versus 0.69±0.03, respectively; P=0.003). In patients not taking warfarin, cases had a similarly lower relative cMGP concentration. Each 0.1 unit reduction in relative cMGP concentration associated with a more than two-fold increase in calciphylaxis risk. Vitamin K deficiency associated with lower relative cMGP concentration in multivariable adjusted analyses (β=−8.99; P=0.04). In conclusion, vitamin K deficiency–mediated reduction in relative cMGP concentration may have a role in the pathogenesis of calciphylaxis. Whether vitamin K supplementation can prevent and/or treat calciphylaxis requires further study.Nigwekar, Sagar U.Bloch, Donald B.Nazarian, Rosalynn M.Vermeer, CeesBooth, Sarah L.Xu, DihuaThadhani, Ravi I.Malhotra, Rajeev2017-01-03T06:06:01-08:00doi:10.1681/ASN.2016060651hwp:resource-id:jnephrol;28/6/1717American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycalcific uremic arteriolopathy, vascular calcification, vitamin K, warfarin, calcium-binding protein, renal dialysisBrief CommunicationsBrief Communicationsbrief-report20172017-06-01June 201710.1681/ASN.20160606511046-66731533-34502017-01-03T06:06:01-08:002017-06Journal of the American Society of NephrologyBrief Communications28661717166717221668
- K-alcification Protection in Dialysis Patients: The Underestimated Phenomenon of Vitamin K Deficiency10.1681/ASN.2017020180Mon, 03 Apr 2017 06:18:22 GMT-07:00K-alcification Protection in Dialysis Patients: The Underestimated Phenomenon of Vitamin K DeficiencyKetteler, MarkusBrandenburg, Vincent Matthias2017-04-03T06:18:22-07:00doi:10.1681/ASN.2017020180hwp:resource-id:jnephrol;28/6/1667American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyvascular calcification, vitamin K, calciphylaxisUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-06-01June 201710.1681/ASN.20170201801046-66731533-34502017-04-03T06:18:22-07:002017-06Journal of the American Society of NephrologyUp Front Matters28661667171716681722
- Neutrophil Extracellular Traps Orchestrate Necroinflammation10.1681/ASN.2017010064Thu, 23 Feb 2017 06:34:26 GMT-08:00Neutrophil Extracellular Traps Orchestrate NecroinflammationPallet, Nicolas2017-02-23T06:34:26-08:00doi:10.1681/ASN.2017010064hwp:resource-id:jnephrol;28/6/1670American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, ischemia-reperfusion, nephritis, apoptosis, Chronic inflammationUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-06-01June 201710.1681/ASN.20170100641046-66731533-34502017-02-23T06:34:26-08:002017-06Journal of the American Society of NephrologyUp Front Matters28661670175316721768
- Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft RecipientsAntibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had de novo DSA. Compared with patients with preexisting DSA ABMR, patients with de novo DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. De novo DSA ABMR was characterized by increased expression of IFNγ-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the de novo DSA ABMR (63% versus 34% at 8 years after rejection, respectively; P<0.001). After adjusting for clinical, histologic, and immunologic characteristics and treatment, we identified de novo DSA ABMR (hazard ratio [HR], 1.82 compared with preexisting DSA ABMR; 95% confidence interval [95% CI], 1.07 to 3.08; P=0.03); low eGFR (<30 ml/min per 1.73 m2) at diagnosis (HR, 3.27; 95% CI, 1.48 to 7.23; P<0.001); ≥0.30 g/g urine protein-to-creatinine ratio (HR, 2.44; 95% CI, 1.47 to 4.09; P<0.001); and presence of cg lesions (HR, 2.25; 95% CI, 1.34 to 3.79; P=0.002) as the main independent determinants of allograft loss. Our findings support the transplant of kidneys into highly sensitized patients and should encourage efforts to monitor patients for de novo DSA.10.1681/ASN.2016070797Thu, 02 Mar 2017 06:54:39 GMT-08:00Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft RecipientsAntibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had de novo DSA. Compared with patients with preexisting DSA ABMR, patients with de novo DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. De novo DSA ABMR was characterized by increased expression of IFNγ-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the de novo DSA ABMR (63% versus 34% at 8 years after rejection, respectively; P<0.001). After adjusting for clinical, histologic, and immunologic characteristics and treatment, we identified de novo DSA ABMR (hazard ratio [HR], 1.82 compared with preexisting DSA ABMR; 95% confidence interval [95% CI], 1.07 to 3.08; P=0.03); low eGFR (<30 ml/min per 1.73 m2) at diagnosis (HR, 3.27; 95% CI, 1.48 to 7.23; P<0.001); ≥0.30 g/g urine protein-to-creatinine ratio (HR, 2.44; 95% CI, 1.47 to 4.09; P<0.001); and presence of cg lesions (HR, 2.25; 95% CI, 1.34 to 3.79; P=0.002) as the main independent determinants of allograft loss. Our findings support the transplant of kidneys into highly sensitized patients and should encourage efforts to monitor patients for de novo DSA.Aubert, OlivierLoupy, AlexandreHidalgo, LuisDuong van Huyen, Jean-PaulHiggins, SarahViglietti, DenisJouven, XavierGlotz, DenisLegendre, ChristopheLefaucheur, CarmenHalloran, Philip F.2017-03-02T06:54:39-08:00doi:10.1681/ASN.2016070797hwp:resource-id:jnephrol;28/6/1912American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydonor-specific anti-HLA antibody, antibody-mediated rejection, molecular, microscope, transplant outcomes, kidney transplantationClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160707971046-66731533-34502017-03-02T06:54:39-08:002017-06Journal of the American Society of NephrologyClinical Research28619121923
- Potassium Sensing by Renal Distal Tubules Requires Kir4.1The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na+/Cl− cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCC helps to retain potassium by increasing electroneutral NaCl reabsorption, therefore reducing Na+/K+ exchange. Yet the mechanisms by which DCT cells sense plasma potassium concentration and transmit the information to the apical membrane are not clear. Here, we tested the hypothesis that the potassium channel Kir4.1 is the potassium sensor of DCT cells. We generated mice in which Kir4.1 could be deleted in the kidney after the mice are fully developed. Deletion of Kir4.1 in these mice led to moderate salt wasting, low BP, and profound potassium wasting. Basolateral membranes of DCT cells were depolarized, nearly devoid of conductive potassium transport, and unresponsive to plasma potassium concentration. Although renal WNK4 abundance increased after Kir4.1 deletion, NCC abundance and function decreased, suggesting that membrane depolarization uncouples WNK kinases from NCC. Together, these results indicate that Kir4.1 mediates potassium sensing by DCT cells and couples this signal to apical transport processes.10.1681/ASN.2016090935Wed, 04 Jan 2017 07:45:12 GMT-08:00Potassium Sensing by Renal Distal Tubules Requires Kir4.1The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na+/Cl− cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCC helps to retain potassium by increasing electroneutral NaCl reabsorption, therefore reducing Na+/K+ exchange. Yet the mechanisms by which DCT cells sense plasma potassium concentration and transmit the information to the apical membrane are not clear. Here, we tested the hypothesis that the potassium channel Kir4.1 is the potassium sensor of DCT cells. We generated mice in which Kir4.1 could be deleted in the kidney after the mice are fully developed. Deletion of Kir4.1 in these mice led to moderate salt wasting, low BP, and profound potassium wasting. Basolateral membranes of DCT cells were depolarized, nearly devoid of conductive potassium transport, and unresponsive to plasma potassium concentration. Although renal WNK4 abundance increased after Kir4.1 deletion, NCC abundance and function decreased, suggesting that membrane depolarization uncouples WNK kinases from NCC. Together, these results indicate that Kir4.1 mediates potassium sensing by DCT cells and couples this signal to apical transport processes.Cuevas, Catherina A.Su, Xiao-TongWang, Ming-XiaoTerker, Andrew S.Lin, Dao-HongMcCormick, James A.Yang, Chao-LingEllison, David H.Wang, Wen-Hui2017-01-04T07:45:12-08:00doi:10.1681/ASN.2016090935hwp:resource-id:jnephrol;28/6/1814American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyslc12a3, thiazide, potassium channels, diuretics, wnk4, spakBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160909351046-66731533-34502017-01-04T07:45:12-08:002017-06Journal of the American Society of NephrologyBasic Research28618141825
- Fibroblast Growth Factor 23 Levels Associate with AKI and Death in Critical IllnessElevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort (n=131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients.10.1681/ASN.2016080836Tue, 27 Dec 2016 05:03:28 GMT-08:00Fibroblast Growth Factor 23 Levels Associate with AKI and Death in Critical IllnessElevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort (n=131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients.Leaf, David E.Jacob, Kirolos A.Srivastava, AnandChen, Margaret E.Christov, MartaJüppner, HaraldSabbisetti, Venkata S.Martin, AlineWolf, MylesWaikar, Sushrut S.2016-12-27T05:03:28-08:00doi:10.1681/ASN.2016080836hwp:resource-id:jnephrol;28/6/1877American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, mortality risk, parathyroid hormone, vitamin DClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160808361046-66731533-34502016-12-27T05:03:28-08:002017-06Journal of the American Society of NephrologyClinical Research28618771885
- Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion InjuryIschemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro. Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI.10.1681/ASN.2016020200Fri, 06 Jan 2017 05:19:28 GMT-08:00Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion InjuryIschemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro. Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI.McCurley, AmyAlimperti, StellaCampos-Bilderback, Silvia B.Sandoval, Ruben M.Calvino, Jenna E.Reynolds, Taylor L.Quigley, CatherineMugford, Joshua W.Polacheck, William J.Gomez, Ivan G.Dovey, JenniferMarsh, GrahamHuang, AngelaQian, FangWeinreb, Paul H.Dolinski, Brian M.Moore, ShaunDuffield, Jeremy S.Chen, Christopher S.Molitoris, Bruce A.Violette, Shelia M.Crackower, Michael A.2017-01-06T05:19:28-08:00doi:10.1681/ASN.2016020200hwp:resource-id:jnephrol;28/6/1741American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, adhesion molecule, vascular, renal ischemiaBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160202001046-66731533-34502017-01-06T05:19:28-08:002017-06Journal of the American Society of NephrologyBasic Research28617411752
- A Trial of Extending Hemodialysis Hours and Quality of LifeThe relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12–15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6–24.0) and 12.0 (interquartile range, 12.0–16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, −0.03 to 0.11]; P=0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, −6.0 [95% confidence interval, −14.8 to 2.7] g/m2; P=0.18). Five deaths occurred in the extended group and two in the standard group (P=0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298).10.1681/ASN.2015111225Wed, 01 Feb 2017 07:11:24 GMT-08:00A Trial of Extending Hemodialysis Hours and Quality of LifeThe relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12–15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6–24.0) and 12.0 (interquartile range, 12.0–16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, −0.03 to 0.11]; P=0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, −6.0 [95% confidence interval, −14.8 to 2.7] g/m2; P=0.18). Five deaths occurred in the extended group and two in the standard group (P=0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298).Jardine, Meg J.Zuo, LiGray, Nicholas A.de Zoysa, Janak R.Chan, Christopher T.Gallagher, Martin P.Monaghan, HelenGrieve, Stuart M.Puranik, RajeshLin, HongliEris, Josette M.Zhang, LingXu, JinshengHoward, KirstenLo, SerigneCass, AlanPerkovic, VladoLin, HongliEris, JosetteSnelling, PaulZhang, LingXu, JinshengZhang, JunliHawley, Carmel M.Van Eps, CarolynCooper, Bruce A.Li, YinhuiSuranyi, Michael G.Wong, JeffreyZuo, LiChen, YuqingLi, YingGray, NicholasChan, Christopher T.de Zoysa, JanakWang, MeiLei, JiangLiu, Zhangsuo,Xue, LanfenChen, NanMao, YonghuiLi, RongshanWang, CailiHuang, WenFu, PingPedagogos, EugeniaWang, KaiZhang, ShengrongRanganathan, DwarakanathanLi, JijunLui, BichengCopland, MichaelPerl, JeffreyKerr, Peter G.Pellicano, RebeccaTalaulikar, GirishYu, RichardBoudville, NeilMount, PeterDivi, MurthyCass, AlanAgar, JohnHoward, KirstenIrish, Ashley2017-02-01T07:11:24-08:00doi:10.1681/ASN.2015111225hwp:resource-id:jnephrol;28/6/1898American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, randomized controlled trials, quality of life, extended dialysis, left ventricular hypertrophyClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20151112251046-66731533-34502017-02-01T07:11:24-08:002017-06Journal of the American Society of NephrologyClinical Research28618981911
- Effect of Tenapanor on Serum Phosphate in Patients Receiving HemodialysisHyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32–7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47–1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%–68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.10.1681/ASN.2016080855Fri, 03 Feb 2017 08:05:17 GMT-08:00Effect of Tenapanor on Serum Phosphate in Patients Receiving HemodialysisHyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32–7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47–1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%–68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.Block, Geoffrey A.Rosenbaum, David P.Leonsson-Zachrisson, MariaÅstrand, MagnusJohansson, SusanneKnutsson, MikaelLangkilde, Anna MariaChertow, Glenn M.2017-02-03T08:05:17-08:00doi:10.1681/ASN.2016080855hwp:resource-id:jnephrol;28/6/1933American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytenapanor, hyperphosphatemia, hemodialysis, chronic kidney disease, NHE3, sodium–hydrogen exchanger 3Clinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160808551046-66731533-34502017-02-03T08:05:17-08:002017-06Journal of the American Society of NephrologyClinical Research28619331942
- A Variant of Peptide Transporter 2 Predicts the Severity of Porphyria-Associated Kidney DiseaseCKD occurs in most patients with acute intermittent porphyria (AIP). During AIP, δ-aminolevulinic acid (ALA) accumulates and promotes tubular cell death and tubulointerstitial damage. The human peptide transporter 2 (PEPT2) expressed by proximal tubular cells mediates the reabsorption of ALA, and variants of PEPT2 have different affinities for ALA. We tested the hypothesis that PEPT2 genotypes affect the severity and prognosis of porphyria-associated kidney disease. We analyzed data from 122 individuals with AIP who were followed from 2003 to 2013 and genotyped for PEPT2. At last follow-up, carriers of the PEPT2*1*1 genotype (higher affinity variant) exhibited worse renal function than carriers of the lower affinity variants PEPT2*1/*2 and PEPT2*2/*2 (mean±SD eGFR: 54.4±19.1, 66.6±23.8, and 78.1±19.9 ml/min per 1.73 m2, respectively). Change in eGFR (mean±SD) over the 10-year period was −11.0±3.3, −2.4±1.9, and 3.4±2.6 ml/min per 1.73 m2 for PEPT2*1/*1, PEPT2*1*2, and PEPT*2*2*2 carriers, respectively. At the end of follow-up, 68% of PEPT2*1*1 carriers had an eGFR<60 ml/min per 1.73 m2, compared with 37% of PEPT2*1*2 carriers and 15% of PEPT2*2*2 carriers. Multiple regression models including all confounders indicated that the PEPT2*1*1 genotype independently associated with an eGFR<60 ml/min per 1.73 m2 (odds ratio, 6.85; 95% confidence interval, 1.34 to 46.20) and an annual decrease in eGFR of >1 ml/min per 1.73 m2 (odds ratio, 3.64; 95% confidence interval, 1.37 to 9.91). Thus, a gene variant is predictive of the severity of a chronic complication of AIP. The therapeutic value of PEPT2 inhibitors in preventing porphyria-associated kidney disease warrants investigation.10.1681/ASN.2016080918Wed, 28 Dec 2016 04:52:03 GMT-08:00A Variant of Peptide Transporter 2 Predicts the Severity of Porphyria-Associated Kidney DiseaseCKD occurs in most patients with acute intermittent porphyria (AIP). During AIP, δ-aminolevulinic acid (ALA) accumulates and promotes tubular cell death and tubulointerstitial damage. The human peptide transporter 2 (PEPT2) expressed by proximal tubular cells mediates the reabsorption of ALA, and variants of PEPT2 have different affinities for ALA. We tested the hypothesis that PEPT2 genotypes affect the severity and prognosis of porphyria-associated kidney disease. We analyzed data from 122 individuals with AIP who were followed from 2003 to 2013 and genotyped for PEPT2. At last follow-up, carriers of the PEPT2*1*1 genotype (higher affinity variant) exhibited worse renal function than carriers of the lower affinity variants PEPT2*1/*2 and PEPT2*2/*2 (mean±SD eGFR: 54.4±19.1, 66.6±23.8, and 78.1±19.9 ml/min per 1.73 m2, respectively). Change in eGFR (mean±SD) over the 10-year period was −11.0±3.3, −2.4±1.9, and 3.4±2.6 ml/min per 1.73 m2 for PEPT2*1/*1, PEPT2*1*2, and PEPT*2*2*2 carriers, respectively. At the end of follow-up, 68% of PEPT2*1*1 carriers had an eGFR<60 ml/min per 1.73 m2, compared with 37% of PEPT2*1*2 carriers and 15% of PEPT2*2*2 carriers. Multiple regression models including all confounders indicated that the PEPT2*1*1 genotype independently associated with an eGFR<60 ml/min per 1.73 m2 (odds ratio, 6.85; 95% confidence interval, 1.34 to 46.20) and an annual decrease in eGFR of >1 ml/min per 1.73 m2 (odds ratio, 3.64; 95% confidence interval, 1.37 to 9.91). Thus, a gene variant is predictive of the severity of a chronic complication of AIP. The therapeutic value of PEPT2 inhibitors in preventing porphyria-associated kidney disease warrants investigation.Tchernitchko, DimitriTavernier, QuentinLamoril, JérômeSchmitt, CarolineTalbi, NeilaLyoumi, SaidRobreau, Anne-MarieKarim, ZoubidaGouya, LaurentThervet, EricKarras, AlexandrePuy, HervéPallet, Nicolas2016-12-28T04:52:03-08:00doi:10.1681/ASN.2016080918hwp:resource-id:jnephrol;28/6/1924American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAcute Intermittent Porphyria, PEPT2, SLC15A2, chronic kidney disease, Delta-aminolevulinic acidClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160809181046-66731533-34502016-12-28T04:52:03-08:002017-06Journal of the American Society of NephrologyClinical Research28619241932
- This Month’s Highlights10.1681/ASN.2017020177Wed, 31 May 2017 01:03:11 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-05-31T13:03:11-07:00doi:10.1681/ASN.2017020177hwp:resource-id:jnephrol;28/6/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-06-01June 201710.1681/ASN.20170201771046-66731533-34502017-05-31T13:03:11-07:002017-06Journal of the American Society of NephrologyThis Month’s Highlights286ii
- Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKDThe pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using 23sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23–78] years). We also assessed total body overhydration (bioimpedance spectroscopy), 24-hour BP, and left ventricular mass (cardiac magnetic resonance imaging). Skin sodium content, but not total body overhydration, correlated with systolic BP (r=0.33, P=0.002). Moreover, skin sodium content correlated more strongly than total body overhydration did with left ventricular mass (r=0.56, P<0.001 versus r=0.35, P<0.001; P<0.01 between the two correlations). Linear regression analysis demonstrated that skin sodium content is a strong explanatory variable for left ventricular mass, unaffected by BP and total body overhydration. In conclusion, we found skin sodium content to be closely linked to left ventricular mass in patients with CKD. Interventions that reduce skin sodium content might improve cardiovascular outcomes in these patients.10.1681/ASN.2016060662Thu, 02 Feb 2017 07:53:15 GMT-08:00Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKDThe pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using 23sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23–78] years). We also assessed total body overhydration (bioimpedance spectroscopy), 24-hour BP, and left ventricular mass (cardiac magnetic resonance imaging). Skin sodium content, but not total body overhydration, correlated with systolic BP (r=0.33, P=0.002). Moreover, skin sodium content correlated more strongly than total body overhydration did with left ventricular mass (r=0.56, P<0.001 versus r=0.35, P<0.001; P<0.01 between the two correlations). Linear regression analysis demonstrated that skin sodium content is a strong explanatory variable for left ventricular mass, unaffected by BP and total body overhydration. In conclusion, we found skin sodium content to be closely linked to left ventricular mass in patients with CKD. Interventions that reduce skin sodium content might improve cardiovascular outcomes in these patients.Schneider, Markus P.Raff, UlrikeKopp, ChristophScheppach, Johannes B.Toncar, SebastianWanner, ChristophSchlieper, GeorgSaritas, TurgayFloege, JürgenSchmid, MatthiasBirukov, AnnaDahlmann, AnkeLinz, PeterJanka, RolfUder, MichaelSchmieder, Roland E.Titze, Jens M.Eckardt, Kai-Uwe2017-02-02T07:53:15-08:00doi:10.1681/ASN.2016060662hwp:resource-id:jnephrol;28/6/1867American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney diseases, left ventricular hypertrophy, sodium, skin, blood pressureClinical ResearchClinical Researchresearch-article20172017-06-01June 201710.1681/ASN.20160606621046-66731533-34502017-02-02T07:53:15-08:002017-06Journal of the American Society of NephrologyClinical Research28618671876
- Vancomycin in the Kidney—A Novel Cast Nephropathy10.1681/ASN.2017010091Tue, 07 Mar 2017 06:25:46 GMT-08:00Vancomycin in the Kidney—A Novel Cast NephropathyStokes, M. Barry2017-03-07T06:25:46-08:00doi:10.1681/ASN.2017010091hwp:resource-id:jnephrol;28/6/1669American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyvancomycin, acute kidney injury, casts, nephropathy, drug nephrotoxicityUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-06-01June 201710.1681/ASN.20170100911046-66731533-34502017-03-07T06:25:46-08:002017-06Journal of the American Society of NephrologyUp Front Matters28661669172316701728
- Complications of the Arteriovenous Fistula: A Systematic ReviewThe implementation of patient-centered care requires an individualized approach to hemodialysis vascular access, on the basis of each patient’s unique balance of risks and benefits. This systematic review aimed to summarize current literature on fistula risks, including rates of complications, to assist with patient-centered decision making. We searched Medline from 2000 to 2014 for English-language studies with prospectively captured data on ≥100 fistulas. We assessed study quality and extracted data on study design, patient characteristics, and outcomes. After screening 2292 citations, 43 articles met our inclusion criteria (61 unique cohorts; n>11,374 fistulas). Median complication rates per 1000 patient days were as follows: 0.04 aneurysms (14 unique cohorts; n=1827 fistulas), 0.11 infections (16 cohorts; n>6439 fistulas), 0.05 steal events (15 cohorts; n>2543 fistulas), 0.24 thrombotic events (26 cohorts; n=4232 fistulas), and 0.03 venous hypertensive events (1 cohort; n=350 fistulas). Risk of bias was high in many studies and event rates were variable, thus we could not present pooled results. Studies generally did not report variables associated with fistula complications, patient comorbidities, vessel characteristics, surgeon experience, or nursing cannulation skill. Overall, we found marked variability in complication rates, partly due to poor quality studies, significant heterogeneity of study populations, and inconsistent definitions. There is an urgent need to standardize reporting of methods and definitions of vascular access complications in future clinical studies to better inform patient and provider decision making.10.1681/ASN.2016040412Wed, 28 Dec 2016 04:52:04 GMT-08:00Complications of the Arteriovenous Fistula: A Systematic ReviewThe implementation of patient-centered care requires an individualized approach to hemodialysis vascular access, on the basis of each patient’s unique balance of risks and benefits. This systematic review aimed to summarize current literature on fistula risks, including rates of complications, to assist with patient-centered decision making. We searched Medline from 2000 to 2014 for English-language studies with prospectively captured data on ≥100 fistulas. We assessed study quality and extracted data on study design, patient characteristics, and outcomes. After screening 2292 citations, 43 articles met our inclusion criteria (61 unique cohorts; n>11,374 fistulas). Median complication rates per 1000 patient days were as follows: 0.04 aneurysms (14 unique cohorts; n=1827 fistulas), 0.11 infections (16 cohorts; n>6439 fistulas), 0.05 steal events (15 cohorts; n>2543 fistulas), 0.24 thrombotic events (26 cohorts; n=4232 fistulas), and 0.03 venous hypertensive events (1 cohort; n=350 fistulas). Risk of bias was high in many studies and event rates were variable, thus we could not present pooled results. Studies generally did not report variables associated with fistula complications, patient comorbidities, vessel characteristics, surgeon experience, or nursing cannulation skill. Overall, we found marked variability in complication rates, partly due to poor quality studies, significant heterogeneity of study populations, and inconsistent definitions. There is an urgent need to standardize reporting of methods and definitions of vascular access complications in future clinical studies to better inform patient and provider decision making.Al-Jaishi, Ahmed A.Liu, Aiden R.Lok, Charmaine E.Zhang, Joyce C.Moist, Louise M.2016-12-28T04:52:04-08:00doi:10.1681/ASN.2016040412hwp:resource-id:jnephrol;28/6/1839American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, chronic hemodialysis, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-06-01June 201710.1681/ASN.20160404121046-66731533-34502016-12-28T04:52:04-08:002017-06Journal of the American Society of NephrologyClinical Epidemiology28618391850
- Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKISevere AKI is often associated with multiorgan dysfunction, but the mechanisms of this remote tissue injury are unknown. We hypothesized that renal necroinflammation releases cytotoxic molecules that may cause remote organ damage. In hypoxia-induced tubular epithelial cell necrosis in vitro, histone secretion from ischemic tubular cells primed neutrophils to form neutrophil extracellular traps. These traps induced tubular epithelial cell death and stimulated neutrophil extracellular trap formation in fresh neutrophils. In vivo, ischemia-reperfusion injury in the mouse kidney induced tubular necrosis, which preceded the expansion of localized and circulating neutrophil extracellular traps and the increased expression of inflammatory and injury-related genes. Pretreatment with inhibitors of neutrophil extracellular trap formation reduced kidney injury. Dual inhibition of neutrophil trap formation and tubular cell necrosis had an additive protective effect. Moreover, pretreatment with antihistone IgG suppressed ischemia-induced neutrophil extracellular trap formation and renal injury. Renal ischemic injury also increased the levels of circulating histones, and we detected neutrophil infiltration and TUNEL-positive cells in the lungs, liver, brain, and heart along with neutrophil extracellular trap accumulation in the lungs. Inhibition of neutrophil extracellular trap formation or of circulating histones reduced these effects as well. These data suggest that tubular necrosis and neutrophil extracellular trap formation accelerate kidney damage and remote organ dysfunction through cytokine and histone release and identify novel molecular targets to limit renal necroinflammation and multiorgan failure.10.1681/ASN.2016080925Tue, 10 Jan 2017 05:09:33 GMT-08:00Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKISevere AKI is often associated with multiorgan dysfunction, but the mechanisms of this remote tissue injury are unknown. We hypothesized that renal necroinflammation releases cytotoxic molecules that may cause remote organ damage. In hypoxia-induced tubular epithelial cell necrosis in vitro, histone secretion from ischemic tubular cells primed neutrophils to form neutrophil extracellular traps. These traps induced tubular epithelial cell death and stimulated neutrophil extracellular trap formation in fresh neutrophils. In vivo, ischemia-reperfusion injury in the mouse kidney induced tubular necrosis, which preceded the expansion of localized and circulating neutrophil extracellular traps and the increased expression of inflammatory and injury-related genes. Pretreatment with inhibitors of neutrophil extracellular trap formation reduced kidney injury. Dual inhibition of neutrophil trap formation and tubular cell necrosis had an additive protective effect. Moreover, pretreatment with antihistone IgG suppressed ischemia-induced neutrophil extracellular trap formation and renal injury. Renal ischemic injury also increased the levels of circulating histones, and we detected neutrophil infiltration and TUNEL-positive cells in the lungs, liver, brain, and heart along with neutrophil extracellular trap accumulation in the lungs. Inhibition of neutrophil extracellular trap formation or of circulating histones reduced these effects as well. These data suggest that tubular necrosis and neutrophil extracellular trap formation accelerate kidney damage and remote organ dysfunction through cytokine and histone release and identify novel molecular targets to limit renal necroinflammation and multiorgan failure.Nakazawa, DaigoKumar, Santhosh V.Marschner, JulianDesai, JyaysiHolderied, AlexanderRath, LukasKraft, FranziskaLei, YutianFukasawa, YuichiroMoeckel, Gilbert W.Angelotti, Maria LuciaLiapis, HelenAnders, Hans-Joachim2017-01-10T05:09:33-08:00doi:10.1681/ASN.2016080925hwp:resource-id:jnephrol;28/6/1753American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIschemic reperfusion injury, NETs, tubular cell death, necroinflammation, AKI related remote organ injuryBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160809251046-66731533-34502017-01-10T05:09:33-08:002017-06Journal of the American Society of NephrologyBasic Research28661753167017681672
- Osmotic Stress–Induced Defective Glial Proteostasis Contributes to Brain Demyelination after Hyponatremia TreatmentAdequate protein folding is necessary for normal cell function and a tightly regulated process that requires proper intracellular ionic strength. In many cell types, imbalance between protein synthesis and degradation can induce endoplasmic reticulum (ER) stress, which if sustained, can in turn lead to cell death. In nematodes, osmotic stress induces massive protein aggregation coupled with unfolded protein response and ER stress. In clinical practice, patients sustaining rapid correction of chronic hyponatremia are at risk of osmotic demyelination syndrome. The intense osmotic stress sustained by brain cells is believed to be the major risk factor for demyelination resulting from astrocyte death, which leads to microglial activation, blood-brain barrier opening, and later, myelin damage. Here, using a rat model of osmotic demyelination, we showed that rapid correction of chronic hyponatremia induces severe alterations in proteostasis characterized by diffuse protein aggregation and ubiquitination. Abrupt correction of hyponatremia resulted in vigorous activation of both the unfolded protein response and ER stress accompanied by increased autophagic activity and apoptosis. Immunofluorescence revealed that most of these processes occurred in astrocytes within regions previously shown to be demyelinated in later stages of this syndrome. These results identify osmotic stress as a potent protein aggregation stimuli in mammalian brain and further suggest that osmotic demyelination might be a consequence of proteostasis failure on severe osmotic stress.10.1681/ASN.2016050509Wed, 25 Jan 2017 05:34:05 GMT-08:00Osmotic Stress–Induced Defective Glial Proteostasis Contributes to Brain Demyelination after Hyponatremia TreatmentAdequate protein folding is necessary for normal cell function and a tightly regulated process that requires proper intracellular ionic strength. In many cell types, imbalance between protein synthesis and degradation can induce endoplasmic reticulum (ER) stress, which if sustained, can in turn lead to cell death. In nematodes, osmotic stress induces massive protein aggregation coupled with unfolded protein response and ER stress. In clinical practice, patients sustaining rapid correction of chronic hyponatremia are at risk of osmotic demyelination syndrome. The intense osmotic stress sustained by brain cells is believed to be the major risk factor for demyelination resulting from astrocyte death, which leads to microglial activation, blood-brain barrier opening, and later, myelin damage. Here, using a rat model of osmotic demyelination, we showed that rapid correction of chronic hyponatremia induces severe alterations in proteostasis characterized by diffuse protein aggregation and ubiquitination. Abrupt correction of hyponatremia resulted in vigorous activation of both the unfolded protein response and ER stress accompanied by increased autophagic activity and apoptosis. Immunofluorescence revealed that most of these processes occurred in astrocytes within regions previously shown to be demyelinated in later stages of this syndrome. These results identify osmotic stress as a potent protein aggregation stimuli in mammalian brain and further suggest that osmotic demyelination might be a consequence of proteostasis failure on severe osmotic stress.Gankam-Kengne, FabriceCouturier, Bruno S.Soupart, AlainBrion, Jean PierreDecaux, Guy2017-01-25T05:34:05-08:00doi:10.1681/ASN.2016050509hwp:resource-id:jnephrol;28/6/1802American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhyponatremia, osmolality, malfolding proteinsBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160505091046-66731533-34502017-01-25T05:34:05-08:002017-06Journal of the American Society of NephrologyBasic Research28282861112180234253716181334253717
- Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor–Related Protein 6Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor–related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/β-catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf–related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo. Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis.10.1681/ASN.2016080826Fri, 27 Jan 2017 05:10:27 GMT-08:00Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor–Related Protein 6Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor–related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/β-catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf–related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo. Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis.Johnson, Bryce G.Ren, ShuyuKaraca, GamzeGomez, Ivan G.Fligny, CécileSmith, BenjaminErgun, AylaLocke, GeorgeGao, BenboHayes, SebastianMacDonnell, ScottDuffield, Jeremy S.2017-01-27T05:10:27-08:00doi:10.1681/ASN.2016080826hwp:resource-id:jnephrol;28/6/1769American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, inflammation, pericytes, DKK1, LRP6, Connective Tissue Growth FactorBasic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160808261046-66731533-34502017-01-27T05:10:27-08:002017-06Journal of the American Society of NephrologyBasic Research28617691782
- Acidosis and Kidney Allograft Survival10.1681/ASN.2017020133Mon, 27 Mar 2017 06:47:49 GMT-07:00Acidosis and Kidney Allograft SurvivalRaphael, Kalani L.Shihab, Fuad S.2017-03-27T06:47:49-07:00doi:10.1681/ASN.2017020133hwp:resource-id:jnephrol;28/6/1672American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic metabolic acidosis, kidney transplantation, transplant outcomes, chronic allograft failure, mortalityUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-06-01June 201710.1681/ASN.20170201331046-66731533-34502017-03-27T06:47:49-07:002017-06Journal of the American Society of NephrologyUp Front Matters28661672188616741897
- Renal Collectrin Protects against Salt-Sensitive Hypertension and Is Downregulated by Angiotensin IICollectrin, encoded by the Tmem27 gene, is a transmembrane glycoprotein with approximately 50% homology with angiotensin converting enzyme 2, but without a catalytic domain. Collectrin is most abundantly expressed in the kidney proximal tubule and collecting duct epithelia, where it has an important role in amino acid transport. Collectrin is also expressed in endothelial cells throughout the vasculature, where it regulates L-arginine uptake. We previously reported that global deletion of collectrin leads to endothelial dysfunction, augmented salt sensitivity, and hypertension. Here, we performed kidney crosstransplants between wild-type (WT) and collectrin knockout (Tmem27Y/-) mice to delineate the specific contribution of renal versus extrarenal collectrin on BP regulation and salt sensitivity. On a high-salt diet, WT mice with Tmem27Y/- kidneys had the highest systolic BP and were the only group to exhibit glomerular mesangial hypercellularity. Additional studies showed that, on a high-salt diet, Tmem27Y/- mice had lower renal blood flow, higher abundance of renal sodium-hydrogen antiporter 3, and lower lithium clearance than WT mice. In WT mice, administration of angiotensin II for 2 weeks downregulated collectrin expression in a type 1 angiotensin II receptor–dependent manner. This downregulation coincided with the onset of hypertension, such that WT and Tmem27Y/- mice had similar levels of hypertension after 2 weeks of angiotensin II administration. Altogether, these data suggest that salt sensitivity is determined by intrarenal collectrin, and increasing the abundance or activity of collectrin may have therapeutic benefits in the treatment of hypertension and salt sensitivity.10.1681/ASN.2016060675Fri, 06 Jan 2017 05:19:27 GMT-08:00Renal Collectrin Protects against Salt-Sensitive Hypertension and Is Downregulated by Angiotensin IICollectrin, encoded by the Tmem27 gene, is a transmembrane glycoprotein with approximately 50% homology with angiotensin converting enzyme 2, but without a catalytic domain. Collectrin is most abundantly expressed in the kidney proximal tubule and collecting duct epithelia, where it has an important role in amino acid transport. Collectrin is also expressed in endothelial cells throughout the vasculature, where it regulates L-arginine uptake. We previously reported that global deletion of collectrin leads to endothelial dysfunction, augmented salt sensitivity, and hypertension. Here, we performed kidney crosstransplants between wild-type (WT) and collectrin knockout (Tmem27Y/-) mice to delineate the specific contribution of renal versus extrarenal collectrin on BP regulation and salt sensitivity. On a high-salt diet, WT mice with Tmem27Y/- kidneys had the highest systolic BP and were the only group to exhibit glomerular mesangial hypercellularity. Additional studies showed that, on a high-salt diet, Tmem27Y/- mice had lower renal blood flow, higher abundance of renal sodium-hydrogen antiporter 3, and lower lithium clearance than WT mice. In WT mice, administration of angiotensin II for 2 weeks downregulated collectrin expression in a type 1 angiotensin II receptor–dependent manner. This downregulation coincided with the onset of hypertension, such that WT and Tmem27Y/- mice had similar levels of hypertension after 2 weeks of angiotensin II administration. Altogether, these data suggest that salt sensitivity is determined by intrarenal collectrin, and increasing the abundance or activity of collectrin may have therapeutic benefits in the treatment of hypertension and salt sensitivity.Chu, Pei-LunGigliotti, Joseph C.Cechova, SylviaBodonyi-Kovacs, GaborChan, FangRalph, Donna LeeHowell, NancyKalantari, KambizKlibanov, Alexander L.Carey, Robert M.McDonough, Alicia A.Le, Thu H.2017-01-06T05:19:27-08:00doi:10.1681/ASN.2016060675hwp:resource-id:jnephrol;28/6/1826American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyangiotensin converting enzyme, hypertension, salt sensitivity, collectrin, Tmem27Basic ResearchBasic Researchresearch-article20172017-06-01June 201710.1681/ASN.20160606751046-66731533-34502017-01-06T05:19:27-08:002017-06Journal of the American Society of NephrologyBasic Research28618261837
- An Elderly Man with Fatigue, Dyspnea, and Kidney Failure10.2215/CJN.13311216Wed, 08 Mar 2017 05:06:56 GMT-08:00An Elderly Man with Fatigue, Dyspnea, and Kidney FailureBomback, Andrew S.2017-03-08T05:06:56-08:00doi:10.2215/CJN.13311216hwp:resource-id:clinjasn;12/5/836American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, drug nephrotoxicity, glomerulonephritisKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnairereview20172017-05-08May 08, 201710.2215/CJN.133112161555-90411555-905X2017-03-08T05:06:56-08:002017-05-08Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire125836838
- Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC Study10.2215/CJN.08560816Thu, 02 Mar 2017 09:14:17 GMT-08:00Urine Kidney Injury Biomarkers and Risks of Cardiovascular Disease Events and All-Cause Death: The CRIC StudyPark, MeyeonHsu, Chi-yuanGo, Alan S.Feldman, Harold I.Xie, DaweiZhang, XiaomingMifflin, TheodoreWaikar, Sushrut S.Sabbisetti, Venkata S.Bonventre, Joseph V.Coresh, JosefNelson, Robert G.Kimmel, Paul L.Kusek, John W.Rahman, MahboobSchelling, Jeffrey R.Vasan, Ramachandran S.Liu, Kathleen D.2017-03-02T09:14:17-08:00doi:10.2215/CJN.08560816hwp:resource-id:clinjasn;12/5/761American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, mortality risk, Acetylglucosaminidase, Aged, Atherosclerosis, Biomarkers, creatinine, Fatty Acid-Binding Proteins, Female, Follow-Up Studies, heart failure, Humans, Lipocalin-2, Middle Aged, Myocardial Infarction, Peripheral Arterial Disease, Renal Insufficiency, Chronic, risk factors, Self Report, Stroke, FABP1 protein, humanOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-05-08May 08, 201710.2215/CJN.085608161555-90411555-905X2017-03-02T09:14:17-08:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125761771
- Update on Lupus NephritisSLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients. This review highlights recent updates in our understanding of disease epidemiology, genetics, pathogenesis, and treatment in an effort to establish a framework for lupus nephritis management that is patient-specific and oriented toward maintaining long-term kidney function in patients with lupus.10.2215/CJN.05780616Mon, 07 Nov 2016 05:47:26 GMT-08:00Update on Lupus NephritisSLE is a chronic inflammatory disease that affects the kidneys in about 50% of patients. Lupus nephritis is a major risk factor for overall morbidity and mortality in SLE, and despite potent anti-inflammatory and immunosuppressive therapies still ends in CKD or ESRD for too many patients. This review highlights recent updates in our understanding of disease epidemiology, genetics, pathogenesis, and treatment in an effort to establish a framework for lupus nephritis management that is patient-specific and oriented toward maintaining long-term kidney function in patients with lupus.Almaani, SalemMeara, AlexaRovin, Brad H.2016-11-07T05:47:26-08:00doi:10.2215/CJN.05780616hwp:resource-id:clinjasn;12/5/825American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysystemic lupus erythematosus, Epidemiology and outcomes, glomerular disease, glomerulonephritis, immunosuppression, nephritis, humans, kidney, kidney failure, chronic, Lupus Erythematosus, Discoid, Lupus Erythematosus, Systemic, lupus nephritis, Renal Insufficiency, Chronic, risk factorsGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-05-08May 08, 201710.2215/CJN.057806161555-90411555-905X2016-11-07T05:47:26-08:002017-05-08Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician125825835
- New Organ Allocation System for Combined Liver-Kidney Transplants and the Availability of Kidneys for Transplant to Patients with Stage 4–5 CKDA new proposal has been created for establishing medical criteria for organ allocation in recipients receiving simultaneous liver-kidney transplants. In this article, we describe the new policy, elaborate on the points of greatest controversy, and offer a perspective on the policy going forward. Although we applaud the fact that simultaneous liver-kidney transplant activity will now be monitored and appreciate the creation of medical criteria for allocation in simultaneous liver-kidney transplants, we argue that some of the criteria proposed, especially those for allocating a kidney to a liver recipient with AKI, are too liberal. We call on the nephrology community to follow the consequences of this new policy and push for a re-examination of the longstanding policy of allocating kidneys to multiorgan transplant recipients before all other candidates. The charge to protect our system of equitable organ allocation is very challenging, but it is a challenge that we must embrace.10.2215/CJN.08480816Tue, 27 Dec 2016 05:03:44 GMT-08:00New Organ Allocation System for Combined Liver-Kidney Transplants and the Availability of Kidneys for Transplant to Patients with Stage 4–5 CKDA new proposal has been created for establishing medical criteria for organ allocation in recipients receiving simultaneous liver-kidney transplants. In this article, we describe the new policy, elaborate on the points of greatest controversy, and offer a perspective on the policy going forward. Although we applaud the fact that simultaneous liver-kidney transplant activity will now be monitored and appreciate the creation of medical criteria for allocation in simultaneous liver-kidney transplants, we argue that some of the criteria proposed, especially those for allocating a kidney to a liver recipient with AKI, are too liberal. We call on the nephrology community to follow the consequences of this new policy and push for a re-examination of the longstanding policy of allocating kidneys to multiorgan transplant recipients before all other candidates. The charge to protect our system of equitable organ allocation is very challenging, but it is a challenge that we must embrace.Asch, William S.Bia, Margaret J.2016-12-27T05:03:44-08:00doi:10.2215/CJN.08480816hwp:resource-id:clinjasn;12/5/848American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologySimultaneous Liver Kidney, Organ allocation, UNOS guidelines, Acute Kidney Injury, Humans, kidney, kidney transplantation, Liver, Liver Transplantation, nephrology, Prospective Studies, Renal Insufficiency, Chronic, Thiadiazines, Transplant Recipients, buprofezinPublic Policy SeriesPublic Policy Seriesresearch-article20172017-05-08May 08, 201710.2215/CJN.084808161555-90411555-905X2016-12-27T05:03:44-08:002017-05-08Clinical Journal of the American Society of NephrologyPublic Policy Series125848852
- Can Preservation Fluid Biomarkers Predict Delayed Graft Function in Transplanted Kidneys?10.2215/CJN.03250317Fri, 05 May 2017 01:00:27 GMT-07:00Can Preservation Fluid Biomarkers Predict Delayed Graft Function in Transplanted Kidneys?Hall, Isaac E.2017-05-05T13:00:27-07:00doi:10.2215/CJN.03250317hwp:resource-id:clinjasn;12/5/715American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrisk factors, chronic allograft failure, Epidemiology and outcomes, ischemia-reperfusion, kidney donation, organ transplant, Biomarkers, delayed graft function, kidney, TransplantsEditorialsEditorialseditorial20172017-05-08May 08, 201710.2215/CJN.032503171555-90411555-905X2017-05-05T13:00:27-07:002017-05-08Clinical Journal of the American Society of NephrologyEditorials1255715817717824
- Risk of Febuxostat-Associated Myopathy in Patients with CKD10.2215/CJN.08280816Thu, 16 Mar 2017 07:37:31 GMT-07:00Risk of Febuxostat-Associated Myopathy in Patients with CKDLiu, Chung-teChen, Chun-YouHsu, Chien-YiHuang, Po-HsunLin, Feng-YenChen, Jaw-WenLin, Shing-Jong2017-03-16T07:37:31-07:00doi:10.2215/CJN.08280816hwp:resource-id:clinjasn;12/5/744American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, febuxostat, myopathy, Confidence Intervals, coronary artery disease, Creatine Kinase, diabetes mellitus, Febuxostat, Fibric Acids, glomerular filtration rate, Gout Suppressants, Humans, Hyperuricemia, Multivariate Analysis, Myositis, Odds Ratio, Renal Insufficiency, Chronic, Retrospective Studies, rhabdomyolysis, Universities, Xanthine OxidaseOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-05-08May 08, 201710.2215/CJN.082808161555-90411555-905X2017-03-16T07:37:31-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125744750
- Adverse Outcomes Associated with Preventable Complications in Hospitalized Patients with CKD10.2215/CJN.09410916Thu, 27 Apr 2017 06:23:08 GMT-07:00Adverse Outcomes Associated with Preventable Complications in Hospitalized Patients with CKDBohlouli, BabakJackson, Terri JurgensTonelli, MarcelloHemmelgarn, BrendaKlarenbach, Scott2017-04-27T06:23:08-07:00doi:10.2215/CJN.09410916hwp:resource-id:clinjasn;12/5/799American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Epidemiology and outcomes, Adult, Alberta, Albumins, creatinine, hospitalization, Humans, Length of Stay, Odds Ratio, Patient Discharge, Patient Readmission, Receptor, Epidermal Growth Factor, Renal Insufficiency, Chronic, Risk, EGFR protein, humanOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20172017-05-08May 08, 201710.2215/CJN.094109161555-90411555-905X2017-04-27T06:23:08-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1255799713806714
- Changes in the Profile of Endovascular Procedures Performed in Freestanding Dialysis Access Centers over 15 Years10.2215/CJN.09730916Tue, 18 Apr 2017 06:26:14 GMT-07:00Changes in the Profile of Endovascular Procedures Performed in Freestanding Dialysis Access Centers over 15 YearsBeathard, Gerald A.Urbanes, ArisLitchfield, Terry2017-04-18T06:26:14-07:00doi:10.2215/CJN.09730916hwp:resource-id:clinjasn;12/5/779American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDialysis access procedures, dialysis access, interventional nephrology, Angioplasty, arteriovenous fistula, Diagnosis-Related Groups, Endovascular Procedures, Humans, Incidence, Prevalence, renal dialysis, Thrombectomy, United StatesOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20172017-05-08May 08, 201710.2215/CJN.097309161555-90411555-905X2017-04-18T06:26:14-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125779786
- Immunogenicity of Augmented Compared With Standard Dose Hepatitis B Vaccine in Pediatric Patients on Dialysis: a Midwest Pediatric Nephrology Consortium Study10.2215/CJN.04750416Tue, 07 Mar 2017 06:06:17 GMT-08:00Immunogenicity of Augmented Compared With Standard Dose Hepatitis B Vaccine in Pediatric Patients on Dialysis: a Midwest Pediatric Nephrology Consortium StudyMisurac, Jason M.VanDeVoorde, Rene G.Kallash, MahmoudIorember, Franca M.Luckritz, Kera E.Rheault, Michelle N.Jetton, Jennifer G.Turman, Martin A.Kapur, GauravTwombley, Katherine E.Hashmat, ShireenWeaver, Donald J.Leiser, Jeffrey D.Nailescu, Corina2017-03-07T06:06:17-08:00doi:10.2215/CJN.04750416hwp:resource-id:clinjasn;12/5/772American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hemodialysis, Hepatitis B, Hepatitis B Vaccines, Adolescent, Adult, Antibody Formation, Child, Hepatitis B Antibodies, Humans, Male, nephrology, renal dialysis, Retrospective Studies, Seroconversion, VaccinationOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20172017-05-08May 08, 201710.2215/CJN.047504161555-90411555-905X2017-03-07T06:06:17-08:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125772778
- Avoiding Preventable Complications in Hospitalized Patients with CKD10.2215/CJN.03240317Thu, 27 Apr 2017 06:23:08 GMT-07:00Avoiding Preventable Complications in Hospitalized Patients with CKDYoung, Eric W.2017-04-27T06:23:08-07:00doi:10.2215/CJN.03240317hwp:resource-id:clinjasn;12/5/713American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHumans, Patients, Renal Insufficiency, ChronicEditorialsEditorialseditorial20172017-05-08May 08, 201710.2215/CJN.032403171555-90411555-905X2017-04-27T06:23:08-07:002017-05-08Clinical Journal of the American Society of NephrologyEditorials1255713799714806
- Serious Illness Conversations in ESRDDialysis-dependent ESRD is a serious illness with high disease burden, morbidity, and mortality. Mortality in the first year on dialysis for individuals over age 75 years old approaches 40%, and even those with better prognoses face multiple hospitalizations and declining functional status. In the last month of life, patients on dialysis over age 65 years old experience higher rates of hospitalization, intensive care unit admission, procedures, and death in hospital than patients with cancer or heart failure, while using hospice services less. This high intensity of care is often inconsistent with the wishes of patients on dialysis but persists due to failure to explore or discuss patient goals, values, and preferences in the context of their serious illness. Fewer than 10% of patients on dialysis report having had a conversation about goals, values, and preferences with their nephrologist, although nearly 90% report wanting this conversation. Many nephrologists shy away from these conversations, because they do not wish to upset their patients, feel that there is too much uncertainty in their ability to predict prognosis, are insecure in their skills at broaching the topic, or have difficulty incorporating the conversations into their clinical workflow. In multiple studies, timely discussions about serious illness care goals, however, have been associated with enhanced goal-consistent care, improved quality of life, and positive family outcomes without an increase in patient distress or anxiety. In this special feature article, we will (1) identify the barriers to serious illness conversations in the dialysis population, (2) review best practices in and specific approaches to conducting serious illness conversations, and (3) offer solutions to overcome barriers as well as practical advice, including specific language and tools, to implement serious illness conversations in the dialysis population.10.2215/CJN.05760516Wed, 28 Dec 2016 04:51:46 GMT-08:00Serious Illness Conversations in ESRDDialysis-dependent ESRD is a serious illness with high disease burden, morbidity, and mortality. Mortality in the first year on dialysis for individuals over age 75 years old approaches 40%, and even those with better prognoses face multiple hospitalizations and declining functional status. In the last month of life, patients on dialysis over age 65 years old experience higher rates of hospitalization, intensive care unit admission, procedures, and death in hospital than patients with cancer or heart failure, while using hospice services less. This high intensity of care is often inconsistent with the wishes of patients on dialysis but persists due to failure to explore or discuss patient goals, values, and preferences in the context of their serious illness. Fewer than 10% of patients on dialysis report having had a conversation about goals, values, and preferences with their nephrologist, although nearly 90% report wanting this conversation. Many nephrologists shy away from these conversations, because they do not wish to upset their patients, feel that there is too much uncertainty in their ability to predict prognosis, are insecure in their skills at broaching the topic, or have difficulty incorporating the conversations into their clinical workflow. In multiple studies, timely discussions about serious illness care goals, however, have been associated with enhanced goal-consistent care, improved quality of life, and positive family outcomes without an increase in patient distress or anxiety. In this special feature article, we will (1) identify the barriers to serious illness conversations in the dialysis population, (2) review best practices in and specific approaches to conducting serious illness conversations, and (3) offer solutions to overcome barriers as well as practical advice, including specific language and tools, to implement serious illness conversations in the dialysis population.Mandel, Ernest I.Bernacki, Rachelle E.Block, Susan D.2016-12-28T04:51:46-08:00doi:10.2215/CJN.05760516hwp:resource-id:clinjasn;12/5/854American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycommunication, end stage kidney disease, dialysis, geriatric nephrology, Anxiety, Communication, Goals, heart failure, Hospices, hospitalization, Humans, Intensive Care Units, Kidney Failure, Chronic, Language, Neoplasms, Patient Care Planning, Prognosis, quality of life, renal dialysis, Uncertainty, WorkflowSpecial FeatureSpecial Featureresearch-article20172017-05-08May 08, 201710.2215/CJN.057605161555-90411555-905X2016-12-28T04:51:46-08:002017-05-08Clinical Journal of the American Society of NephrologySpecial Feature125854863
- Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial10.2215/CJN.10771016Mon, 20 Mar 2017 07:24:40 GMT-07:00Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled TrialMcMullan, Ciaran J.Borgi, LeaFisher, NaomiCurhan, GaryForman, John2017-03-20T07:24:40-07:00doi:10.2215/CJN.10771016hwp:resource-id:clinjasn;12/5/807American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyUric acid, BP, allopurinol, probenecid, renin angiotensin system, randomized controlled trials, urate, urate lowering therapy, placebo controlledOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20172017-05-08May 08, 201710.2215/CJN.107710161555-90411555-905X2017-03-20T07:24:40-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125807816
- Qualitative Interviews Exploring Palliative Care Perspectives of Latinos on Dialysis10.2215/CJN.10260916Wed, 12 Apr 2017 12:03:08 GMT-07:00Qualitative Interviews Exploring Palliative Care Perspectives of Latinos on DialysisCervantes, LiliaJones, JacquelineLinas, StuartFischer, Stacy2017-04-12T12:03:08-07:00doi:10.2215/CJN.10260916hwp:resource-id:clinjasn;12/5/788American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, end-stage renal disease, ethnicity, quality of life, Advance Care Planning, Advance Directives, Chronic Disease, Communication Barriers, Fear, Health Literacy, Hispanic Americans, Hospice Care, Hospices, Humans, Kidney Failure, Chronic, Linguistics, Palliative Care, Patient Preference, Patient-Centered Care, Punishment, Qualitative Research, renal dialysisOriginal ArticlesGeriatric and Palliative NephrologyOriginal ArticlesGeriatric and Palliative Nephrologyresearch-article20172017-05-08May 08, 201710.2215/CJN.102609161555-90411555-905X2017-04-12T12:03:08-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles125788798
- Proteins in Preservation Fluid as Predictors of Delayed Graft Function in Kidneys from Donors after Circulatory Death10.2215/CJN.10701016Fri, 05 May 2017 01:00:27 GMT-07:00Proteins in Preservation Fluid as Predictors of Delayed Graft Function in Kidneys from Donors after Circulatory Deathvan Balkom, Bas W.M.Gremmels, HendrikOoms, Liselotte S.S.Toorop, Raechel J.Dor, Frank J.M.F.de Jong, Olivier G.Michielsen, Laura A.de Borst, Gert J.de Jager, WilcoAbrahams, Alferso C.van Zuilen, Arjan D.Verhaar, Marianne C.2017-05-05T13:00:27-07:00doi:10.2215/CJN.10701016hwp:resource-id:clinjasn;12/5/817American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal transplantation, transplant outcomes, ischemia-reperfusion, cytokinesOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-05-08May 08, 201710.2215/CJN.107010161555-90411555-905X2017-05-05T13:00:27-07:002017-05-08Clinical Journal of the American Society of NephrologyOriginal Articles1255817715824717
- Understanding Histolopathologic Characteristics to Predict Renal Outcomes in Lupus Nephritis10.2215/CJN.03490317Thu, 04 May 2017 01:22:14 GMT-07:00Understanding Histolopathologic Characteristics to Predict Renal Outcomes in Lupus NephritisTesar, VladimirHruskova, Zdenka2017-05-04T13:22:14-07:00doi:10.2215/CJN.03490317hwp:resource-id:clinjasn;12/5/711American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhistopathology, kidney, lupus nephritisEditorialsEditorialseditorial20172017-05-08May 08, 201710.2215/CJN.034903171555-90411555-905X2017-05-04T13:22:14-07:002017-05-08Clinical Journal of the American Society of NephrologyEditorials1255711734712743
- Racial and Ethnic Disparities in Survival of Children with ESRDObservational studies have reported that black and Hispanic adults receiving maintenance dialysis survive longer than non–Hispanic white counterparts. Whether there are racial disparities in survival of children with ESRD is not clear. We compared mortality risk among non–Hispanic black, Hispanic, and non–Hispanic white children who started RRT between 1995 and 2011 and were followed through 2012. We examined all-cause mortality using adjusted Cox models. Of 12,123 children included for analysis, 1600 died during the median follow-up of 7.1 years. Approximately 25% of children were non-Hispanic black, and 26% of children were of Hispanic ethnicity. Non–Hispanic black children had a 36% higher risk of death (95% confidence interval [95% CI], 1.21 to 1.52) and Hispanic children had a 34% lower risk of death (95% CI, 0.57 to 0.77) than non–Hispanic white children. Adjustment for transplant as a time-dependent covariate abolished the higher risk of death in non–Hispanic black children (hazard ratio, 0.99; 95% CI, 0.88 to 1.12) but did not attenuate the finding of a lower risk of death in Hispanic children (hazard ratio, 0.59; 95% CI, 0.51 to 0.68). In conclusion, Hispanic children had lower mortality than non–Hispanic white children. Non–Hispanic black children had higher mortality than non–Hispanic white children, which was related to differences in access to transplantation by race. Parity in access to transplantation in children and improvements in strategies to prolong graft survival could substantially reduce disparities in mortality risk of non–Hispanic black children treated with RRT.10.1681/ASN.2016060706Thu, 29 Dec 2016 04:46:22 GMT-08:00Racial and Ethnic Disparities in Survival of Children with ESRDObservational studies have reported that black and Hispanic adults receiving maintenance dialysis survive longer than non–Hispanic white counterparts. Whether there are racial disparities in survival of children with ESRD is not clear. We compared mortality risk among non–Hispanic black, Hispanic, and non–Hispanic white children who started RRT between 1995 and 2011 and were followed through 2012. We examined all-cause mortality using adjusted Cox models. Of 12,123 children included for analysis, 1600 died during the median follow-up of 7.1 years. Approximately 25% of children were non-Hispanic black, and 26% of children were of Hispanic ethnicity. Non–Hispanic black children had a 36% higher risk of death (95% confidence interval [95% CI], 1.21 to 1.52) and Hispanic children had a 34% lower risk of death (95% CI, 0.57 to 0.77) than non–Hispanic white children. Adjustment for transplant as a time-dependent covariate abolished the higher risk of death in non–Hispanic black children (hazard ratio, 0.99; 95% CI, 0.88 to 1.12) but did not attenuate the finding of a lower risk of death in Hispanic children (hazard ratio, 0.59; 95% CI, 0.51 to 0.68). In conclusion, Hispanic children had lower mortality than non–Hispanic white children. Non–Hispanic black children had higher mortality than non–Hispanic white children, which was related to differences in access to transplantation by race. Parity in access to transplantation in children and improvements in strategies to prolong graft survival could substantially reduce disparities in mortality risk of non–Hispanic black children treated with RRT.Ku, ElaineMcCulloch, Charles E.Grimes, Barbara A.Johansen, Kirsten L.2016-12-29T04:46:22-08:00doi:10.1681/ASN.2016060706hwp:resource-id:jnephrol;28/5/1584American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyracial disparity, mortality risk, pediatric nephrologyClinical EpidemiologyClinical Epidemiologyresearch-article20172017-05-01May 201710.1681/ASN.20160607061046-66731533-34502016-12-29T04:46:22-08:002017-05Journal of the American Society of NephrologyClinical Epidemiology28551584133415911336
- Decoding Acute Myocardial Infarction among Patients on Dialysis10.1681/ASN.2017030226Wed, 12 Apr 2017 12:47:47 GMT-07:00Decoding Acute Myocardial Infarction among Patients on DialysisHoward, Charles E.McCullough, Peter A.2017-04-12T12:47:47-07:00doi:10.1681/ASN.2017030226hwp:resource-id:jnephrol;28/5/1337American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, cardiovascular disease, ICD-9-CM codesUp Front MattersPerspectiveUp Front MattersPerspectiveeditorial20172017-05-01May 201710.1681/ASN.20170302261046-66731533-34502017-04-12T12:47:47-07:002017-05Journal of the American Society of NephrologyUp Front Matters28513371339
- MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous NephropathyEpitopes of phospholipase A2 receptor (PLA2R), the target antigen in idiopathic membranous nephropathy (iMN), must be presented by the HLA–encoded MHC class II molecules to stimulate autoantibody production. A genome–wide association study identified risk alleles at HLA and PLA2R loci, with the top variant rs2187668 within HLA-DQA1 showing a risk effect greater than that of the top variant rs4664308 within PLA2R1. How the HLA risk alleles affect epitope presentation by MHC class II molecules in iMN is unknown. Here, we genotyped 261 patients with iMN and 599 healthy controls at the HLA-DRB1, HLA-DQA1, HLA-DQB1, and HLA-DPB1 loci with four-digit resolution and extracted the encoded amino acid sequences from the IMGT/HLA database. We predicted T cell epitopes of PLA2R and constructed MHC-DR molecule-PLA2R peptide-T cell receptor structures using Modeler. We identified DRB1*1501 (odds ratio, 4.65; 95% confidence interval [95% CI], 3.39 to 6.41; P<0.001) and DRB1*0301 (odds ratio, 3.96; 95% CI, 2.61 to 6.05; P<0.001) as independent risk alleles for iMN and associated with circulating anti–PLA2R antibodies. Strong gene-gene interaction was noted between rs4664308(AA) and HLA-DRB1*1501/DRB1*0301. Amino acid positions 13 (P<0.001) and 71 (P<0.001) in the MHC-DRβ1 chain independently associated with iMN. Structural models showed that arginine13 and alanine71, encoded by DRB1*1501, and lysine71, encoded by DRB1*0301, facilitate interactions with T cell epitopes of PLA2R. In conclusion, we identified two risk alleles of HLA class II genes and three amino acid residues on positions 13 and 71 of the MHC-DRβ1 chain that may confer susceptibility to iMN by presenting T cell epitopes on PLA2R.10.1681/ASN.2016020114Wed, 16 Nov 2016 06:59:47 GMT-08:00MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous NephropathyEpitopes of phospholipase A2 receptor (PLA2R), the target antigen in idiopathic membranous nephropathy (iMN), must be presented by the HLA–encoded MHC class II molecules to stimulate autoantibody production. A genome–wide association study identified risk alleles at HLA and PLA2R loci, with the top variant rs2187668 within HLA-DQA1 showing a risk effect greater than that of the top variant rs4664308 within PLA2R1. How the HLA risk alleles affect epitope presentation by MHC class II molecules in iMN is unknown. Here, we genotyped 261 patients with iMN and 599 healthy controls at the HLA-DRB1, HLA-DQA1, HLA-DQB1, and HLA-DPB1 loci with four-digit resolution and extracted the encoded amino acid sequences from the IMGT/HLA database. We predicted T cell epitopes of PLA2R and constructed MHC-DR molecule-PLA2R peptide-T cell receptor structures using Modeler. We identified DRB1*1501 (odds ratio, 4.65; 95% confidence interval [95% CI], 3.39 to 6.41; P<0.001) and DRB1*0301 (odds ratio, 3.96; 95% CI, 2.61 to 6.05; P<0.001) as independent risk alleles for iMN and associated with circulating anti–PLA2R antibodies. Strong gene-gene interaction was noted between rs4664308(AA) and HLA-DRB1*1501/DRB1*0301. Amino acid positions 13 (P<0.001) and 71 (P<0.001) in the MHC-DRβ1 chain independently associated with iMN. Structural models showed that arginine13 and alanine71, encoded by DRB1*1501, and lysine71, encoded by DRB1*0301, facilitate interactions with T cell epitopes of PLA2R. In conclusion, we identified two risk alleles of HLA class II genes and three amino acid residues on positions 13 and 71 of the MHC-DRβ1 chain that may confer susceptibility to iMN by presenting T cell epitopes on PLA2R.Cui, ZhaoXie, Li-junChen, Fang-jinPei, Zhi-yongZhang, Li-jieQu, ZhenHuang, JingGu, Qiu-huaZhang, Yi-miaoWang, XinWang, FangMeng, Li-qiangLiu, GangZhou, Xu-jieZhu, LiLv, Ji-chengLiu, FanZhang, HongLiao, Yun-huaLai, Lu-huaRonco, PierreZhao, Ming-hui2016-11-16T06:59:47-08:00doi:10.1681/ASN.2016020114hwp:resource-id:jnephrol;28/5/1651American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologygene expression, immunology, membranous nephropathyClinical ResearchClinical Researchresearch-article20172017-05-01May 201710.1681/ASN.20160201141046-66731533-34502016-11-16T06:59:47-08:002017-05Journal of the American Society of NephrologyClinical Research28551651133116641334
- Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell NephrocyteSteroid-resistant nephrotic syndrome is characterized by podocyte dysfunction. Drosophila garland cell nephrocytes are podocyte-like cells and thus provide a potential in vivo model in which to study the pathogenesis of nephrotic syndrome. However, relevant pathomechanisms of nephrotic syndrome have not been studied in nephrocytes. Here, we discovered that two Drosophila slit diaphragm proteins, orthologs of the human genes encoding nephrin and nephrin-like protein 1, colocalize within a fingerprint-like staining pattern that correlates with ultrastructural morphology. Using RNAi and conditional CRISPR/Cas9 in nephrocytes, we found this pattern depends on the expression of both orthologs. Tracer endocytosis by nephrocytes required Cubilin and reflected size selectivity analogous to that of glomerular function. Using RNAi and tracer endocytosis as a functional read-out, we screened Drosophila orthologs of human monogenic causes of nephrotic syndrome and observed conservation of the central pathogenetic alterations. We focused on the coenzyme Q10 (CoQ10) biosynthesis gene Coq2, the silencing of which disrupted slit diaphragm morphology. Restoration of CoQ10 synthesis by vanillic acid partially rescued the phenotypic and functional alterations induced by Coq2-RNAi. Notably, Coq2 colocalized with mitochondria, and Coq2 silencing increased the formation of reactive oxygen species (ROS). Silencing of ND75, a subunit of the mitochondrial respiratory chain that controls ROS formation independently of CoQ10, phenocopied the effect of Coq2-RNAi. Moreover, the ROS scavenger glutathione partially rescued the effects of Coq2-RNAi. In conclusion, Drosophila garland cell nephrocytes provide a model with which to study the pathogenesis of nephrotic syndrome, and ROS formation may be a pathomechanism of COQ2-nephropathy.10.1681/ASN.2016050517Thu, 08 Dec 2016 06:53:12 GMT-08:00Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell NephrocyteSteroid-resistant nephrotic syndrome is characterized by podocyte dysfunction. Drosophila garland cell nephrocytes are podocyte-like cells and thus provide a potential in vivo model in which to study the pathogenesis of nephrotic syndrome. However, relevant pathomechanisms of nephrotic syndrome have not been studied in nephrocytes. Here, we discovered that two Drosophila slit diaphragm proteins, orthologs of the human genes encoding nephrin and nephrin-like protein 1, colocalize within a fingerprint-like staining pattern that correlates with ultrastructural morphology. Using RNAi and conditional CRISPR/Cas9 in nephrocytes, we found this pattern depends on the expression of both orthologs. Tracer endocytosis by nephrocytes required Cubilin and reflected size selectivity analogous to that of glomerular function. Using RNAi and tracer endocytosis as a functional read-out, we screened Drosophila orthologs of human monogenic causes of nephrotic syndrome and observed conservation of the central pathogenetic alterations. We focused on the coenzyme Q10 (CoQ10) biosynthesis gene Coq2, the silencing of which disrupted slit diaphragm morphology. Restoration of CoQ10 synthesis by vanillic acid partially rescued the phenotypic and functional alterations induced by Coq2-RNAi. Notably, Coq2 colocalized with mitochondria, and Coq2 silencing increased the formation of reactive oxygen species (ROS). Silencing of ND75, a subunit of the mitochondrial respiratory chain that controls ROS formation independently of CoQ10, phenocopied the effect of Coq2-RNAi. Moreover, the ROS scavenger glutathione partially rescued the effects of Coq2-RNAi. In conclusion, Drosophila garland cell nephrocytes provide a model with which to study the pathogenesis of nephrotic syndrome, and ROS formation may be a pathomechanism of COQ2-nephropathy.Hermle, TobiasBraun, Daniela A.Helmstädter, MartinHuber, Tobias B.Hildebrandt, Friedhelm2016-12-08T06:53:12-08:00doi:10.1681/ASN.2016050517hwp:resource-id:jnephrol;28/5/1521American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologynephrocyte, Drosophila, nephrotic syndrome, COQ2, garland cell, SRNSBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160505171046-66731533-34502016-12-08T06:53:12-08:002017-05Journal of the American Society of NephrologyBasic Research28515211533
- Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion InjuryAn accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora–depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80+ renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora–depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80+ renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury.10.1681/ASN.2016030255Wed, 07 Dec 2016 09:39:22 GMT-08:00Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion InjuryAn accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora–depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80+ renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora–depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80+ renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury.Emal, DibaRampanelli, ElenaStroo, IngridButter, Loes M.Teske, Gwendoline J.Claessen, NikeStokman, GeurtFlorquin, SandrineLeemans, Jaklien C.Dessing, Mark C.2016-12-07T09:39:22-08:00doi:10.1681/ASN.2016030255hwp:resource-id:jnephrol;28/5/1450American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, macrophages, immunologyBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160302551046-66731533-34502016-12-07T09:39:22-08:002017-05Journal of the American Society of NephrologyBasic Research28514501461
- Intercalated Cell Depletion and Vacuolar H+-ATPase Mistargeting in an Ae1 R607H Knockin ModelDistal nephron acid secretion is mediated by highly specialized type A intercalated cells (A-ICs), which contain vacuolar H+-ATPase (V-type ATPase)-rich vesicles that fuse with the apical plasma membrane on demand. Intracellular bicarbonate generated by luminal H+ secretion is removed by the basolateral anion-exchanger AE1. Chronically reduced renal acid excretion in distal renal tubular acidosis (dRTA) may lead to nephrocalcinosis and renal failure. Studies in MDCK monolayers led to the proposal of a dominant-negative trafficking mechanism to explain AE1-associated dominant dRTA. To test this hypothesis in vivo, we generated an Ae1 R607H knockin mouse, which corresponds to the most common dominant dRTA mutation in human AE1, R589H. Compared with wild-type mice, heterozygous and homozygous R607H knockin mice displayed incomplete dRTA characterized by compensatory upregulation of the Na+/HCO3− cotransporter NBCn1. Red blood cell Ae1-mediated anion-exchange activity and surface polypeptide expression did not change. Mutant mice expressed far less Ae1 in A-ICs, but basolateral targeting of the mutant protein was preserved. Notably, mutant mice also exhibited reduced expression of V-type ATPase and compromised targeting of this proton pump to the plasma membrane upon acid challenge. Accumulation of p62- and ubiquitin-positive material in A-ICs of knockin mice suggested a defect in the degradative pathway, which may explain the observed loss of A-ICs. R607H knockin did not affect type B intercalated cells. We propose that reduced basolateral anion-exchange activity in A-ICs inhibits trafficking and regulation of V-type ATPase, compromising luminal H+ secretion and possibly lysosomal acidification.10.1681/ASN.2016020169Thu, 08 Dec 2016 06:53:07 GMT-08:00Intercalated Cell Depletion and Vacuolar H+-ATPase Mistargeting in an Ae1 R607H Knockin ModelDistal nephron acid secretion is mediated by highly specialized type A intercalated cells (A-ICs), which contain vacuolar H+-ATPase (V-type ATPase)-rich vesicles that fuse with the apical plasma membrane on demand. Intracellular bicarbonate generated by luminal H+ secretion is removed by the basolateral anion-exchanger AE1. Chronically reduced renal acid excretion in distal renal tubular acidosis (dRTA) may lead to nephrocalcinosis and renal failure. Studies in MDCK monolayers led to the proposal of a dominant-negative trafficking mechanism to explain AE1-associated dominant dRTA. To test this hypothesis in vivo, we generated an Ae1 R607H knockin mouse, which corresponds to the most common dominant dRTA mutation in human AE1, R589H. Compared with wild-type mice, heterozygous and homozygous R607H knockin mice displayed incomplete dRTA characterized by compensatory upregulation of the Na+/HCO3− cotransporter NBCn1. Red blood cell Ae1-mediated anion-exchange activity and surface polypeptide expression did not change. Mutant mice expressed far less Ae1 in A-ICs, but basolateral targeting of the mutant protein was preserved. Notably, mutant mice also exhibited reduced expression of V-type ATPase and compromised targeting of this proton pump to the plasma membrane upon acid challenge. Accumulation of p62- and ubiquitin-positive material in A-ICs of knockin mice suggested a defect in the degradative pathway, which may explain the observed loss of A-ICs. R607H knockin did not affect type B intercalated cells. We propose that reduced basolateral anion-exchange activity in A-ICs inhibits trafficking and regulation of V-type ATPase, compromising luminal H+ secretion and possibly lysosomal acidification.Mumtaz, RizwanTrepiccione, FrancescoHennings, J. ChristopherHuebner, Antje K.Serbin, BettinaPicard, NicolasUllah, A. K. M. ShahidPăunescu, Teodor G.Capen, Diane E.Lashhab, Rawad M.Mouro-Chanteloup, IsabelleAlper, Seth L.Wagner, Carsten A.Cordat, EmmanuelleBrown, DennisEladari, DominiqueHübner, Christian A.2016-12-08T06:53:07-08:00doi:10.1681/ASN.2016020169hwp:resource-id:jnephrol;28/5/1507American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCell & Transport Physiology, chronic metabolic acidosis, distal tubule, genetic renal disease, ion transport, transgenic mouseBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160201691046-66731533-34502016-12-08T06:53:07-08:002017-05Journal of the American Society of NephrologyBasic Research28515071520
- Genetic Variants Associated with Circulating Parathyroid HormoneParathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10−53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10−17), rs219779 adjacent to CLDN14 (P=3.5 × 10−16), rs4443100 near RTDR1 (P=8.7 × 10−9), and rs73186030 near CASR (P=4.8 × 10−8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.10.1681/ASN.2016010069Wed, 07 Dec 2016 09:39:24 GMT-08:00Genetic Variants Associated with Circulating Parathyroid HormoneParathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10−53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10−17), rs219779 adjacent to CLDN14 (P=3.5 × 10−16), rs4443100 near RTDR1 (P=8.7 × 10−9), and rs73186030 near CASR (P=4.8 × 10−8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.Robinson-Cohen, CassianneLutsey, Pamela L.Kleber, Marcus E.Nielson, Carrie M.Mitchell, Braxton D.Bis, Joshua C.Eny, Karen M.Portas, LauraEriksson, JoelLorentzon, MattiasKoller, Daniel L.Milaneschi, YuriTeumer, AlexanderPilz, StefanNethander, MariaSelvin, ElizabethTang, WeihongWeng, Lu-ChenWong, Hoi SuenLai, DongbingPeacock, MunroHannemann, AnkeVölker, UweHomuth, GeorgNauk, MatthiasMurgia, FedericoPattee, Jack W.Orwoll, EricZmuda, Joseph M.Riancho, Jose AntonioWolf, MylesWilliams, FrancesPenninx, BrendaEcons, Michael J.Ryan, Kathleen A.Ohlsson, ClaesPaterson, Andrew D.Psaty, Bruce M.Siscovick, David S.Rotter, Jerome I.Pirastu, MarioStreeten, ElizabethMärz, WinfriedFox, CarolineCoresh, JosefWallaschofski, HenriPankow, James S.de Boer, Ian H.Kestenbaum, Bryan2016-12-07T09:39:24-08:00doi:10.1681/ASN.2016010069hwp:resource-id:jnephrol;28/5/1553American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyparathyroid hormone, mineral metabolism, human genetics, genome-wide association studyClinical EpidemiologyClinical Epidemiologyresearch-article20172017-05-01May 201710.1681/ASN.20160100691046-66731533-34502016-12-07T09:39:24-08:002017-05Journal of the American Society of NephrologyClinical Epidemiology28515531565
- Genetic Complexities of the HLA Region and Idiopathic Membranous Nephropathy10.1681/ASN.2017030283Mon, 10 Apr 2017 06:19:15 GMT-07:00Genetic Complexities of the HLA Region and Idiopathic Membranous NephropathyMladkova, NikolKiryluk, Krzysztof2017-04-10T06:19:15-07:00doi:10.1681/ASN.2017030283hwp:resource-id:jnephrol;28/5/1331American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, HLA, autoimmunity, genome wide association studies (GWAS), human genetics, kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-05-01May 201710.1681/ASN.20170302831046-66731533-34502017-04-10T06:19:15-07:002017-05Journal of the American Society of NephrologyUp Front Matters28555133116421651133416501664
- (Re)Building a Kidney(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses.10.1681/ASN.2016101077Tue, 17 Jan 2017 07:34:12 GMT-08:00(Re)Building a Kidney(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses.Oxburgh, LeifCarroll, Thomas J.Cleaver, OndineGossett, Daniel R.Hoshizaki, Deborah K.Hubbell, Jeffrey A.Humphreys, Benjamin D.Jain, SanjayJensen, JanKaplan, David L.Kesselman, CarlKetchum, Christian J.Little, Melissa H.McMahon, Andrew P.Shankland, Stuart J.Spence, Jason R.Valerius, M. ToddWertheim, Jason A.Wessely, OliverZheng, YingDrummond, Iain A.2017-01-17T07:34:12-08:00doi:10.1681/ASN.2016101077hwp:resource-id:jnephrol;28/5/1370American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyRegeneration, Organogenesis, Organoid, Directed differentiationUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20172017-05-01May 201710.1681/ASN.20161010771046-66731533-34502017-01-17T07:34:12-08:002017-05Journal of the American Society of NephrologyUp Front Matters28513701378
- Immunologic Effects of the Renin-Angiotensin SystemInappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, RAS inhibitors limit secondary immune activation responding to hemodynamic injury in the target organ. However, RAS activation in hematopoietic cells has immunologic effects that diverge from those of RAS stimulation in the kidney and vasculature. In preclinical studies, activating type 1 angiotensin (AT1) receptors in T lymphocytes and myeloid cells blunts the polarization of these cells toward proinflammatory phenotypes, protecting the kidney from hypertensive injury and fibrosis. These endogenous functions of immune AT1 receptors temper the pathogenic actions of renal and vascular AT1 receptors during hypertension. By counteracting the effects of AT1 receptor stimulation in the target organ, exogenous administration of AT2 receptor agonists or angiotensin 1–7 analogs may similarly limit inflammatory injury to the heart and kidney. Moreover, although angiotensin II is the classic effector molecule of the RAS, several RAS enzymes affect immune homeostasis independently of canonic angiotensin II generation. Thus, as reviewed here, multiple components of the RAS signaling cascade influence inflammatory cell phenotype and function with unpredictable and context-specific effects on innate and adaptive immunity.10.1681/ASN.2016101066Wed, 01 Feb 2017 07:11:23 GMT-08:00Immunologic Effects of the Renin-Angiotensin SystemInappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, RAS inhibitors limit secondary immune activation responding to hemodynamic injury in the target organ. However, RAS activation in hematopoietic cells has immunologic effects that diverge from those of RAS stimulation in the kidney and vasculature. In preclinical studies, activating type 1 angiotensin (AT1) receptors in T lymphocytes and myeloid cells blunts the polarization of these cells toward proinflammatory phenotypes, protecting the kidney from hypertensive injury and fibrosis. These endogenous functions of immune AT1 receptors temper the pathogenic actions of renal and vascular AT1 receptors during hypertension. By counteracting the effects of AT1 receptor stimulation in the target organ, exogenous administration of AT2 receptor agonists or angiotensin 1–7 analogs may similarly limit inflammatory injury to the heart and kidney. Moreover, although angiotensin II is the classic effector molecule of the RAS, several RAS enzymes affect immune homeostasis independently of canonic angiotensin II generation. Thus, as reviewed here, multiple components of the RAS signaling cascade influence inflammatory cell phenotype and function with unpredictable and context-specific effects on innate and adaptive immunity.Crowley, Steven D.Rudemiller, Nathan P.2017-02-01T07:11:23-08:00doi:10.1681/ASN.2016101066hwp:resource-id:jnephrol;28/5/1350American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, hypertension, renin angiotensin systemUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-05-01May 201710.1681/ASN.20161010661046-66731533-34502017-02-01T07:11:23-08:002017-05Journal of the American Society of NephrologyUp Front Matters28513501361
- Novel Paradigms of Salt and HypertensionSalt resistance/sensitivity refers specifically to the effect of dietary sodium chloride (salt) intake on BP. Increased dietary salt intake promotes an early and uniform expansion of extracellular fluid volume and increased cardiac output. To compensate for these hemodynamic changes and maintain constant BP in salt resistance, renal and peripheral vascular resistance falls and is associated with an increase in production of nitric oxide. In contrast, the decline in peripheral vascular resistance and the increase in nitric oxide are impaired or absent in salt sensitivity, promoting an increase in BP in these individuals. Endothelial dysfunction may pose a particularly significant risk factor in the development of salt sensitivity and subsequent hypertension. Vulnerable salt-sensitive populations may have in common underlying endothelial dysfunction due to genetic or environmental influences. These individuals may be very sensitive to the hemodynamic stress of increased effective blood volume, setting in motion untoward molecular and biochemical events that lead to overproduction of TGF-β, oxidative stress, and limited bioavailable nitric oxide. Finally, chronic high-salt ingestion produces endothelial dysfunction, even in salt-resistant subjects. Thus, the complex syndrome of salt sensitivity may be a function of the endothelium, which is integrally involved in the vascular responses to high salt intake.10.1681/ASN.2016080927Mon, 20 Feb 2017 05:25:56 GMT-08:00Novel Paradigms of Salt and HypertensionSalt resistance/sensitivity refers specifically to the effect of dietary sodium chloride (salt) intake on BP. Increased dietary salt intake promotes an early and uniform expansion of extracellular fluid volume and increased cardiac output. To compensate for these hemodynamic changes and maintain constant BP in salt resistance, renal and peripheral vascular resistance falls and is associated with an increase in production of nitric oxide. In contrast, the decline in peripheral vascular resistance and the increase in nitric oxide are impaired or absent in salt sensitivity, promoting an increase in BP in these individuals. Endothelial dysfunction may pose a particularly significant risk factor in the development of salt sensitivity and subsequent hypertension. Vulnerable salt-sensitive populations may have in common underlying endothelial dysfunction due to genetic or environmental influences. These individuals may be very sensitive to the hemodynamic stress of increased effective blood volume, setting in motion untoward molecular and biochemical events that lead to overproduction of TGF-β, oxidative stress, and limited bioavailable nitric oxide. Finally, chronic high-salt ingestion produces endothelial dysfunction, even in salt-resistant subjects. Thus, the complex syndrome of salt sensitivity may be a function of the endothelium, which is integrally involved in the vascular responses to high salt intake.Feng, WenguangDell’Italia, Louis J.Sanders, Paul W.2017-02-20T05:25:56-08:00doi:10.1681/ASN.2016080927hwp:resource-id:jnephrol;28/5/1362American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, nitric oxide, TGF-beta, endothelium, hypertensionUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-05-01May 201710.1681/ASN.20160809271046-66731533-34502017-02-20T05:25:56-08:002017-05Journal of the American Society of NephrologyUp Front Matters28513621369
- Diagnosis and Treatment of Hyponatremia: Compilation of the GuidelinesHyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.10.1681/ASN.2016101139Tue, 07 Feb 2017 05:19:37 GMT-08:00Diagnosis and Treatment of Hyponatremia: Compilation of the GuidelinesHyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.Hoorn, Ewout J.Zietse, Robert2017-02-07T05:19:37-08:00doi:10.1681/ASN.2016101139hwp:resource-id:jnephrol;28/5/1340American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycerebral edema, copeptin, vasopressin, urea, vasopressin receptor antagonist, osmotic demyelination syndromeUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-05-01May 201710.1681/ASN.20161011391046-66731533-34502017-02-07T05:19:37-08:002017-05Journal of the American Society of NephrologyUp Front Matters28513401349
- Lesson Learned in Mortality and Kidney Transplant Outcomes among Pediatric Dialysis Patients10.1681/ASN.2017010017Tue, 07 Mar 2017 06:25:46 GMT-08:00Lesson Learned in Mortality and Kidney Transplant Outcomes among Pediatric Dialysis PatientsLaster, MarcianaNorris, Keith C.2017-03-07T06:25:46-08:00doi:10.1681/ASN.2017010017hwp:resource-id:jnephrol;28/5/1334American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, transplantation, mortality, Ethnic minorityUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-05-01May 201710.1681/ASN.20170100171046-66731533-34502017-03-07T06:25:46-08:002017-05Journal of the American Society of NephrologyUp Front Matters28551334158413361591
- Dementia and Alzheimer's Disease among Older Kidney Transplant RecipientsOlder patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked to Medicare claims through the US Renal Data System. We estimated dementia and AD risk (cumulative incidence) and studied factors associated with these sequelae using competing risks models. We estimated the risk of death-censored graft loss and mortality after developing dementia or the AD subtype of dementia, separately, using adjusted Cox proportional hazards models. Older recipients had a 10-year dementia risk ranging from 5.1% for recipients aged 55–60 years to 17.0% for recipients aged ≥75 years; 10-year AD risk ranged from 1.0% to 6.7%, respectively. The strongest predictors for dementia and AD were older recipient age and pretransplant diabetes. The 10-year graft loss risk was 28.8% for those who did not develop dementia and 43.1% for those who did, and the corresponding mortality risks were 55.7% and 89.9%, respectively. Older recipients with dementia had a 1.52-fold (95% confidence interval, 1.39 to 1.68) increased risk of graft loss and a 2.38-fold (95% confidence interval, 2.26 to 2.49) increased risk of mortality. We observed similar results for AD. We conclude that older KT recipients have a high risk of post-KT dementia and AD, and these sequelae associate with a profound effect on patient and graft survival.10.1681/ASN.2016080816Thu, 15 Dec 2016 06:36:00 GMT-08:00Dementia and Alzheimer's Disease among Older Kidney Transplant RecipientsOlder patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked to Medicare claims through the US Renal Data System. We estimated dementia and AD risk (cumulative incidence) and studied factors associated with these sequelae using competing risks models. We estimated the risk of death-censored graft loss and mortality after developing dementia or the AD subtype of dementia, separately, using adjusted Cox proportional hazards models. Older recipients had a 10-year dementia risk ranging from 5.1% for recipients aged 55–60 years to 17.0% for recipients aged ≥75 years; 10-year AD risk ranged from 1.0% to 6.7%, respectively. The strongest predictors for dementia and AD were older recipient age and pretransplant diabetes. The 10-year graft loss risk was 28.8% for those who did not develop dementia and 43.1% for those who did, and the corresponding mortality risks were 55.7% and 89.9%, respectively. Older recipients with dementia had a 1.52-fold (95% confidence interval, 1.39 to 1.68) increased risk of graft loss and a 2.38-fold (95% confidence interval, 2.26 to 2.49) increased risk of mortality. We observed similar results for AD. We conclude that older KT recipients have a high risk of post-KT dementia and AD, and these sequelae associate with a profound effect on patient and graft survival.McAdams-DeMarco, Mara A.Bae, SunjaeChu, NadiaGross, Alden L.Brown, Charles H.Oh, EstherRosenberg, PaulNeufeld, Karin J.Varadhan, RaviAlbert, MarilynWalston, JeremySegev, Dorry L.2016-12-15T06:36:00-08:00doi:10.1681/ASN.2016080816hwp:resource-id:jnephrol;28/5/1575American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydementia, kidney transplantation, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-05-01May 201710.1681/ASN.20160808161046-66731533-34502016-12-15T06:36:00-08:002017-05Journal of the American Society of NephrologyClinical Epidemiology28515751583
- Moss-Produced, Glycosylation-Optimized Human Factor H for Therapeutic Application in Complement DisordersGenetic defects in complement regulatory proteins can lead to severe renal diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies, and age-related macular degeneration. The majority of the mutations found in patients with these diseases affect the glycoprotein complement factor H, the main regulator of the alternative pathway of complement activation. Therapeutic options are limited, and novel treatments, specifically those targeting alternative pathway activation, are highly desirable. Substitution with biologically active factor H could potentially treat a variety of diseases that involve increased alternative pathway activation, but no therapeutic factor H is commercially available. We recently reported the expression of full-length recombinant factor H in moss (Physcomitrella patens). Here, we present the production of an improved moss-derived recombinant human factor H devoid of potentially immunogenic plant–specific sugar residues on protein N-glycans, yielding approximately 1 mg purified moss–derived human factor H per liter of initial P. patens culture after a multistep purification process. This glycosylation-optimized factor H showed full in vitro complement regulatory activity similar to that of plasma-derived factor H and efficiently blocked LPS-induced alternative pathway activation and hemolysis induced by sera from patients with atypical hemolytic uremic syndrome. Furthermore, injection of moss-derived factor H reduced C3 deposition and increased serum C3 levels in a murine model of C3 glomerulopathy. Thus, we consider moss-produced recombinant human factor H a promising pharmaceutical product for therapeutic intervention in patients suffering from complement dysregulation.10.1681/ASN.2015070745Thu, 08 Dec 2016 06:53:09 GMT-08:00Moss-Produced, Glycosylation-Optimized Human Factor H for Therapeutic Application in Complement DisordersGenetic defects in complement regulatory proteins can lead to severe renal diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies, and age-related macular degeneration. The majority of the mutations found in patients with these diseases affect the glycoprotein complement factor H, the main regulator of the alternative pathway of complement activation. Therapeutic options are limited, and novel treatments, specifically those targeting alternative pathway activation, are highly desirable. Substitution with biologically active factor H could potentially treat a variety of diseases that involve increased alternative pathway activation, but no therapeutic factor H is commercially available. We recently reported the expression of full-length recombinant factor H in moss (Physcomitrella patens). Here, we present the production of an improved moss-derived recombinant human factor H devoid of potentially immunogenic plant–specific sugar residues on protein N-glycans, yielding approximately 1 mg purified moss–derived human factor H per liter of initial P. patens culture after a multistep purification process. This glycosylation-optimized factor H showed full in vitro complement regulatory activity similar to that of plasma-derived factor H and efficiently blocked LPS-induced alternative pathway activation and hemolysis induced by sera from patients with atypical hemolytic uremic syndrome. Furthermore, injection of moss-derived factor H reduced C3 deposition and increased serum C3 levels in a murine model of C3 glomerulopathy. Thus, we consider moss-produced recombinant human factor H a promising pharmaceutical product for therapeutic intervention in patients suffering from complement dysregulation.Michelfelder, StefanParsons, JulianaBohlender, Lennard L.Hoernstein, Sebastian N.W.Niederkrüger, HolgerBusch, AndreasKrieghoff, NicolaKoch, JonasFode, BenjaminSchaaf, AndreasFrischmuth, ThomasPohl, MartinZipfel, Peter F.Reski, RalfDecker, Eva L.Häffner, Karsten2016-12-08T06:53:09-08:00doi:10.1681/ASN.2015070745hwp:resource-id:jnephrol;28/5/1462American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, complement, pediatric nephrology, atypical hemolytic uremic syndrome, FHmoss, C3 glomerulopathyBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20150707451046-66731533-34502016-12-08T06:53:09-08:002017-05Journal of the American Society of NephrologyBasic Research28551462i1474i
- The Urine Preservative Acetic Acid Degrades Urine Protein: Implications for Urine Biorepositories and the AASK Cohort StudyPatients enrolled in the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study who exhibited overt proteinuria have been reported to show high nonalbumin proteinuria (NAP), which is characteristic of a tubulopathy. To determine whether African American Study of Kidney Disease and Hypertension nephropathy (AASK-N) is a tubulopathy, we obtained urine samples of 37 patients with AASK-N, with 24-hour protein-to-creatinine ratios (milligrams per milligram) ranging from 0.2 to 1.0, from the National Institute of Diabetes and Digestive Kidney Diseases repository and tested for seven markers of tubular proteinuria. By protocol, each sample had been collected in acetic acid (0.5%; mean final concentration). Compared with samples from patients with lupus nephritis or healthy black controls, AASK-N samples had lower amounts of six markers. Four markers (albumin, β-2-microglobulin, cystatin C, and osteopontin) were undetectable in most AASK-N samples. Examination by SDS-PAGE followed by protein staining revealed protein profiles indicative of severe protein degradation in 34 of 37 AASK-N urine samples. Treatment of lupus nephritis urine samples with 0.5% acetic acid produced the same protein degradation profile as that of AASK-N urine. We conclude that the increased NAP in AASK-N is an artifact of acetic acid–mediated degradation of albumin. The AASK-N repository urine samples have been compromised by the acetic acid preservative.10.1681/ASN.2016080886Thu, 19 Jan 2017 06:14:45 GMT-08:00The Urine Preservative Acetic Acid Degrades Urine Protein: Implications for Urine Biorepositories and the AASK Cohort StudyPatients enrolled in the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study who exhibited overt proteinuria have been reported to show high nonalbumin proteinuria (NAP), which is characteristic of a tubulopathy. To determine whether African American Study of Kidney Disease and Hypertension nephropathy (AASK-N) is a tubulopathy, we obtained urine samples of 37 patients with AASK-N, with 24-hour protein-to-creatinine ratios (milligrams per milligram) ranging from 0.2 to 1.0, from the National Institute of Diabetes and Digestive Kidney Diseases repository and tested for seven markers of tubular proteinuria. By protocol, each sample had been collected in acetic acid (0.5%; mean final concentration). Compared with samples from patients with lupus nephritis or healthy black controls, AASK-N samples had lower amounts of six markers. Four markers (albumin, β-2-microglobulin, cystatin C, and osteopontin) were undetectable in most AASK-N samples. Examination by SDS-PAGE followed by protein staining revealed protein profiles indicative of severe protein degradation in 34 of 37 AASK-N urine samples. Treatment of lupus nephritis urine samples with 0.5% acetic acid produced the same protein degradation profile as that of AASK-N urine. We conclude that the increased NAP in AASK-N is an artifact of acetic acid–mediated degradation of albumin. The AASK-N repository urine samples have been compromised by the acetic acid preservative.Almaani, SalemHebert, Lee A.Rovin, Brad H.Birmingham, Daniel J.2017-01-19T06:14:45-08:00doi:10.1681/ASN.2016080886hwp:resource-id:jnephrol;28/5/1394American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), albuminuria, urine preservationBrief CommunicationsBrief Communicationsbrief-report20172017-05-01May 201710.1681/ASN.20160808861046-66731533-34502017-01-19T06:14:45-08:002017-05Journal of the American Society of NephrologyBrief Communications28551394i1398i
- High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the KidneyExcessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation. Pulse-chase experiments revealed that the accumulated lipids originated from cellular membranes. In mice with induced PTC-specific ablation of autophagy, PTCs of HFD-mice exhibited greater accumulation of ubiquitin-positive protein aggregates normally removed by autophagy than did PTCs of mice fed a normal diet. Furthermore, HFD-mice had no capacity to augment autophagic activity upon another pathologic stress. Autophagy ablation also exaggerated HFD-induced mitochondrial dysfunction and inflammasome activation. Moreover, renal ischemia-reperfusion induced greater injury in HFD-mice than in mice fed a normal diet, and ablation of autophagy further exacerbated this effect. Finally, we detected similarly enhanced phospholipid accumulation in enlarged lysosomes and impaired autophagic flux in the kidneys of obese patients compared with nonobese patients. These findings provide key insights regarding the pathophysiology of lipotoxicity in the kidney and clues to a novel treatment for obesity-related kidney diseases.10.1681/ASN.2016070731Thu, 08 Dec 2016 06:53:08 GMT-08:00High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the KidneyExcessive fat intake contributes to the progression of metabolic diseases via cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation. Pulse-chase experiments revealed that the accumulated lipids originated from cellular membranes. In mice with induced PTC-specific ablation of autophagy, PTCs of HFD-mice exhibited greater accumulation of ubiquitin-positive protein aggregates normally removed by autophagy than did PTCs of mice fed a normal diet. Furthermore, HFD-mice had no capacity to augment autophagic activity upon another pathologic stress. Autophagy ablation also exaggerated HFD-induced mitochondrial dysfunction and inflammasome activation. Moreover, renal ischemia-reperfusion induced greater injury in HFD-mice than in mice fed a normal diet, and ablation of autophagy further exacerbated this effect. Finally, we detected similarly enhanced phospholipid accumulation in enlarged lysosomes and impaired autophagic flux in the kidneys of obese patients compared with nonobese patients. These findings provide key insights regarding the pathophysiology of lipotoxicity in the kidney and clues to a novel treatment for obesity-related kidney diseases.Yamamoto, TakeshiTakabatake, YoshitsuguTakahashi, AtsushiKimura, TomonoriNamba, TomokoMatsuda, JunMinami, SatoshiKaimori, Jun-yaMatsui, IsaoMatsusaka, TaijiNiimura, FumioYanagita, MotokoIsaka, Yoshitaka2016-12-08T06:53:08-08:00doi:10.1681/ASN.2016070731hwp:resource-id:jnephrol;28/5/1534American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyautophagy, autophagic flux, lysosome, mitochondria, inflammasomeBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160707311046-66731533-34502016-12-08T06:53:08-08:002017-05Journal of the American Society of NephrologyBasic Research28515341551
- Characterization of Classical and Nonclassical Fabry Disease: A Multicenter StudyFabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; P<0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40; P<0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (P<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.10.1681/ASN.2016090964Thu, 15 Dec 2016 06:36:00 GMT-08:00Characterization of Classical and Nonclassical Fabry Disease: A Multicenter StudyFabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00; P<0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40; P<0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (P<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.Arends, MaartenWanner, ChristophHughes, DerralynnMehta, AtulOder, DanielWatkinson, Oliver T.Elliott, Perry M.Linthorst, Gabor E.Wijburg, Frits A.Biegstraaten, MariekeHollak, Carla E.2016-12-15T06:36:00-08:00doi:10.1681/ASN.2016090964hwp:resource-id:jnephrol;28/5/1631American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyFabry-s disease, alpha galactosidase A, natural history, natural disease course, phenotypeClinical ResearchClinical Researchresearch-article20172017-05-01May 201710.1681/ASN.20160909641046-66731533-34502016-12-15T06:36:00-08:002017-05Journal of the American Society of NephrologyClinical Research28551631i1641i
- HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous NephropathyIdiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN. After adjusting for HLA-DRB1*15:01 and HLA-DRB3*02:02, no other alleles showed significant association with PLA2R-related MN. A replication study in an independent cohort of 293 participants with PLA2R-related MN and 285 healthy controls validated these findings. In a joint analysis, a multivariate logistic regression model confirmed that HLA-DRB1*15:01 (odds ratio [OR], 24.9; 95% confidence interval [95% CI], 15.3 to 42.6; P=2.3×10−35) and HLA-DRB3*02:02 (OR, 17.7; 95% CI, 11.0 to 30.3; P=8.0×10−29) independently and strongly associated with PLA2R-related MN. As many as 98.7% of patients with PLA2R-related MN, compared with 43.9% of control subjects, carried at least one HLA risk allele. Subjects with either risk allele had higher odds of developing PLA2R-related MN than those without a risk allele (OR, 98.9; 95% CI, 44.4 to 281.7; P=2.5×10−23). These HLA risk alleles also associated with the age at disease onset in patients with PLA2R-related MN. In conclusion, our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with PLA2R-related MN in the Chinese population.10.1681/ASN.2016060644Tue, 27 Dec 2016 05:03:29 GMT-08:00HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous NephropathyIdiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN. After adjusting for HLA-DRB1*15:01 and HLA-DRB3*02:02, no other alleles showed significant association with PLA2R-related MN. A replication study in an independent cohort of 293 participants with PLA2R-related MN and 285 healthy controls validated these findings. In a joint analysis, a multivariate logistic regression model confirmed that HLA-DRB1*15:01 (odds ratio [OR], 24.9; 95% confidence interval [95% CI], 15.3 to 42.6; P=2.3×10−35) and HLA-DRB3*02:02 (OR, 17.7; 95% CI, 11.0 to 30.3; P=8.0×10−29) independently and strongly associated with PLA2R-related MN. As many as 98.7% of patients with PLA2R-related MN, compared with 43.9% of control subjects, carried at least one HLA risk allele. Subjects with either risk allele had higher odds of developing PLA2R-related MN than those without a risk allele (OR, 98.9; 95% CI, 44.4 to 281.7; P=2.5×10−23). These HLA risk alleles also associated with the age at disease onset in patients with PLA2R-related MN. In conclusion, our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with PLA2R-related MN in the Chinese population.Le, Wei-BoShi, Jing-SongZhang, TaoLiu, LeiQin, Hua-ZhangLiang, ShaoShanZhang, Yuan-WeiZheng, Cun-XiaJiang, SongQin, Wei-SongZhang, Hai-TaoLiu, Zhi-Hong2016-12-27T05:03:29-08:00doi:10.1681/ASN.2016060644hwp:resource-id:jnephrol;28/5/1642American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, human leukocyte antigen, autoimmune disease, HLA Typing, Target sequencingClinical ResearchClinical Researchresearch-article20172017-05-01May 201710.1681/ASN.20160606441046-66731533-34502016-12-27T05:03:29-08:002017-05Journal of the American Society of NephrologyClinical Research28551642133116501334
- Clot Structure: A Potent Mortality Risk Factor in Patients on HemodialysisPatients with CKD on hemodialysis exhibit increased cardiovascular risk. Fibrin clot structure and clot lysis are crucially involved in development of cardiovascular events, but little is known about the influence of clot density on outcome in patients on hemodialysis. We determined fibrin clot structure parameters and effect on mortality in a prospective cohort of 171 patients on chronic hemodialysis (mean±SD age =59±11 years old; 54% men) using a validated turbidimetric assay. Kaplan–Meier analysis revealed that patients on hemodialysis with a denser clot structure had increased all–cause and cardiovascular mortality risks (log rank P=0.004 and P=0.003, respectively). Multivariate Cox regression models (adjusted for age, diabetes, sex, and duration of dialysis or fibrinogen, C-reactive protein, and complement C3) confirmed that denser clots are independently related to mortality risk. We also purified fibrinogen from healthy controls and patients on hemodialysis using the calcium–dependent IF-1 mAb against fibrinogen for additional investigation using mass spectrometric analysis and electron microscopy. Whereas purified fibrinogen from healthy controls displayed no post-translational modifications, fibrinogen from patients on hemodialysis was glycosylated and guanidinylated. Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots from fibrinogen of control individuals (mean±SD =63±2 and 77±2 nm, respectively; P<0.001). In vitro guanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers, suggesting that difference in fiber thickness might be at least partially due to post-translational modifications. Thus, in patients on hemodialysis, a denser clot structure may be a potent independent risk factor for mortality.10.1681/ASN.2016030336Thu, 05 Jan 2017 05:14:56 GMT-08:00Clot Structure: A Potent Mortality Risk Factor in Patients on HemodialysisPatients with CKD on hemodialysis exhibit increased cardiovascular risk. Fibrin clot structure and clot lysis are crucially involved in development of cardiovascular events, but little is known about the influence of clot density on outcome in patients on hemodialysis. We determined fibrin clot structure parameters and effect on mortality in a prospective cohort of 171 patients on chronic hemodialysis (mean±SD age =59±11 years old; 54% men) using a validated turbidimetric assay. Kaplan–Meier analysis revealed that patients on hemodialysis with a denser clot structure had increased all–cause and cardiovascular mortality risks (log rank P=0.004 and P=0.003, respectively). Multivariate Cox regression models (adjusted for age, diabetes, sex, and duration of dialysis or fibrinogen, C-reactive protein, and complement C3) confirmed that denser clots are independently related to mortality risk. We also purified fibrinogen from healthy controls and patients on hemodialysis using the calcium–dependent IF-1 mAb against fibrinogen for additional investigation using mass spectrometric analysis and electron microscopy. Whereas purified fibrinogen from healthy controls displayed no post-translational modifications, fibrinogen from patients on hemodialysis was glycosylated and guanidinylated. Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots from fibrinogen of control individuals (mean±SD =63±2 and 77±2 nm, respectively; P<0.001). In vitro guanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers, suggesting that difference in fiber thickness might be at least partially due to post-translational modifications. Thus, in patients on hemodialysis, a denser clot structure may be a potent independent risk factor for mortality.Schuett, KatharinaSavvaidis, AnnaMaxeiner, SebastianLysaja, KatharinaJankowski, VeraSchirmer, Stephan H.Dimkovic, NadaBoor, PeterKaesler, NadineDekker, Friedo W.Floege, JürgenMarx, NikolausSchlieper, Georg2017-01-05T05:14:56-08:00doi:10.1681/ASN.2016030336hwp:resource-id:jnephrol;28/5/1622American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis patients, uremia, chronic kidney disease, clot, mortality, coagulopathyClinical ResearchClinical Researchresearch-article20172017-05-01May 201710.1681/ASN.20160303361046-66731533-34502017-01-05T05:14:56-08:002017-05Journal of the American Society of NephrologyClinical Research28551622i1630i
- Investigations of Glucocorticoid Action in GNFor several decades, glucocorticoids have been used empirically to treat rapid progressive GN. It is commonly assumed that glucocorticoids act primarily by dampening the immune response, but the mechanisms remain incompletely understood. In this study, we inactivated the glucocorticoid receptor (GR) specifically in kidney epithelial cells using Pax8-Cre/GRfl/fl mice. Pax8-Cre/GRfl/fl mice did not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic serum to induce crescentic nephritis (rapidly progressive GN), this genetic inactivation of the GR in kidney epithelial cells exerted renal benefits, including inhibition of albuminuria and cellular crescent formation, similar to the renal benefits observed with high-dose prednisolone in control mice. However, genetic inactivation of the GR in kidney epithelial cells did not induce the immunosuppressive effects observed with prednisolone. In vitro, prednisolone and the pharmacologic GR antagonist mifepristone each acted directly on primary cultures of parietal epithelial cells, inhibiting cellular outgrowth and proliferation. In wild-type mice, pharmacologic treatment with the GR antagonist mifepristone also attenuated disease as effectively as high-dose prednisolone without the systemic immunosuppressive effects. Collectively, these data show that glucocorticoids act directly on activated glomerular parietal epithelial cells in crescentic nephritis. Furthermore, we identified a novel therapeutic approach in crescentic nephritis, that of glucocorticoid antagonism, which was at least as effective as high-dose prednisolone with potentially fewer adverse effects.10.1681/ASN.2016010060Mon, 28 Nov 2016 07:20:42 GMT-08:00Investigations of Glucocorticoid Action in GNFor several decades, glucocorticoids have been used empirically to treat rapid progressive GN. It is commonly assumed that glucocorticoids act primarily by dampening the immune response, but the mechanisms remain incompletely understood. In this study, we inactivated the glucocorticoid receptor (GR) specifically in kidney epithelial cells using Pax8-Cre/GRfl/fl mice. Pax8-Cre/GRfl/fl mice did not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic serum to induce crescentic nephritis (rapidly progressive GN), this genetic inactivation of the GR in kidney epithelial cells exerted renal benefits, including inhibition of albuminuria and cellular crescent formation, similar to the renal benefits observed with high-dose prednisolone in control mice. However, genetic inactivation of the GR in kidney epithelial cells did not induce the immunosuppressive effects observed with prednisolone. In vitro, prednisolone and the pharmacologic GR antagonist mifepristone each acted directly on primary cultures of parietal epithelial cells, inhibiting cellular outgrowth and proliferation. In wild-type mice, pharmacologic treatment with the GR antagonist mifepristone also attenuated disease as effectively as high-dose prednisolone without the systemic immunosuppressive effects. Collectively, these data show that glucocorticoids act directly on activated glomerular parietal epithelial cells in crescentic nephritis. Furthermore, we identified a novel therapeutic approach in crescentic nephritis, that of glucocorticoid antagonism, which was at least as effective as high-dose prednisolone with potentially fewer adverse effects.Kuppe, Christophvan Roeyen, ClaudiaLeuchtle, KatjaKabgani, NazaninVogt, MichaelVan Zandvoort, MarcSmeets, BartFloege, JürgenGröne, Hermann-JosefMoeller, Marcus J.2016-11-28T07:20:42-08:00doi:10.1681/ASN.2016010060hwp:resource-id:jnephrol;28/5/1408American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycortisol, glomerulonephritis, podocyte, parietal epithelial cellsBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160100601046-66731533-34502016-11-28T07:20:42-08:002017-05Journal of the American Society of NephrologyBasic Research28551408i1420i
- Preventing the Progression of AKI to CKD: The Role of Mitochondria10.1681/ASN.2017020146Thu, 23 Mar 2017 07:24:44 GMT-07:00Preventing the Progression of AKI to CKD: The Role of Mitochondriade Seigneux, SophieMartin, Pierre-Yves2017-03-23T07:24:44-07:00doi:10.1681/ASN.2017020146hwp:resource-id:jnephrol;28/5/1327American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymitochondria, AKI, CKDUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-05-01May 201710.1681/ASN.20170201461046-66731533-34502017-03-23T07:24:44-07:002017-05Journal of the American Society of NephrologyUp Front Matters28551327143713291449
- Trends in Discharge Claims for Acute Myocardial Infarction among Patients on DialysisAnalysis of a contemporary cohort of patients on dialysis revealed that mortality from acute myocardial infarction (AMI) has decreased, whereas the prevalence of AMI has increased markedly, particularly among patients with non-ST elevation myocardial infarction (NSTEMI). Using inpatient discharge diagnosis codes (1993–2008), we determined that proportions of AMI claims decreased in the primary position (from 65% to 52%) but increased in the secondary position (from 35% to 48%). Proportions of NSTEMI codes increased remarkably in both the primary and secondary positions. The progressive increase in diagnostic claims for secondary AMI identifies a unique high-risk population and has important clinical, economic, and epidemiologic implications among patients on dialysis.10.1681/ASN.2016050560Mon, 20 Feb 2017 05:25:57 GMT-08:00Trends in Discharge Claims for Acute Myocardial Infarction among Patients on DialysisAnalysis of a contemporary cohort of patients on dialysis revealed that mortality from acute myocardial infarction (AMI) has decreased, whereas the prevalence of AMI has increased markedly, particularly among patients with non-ST elevation myocardial infarction (NSTEMI). Using inpatient discharge diagnosis codes (1993–2008), we determined that proportions of AMI claims decreased in the primary position (from 65% to 52%) but increased in the secondary position (from 35% to 48%). Proportions of NSTEMI codes increased remarkably in both the primary and secondary positions. The progressive increase in diagnostic claims for secondary AMI identifies a unique high-risk population and has important clinical, economic, and epidemiologic implications among patients on dialysis.Shroff, Gautam R.Li, ShulingHerzog, Charles A.2017-02-20T05:25:57-08:00doi:10.1681/ASN.2016050560hwp:resource-id:jnephrol;28/5/1379American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, Myocardial infarction, Epidemiology and outcomesUp Front MattersClinical CommentaryUp Front MattersClinical Commentaryarticle-commentary20172017-05-01May 201710.1681/ASN.20160505601046-66731533-34502017-02-20T05:25:57-08:002017-05Journal of the American Society of NephrologyUp Front Matters28513791383
- Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal FibrosisRenal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase (Hck), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration–approved drug, potently binds Hck with high selectivity. In vitro, Hck overexpression activated the TGF-β/Smad3 pathway, whereas HCK knockdown inhibited it. Treatment of tubular cells with dasatinib reduced the expression of Col1a1. Dasatinib also reduced proliferation and α-SMA expression in fibroblasts. In a murine model with unilateral ureteric obstruction, pretreatment with dasatinib significantly reduced the upregulation of profibrotic markers, phosphorylation of Smad3, and renal fibrosis observed in kidneys pretreated with vehicle alone. Dasatinib treatment also improved renal function, reduced albuminuria, and inhibited expression of profibrotic markers in animal models with lupus nephritis and folic acid nephropathy. These data suggest that Hck is a key mediator of renal fibrosis and dasatinib could be developed as an antifibrotic drug.10.1681/ASN.2016020238Wed, 07 Dec 2016 09:39:23 GMT-08:00Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal FibrosisRenal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase (Hck), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration–approved drug, potently binds Hck with high selectivity. In vitro, Hck overexpression activated the TGF-β/Smad3 pathway, whereas HCK knockdown inhibited it. Treatment of tubular cells with dasatinib reduced the expression of Col1a1. Dasatinib also reduced proliferation and α-SMA expression in fibroblasts. In a murine model with unilateral ureteric obstruction, pretreatment with dasatinib significantly reduced the upregulation of profibrotic markers, phosphorylation of Smad3, and renal fibrosis observed in kidneys pretreated with vehicle alone. Dasatinib treatment also improved renal function, reduced albuminuria, and inhibited expression of profibrotic markers in animal models with lupus nephritis and folic acid nephropathy. These data suggest that Hck is a key mediator of renal fibrosis and dasatinib could be developed as an antifibrotic drug.Wei, ChengguoLi, LiMenon, Madhav C.Zhang, WeijiaFu, JiaKidd, BrianKeung, Karen L.Woytovich, ChristopherGreene, IlanaXiao, WenzhenSalem, FadiYi, ZhengziHe, John CijiangDudley, Joel T.Murphy, Barbara2016-12-07T09:39:23-08:00doi:10.1681/ASN.2016020238hwp:resource-id:jnephrol;28/5/1385American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal allograft injury, Hck, dasatinib, renal fibrosisBrief CommunicationsBrief Communicationsbrief-report20172017-05-01May 201710.1681/ASN.20160202381046-66731533-34502016-12-07T09:39:23-08:002017-05Journal of the American Society of NephrologyBrief Communications28513851393
- Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome TubulopathyLowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule–specific inactivation of Inpp5b on a global Ocrl–knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia. At the cellular level, we observed a striking impairment of clathrin-dependent and -independent endocytosis in proximal tubules, phenocopying what has been reported for Dent disease caused by mutations in the gene encoding endosomal proton-chloride exchange transporter 5. These results suggest that the functions of OCRL/INPP5B and proton-chloride exchange transporter 5 converge on shared mechanisms, the impairment of which has a dramatic effect on proximal tubule endocytosis.10.1681/ASN.2016080913Mon, 28 Nov 2016 07:20:41 GMT-08:00Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome TubulopathyLowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule–specific inactivation of Inpp5b on a global Ocrl–knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia. At the cellular level, we observed a striking impairment of clathrin-dependent and -independent endocytosis in proximal tubules, phenocopying what has been reported for Dent disease caused by mutations in the gene encoding endosomal proton-chloride exchange transporter 5. These results suggest that the functions of OCRL/INPP5B and proton-chloride exchange transporter 5 converge on shared mechanisms, the impairment of which has a dramatic effect on proximal tubule endocytosis.Inoue, KazunoriBalkin, Daniel M.Liu, LijuanNandez, RamiroWu, YumeiTian, XuefeiWang, TongNussbaum, RobertDe Camilli, PietroIshibe, Shuta2016-11-28T07:20:41-08:00doi:10.1681/ASN.2016080913hwp:resource-id:jnephrol;28/5/1399American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyendocytosis, OCRL, INPP5B, Lowe syndrome, proximal tubulopathyBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160809131046-66731533-34502016-11-28T07:20:41-08:002017-05Journal of the American Society of NephrologyBasic Research28513991407
- NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GNDe novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NFκB and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN. Mice lacking expression of periostin displayed preserved renal function and structure during GN. Furthermore, delayed administration of periostin antisense oligonucleotides in wild-type animals with GN reversed already established proteinuria, diminished tissue inflammation, and improved renal structure. Lack of periostin expression also blunted the de novo renal expression of integrin-β3 and phosphorylation of focal adhesion kinase and AKT, known mediators of integrin-β3 signaling that affect cell motility and survival, observed during GN in wild-type animals. In vitro, recombinant periostin increased the expression of integrin-β3 and the concomitant phosphorylation of focal adhesion kinase and AKT in podocytes. Notably, periostin and integrin-β3 were highly colocalized in biopsy specimens from patients with inflammatory GN. These results demonstrate that interplay between periostin and renal inflammation orchestrates inflammatory and fibrotic responses, driving podocyte damage through downstream activation of integrin-β3 signaling. Targeting periostin may be a novel therapeutic strategy for treating CKD.10.1681/ASN.2016070709Mon, 05 Dec 2016 08:14:56 GMT-08:00NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GNDe novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NFκB and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN. Mice lacking expression of periostin displayed preserved renal function and structure during GN. Furthermore, delayed administration of periostin antisense oligonucleotides in wild-type animals with GN reversed already established proteinuria, diminished tissue inflammation, and improved renal structure. Lack of periostin expression also blunted the de novo renal expression of integrin-β3 and phosphorylation of focal adhesion kinase and AKT, known mediators of integrin-β3 signaling that affect cell motility and survival, observed during GN in wild-type animals. In vitro, recombinant periostin increased the expression of integrin-β3 and the concomitant phosphorylation of focal adhesion kinase and AKT in podocytes. Notably, periostin and integrin-β3 were highly colocalized in biopsy specimens from patients with inflammatory GN. These results demonstrate that interplay between periostin and renal inflammation orchestrates inflammatory and fibrotic responses, driving podocyte damage through downstream activation of integrin-β3 signaling. Targeting periostin may be a novel therapeutic strategy for treating CKD.Prakoura, NikiKavvadas, PanagiotisKormann, RaphaёlDussaule, Jean-ClaudeChadjichristos, Christos E.Chatziantoniou, Christos2016-12-05T08:14:56-08:00doi:10.1681/ASN.2016070709hwp:resource-id:jnephrol;28/5/1475American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, transcription regulation, macrophages, cell-matrix interactions, Pathophysiology of Renal Disease and ProgressionBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160707091046-66731533-34502016-12-05T08:14:56-08:002017-05Journal of the American Society of NephrologyBasic Research28514751490
- The Use of Sildenafil for Glomerular Disease10.1681/ASN.2017020171Thu, 30 Mar 2017 06:09:01 GMT-07:00The Use of Sildenafil for Glomerular DiseaseTardi, Nicholas J.Reiser, Jochen2017-03-30T06:09:01-07:00doi:10.1681/ASN.2017020171hwp:resource-id:jnephrol;28/5/1329American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologysildenafil, TRPC6, glomerular disease, podocyte injury, PPAR gammaUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-05-01May 201710.1681/ASN.20170201711046-66731533-34502017-03-30T06:09:01-07:002017-05Journal of the American Society of NephrologyUp Front Matters28551329149113311505
- This Month’s Highlights10.1681/ASN.2017020121Fri, 28 Apr 2017 01:00:57 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-04-28T13:00:57-07:00doi:10.1681/ASN.2017020121hwp:resource-id:jnephrol;28/5/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-05-01May 201710.1681/ASN.20170201211046-66731533-34502017-04-28T13:00:57-07:002017-05Journal of the American Society of NephrologyThis Month’s Highlights285555555i139414081421146216221631i139814201436147416301641
- MAGI2 Mutations Cause Congenital Nephrotic SyndromeSteroid–resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain ≤30% of patients with hereditary cases and only 20% of patients with sporadic cases. The proteins encoded by these genes are expressed in podocytes, and malfunction of these proteins leads to a universal end point of podocyte injury, glomerular filtration barrier disruption, and SRNS. Here, we identified novel disease–causing mutations in membrane–associated guanylate kinase, WW, and PDZ domain–containing 2 (MAGI2) through whole-exome sequencing of a deeply phenotyped cohort of patients with congenital, childhood–onset SRNS. Although MAGI2 has been shown to interact with nephrin and regulate podocyte cytoskeleton and slit diaphragm dynamics, MAGI2 mutations have not been described in human SRNS. We detected two unique frameshift mutations and one duplication in three patients (two families); two siblings shared the same homozygous frameshift mutation, whereas one individual with sporadic SRNS exhibited compound heterozygosity. Two mutations were predicted to introduce premature stop codons, and one was predicted to result in read through of the normal translational termination codon. Immunohistochemistry in kidney sections from these patients revealed that mutations resulted in lack of or diminished podocyte MAGI2 expression. Our data support the finding that mutations in the MAGI2 gene are causal for congenital SRNS.10.1681/ASN.2016040387Thu, 08 Dec 2016 06:53:12 GMT-08:00MAGI2 Mutations Cause Congenital Nephrotic SyndromeSteroid–resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain ≤30% of patients with hereditary cases and only 20% of patients with sporadic cases. The proteins encoded by these genes are expressed in podocytes, and malfunction of these proteins leads to a universal end point of podocyte injury, glomerular filtration barrier disruption, and SRNS. Here, we identified novel disease–causing mutations in membrane–associated guanylate kinase, WW, and PDZ domain–containing 2 (MAGI2) through whole-exome sequencing of a deeply phenotyped cohort of patients with congenital, childhood–onset SRNS. Although MAGI2 has been shown to interact with nephrin and regulate podocyte cytoskeleton and slit diaphragm dynamics, MAGI2 mutations have not been described in human SRNS. We detected two unique frameshift mutations and one duplication in three patients (two families); two siblings shared the same homozygous frameshift mutation, whereas one individual with sporadic SRNS exhibited compound heterozygosity. Two mutations were predicted to introduce premature stop codons, and one was predicted to result in read through of the normal translational termination codon. Immunohistochemistry in kidney sections from these patients revealed that mutations resulted in lack of or diminished podocyte MAGI2 expression. Our data support the finding that mutations in the MAGI2 gene are causal for congenital SRNS.Bierzynska, AgnieszkaSoderquest, KatrinaDean, PhilipColby, ElizabethRollason, RuthJones, CarolineInward, Carol D.McCarthy, Hugh J.Simpson, Michael A.Lord, Graham M.Williams, MaggieWelsh, Gavin I.Koziell, Ania B.Saleem, Moin A.Bierzynska, AgnieszkaSoderquest, KatrinaDean, PhilipColby, ElizabethRollason, RuthJones, CarolineInward, Carol D.McCarthy, Hugh J.Simpson, Michael A.Lord, Graham M.Williams, MaggieWelsh, Gavin I.Koziell, Ania B.Saleem, Moin A.2016-12-08T06:53:12-08:00doi:10.1681/ASN.2016040387hwp:resource-id:jnephrol;28/5/1614American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, genetic renal disease, nephrin, familial nephropathy, proteinuria, nephrotic syndromeClinical ResearchClinical Researchresearch-article20172017-05-01May 201710.1681/ASN.20160403871046-66731533-34502016-12-08T06:53:12-08:002017-05Journal of the American Society of NephrologyClinical Research28516141621
- Pregnancy Outcomes after Clinical Recovery from AKIThe effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, including preeclampsia. AKI was defined as rise in serum creatinine concentration to 1.5-fold above baseline. We compared pregnancy outcomes in women with r-AKI without history of CKD (eGFR>90 ml/min per 1.73 m2 before conception; n=105) with outcomes in women without kidney disease (controls; n=24,640). The r-AKI and control groups had similar prepregnancy serum creatinine measurements (0.70±0.20 versus 0.69±0.10 mg/dl; P=0.36). However, women with r-AKI had increased rates of preeclampsia compared with controls (23% versus 4%; P<0.001). Infants of women with r-AKI were born earlier than infants of controls (37.6±3.6 versus 39.2±2.2 weeks; P<0.001), with increased rates of small for gestational age births (15% versus 8%; P=0.03). After multivariate adjustment, r-AKI associated with increased risk for preeclampsia (adjusted odds ratio [aOR], 5.9; 95% confidence interval [95% CI], 3.6 to 9.7) and adverse fetal outcomes (aOR, 2.4; 95% CI, 1.6 to 3.7). When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic BP, parity, and diabetes status, r-AKI remained associated with preeclampsia (OR, 4.7; 95% CI, 2.1 to 10.1) and adverse fetal outcomes (OR, 2.1; 95% CI, 1.2 to 3.7). Thus, a past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy.10.1681/ASN.2016070806Thu, 22 Dec 2016 08:18:40 GMT-08:00Pregnancy Outcomes after Clinical Recovery from AKIThe effect of clinically recovered AKI (r-AKI) on future pregnancy outcomes is unknown. We retrospectively studied all women who delivered infants between 1998 and 2007 at Massachusetts General Hospital to assess whether a previous episode of r-AKI associated with subsequent adverse maternal and fetal outcomes, including preeclampsia. AKI was defined as rise in serum creatinine concentration to 1.5-fold above baseline. We compared pregnancy outcomes in women with r-AKI without history of CKD (eGFR>90 ml/min per 1.73 m2 before conception; n=105) with outcomes in women without kidney disease (controls; n=24,640). The r-AKI and control groups had similar prepregnancy serum creatinine measurements (0.70±0.20 versus 0.69±0.10 mg/dl; P=0.36). However, women with r-AKI had increased rates of preeclampsia compared with controls (23% versus 4%; P<0.001). Infants of women with r-AKI were born earlier than infants of controls (37.6±3.6 versus 39.2±2.2 weeks; P<0.001), with increased rates of small for gestational age births (15% versus 8%; P=0.03). After multivariate adjustment, r-AKI associated with increased risk for preeclampsia (adjusted odds ratio [aOR], 5.9; 95% confidence interval [95% CI], 3.6 to 9.7) and adverse fetal outcomes (aOR, 2.4; 95% CI, 1.6 to 3.7). When women with r-AKI and controls were matched 1:2 by age, race, body mass index, diastolic BP, parity, and diabetes status, r-AKI remained associated with preeclampsia (OR, 4.7; 95% CI, 2.1 to 10.1) and adverse fetal outcomes (OR, 2.1; 95% CI, 1.2 to 3.7). Thus, a past episode of AKI, despite return to normal renal function before pregnancy, associated with adverse outcomes in pregnancy.Tangren, Jessica SheehanPowe, Camille E.Ankers, ElizabethEcker, JeffreyBramham, KateHladunewich, Michelle A.Karumanchi, S. AnanthThadhani, Ravi2016-12-22T08:18:40-08:00doi:10.1681/ASN.2016070806hwp:resource-id:jnephrol;28/5/1566American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, pregnancy, preeclampsia, clinical epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20172017-05-01May 201710.1681/ASN.20160708061046-66731533-34502016-12-22T08:18:40-08:002017-05Journal of the American Society of NephrologyClinical Epidemiology28515661574
- Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GNIn C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.10.1681/ASN.2016030343Tue, 17 Jan 2017 07:34:13 GMT-08:00Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GNIn C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.Marinozzi, Maria ChiaraRoumenina, Lubka T.Chauvet, SophieHertig, AlexandreBertrand, DominiqueOlagne, JéromeFrimat, MarieUlinski, TimDeschênes, GeorgesBurtey, StephaneDelahousse, MichelMoulin, BrunoLegendre, ChristopheFrémeaux-Bacchi, VéroniqueLe Quintrec, Moglie2017-01-17T07:34:13-08:00doi:10.1681/ASN.2016030343hwp:resource-id:jnephrol;28/5/1603American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic glomerulonephritis, complement, clinical immunologyClinical ResearchClinical Researchresearch-article20172017-05-01May 201710.1681/ASN.20160303431046-66731533-34502017-01-17T07:34:13-08:002017-05Journal of the American Society of NephrologyClinical Research28516031613
- Sildenafil Prevents Podocyte Injury via PPAR-γ–Mediated TRPC6 InhibitionTransient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expression in podocytes induce glomerular injury and proteinuria. Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although the mechanism is unknown. Peroxisome proliferator–activated receptor γ (PPAR-γ) is a downstream target of sildenafil in the cyclic guanosine monophosphate (cGMP)–activated protein kinase G (PKG) axis. PPAR-γ agonists, like pioglitazone, appear antiproteinuric. We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ–dependent mechanisms, thereby counteracting podocyte injury and proteinuria. Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3′,5′-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro. Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP. We observed similar effects on TRPC6 promoter activity and TRPC6–dependent calcium influx. Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter. Sildenafil or pioglitazone treatment prevented proteinuria and the increased TRPC6 expression in rats with adriamycin-induced nephropathy and mice with hyperglycemia-induced renal injury. Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil. Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity. Because sildenafil is approved for clinical use, our results suggest that additional clinical study of its antiproteinuric effect in glomerular disease is warranted.10.1681/ASN.2015080885Mon, 28 Nov 2016 07:20:43 GMT-08:00Sildenafil Prevents Podocyte Injury via PPAR-γ–Mediated TRPC6 InhibitionTransient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expression in podocytes induce glomerular injury and proteinuria. Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although the mechanism is unknown. Peroxisome proliferator–activated receptor γ (PPAR-γ) is a downstream target of sildenafil in the cyclic guanosine monophosphate (cGMP)–activated protein kinase G (PKG) axis. PPAR-γ agonists, like pioglitazone, appear antiproteinuric. We hypothesized that sildenafil inhibits TRPC6 expression in podocytes through PPAR-γ–dependent mechanisms, thereby counteracting podocyte injury and proteinuria. Treatment with sildenafil, the cGMP derivative 8-bromoguanosine 3′,5′-cyclic monophosphate sodium salt (8-Br-cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced TRPC6 expression in vitro. Knockdown or application of antagonists of PKG or PPAR-γ enhanced TRPC6 expression in podocytes and counteracted effects of sildenafil and 8-Br-cGMP. We observed similar effects on TRPC6 promoter activity and TRPC6–dependent calcium influx. Chromatin immunoprecipitation showed PPAR-γ binding to the TRPC6 promoter. Sildenafil or pioglitazone treatment prevented proteinuria and the increased TRPC6 expression in rats with adriamycin-induced nephropathy and mice with hyperglycemia-induced renal injury. Rats receiving PPAR-γ antagonists displayed proteinuria and increased podocyte TRPC6 expression, as did podocyte-specific PPAR-γ knockout mice, which were more sensitive to adriamycin and not protected by sildenafil. Thus, sildenafil ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG-dependent binding of PPAR-γ to the TRPC6 promoter, which inhibits TRPC6 promoter activity, expression, and activity. Because sildenafil is approved for clinical use, our results suggest that additional clinical study of its antiproteinuric effect in glomerular disease is warranted.Sonneveld, RamonHoenderop, Joost G.Isidori, Andrea M.Henique, CaroleDijkman, Henry B.Berden, Jo H.Tharaux, Pierre-Louisvan der Vlag, JohanNijenhuis, Tom2016-11-28T07:20:43-08:00doi:10.1681/ASN.2015080885hwp:resource-id:jnephrol;28/5/1491American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, ion channel, podocyte, signaling, glomerulosclerosis, focal segmental glomerulosclerosisBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20150808851046-66731533-34502016-11-28T07:20:43-08:002017-05Journal of the American Society of NephrologyBasic Research28551491132915051331
- Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKIOverexpression of the proximal tubular enzyme myo-inositol oxygenase (MIOX) induces oxidant stress in vitro. However, the relevance of MIOX to tubular pathobiology remains enigmatic. To investigate the role of MIOX in cisplatin-induced tubular AKI, we generated conditional MIOX-overexpressing transgenic (MIOX-TG) mice and MIOX-knockout (MIOX−/−) mice with tubule-specific MIOX overexpression or knockout, respectively. Compared with cisplatin-treated wild-type (WT) mice, cisplatin-treated MIOX-TG mice had even greater increases in urea, creatinine, and KIM-1 levels and more tubular injury and apoptosis, but these effects were attenuated in cisplatin-treated MIOX−/− mice. Similarly, MIOX-TG mice had the highest and MIOX−/− mice had the lowest renal levels of Bax, cleaved caspase-3, and NADPH oxidase-4 expression and reactive oxygen species (ROS) generation after cisplatin treatment. In vitro, cisplatin dose-dependently increased ROS generation in LLC-PK1 cells. Furthermore, MIOX overexpression in these cells accentuated cisplatin-induced ROS generation and perturbations in the ratio of GSH to oxidized GSH, whereas MIOX-siRNA or N-acetyl cysteine treatment attenuated these effects. Additionally, the cisplatin-induced enhancement of p53 activation, NF-κB binding to DNA, and NF-κB nuclear translocation in WT mice was exacerbated in MIOX-TG mice but absent in MIOX−/− mice. In vitro, MIOX-siRNA or NAC treatment reduced the dose-dependent increase in p53 expression induced by cisplatin. We also observed a remarkable influx of inflammatory cells and upregulation of cytokines in kidneys of cisplatin-treated MIOX-TG mice. Finally, analysis of genomic DNA in WT mice revealed cisplatin-induced hypomethylation of the MIOX promoter. These data suggest that MIOX overexpression exacerbates, whereas MIOX gene disruption protects against, cisplatin-induced AKI.10.1681/ASN.2016070744Mon, 28 Nov 2016 07:20:43 GMT-08:00Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKIOverexpression of the proximal tubular enzyme myo-inositol oxygenase (MIOX) induces oxidant stress in vitro. However, the relevance of MIOX to tubular pathobiology remains enigmatic. To investigate the role of MIOX in cisplatin-induced tubular AKI, we generated conditional MIOX-overexpressing transgenic (MIOX-TG) mice and MIOX-knockout (MIOX−/−) mice with tubule-specific MIOX overexpression or knockout, respectively. Compared with cisplatin-treated wild-type (WT) mice, cisplatin-treated MIOX-TG mice had even greater increases in urea, creatinine, and KIM-1 levels and more tubular injury and apoptosis, but these effects were attenuated in cisplatin-treated MIOX−/− mice. Similarly, MIOX-TG mice had the highest and MIOX−/− mice had the lowest renal levels of Bax, cleaved caspase-3, and NADPH oxidase-4 expression and reactive oxygen species (ROS) generation after cisplatin treatment. In vitro, cisplatin dose-dependently increased ROS generation in LLC-PK1 cells. Furthermore, MIOX overexpression in these cells accentuated cisplatin-induced ROS generation and perturbations in the ratio of GSH to oxidized GSH, whereas MIOX-siRNA or N-acetyl cysteine treatment attenuated these effects. Additionally, the cisplatin-induced enhancement of p53 activation, NF-κB binding to DNA, and NF-κB nuclear translocation in WT mice was exacerbated in MIOX-TG mice but absent in MIOX−/− mice. In vitro, MIOX-siRNA or NAC treatment reduced the dose-dependent increase in p53 expression induced by cisplatin. We also observed a remarkable influx of inflammatory cells and upregulation of cytokines in kidneys of cisplatin-treated MIOX-TG mice. Finally, analysis of genomic DNA in WT mice revealed cisplatin-induced hypomethylation of the MIOX promoter. These data suggest that MIOX overexpression exacerbates, whereas MIOX gene disruption protects against, cisplatin-induced AKI.Dutta, Rajesh K.Kondeti, Vinay K.Sharma, IshaChandel, Navdeep S.Quaggin, Susan E.Kanwar, Yashpal S.2016-11-28T07:20:43-08:00doi:10.1681/ASN.2016070744hwp:resource-id:jnephrol;28/5/1421American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyoxidative stress, cisplatin nephrotoxicity, reactive oxygen species, renal injury, myo-inositol oxygenaseBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160707441046-66731533-34502016-11-28T07:20:43-08:002017-05Journal of the American Society of NephrologyBasic Research28551421i1436i
- Mitochondria Protection after Acute Ischemia Prevents Prolonged Upregulation of IL-1β and IL-18 and Arrests CKDThe innate immune system has been implicated in both AKI and CKD. Damaged mitochondria release danger molecules, such as reactive oxygen species, DNA, and cardiolipin, which can cause NLRP3 inflammasome activation and upregulation of IL-18 and IL-1β. It is not known if mitochondrial damage persists long after ischemia to sustain chronic inflammasome activation. We conducted a 9-month study in Sprague–Dawley rats after 45 minutes of bilateral renal ischemia. We detected glomerular and peritubular capillary rarefaction, macrophage infiltration, and fibrosis at 1 month. Transmission electron microscopy revealed mitochondrial degeneration, mitophagy, and deformed foot processes in podocytes. These changes progressed over the study period, with a persistent increase in renal cortical expression of IL-18, IL-1β, and TGF-β, despite a gradual decline in TNF-α expression and macrophage infiltration. Treatment with a mitoprotective agent (SS-31; elamipretide) for 6 weeks, starting 1 month after ischemia, preserved mitochondrial integrity, ameliorated expression levels of all inflammatory markers, restored glomerular capillaries and podocyte structure, and arrested glomerulosclerosis and interstitial fibrosis. Further, helium ion microscopy vividly demonstrated the restoration of podocyte structure by SS-31. The protection by SS-31 was sustained for ≥6 months after treatment ended, with normalization of IL-18 and IL-1β expression. These results support a role for mitochondrial damage in inflammasome activation and CKD and suggest mitochondrial protection as a novel therapeutic approach that can arrest the progression of CKD. Notably, SS-31 is effective when given long after AKI and provides persistent protection after termination of drug treatment.10.1681/ASN.2016070761Wed, 23 Nov 2016 09:30:59 GMT-08:00Mitochondria Protection after Acute Ischemia Prevents Prolonged Upregulation of IL-1β and IL-18 and Arrests CKDThe innate immune system has been implicated in both AKI and CKD. Damaged mitochondria release danger molecules, such as reactive oxygen species, DNA, and cardiolipin, which can cause NLRP3 inflammasome activation and upregulation of IL-18 and IL-1β. It is not known if mitochondrial damage persists long after ischemia to sustain chronic inflammasome activation. We conducted a 9-month study in Sprague–Dawley rats after 45 minutes of bilateral renal ischemia. We detected glomerular and peritubular capillary rarefaction, macrophage infiltration, and fibrosis at 1 month. Transmission electron microscopy revealed mitochondrial degeneration, mitophagy, and deformed foot processes in podocytes. These changes progressed over the study period, with a persistent increase in renal cortical expression of IL-18, IL-1β, and TGF-β, despite a gradual decline in TNF-α expression and macrophage infiltration. Treatment with a mitoprotective agent (SS-31; elamipretide) for 6 weeks, starting 1 month after ischemia, preserved mitochondrial integrity, ameliorated expression levels of all inflammatory markers, restored glomerular capillaries and podocyte structure, and arrested glomerulosclerosis and interstitial fibrosis. Further, helium ion microscopy vividly demonstrated the restoration of podocyte structure by SS-31. The protection by SS-31 was sustained for ≥6 months after treatment ended, with normalization of IL-18 and IL-1β expression. These results support a role for mitochondrial damage in inflammasome activation and CKD and suggest mitochondrial protection as a novel therapeutic approach that can arrest the progression of CKD. Notably, SS-31 is effective when given long after AKI and provides persistent protection after termination of drug treatment.Szeto, Hazel H.Liu, ShaoyiSoong, YiSeshan, Surya V.Cohen-Gould, LeonaManichev, ViacheslavFeldman, Leonard C.Gustafsson, Torgny2016-11-23T09:30:59-08:00doi:10.1681/ASN.2016070761hwp:resource-id:jnephrol;28/5/1437American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyPodocytes, innate immunity, inflammasome, microvascular rarefaction, SS- 31, ElamipretideBasic ResearchBasic Researchresearch-article20172017-05-01May 201710.1681/ASN.20160707611046-66731533-34502016-11-23T09:30:59-08:002017-05Journal of the American Society of NephrologyBasic Research28551437132714491329
- Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 TrialThe vasopressin–cAMP–osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, and whether change in Uosm associated with key trial end points. At baseline, lower Uosm independently associated with female sex, presence of hypertension, lower eGFR, higher total kidney volume (TKV), and higher age. Tolvaptan consistently reduced Uosm by 200–300 mOsm/kg over 36 months. The Uosm response to tolvaptan depended on baseline eGFR and Uosm. Subjects with greater change in Uosm experienced a significant reduction in clinical progression events. Among subjects receiving tolvaptan, those with a greater suppression of Uosm had slower renal function decline. Assessment at follow-up, off medication, revealed a significant decrease in Uosm in both placebo and treated groups. Tolvaptan significantly increased plasma osmolality, which returned to baseline at follow-up. In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm. The greatest renal benefit occurred in subjects achieving greater suppression of Uosm, that is, those with better eGFR at baseline. These results support the link between vasopressin V2 receptor signaling and ADPKD progression.10.1681/ASN.2016040448Mon, 05 Dec 2016 08:14:54 GMT-08:00Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 TrialThe vasopressin–cAMP–osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, and whether change in Uosm associated with key trial end points. At baseline, lower Uosm independently associated with female sex, presence of hypertension, lower eGFR, higher total kidney volume (TKV), and higher age. Tolvaptan consistently reduced Uosm by 200–300 mOsm/kg over 36 months. The Uosm response to tolvaptan depended on baseline eGFR and Uosm. Subjects with greater change in Uosm experienced a significant reduction in clinical progression events. Among subjects receiving tolvaptan, those with a greater suppression of Uosm had slower renal function decline. Assessment at follow-up, off medication, revealed a significant decrease in Uosm in both placebo and treated groups. Tolvaptan significantly increased plasma osmolality, which returned to baseline at follow-up. In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm. The greatest renal benefit occurred in subjects achieving greater suppression of Uosm, that is, those with better eGFR at baseline. These results support the link between vasopressin V2 receptor signaling and ADPKD progression.Devuyst, OlivierChapman, Arlene B.Gansevoort, Ron T.Higashihara, EijiPerrone, Ronald D.Torres, Vicente E.Blais, Jaime D.Zhou, WenOuyang, JohnCzerwiec, Frank S.2016-12-05T08:14:54-08:00doi:10.1681/ASN.2016040448hwp:resource-id:jnephrol;28/5/1592American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, vasopressin, cyclic AMP, collecting ducts, water transportClinical EpidemiologyClinical Epidemiologyresearch-article20172017-05-01May 201710.1681/ASN.20160404481046-66731533-34502016-12-05T08:14:54-08:002017-05Journal of the American Society of NephrologyClinical Epidemiology28515921602
- Erratum10.1681/ASN.2017020168Fri, 28 Apr 2017 01:00:57 GMT-07:00ErratumAmerican Society of Nephrology2017-04-28T13:00:57-07:00doi:10.1681/ASN.2017020168hwp:resource-id:jnephrol;28/5/1665American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20172017-05-01May 201710.1681/ASN.20170201681046-66731533-34502017-04-28T13:00:57-07:002017-05Journal of the American Society of NephrologyErratum28285216656911665701
- Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant Recipients10.2215/CJN.09850916Mon, 27 Mar 2017 06:52:34 GMT-07:00Spine Trabecular Bone Score as an Indicator of Bone Microarchitecture at the Peripheral Skeleton in Kidney Transplant RecipientsLuckman, MatthewHans, DidierCortez, NataliaNishiyama, Kyle K.Agarawal, SanchitaZhang, ChengchenNikkel, LucasIyer, SapnaFusaro, MariaGuo, Edward X.McMahon, Donald J.Shane, ElizabethNickolas, Thomas L.2017-03-27T06:52:34-07:00doi:10.2215/CJN.09850916hwp:resource-id:clinjasn;12/4/644American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal osteodystrophy, renal transplantation, mineral metabolism, Absorptiometry, Photon, Adrenal Cortex Hormones, Adult, Bone Density, Bone and Bones, Follow-Up Studies, Fractures, Bone, Humans, kidney transplantation, Porosity, Radius, Spine, TomographyOriginal ArticlesMineral Metabolism/Bone DiseaseOriginal ArticlesMineral Metabolism/Bone Diseaseresearch-article20172017-04-03April 03, 201710.2215/CJN.098509161555-90411555-905X2017-03-27T06:52:34-07:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles1244644562652564
- Noninvasive Imaging of Bone Microarchitecture in Patients Receiving Renal Transplant: Can it Replace Histology?10.2215/CJN.02210217Mon, 27 Mar 2017 06:52:33 GMT-07:00Noninvasive Imaging of Bone Microarchitecture in Patients Receiving Renal Transplant: Can it Replace Histology?Coco, MariaPullman, James M.2017-03-27T06:52:33-07:00doi:10.2215/CJN.02210217hwp:resource-id:clinjasn;12/4/562American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymetabolic bone disease, renal transplantation, Bone and Bones, Histological Techniques, Humans, kidney transplantationEditorialsEditorialseditorial20172017-04-03April 03, 201710.2215/CJN.022102171555-90411555-905X2017-03-27T06:52:33-07:002017-04-03Clinical Journal of the American Society of NephrologyEditorials1244562644564652
- Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients10.2215/CJN.07090716Fri, 03 Feb 2017 07:56:23 GMT-08:00Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant RecipientsJeon, Hee JungKim, Yong ChulPark, SeokwooKim, Clara TammyHa, JongwonHan, Duck JongOh, JieunLim, Chun SooJung, In MokAhn, CurieKim, Yon SuLee, Jung PyoKim, Young Hoon2017-02-03T07:56:23-08:00doi:10.2215/CJN.07090716hwp:resource-id:clinjasn;12/4/653American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymortality, graft survival, phosphorus, cardiovascular diseases, confidence intervals, diabetes mellitus, follow-up studies, glomerular filtration rate, graft survival, humans, hyperphosphatemia, hypophosphatemia, incidence, kidney, kidney transplantation, living donors, male, multivariate analysis, phosphorus, phosphorus, dietary, proportional hazards models, retrospective studies, survival analysisOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-04-03April 03, 201710.2215/CJN.070907161555-90411555-905X2017-02-03T07:56:23-08:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124653662
- Donor-Recipient Weight and Sex Mismatch and the Risk of Graft Loss in Renal Transplantation10.2215/CJN.07660716Thu, 30 Mar 2017 06:21:36 GMT-07:00Donor-Recipient Weight and Sex Mismatch and the Risk of Graft Loss in Renal TransplantationMiller, Amanda J.Kiberd, Bryce A.Alwayn, Ian P.Odutayo, AyoTennankore, Karthik K.2017-03-30T06:21:36-07:00doi:10.2215/CJN.07660716hwp:resource-id:clinjasn;12/4/669American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, graft failure, size mismatch, sex mismatch, female, graft survival, kidney, male, nephrons, proportional hazards models, registries, sex characteristics, tissue donors, transplant recipients, United StatesOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-04-03April 03, 201710.2215/CJN.076607161555-90411555-905X2017-03-30T06:21:36-07:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles1244669565676567
- A Case-Based Analysis of Whether Living Related Donors Listed for Transplant Share ESRD Causes with Their Recipients10.2215/CJN.11421116Wed, 01 Mar 2017 06:46:46 GMT-08:00A Case-Based Analysis of Whether Living Related Donors Listed for Transplant Share ESRD Causes with Their RecipientsMatas, Arthur J.Hays, Rebecca E.Ibrahim, Hassan N.2017-03-01T06:46:46-08:00doi:10.2215/CJN.11421116hwp:resource-id:clinjasn;12/4/663American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOutcomes, living, kidney, donation, transplant, live kidney donor, ESRD, Counseling, Donor Selection, Humans, hypertension, Kidney Failure, Chronic, kidney transplantation, risk factors, Tissue Donors, Tissue and Organ Procurement, United StatesOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-04-03April 03, 201710.2215/CJN.114211161555-90411555-905X2017-03-01T06:46:46-08:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124663668
- Hypocalcemia in a Patient with Cancer10.2215/CJN.13241216Wed, 08 Mar 2017 05:06:56 GMT-08:00Hypocalcemia in a Patient with CancerRosner, Mitchell H.2017-03-08T05:06:56-08:00doi:10.2215/CJN.13241216hwp:resource-id:clinjasn;12/4/696American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypocalcemia, denosumab, parathyroid hormone, Humans, Neoplasms, ThyroidectomyKidney Case Conference: Nephrology Quiz and QuestionnaireKidney Case Conference: Nephrology Quiz and Questionnaireresearch-article20172017-04-03April 03, 201710.2215/CJN.132412161555-90411555-905X2017-03-08T05:06:56-08:002017-04-03Clinical Journal of the American Society of NephrologyKidney Case Conference: Nephrology Quiz and Questionnaire124696699
- IgA NephropathyIgA nephropathy (IgAN) is a leading cause of CKD and renal failure. Recent international collaborative efforts have led to important discoveries that have improved our understanding of some of the key steps involved in the immunopathogenesis of IgAN. Furthermore, establishment of multicenter networks has contributed to rigorous design and execution of clinical trials that have provided important insights regarding immunotherapy in IgAN. In this article, we review emerging developments in clinical and translational IgAN research and describe how these novel findings will influence future strategies to improve the outcome of patients with IgAN.10.2215/CJN.07420716Fri, 03 Feb 2017 07:56:24 GMT-08:00IgA NephropathyIgA nephropathy (IgAN) is a leading cause of CKD and renal failure. Recent international collaborative efforts have led to important discoveries that have improved our understanding of some of the key steps involved in the immunopathogenesis of IgAN. Furthermore, establishment of multicenter networks has contributed to rigorous design and execution of clinical trials that have provided important insights regarding immunotherapy in IgAN. In this article, we review emerging developments in clinical and translational IgAN research and describe how these novel findings will influence future strategies to improve the outcome of patients with IgAN.Rodrigues, Jennifer C.Haas, MarkReich, Heather N.2017-02-03T07:56:24-08:00doi:10.2215/CJN.07420716hwp:resource-id:clinjasn;12/4/677American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerulonephritis, IgA nephropathy, kidney, immunosuppression, review, corticosteroids, pathology, crescents, glomerulonephritis, IGA, humans, immunotherapy, renal insufficiency, renal insufficiency, chronic, translational medical researchGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-04-03April 03, 201710.2215/CJN.074207161555-90411555-905X2017-02-03T07:56:24-08:002017-04-03Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician124677686
- Association between Monocyte Count and Risk of Incident CKD and Progression to ESRD10.2215/CJN.09710916Mon, 27 Mar 2017 06:52:34 GMT-07:00Association between Monocyte Count and Risk of Incident CKD and Progression to ESRDBowe, BenjaminXie, YanXian, HongLi, TingtingAl-Aly, Ziyad2017-03-27T06:52:34-07:00doi:10.2215/CJN.09710916hwp:resource-id:clinjasn;12/4/603American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, end stage kidney disease, Epidemiology and outcomes, ESRD, renal function decline, renal progression, white blood cell, chemokine, chemokine receptor, eGFR decline, eGFR slope, creatinine, Disease Progression, Epidemiologic Studies, Follow-Up Studies, kidney, Kidney Failure, Chronic, kidney transplantation, Monocytes, renal dialysis, Renal Insufficiency, Chronic, United States, VeteransOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-04-03April 03, 201710.2215/CJN.097109161555-90411555-905X2017-03-27T06:52:34-07:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124603613
- Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986–201510.2215/CJN.10871016Tue, 21 Mar 2017 08:44:15 GMT-07:00Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986–2015O’Shaughnessy, Michelle M.Hogan, Susan L.Poulton, Caroline J.Falk, Ronald J.Singh, Harsharan K.Nickeleit, VolkerJennette, J. Charles2017-03-21T08:44:15-07:00doi:10.2215/CJN.10871016hwp:resource-id:clinjasn;12/4/614American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, clinical epidemiology, renal biopsy, histopathology, Adult, African Americans, Aged, Antibodies, Antineutrophil Cytoplasmic, Biopsy, Cross-Sectional Studies, Demography, Diabetic Nephropathies, Environmental Exposure, European Continental Ancestry Group, glomerulonephritis, Hispanic Americans, Humans, Kidney Glomerulus, lupus nephritis, Male, Middle Aged, Nephrosis, Lipoid, MeSH Browser: Southeastern United States Southeastern United StatesOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-04-03April 03, 201710.2215/CJN.108710161555-90411555-905X2017-03-21T08:44:15-07:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles1244614556623558
- Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients10.2215/CJN.08730816Mon, 13 Feb 2017 05:19:06 GMT-08:00Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis PatientsChang, Tae IkStreja, ElaniSoohoo, MelissaKim, Tae WooRhee, Connie M.Kovesdy, Csaba P.Kashyap, Moti L.Vaziri, Nosratola D.Kalantar-Zadeh, KamyarMoradi, Hamid2017-02-13T05:19:06-08:00doi:10.2215/CJN.08730816hwp:resource-id:clinjasn;12/4/591American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyLipids, triglyceride, high-density lipoprotein cholesterol, mortality, hemodialysis, Cholesterol, Cholesterol, HDL, Confidence Intervals, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Kidney Failure, Chronic, Lipoproteins, HDL, renal dialysis, risk factors, TriglyceridesOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-04-03April 03, 201710.2215/CJN.087308161555-90411555-905X2017-02-13T05:19:06-08:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124591602
- Association of TNF Receptor 2 and CRP with GFR Decline in the General Nondiabetic Population10.2215/CJN.09280916Thu, 02 Feb 2017 07:36:26 GMT-08:00Association of TNF Receptor 2 and CRP with GFR Decline in the General Nondiabetic PopulationSchei, JørgenStefansson, Vidar Tor NyborgEriksen, Bjørn OdvarJenssen, Trond GeirSolbu, Marit DahlWilsgaard, TomMelsom, Toralf2017-02-02T07:36:26-08:00doi:10.2215/CJN.09280916hwp:resource-id:clinjasn;12/4/624American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGFR decline, chronic kidney disease, soluble TNF receptors, Inflammation, Measured GFR, cytokines, aging, C-Reactive Protein, Cardiovascular Diseases, diabetes mellitus, Follow-Up Studies, glomerular filtration rate, TNFRSF1B protein, human, Humans, Iohexol, kidney, Kidney Function Tests, Logistic Models, Middle Aged, Odds Ratio, Receptors, Tumor Necrosis Factor, Type II, Renal Insufficiency, Chronic, Surveys and QuestionnairesOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-04-03April 03, 201710.2215/CJN.092809161555-90411555-905X2017-02-02T07:36:26-08:002017-04-03Clinical Journal of the American Society of NephrologyOriginal Articles124624634
- Commentary on Symptom Management of the Patient with CKD: The Role of Dialysis10.2215/CJN.11781116Wed, 01 Feb 2017 07:04:32 GMT-08:00Commentary on Symptom Management of the Patient with CKD: The Role of DialysisKestenbaum, BryanSeliger, Stephen L.2017-02-01T07:04:32-08:00doi:10.2215/CJN.11781116hwp:resource-id:clinjasn;12/4/694American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyFluid Therapy, Humans, Palliative Care, Renal Insufficiency, Chronic, renal dialysisCommentaryCommentaryarticle-commentary20172017-04-03April 03, 201710.2215/CJN.117811161555-90411555-905X2017-02-01T07:04:32-08:002017-04-03Clinical Journal of the American Society of NephrologyCommentary1244694687695693
- Symptom Management of the Patient with CKD: The Role of DialysisAs kidney disease progresses, patients often experience a variety of symptoms. A challenge for the nephrologist is to help determine if these symptoms are related to advancing CKD or the effect of various comorbidities and/or medications prescribed. The clinician also must decide the timing of dialysis initiation. The initiation of dialysis can have a variable effect on quality of life measures and the alleviation of uremic signs and symptoms, such as anorexia, fatigue, cognitive impairment, depressive symptoms, pruritus, and sleep disturbances. Thus, the initiation of dialysis should be a shared decision–making process among the patient, the family and the nephrology team; information should be provided, in an ongoing dialogue, to patients and their families concerning the benefits, risks, and effect of dialysis therapies on their lives.10.2215/CJN.01650216Wed, 01 Feb 2017 07:04:31 GMT-08:00Symptom Management of the Patient with CKD: The Role of DialysisAs kidney disease progresses, patients often experience a variety of symptoms. A challenge for the nephrologist is to help determine if these symptoms are related to advancing CKD or the effect of various comorbidities and/or medications prescribed. The clinician also must decide the timing of dialysis initiation. The initiation of dialysis can have a variable effect on quality of life measures and the alleviation of uremic signs and symptoms, such as anorexia, fatigue, cognitive impairment, depressive symptoms, pruritus, and sleep disturbances. Thus, the initiation of dialysis should be a shared decision–making process among the patient, the family and the nephrology team; information should be provided, in an ongoing dialogue, to patients and their families concerning the benefits, risks, and effect of dialysis therapies on their lives.Cabrera, Valerie JorgeHansson, JoniKliger, Alan S.Finkelstein, Fredric O.2017-02-01T07:04:31-08:00doi:10.2215/CJN.01650216hwp:resource-id:clinjasn;12/4/687American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinitiation of dialysis, uremic symptoms, Anorexia, Cognition Disorders, Decision Making, depression, Fatigue, Humans, nephrology, Palliative Care, Pruritus, quality of life, renal dialysis, Sleep Wake Disorders, Renal Insufficiency, ChronicEvidence-Based NephrologyEvidence-Based Nephrologyarticle-commentary20172017-04-03April 03, 201710.2215/CJN.016502161555-90411555-905X2017-02-01T07:04:31-08:002017-04-03Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology1244687694693695
- Managing Complexity in Older Patients with CKD10.2215/CJN.02340317Fri, 07 Apr 2017 01:00:29 GMT-07:00Managing Complexity in Older Patients with CKDWeiss, Jessica W.Boyd, Cynthia M.2017-04-07T13:00:29-07:00doi:10.2215/CJN.02340317hwp:resource-id:clinjasn;12/4/559American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, complexity, elderly, Humans, Renal Insufficiency, ChronicEditorialsEditorialseditorial20172017-04-03April 03, 201710.2215/CJN.023403171555-90411555-905X2017-04-07T13:00:29-07:002017-04-03Clinical Journal of the American Society of NephrologyEditorials1244559635561643
- Can Renal Biopsy Be Used to Estimate Total Nephron Number?10.2215/CJN.02290217Thu, 23 Mar 2017 07:14:53 GMT-07:00Can Renal Biopsy Be Used to Estimate Total Nephron Number?Charlton, Jennifer R.Abitbol, Carolyn L.2017-03-23T07:14:53-07:00doi:10.2215/CJN.02290217hwp:resource-id:clinjasn;12/4/553American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiopsy, Nephrectomy, NephronsEditorialsEditorialseditorial20172017-04-03April 03, 201710.2215/CJN.022902171555-90411555-905X2017-03-23T07:14:53-07:002017-04-03Clinical Journal of the American Society of NephrologyEditorials1244553585555590
- Donor Quality in the Eye of the Beholder: Interactions between Nonimmunologic Recipient and Donor Factors as Determinants of Graft Survival10.2215/CJN.02180217Thu, 30 Mar 2017 06:21:36 GMT-07:00Donor Quality in the Eye of the Beholder: Interactions between Nonimmunologic Recipient and Donor Factors as Determinants of Graft SurvivalFoster, Bethany J.Gupta, Indra Rani2017-03-30T06:21:36-07:00doi:10.2215/CJN.02180217hwp:resource-id:clinjasn;12/4/565American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygraft outcomes, donor factors, recipient factors, matching, Graft Survival, kidney transplantation, Tissue DonorsEditorialsEditorialseditorial20172017-04-03April 03, 201710.2215/CJN.021802171555-90411555-905X2017-03-30T06:21:36-07:002017-04-03Clinical Journal of the American Society of NephrologyEditorials1244565669567676
- Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and TreatmentAn absolute, supraphysiologic elevation in GFR is observed early in the natural history in 10%–67% and 6%–73% of patients with type 1 and type 2 diabetes, respectively. Moreover, at the single-nephron level, diabetes-related renal hemodynamic alterations—as an adaptation to reduction in functional nephron mass and/or in response to prevailing metabolic and (neuro)hormonal stimuli—increase glomerular hydraulic pressure and transcapillary convective flux of ultrafiltrate and macromolecules. This phenomenon, known as glomerular hyperfiltration, classically has been hypothesized to predispose to irreversible nephron damage, thereby contributing to initiation and progression of kidney disease in diabetes. However, dedicated studies with appropriate diagnostic measures and clinically relevant end points are warranted to confirm this assumption. In this review, we summarize the hitherto proposed mechanisms involved in diabetic hyperfiltration, focusing on ultrastructural, vascular, and tubular factors. Furthermore, we review available evidence on the clinical significance of hyperfiltration in diabetes and discuss currently available and emerging interventions that may attenuate this renal hemodynamic abnormality. The revived interest in glomerular hyperfiltration as a prognostic and pathophysiologic factor in diabetes may lead to improved and timely detection of (progressive) kidney disease, and could provide new therapeutic opportunities in alleviating the renal burden in this population.10.1681/ASN.2016060666Tue, 31 Jan 2017 05:27:40 GMT-08:00Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and TreatmentAn absolute, supraphysiologic elevation in GFR is observed early in the natural history in 10%–67% and 6%–73% of patients with type 1 and type 2 diabetes, respectively. Moreover, at the single-nephron level, diabetes-related renal hemodynamic alterations—as an adaptation to reduction in functional nephron mass and/or in response to prevailing metabolic and (neuro)hormonal stimuli—increase glomerular hydraulic pressure and transcapillary convective flux of ultrafiltrate and macromolecules. This phenomenon, known as glomerular hyperfiltration, classically has been hypothesized to predispose to irreversible nephron damage, thereby contributing to initiation and progression of kidney disease in diabetes. However, dedicated studies with appropriate diagnostic measures and clinically relevant end points are warranted to confirm this assumption. In this review, we summarize the hitherto proposed mechanisms involved in diabetic hyperfiltration, focusing on ultrastructural, vascular, and tubular factors. Furthermore, we review available evidence on the clinical significance of hyperfiltration in diabetes and discuss currently available and emerging interventions that may attenuate this renal hemodynamic abnormality. The revived interest in glomerular hyperfiltration as a prognostic and pathophysiologic factor in diabetes may lead to improved and timely detection of (progressive) kidney disease, and could provide new therapeutic opportunities in alleviating the renal burden in this population.Tonneijck, LennartMuskiet, Marcel H.A.Smits, Mark M.van Bommel, Erik J.Heerspink, Hiddo J.L.van Raalte, Daniël H.Joles, Jaap A.2017-01-31T05:27:40-08:00doi:10.1681/ASN.2016060666hwp:resource-id:jnephrol;28/4/1023American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes, diabetic nephropathy, glomerular hyperfiltration, glomerular filtration rate, albuminuriaUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-04-01April 201710.1681/ASN.20160606661046-66731533-34502017-01-31T05:27:40-08:002017-04Journal of the American Society of NephrologyUp Front Matters28410231039
- Insights into Diabetic Kidney Disease Using Urinary Proteomics and BioinformaticsA number of proteomic and peptidomic analyses of urine from diabetic subjects have been published in the quest for a biomarker that predicts progression of nephropathy. Less attention has been paid to the relationships between urinary proteins and the underlying biological processes revealed by the analyses. In this review, we focus on the biological processes identified by studying urinary proteins and protein-protein interactions at each stage of diabetic nephropathy to provide an overview of the events underlying progression of kidney disease reflected in the urine. In uncomplicated diabetes, proteomic/peptidomic analyses indicate that early activation of fibrotic pathways in the kidney occurs before the onset of microalbuminuria. In incipient nephropathy, when albumin excretion rates are abnormal, proteomic/peptidomic analyses suggest that changes in glomerular permselectivity and tubular reabsorption account, at least in part, for the proteins and peptides that appear in the urine. Finally, overt nephropathy is characterized by proteins involved in wound healing, ongoing fibrosis, and inflammation. These findings suggest that there is a spectrum of biological processes in the diabetic kidney and that assessing protein networks may be more informative than individual markers with respect to the stage of disease and the risk of progression.10.1681/ASN.2016091018Fri, 03 Feb 2017 08:05:16 GMT-08:00Insights into Diabetic Kidney Disease Using Urinary Proteomics and BioinformaticsA number of proteomic and peptidomic analyses of urine from diabetic subjects have been published in the quest for a biomarker that predicts progression of nephropathy. Less attention has been paid to the relationships between urinary proteins and the underlying biological processes revealed by the analyses. In this review, we focus on the biological processes identified by studying urinary proteins and protein-protein interactions at each stage of diabetic nephropathy to provide an overview of the events underlying progression of kidney disease reflected in the urine. In uncomplicated diabetes, proteomic/peptidomic analyses indicate that early activation of fibrotic pathways in the kidney occurs before the onset of microalbuminuria. In incipient nephropathy, when albumin excretion rates are abnormal, proteomic/peptidomic analyses suggest that changes in glomerular permselectivity and tubular reabsorption account, at least in part, for the proteins and peptides that appear in the urine. Finally, overt nephropathy is characterized by proteins involved in wound healing, ongoing fibrosis, and inflammation. These findings suggest that there is a spectrum of biological processes in the diabetic kidney and that assessing protein networks may be more informative than individual markers with respect to the stage of disease and the risk of progression.Van, Julie A.D.Scholey, James W.Konvalinka, Ana2017-02-03T08:05:16-08:00doi:10.1681/ASN.2016091018hwp:resource-id:jnephrol;28/4/1050American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologybioinformatics, diabetic kidney disease, urinary proteomicsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-04-01April 201710.1681/ASN.20160910181046-66731533-34502017-02-03T08:05:16-08:002017-04Journal of the American Society of NephrologyUp Front Matters28410501061
- Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An UpdateThe renin-angiotensin system (RAS) has a pivotal role in the maintenance of extracellular volume homeostasis and blood pressure through complex mechanisms. Apart from the well known systemic RAS, occurrence of a local RAS has been documented in multiple tissues, including the kidney. A large body of recent evidence from pharmacologic and genetic studies, particularly those using various transgenic approaches to manipulate intrarenal levels of RAS components, has established the important role of intrarenal RAS in hypertension. Recent studies have also begun to unravel the molecular mechanisms that govern intrarenal RAS activity. This local system is under the control of complex regulatory networks consisting of positive regulators of (pro)renin receptor, Wnt/β-catenin signaling, and PGE2/PGE2 receptor EP4 subtype, and negative regulators of Klotho, vitamin D receptor, and liver X receptors. This review highlights recent advances in defining the regulation and function of intrarenal RAS as a unique entity separate from systemic angiotensin II generation.10.1681/ASN.2016070734Thu, 02 Mar 2017 06:54:38 GMT-08:00Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An UpdateThe renin-angiotensin system (RAS) has a pivotal role in the maintenance of extracellular volume homeostasis and blood pressure through complex mechanisms. Apart from the well known systemic RAS, occurrence of a local RAS has been documented in multiple tissues, including the kidney. A large body of recent evidence from pharmacologic and genetic studies, particularly those using various transgenic approaches to manipulate intrarenal levels of RAS components, has established the important role of intrarenal RAS in hypertension. Recent studies have also begun to unravel the molecular mechanisms that govern intrarenal RAS activity. This local system is under the control of complex regulatory networks consisting of positive regulators of (pro)renin receptor, Wnt/β-catenin signaling, and PGE2/PGE2 receptor EP4 subtype, and negative regulators of Klotho, vitamin D receptor, and liver X receptors. This review highlights recent advances in defining the regulation and function of intrarenal RAS as a unique entity separate from systemic angiotensin II generation.Yang, TianxinXu, Chuanming2017-03-02T06:54:38-08:00doi:10.1681/ASN.2016070734hwp:resource-id:jnephrol;28/4/1040American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyintrarenal renin-angiotensin system, (pro)renin receptor, prostaglandin E4 receptors, Klotho, β-cateninUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-04-01April 201710.1681/ASN.20160707341046-66731533-34502017-03-02T06:54:38-08:002017-04Journal of the American Society of NephrologyUp Front Matters28410401049
- Polyomavirus Reactivation and Immune Responses to Kidney-Specific Self-Antigens in TransplantationHumoral immune responses against donor antigens are important determinants of long-term transplant outcomes. Reactivation of the polyomavirus BK has been associated with de novo antibodies against mismatched donor HLA antigens in kidney transplantation. The effect of polyomavirus reactivation (BK viremia or JC viruria) on antibodies to kidney-specific self-antigens is unknown. We previously reported excellent 5-year outcomes after minimization of immunosuppression for BK viremia and after no intervention for JC viruria. Here, we report the 10-year results of this trial (n=193) along with a nested case-control study (n=40) to explore associations between polyomavirus reactivation and immune responses to the self-antigens fibronectin (FN) and collagen type-IV (Col-IV). Consistent with 5-year findings, subjects taking tacrolimus, compared with those taking cyclosporin, had less acute rejection (11% versus 22%, P=0.05) and graft loss (9% versus 22%, P=0.01) along with better transplant function (eGFR 65±19 versus 50±24 ml/min per 1.73 m2, P<0.001) at 10 years. Subjects undergoing immunosuppression reduction for BK viremia had 10-year outcomes similar to those without viremia. In the case-control study, antibodies to FN/Col-IV were more prevalent during year 1 in subjects with polyomavirus reactivation than in those without reactivation (48% versus 11%, P=0.04). Subjects with antibodies to FN/Col-IV had more acute rejection than did those without these antibodies (38% versus 8%, P=0.02). These data demonstrate the long-term safety and effectiveness of minimizing immunosuppression to treat BK viremia. Furthermore, these results indicate that polyomavirus reactivation associates with immune responses to kidney-specific self-antigens that may increase the risk for acute rejection through unclear mechanisms.10.1681/ASN.2016030285Mon, 07 Nov 2016 05:44:12 GMT-08:00Polyomavirus Reactivation and Immune Responses to Kidney-Specific Self-Antigens in TransplantationHumoral immune responses against donor antigens are important determinants of long-term transplant outcomes. Reactivation of the polyomavirus BK has been associated with de novo antibodies against mismatched donor HLA antigens in kidney transplantation. The effect of polyomavirus reactivation (BK viremia or JC viruria) on antibodies to kidney-specific self-antigens is unknown. We previously reported excellent 5-year outcomes after minimization of immunosuppression for BK viremia and after no intervention for JC viruria. Here, we report the 10-year results of this trial (n=193) along with a nested case-control study (n=40) to explore associations between polyomavirus reactivation and immune responses to the self-antigens fibronectin (FN) and collagen type-IV (Col-IV). Consistent with 5-year findings, subjects taking tacrolimus, compared with those taking cyclosporin, had less acute rejection (11% versus 22%, P=0.05) and graft loss (9% versus 22%, P=0.01) along with better transplant function (eGFR 65±19 versus 50±24 ml/min per 1.73 m2, P<0.001) at 10 years. Subjects undergoing immunosuppression reduction for BK viremia had 10-year outcomes similar to those without viremia. In the case-control study, antibodies to FN/Col-IV were more prevalent during year 1 in subjects with polyomavirus reactivation than in those without reactivation (48% versus 11%, P=0.04). Subjects with antibodies to FN/Col-IV had more acute rejection than did those without these antibodies (38% versus 8%, P=0.02). These data demonstrate the long-term safety and effectiveness of minimizing immunosuppression to treat BK viremia. Furthermore, these results indicate that polyomavirus reactivation associates with immune responses to kidney-specific self-antigens that may increase the risk for acute rejection through unclear mechanisms.Seifert, Michael E.Gunasekaran, MuthukumarHorwedel, Timothy A.Daloul, ReemStorch, Gregory A.Mohanakumar, ThalachallourBrennan, Daniel C.2016-11-07T05:44:12-08:00doi:10.1681/ASN.2016030285hwp:resource-id:jnephrol;28/4/1314American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant outcomes, virology, immunosuppressionClinical ResearchClinical Researchresearch-article20172017-04-01April 201710.1681/ASN.20160302851046-66731533-34502016-11-07T05:44:12-08:002017-04Journal of the American Society of NephrologyClinical Research28413141325
- Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical TrialPrevious studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.10.1681/ASN.2016030378Thu, 01 Dec 2016 05:08:59 GMT-08:00Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical TrialPrevious studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.Manfredini, FabioMallamaci, FrancescaD’Arrigo, GraziellaBaggetta, RossellaBolignano, DavideTorino, ClaudiaLamberti, NicolaBertoli, SilvioCiurlino, DanieleRocca-Rey, LisaBarillà, AntonioBattaglia, YuriRapanà, Renato MarioZuccalà, AlessandroBonanno, GraziellaFatuzzo, PasqualeRapisarda, FrancescoRastelli, StefaniaFabrizi, FabrizioMessa, PiergiorgioDe Paola, LucianoLombardi, LuigiCupisti, AdamascoFuiano, GiorgioLucisano, GaetanoSummaria, ChiaraFelisatti, MichelePozzato, EnricoMalagoni, Anna MariaCastellino, PietroAucella, FilippoAbd ElHafeez, SamarProvenzano, Pasquale FabioTripepi, GiovanniCatizone, LuigiZoccali, Carmine2016-12-01T05:08:59-08:00doi:10.1681/ASN.2016030378hwp:resource-id:jnephrol;28/4/1259American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, CKD, exercise, physical functioning, rehabilitation, six minute walking testClinical EpidemiologyClinical Epidemiologyresearch-article20172017-04-01April 201710.1681/ASN.20160303781046-66731533-34502016-12-01T05:08:59-08:002017-04Journal of the American Society of NephrologyClinical Epidemiology28294471259i20281268i2028
- Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic SyndromeGlucocorticoid treatment is the first choice therapy for adults with minimal change nephrotic syndrome; however, this therapy associates with many adverse effects. Tacrolimus may be an alternative to conventional glucocorticoid therapy. To investigate this possibility, we conducted a prospective, randomized, controlled trial (WHO International Clinical Trials Registry Platform: ChiCTR-TRC-11001454) in eight renal units across China. We randomized enrolled patients with adult–onset minimal change nephrotic syndrome (n=119) to receive glucocorticoid therapy or tacrolimus after intravenous methylprednisolone (0.8 mg/kg per day) for 10 days. Patients received a conventional glucocorticoid regimen or tacrolimus monotherapy, starting with 0.05 mg/kg per day (target trough whole–blood level of 4–8 ng/ml) for 16–20 weeks and subsequently tapering over approximately 18 weeks. Remission occurred in 51 of 53 (96.2%; all complete remission) glucocorticoid-treated patients and 55 of 56 (98.3%; 52 complete and three partial remission) tacrolimus-treated patients (P=0.61 for remission; P=0.68 for complete remission). The groups had similar mean time to remission (P=0.55). Relapse occurred in 49.0% and 45.5% of the glucocorticoid- and tacrolimus-treated patients, respectively (P=0.71), with similar time to relapse (P=0.86). Seven (13.7%) glucocorticoid-treated and four (7.3%) tacrolimus-treated patients suffered frequent relapse (P=0.28); five glucocorticoid-treated and two tacrolimus-treated patients became drug dependent (P=0.26). Adverse events occurred more frequently in the glucocorticoid group (128 versus 81 in the tacrolimus group). Seven adverse events in the glucocorticoid group and two adverse events in the tacrolimus group were serious. Consequently, tacrolimus monotherapy after short–term intravenous methylprednisolone is noninferior to conventional glucocorticoid treatment for adult–onset minimal change nephrotic syndrome in this cohort.10.1681/ASN.2016030342Wed, 02 Nov 2016 01:07:16 GMT-07:00Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic SyndromeGlucocorticoid treatment is the first choice therapy for adults with minimal change nephrotic syndrome; however, this therapy associates with many adverse effects. Tacrolimus may be an alternative to conventional glucocorticoid therapy. To investigate this possibility, we conducted a prospective, randomized, controlled trial (WHO International Clinical Trials Registry Platform: ChiCTR-TRC-11001454) in eight renal units across China. We randomized enrolled patients with adult–onset minimal change nephrotic syndrome (n=119) to receive glucocorticoid therapy or tacrolimus after intravenous methylprednisolone (0.8 mg/kg per day) for 10 days. Patients received a conventional glucocorticoid regimen or tacrolimus monotherapy, starting with 0.05 mg/kg per day (target trough whole–blood level of 4–8 ng/ml) for 16–20 weeks and subsequently tapering over approximately 18 weeks. Remission occurred in 51 of 53 (96.2%; all complete remission) glucocorticoid-treated patients and 55 of 56 (98.3%; 52 complete and three partial remission) tacrolimus-treated patients (P=0.61 for remission; P=0.68 for complete remission). The groups had similar mean time to remission (P=0.55). Relapse occurred in 49.0% and 45.5% of the glucocorticoid- and tacrolimus-treated patients, respectively (P=0.71), with similar time to relapse (P=0.86). Seven (13.7%) glucocorticoid-treated and four (7.3%) tacrolimus-treated patients suffered frequent relapse (P=0.28); five glucocorticoid-treated and two tacrolimus-treated patients became drug dependent (P=0.26). Adverse events occurred more frequently in the glucocorticoid group (128 versus 81 in the tacrolimus group). Seven adverse events in the glucocorticoid group and two adverse events in the tacrolimus group were serious. Consequently, tacrolimus monotherapy after short–term intravenous methylprednisolone is noninferior to conventional glucocorticoid treatment for adult–onset minimal change nephrotic syndrome in this cohort.Li, XiayuLiu, ZhangsuoWang, LiWang, RongDing, GuohuaShi, WeiFu, PingHe, YaniCheng, GenyangWu, ShukunChen, BingDu, JuanYe, ZhimingTao, YeHuo, BengangLi, HengChen, Jianghua2016-11-02T13:07:16-07:00doi:10.1681/ASN.2016030342hwp:resource-id:jnephrol;28/4/1286American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytacrolimus, monotherapy, adults, minimal change nephrotic syndrome, clinical trialClinical ResearchClinical Researchresearch-article20172017-04-01April 201710.1681/ASN.20160303421046-66731533-34502016-11-02T13:07:16-07:002017-04Journal of the American Society of NephrologyClinical Research28412861295
- Intradialytic Cardiac Magnetic Resonance Imaging to Assess Cardiovascular Responses in a Short-Term Trial of Hemodiafiltration and HemodialysisHemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32–72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, and myocardial perfusion. Patients had mean±SEM ultrafiltration rates of 3.8±2.9 ml/kg per hour during HD and 4.4±2.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI.10.1681/ASN.2016060686Thu, 10 Nov 2016 09:07:18 GMT-08:00Intradialytic Cardiac Magnetic Resonance Imaging to Assess Cardiovascular Responses in a Short-Term Trial of Hemodiafiltration and HemodialysisHemodynamic stress during hemodialysis (HD) results in recurrent segmental ischemic injury (myocardial stunning) that drives cumulative cardiac damage. We performed a fully comprehensive study of the cardiovascular effect of dialysis sessions using intradialytic cardiac magnetic resonance imaging (MRI) to examine the comparative acute effects of standard HD versus hemodiafiltration (HDF) in stable patients. We randomly allocated 12 patients on HD (ages 32–72 years old) to either HD or HDF. Patients were stabilized on a modality for 2 weeks before undergoing serial cardiac MRI assessment during dialysis. Patients then crossed over to the other modality and were rescanned after 2 weeks. Cardiac MRI measurements included cardiac index, stroke volume index, global and regional contractile function (myocardial strain), coronary artery flow, and myocardial perfusion. Patients had mean±SEM ultrafiltration rates of 3.8±2.9 ml/kg per hour during HD and 4.4±2.5 ml/kg per hour during HDF (P=0.29), and both modalities provided a similar degree of cooling. All measures of systolic contractile function fell during HD and HDF, with partial recovery after dialysis. All patients experienced some degree of segmental left ventricular dysfunction, with severity proportional to ultrafiltration rate and BP reduction. Myocardial perfusion decreased significantly during HD and HDF. Treatment modality did not influence any of the cardiovascular responses to dialysis. In conclusion, in this randomized, crossover study, there was no significant difference in the cardiovascular response to HDF or HD with cooled dialysate as assessed with intradialytic MRI.Buchanan, CharlotteMohammed, AzharuddinCox, EleanorKöhler, KatrinCanaud, BernardTaal, Maarten W.Selby, Nicholas M.Francis, SusanMcIntyre, Chris W.2016-11-10T09:07:18-08:00doi:10.1681/ASN.2016060686hwp:resource-id:jnephrol;28/4/1269American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, hemodiafiltration, cardiac MRI, randomized controlled trials, myocardial stunningClinical ResearchClinical Researchresearch-article20172017-04-01April 201710.1681/ASN.20160606861046-66731533-34502016-11-10T09:07:18-08:002017-04Journal of the American Society of NephrologyClinical Research28441269101312771015
- Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older AdultsWithin monocytes, 1,25-dihydroxyvitamin D [1,25(OH)2D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 (FGF23) decreases 1,25(OH)2D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between FGF23 concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m2 [n=832] or urine albumin-to-creatinine ratio >30 mg/g [n=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma FGF23 concentration was 70 (interquartile range, 53–99) relative units per milliliter. In fully adjusted models, higher FGF23 concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of FGF23) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), FGF23 concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of FGF23, respectively (P=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma FGF23 concentrations independently associated with the risk of first infection-related hospitalization.10.1681/ASN.2016040401Thu, 10 Nov 2016 09:07:20 GMT-08:00Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older AdultsWithin monocytes, 1,25-dihydroxyvitamin D [1,25(OH)2D] is important for production of cathelicidins, which in turn, are critical for antibacterial action. Fibroblast growth factor 23 (FGF23) decreases 1,25(OH)2D production and thus, could increase infection risk. We examined this possibility in 3141 community-dwelling adults ages ≥65 years old at baseline in the Cardiovascular Health Study using Cox proportional hazards models to examine the association between FGF23 concentrations and first infection-related hospitalizations and determine whether associations differed by the presence of CKD (eGFR<60 ml/min per 1.73 m2 [n=832] or urine albumin-to-creatinine ratio >30 mg/g [n=577]). Mean±SD age of participants was 78±5 years old, 60% of participants were women, and the median plasma FGF23 concentration was 70 (interquartile range, 53–99) relative units per milliliter. In fully adjusted models, higher FGF23 concentrations associated with higher risk of first infection-related hospitalization (hazard ratio [HR], 1.11; 95% confidence interval [95% CI], 1.03 to 1.20 per doubling of FGF23) during a median follow-up of 8.6 years. In participants with or without CKD (defined by eGFR), FGF23 concentration associated with first infection-related hospitalization with HRs of 1.24 (95% CI, 1.08 to 1.42) and 1.06 (95% CI, 0.97 to 1.17) per doubling of FGF23, respectively (P=0.13 for interaction). Associations did not differ between groups when stratified by urine albumin-to-creatinine ratio. In sensitivity analyses, the addition of serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone, and 24,25-dihydroxyvitamin D did not meaningfully change the estimates. In conclusion, in community-dwelling older adults, higher plasma FGF23 concentrations independently associated with the risk of first infection-related hospitalization.Nowak, Kristen L.Bartz, Traci M.Dalrymple, Loriende Boer, Ian H.Kestenbaum, BryanShlipak, Michael G.Garimella, Pranav S.Ix, Joachim H.Chonchol, Michel2016-11-10T09:07:20-08:00doi:10.1681/ASN.2016040401hwp:resource-id:jnephrol;28/4/1239American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyaging, chronic kidney disease, clinical epidemiology, mineral metabolism, infectionClinical EpidemiologyClinical Epidemiologyresearch-article20172017-04-01April 201710.1681/ASN.20160404011046-66731533-34502016-11-10T09:07:20-08:002017-04Journal of the American Society of NephrologyClinical Epidemiology28441239i1246i
- IL-6 Trans–Signaling Links Inflammation with Angiogenesis in the Peritoneal MembraneVascular endothelial growth factor (VEGF) is implicated in the peritoneal membrane remodeling that limits ultrafiltration in patients on peritoneal dialysis (PD). Although the exact mechanism of VEGF induction in PD is unclear, VEGF concentrations in drained dialysate correlate with IL-6 levels, suggesting a link between these cytokines. Human peritoneal mesothelial cells (HPMCs), the main source of IL-6 and VEGF in the peritoneum, do not bear the cognate IL-6 receptor and are thus unable to respond to classic IL-6 receptor signaling. Here, we investigated whether VEGF release by HPMCs is controlled by IL-6 in combination with its soluble receptor (IL-6 trans–signaling). Although treatment with either IL-6 or soluble IL-6 receptor (sIL-6R) alone had no effect on VEGF production, stimulation of HPMCs with IL-6 in combination with sIL-6R promoted VEGF expression and secretion through a transcriptional mechanism involving STAT3 and SP4. Conditioned medium from HPMCs cultured with IL-6 and sIL-6R promoted angiogenic endothelial tube formation, which could be blocked by silencing SP4. In vivo, induction of peritoneal inflammation in wild-type and IL-6–deficient mice showed IL-6 involvement in the control of Sp4 and Vegf expression and new vessel formation, confirming the role of IL-6 trans–signaling in these processes. Taken together, these findings identify a novel mechanism linking IL-6 trans–signaling and angiogenesis in the peritoneal membrane.10.1681/ASN.2015101169Fri, 11 Nov 2016 06:20:20 GMT-08:00IL-6 Trans–Signaling Links Inflammation with Angiogenesis in the Peritoneal MembraneVascular endothelial growth factor (VEGF) is implicated in the peritoneal membrane remodeling that limits ultrafiltration in patients on peritoneal dialysis (PD). Although the exact mechanism of VEGF induction in PD is unclear, VEGF concentrations in drained dialysate correlate with IL-6 levels, suggesting a link between these cytokines. Human peritoneal mesothelial cells (HPMCs), the main source of IL-6 and VEGF in the peritoneum, do not bear the cognate IL-6 receptor and are thus unable to respond to classic IL-6 receptor signaling. Here, we investigated whether VEGF release by HPMCs is controlled by IL-6 in combination with its soluble receptor (IL-6 trans–signaling). Although treatment with either IL-6 or soluble IL-6 receptor (sIL-6R) alone had no effect on VEGF production, stimulation of HPMCs with IL-6 in combination with sIL-6R promoted VEGF expression and secretion through a transcriptional mechanism involving STAT3 and SP4. Conditioned medium from HPMCs cultured with IL-6 and sIL-6R promoted angiogenic endothelial tube formation, which could be blocked by silencing SP4. In vivo, induction of peritoneal inflammation in wild-type and IL-6–deficient mice showed IL-6 involvement in the control of Sp4 and Vegf expression and new vessel formation, confirming the role of IL-6 trans–signaling in these processes. Taken together, these findings identify a novel mechanism linking IL-6 trans–signaling and angiogenesis in the peritoneal membrane.Catar, RusanWitowski, JanuszZhu, NanLücht, ChristianDerrac Soria, AliciaUceda Fernandez, JavierChen, LeiJones, Simon A.Fielding, Ceri A.Rudolf, AndrasTopley, NicholasDragun, DuskaJörres, Achim2016-11-11T06:20:20-08:00doi:10.1681/ASN.2015101169hwp:resource-id:jnephrol;28/4/1188American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, peritoneal membrane, vascular endothelial growth factor, Cell SignalingBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20151011691046-66731533-34502016-11-11T06:20:20-08:002017-04Journal of the American Society of NephrologyBasic Research28411881199
- Constipation and Incident CKDConstipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m2, we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope <−10, −10 to <−5, and −5 to <−1 versus −1 to <0 ml/min per 1.73 m2 per year, 1.17; 95% CI, 1.14 to 1.20; 1.07; 95% CI, 1.04 to 1.09; and 1.01; 95% CI, 1.00 to 1.03, respectively). More severe constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms.10.1681/ASN.2016060656Thu, 10 Nov 2016 09:07:19 GMT-08:00Constipation and Incident CKDConstipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m2, we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope <−10, −10 to <−5, and −5 to <−1 versus −1 to <0 ml/min per 1.73 m2 per year, 1.17; 95% CI, 1.14 to 1.20; 1.07; 95% CI, 1.04 to 1.09; and 1.01; 95% CI, 1.00 to 1.03, respectively). More severe constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms.Sumida, KeiichiMolnar, Miklos Z.Potukuchi, Praveen K.Thomas, FridtjofLu, Jun LingMatsushita, KunihiroYamagata, KunihiroKalantar-Zadeh, KamyarKovesdy, Csaba P.2016-11-10T09:07:19-08:00doi:10.1681/ASN.2016060656hwp:resource-id:jnephrol;28/4/1248American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, end-stage renal disease, glomerular filtration rate, Epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20172017-04-01April 201710.1681/ASN.20160606561046-66731533-34502016-11-10T09:07:19-08:002017-04Journal of the American Society of NephrologyClinical Epidemiology28412481258
- Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA NephropathyThe TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody–producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis. In IgAN GC, antigen–experienced IgD−CD38+/−CD19+ B cells expressing a switched IgG/IgA B cell receptor produced APRIL. Notably, these GC B cells expressed mRNA encoding the common cleavable APRIL-α but also, the less frequent APRIL-δ/ζ mRNA, which encodes a protein that lacks a furin cleavage site and is, thus, the uncleavable membrane-bound form. Significant correlation between TLR9 and APRIL expression levels existed in tonsils from patients with IgAN. In vitro, repeated TLR9 stimulation induced APRIL expression in tonsillar B cells from control patients with tonsillitis. Clinically, aberrant APRIL expression in tonsillar GC correlated with greater proteinuria, and patients with IgAN and aberrant APRIL overexpression in tonsillar GC responded well to tonsillectomy, with parallel decreases in serum levels of galactose-deficient IgA1. Taken together, our data indicate that antibody disorders in IgAN associate with TLR9–induced aberrant expression of APRIL in tonsillar GC B cells.10.1681/ASN.2016050496Mon, 05 Dec 2016 08:14:53 GMT-08:00Toll-Like Receptor 9 Stimulation Induces Aberrant Expression of a Proliferation-Inducing Ligand by Tonsillar Germinal Center B Cells in IgA NephropathyThe TNF family member a proliferation-inducing ligand (APRIL; also known as TNFSF13), produced by myeloid cells, participates in the generation and survival of antibody–producing plasma cells. We studied the potential role of APRIL in the pathogenesis of IgA nephropathy (IgAN). We found that a significant proportion of germinal centers (GCs) in tonsils of patients with IgAN contained cells aberrantly producing APRIL, contributing to an overall upregulation of tonsillar APRIL expression compared with that in tonsils of control patients with tonsillitis. In IgAN GC, antigen–experienced IgD−CD38+/−CD19+ B cells expressing a switched IgG/IgA B cell receptor produced APRIL. Notably, these GC B cells expressed mRNA encoding the common cleavable APRIL-α but also, the less frequent APRIL-δ/ζ mRNA, which encodes a protein that lacks a furin cleavage site and is, thus, the uncleavable membrane-bound form. Significant correlation between TLR9 and APRIL expression levels existed in tonsils from patients with IgAN. In vitro, repeated TLR9 stimulation induced APRIL expression in tonsillar B cells from control patients with tonsillitis. Clinically, aberrant APRIL expression in tonsillar GC correlated with greater proteinuria, and patients with IgAN and aberrant APRIL overexpression in tonsillar GC responded well to tonsillectomy, with parallel decreases in serum levels of galactose-deficient IgA1. Taken together, our data indicate that antibody disorders in IgAN associate with TLR9–induced aberrant expression of APRIL in tonsillar GC B cells.Muto, MasahiroManfroi, BenoitSuzuki, HitoshiJoh, KensukeNagai, MasaakiWakai, SachikoRighini, ChristianMaiguma, MasayukiIzui, ShozoTomino, YasuhikoHuard, BertrandSuzuki, Yusuke2016-12-05T08:14:53-08:00doi:10.1681/ASN.2016050496hwp:resource-id:jnephrol;28/4/1227American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, immunology, cytokinesBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160504961046-66731533-34502016-12-05T08:14:53-08:002017-04Journal of the American Society of NephrologyBasic Research28441227i1238i
- A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal DysfunctionIgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody–producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy–proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin–converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8–2.4) mg/dl, and proteinuria was 2.1 (0.6–5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose–deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.10.1681/ASN.2016060640Mon, 07 Nov 2016 05:44:10 GMT-08:00A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal DysfunctionIgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody–producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy–proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin–converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8–2.4) mg/dl, and proteinuria was 2.1 (0.6–5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose–deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.Lafayette, Richard A.Canetta, Pietro A.Rovin, Brad H.Appel, Gerald B.Novak, JanNath, Karl A.Sethi, SanjeevTumlin, James A.Mehta, KshamaHogan, MarieErickson, StephenJulian, Bruce A.Leung, NelsonEnders, Felicity T.Brown, RhubellKnoppova, BarboraHall, StacyFervenza, Fernando C.2016-11-07T05:44:10-08:00doi:10.1681/ASN.2016060640hwp:resource-id:jnephrol;28/4/1306American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, proteinuria, rituximabClinical ResearchClinical Researchresearch-article20172017-04-01April 201710.1681/ASN.20160606401046-66731533-34502016-11-07T05:44:10-08:002017-04Journal of the American Society of NephrologyClinical Research28441306i1313i
- Arterial and Cellular Inflammation in Patients with CKDCKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts future cardiovascular events in the general population. We hypothesized that subjects with CKD have increased arterial and cellular inflammation, reflected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET/CT) of the arterial wall and a migratory phenotype of monocytes. We assessed 18F-FDG uptake in the arterial wall in 14 patients with CKD (mean±SD age: 59±5 years, mean±SD eGFR: 37±12 ml/min per 1.73 m2) but without cardiovascular diseases, diabetes, or inflammatory conditions and in 14 control subjects (mean age: 60±11 years, mean eGFR: 86±16 ml/min per 1.73 m2). Compared with controls, patients with CKD showed increased arterial inflammation, quantified as target-to-background ratio (TBR) in the aorta (TBRmax: CKD, 3.14±0.70 versus control, 2.12±0.27; P=0.001) and the carotid arteries (TBRmax: CKD, 2.45±0.65 versus control, 1.66±0.27; P<0.001). Characterization of circulating monocytes using flow cytometry revealed increased chemokine receptor expression and enhanced transendothelial migration capacity in patients with CKD compared with controls. In conclusion, this increased arterial wall inflammation, observed in patients with CKD but without overt atherosclerotic disease and with few traditional risk factors, may contribute to the increased cardiovascular risk associated with CKD. The concomitant elevation of monocyte activity may provide novel therapeutic targets for attenuating this inflammation and thereby preventing CKD-associated cardiovascular disease.10.1681/ASN.2016030317Mon, 31 Oct 2016 09:16:40 GMT-07:00Arterial and Cellular Inflammation in Patients with CKDCKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts future cardiovascular events in the general population. We hypothesized that subjects with CKD have increased arterial and cellular inflammation, reflected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET/CT) of the arterial wall and a migratory phenotype of monocytes. We assessed 18F-FDG uptake in the arterial wall in 14 patients with CKD (mean±SD age: 59±5 years, mean±SD eGFR: 37±12 ml/min per 1.73 m2) but without cardiovascular diseases, diabetes, or inflammatory conditions and in 14 control subjects (mean age: 60±11 years, mean eGFR: 86±16 ml/min per 1.73 m2). Compared with controls, patients with CKD showed increased arterial inflammation, quantified as target-to-background ratio (TBR) in the aorta (TBRmax: CKD, 3.14±0.70 versus control, 2.12±0.27; P=0.001) and the carotid arteries (TBRmax: CKD, 2.45±0.65 versus control, 1.66±0.27; P<0.001). Characterization of circulating monocytes using flow cytometry revealed increased chemokine receptor expression and enhanced transendothelial migration capacity in patients with CKD compared with controls. In conclusion, this increased arterial wall inflammation, observed in patients with CKD but without overt atherosclerotic disease and with few traditional risk factors, may contribute to the increased cardiovascular risk associated with CKD. The concomitant elevation of monocyte activity may provide novel therapeutic targets for attenuating this inflammation and thereby preventing CKD-associated cardiovascular disease.Bernelot Moens, Sophie J.Verweij, Simone L.van der Valk, Fleur M.van Capelleveen, Julian C.Kroon, JeffreyVersloot, MirandaVerberne, Hein J.Marquering, Henk A.Duivenvoorden, RaphaëlVogt, LiffertStroes, Erik S.G.2016-10-31T09:16:40-07:00doi:10.1681/ASN.2016030317hwp:resource-id:jnephrol;28/4/1278American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, Chronic inflammation, chemokine receptorClinical ResearchClinical Researchresearch-article20172017-04-01April 201710.1681/ASN.20160303171046-66731533-34502016-10-31T09:16:40-07:002017-04Journal of the American Society of NephrologyClinical Research28412781285
- Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury. MR blockade by the novel nonsteroidal MR antagonist, finerenone, or genetic deletion of MR in SMCs associated with weaker oxidative stress production. Moreover, ischemic kidneys had higher levels of Rac1-GTP, required for NADPH oxidase activation, than sham control kidneys, and genetic deletion of Rac1 in SMCs protected against AKI. Furthermore, genetic deletion of MR in SMCs blunted the production of Rac1-GTP after IR. Pharmacologic inhibition of MR also prevented AKI induced by IR in the Large White pig. Altogether, we show that MR antagonism, or deletion of the MR gene in SMCs, limited the renal injury induced by IR through effects on Rac1-mediated MR signaling. The benefits of MR antagonism in the pig provide a rational basis for future clinical trials assessing the benefits of this approach in patients with IR-mediated AKI.10.1681/ASN.2016040477Fri, 13 Jan 2017 12:20:55 GMT-08:00Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury. MR blockade by the novel nonsteroidal MR antagonist, finerenone, or genetic deletion of MR in SMCs associated with weaker oxidative stress production. Moreover, ischemic kidneys had higher levels of Rac1-GTP, required for NADPH oxidase activation, than sham control kidneys, and genetic deletion of Rac1 in SMCs protected against AKI. Furthermore, genetic deletion of MR in SMCs blunted the production of Rac1-GTP after IR. Pharmacologic inhibition of MR also prevented AKI induced by IR in the Large White pig. Altogether, we show that MR antagonism, or deletion of the MR gene in SMCs, limited the renal injury induced by IR through effects on Rac1-mediated MR signaling. The benefits of MR antagonism in the pig provide a rational basis for future clinical trials assessing the benefits of this approach in patients with IR-mediated AKI.Barrera-Chimal, JonatanAndré-Grégoire, GwennanNguyen dinh Cat, AurelieLechner, Sebastian M.Cau, JérômePrince, SoniaKolkhof, PeterLoirand, GervaiseSauzeau, VincentHauet, ThierryJaisser, Frédéric2017-01-13T12:20:55-08:00doi:10.1681/ASN.2016040477hwp:resource-id:jnephrol;28/4/1216American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, oxidative stress, vascular, aldosteroneBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160404771046-66731533-34502017-01-13T12:20:55-08:002017-04Journal of the American Society of NephrologyBasic Research28412161226
- Mitochondrial NADP+-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion InjuryMitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult.10.1681/ASN.2016030349Mon, 07 Nov 2016 05:44:13 GMT-08:00Mitochondrial NADP+-Dependent Isocitrate Dehydrogenase Deficiency Exacerbates Mitochondrial and Cell Damage after Kidney Ischemia-Reperfusion InjuryMitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate, synthesizing NADPH, which is essential for mitochondrial redox balance. Ischemia-reperfusion (I/R) is one of most common causes of AKI. I/R disrupts the mitochondrial redox balance, resulting in oxidative damage to mitochondria and cells. Here, we investigated the role of IDH2 in I/R-induced AKI. I/R injury in mice led to the inactivation of IDH2 in kidney tubule cells. Idh2 gene deletion exacerbated the I/R-induced increase in plasma creatinine and BUN levels and the histologic evidence of tubule injury, and augmented the reduction of NADPH levels and the increase in oxidative stress observed in the kidney after I/R. Furthermore, Idh2 gene deletion exacerbated I/R-induced mitochondrial dysfunction and morphologic fragmentation, resulting in severe apoptosis in kidney tubule cells. In cultured mouse kidney proximal tubule cells, Idh2 gene downregulation enhanced the mitochondrial damage and apoptosis induced by treatment with hydrogen peroxide. This study demonstrates that Idh2 gene deletion exacerbates mitochondrial damage and tubular cell death via increased oxidative stress, suggesting that IDH2 is an important mitochondrial antioxidant enzyme that protects cells from I/R insult.Han, Sang JunJang, Hee-SeongNoh, Mi RaKim, JinuKong, Min JungKim, Jee InPark, Jeen-WooPark, Kwon Moo2016-11-07T05:44:13-08:00doi:10.1681/ASN.2016030349hwp:resource-id:jnephrol;28/4/1200American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyMitochondrial isocitrate dehydrogenase, Kidney ischemia reperfusion, NADPH, Reactive oxidative speciesBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160303491046-66731533-34502016-11-07T05:44:13-08:002017-04Journal of the American Society of NephrologyBasic Research28412001215
- Gene-Specific DNA Methylation Changes Predict Remission in Patients with ANCA-Associated VasculitisANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate with changes in epigenetic silencing modifications. Altered histone modifications implicated in gene silencing associate with aberrant autoantigen expression. To establish a link between DNA methylation, a model epigenetic gene silencing modification, and autoantigen gene expression and disease status in ANCA-associated vasculitis, we measured gene-specific DNA methylation of the autoantigen genes myeloperoxidase (MPO) and proteinase 3 (PRTN3) in leukocytes of patients with ANCA-associated vasculitis observed longitudinally (n=82) and of healthy controls (n=32). Patients with active disease demonstrated hypomethylation of MPO and PRTN3 and increased expression of the autoantigens; in remission, DNA methylation generally increased. Longitudinal analysis revealed that patients with ANCA-associated vasculitis could be divided into two groups, on the basis of whether DNA methylation increased or decreased from active disease to remission. In patients with increased DNA methylation, MPO and PRTN3 expression correlated with DNA methylation. Kaplan–Meier estimate of relapse revealed patients with increased DNA methylation at the PRTN3 promoter had a significantly greater probability of a relapse-free period (P<0.001), independent of ANCA serotype. Patients with decreased DNA methylation at the PRTN3 promoter had a greater risk of relapse (hazard ratio, 4.55; 95% confidence interval, 2.09 to 9.91). Thus, changes in the DNA methylation status of the PRTN3 promoter may predict the likelihood of stable remission and explain autoantigen gene regulation.10.1681/ASN.2016050548Mon, 07 Nov 2016 05:44:11 GMT-08:00Gene-Specific DNA Methylation Changes Predict Remission in Patients with ANCA-Associated VasculitisANCA-associated vasculitis is an autoimmune condition characterized by vascular inflammation and organ damage. Pharmacologically induced remission of this condition is complicated by relapses. Potential triggers of relapse are immunologic challenges and environmental insults, both of which associate with changes in epigenetic silencing modifications. Altered histone modifications implicated in gene silencing associate with aberrant autoantigen expression. To establish a link between DNA methylation, a model epigenetic gene silencing modification, and autoantigen gene expression and disease status in ANCA-associated vasculitis, we measured gene-specific DNA methylation of the autoantigen genes myeloperoxidase (MPO) and proteinase 3 (PRTN3) in leukocytes of patients with ANCA-associated vasculitis observed longitudinally (n=82) and of healthy controls (n=32). Patients with active disease demonstrated hypomethylation of MPO and PRTN3 and increased expression of the autoantigens; in remission, DNA methylation generally increased. Longitudinal analysis revealed that patients with ANCA-associated vasculitis could be divided into two groups, on the basis of whether DNA methylation increased or decreased from active disease to remission. In patients with increased DNA methylation, MPO and PRTN3 expression correlated with DNA methylation. Kaplan–Meier estimate of relapse revealed patients with increased DNA methylation at the PRTN3 promoter had a significantly greater probability of a relapse-free period (P<0.001), independent of ANCA serotype. Patients with decreased DNA methylation at the PRTN3 promoter had a greater risk of relapse (hazard ratio, 4.55; 95% confidence interval, 2.09 to 9.91). Thus, changes in the DNA methylation status of the PRTN3 promoter may predict the likelihood of stable remission and explain autoantigen gene regulation.Jones, Britta E.Yang, JiajinMuthigi, AkhilHogan, Susan L.Hu, YichunStarmer, JoshuaHenderson, Candace D.Poulton, Caroline J.Brant, Elizabeth J.Pendergraft, William F.Jennette, J. CharlesFalk, Ronald J.Ciavatta, Dominic J.2016-11-07T05:44:11-08:00doi:10.1681/ASN.2016050548hwp:resource-id:jnephrol;28/4/1175American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, vasculitis, gene expression, DNA methylation, epigeneticsBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160505481046-66731533-34502016-11-07T05:44:11-08:002017-04Journal of the American Society of NephrologyBasic Research28441175101111871013
- In Remembrance of Dr. Jared James Grantham, JASN’s Founding Editor-in-Chief10.1681/ASN.2017010111Thu, 16 Mar 2017 07:18:01 GMT-07:00In Remembrance of Dr. Jared James Grantham, JASN’s Founding Editor-in-ChiefNath, Karl A.O’Brien, Bonnie2017-03-16T07:18:01-07:00doi:10.1681/ASN.2017010111hwp:resource-id:jnephrol;28/4/1005American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyJared Grantham, obituary, in memoriamUp Front MattersObituaryUp Front MattersObituaryresearch-article20172017-04-01April 201710.1681/ASN.20170101111046-66731533-34502017-03-16T07:18:01-07:002017-04Journal of the American Society of NephrologyUp Front Matters28410051007
- APOL1-G1 in Nephrocytes Induces Hypertrophy and Accelerates Cell DeathPeople of African ancestry carrying certain APOL1 mutant alleles are at elevated risk of developing renal diseases. However, the mechanisms underlying APOL1-associated renal diseases are unknown. Because the APOL1 gene is unique to humans and some primates, new animal models are needed to understand the function of APOL1 in vivo. We generated transgenic Drosophila fly lines expressing the human APOL1 wild type allele (G0) or the predominant APOL1 risk allele (G1) in different tissues. Ubiquitous expression of APOL1 G0 or G1 in Drosophila induced lethal phenotypes, and G1 was more toxic than was G0. Selective expression of the APOL1 G0 or G1 transgene in nephrocytes, fly cells homologous to mammalian podocytes, induced increased endocytic activity and accumulation of hemolymph proteins, dextran particles, and silver nitrate. As transgenic flies with either allele aged, nephrocyte function declined, cell size increased, and nephrocytes died prematurely. Compared with G0-expressing cells, however, G1-expressing cells showed more dramatic phenotypes, resembling those observed in cultured mammalian podocytes overexpressing APOL1-G1. Expressing the G0 or G1 APOL1 transgene in nephrocytes also impaired the acidification of organelles. We conclude that expression of an APOL1 transgene initially enhances nephrocyte function, causing hypertrophy and subsequent cell death. This new Drosophila model uncovers a novel mechanism by which upregulated expression of APOL1-G1 could precipitate renal disease in humans. Furthermore, this model may facilitate the identification of APOL1–interacting molecules that could serve as new drug targets to treat APOL1-associated renal diseases.10.1681/ASN.2016050550Fri, 18 Nov 2016 11:00:32 GMT-08:00APOL1-G1 in Nephrocytes Induces Hypertrophy and Accelerates Cell DeathPeople of African ancestry carrying certain APOL1 mutant alleles are at elevated risk of developing renal diseases. However, the mechanisms underlying APOL1-associated renal diseases are unknown. Because the APOL1 gene is unique to humans and some primates, new animal models are needed to understand the function of APOL1 in vivo. We generated transgenic Drosophila fly lines expressing the human APOL1 wild type allele (G0) or the predominant APOL1 risk allele (G1) in different tissues. Ubiquitous expression of APOL1 G0 or G1 in Drosophila induced lethal phenotypes, and G1 was more toxic than was G0. Selective expression of the APOL1 G0 or G1 transgene in nephrocytes, fly cells homologous to mammalian podocytes, induced increased endocytic activity and accumulation of hemolymph proteins, dextran particles, and silver nitrate. As transgenic flies with either allele aged, nephrocyte function declined, cell size increased, and nephrocytes died prematurely. Compared with G0-expressing cells, however, G1-expressing cells showed more dramatic phenotypes, resembling those observed in cultured mammalian podocytes overexpressing APOL1-G1. Expressing the G0 or G1 APOL1 transgene in nephrocytes also impaired the acidification of organelles. We conclude that expression of an APOL1 transgene initially enhances nephrocyte function, causing hypertrophy and subsequent cell death. This new Drosophila model uncovers a novel mechanism by which upregulated expression of APOL1-G1 could precipitate renal disease in humans. Furthermore, this model may facilitate the identification of APOL1–interacting molecules that could serve as new drug targets to treat APOL1-associated renal diseases.Fu, YulongZhu, Jun-yiRichman, AdamZhang, YiXie, XuefangDas, Jharna R.Li, JinliangRay, Patricio E.Han, Zhe2016-11-18T11:00:32-08:00doi:10.1681/ASN.2016050550hwp:resource-id:jnephrol;28/4/1106American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, genetic renal disease, cell biology and structure, cell survivalBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160505501046-66731533-34502016-11-18T11:00:32-08:002017-04Journal of the American Society of NephrologyBasic Research28441106100811161011
- This Month’s Highlights10.1681/ASN.2016121379Fri, 31 Mar 2017 01:00:45 GMT-07:00This Month’s HighlightsAmerican Society of Nephrology2017-03-31T13:00:45-07:00doi:10.1681/ASN.2016121379hwp:resource-id:jnephrol;28/4/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsresearch-article20172017-04-01April 201710.1681/ASN.20161213791046-66731533-34502017-03-31T13:00:45-07:002017-04Journal of the American Society of NephrologyThis Month’s Highlights284444444i114511621227123912591306i116111741238124612681313
- Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble KlothoαKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice. Stable delivery of adeno-associated virus (AAV) expressing cKL to diabetic endothelial nitric oxide synthase–deficient mice or αKL-null mice reduced serum phosphate levels. Acute injection of recombinant cKL downregulated the renal sodium-phosphate cotransporter Npt2a in αKL-null mice supporting direct actions of cKL in the absence of mKL. αKL-null mice with sustained AAV-cKL expression had a 74%–78% reduction in aorta mineral content and a 72%–77% reduction in mineral volume compared with control-treated counterparts (P<0.01). Treatment of UMR-106 osteoblastic cells with cKL + FGF23 increased the phosphorylation of extracellular signal–regulated kinase 1/2 and induced Fgf23 expression. CRISPR/Cas9-mediated deletion of fibroblast growth factor receptor 1 (FGFR1) or pretreatment with inhibitors of mitogen–activated kinase kinase 1 or FGFR ablated these responses. In summary, sustained cKL treatment reduced hyperphosphatemia in a mouse model of CKD-mineral bone disorder, and it reduced hyperphosphatemia and prevented VC in mice without endogenous αKL. Furthermore, cKL stimulated Fgf23 in an FGFR1-dependent manner in bone cells. Collectively, these findings indicate that cKL has mKL-independent activity and suggest the potential for enhancing cKL activity in diseases of hyperphosphatemia with associated VC.10.1681/ASN.2015111266Fri, 11 Nov 2016 06:20:19 GMT-08:00Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble KlothoαKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice. Stable delivery of adeno-associated virus (AAV) expressing cKL to diabetic endothelial nitric oxide synthase–deficient mice or αKL-null mice reduced serum phosphate levels. Acute injection of recombinant cKL downregulated the renal sodium-phosphate cotransporter Npt2a in αKL-null mice supporting direct actions of cKL in the absence of mKL. αKL-null mice with sustained AAV-cKL expression had a 74%–78% reduction in aorta mineral content and a 72%–77% reduction in mineral volume compared with control-treated counterparts (P<0.01). Treatment of UMR-106 osteoblastic cells with cKL + FGF23 increased the phosphorylation of extracellular signal–regulated kinase 1/2 and induced Fgf23 expression. CRISPR/Cas9-mediated deletion of fibroblast growth factor receptor 1 (FGFR1) or pretreatment with inhibitors of mitogen–activated kinase kinase 1 or FGFR ablated these responses. In summary, sustained cKL treatment reduced hyperphosphatemia in a mouse model of CKD-mineral bone disorder, and it reduced hyperphosphatemia and prevented VC in mice without endogenous αKL. Furthermore, cKL stimulated Fgf23 in an FGFR1-dependent manner in bone cells. Collectively, these findings indicate that cKL has mKL-independent activity and suggest the potential for enhancing cKL activity in diseases of hyperphosphatemia with associated VC.Hum, Julia M.O’Bryan, Linda M.Tatiparthi, Arun K.Cass, Taryn A.Clinkenbeard, Erica L.Cramer, Martin S.Bhaskaran, ManojJohnson, Robert L.Wilson, Jonathan M.Smith, Rosamund C.White, Kenneth E.2016-11-11T06:20:19-08:00doi:10.1681/ASN.2015111266hwp:resource-id:jnephrol;28/4/1162American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyFGF23, hyperphosphatemia, alpha-klotho, osteocyte, bone, db/db-eNOSBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20151112661046-66731533-34502016-11-11T06:20:19-08:002017-04Journal of the American Society of NephrologyBasic Research28441162i1174i
- Epigenetic Modifications in ANCA-Associated Vasculitis: Potential for Insights into Disease Pathogenesis and Prediction of Outcome?10.1681/ASN.2016111260Tue, 03 Jan 2017 06:06:01 GMT-08:00Epigenetic Modifications in ANCA-Associated Vasculitis: Potential for Insights into Disease Pathogenesis and Prediction of Outcome?Oates, ThomasSalama, Alan D.2017-01-03T06:06:01-08:00doi:10.1681/ASN.2016111260hwp:resource-id:jnephrol;28/4/1011American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, vasculitis, epigenetics, glomerulonephritisUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-04-01April 201710.1681/ASN.20161112601046-66731533-34502017-01-03T06:06:01-08:002017-04Journal of the American Society of NephrologyUp Front Matters28441011117510131187
- APOL1–Mediated Cell Injury Involves Disruption of Conserved Trafficking ProcessesAPOL1 harbors C–terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub–Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D. melanogaster, with no effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human disease risk. We also observed a congruent pattern of cellular damage with tissue-specific expression of APOL1. In particular, expression of APOL1 risk variants in D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic tracer atrial natriuretic factor-red fluorescent protein at early stages and nephrocyte loss at later stages. We also observed differential toxicity of the APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae, including impairment of vacuole acidification. Yeast strains defective in endosomal trafficking or organelle acidification but not those defective in autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes. This finding should facilitate the identification of cell injury pathways and corresponding therapeutic targets of interest in these amenable experimental platforms.10.1681/ASN.2016050546Fri, 18 Nov 2016 11:00:33 GMT-08:00APOL1–Mediated Cell Injury Involves Disruption of Conserved Trafficking ProcessesAPOL1 harbors C–terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub–Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D. melanogaster, with no effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human disease risk. We also observed a congruent pattern of cellular damage with tissue-specific expression of APOL1. In particular, expression of APOL1 risk variants in D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic tracer atrial natriuretic factor-red fluorescent protein at early stages and nephrocyte loss at later stages. We also observed differential toxicity of the APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae, including impairment of vacuole acidification. Yeast strains defective in endosomal trafficking or organelle acidification but not those defective in autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes. This finding should facilitate the identification of cell injury pathways and corresponding therapeutic targets of interest in these amenable experimental platforms.Kruzel-Davila, EttyShemer, RevitalOfir, AyalaBavli-Kertselli, IraDarlyuk-Saadon, IlonaOren-Giladi, PazitWasser, Walter G.Magen, DaniellaZaknoun, EidSchuldiner, MayaSalzberg, AdiKornitzer, DanielMarelja, ZvonimirSimons, MatiasSkorecki, Karl2016-11-18T11:00:33-08:00doi:10.1681/ASN.2016050546hwp:resource-id:jnephrol;28/4/1117American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyendocytic trafficking, Apolipoprotein L1, chronic kidney disease, nephrocyte, acidificationBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160505461046-66731533-34502016-11-18T11:00:33-08:002017-04Journal of the American Society of NephrologyBasic Research28441117100811301011
- Changes in Cardiac Output and Perfusion during Hemodialysis and Hemodiafiltration Treatments Determined by Cardiac Magnetic Resonance Imaging10.1681/ASN.2016111257Thu, 09 Feb 2017 05:17:48 GMT-08:00Changes in Cardiac Output and Perfusion during Hemodialysis and Hemodiafiltration Treatments Determined by Cardiac Magnetic Resonance ImagingBlankestijn, Peter J.Davenport, Andrew2017-02-09T05:17:48-08:00doi:10.1681/ASN.2016111257hwp:resource-id:jnephrol;28/4/1013American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, Hemodynamics and Vascular Regulation, hemodiafiltration, magnetic resonance imaging, cardiac functionUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-04-01April 201710.1681/ASN.20161112571046-66731533-34502017-02-09T05:17:48-08:002017-04Journal of the American Society of NephrologyUp Front Matters28441013126910151277
- Low Sodium Diet, Vitamin D, or Both for RAASi-Resistant, Residual, Proteinuria in CKD? The ViRTUE Trial Points the Way Forward but Is Not the Last Word10.1681/ASN.2016121321Tue, 28 Feb 2017 07:21:56 GMT-08:00Low Sodium Diet, Vitamin D, or Both for RAASi-Resistant, Residual, Proteinuria in CKD? The ViRTUE Trial Points the Way Forward but Is Not the Last WordGoldsmith, DavidThadhani, Ravi I.2017-02-28T07:21:56-08:00doi:10.1681/ASN.2016121321hwp:resource-id:jnephrol;28/4/1016American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyVitamin D, proteinuria, TrialUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-04-01April 201710.1681/ASN.20161213211046-66731533-34502017-02-28T07:21:56-08:002017-04Journal of the American Society of NephrologyUp Front Matters28441016129610191305
- Most ApoL1 Is Secreted by the LiverTwo coding sequence variants in the APOL1 gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1. Our findings confirm that the liver is indeed the main source of circulating ApoL1. However, the liver is not the sole source of circulating ApoL1, because we found that residual amounts of native ApoL1 continued to circulate in the blood, even after the liver transplant.10.1681/ASN.2016040441Thu, 08 Dec 2016 06:53:10 GMT-08:00Most ApoL1 Is Secreted by the LiverTwo coding sequence variants in the APOL1 gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1. Our findings confirm that the liver is indeed the main source of circulating ApoL1. However, the liver is not the sole source of circulating ApoL1, because we found that residual amounts of native ApoL1 continued to circulate in the blood, even after the liver transplant.Shukha, KhuloudMueller, Jessica L.Chung, Raymond T.Curry, Michael P.Friedman, David J.Pollak, Martin R.Berg, Anders H.2016-12-08T06:53:10-08:00doi:10.1681/ASN.2016040441hwp:resource-id:jnephrol;28/4/1079American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, transplantation, apoptosis, Pathophysiology of Renal Disease and Progression, kidney diseaseBrief CommunicationsBrief Communicationsbrief-report20172017-04-01April 201710.1681/ASN.20160404411046-66731533-34502016-12-08T06:53:10-08:002017-04Journal of the American Society of NephrologyBrief Communications28410791083
- Sphingosine Kinase 2 Deficiency Attenuates Kidney Fibrosis via IFN-γMaladaptive repair after AKI may lead to progressive fibrosis and decline in kidney function. Sphingosine 1-phosphate has an important role in kidney injury and pleiotropic effects in fibrosis. We investigated the involvement of sphingosine kinase 1 and 2 (SphK1 and SphK2), which phosphorylate sphingosine to produce sphingosine 1-phosphate, in kidney fibrosis induced by folic acid (FA) or unilateral ischemia-reperfusion injury. Analysis of Masson trichrome staining and fibrotic marker protein and mRNA expression 14 days after AKI revealed that wild-type (WT) and Sphk1−/− mice exhibited more kidney fibrosis than Sphk2−/− mice. Furthermore, kidneys of FA-treated WT and Sphk1−/− mice had greater immune cell infiltration and expression of fibrotic and inflammatory markers than kidneys of FA-treated Sphk2−/− mice. In contrast, kidneys of Sphk2−/− mice exhibited greater expression of Ifng and IFN-γ–responsive genes (Cxcl9 and Cxcl10) than kidneys of WT or Sphk1−/− mice did at this time point. Splenic T cells from untreated Sphk2−/− mice were hyperproliferative and produced more IFN-γ than did those of WT or Sphk1−/− mice. IFN-γ blocking antibody administered to Sphk2−/− mice or deletion of Ifng (Sphk2−/−Ifng−/− mice) blocked the protective effect of SphK2 deficiency in fibrosis. Moreover, adoptive transfer of Sphk2−/− (but not Sphk2−/−Ifng−/−) CD4 T cells into WT mice blocked FA-induced fibrosis. Finally, a selective SphK2 inhibitor blocked FA-induced kidney fibrosis in WT mice. These studies demonstrate that SphK2 inhibition may serve as a novel therapeutic approach for attenuating kidney fibrosis.10.1681/ASN.2016030306Mon, 31 Oct 2016 09:16:39 GMT-07:00Sphingosine Kinase 2 Deficiency Attenuates Kidney Fibrosis via IFN-γMaladaptive repair after AKI may lead to progressive fibrosis and decline in kidney function. Sphingosine 1-phosphate has an important role in kidney injury and pleiotropic effects in fibrosis. We investigated the involvement of sphingosine kinase 1 and 2 (SphK1 and SphK2), which phosphorylate sphingosine to produce sphingosine 1-phosphate, in kidney fibrosis induced by folic acid (FA) or unilateral ischemia-reperfusion injury. Analysis of Masson trichrome staining and fibrotic marker protein and mRNA expression 14 days after AKI revealed that wild-type (WT) and Sphk1−/− mice exhibited more kidney fibrosis than Sphk2−/− mice. Furthermore, kidneys of FA-treated WT and Sphk1−/− mice had greater immune cell infiltration and expression of fibrotic and inflammatory markers than kidneys of FA-treated Sphk2−/− mice. In contrast, kidneys of Sphk2−/− mice exhibited greater expression of Ifng and IFN-γ–responsive genes (Cxcl9 and Cxcl10) than kidneys of WT or Sphk1−/− mice did at this time point. Splenic T cells from untreated Sphk2−/− mice were hyperproliferative and produced more IFN-γ than did those of WT or Sphk1−/− mice. IFN-γ blocking antibody administered to Sphk2−/− mice or deletion of Ifng (Sphk2−/−Ifng−/− mice) blocked the protective effect of SphK2 deficiency in fibrosis. Moreover, adoptive transfer of Sphk2−/− (but not Sphk2−/−Ifng−/−) CD4 T cells into WT mice blocked FA-induced fibrosis. Finally, a selective SphK2 inhibitor blocked FA-induced kidney fibrosis in WT mice. These studies demonstrate that SphK2 inhibition may serve as a novel therapeutic approach for attenuating kidney fibrosis.Bajwa, AmandeepHuang, LipingKurmaeva, ElviraYe, HongDondeti, Krishna R.Chroscicki, PiotrFoley, Leah S.Balogun, Z. AyoadeAlexander, Kyle J.Park, HojungLynch, Kevin R.Rosin, Diane L.Okusa, Mark D.2016-10-31T09:16:39-07:00doi:10.1681/ASN.2016030306hwp:resource-id:jnephrol;28/4/1145American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologysphingolipid, T cells, renal fibrosis, folic acid, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160303061046-66731533-34502016-10-31T09:16:39-07:002017-04Journal of the American Society of NephrologyBasic Research28441145i1161i
- APOL1 Renal-Risk Variants Induce Mitochondrial DysfunctionAPOL1 G1 and G2 variants facilitate kidney disease in blacks. To elucidate the pathways whereby these variants contribute to disease pathogenesis, we established HEK293 cell lines stably expressing doxycycline-inducible (Tet-on) reference APOL1 G0 or the G1 and G2 renal-risk variants, and used Illumina human HT-12 v4 arrays and Affymetrix HTA 2.0 arrays to generate global gene expression data with doxycycline induction. Significantly altered pathways identified through bioinformatics analyses involved mitochondrial function; results from immunoblotting, immunofluorescence, and functional assays validated these findings. Overexpression of APOL1 by doxycycline induction in HEK293 Tet-on G1 and G2 cells led to impaired mitochondrial function, with markedly reduced maximum respiration rate, reserve respiration capacity, and mitochondrial membrane potential. Impaired mitochondrial function occurred before intracellular potassium depletion or reduced cell viability occurred. Analysis of global gene expression profiles in nondiseased primary proximal tubule cells from black patients revealed that the nicotinate phosphoribosyltransferase gene, responsible for NAD biosynthesis, was among the top downregulated transcripts in cells with two APOL1 renal-risk variants compared with those without renal-risk variants; nicotinate phosphoribosyltransferase also displayed gene expression patterns linked to mitochondrial dysfunction in HEK293 Tet-on APOL1 cell pathway analyses. These results suggest a pivotal role for mitochondrial dysfunction in APOL1-associated kidney disease.10.1681/ASN.2016050567Mon, 07 Nov 2016 05:44:14 GMT-08:00APOL1 Renal-Risk Variants Induce Mitochondrial DysfunctionAPOL1 G1 and G2 variants facilitate kidney disease in blacks. To elucidate the pathways whereby these variants contribute to disease pathogenesis, we established HEK293 cell lines stably expressing doxycycline-inducible (Tet-on) reference APOL1 G0 or the G1 and G2 renal-risk variants, and used Illumina human HT-12 v4 arrays and Affymetrix HTA 2.0 arrays to generate global gene expression data with doxycycline induction. Significantly altered pathways identified through bioinformatics analyses involved mitochondrial function; results from immunoblotting, immunofluorescence, and functional assays validated these findings. Overexpression of APOL1 by doxycycline induction in HEK293 Tet-on G1 and G2 cells led to impaired mitochondrial function, with markedly reduced maximum respiration rate, reserve respiration capacity, and mitochondrial membrane potential. Impaired mitochondrial function occurred before intracellular potassium depletion or reduced cell viability occurred. Analysis of global gene expression profiles in nondiseased primary proximal tubule cells from black patients revealed that the nicotinate phosphoribosyltransferase gene, responsible for NAD biosynthesis, was among the top downregulated transcripts in cells with two APOL1 renal-risk variants compared with those without renal-risk variants; nicotinate phosphoribosyltransferase also displayed gene expression patterns linked to mitochondrial dysfunction in HEK293 Tet-on APOL1 cell pathway analyses. These results suggest a pivotal role for mitochondrial dysfunction in APOL1-associated kidney disease.Ma, LijunChou, Jeff W.Snipes, James A.Bharadwaj, Manish S.Craddock, Ann L.Cheng, DongmeiWeckerle, AllisonPetrovic, SnezanaHicks, Pamela J.Hemal, Ashok K.Hawkins, Gregory A.Miller, Lance D.Molina, Anthony J.A.Langefeld, Carl D.Murea, MarianaParks, John S.Freedman, Barry I.2016-11-07T05:44:14-08:00doi:10.1681/ASN.2016050567hwp:resource-id:jnephrol;28/4/1093American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, APOL1, mitochondriaBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160505671046-66731533-34502016-11-07T05:44:14-08:002017-04Journal of the American Society of NephrologyBasic Research28441093100811051011
- Protein Kinase Cδ Suppresses Autophagy to Induce Kidney Cell Apoptosis in Cisplatin NephrotoxicityNephrotoxicity is a major adverse effect in cisplatin chemotherapy, and renoprotective approaches are unavailable. Recent work unveiled a critical role of protein kinase Cδ (PKCδ) in cisplatin nephrotoxicity and further demonstrated that inhibition of PKCδ not only protects kidneys but enhances the chemotherapeutic effect of cisplatin in tumors; however, the underlying mechanisms remain elusive. Here, we show that cisplatin induced rapid activation of autophagy in cultured kidney tubular cells and in the kidneys of injected mice. Cisplatin also induced the phosphorylation of mammalian target of rapamycin (mTOR), p70S6 kinase downstream of mTOR, and serine/threonine-protein kinase ULK1, a component of the autophagy initiating complex. In vitro, pharmacologic inhibition of mTOR, directly or through inhibition of AKT, enhanced autophagy after cisplatin treatment. Notably, in both cells and kidneys, blockade of PKCδ suppressed the cisplatin-induced phosphorylation of AKT, mTOR, p70S6 kinase, and ULK1 resulting in upregulation of autophagy. Furthermore, constitutively active and inactive forms of PKCδ respectively enhanced and suppressed cisplatin-induced apoptosis in cultured cells. In mechanistic studies, we showed coimmunoprecipitation of PKCδ and AKT from lysates of cisplatin-treated cells and direct phosphorylation of AKT at serine-473 by PKCδ in vitro. Finally, administration of the PKCδ inhibitor rottlerin with cisplatin protected against cisplatin nephrotoxicity in wild-type mice, but not in renal autophagy–deficient mice. Together, these results reveal a pathway consisting of PKCδ, AKT, mTOR, and ULK1 that inhibits autophagy in cisplatin nephrotoxicity. PKCδ mediates cisplatin nephrotoxicity at least in part by suppressing autophagy, and accordingly, PKCδ inhibition protects kidneys by upregulating autophagy.10.1681/ASN.2016030337Mon, 31 Oct 2016 09:16:38 GMT-07:00Protein Kinase Cδ Suppresses Autophagy to Induce Kidney Cell Apoptosis in Cisplatin NephrotoxicityNephrotoxicity is a major adverse effect in cisplatin chemotherapy, and renoprotective approaches are unavailable. Recent work unveiled a critical role of protein kinase Cδ (PKCδ) in cisplatin nephrotoxicity and further demonstrated that inhibition of PKCδ not only protects kidneys but enhances the chemotherapeutic effect of cisplatin in tumors; however, the underlying mechanisms remain elusive. Here, we show that cisplatin induced rapid activation of autophagy in cultured kidney tubular cells and in the kidneys of injected mice. Cisplatin also induced the phosphorylation of mammalian target of rapamycin (mTOR), p70S6 kinase downstream of mTOR, and serine/threonine-protein kinase ULK1, a component of the autophagy initiating complex. In vitro, pharmacologic inhibition of mTOR, directly or through inhibition of AKT, enhanced autophagy after cisplatin treatment. Notably, in both cells and kidneys, blockade of PKCδ suppressed the cisplatin-induced phosphorylation of AKT, mTOR, p70S6 kinase, and ULK1 resulting in upregulation of autophagy. Furthermore, constitutively active and inactive forms of PKCδ respectively enhanced and suppressed cisplatin-induced apoptosis in cultured cells. In mechanistic studies, we showed coimmunoprecipitation of PKCδ and AKT from lysates of cisplatin-treated cells and direct phosphorylation of AKT at serine-473 by PKCδ in vitro. Finally, administration of the PKCδ inhibitor rottlerin with cisplatin protected against cisplatin nephrotoxicity in wild-type mice, but not in renal autophagy–deficient mice. Together, these results reveal a pathway consisting of PKCδ, AKT, mTOR, and ULK1 that inhibits autophagy in cisplatin nephrotoxicity. PKCδ mediates cisplatin nephrotoxicity at least in part by suppressing autophagy, and accordingly, PKCδ inhibition protects kidneys by upregulating autophagy.Zhang, DongshanPan, JianXiang, XudongLiu, YuDong, GuieLivingston, Man J.Chen, Jian-KangYin, Xiao-MingDong, Zheng2016-10-31T09:16:38-07:00doi:10.1681/ASN.2016030337hwp:resource-id:jnephrol;28/4/1131American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, apoptosis, nephrotoxicityBasic ResearchBasic Researchresearch-article20172017-04-01April 201710.1681/ASN.20160303371046-66731533-34502016-10-31T09:16:38-07:002017-04Journal of the American Society of NephrologyBasic Research28411311144
- Identifying the Intracellular Function of APOL110.1681/ASN.2016111262Tue, 14 Feb 2017 05:59:02 GMT-08:00Identifying the Intracellular Function of APOL1Bruggeman, Leslie A.O’Toole, John F.Sedor, John R.2017-02-14T05:59:02-08:00doi:10.1681/ASN.2016111262hwp:resource-id:jnephrol;28/4/1008American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, human genetics, cell deathUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-04-01April 201710.1681/ASN.20161112621046-66731533-34502017-02-14T05:59:02-08:002017-04Journal of the American Society of NephrologyUp Front Matters28444410081106111710931011111611301105
- Access to Kidney Transplantation among HIV-Infected Waitlist Candidates10.2215/CJN.07460716Thu, 23 Feb 2017 06:34:04 GMT-08:00Access to Kidney Transplantation among HIV-Infected Waitlist CandidatesLocke, Jayme E.Mehta, ShikhaSawinski, DeirdreGustafson, SallyShelton, Brittany A.Reed, Rhiannon D.MacLennan, PaulBolch, CharlotteDurand, ChristineMassie, AllanMannon, Roslyn B.Gaston, RobertSaag, MichaelOverton, TurnerSegev, Dorry L.2017-02-23T06:34:04-08:00doi:10.2215/CJN.07460716hwp:resource-id:clinjasn;12/3/467American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, HIV, African Continental Ancestry Group, Coinfection, HIV Infections, HIV-1, Hepatitis C, Humans, Kidney Failure, Chronic, kidney transplantation, Living Donors, Male, renal dialysisOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20172017-03-07March 07, 201710.2215/CJN.074607161555-90411555-905X2017-02-23T06:34:04-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1233467385475387
- Linguistic Isolation and Access to the Active Kidney Transplant Waiting List in the United States10.2215/CJN.07150716Thu, 09 Feb 2017 05:17:24 GMT-08:00Linguistic Isolation and Access to the Active Kidney Transplant Waiting List in the United StatesTalamantes, EfrainNorris, Keith C.Mangione, Carol M.Moreno, GerardoWaterman, Amy D.Peipert, John D.Bunnapradist, SuphamaiHuang, Edmund2017-02-09T05:17:24-08:00doi:10.2215/CJN.07150716hwp:resource-id:clinjasn;12/3/483American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, ethnicity, language, waitlist, raceOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-03-07March 07, 201710.2215/CJN.071507161555-90411555-905X2017-02-09T05:17:24-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1233483380492381
- Perspectives of Older Kidney Transplant Recipients on Kidney Transplantation10.2215/CJN.05890616Tue, 31 Jan 2017 08:16:53 GMT-08:00Perspectives of Older Kidney Transplant Recipients on Kidney TransplantationPinter, JuleHanson, Camilla S.Chapman, Jeremy R.Wong, GermaineCraig, Jonathan C.Schell, Jane O.Tong, Allison2017-01-31T08:16:53-08:00doi:10.2215/CJN.05890616hwp:resource-id:clinjasn;12/3/443American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, quality of life, transplant outcomes, adolescent, aging, anxiety, Australia, cognition disorders, comorbidity, goals, graft survival, humans, immunosuppression, kidney transplantation, longevity, medical futility, moral obligations, motivation, negotiating, self-care, transplant recipients, uncertaintyOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20172017-03-07March 07, 201710.2215/CJN.058906161555-90411555-905X2017-01-31T08:16:53-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles123443453
- Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial10.2215/CJN.07600716Fri, 17 Feb 2017 05:35:25 GMT-08:00Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized TrialSchnuelle, PeterSchmitt, Wilhelm H.Weiss, ChristelHabicht, AntjeRenders, LutzZeier, MartinDrüschler, FelixHeller, KatharinaPisarski, PrzemyslawBanas, BernhardKrämer, Bernhard K.Jung, MatthiasLopau, KaiOlbricht, Christoph J.Weihprecht, HorstSchenker, PeterDe Fijter, Johan W.Yard, Benito A.Benck, Urs2017-02-17T05:35:25-08:00doi:10.2215/CJN.07600716hwp:resource-id:clinjasn;12/3/493American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycadaver organ transplantation, ischemia-reperfusion, renal protection, renal transplantation, outcomes, dopamine, brain-dead donor, donor pretreatment, arm, brain, brain death, confidence intervals, death, dopamine, follow-up studies, graft survival, humans, intention to treat analysis, kidney transplantation, survival analysis, tissue donors, transplantsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-03-07March 07, 201710.2215/CJN.076007161555-90411555-905X2017-02-17T05:35:25-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1233493388501390
- Focal Segmental GlomerulosclerosisFocal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant–important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele–associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.10.2215/CJN.05960616Mon, 27 Feb 2017 07:22:10 GMT-08:00Focal Segmental GlomerulosclerosisFocal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant–important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele–associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.Rosenberg, Avi Z.Kopp, Jeffrey B.2017-02-27T07:22:10-08:00doi:10.2215/CJN.05960616hwp:resource-id:clinjasn;12/3/502American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, immunosuppression, Alleles, Biopsy, Body Size, Fluorescent Antibody Technique, Genetic Testing, Segmental glomerulosclerosis, Glomerulosclerosis, Focal Segmental, Humans, hypertrophy, kidney, Kidney Diseases, Kidney Glomerulus, kidney transplantation, Microscopy, Electron, Mutation, Penetrance, Podocytes, WorkloadGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-03-07March 07, 201710.2215/CJN.059606161555-90411555-905X2017-02-27T07:22:10-08:002017-03-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician1231250218895171889
- Opportunities and Challenges for Kidney Donation from and to HIV-Positive Individuals10.2215/CJN.00740117Thu, 23 Feb 2017 06:34:03 GMT-08:00Opportunities and Challenges for Kidney Donation from and to HIV-Positive IndividualsChandran, SindhuStock, Peter G.2017-02-23T06:34:03-08:00doi:10.2215/CJN.00740117hwp:resource-id:clinjasn;12/3/385American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHIV kidney transplantation, HIV Seropositivity, Humans, Nephrectomy, Tissue and Organ HarvestingEditorialsEditorialseditorial20172017-03-07March 07, 201710.2215/CJN.007401171555-90411555-905X2017-02-23T06:34:03-08:002017-03-07Clinical Journal of the American Society of NephrologyEditorials1233385467387475
- Optimizing Graft Survival by Pretreatment of the Donor10.2215/CJN.00900117Fri, 17 Feb 2017 05:35:25 GMT-08:00Optimizing Graft Survival by Pretreatment of the DonorFeng, Sandy2017-02-17T05:35:25-08:00doi:10.2215/CJN.00900117hwp:resource-id:clinjasn;12/3/388American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydelayed graft function, transplant outcomes, Graft Survival, kidney transplantation, Tissue DonorsEditorialsEditorialseditorial20172017-03-07March 07, 201710.2215/CJN.009001171555-90411555-905X2017-02-17T05:35:25-08:002017-03-07Clinical Journal of the American Society of NephrologyEditorials12333388493435390501442
- Consolidation in the Dialysis Industry, Patient Choice, and Local Market CompetitionThe Medicare program insures >80% of patients with ESRD in the United States. An emphasis on reducing outpatient dialysis costs has motivated consolidation among dialysis providers, with two for-profit corporations now providing dialysis for >70% of patients. It is unknown whether industry consolidation has affected patients’ ability to choose among competing dialysis providers. We identified patients receiving in-center hemodialysis at the start of 2001 and 2011 from the national ESRD registry and ascertained dialysis facility ownership. For each hospital service area, we determined the maximum distance within which 90% of patients traveled to receive dialysis in 2001. We compared the numbers of competing dialysis providers within that same distance between 2001 and 2011. Additionally, we examined the Herfindahl–Hirschman Index, a metric of market concentration ranging from near zero (perfect competition) to one (monopoly) for each hospital service area. Between 2001 and 2011, the number of different uniquely owned competing providers decreased 8%. However, increased facility entry into markets to meet rising demand for care offset the effect of provider consolidation on the number of choices available to patients. The number of dialysis facilities in the United States increased by 54%, and patients experienced an average 10% increase in the number of competing proximate facilities from which they could choose to receive dialysis (P<0.001). Local markets were highly concentrated in both 2001 and 2011 (mean Herfindahl–Hirschman Index =0.46; SD=0.2 for both years), but overall market concentration did not materially change. In summary, a decade of consolidation in the United States dialysis industry did not (on average) limit patient choice or result in more concentrated local markets. However, because dialysis markets remained highly concentrated, it will be important to understand whether market competition affects prices paid by private insurers, access to dialysis care, quality of care, and associated health outcomes.10.2215/CJN.06340616Wed, 09 Nov 2016 07:49:07 GMT-08:00Consolidation in the Dialysis Industry, Patient Choice, and Local Market CompetitionThe Medicare program insures >80% of patients with ESRD in the United States. An emphasis on reducing outpatient dialysis costs has motivated consolidation among dialysis providers, with two for-profit corporations now providing dialysis for >70% of patients. It is unknown whether industry consolidation has affected patients’ ability to choose among competing dialysis providers. We identified patients receiving in-center hemodialysis at the start of 2001 and 2011 from the national ESRD registry and ascertained dialysis facility ownership. For each hospital service area, we determined the maximum distance within which 90% of patients traveled to receive dialysis in 2001. We compared the numbers of competing dialysis providers within that same distance between 2001 and 2011. Additionally, we examined the Herfindahl–Hirschman Index, a metric of market concentration ranging from near zero (perfect competition) to one (monopoly) for each hospital service area. Between 2001 and 2011, the number of different uniquely owned competing providers decreased 8%. However, increased facility entry into markets to meet rising demand for care offset the effect of provider consolidation on the number of choices available to patients. The number of dialysis facilities in the United States increased by 54%, and patients experienced an average 10% increase in the number of competing proximate facilities from which they could choose to receive dialysis (P<0.001). Local markets were highly concentrated in both 2001 and 2011 (mean Herfindahl–Hirschman Index =0.46; SD=0.2 for both years), but overall market concentration did not materially change. In summary, a decade of consolidation in the United States dialysis industry did not (on average) limit patient choice or result in more concentrated local markets. However, because dialysis markets remained highly concentrated, it will be important to understand whether market competition affects prices paid by private insurers, access to dialysis care, quality of care, and associated health outcomes.Erickson, Kevin F.Zheng, YuanchaoWinkelmayer, Wolfgang C.Ho, VivianBhattacharya, JayChertow, Glenn M.2016-11-09T07:49:07-08:00doi:10.2215/CJN.06340616hwp:resource-id:clinjasn;12/3/536American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, Economic Analysis, United States Renal Data System, patient choice, health policy, Choice Behavior, Humans, Insurance, Insurance Carriers, Kidney Failure, Chronic, Medicare, Outpatients, Ownership, peritoneal dialysis, Registries, renal dialysis, Renal Insufficiency, Chronic, United StatesPublic Policy SeriesPublic Policy Seriesresearch-article20172017-03-07March 07, 201710.2215/CJN.063406161555-90411555-905X2016-11-09T07:49:07-08:002017-03-07Clinical Journal of the American Society of NephrologyPublic Policy Series123536545
- Is the End in Sight for the “Don’t Ask, Don’t Tell” Approach to Advance Care Planning?10.2215/CJN.00980117Thu, 23 Feb 2017 06:34:03 GMT-08:00Is the End in Sight for the “Don’t Ask, Don’t Tell” Approach to Advance Care Planning?Carson, Rachel C.Bernacki, Rachelle2017-02-23T06:34:03-08:00doi:10.2215/CJN.00980117hwp:resource-id:clinjasn;12/3/380American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyadvance care planning, kidney failure, chronic, renal dialysis, advance directives, palliative medicine, electronic health recordsEditorialsEditorialseditorial20172017-03-07March 07, 201710.2215/CJN.009801171555-90411555-905X2017-02-23T06:34:03-08:002017-03-07Clinical Journal of the American Society of NephrologyEditorials12333380435483381442492
- When All You Have Is a Hammer: The Need for Tools to Define and Apply Patient-Centered Outcomes in Hemodialysis10.2215/CJN.00550117Tue, 21 Feb 2017 05:49:08 GMT-08:00When All You Have Is a Hammer: The Need for Tools to Define and Apply Patient-Centered Outcomes in HemodialysisBowling, C. BarrettPlantinga, Laura C.2017-02-21T05:49:08-08:00doi:10.2215/CJN.00550117hwp:resource-id:clinjasn;12/3/382American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHousehold Articles, Humans, Outcome Assessment, renal dialysisEditorialsEditorialseditorial20172017-03-07March 07, 201710.2215/CJN.005501171555-90411555-905X2017-02-21T05:49:08-08:002017-03-07Clinical Journal of the American Society of NephrologyEditorials1233382454384466
- Risk of Hypertension among First-Time Symptomatic Kidney Stone Formers10.2215/CJN.06600616Wed, 01 Feb 2017 07:04:32 GMT-08:00Risk of Hypertension among First-Time Symptomatic Kidney Stone FormersKittanamongkolchai, WonngarmMara, Kristin C.Mehta, Ramila A.Vaughan, Lisa E.Denic, AleksandarKnoedler, John J.Enders, Felicity T.Lieske, John C.Rule, Andrew D.2017-02-01T07:04:32-08:00doi:10.2215/CJN.06600616hwp:resource-id:clinjasn;12/3/476American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, Thiazide diuretics, chronic kidney disease, Epidemiology, Alcoholism, Body Mass Index, Comorbidity, coronary artery disease, creatinine, diabetes mellitus, Dyslipidemias, Follow-Up Studies, Gout, Humans, hypertension, Kidney Calculi, Male, Renal Insufficiency, Chronic, Tobacco Use, Sodium Chloride Symporter InhibitorsOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20172017-03-07March 07, 201710.2215/CJN.066006161555-90411555-905X2017-02-01T07:04:32-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles123476482
- Prognostic Value of Residual Urine Volume, GFR by 24-hour Urine Collection, and eGFR in Patients Receiving Dialysis10.2215/CJN.05520516Wed, 22 Feb 2017 04:51:00 GMT-08:00Prognostic Value of Residual Urine Volume, GFR by 24-hour Urine Collection, and eGFR in Patients Receiving DialysisLee, Mi JungPark, Jung TakPark, Kyoung SookKwon, Young EunOh, Hyung JungYoo, Tae-HyunKim, Yong-LimKim, Yon SuYang, Chul WooKim, Nam-HoKang, Shin-WookHan, Seung Hyeok2017-02-22T04:51:00-08:00doi:10.2215/CJN.05520516hwp:resource-id:clinjasn;12/3/426American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end-stage renal disease, glomerular filtration rate, mortality, residual kidney function, urine volumeOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20172017-03-07March 07, 201710.2215/CJN.055205161555-90411555-905X2017-02-22T04:51:00-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1233426377434379
- Advance Directives and End-of-Life Care among Nursing Home Residents Receiving Maintenance Dialysis10.2215/CJN.07510716Thu, 05 Jan 2017 05:15:17 GMT-08:00Advance Directives and End-of-Life Care among Nursing Home Residents Receiving Maintenance DialysisKurella Tamura, ManjulaMontez-Rath, Maria E.Hall, Yoshio N.Katz, RonitO’Hare, Ann M.2017-01-05T05:15:17-08:00doi:10.2215/CJN.07510716hwp:resource-id:clinjasn;12/3/435American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, ESRD, advance directives, hospice care, hospices, hospitalization, humans, inpatients, intensive care units, kidney failure, chronic, Medicare, nursing homes, prevalence, renal dialysis, terminal care, United StatesOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20172017-03-07March 07, 201710.2215/CJN.075107161555-90411555-905X2017-01-05T05:15:17-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles12333435380388442381390
- Risk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA–Associated GN10.2215/CJN.06200616Wed, 01 Feb 2017 07:04:32 GMT-08:00Risk Factors for Renal Survival in Chinese Patients with Myeloperoxidase-ANCA–Associated GNChen, YinghuaBao, HaoLiu, ZhengzhaoLiu, XiaGao, ErzhiZeng, CaihongZhang, HaitaoLiu, ZhihongHu, Weixin2017-02-01T07:04:32-08:00doi:10.2215/CJN.06200616hwp:resource-id:clinjasn;12/3/417American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, vasculitis, histopathology, Antibodies, Antineutrophil Cytoplasmic, Biopsy, Confidence Intervals, Follow-Up Studies, glomerulonephritis, Glucocorticoids, Humans, hypoalbuminemia, kidney, Kidney Failure, Chronic, Kidney Glomerulus, Mycophenolic Acid, Neutrophils, Peroxidase, Retrospective Studies, risk factors, Serum Albumin, mycophenolate mofetilOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20172017-03-07March 07, 201710.2215/CJN.062006161555-90411555-905X2017-02-01T07:04:32-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles123417425
- A Randomized Crossover Trial of Dietary Sodium Restriction in Stage 3–4 CKD10.2215/CJN.01120216Thu, 16 Feb 2017 05:52:29 GMT-08:00A Randomized Crossover Trial of Dietary Sodium Restriction in Stage 3–4 CKDSaran, RajivPadilla, Robin L.Gillespie, Brenda W.Heung, MichaelHummel, Scott L.Derebail, Vimal KumarPitt, BertramLevin, Nathan W.Zhu, FansanAbbas, Samer R.Liu, LiKotanko, PeterKlemmer, Philip2017-02-16T05:52:29-08:00doi:10.2215/CJN.01120216hwp:resource-id:clinjasn;12/3/399American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysalt sensitivity, crossover design, ambulatory blood pressure monitoring, bioelectrical impedance, motivational interviewingOriginal ArticlesChronic Kidney DiseasesOriginal ArticlesChronic Kidney Diseasesresearch-article20172017-03-07March 07, 201710.2215/CJN.011202161555-90411555-905X2017-02-16T05:52:29-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles123399407
- Recognition and Management of Resistant HypertensionDespite improvements in hypertension awareness and treatment, 30%–60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events.10.2215/CJN.06180616Mon, 28 Nov 2016 07:51:29 GMT-08:00Recognition and Management of Resistant HypertensionDespite improvements in hypertension awareness and treatment, 30%–60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events.Braam, BrankoTaler, Sandra J.Rahman, MahboobFillaus, Jennifer A.Greco, Barbara A.Forman, John P.Reisin, EfrainCohen, Debbie L.Saklayen, Mohammad G.Hedayati, S. Susan2016-11-28T07:51:29-08:00doi:10.2215/CJN.06180616hwp:resource-id:clinjasn;12/3/524American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, chronic kidney disease, cardiovascular disease, renal denvervation, sodium intake, Antihypertensive Agents, Denervation, diuretics, Humans, hypertension, kidney, Life Style, Mineralocorticoid Receptor, Antagonists, Pressoreceptors, Renal Insufficiency, ChronicIn-Depth ReviewIn-Depth Reviewreview-article20172017-03-07March 07, 201710.2215/CJN.061806161555-90411555-905X2016-11-28T07:51:29-08:002017-03-07Clinical Journal of the American Society of NephrologyIn-Depth Review123524535
- Cognitive Testing in Patients with CKD: The Problem of Missing Cases10.2215/CJN.03670316Wed, 01 Feb 2017 07:04:31 GMT-08:00Cognitive Testing in Patients with CKD: The Problem of Missing CasesNeumann, DeniseRobinski, MaxiMau, WilfriedGirndt, Matthias2017-02-01T07:04:31-08:00doi:10.2215/CJN.03670316hwp:resource-id:clinjasn;12/3/391American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNeurocognition, CORETH, ESRD, Cognitive Functioning, Case Exclusion, Preclusion, hemodialysis, Cognition, Comorbidity, depression, Health Resources, Humans, Language, Motivation, Motor Skills, peritoneal dialysis, renal dialysis, Renal Insufficiency, Chronic, Surveys and Questionnaires, Trail Making Test, Vision DisordersOriginal ArticlesChronic Kidney DiseasesOriginal ArticlesChronic Kidney Diseasesresearch-article20172017-03-07March 07, 201710.2215/CJN.036703161555-90411555-905X2017-02-01T07:04:31-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles123391398
- Preservation of Residual Kidney Function and Urine Volume in Patients on Dialysis10.2215/CJN.00330117Wed, 22 Feb 2017 04:50:59 GMT-08:00Preservation of Residual Kidney Function and Urine Volume in Patients on DialysisKrediet, Raymond T.2017-02-22T04:50:59-08:00doi:10.2215/CJN.00330117hwp:resource-id:clinjasn;12/3/377American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney failure, dialysis, diuretics, peritoneal dialysis, hemodialysis, Fluid Therapy, Humans, renal dialysis, Urinary Tract Physiological PhenomenaEditorialsEditorialseditorial20172017-03-07March 07, 201710.2215/CJN.003301171555-90411555-905X2017-02-22T04:50:59-08:002017-03-07Clinical Journal of the American Society of NephrologyEditorials1233377426379434
- Nephrologists’ Perspectives on Defining and Applying Patient-Centered Outcomes in Hemodialysis10.2215/CJN.08370816Tue, 21 Feb 2017 05:49:09 GMT-08:00Nephrologists’ Perspectives on Defining and Applying Patient-Centered Outcomes in HemodialysisTong, AllisonWinkelmayer, Wolfgang C.Wheeler, David C.van Biesen, WimTugwell, PeterManns, BradenHemmelgarn, BrendaHarris, TessCrowe, SallyJu, AngelaO’Lone, EmmaEvangelidis, NicoleCraig, Jonathan C.,2017-02-21T05:49:09-08:00doi:10.2215/CJN.08370816hwp:resource-id:clinjasn;12/3/454American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, qualitative research, Australia, Austria, Belgium, Canada, Chronic Disease, Comorbidity, Decision Making, Germany, Goals, Great Britain, Humans, nephrology, New Zealand, Patient Selection, Patient-Centered Care, Physician-Patient Relations, quality of life, renal dialysis, Singapore, Uncertainty, United StatesOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20172017-03-07March 07, 201710.2215/CJN.083708161555-90411555-905X2017-02-21T05:49:09-08:002017-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1233454382466384
- What Are We Doing? A Survey of United States Nephrology Fellowship Program DirectorsInterest in nephrology has been declining in recent years. Long work hours and a poor work/life balance may be partially responsible, and may also affect a fellowship’s educational mission. We surveyed nephrology program directors using a web-based survey in order to define current clinical and educational practice patterns and identify areas for improvement. Our survey explored fellowship program demographics, fellows’ workload, call structure, and education. Program directors were asked to estimate the average and maximum number of patients on each of their inpatient services, the number of patients seen by fellows in clinic, and to provide details regarding their overnight and weekend call. In addition, we asked about number of and composition of didactic conferences. Sixty-eight out of 148 program directors responded to the survey (46%). The average number of fellows per program was approximately seven. The busiest inpatient services had a mean of 21.5±5.9 patients on average and 33.8±10.7 at their maximum. The second busiest services had an average and maximum of 15.6±6.0 and 24.5±10.8 patients, respectively. Transplant-only services had fewer patients than other service compositions. A minority of services (14.5%) employed physician extenders. Fellows most commonly see patients during a single weekly continuity clinic, with a typical fellow-to-faculty ratio of 2:1. The majority of programs do not alter outpatient responsibilities during inpatient service time. Most programs (approximately 75%) divided overnight and weekend call responsibilities equally between first year and more senior fellows. Educational practices varied widely between programs. Our survey underscores the large variety in workload, practice patterns, and didactics at different institutions and provides a framework to help improve the service/education balance in nephrology fellowships.10.2215/CJN.06530616Mon, 05 Dec 2016 07:57:53 GMT-08:00What Are We Doing? A Survey of United States Nephrology Fellowship Program DirectorsInterest in nephrology has been declining in recent years. Long work hours and a poor work/life balance may be partially responsible, and may also affect a fellowship’s educational mission. We surveyed nephrology program directors using a web-based survey in order to define current clinical and educational practice patterns and identify areas for improvement. Our survey explored fellowship program demographics, fellows’ workload, call structure, and education. Program directors were asked to estimate the average and maximum number of patients on each of their inpatient services, the number of patients seen by fellows in clinic, and to provide details regarding their overnight and weekend call. In addition, we asked about number of and composition of didactic conferences. Sixty-eight out of 148 program directors responded to the survey (46%). The average number of fellows per program was approximately seven. The busiest inpatient services had a mean of 21.5±5.9 patients on average and 33.8±10.7 at their maximum. The second busiest services had an average and maximum of 15.6±6.0 and 24.5±10.8 patients, respectively. Transplant-only services had fewer patients than other service compositions. A minority of services (14.5%) employed physician extenders. Fellows most commonly see patients during a single weekly continuity clinic, with a typical fellow-to-faculty ratio of 2:1. The majority of programs do not alter outpatient responsibilities during inpatient service time. Most programs (approximately 75%) divided overnight and weekend call responsibilities equally between first year and more senior fellows. Educational practices varied widely between programs. Our survey underscores the large variety in workload, practice patterns, and didactics at different institutions and provides a framework to help improve the service/education balance in nephrology fellowships.Liebman, Scott E.Moore, Catherine A.Monk, Rebeca D.Rizvi, Mahrukh S.2016-12-05T07:57:53-08:00doi:10.2215/CJN.06530616hwp:resource-id:clinjasn;12/3/518American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrology fellowship, education, survey, demography, faculty, fellowships and scholarships, humans, inpatients, internet, minority groups, nephrology, outpatients, physician assistants, religious missions, surveys and questionnaires, United States, workloadEducation SeriesEducation Seriesresearch-article20172017-03-07March 07, 201710.2215/CJN.065306161555-90411555-905X2016-12-05T07:57:53-08:002017-03-07Clinical Journal of the American Society of NephrologyEducation Series123518523
- Use of Causal Diagrams to Inform the Design and Interpretation of Observational Studies: An Example from the Study of Heart and Renal Protection (SHARP)Observational studies often seek to estimate the causal relevance of an exposure to an outcome of interest. However, many possible biases can arise when estimating such relationships, in particular bias because of confounding. To control for confounding properly, careful consideration of the nature of the assumed relationships between the exposure, the outcome, and other characteristics is required. Causal diagrams provide a simple graphic means of displaying such relationships, describing the assumptions made, and allowing for the identification of a set of characteristics that should be taken into account (i.e., adjusted for) in any analysis. Furthermore, causal diagrams can be used to identify other possible sources of bias (such as selection bias), which if understood from the outset, can inform the planning of appropriate analyses. In this article, we review the basic theory of causal diagrams and describe some of the methods available to identify which characteristics need to be taken into account when estimating the total effect of an exposure on an outcome. In doing so, we review the concept of collider bias and show how it is inappropriate to adjust for characteristics that may be influenced, directly or indirectly, by both the exposure and the outcome of interest. A motivating example is taken from the Study of Heart and Renal Protection, in which the relevance of smoking to progression to ESRD is considered.10.2215/CJN.02430316Tue, 23 Aug 2016 06:55:48 GMT-07:00Use of Causal Diagrams to Inform the Design and Interpretation of Observational Studies: An Example from the Study of Heart and Renal Protection (SHARP)Observational studies often seek to estimate the causal relevance of an exposure to an outcome of interest. However, many possible biases can arise when estimating such relationships, in particular bias because of confounding. To control for confounding properly, careful consideration of the nature of the assumed relationships between the exposure, the outcome, and other characteristics is required. Causal diagrams provide a simple graphic means of displaying such relationships, describing the assumptions made, and allowing for the identification of a set of characteristics that should be taken into account (i.e., adjusted for) in any analysis. Furthermore, causal diagrams can be used to identify other possible sources of bias (such as selection bias), which if understood from the outset, can inform the planning of appropriate analyses. In this article, we review the basic theory of causal diagrams and describe some of the methods available to identify which characteristics need to be taken into account when estimating the total effect of an exposure on an outcome. In doing so, we review the concept of collider bias and show how it is inappropriate to adjust for characteristics that may be influenced, directly or indirectly, by both the exposure and the outcome of interest. A motivating example is taken from the Study of Heart and Renal Protection, in which the relevance of smoking to progression to ESRD is considered.Staplin, NatalieHerrington, William G.Judge, Parminder K.Reith, Christina A.Haynes, RichardLandray, Martin J.Baigent, ColinEmberson, Jonathan2016-08-23T06:55:48-07:00doi:10.2215/CJN.02430316hwp:resource-id:clinjasn;12/3/546American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and outcomes, observational studies, causal diagrams, Bias (Epidemiology), kidney, Kidney Failure, Chronic, Motivation, Renal Insufficiency, Chronic, Selection Bias, SmokingSpecial FeatureSpecial Featureresearch-article20172017-03-07March 07, 201710.2215/CJN.024303161555-90411555-905X2016-08-23T06:55:48-07:002017-03-07Clinical Journal of the American Society of NephrologySpecial Feature123546552
- Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal TubuleKidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[18F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs.10.1681/ASN.2016050510Mon, 12 Sep 2016 09:51:38 GMT-07:00Dapagliflozin Binds Specifically to Sodium-Glucose Cotransporter 2 in the Proximal Renal TubuleKidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[18F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs.Ghezzi, ChiaraYu, Amy S.Hirayama, Bruce A.Kepe, VladimirLiu, JieScafoglio, ClaudioPowell, David R.Huang, Sung-ChengSatyamurthy, NagichettiarBarrio, Jorge R.Wright, Ernest M.2016-09-12T09:51:38-07:00doi:10.1681/ASN.2016050510hwp:resource-id:jnephrol;28/3/802American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologySGLT2, Dapagliflozin, diabetes mellitus, microPETBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160505101046-66731533-34502016-09-12T09:51:38-07:002017-03Journal of the American Society of NephrologyBasic Research283802810
- Anti–TGF-β1 Antibody Therapy in Patients with Diabetic NephropathyTGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1–specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3–3.3 mg/dl for women and 1.5–3.5 mg/dl for men (or eGFR of 20–60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-β1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-β1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-β1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.10.1681/ASN.2015111230Mon, 19 Sep 2016 10:04:57 GMT-07:00Anti–TGF-β1 Antibody Therapy in Patients with Diabetic NephropathyTGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1–specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3–3.3 mg/dl for women and 1.5–3.5 mg/dl for men (or eGFR of 20–60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-β1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-β1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-β1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.Voelker, JamesBerg, Paul H.Sheetz, MatthewDuffin, KevinShen, TongMoser, BrianGreene, TomBlumenthal, Samuel S.Rychlik, IvanYagil, YoramZaoui, PhilippeLewis, Julia B.2016-09-19T10:04:57-07:00doi:10.1681/ASN.2015111230hwp:resource-id:jnephrol;28/3/953American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyDiabetic Kidney Disease, Transforming growth factor beta, proteinuria, renal fibrosisClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20151112301046-66731533-34502016-09-19T10:04:57-07:002017-03Journal of the American Society of NephrologyClinical Research283953962
- Gli1+ Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular InjuryPeritubular capillary rarefaction is hypothesized to contribute to the increased risk of future CKD after AKI. Here, we directly tested the role of Gli1+ kidney pericytes in the maintenance of peritubular capillary health, and the consequences of pericyte loss during injury. Using bigenic Gli1-CreERt2; R26tdTomato reporter mice, we observed increased distance between Gli1+ pericytes and endothelial cells after AKI (mean±SEM: 3.3±0.1 µm before injury versus 12.5±0.2 µm after injury; P<0.001). Using a genetic ablation model, we asked whether pericyte loss alone is sufficient for capillary destabilization. Ten days after pericyte ablation, we observed endothelial cell damage by electron microscopy. Furthermore, pericyte loss led to significantly reduced capillary number at later time points (mean±SEM capillaries/high-power field: 67.6±4.7 in control versus 44.1±4.8 at 56 days; P<0.05) and increased cross-sectional area (mean±SEM: 21.9±0.4 µm2 in control versus 24.1±0.6 µm2 at 10 days; P<0.01 and 24.6±0.6 µm2 at 56 days; P<0.001). Pericyte ablation also led to hypoxic focal and subclinical tubular injury, reflected by transient expression of Kim1 and vimentin in scattered proximal tubule segments. This analysis provides direct evidence that AKI causes pericyte detachment from capillaries, and that pericyte loss is sufficient to trigger transient tubular injury and permanent peritubular capillary rarefaction.10.1681/ASN.2016030297Tue, 13 Sep 2016 07:22:27 GMT-07:00Gli1+ Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular InjuryPeritubular capillary rarefaction is hypothesized to contribute to the increased risk of future CKD after AKI. Here, we directly tested the role of Gli1+ kidney pericytes in the maintenance of peritubular capillary health, and the consequences of pericyte loss during injury. Using bigenic Gli1-CreERt2; R26tdTomato reporter mice, we observed increased distance between Gli1+ pericytes and endothelial cells after AKI (mean±SEM: 3.3±0.1 µm before injury versus 12.5±0.2 µm after injury; P<0.001). Using a genetic ablation model, we asked whether pericyte loss alone is sufficient for capillary destabilization. Ten days after pericyte ablation, we observed endothelial cell damage by electron microscopy. Furthermore, pericyte loss led to significantly reduced capillary number at later time points (mean±SEM capillaries/high-power field: 67.6±4.7 in control versus 44.1±4.8 at 56 days; P<0.05) and increased cross-sectional area (mean±SEM: 21.9±0.4 µm2 in control versus 24.1±0.6 µm2 at 10 days; P<0.01 and 24.6±0.6 µm2 at 56 days; P<0.001). Pericyte ablation also led to hypoxic focal and subclinical tubular injury, reflected by transient expression of Kim1 and vimentin in scattered proximal tubule segments. This analysis provides direct evidence that AKI causes pericyte detachment from capillaries, and that pericyte loss is sufficient to trigger transient tubular injury and permanent peritubular capillary rarefaction.Kramann, RafaelWongboonsin, JanewitChang-Panesso, MonicaMachado, Flavia G.Humphreys, Benjamin D.2016-09-13T07:22:27-07:00doi:10.1681/ASN.2016030297hwp:resource-id:jnephrol;28/3/776American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, pericyte, capillary, CKDBrief CommunicationsBrief Communicationsbrief-report20172017-03-01March 201710.1681/ASN.20160302971046-66731533-34502016-09-13T07:22:27-07:002017-03Journal of the American Society of NephrologyBrief Communications2833776717784719
- HDL Cholesterol Efflux Does Not Predict Cardiovascular Risk in Hemodialysis PatientsThe cardioprotective effect of HDL is thought to be largely determined by its cholesterol efflux capacity, which was shown to inversely correlate with atherosclerotic cardiovascular disease in populations with normal kidney function. Patients with ESRD suffer an exceptionally high cardiovascular risk not fully explained by traditional risk factors. Here, in a post hoc analysis in 1147 patients with type 2 diabetes mellitus on hemodialysis who participated in the German Diabetes Dialysis Study (4D Study), we investigated whether the HDL cholesterol efflux capacity is predictive for cardiovascular risk. Efflux capacity was quantified by incubating human macrophage foam cells with apoB-depleted serum. During a median follow-up of 4.1 years, 423 patients reached the combined primary end point (composite of cardiac death, nonfatal myocardial infarction, and stroke), 410 patients experienced cardiac events, and 561 patients died. Notably, in Cox regression analyses, we found no association of efflux capacity with the combined primary end point (hazard ratio [HR], 0.96; 95% confidence interval [95% CI], 0.88 to 1.06; P=0.42), cardiac events (HR, 0.92; 95% CI, 0.83 to 1.02; P=0.11), or all-cause mortality (HR, 0.96; 95% CI, 0.88 to 1.05; P=0.39). In conclusion, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in this cohort of patients with diabetes on hemodialysis.10.1681/ASN.2016030262Fri, 09 Sep 2016 09:59:12 GMT-07:00HDL Cholesterol Efflux Does Not Predict Cardiovascular Risk in Hemodialysis PatientsThe cardioprotective effect of HDL is thought to be largely determined by its cholesterol efflux capacity, which was shown to inversely correlate with atherosclerotic cardiovascular disease in populations with normal kidney function. Patients with ESRD suffer an exceptionally high cardiovascular risk not fully explained by traditional risk factors. Here, in a post hoc analysis in 1147 patients with type 2 diabetes mellitus on hemodialysis who participated in the German Diabetes Dialysis Study (4D Study), we investigated whether the HDL cholesterol efflux capacity is predictive for cardiovascular risk. Efflux capacity was quantified by incubating human macrophage foam cells with apoB-depleted serum. During a median follow-up of 4.1 years, 423 patients reached the combined primary end point (composite of cardiac death, nonfatal myocardial infarction, and stroke), 410 patients experienced cardiac events, and 561 patients died. Notably, in Cox regression analyses, we found no association of efflux capacity with the combined primary end point (hazard ratio [HR], 0.96; 95% confidence interval [95% CI], 0.88 to 1.06; P=0.42), cardiac events (HR, 0.92; 95% CI, 0.83 to 1.02; P=0.11), or all-cause mortality (HR, 0.96; 95% CI, 0.88 to 1.05; P=0.39). In conclusion, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in this cohort of patients with diabetes on hemodialysis.Kopecky, ChantalEbtehaj, SanamGenser, BerndDrechsler, ChristianeKrane, VeraAntlanger, MarliesKovarik, Johannes J.Kaltenecker, Christopher C.Parvizi, MojtabaWanner, ChristophWeichhart, ThomasSäemann, Marcus D.Tietge, Uwe J.F.2016-09-09T09:59:12-07:00doi:10.1681/ASN.2016030262hwp:resource-id:jnephrol;28/3/769American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, cardiovascular, risk factors, HDL, cholesterol effluxBrief CommunicationsBrief Communicationsbrief-report20172017-03-01March 201710.1681/ASN.20160302621046-66731533-34502016-09-09T09:59:12-07:002017-03Journal of the American Society of NephrologyBrief Communications283769775
- Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort StudyThe rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome–wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10−6 for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42×10−7; replication P=0.039; combined P=7.42×10−9). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90×10−6). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44×10−4) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.10.1681/ASN.2015101152Tue, 11 Oct 2016 06:07:40 GMT-07:00Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort StudyThe rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome–wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10−6 for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42×10−7; replication P=0.039; combined P=7.42×10−9). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90×10−6). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44×10−4) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.Parsa, AfshinKanetsky, Peter A.Xiao, RuiGupta, JayantaMitra, NanditaLimou, SophieXie, DaweiXu, HuichunAnderson, Amanda HyreOjo, AkinloluKusek, John W.Lora, Claudia M.Hamm, L. LeeHe, JiangSandholm, NiinaJeff, JaninaRaj, Dominic E.Böger, Carsten A.Bottinger, ErwinSalimi, ShabnamParekh, Rulan S.Adler, Sharon G.Langefeld, Carl D.Bowden, Donald W.,Groop, Per-HenrikForsblom, CarolFreedman, Barry I.Lipkowitz, MichaelFox, Caroline S.Winkler, Cheryl A.Feldman, Harold I.Iyengar, Sudha K.Sedor, John R.Freedman, Barry I.Kao, W.H. LindaKretzler, MatthiasKeller, Benjamin J.Abboud, Hanna E.Adler, Sharon G.Best, Lyle G.Bowden, Donald W.Burlock, AllisonChen, Yii-Der IdaCole, Shelley A.Comeau, Mary E.Curtis, Jeffrey M.Divers, JasminDrechsler, ChristianeDuggirala, RaviElston, Robert C.Guo, XiuqingHuang, HuatengHoffman, Michael MarcusHoward, Barbara V.Ipp, EliKimmel, Paul L.Klag, Michael J.Knowler, William C.Kohn, Orly F.Leak, Tennille S.Leehey, David J.Li, ManMalhotra, AlkaMärz, WinfriedNair, VijiNelson, Robert G.Nicholas, Susanne B.O’Brien, Stephen J.Pahl, Madeleine V.Parekh, Rulan S.Pezzolesi, Marcus G.Rasooly, Rebekah S.Rotimi, Charles N.Rotter, Jerome I.Schelling, Jeffrey R.Seldin, Michael F.Shah, Vallabh O.Smiles, Adam M.Smith, Michael W.Taylor, Kent D.Thameem, FarookThornley-Brown, Denyse P.Truitt, Barbara J.Wanner, ChristophWeil, E. JenniferWinkler, Cheryl A.Zager, Philip G.Igo, Robert P.Hanson, Robert L.Langefeld, Carl D.Appel, Lawrence J.Go, Alan S.Lash, James P.Rahman, MahboobTownsend, Raymond R.2016-10-11T06:07:40-07:00doi:10.1681/ASN.2015101152hwp:resource-id:jnephrol;28/3/923American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, human genetics, polymorphisms, progression of chronic renal failureClinical EpidemiologyClinical Epidemiologyresearch-article20172017-03-01March 201710.1681/ASN.20151011521046-66731533-34502016-10-11T06:07:40-07:002017-03Journal of the American Society of NephrologyClinical Epidemiology283923934
- Risk Factors for Severe Renal Disease in Bardet–Biedl SyndromeBardet–Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1–19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet–Biedl syndrome–related renal disease attending the United Kingdom national Bardet–Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4–5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10, mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b–5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet–Biedl syndrome and identifies risk factors to be considered in genetic counseling.10.1681/ASN.2015091029Thu, 22 Sep 2016 06:18:21 GMT-07:00Risk Factors for Severe Renal Disease in Bardet–Biedl SyndromeBardet–Biedl syndrome is a rare autosomal recessive, multisystem disease characterized by retinal dystrophy, renal malformation, obesity, intellectual disability, polydactyly, and hypogonadism. Nineteen disease-causing genes (BBS1–19) have been identified, of which mutations in BBS1 are most common in North America and Europe. A hallmark of the disease, renal malformation is heterogeneous and is a cause of morbidity and mortality through the development of CKD. We studied the prevalence and severity of CKD in 350 patients with Bardet–Biedl syndrome–related renal disease attending the United Kingdom national Bardet–Biedl syndrome clinics to further elucidate the phenotype and identify risk indicators of CKD. Overall, 31% of children and 42% of adults had CKD; 6% of children and 8% of adults had stage 4–5 CKD. In children, renal disease was often detected within the first year of life. Analysis of the most commonly mutated disease-associated genes revealed that, compared with two truncating mutations, two missense mutations associated with less severe CKD in adults. Moreover, compared with mutations in BBS10, mutations in BBS1 associated with less severe CKD or lack of CKD in adults. Finally, 51% of patients with available ultrasounds had structural renal abnormalities, and 35% of adults were hypertensive. The presence of structural abnormalities or antihypertensive medication also correlated statistically with stage 3b–5 CKD. This study describes the largest reported cohort of patients with renal disease in Bardet–Biedl syndrome and identifies risk factors to be considered in genetic counseling.Forsythe, ElizabethSparks, KathrynBest, SunaynaBorrows, SarahHoskins, BethanSabir, AtafBarrett, TimothyWilliams, DeniseMohammed, ShehlaGoldsmith, DavidMilford, David V.Bockenhauer, DetlefFoggensteiner, LukasBeales, Philip L.2016-09-22T06:18:21-07:00doi:10.1681/ASN.2015091029hwp:resource-id:jnephrol;28/3/963American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, ESRD, human genetics, risk factorsClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20150910291046-66731533-34502016-09-22T06:18:21-07:002017-03Journal of the American Society of NephrologyClinical Research283963970
- SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and FunctionGenome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10−7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10−8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.10.1681/ASN.2016020131Mon, 05 Dec 2016 08:14:56 GMT-08:00SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and FunctionGenome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10−7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10−8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.Li, ManLi, YongWeeks, OliviaMijatovic, VladanTeumer, AlexanderHuffman, Jennifer E.Tromp, GerardFuchsberger, ChristianGorski, MathiasLyytikäinen, Leo-PekkaNutile, TeresaSedaghat, SanazSorice, RossellaTin, AdrienneYang, QiongAhluwalia, Tarunveer S.Arking, Dan E.Bihlmeyer, Nathan A.Böger, Carsten A.Carroll, Robert J.Chasman, Daniel I.Cornelis, Marilyn C.Dehghan, AbbasFaul, Jessica D.Feitosa, Mary F.Gambaro, GiovanniGasparini, PaoloGiulianini, FrancoHeid, IrisHuang, JinyanImboden, MedeaJackson, Anne U.Jeff, JaninaJhun, Min A.Katz, RonitKifley, AnnetteKilpeläinen, Tuomas O.Kumar, AshishLaakso, MarkkuLi-Gao, RuifangLohman, KurtLu, YingchangMägi, ReedikMalerba, GiovanniMihailov, EvelinMohlke, Karen L.Mook-Kanamori, Dennis O.Robino, AntoniettaRuderfer, DouglasSalvi, ErikaSchick, Ursula M.Schulz, Christina-AlexandraSmith, Albert V.Smith, Jennifer A.Traglia, MichelaYerges-Armstrong, Laura M.Zhao, WeiGoodarzi, Mark O.Kraja, Aldi T.Liu, ChunyuWessel, Jennifer,,Boerwinkle, EricBorecki, Ingrid B.Bork-Jensen, JetteBottinger, Erwin P.Braga, DanieleBrandslund, IvanBrody, Jennifer A.Campbell, ArchieCarey, David J.Christensen, CramerCoresh, JosefCrook, ErrolCurhan, Gary C.Cusi, Danielede Boer, Ian H.de Vries, Aiko P.J.Denny, Joshua C.Devuyst, OlivierDreisbach, Albert W.Endlich, KarlhansEsko, TõnuFranco, Oscar H.Fulop, TiborGerhard, Glenn S.Glümer, CharlotteGottesman, OmriGrarup, NielsGudnason, VilmundurHansen, TorbenHarris, Tamara B.Hayward, CarolineHocking, LynneHofman, AlbertHu, Frank B.Husemoen, Lise Lotte N.Jackson, Rebecca D.Jørgensen, TorbenJørgensen, Marit E.Kähönen, MikaKardia, Sharon L.R.König, WolfgangKooperberg, CharlesKriebel, JenniferLauner, Lenore J.Lauritzen, TorstenLehtimäki, TerhoLevy, DanielLinksted, PamelaLinneberg, AllanLiu, YongmeiLoos, Ruth J.F.Lupo, AntonioMeisinger, ChristineMelander, OlleMetspalu, AndresMitchell, PaulNauck, MatthiasNürnberg, PeterOrho-Melander, MarjuParsa, AfshinPedersen, OlufPeters, AnnettePeters, UlrikePolasek, OzrenPorteous, DavidProbst-Hensch, Nicole M.Psaty, Bruce M.Qi, LuRaitakari, Olli T.Reiner, Alex P.Rettig, RainerRidker, Paul M.Rivadeneira, FernandoRossouw, Jacques E.Schmidt, FrankSiscovick, DavidSoranzo, NicoleStrauch, KonstantinToniolo, DanielaTurner, Stephen T.Uitterlinden, André G.Ulivi, SheilaVelayutham, DineshVölker, UweVölzke, HenryWaldenberger, MelanieWang, Jie JinWeir, David R.Witte, DanielKuivaniemi, HelenaFox, Caroline S.Franceschini, NoraGoessling, WolframKöttgen, AnnaChu, Audrey Y.Wessel, JenniferChu, Audrey Y.Willems, Sara M.Wang, ShuaiYaghootkar, HaniehBrody, Jennifer A.Dauriz, MarcoHivert, Marie-FranceRaghavan, SridharanLipovich, LeonardHidalgo, BerthaFox, KeoluHuffman, Jennifer E.An, PingLu, YingchangRasmussen-Torvik, Laura J.Grarup, NielsEhm, Margaret G.,Baldridge, Abigail S.Stančáková, AlenaAbrol, RavinderBesse, Ce´lineBoland, AnneBork-Jensen, JetteFornage, MyriamFreitag, Daniel F.Garcia, Melissa E.Guo, XiuqingHara, KazuoIsaacs, AaronJakobsdottir, JohannaLange, Leslie A.Layton, Jill C.Li, ManZhao, Jing HuaMeidtner, KarinaMorrison, Alanna C.Nalls, Mike A.Peters, Marjolein J.Sabater-Lleal, MariaSchurmann, ClaudiaSilveira, AngelaSmith, Albert V.Southam, LorraineStoiber, Marcus H.Strawbridge, Rona J.Taylor, Kent D.Varga, Tibor V.Allin, Kristine H.Amin, NajafAponte, Jennifer L.Aung, TinBarbieri, CaterinaBihlmeyer, Nathan A.Boehnke, MichaelBombieri, CristinaBowden, Donald W.Burns, Sean M.Chen, YuningChen, Yii-DerICheng, Ching-YuCorrea, AdolfoCzajkowski, JacekDehghan, AbbasEhret, Georg B.Eiriksdottir, GudnyEscher, Stefan A.Farmaki, Aliki-EleniFrånberg, MattiasGambaro, GiovanniGiulianini, FrancoGoddard, William A.Goel, AnujGottesman, OmriGrove, Megan L.Gustafsson, StefanHai, YangHallmans, Go¨ranHeo, JiyoungHoffmann, PerIkram, Mohammad K.Jensen, Richard A.Jørgensen, Marit E.Jørgensen, TorbenKaraleftheri, MariaKhor, Chiea C.Kirkpatrick, AndreaKraja, Aldi T.Kuusisto, JohannaLange, Ethan M.Lee, T.Lee, Wen-JaneLeong, AaronLiao, JieminLiu, ChunyuLiu, YongmeiLindgren, Cecilia M.Linneberg, AllanMalerba, GiovanniMamakou, VasilikiMarouli, EiriniMaruthur, Nisa M.Matchan, AngelaMcKean-Cowdin, RobertaMcLeod, OlgaMetcalf, Ginger A.Mohlke, Karen L.Muzny, Donna M.Ntalla, IoannaPalmer, Nicholette D.Pasko, DorotaPeter, AndreasRayner, Nigel W.Renstro¨m, FridaRice, KenSala, Cinzia F.Sennblad, BengtSerafetinidis, IoannisSmith, Jennifer A.Soranzo, NicoleSpeliotes, Elizabeth K.Stahl, Eli A.Stirrups, KathleenTentolouris, NikosThanopoulou, AnastasiaTorres, MinaTraglia, MichelaTsafantakis, EmmanouilJavad, SundasYanek, Lisa R.Zengini, EleniBecker, Diane M.Bis, Joshua C.Brown, James B.Cupples, L. AdrienneHansen, TorbenIngelsson, ErikKarter, Andrew J.Lorenzo, CarlosMathias, Rasika A.Norris, Jill M.Peloso, Gina M.Sheu, Wayne H.-H.Toniolo, DanielaVaidya, DhananjayVarma, RohitWagenknecht, Lynne E.Boeing, HeinerBottinger, Erwin P.Dedoussis, GeorgeDeloukas, PanosFerrannini, EleFranco, Oscar H.Franks, Paul W.Gibbs, Richard A.Gudnason, VilmundurHamsten, AndersHarris, Tamara B.Hattersley, Andrew T.Hayward, CarolineHofman, AlbertJansson, Jan-HåkanLangenberg, ClaudiaLauner, Lenore J.Levy, DanielOostra, Ben A.O’Donnell, Christopher J.O’Rahilly, StephenPadmanabhan, SandoshPankow, James S.Polasek, OzrenProvince, Michael A.Rich, Stephen S.Ridker, Paul M.Rudan, IgorSchulze, Matthias B.Smith, Blair H.Uitterlinden, Andre´ G.Walker, MarkWatkins, HughWong, Tien Y.Zeggini, EleftheriaConsortiumy, The EPIC-InterActLaakso, MarkkuBorecki, Ingrid B.Chasman, Daniel I.Pedersen, OlufPsaty, Bruce M.Tai, E. Shyongvan Duijn, Cornelia M.Wareham, Nicholas J.Waterworth, Dawn M.Boerwinkle, EricKao, W.H. LindaFlorez, Jose C.Loos, Ruth J.F.Wilson, James G.Frayling, Timothy M.Siscovick, David S.Dupuis, Jose´eRotter, Jerome I.Meigs, James B.Scott, Robert A.Goodarzi, Mark O.Liu, ChunyuKraja, Aldi T.Smith, Jennifer A.Brody, Jennifer A.Franceschini, NoraBis, Joshua C.Rice, KennethMorrison, Alanna C.Lu, YingchangWeiss, StefanGuo, XiuqingPalmas, WalterMartin, Lisa W.Chen, Yii-Der IdaSurendran, PraveenDrenos, FotiosCook, James P.Auer, Paul L.Chu, Audrey Y.Giri, AyushZhao, WeiJakobsdottir, JohannaLin, Li-AnStafford, Jeanette M.Amin, NajafMei, HaoYao, JieVoorman, Arend,,,,,,Larson, Martin G.Grove, Megan L.Smith, Albert V.Hwang, Shih-JenChen, HanHuan, TianxiaoKosova, GulumStitziel, Nathan O.Kathiresan, SekarSamani, NileshSchunkert, HeribertDeloukas, PanosGenetics, Myocardial Infarction,Li, ManFuchsberger, ChristianPattaro, CristianGorski, Mathias,Kooperberg, CharlesPapanicolaou, George J.Rossouw, Jacques E.Faul, Jessica D.Kardia, Sharon L.R.Bouchard, ClaudeRaffel, Leslie J.Uitterlinden, André G.Franco, Oscar H.Vasan, Ramachandran S.O'Donnell, Christopher J.Taylor, Kent D.Liu, KiangBottinger, Erwin P.Gottesman, OmriDaw, E. WarwickGiulianini, FrancoGanesh, SanthiSalfati, EliasHarris, Tamara B.Launer, Lenore J.Dörr, MarcusFelix, Stephan B.Rettig, RainerVölzke, HenryKim, EricLee, Wen-JaneLee, TeSheu, Wayne H-HTsosie, Krystal S.Edwards, Digna R. VelezLiu, YongmeiCorrea, AdolfoWeir, David R.Völker, UweRidker, Paul MBoerwinkle, EricGudnason, VilmundurReiner, Alexander P.van Duijn, Cornelia M.Borecki, Ingrid B.Edwards, Todd L.Chakravarti, AravindaRotter, Jerome I.Psaty, Bruce M.Loos, Ruth J.F.Fornage, MyriamEhret, GeorgNewton-Cheh, ChristopherLevy, DanielChasman, Daniel I.2016-12-05T08:14:56-08:00doi:10.1681/ASN.2016020131hwp:resource-id:jnephrol;28/3/981American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal function, human genetics, kidney developmentClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20160201311046-66731533-34502016-12-05T08:14:56-08:002017-03Journal of the American Society of NephrologyClinical Research283981994
- Bicarbonate Balance and Prescription in ESRDThe optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional studies in hemodialysis have been limited and inconsistent in their findings, whereas more compelling data are available from interventional studies in peritoneal dialysis. Both high and low serum bicarbonate levels associate with an increased risk of mortality in patients receiving hemodialysis, but high values are a marker for poor nutrition and comorbidity and are often highly variable from month to month. Measurement of pH would likely provide useful additional data. Concern has arisen regarding high-bicarbonate dialysate and dialysis-induced alkalemia, but whether these truly cause harm remains to be determined. The available evidence is insufficient for determining the optimal target for therapy at this time.10.1681/ASN.2016070780Wed, 23 Nov 2016 09:30:59 GMT-08:00Bicarbonate Balance and Prescription in ESRDThe optimal approach to managing acid-base balance is less well defined for patients receiving hemodialysis than for those receiving peritoneal dialysis. Interventional studies in hemodialysis have been limited and inconsistent in their findings, whereas more compelling data are available from interventional studies in peritoneal dialysis. Both high and low serum bicarbonate levels associate with an increased risk of mortality in patients receiving hemodialysis, but high values are a marker for poor nutrition and comorbidity and are often highly variable from month to month. Measurement of pH would likely provide useful additional data. Concern has arisen regarding high-bicarbonate dialysate and dialysis-induced alkalemia, but whether these truly cause harm remains to be determined. The available evidence is insufficient for determining the optimal target for therapy at this time.Abramowitz, Matthew K.2016-11-23T09:30:59-08:00doi:10.1681/ASN.2016070780hwp:resource-id:jnephrol;28/3/726American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, acidosis, electrolytesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-03-01March 201710.1681/ASN.20160707801046-66731533-34502016-11-23T09:30:59-08:002017-03Journal of the American Society of NephrologyUp Front Matters283726734
- Progress in Understanding the Genetics of Calcium-Containing NephrolithiasisRenal stone disease is a frequent condition, causing a huge burden on health care systems globally. Calcium-based calculi account for around 75% of renal stone disease and the incidence of these calculi is increasing, suggesting environmental and dietary factors are acting upon a preexisting genetic background. The familial nature and significant heritability of stone disease is known, and recent genetic studies have successfully identified genes that may be involved in renal stone formation. The detection of monogenic causes of renal stone disease has been made more feasible by the use of high-throughput sequencing technologies and has also facilitated the discovery of novel monogenic causes of stone disease. However, the majority of calcium stone formers remain of undetermined genotype. Genome-wide association studies and candidate gene studies implicate a series of genes involved in renal tubular handling of lithogenic substrates, such as calcium, oxalate, and phosphate, and of inhibitors of crystallization, such as citrate and magnesium. Additionally, expression profiling of renal tissues from stone formers provides a novel way to explore disease pathways. New animal models to explore these recently-identified mechanisms and therapeutic interventions are being tested, which hopefully will provide translational insights to stop the growing incidence of nephrolithiasis.10.1681/ASN.2016050576Thu, 08 Dec 2016 06:53:11 GMT-08:00Progress in Understanding the Genetics of Calcium-Containing NephrolithiasisRenal stone disease is a frequent condition, causing a huge burden on health care systems globally. Calcium-based calculi account for around 75% of renal stone disease and the incidence of these calculi is increasing, suggesting environmental and dietary factors are acting upon a preexisting genetic background. The familial nature and significant heritability of stone disease is known, and recent genetic studies have successfully identified genes that may be involved in renal stone formation. The detection of monogenic causes of renal stone disease has been made more feasible by the use of high-throughput sequencing technologies and has also facilitated the discovery of novel monogenic causes of stone disease. However, the majority of calcium stone formers remain of undetermined genotype. Genome-wide association studies and candidate gene studies implicate a series of genes involved in renal tubular handling of lithogenic substrates, such as calcium, oxalate, and phosphate, and of inhibitors of crystallization, such as citrate and magnesium. Additionally, expression profiling of renal tissues from stone formers provides a novel way to explore disease pathways. New animal models to explore these recently-identified mechanisms and therapeutic interventions are being tested, which hopefully will provide translational insights to stop the growing incidence of nephrolithiasis.Sayer, John A.2016-12-08T06:53:11-08:00doi:10.1681/ASN.2016050576hwp:resource-id:jnephrol;28/3/748American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, kidney stones, molecular genetics, polymorphisms, Vitamin DUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-03-01March 201710.1681/ASN.20160505761046-66731533-34502016-12-08T06:53:11-08:002017-03Journal of the American Society of NephrologyUp Front Matters283748759
- A Randomized Trial to Reduce Disparities in Referral for Transplant EvaluationGeorgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility–based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral. The intervention consisted of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients conducted from January to December of 2014. We examined the proportion of patients with prevalent ESRD in each facility referred for transplant within 1 year as the primary outcome, and disparity in the referral of black and white patients as a secondary outcome. Compared with control facilities, intervention facilities referred a higher proportion of patients for transplant at 12 months (adjusted mean difference [aMD], 7.3%; 95% confidence interval [95% CI], 5.5% to 9.2%; odds ratio, 1.75; 95% CI, 1.36 to 2.26). The difference between intervention and control facilities in the proportion of patients referred for transplant was higher among black patients (aMD, 6.4%; 95% CI, 4.3% to 8.6%) than white patients (aMD, 3.7%; 95% CI, 1.6% to 5.9%; P<0.05). In conclusion, this intervention increased referral and improved equity in kidney transplant referral for patients on dialysis in Georgia; long-term follow-up is needed to determine whether these effects led to more transplants.10.1681/ASN.2016030320Thu, 13 Oct 2016 06:15:23 GMT-07:00A Randomized Trial to Reduce Disparities in Referral for Transplant EvaluationGeorgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility–based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral. The intervention consisted of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients conducted from January to December of 2014. We examined the proportion of patients with prevalent ESRD in each facility referred for transplant within 1 year as the primary outcome, and disparity in the referral of black and white patients as a secondary outcome. Compared with control facilities, intervention facilities referred a higher proportion of patients for transplant at 12 months (adjusted mean difference [aMD], 7.3%; 95% confidence interval [95% CI], 5.5% to 9.2%; odds ratio, 1.75; 95% CI, 1.36 to 2.26). The difference between intervention and control facilities in the proportion of patients referred for transplant was higher among black patients (aMD, 6.4%; 95% CI, 4.3% to 8.6%) than white patients (aMD, 3.7%; 95% CI, 1.6% to 5.9%; P<0.05). In conclusion, this intervention increased referral and improved equity in kidney transplant referral for patients on dialysis in Georgia; long-term follow-up is needed to determine whether these effects led to more transplants.Patzer, Rachel E.Paul, SudeshnaPlantinga, LauraGander, JenniferSauls, LeighannKrisher, JennaMulloy, Laura L.Gibney, Eric M.Browne, TeriZayas, Carlos F.McClellan, William M.Arriola, Kimberly JacobPastan, Stephen O.Patzer, Rachel E.Paul, SudeshnaPlantinga, LauraGander, JenniferSauls, LeighannKrisher, JennaMulloy, Laura L.Gibney, Eric M.Browne, TeriZayas, Carlos F.McClellan, William M.Arriola, Kimberly JacobPastan, Stephen O.2016-10-13T06:15:23-07:00doi:10.1681/ASN.2016030320hwp:resource-id:jnephrol;28/3/935American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, dialysis facility, randomized trial, education, staff, community-based participatory researchClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20160303201046-66731533-34502016-10-13T06:15:23-07:002017-03Journal of the American Society of NephrologyClinical Research2833935721942723
- Targeting eIF5A Hypusination Prevents Anoxic Cell Death through Mitochondrial Silencing and Improves Kidney Transplant OutcomeThe eukaryotic initiation factor 5A (eIF5A), which is highly conserved throughout evolution, has the unique characteristic of post-translational activation through hypusination. This modification is catalyzed by two enzymatic steps involving deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Notably, eIF5A may be involved in regulating the lifespan of Drosophila during long-term hypoxia. Therefore, we investigated the possibility of a link between eIF5A hypusination and cellular resistance to hypoxia/anoxia. Pharmacologic targeting of DHPS by N1-guanyl-1,7-diaminoheptane (GC7) or RNA interference–mediated inhibition of DHPS or DOHH induced tolerance to anoxia in immortalized mouse renal proximal cells. Furthermore, GC7 treatment of cells reversibly induced a metabolic shift toward glycolysis as well as mitochondrial remodeling and led to downregulated expression and activity of respiratory chain complexes, features characteristic of mitochondrial silencing. GC7 treatment also attenuated anoxia-induced generation of reactive oxygen species in these cells and in normoxic conditions, decreased the mitochondrial oxygen consumption rate of cultured cells and mice. In rats, intraperitoneal injection of GC7 substantially reduced renal levels of hypusinated eIF5A and protected against ischemia-reperfusion–induced renal injury. Finally, in the preclinical pig kidney transplant model, intravenous injection of GC7 before kidney removal significantly improved graft function recovery and late graft function and reduced interstitial fibrosis after transplant. This unconventional signaling pathway offers an innovative therapeutic target for treating hypoxic-ischemic human diseases and organ transplantation.10.1681/ASN.2016010012Fri, 09 Sep 2016 09:59:13 GMT-07:00Targeting eIF5A Hypusination Prevents Anoxic Cell Death through Mitochondrial Silencing and Improves Kidney Transplant OutcomeThe eukaryotic initiation factor 5A (eIF5A), which is highly conserved throughout evolution, has the unique characteristic of post-translational activation through hypusination. This modification is catalyzed by two enzymatic steps involving deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Notably, eIF5A may be involved in regulating the lifespan of Drosophila during long-term hypoxia. Therefore, we investigated the possibility of a link between eIF5A hypusination and cellular resistance to hypoxia/anoxia. Pharmacologic targeting of DHPS by N1-guanyl-1,7-diaminoheptane (GC7) or RNA interference–mediated inhibition of DHPS or DOHH induced tolerance to anoxia in immortalized mouse renal proximal cells. Furthermore, GC7 treatment of cells reversibly induced a metabolic shift toward glycolysis as well as mitochondrial remodeling and led to downregulated expression and activity of respiratory chain complexes, features characteristic of mitochondrial silencing. GC7 treatment also attenuated anoxia-induced generation of reactive oxygen species in these cells and in normoxic conditions, decreased the mitochondrial oxygen consumption rate of cultured cells and mice. In rats, intraperitoneal injection of GC7 substantially reduced renal levels of hypusinated eIF5A and protected against ischemia-reperfusion–induced renal injury. Finally, in the preclinical pig kidney transplant model, intravenous injection of GC7 before kidney removal significantly improved graft function recovery and late graft function and reduced interstitial fibrosis after transplant. This unconventional signaling pathway offers an innovative therapeutic target for treating hypoxic-ischemic human diseases and organ transplantation.Melis, NicolasRubera, IsabelleCougnon, MarcGiraud, SébastienMograbi, BahariaBelaid, AminePisani, Didier F.Huber, Stephan M.Lacas-Gervais, SandraFragaki, KonstantinaBlondeau, NicolasVigne, PaulFrelin, ChristianHauet, ThierryDuranton, ChristopheTauc, Michel2016-09-09T09:59:13-07:00doi:10.1681/ASN.2016010012hwp:resource-id:jnephrol;28/3/811American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycell survival, hypoxia, ischemia, transplant outcomes, kidney transplantation, renal cell biologyBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160100121046-66731533-34502016-09-09T09:59:13-07:002017-03Journal of the American Society of NephrologyBasic Research283811822
- Should Transplant Referral Be a Clinical Performance Measure?10.1681/ASN.2016111169Mon, 05 Dec 2016 08:14:54 GMT-08:00Should Transplant Referral Be a Clinical Performance Measure?Sehgal, Ashwini R.2016-12-05T08:14:54-08:00doi:10.1681/ASN.2016111169hwp:resource-id:jnephrol;28/3/721American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, transplant outcomes, quality of careUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-03-01March 201710.1681/ASN.20161111691046-66731533-34502016-12-05T08:14:54-08:002017-03Journal of the American Society of NephrologyUp Front Matters2833721935723942
- Moving Biomarkers toward Clinical Implementation in Kidney TransplantationLong-term kidney transplant outcomes remain suboptimal, delineating an unmet medical need. Although current immunosuppressive therapy in kidney transplant recipients is effective, dosing is conventionally adjusted empirically on the basis of time after transplant or altered in response to detection of kidney dysfunction, histologic evidence of allograft damage, or infection. Such strategies tend to detect allograft rejection after significant injury has already occurred, fail to detect chronic subclinical inflammation that can negatively affect graft survival, and ignore specific risks and immune mechanisms that differentially contribute to allograft damage among transplant recipients. Assays and biomarkers that reliably quantify and/or predict the risk of allograft injury have the potential to overcome these deficits and thereby, aid clinicians in optimizing immunosuppressive regimens. Herein, we review the data on candidate biomarkers that we contend have the highest potential to become clinically useful surrogates in kidney transplant recipients, including functional T cell assays, urinary gene and protein assays, peripheral blood cell gene expression profiles, and allograft gene expression profiles. We identify barriers to clinical biomarker adoption in the transplant field and suggest strategies for moving biomarker-based individualization of transplant care from a research hypothesis to clinical implementation.10.1681/ASN.2016080858Fri, 06 Jan 2017 05:19:28 GMT-08:00Moving Biomarkers toward Clinical Implementation in Kidney TransplantationLong-term kidney transplant outcomes remain suboptimal, delineating an unmet medical need. Although current immunosuppressive therapy in kidney transplant recipients is effective, dosing is conventionally adjusted empirically on the basis of time after transplant or altered in response to detection of kidney dysfunction, histologic evidence of allograft damage, or infection. Such strategies tend to detect allograft rejection after significant injury has already occurred, fail to detect chronic subclinical inflammation that can negatively affect graft survival, and ignore specific risks and immune mechanisms that differentially contribute to allograft damage among transplant recipients. Assays and biomarkers that reliably quantify and/or predict the risk of allograft injury have the potential to overcome these deficits and thereby, aid clinicians in optimizing immunosuppressive regimens. Herein, we review the data on candidate biomarkers that we contend have the highest potential to become clinically useful surrogates in kidney transplant recipients, including functional T cell assays, urinary gene and protein assays, peripheral blood cell gene expression profiles, and allograft gene expression profiles. We identify barriers to clinical biomarker adoption in the transplant field and suggest strategies for moving biomarker-based individualization of transplant care from a research hypothesis to clinical implementation.Menon, Madhav C.Murphy, BarbaraHeeger, Peter S.2017-01-06T05:19:28-08:00doi:10.1681/ASN.2016080858hwp:resource-id:jnephrol;28/3/735American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant outcomes, transplantation, biomarkerUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-03-01March 201710.1681/ASN.20160808581046-66731533-34502017-01-06T05:19:28-08:002017-03Journal of the American Society of NephrologyUp Front Matters283735747
- This Month's Highlights10.1681/ASN.2016111228Tue, 28 Feb 2017 01:00:45 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2017-02-28T13:00:45-08:00doi:10.1681/ASN.2016111228hwp:resource-id:jnephrol;28/3/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20172017-03-01March 201710.1681/ASN.20161112281046-66731533-34502017-02-28T13:00:45-08:002017-03Journal of the American Society of NephrologyThis Month's Highlights283ii
- IL-1 Inhibition and Vascular Function in CKDVascular endothelial dysfunction and increased arterial stiffness contribute to increased cardiovascular risk in patients with CKD who exhibit chronic systemic inflammation. Because chronic inflammation contributes to vascular dysfunction, blocking inflammation may reduce cardiovascular risk in patients with CKD. In a two-site, double-blind trial, we randomized 42 adult patients with stage 3–4 CKD who were already receiving optimal background therapy to receive either IL-1 trap rilonacept or placebo for 12 weeks. Coprimary end points included change in brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV) after 4, 8, and 12 weeks. Exploratory end points included change in high-sensitivity C-reactive protein (hsCRP), FMDBA after acute ascorbic acid infusion, and vascular endothelial cell protein expression of NADPH oxidase. Participants were 63±11 (mean±SD) years of age and 24% were women; mean eGFR was 38±13 ml/min per 1.73 m2. Compared with placebo, rilonacept improved FMDBA (baseline: 3.36%±2.06% [mean±SD], 12 weeks: 2.45%±2.29% with placebo and baseline: 3.75%±3.12%, 12 weeks: 4.86%±3.20% with rilonacept; P<0.01), without changing aPWV (P=0.56). Rilonacept also reduced hsCRP levels (median [interquartile range]) (baseline: 4.60 [1.90–8.22] mg/L, 12 weeks: 2.16 [0.92–7.38] mg/L; P<0.01) and endothelial cell NADPH oxidase expression (P<0.05). Acute infusion of ascorbic acid to inhibit superoxide production associated with a nonsignificant trend toward increased FMDBA in the placebo group (P=0.07) but not the rilonacept group (P=0.56). Rilonacept was well tolerated (five adverse events versus two with placebo). In conclusion, treatment with an IL-1 trap improved FMDBA without changing aPWV and reduced systemic inflammation in patients with CKD.10.1681/ASN.2016040453Mon, 19 Sep 2016 10:04:58 GMT-07:00IL-1 Inhibition and Vascular Function in CKDVascular endothelial dysfunction and increased arterial stiffness contribute to increased cardiovascular risk in patients with CKD who exhibit chronic systemic inflammation. Because chronic inflammation contributes to vascular dysfunction, blocking inflammation may reduce cardiovascular risk in patients with CKD. In a two-site, double-blind trial, we randomized 42 adult patients with stage 3–4 CKD who were already receiving optimal background therapy to receive either IL-1 trap rilonacept or placebo for 12 weeks. Coprimary end points included change in brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV) after 4, 8, and 12 weeks. Exploratory end points included change in high-sensitivity C-reactive protein (hsCRP), FMDBA after acute ascorbic acid infusion, and vascular endothelial cell protein expression of NADPH oxidase. Participants were 63±11 (mean±SD) years of age and 24% were women; mean eGFR was 38±13 ml/min per 1.73 m2. Compared with placebo, rilonacept improved FMDBA (baseline: 3.36%±2.06% [mean±SD], 12 weeks: 2.45%±2.29% with placebo and baseline: 3.75%±3.12%, 12 weeks: 4.86%±3.20% with rilonacept; P<0.01), without changing aPWV (P=0.56). Rilonacept also reduced hsCRP levels (median [interquartile range]) (baseline: 4.60 [1.90–8.22] mg/L, 12 weeks: 2.16 [0.92–7.38] mg/L; P<0.01) and endothelial cell NADPH oxidase expression (P<0.05). Acute infusion of ascorbic acid to inhibit superoxide production associated with a nonsignificant trend toward increased FMDBA in the placebo group (P=0.07) but not the rilonacept group (P=0.56). Rilonacept was well tolerated (five adverse events versus two with placebo). In conclusion, treatment with an IL-1 trap improved FMDBA without changing aPWV and reduced systemic inflammation in patients with CKD.Nowak, Kristen L.Chonchol, MichelIkizler, Talat AlpFarmer-Bailey, HeatherSalas, NatjalieChaudhry, RafiaWang, WeiSmits, GerardTengesdal, IsakDinarello, Charles A.Hung, Adriana M.2016-09-19T10:04:58-07:00doi:10.1681/ASN.2016040453hwp:resource-id:jnephrol;28/3/971American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical trial, chronic kidney disease, endothelium, pulse wave velocity, randomized controlled trials, vascularClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20160404531046-66731533-34502016-09-19T10:04:58-07:002017-03Journal of the American Society of NephrologyClinical Research2833971723980725
- Transmembrane TNF-α Facilitates HIV-1 Infection of Podocytes Cultured from Children with HIV-Associated NephropathyStudies have shown that podocytes and renal tubular epithelial cells from patients with HIV-associated nephropathy (HIVAN) express HIV-1 transcripts, suggesting that productive infection of renal epithelial cells precipitates development of HIVAN. However, podocytes and renal tubular epithelial cells do not express CD4 receptors, and it is unclear how these cells become productively infected in vivo. We investigated the mechanisms underlying the infection by HIV-1 of podocytes cultured from the urine of children with HIVAN. We observed low–level productive infection on exposure of these cells to primary cell-free HIV-1 supernatants. However, envelope–defective recombinant HIV-1 did not infect the renal epithelial cell lines. Moreover, treatment of podocytes to inhibit endocytic transport or dynamin activity or remove cell surface heparan sulfate proteoglycans reduced infection efficiency. Transfection of CD4− 293T cells with a cDNA expression library developed from a podocyte cell line derived from a child with HIVAN led to the identification of TNF-α as a possible mediator of HIV-1 infection. Overexpression of transmembrane TNF-α in cultured CD4− renal tubular epithelial cells, 293T cells, and HeLa cells enabled the infection of these cells; exposure to soluble TNF-α did not. Immunohistochemistry showed TNF-α expression in podocytes of renal sections from children with HIVAN. Furthermore, we found that TNF-α enhanced NF-κB activation and integration of HIV-1 into the podocyte DNA. Finally, inhibition of dynamin activity blocked TNF-α–mediated infection. These data establish a role for transmembrane TNF-α in facilitating the viral entry and integration of HIV-1 into the DNA of renal epithelial cells.10.1681/ASN.2016050564Thu, 03 Nov 2016 05:37:37 GMT-07:00Transmembrane TNF-α Facilitates HIV-1 Infection of Podocytes Cultured from Children with HIV-Associated NephropathyStudies have shown that podocytes and renal tubular epithelial cells from patients with HIV-associated nephropathy (HIVAN) express HIV-1 transcripts, suggesting that productive infection of renal epithelial cells precipitates development of HIVAN. However, podocytes and renal tubular epithelial cells do not express CD4 receptors, and it is unclear how these cells become productively infected in vivo. We investigated the mechanisms underlying the infection by HIV-1 of podocytes cultured from the urine of children with HIVAN. We observed low–level productive infection on exposure of these cells to primary cell-free HIV-1 supernatants. However, envelope–defective recombinant HIV-1 did not infect the renal epithelial cell lines. Moreover, treatment of podocytes to inhibit endocytic transport or dynamin activity or remove cell surface heparan sulfate proteoglycans reduced infection efficiency. Transfection of CD4− 293T cells with a cDNA expression library developed from a podocyte cell line derived from a child with HIVAN led to the identification of TNF-α as a possible mediator of HIV-1 infection. Overexpression of transmembrane TNF-α in cultured CD4− renal tubular epithelial cells, 293T cells, and HeLa cells enabled the infection of these cells; exposure to soluble TNF-α did not. Immunohistochemistry showed TNF-α expression in podocytes of renal sections from children with HIVAN. Furthermore, we found that TNF-α enhanced NF-κB activation and integration of HIV-1 into the podocyte DNA. Finally, inhibition of dynamin activity blocked TNF-α–mediated infection. These data establish a role for transmembrane TNF-α in facilitating the viral entry and integration of HIV-1 into the DNA of renal epithelial cells.Li, JinliangDas, Jharna R.Tang, PingtaoHan, ZheJaiswal, Jyoti K.Ray, Patricio E.2016-11-03T05:37:37-07:00doi:10.1681/ASN.2016050564hwp:resource-id:jnephrol;28/3/862American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyHIV nephropathy, children, cytokines, pediatric nephrology, podocyte, renal tubular epithelial cellsBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160505641046-66731533-34502016-11-03T05:37:37-07:002017-03Journal of the American Society of NephrologyBasic Research28333862717719875719721
- Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in PodocytesTyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14–3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes.10.1681/ASN.2016040414Wed, 14 Sep 2016 07:22:11 GMT-07:00Synaptopodin Is a Coincidence Detector of Tyrosine versus Serine/Threonine Phosphorylation for the Modulation of Rho Protein Crosstalk in PodocytesTyrosine and serine/threonine signal-transduction pathways influence many aspects of cell behavior, including the spatial and temporal regulation of the actin cytoskeleton. However, little is known about how input from diverse tyrosine and serine/threonine kinases is integrated to control Rho protein crosstalk and actin remodeling, which are critically important in podocyte health and disease. Here we unveil the proteolytically-regulated, actin organizing protein synaptopodin as a coincidence detector of tyrosine versus serine/threonine phosphorylation. We show that serine/threonine and tyrosine kinases duel for synaptopodin stability versus degradation. EGFR/Src-mediated tyrosine phosphorylation of synaptopodin in podocytes promotes binding to the serine/threonine phosphatase calcineurin. This leads to the loss of 14–3-3 binding, resulting in synaptopodin degradation, Vav2 activation, enhanced Rac1 signaling, and ultimate loss of stress fibers. Our studies reveal how synaptopodin, a single proteolytically-controlled protein, integrates antagonistic tyrosine versus serine/threonine phosphorylation events for the dynamic control of the actin cytoskeleton in podocytes.Buvall, LisaWallentin, HannaSieber, JonasAndreeva, SvetlanaChoi, Hoon YoungMundel, PeterGreka, Anna2016-09-14T07:22:11-07:00doi:10.1681/ASN.2016040414hwp:resource-id:jnephrol;28/3/837American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyTRPC5, cytoskeleton, Rac1, FSGS, glomerular disease, EGFRBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160404141046-66731533-34502016-09-14T07:22:11-07:002017-03Journal of the American Society of NephrologyBasic Research283837851
- Mitogen-Activated Protein Kinase 14 Promotes AKIAn improved understanding of pathogenic pathways in AKI may identify novel therapeutic approaches. Previously, we conducted unbiased liquid chromatography-tandem mass spectrometry–based protein expression profiling of the renal proteome in mice with acute folate nephropathy. Here, analysis of the dataset identified enrichment of pathways involving NFκB in the kidney cortex, and a targeted data mining approach identified components of the noncanonical NFκB pathway, including the upstream kinase mitogen-activated protein kinase kinase kinase 14 (MAP3K14), the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, as upregulated. Immunohistochemistry localized MAP3K14 expression to tubular cells in acute folate nephropathy and human AKI. In vivo, kidney expression levels of NFκB2 p100 and p52 increased rapidly after folic acid injection, as did DNA binding of RelB and NFκB2, detected in nuclei isolated from the kidneys. Compared with wild-type mice, MAP3K14 activity–deficient aly/aly (MAP3K14aly/aly) mice had less kidney dysfunction, inflammation, and apoptosis in acute folate nephropathy and less kidney dysfunction and a lower mortality rate in cisplatin-induced AKI. The exchange of bone marrow between wild-type and MAP3K14aly/aly mice did not affect the survival rate of either group after folic acid injection. In cultured tubular cells, MAP3K14 small interfering RNA targeting decreased inflammation and cell death. Additionally, cell culture and in vivo studies identified the chemokines MCP-1, RANTES, and CXCL10 as MAP3K14 targets in tubular cells. In conclusion, MAP3K14 promotes kidney injury through promotion of inflammation and cell death and is a promising novel therapeutic target.10.1681/ASN.2015080898Mon, 12 Sep 2016 09:51:39 GMT-07:00Mitogen-Activated Protein Kinase 14 Promotes AKIAn improved understanding of pathogenic pathways in AKI may identify novel therapeutic approaches. Previously, we conducted unbiased liquid chromatography-tandem mass spectrometry–based protein expression profiling of the renal proteome in mice with acute folate nephropathy. Here, analysis of the dataset identified enrichment of pathways involving NFκB in the kidney cortex, and a targeted data mining approach identified components of the noncanonical NFκB pathway, including the upstream kinase mitogen-activated protein kinase kinase kinase 14 (MAP3K14), the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, as upregulated. Immunohistochemistry localized MAP3K14 expression to tubular cells in acute folate nephropathy and human AKI. In vivo, kidney expression levels of NFκB2 p100 and p52 increased rapidly after folic acid injection, as did DNA binding of RelB and NFκB2, detected in nuclei isolated from the kidneys. Compared with wild-type mice, MAP3K14 activity–deficient aly/aly (MAP3K14aly/aly) mice had less kidney dysfunction, inflammation, and apoptosis in acute folate nephropathy and less kidney dysfunction and a lower mortality rate in cisplatin-induced AKI. The exchange of bone marrow between wild-type and MAP3K14aly/aly mice did not affect the survival rate of either group after folic acid injection. In cultured tubular cells, MAP3K14 small interfering RNA targeting decreased inflammation and cell death. Additionally, cell culture and in vivo studies identified the chemokines MCP-1, RANTES, and CXCL10 as MAP3K14 targets in tubular cells. In conclusion, MAP3K14 promotes kidney injury through promotion of inflammation and cell death and is a promising novel therapeutic target.Ortiz, AlbertoHusi, HolgerGonzalez-Lafuente, LauraValiño-Rivas, LaraFresno, ManuelSanz, Ana BelenMullen, WilliamAlbalat, AmayaMezzano, SergioVlahou, ToniaMischak, HaraldSanchez-Niño, Maria Dolores2016-09-12T09:51:39-07:00doi:10.1681/ASN.2015080898hwp:resource-id:jnephrol;28/3/823American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychemokine, renal failure, kidney tubule, renal injury, acute kidney injuryBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20150808981046-66731533-34502016-09-12T09:51:39-07:002017-03Journal of the American Society of NephrologyBasic Research283823836
- Pericytes Preserve Capillary Integrity to Prevent Kidney Hypoxia10.1681/ASN.2016111157Thu, 15 Dec 2016 06:36:00 GMT-08:00Pericytes Preserve Capillary Integrity to Prevent Kidney HypoxiaVenkatachalam, Manjeri A.Weinberg, Joel M.2016-12-15T06:36:00-08:00doi:10.1681/ASN.2016111157hwp:resource-id:jnephrol;28/3/717American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypericytes, peritubular capillaries, hypoxia, acute kidney injury, ischemia, Gli1Up Front MattersEditorialsUp Front MattersEditorialseditorial20172017-03-01March 201710.1681/ASN.20161111571046-66731533-34502016-12-15T06:36:00-08:002017-03Journal of the American Society of NephrologyUp Front Matters28333717776862719784875
- Membranous Nephropathy: Quantifying Remission Duration on OutcomeAlthough change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy–proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4–3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.10.1681/ASN.2015111262Tue, 18 Oct 2016 05:21:45 GMT-07:00Membranous Nephropathy: Quantifying Remission Duration on OutcomeAlthough change in proteinuria has been proposed as a surrogate for long-term prognosis in membranous nephropathy (MGN), variability in proteinuria levels and lag between these changes and acceptable end points, such as ESRD, has limited its utility. This cohort study examined the prognostic significance of remission duration in 376 patients with biopsy–proven idiopathic/primary MGN who achieved a remission after a period of nephrotic-range proteinuria. We defined complete remission (CR), partial remission (PR), and relapse as proteinuria ≤0.3, 0.4–3.4, and ≥3.5 g/d after CR or PR, respectively. The exposure variable was the remission status of patients at fixed landmarks (3, 6, 12, 24, and 36 months) after the date of first remission. The primary outcome was ESRD or 50% reduction in eGFR. We fitted Cox proportional hazards models to examine the association of remission status at each landmark and the primary end point. Persistent remission associated with unadjusted hazard ratios for the primary outcome that ranged by landmark from 0.35 (95% confidence interval, 0.20 to 0.61) to 0.56 (95% confidence interval, 0.31 to 1.04). Separate analyses for PR and CR yielded similar results. After adjustment, maintaining remission associated with significantly reduced risk of the primary outcome at all landmarks. Durable remissions associated with improved renal survival. Although the longer the remission, the greater the improvement, patients with remission durations as short as 3 months had improved renal prognosis compared with patients who relapsed. This study validates and quantifies PR and CR as surrogates for long-term outcome in MGN.Cattran, Daniel C.Kim, Esther D.Reich, HeatherHladunewich, MichelleKim, S. Joseph,2016-10-18T05:21:45-07:00doi:10.1681/ASN.2015111262hwp:resource-id:jnephrol;28/3/995American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, glomerulonephritis, membranous nephropathy, renal progression, survival, proteinuriaClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20151112621046-66731533-34502016-10-18T05:21:45-07:002017-03Journal of the American Society of NephrologyClinical Research2839951003
- HIV-1 Infection of Renal Cells in HIV-Associated Nephropathy10.1681/ASN.2016111171Mon, 09 Jan 2017 05:00:54 GMT-08:00HIV-1 Infection of Renal Cells in HIV-Associated NephropathyBruggeman, Leslie A.2017-01-09T05:00:54-08:00doi:10.1681/ASN.2016111171hwp:resource-id:jnephrol;28/3/719American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, HIV nephropathy, inflammationUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-03-01March 201710.1681/ASN.20161111711046-66731533-34502017-01-09T05:00:54-08:002017-03Journal of the American Society of NephrologyUp Front Matters2833719862721875
- Vascular Function and Uric Acid-Lowering in Stage 3 CKDHyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus. We measured vascular endothelial function by brachial artery flow-mediated dilation. No significant differences existed between groups at baseline; 61% of the participants had diabetes mellitus in both groups. The placebo and the allopurinol groups had baseline serum uric acid levels (SDs) of 8.7 (1.6) mg/dl and 8.3 (1.4) mg/dl, respectively, and baseline flow-mediated dilation values (SDs) of 6.0% (5.0%) and 4.8% (5.0%), respectively. Compared with placebo, allopurinol lowered serum uric acid significantly but did not improve endothelial function. In participants without diabetes mellitus, allopurinol associated with a trend toward improved flow-mediated dilation (+1.4% [3.9%] versus −0.7% [4.1%] with placebo), but this was not statistically significant (P=0.26). Furthermore, we did not detect significant differences between groups in BP or serum levels of markers of inflammation and oxidative stress. In conclusion, allopurinol effectively and safely lowered serum uric acid levels in adults with stage 3 CKD and asymptomatic hyperuricemia but did not improve endothelial function in this sample of patients.10.1681/ASN.2016050521Mon, 12 Sep 2016 09:51:40 GMT-07:00Vascular Function and Uric Acid-Lowering in Stage 3 CKDHyperuricemia may contribute to endothelial dysfunction in CKD. We evaluated whether lowering serum uric acid levels with allopurinol improves endothelial dysfunction in 80 participants ≥18 years of age with stage 3 CKD and asymptomatic hyperuricemia (≥7 mg/dl in men and ≥6 mg/dl in women) randomized in a double-blinded manner to receive placebo or allopurinol for 12 weeks. Randomization was stratified according to presence or absence of diabetes mellitus. We measured vascular endothelial function by brachial artery flow-mediated dilation. No significant differences existed between groups at baseline; 61% of the participants had diabetes mellitus in both groups. The placebo and the allopurinol groups had baseline serum uric acid levels (SDs) of 8.7 (1.6) mg/dl and 8.3 (1.4) mg/dl, respectively, and baseline flow-mediated dilation values (SDs) of 6.0% (5.0%) and 4.8% (5.0%), respectively. Compared with placebo, allopurinol lowered serum uric acid significantly but did not improve endothelial function. In participants without diabetes mellitus, allopurinol associated with a trend toward improved flow-mediated dilation (+1.4% [3.9%] versus −0.7% [4.1%] with placebo), but this was not statistically significant (P=0.26). Furthermore, we did not detect significant differences between groups in BP or serum levels of markers of inflammation and oxidative stress. In conclusion, allopurinol effectively and safely lowered serum uric acid levels in adults with stage 3 CKD and asymptomatic hyperuricemia but did not improve endothelial function in this sample of patients.Jalal, Diana I.Decker, EmilyPerrenoud, LoniNowak, Kristen L.Bispham, NinaMehta, TapanSmits, GerardYou, ZhiyingSeals, DouglasChonchol, MichelJohnson, Richard J.2016-09-12T09:51:40-07:00doi:10.1681/ASN.2016050521hwp:resource-id:jnephrol;28/3/943American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyuric acid, allopurinol, CKD, flow-mediated dilationClinical ResearchClinical Researchresearch-article20172017-03-01March 201710.1681/ASN.20160505211046-66731533-34502016-09-12T09:51:40-07:002017-03Journal of the American Society of NephrologyClinical Research283943952
- Oxalobacter formigenes–Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial CellsHyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O. formigenes culture conditioned medium (CM) on apical 14C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium, O. formigenes CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from Lactobacillus acidophilus did not. Treating the O. formigenes CM with heat or pepsin completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the O. formigenes–derived factors have molecular masses of 10–30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of O. formigenes CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that O. formigenes–derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with O. formigenes CM reflects the in vivo retention of biologic activity and the therapeutic potential of these factors.10.1681/ASN.2016020132Thu, 13 Oct 2016 06:15:23 GMT-07:00Oxalobacter formigenes–Derived Bioactive Factors Stimulate Oxalate Transport by Intestinal Epithelial CellsHyperoxaluria is a major risk factor for kidney stones and has no specific therapy, although Oxalobacter formigenes colonization is associated with reduced stone risk. O. formigenes interacts with colonic epithelium and induces colonic oxalate secretion, thereby reducing urinary oxalate excretion, via an unknown secretagogue. The difficulties in sustaining O. formigenes colonization underscore the need to identify the derived factors inducing colonic oxalate secretion. We therefore evaluated the effects of O. formigenes culture conditioned medium (CM) on apical 14C-oxalate uptake by human intestinal Caco-2-BBE cells. Compared with control medium, O. formigenes CM significantly stimulated oxalate uptake (>2.4-fold), whereas CM from Lactobacillus acidophilus did not. Treating the O. formigenes CM with heat or pepsin completely abolished this bioactivity, and selective ultrafiltration of the CM revealed that the O. formigenes–derived factors have molecular masses of 10–30 kDa. Treatment with the protein kinase A inhibitor H89 or the anion exchange inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid completely blocked the CM-induced oxalate transport. Knockdown of the oxalate transporter SLC26A6 also significantly restricted the induction of oxalate transport by CM. In a mouse model of primary hyperoxaluria type 1, rectal administration of O. formigenes CM significantly reduced (>32.5%) urinary oxalate excretion and stimulated (>42%) distal colonic oxalate secretion. We conclude that O. formigenes–derived bioactive factors stimulate oxalate transport in intestinal cells through mechanisms including PKA activation. The reduction in urinary oxalate excretion in hyperoxaluric mice treated with O. formigenes CM reflects the in vivo retention of biologic activity and the therapeutic potential of these factors.Arvans, DonnaJung, Yong-ChulAntonopoulos, DionysiosKoval, JasonGranja, IgnacioBashir, MohamedKarrar, EltayebRoy-Chowdhury, JayantaMusch, MarkAsplin, JohnChang, EugeneHassan, Hatim2016-10-13T06:15:23-07:00doi:10.1681/ASN.2016020132hwp:resource-id:jnephrol;28/3/876American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyintestinal oxalate transport, secreted bioactive factors, Oxalobacter formigenes, PKA, SLC26A6Basic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160201321046-66731533-34502016-10-13T06:15:23-07:002017-03Journal of the American Society of NephrologyBasic Research283876887
- Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone DiseaseIntrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.10.1681/ASN.2016040486Fri, 09 Sep 2016 09:59:12 GMT-07:00Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone DiseaseIntrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2-, and Tnfr1/2-deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo, and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.Mulay, Shrikant R.Eberhard, Jonathan N.Desai, JyaysiMarschner, Julian A.Kumar, Santhosh V.R.Weidenbusch, MarcGrigorescu, MelissaLech, MaciejEltrich, NuruMüller, LisaHans, WolfgangHrabě de Angelis, MartinVielhauer, VolkerHoppe, BerndAsplin, JohnBurzlaff, NicolaiHerrmann, MartinEvan, AndrewAnders, Hans-Joachim2016-09-09T09:59:12-07:00doi:10.1681/ASN.2016040486hwp:resource-id:jnephrol;28/3/761American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyChronic inflammation, Hyperoxaluria, Kidney stone, pathologyBrief CommunicationsBrief Communicationsbrief-report20172017-03-01March 201710.1681/ASN.20160404861046-66731533-34502016-09-09T09:59:12-07:002017-03Journal of the American Society of NephrologyBrief Communications283761768
- African Ancestry–Specific Alleles and Kidney Disease Risk in Hispanics/LatinosAfrican ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry–specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit β gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios. Overall, 41.4% of participants were male, 44.6% of participants had a Caribbean background, and the mean age of all participants was 46.1 years. The Caribbean background group, compared with the Mainland background group, had a higher frequency of two APOL1 alleles (1.0% versus 0.1%) and the HBB variant (2.0% versus 0.7%). In the Caribbean background group, presence of APOL1 alleles (2 versus 0/1 copies) or the HBB variant (1 versus 0 copies) were significantly associated with albuminuria (odds ratio [OR], 3.2; 95% confidence interval [95% CI], 1.7 to 6.1; and OR, 2.6; 95% CI, 1.8 to 3.8, respectively) and albuminuria and/or eGFR<60 ml/min per 1.73 m2 (OR, 2.9; 95% CI, 1.5 to 5.4; and OR, 2.4; 95% CI, 1.7 to 3.5, respectively). The urine albumin-to-creatinine ratio genome-wide association scan identified associations with the HBB variant among all participants, with the strongest association in the Caribbean background group (P=3.1×10−10 versus P=9.3×10−3 for the Mainland background group). In conclusion, African-specific alleles associate with CKD in Hispanics/Latinos, but allele frequency varies by Hispanic/Latino background/ancestry.10.1681/ASN.2016030357Tue, 20 Sep 2016 07:11:24 GMT-07:00African Ancestry–Specific Alleles and Kidney Disease Risk in Hispanics/LatinosAfrican ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry–specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit β gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios. Overall, 41.4% of participants were male, 44.6% of participants had a Caribbean background, and the mean age of all participants was 46.1 years. The Caribbean background group, compared with the Mainland background group, had a higher frequency of two APOL1 alleles (1.0% versus 0.1%) and the HBB variant (2.0% versus 0.7%). In the Caribbean background group, presence of APOL1 alleles (2 versus 0/1 copies) or the HBB variant (1 versus 0 copies) were significantly associated with albuminuria (odds ratio [OR], 3.2; 95% confidence interval [95% CI], 1.7 to 6.1; and OR, 2.6; 95% CI, 1.8 to 3.8, respectively) and albuminuria and/or eGFR<60 ml/min per 1.73 m2 (OR, 2.9; 95% CI, 1.5 to 5.4; and OR, 2.4; 95% CI, 1.7 to 3.5, respectively). The urine albumin-to-creatinine ratio genome-wide association scan identified associations with the HBB variant among all participants, with the strongest association in the Caribbean background group (P=3.1×10−10 versus P=9.3×10−3 for the Mainland background group). In conclusion, African-specific alleles associate with CKD in Hispanics/Latinos, but allele frequency varies by Hispanic/Latino background/ancestry.Kramer, Holly J.Stilp, Adrienne M.Laurie, Cathy C.Reiner, Alex P.Lash, JamesDaviglus, Martha L.Rosas, Sylvia E.Ricardo, Ana C.Tayo, Bamidele O.Flessner, Michael F.Kerr, Kathleen F.Peralta, CarmenDurazo-Arvizu, RamonConomos, MattThornton, TimothyRotter, JeromeTaylor, Kent D.Cai, JainwenEckfeldt, JohnChen, HanPapanicolau, GeorgeFranceschini, Nora2016-09-20T07:11:24-07:00doi:10.1681/ASN.2016030357hwp:resource-id:jnephrol;28/3/915American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyHispanic, Latino, albuminuria, chronic kidney disease, genetic variants, African ancestryClinical EpidemiologyClinical Epidemiologyresearch-article20172017-03-01March 201710.1681/ASN.20160303571046-66731533-34502016-09-20T07:11:24-07:002017-03Journal of the American Society of NephrologyClinical Epidemiology283915922
- Lats1/2 Regulate Yap/Taz to Control Nephron Progenitor Epithelialization and Inhibit Myofibroblast FormationIn the kidney, formation of the functional filtration units, the nephrons, is essential for postnatal life. During development, mesenchymal progenitors tightly regulate the balance between self-renewal and differentiation to give rise to all nephron epithelia. Here, we investigated the functions of the Hippo pathway serine/threonine-protein kinases Lats1 and Lats2, which phosphorylate and inhibit the transcriptional coactivators Yap and Taz, in nephron progenitor cells. Genetic deletion of Lats1 and Lats2 in nephron progenitors of mice led to disruption of nephrogenesis, with an accumulation of spindle-shaped cells in both cortical and medullary regions of the kidney. Lineage-tracing experiments revealed that the cells that accumulated in the interstitium derived from nephron progenitor cells and expressed E-cadherin as well as vimentin, a myofibroblastic marker not usually detected after mesenchymal-to-epithelial transition. The accumulation of these interstitial cells associated with collagen deposition and ectopic expression of the myofibroblastic markers vimentin and α-smooth-muscle actin in developing kidneys. Although these myofibroblastic cells had high Yap and Taz accumulation in the nucleus concomitant with a loss of phosphorylated Yap, reduction of Yap and/or Taz expression levels completely rescued the Lats1/2 phenotype. Taken together, our results demonstrate that Lats1/2 kinases restrict Yap/Taz activities to promote nephron progenitor cell differentiation in the mammalian kidney. Notably, our data also show that myofibroblastic cells can differentiate from nephron progenitors.10.1681/ASN.2016060611Mon, 19 Sep 2016 10:04:56 GMT-07:00Lats1/2 Regulate Yap/Taz to Control Nephron Progenitor Epithelialization and Inhibit Myofibroblast FormationIn the kidney, formation of the functional filtration units, the nephrons, is essential for postnatal life. During development, mesenchymal progenitors tightly regulate the balance between self-renewal and differentiation to give rise to all nephron epithelia. Here, we investigated the functions of the Hippo pathway serine/threonine-protein kinases Lats1 and Lats2, which phosphorylate and inhibit the transcriptional coactivators Yap and Taz, in nephron progenitor cells. Genetic deletion of Lats1 and Lats2 in nephron progenitors of mice led to disruption of nephrogenesis, with an accumulation of spindle-shaped cells in both cortical and medullary regions of the kidney. Lineage-tracing experiments revealed that the cells that accumulated in the interstitium derived from nephron progenitor cells and expressed E-cadherin as well as vimentin, a myofibroblastic marker not usually detected after mesenchymal-to-epithelial transition. The accumulation of these interstitial cells associated with collagen deposition and ectopic expression of the myofibroblastic markers vimentin and α-smooth-muscle actin in developing kidneys. Although these myofibroblastic cells had high Yap and Taz accumulation in the nucleus concomitant with a loss of phosphorylated Yap, reduction of Yap and/or Taz expression levels completely rescued the Lats1/2 phenotype. Taken together, our results demonstrate that Lats1/2 kinases restrict Yap/Taz activities to promote nephron progenitor cell differentiation in the mammalian kidney. Notably, our data also show that myofibroblastic cells can differentiate from nephron progenitors.McNeill, HelenReginensi, Antoine2016-09-19T10:04:56-07:00doi:10.1681/ASN.2016060611hwp:resource-id:jnephrol;28/3/852American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyHippo pathway, Lats1/2, Yap/Taz, MET, nephron, MyofibroblastBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160606111046-66731533-34502016-09-19T10:04:56-07:002017-03Journal of the American Society of NephrologyBasic Research283852861
- Proximal Tubule CD73 Is Critical in Renal Ischemia-Reperfusion Injury ProtectionCD73-derived adenosine plays an anti-inflammatory role in various organs. However, its role in renal ischemia-reperfusion injury (IRI) is controversial. We targeted CD73 mutant mice to determine the function of CD73 expressed by various renal cell types under mild IRI conditions. Mice with CD73 deletion in proximal tubules exhibited exacerbated IRI, comparable with that of CD73−/− mice compared with WT mice. Mice with CD73 deletions in other cell types, including cortical type 1 fibroblast–like cells, mesangial cells, macrophages, and dendritic cells, showed small or no increases in injury above control mice when subjected to threshold levels of ischemia. Results from adoptive transfer experiments between WT and CD73−/− mice and pharmacologic studies modulating enzymatic activity of CD73 and extracellular adenosine levels supported a critical role of adenosine generated by proximal tubule CD73 expression in abrogating IRI. Renal adenosine levels were lower before and after ischemia in CD73-deficient mice. However, reduction in total acid–extractable renal adenosine levels was inadequate to explain the marked difference in kidney injury in these CD73-deficient mice. Furthermore, CD73 inhibition and enzyme replacement studies showed no change in total kidney adenosine levels in treated mice compared with vehicle-treated controls. Protection from IRI in neutrophil–depleted WT recipients was sustained by repopulation with bone marrow neutrophils from WT mice but not by those lacking adenosine 2a receptors (from Adora2a−/− mice). These data support the thesis that local adenosine generated by cells at the injury site is critical for protection from IRI through bone marrow–derived adenosine 2a receptors.10.1681/ASN.2016020229Wed, 14 Sep 2016 07:22:12 GMT-07:00Proximal Tubule CD73 Is Critical in Renal Ischemia-Reperfusion Injury ProtectionCD73-derived adenosine plays an anti-inflammatory role in various organs. However, its role in renal ischemia-reperfusion injury (IRI) is controversial. We targeted CD73 mutant mice to determine the function of CD73 expressed by various renal cell types under mild IRI conditions. Mice with CD73 deletion in proximal tubules exhibited exacerbated IRI, comparable with that of CD73−/− mice compared with WT mice. Mice with CD73 deletions in other cell types, including cortical type 1 fibroblast–like cells, mesangial cells, macrophages, and dendritic cells, showed small or no increases in injury above control mice when subjected to threshold levels of ischemia. Results from adoptive transfer experiments between WT and CD73−/− mice and pharmacologic studies modulating enzymatic activity of CD73 and extracellular adenosine levels supported a critical role of adenosine generated by proximal tubule CD73 expression in abrogating IRI. Renal adenosine levels were lower before and after ischemia in CD73-deficient mice. However, reduction in total acid–extractable renal adenosine levels was inadequate to explain the marked difference in kidney injury in these CD73-deficient mice. Furthermore, CD73 inhibition and enzyme replacement studies showed no change in total kidney adenosine levels in treated mice compared with vehicle-treated controls. Protection from IRI in neutrophil–depleted WT recipients was sustained by repopulation with bone marrow neutrophils from WT mice but not by those lacking adenosine 2a receptors (from Adora2a−/− mice). These data support the thesis that local adenosine generated by cells at the injury site is critical for protection from IRI through bone marrow–derived adenosine 2a receptors.Sung, Sun-sang J.Li, LiHuang, LipingLawler, JessicaYe, HongRosin, Diane L.Vincent, Issah S.Le, Thu H.Yu, JingGörldt, NicoleSchrader, JürgenOkusa, Mark D.2016-09-14T07:22:12-07:00doi:10.1681/ASN.2016020229hwp:resource-id:jnephrol;28/3/888American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, ischemia-reperfusion, renal proximal tubule cell, creatinine, Immunology and pathologyBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160202291046-66731533-34502016-09-14T07:22:12-07:002017-03Journal of the American Society of NephrologyBasic Research283888902
- Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney FibrosisKidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium. In vitro, TNC selectively promoted renal interstitial fibroblast proliferation, bromodeoxyuridine incorporation, and the expression of proliferation-related genes. The mitogenic activity of TNC required the integrin/focal adhesion kinase/mitogen-activated protein kinase signaling cascade. Using decellularized extracellular matrix scaffolds, we found that TNC-enriched scaffolds facilitated fibroblast proliferation, whereas TNC-deprived scaffolds inhibited proliferation. Matrix scaffold prepared from fibrotic kidney also promoted greater ex vivo fibroblast proliferation than did scaffolds prepared from healthy kidney. Conversely, small interfering RNA-mediated knockdown of TNC in vivo repressed injury-induced fibroblast expansion and renal fibrosis. These studies identify TNC as a major constituent of the fibrogenic niche that promotes fibroblast proliferation, and illustrate a pivotal role for the TNC-enriched microenvironment in kidney fibrogenesis.10.1681/ASN.2016020165Fri, 09 Sep 2016 09:59:11 GMT-07:00Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney FibrosisKidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium. In vitro, TNC selectively promoted renal interstitial fibroblast proliferation, bromodeoxyuridine incorporation, and the expression of proliferation-related genes. The mitogenic activity of TNC required the integrin/focal adhesion kinase/mitogen-activated protein kinase signaling cascade. Using decellularized extracellular matrix scaffolds, we found that TNC-enriched scaffolds facilitated fibroblast proliferation, whereas TNC-deprived scaffolds inhibited proliferation. Matrix scaffold prepared from fibrotic kidney also promoted greater ex vivo fibroblast proliferation than did scaffolds prepared from healthy kidney. Conversely, small interfering RNA-mediated knockdown of TNC in vivo repressed injury-induced fibroblast expansion and renal fibrosis. These studies identify TNC as a major constituent of the fibrogenic niche that promotes fibroblast proliferation, and illustrate a pivotal role for the TNC-enriched microenvironment in kidney fibrogenesis.Fu, HaiyanTian, YuanZhou, LiliZhou, DongTan, Roderick J.Stolz, Donna B.Liu, Youhua2016-09-09T09:59:11-07:00doi:10.1681/ASN.2016020165hwp:resource-id:jnephrol;28/3/785American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, extracellular matrix, fibroblastBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160201651046-66731533-34502016-09-09T09:59:11-07:002017-03Journal of the American Society of NephrologyBasic Research283785801
- Acute Adaption to Oral or Intravenous Phosphate Requires Parathyroid HormonePhosphate (Pi) homeostasis is regulated by renal, intestinal, and endocrine mechanisms through which Pi intake stimulates parathyroid hormone (PTH) and fibroblast growth factor-23 secretion, increasing phosphaturia. Mechanisms underlying the early adaptive phase and the role of the intestine, however, remain ill defined. We investigated mineral, endocrine, and renal responses during the first 4 hours after intravenous and intragastric Pi loading in rats. Intravenous Pi loading (0.5 mmol) caused a transient rise in plasma Pi levels and creatinine clearance and an increase in phosphaturia within 10 minutes. Plasma calcium levels fell and PTH levels increased within 10 minutes and remained low or high, respectively. Fibroblast growth factor-23, 1,25-(OH)2-vitamin D3, and insulin concentrations did not respond, but plasma dopamine levels increased by 4 hours. In comparison, gastric Pi loading elicited similar but delayed phosphaturia and endocrine responses but did not affect plasma mineral levels. Either intravenous or gastric loading led to decreased expression and activity of renal Pi transporters after 4 hours. In parathyroidectomized rats, however, only intravenous Pi loading caused phosphaturia, which was blunted and transient compared with that in intact rats. Intravenous but not gastric Pi loading in parathyroidectomized rats also led to higher creatinine clearance and lower plasma calcium levels but did not reduce the expression or activity of Pi transporters. This evidence suggests that an intravenous or intestinal Pi bolus causes rapid phosphaturia through mechanisms requiring PTH and downregulation of renal Pi transporters but does not support a role of the intestine in stimulating renal clearance of Pi.10.1681/ASN.2016010082Thu, 06 Oct 2016 07:08:12 GMT-07:00Acute Adaption to Oral or Intravenous Phosphate Requires Parathyroid HormonePhosphate (Pi) homeostasis is regulated by renal, intestinal, and endocrine mechanisms through which Pi intake stimulates parathyroid hormone (PTH) and fibroblast growth factor-23 secretion, increasing phosphaturia. Mechanisms underlying the early adaptive phase and the role of the intestine, however, remain ill defined. We investigated mineral, endocrine, and renal responses during the first 4 hours after intravenous and intragastric Pi loading in rats. Intravenous Pi loading (0.5 mmol) caused a transient rise in plasma Pi levels and creatinine clearance and an increase in phosphaturia within 10 minutes. Plasma calcium levels fell and PTH levels increased within 10 minutes and remained low or high, respectively. Fibroblast growth factor-23, 1,25-(OH)2-vitamin D3, and insulin concentrations did not respond, but plasma dopamine levels increased by 4 hours. In comparison, gastric Pi loading elicited similar but delayed phosphaturia and endocrine responses but did not affect plasma mineral levels. Either intravenous or gastric loading led to decreased expression and activity of renal Pi transporters after 4 hours. In parathyroidectomized rats, however, only intravenous Pi loading caused phosphaturia, which was blunted and transient compared with that in intact rats. Intravenous but not gastric Pi loading in parathyroidectomized rats also led to higher creatinine clearance and lower plasma calcium levels but did not reduce the expression or activity of Pi transporters. This evidence suggests that an intravenous or intestinal Pi bolus causes rapid phosphaturia through mechanisms requiring PTH and downregulation of renal Pi transporters but does not support a role of the intestine in stimulating renal clearance of Pi.Thomas, LintoBettoni, CarlaKnöpfel, ThomasHernando, NatiBiber, JürgWagner, Carsten A.2016-10-06T07:08:12-07:00doi:10.1681/ASN.2016010082hwp:resource-id:jnephrol;28/3/903American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate uptake, parathyroid hormone, intestine, phosphate-sensingBasic ResearchBasic Researchresearch-article20172017-03-01March 201710.1681/ASN.20160100821046-66731533-34502016-10-06T07:08:12-07:002017-03Journal of the American Society of NephrologyBasic Research283903914
- Inflammation as a Therapeutic Target To Improve Vascular Function in Kidney Disease10.1681/ASN.2016111173Tue, 03 Jan 2017 06:06:01 GMT-08:00Inflammation as a Therapeutic Target To Improve Vascular Function in Kidney DiseaseWalther, Carl P.Navaneethan, Sankar D.2017-01-03T06:06:01-08:00doi:10.1681/ASN.2016111173hwp:resource-id:jnephrol;28/3/723American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyInflammation, chronic kidney disease, interleukins, vascular diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-03-01March 201710.1681/ASN.20161111731046-66731533-34502017-01-03T06:06:01-08:002017-03Journal of the American Society of NephrologyUp Front Matters2833723971725980
- Mean Corpuscular Volume and Mortality in Patients with CKD10.2215/CJN.00970116Tue, 31 Jan 2017 08:16:54 GMT-08:00Mean Corpuscular Volume and Mortality in Patients with CKDHsieh, Yao-PengChang, Chia-ChuKor, Chew-TengYang, YuWen, Yao-KoChiu, Ping-Fang2017-01-31T08:16:54-08:00doi:10.2215/CJN.00970116hwp:resource-id:clinjasn;12/2/237American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, mean corpuscular volume (MCV), mortality, anemia, Biomarkers, Cohort Studies, Confidence Intervals, Demography, Diagnosis, Differential, Erythrocyte Indices, Erythrocytes, Follow-Up Studies, Humans, Regression Analysis, Renal Insufficiency, Chronic, Retrospective Studies, RiskOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-02-07February 07, 201710.2215/CJN.009701161555-90411555-905X2017-01-31T08:16:54-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122237244
- The Relation of Serum Potassium Concentration with Cardiovascular Events and Mortality in Community-Living Individuals10.2215/CJN.06290616Tue, 31 Jan 2017 08:16:54 GMT-08:00The Relation of Serum Potassium Concentration with Cardiovascular Events and Mortality in Community-Living IndividualsHughes-Austin, Jan M.Rifkin, Dena E.Beben, TomaszKatz, RonitSarnak, Mark J.Deo, RajatHoofnagle, Andrew N.Homma, ShunichiSiscovick, David S.Sotoodehnia, NonaPsaty, Bruce M.de Boer, Ian H.Kestenbaum, BryanShlipak, Michael G.Ix, Joachim H.2017-01-31T08:16:54-08:00doi:10.2215/CJN.06290616hwp:resource-id:clinjasn;12/2/245American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and outcomes, mortality risk, serum potassium, Atherosclerosis, Cardiovascular Diseases, Demography, diuretics, Ethnic Groups, glomerular filtration rate, Humans, Hyperkalemia, Potassium, Proportional Hazards Models, Reference Values, Renal Insufficiency, Chronic, risk factorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-02-07February 07, 201710.2215/CJN.062906161555-90411555-905X2017-01-31T08:16:54-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1222245220252221
- Maternal Smoking during Pregnancy, Household Smoking after the Child’s Birth, and Childhood Proteinuria at Age 3 Years10.2215/CJN.05980616Thu, 22 Dec 2016 06:54:07 GMT-08:00Maternal Smoking during Pregnancy, Household Smoking after the Child’s Birth, and Childhood Proteinuria at Age 3 YearsShinzawa, MakiTanaka, ShiroTokumasu, HironobuTakada, DaisukeTsukamoto, TatsuoYanagita, MotokoKawakami, Koji2016-12-22T18:54:07-08:00doi:10.2215/CJN.05980616hwp:resource-id:clinjasn;12/2/253American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymaternal smoking, household smoking, childhood proteinuria, Kobe Offspring StudyOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-02-07February 07, 201710.2215/CJN.059806161555-90411555-905X2016-12-22T18:54:07-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122253260
- Dual Antiplatelet Therapy and Clinical Outcomes after Coronary Drug-Eluting Stent Implantation in Patients on Hemodialysis10.2215/CJN.04430416Tue, 07 Feb 2017 01:00:34 GMT-08:00Dual Antiplatelet Therapy and Clinical Outcomes after Coronary Drug-Eluting Stent Implantation in Patients on HemodialysisChen, Yung-TaiChen, Hung-TaHsu, Chien-YiChao, Pei-WenKuo, Shu-ChenOu, Shuo-MingShih, Chia-Jen2017-02-07T13:00:34-08:00doi:10.2215/CJN.04430416hwp:resource-id:clinjasn;12/2/262American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, coronary artery disease, Epidemiology and outcomes, Cohort, Studies, Drug-Eluting Stents, Hemorrhage, Humans, Myocardial Infarction, National Health Programs, Odds Ratio, Propensity Score, renal dialysis, Risk Assessment, Stroke, Taiwan, Treatment Outcome, 2′-deoxythymidylyl-(3′-5′)-2′-deoxyadenosineOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-02-07February 07, 201710.2215/CJN.044304161555-90411555-905X2017-02-07T13:00:34-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122262271
- Healthy Dietary Patterns and Risk of Mortality and ESRD in CKD: A Meta-Analysis of Cohort Studies10.2215/CJN.06190616Thu, 08 Dec 2016 06:52:31 GMT-08:00Healthy Dietary Patterns and Risk of Mortality and ESRD in CKD: A Meta-Analysis of Cohort StudiesKelly, Jaimon T.Palmer, Suetonia C.Wai, Shu NingRuospo, MarinellaCarrero, Juan-JesusCampbell, Katrina L.Strippoli, Giovanni F. M.2016-12-08T06:52:31-08:00doi:10.2215/CJN.06190616hwp:resource-id:clinjasn;12/2/272American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNutrition, chronic kidney disease, mortality, dialysis, diet quality, dietary patterns, Adult, Carbohydrates, Cohort Studies, Confidence Intervals, diet, Dietary Fiber, Edible Grain, Fabaceae, Fruit, Humans, Kidney Failure, Chronic, Longitudinal Studies, Red Meat, Risk, Sodium, Vegetables, Whole GrainsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20172017-02-07February 07, 201710.2215/CJN.061906161555-90411555-905X2016-12-08T06:52:31-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122272279
- A Decision-Making Algorithm for Initiation and Discontinuation of RRT in Severe AKI10.2215/CJN.07170716Tue, 24 Jan 2017 06:06:05 GMT-08:00A Decision-Making Algorithm for Initiation and Discontinuation of RRT in Severe AKIMendu, Mallika L.Ciociolo, George R.McLaughlin, Sarah R.Graham, Dionne A.Ghazinouri, RoyaParmar, SiddharthGrossier, AlissaRosen, RebeccaLaskowski, Karl R.Riella, Leonardo V.Robinson, Emily S.Charytan, David M.Bonventre, Joseph V.Greenberg, Jeffrey O.Waikar, Sushrut S.2017-01-24T06:06:05-08:00doi:10.2215/CJN.07170716hwp:resource-id:clinjasn;12/2/228American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, clinical nephrology, hemodialysis, Acute Kidney Injury, Albumins, Algorithms, Clinical Decision-Making, Hospital Mortality, Humans, Intensive Care Units, Prospective Studies, Renal Replacement Therapy, RiskOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20172017-02-07February 07, 201710.2215/CJN.071707161555-90411555-905X2017-01-24T06:06:05-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1222228217236219
- Minimal Change DiseaseMinimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%–90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.10.2215/CJN.05000516Fri, 09 Dec 2016 06:58:13 GMT-08:00Minimal Change DiseaseMinimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%–90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis.Vivarelli, MarinaMassella, LauraRuggiero, BarbaraEmma, Francesco2016-12-09T06:58:13-08:00doi:10.2215/CJN.05000516hwp:resource-id:clinjasn;12/2/332American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, podocyte, proteinuria, pediatric nephrology, renal, pathologyGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20172017-02-07February 07, 201710.2215/CJN.050005161555-90411555-905X2016-12-09T06:58:13-08:002017-02-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician122332345
- Preventing Emergency Department Use among Patients with CKD: It Starts with Awareness10.2215/CJN.12881216Tue, 24 Jan 2017 06:06:06 GMT-08:00Preventing Emergency Department Use among Patients with CKD: It Starts with AwarenessPatzer, Rachel E.Schrager, Justin D.Pastan, Stephen O.2017-01-24T06:06:06-08:00doi:10.2215/CJN.12881216hwp:resource-id:clinjasn;12/2/225American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, Epidemiology and outcomes, ESRD, hospitalization, Awareness, Emergency Service, Hospital, Humans, Renal Insufficiency, ChronicEditorialsEditorialseditorial20172017-02-07February 07, 201710.2215/CJN.128812161555-90411555-905X2017-01-24T06:06:06-08:002017-02-07Clinical Journal of the American Society of NephrologyEditorials1222225304227314
- New Opportunities for Funding Dialysis-Dependent Undocumented IndividualsThe cost of dialysis for the estimated 6500 dialysis-dependent undocumented individuals with kidney failure in the United States is high, the quality of dialysis care they receive is poor, and their treatment varies regionally. Some regions use state and matched federal funds to cover regularly scheduled dialysis treatments, while others provide treatment only in emergent life-threatening conditions. Nephrologists caring for patients who receive emergent dialysis are tasked with the difficult moral dilemma of determining “who gets dialysis that day.” Without a path to citizenship and by exclusion from the federal marketplace exchanges, undocumented individuals have limited options for their treatment. A novel opportunity to provide scheduled dialysis for this population is through the purchase of insurance off the exchange. Plans purchased off the exchange must still abide by the 2014 provision of the Patient Protection and Affordable Care Act, which prohibits insurance companies from denying coverage based on a preexisting health condition. In 2015 and 2016, >100 patients previously receiving only emergent dialysis at the two largest safety-net hospital systems in Texas obtained off-the-exchange commercial health insurance plans. These undocumented patients now receive scheduled dialysis treatments, which has improved their care and quality of life, as well as decompressed the overburdened hospital systems. The long-term sustainability of this option is not known. Socially responsive and visionary policymakers allowing the move into this bold, new direction deserve special appreciation.10.2215/CJN.03680316Tue, 30 Aug 2016 06:16:51 GMT-07:00New Opportunities for Funding Dialysis-Dependent Undocumented IndividualsThe cost of dialysis for the estimated 6500 dialysis-dependent undocumented individuals with kidney failure in the United States is high, the quality of dialysis care they receive is poor, and their treatment varies regionally. Some regions use state and matched federal funds to cover regularly scheduled dialysis treatments, while others provide treatment only in emergent life-threatening conditions. Nephrologists caring for patients who receive emergent dialysis are tasked with the difficult moral dilemma of determining “who gets dialysis that day.” Without a path to citizenship and by exclusion from the federal marketplace exchanges, undocumented individuals have limited options for their treatment. A novel opportunity to provide scheduled dialysis for this population is through the purchase of insurance off the exchange. Plans purchased off the exchange must still abide by the 2014 provision of the Patient Protection and Affordable Care Act, which prohibits insurance companies from denying coverage based on a preexisting health condition. In 2015 and 2016, >100 patients previously receiving only emergent dialysis at the two largest safety-net hospital systems in Texas obtained off-the-exchange commercial health insurance plans. These undocumented patients now receive scheduled dialysis treatments, which has improved their care and quality of life, as well as decompressed the overburdened hospital systems. The long-term sustainability of this option is not known. Socially responsive and visionary policymakers allowing the move into this bold, new direction deserve special appreciation.Raghavan, Rajeev2016-08-30T06:16:51-07:00doi:10.2215/CJN.03680316hwp:resource-id:clinjasn;12/2/370American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, clinical nephrology, Economic Impact, Clinical Protocols, Financial, Management, Fluid Therapy, Health Insurance Exchanges, humans, morals, Patient Protection and Affordable Care Act, quality of life, renal dialysis, Renal Insufficiency, Safety-net Providers, Texas, United StatesPublic Policy SeriesPublic Policy Seriesresearch-article20172017-02-07February 07, 201710.2215/CJN.036803161555-90411555-905X2016-08-30T06:16:51-07:002017-02-07Clinical Journal of the American Society of NephrologyPublic Policy Series122370375
- Integrating Quality Improvement Education into the Nephrology Curricular Milestones Framework and the Clinical Learning Environment ReviewThe Accreditation Council for Graduate Medical Education requires that trainees show progressive milestone attainment in the practice–based learning and systems–based practice competencies. As part of the Clinical Learning Environment Review, sponsoring hospitals must educate trainees in health care quality improvement, provide them with specialty–specific quality data, and ensure trainee participation in quality improvement activities and committees. Subspecialty–specific quality improvement curricula in nephrology training programs have not been reported, although considerable curricular and assessment material exists for specialty residencies, including tools for assessing trainee and faculty competence. Nephrology–specific didactic material exists to assist nephrology fellows and faculty mentors in designing and implementing quality improvement projects. Nephrology is notable among internal medicine subspecialties for the emphasis placed on adherence to quality thresholds—specifically for chronic RRT shown by the Centers for Medicare and Medicaid Services Quality Incentive Program. We have developed a nephrology-specific curriculum that meets Accreditation Council for Graduate Medical Education and Clinical Learning Environment Review requirements, acknowledges regulatory quality improvement requirements, integrates with ongoing divisional quality improvement activities, and has improved clinical care and the training program. In addition to didactic training in quality improvement, we track trainee compliance with Kidney Disease Improving Global Outcomes CKD and ESRD quality indicators (emphasizing Quality Improvement Program indicators), and fellows collaborate on a yearly multidisciplinary quality improvement project. Over the past 6 years, each fellowship class has, on the basis of a successful quality improvement project, shown milestone achievement in Systems-Based Practice and Practice-Based Learning. Fellow quality improvement projects have improved nephrology clinical care within the institution and introduced new educational and assessment tools to the training program. All have been opportunities for quality improvement scholarship. The curriculum prepares fellows to apply quality improvement principals in independent clinical practice—while showing milestone advancement and divisional compliance with Clinical Learning Environment Review requirements.10.2215/CJN.04740416Thu, 10 Nov 2016 08:52:35 GMT-08:00Integrating Quality Improvement Education into the Nephrology Curricular Milestones Framework and the Clinical Learning Environment ReviewThe Accreditation Council for Graduate Medical Education requires that trainees show progressive milestone attainment in the practice–based learning and systems–based practice competencies. As part of the Clinical Learning Environment Review, sponsoring hospitals must educate trainees in health care quality improvement, provide them with specialty–specific quality data, and ensure trainee participation in quality improvement activities and committees. Subspecialty–specific quality improvement curricula in nephrology training programs have not been reported, although considerable curricular and assessment material exists for specialty residencies, including tools for assessing trainee and faculty competence. Nephrology–specific didactic material exists to assist nephrology fellows and faculty mentors in designing and implementing quality improvement projects. Nephrology is notable among internal medicine subspecialties for the emphasis placed on adherence to quality thresholds—specifically for chronic RRT shown by the Centers for Medicare and Medicaid Services Quality Incentive Program. We have developed a nephrology-specific curriculum that meets Accreditation Council for Graduate Medical Education and Clinical Learning Environment Review requirements, acknowledges regulatory quality improvement requirements, integrates with ongoing divisional quality improvement activities, and has improved clinical care and the training program. In addition to didactic training in quality improvement, we track trainee compliance with Kidney Disease Improving Global Outcomes CKD and ESRD quality indicators (emphasizing Quality Improvement Program indicators), and fellows collaborate on a yearly multidisciplinary quality improvement project. Over the past 6 years, each fellowship class has, on the basis of a successful quality improvement project, shown milestone achievement in Systems-Based Practice and Practice-Based Learning. Fellow quality improvement projects have improved nephrology clinical care within the institution and introduced new educational and assessment tools to the training program. All have been opportunities for quality improvement scholarship. The curriculum prepares fellows to apply quality improvement principals in independent clinical practice—while showing milestone advancement and divisional compliance with Clinical Learning Environment Review requirements.Prince, Lisa K.Little, Dustin J.Schexneider, Katherine I.Yuan, Christina M.2016-11-10T08:52:35-08:00doi:10.2215/CJN.04740416hwp:resource-id:clinjasn;12/2/349American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyquality improvement, CLER, curriculum, milestones, Accreditation, Achievement, Centers for Medicare and Medicaid Services (U.S.), Curriculum, Education, Medical, Graduate, Faculty, Fellowships and Scholarships, Internal Medicine, Internship and Residency, Kidney Failure, Chronic, Mentors, nephrology, Quality Improvement, Renal Insufficiency, Chronic, Renal Replacement Therapy, United StatesEducation SeriesEducation Seriesresearch-article20172017-02-07February 07, 201710.2215/CJN.047404161555-90411555-905X2016-11-10T08:52:35-08:002017-02-07Clinical Journal of the American Society of NephrologyEducation Series122349356
- The CKD Classification System in the Precision Medicine Era10.2215/CJN.09310916Wed, 30 Nov 2016 05:18:25 GMT-08:00The CKD Classification System in the Precision Medicine EraHall, Yoshio N.Himmelfarb, Jonathan2016-11-30T05:18:25-08:00doi:10.2215/CJN.09310916hwp:resource-id:clinjasn;12/2/346American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyckd, precision medicine, GFRCommentaryCommentaryarticle-commentary20172017-02-07February 07, 201710.2215/CJN.093109161555-90411555-905X2016-11-30T05:18:25-08:002017-02-07Clinical Journal of the American Society of NephrologyCommentary122346348
- Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial10.2215/CJN.02120216Thu, 26 Jan 2017 05:09:57 GMT-08:00Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility TrialFriedli, KarinGuirguis, AymanAlmond, MichaelDay, ClaraChilcot, JosephDa Silva-Gane, MariaDavenport, AndrewFineberg, Naomi A.Spencer, BenjaminWellsted, DavidFarrington, Ken2017-01-26T05:09:57-08:00doi:10.2215/CJN.02120216hwp:resource-id:clinjasn;12/2/280American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologySertraline, Placebos, Antidepressive Agents, Feasibility Studies, depression, Controlled Clinical Trials, Randomized, hemodialysis, Depressive Disorder, Major, Double-Blind Method, Follow-Up Studies, Humans, Personality Inventory, Psychiatric Status Rating Scales, renal dialysis, Risk AssessmentOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20172017-02-07February 07, 201710.2215/CJN.021202161555-90411555-905X2017-01-26T05:09:57-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1222280222286224
- We Need to Talk about Depression and Dialysis: but What Questions Should We Ask, and Does Anyone Know the Answers?10.2215/CJN.13031216Thu, 26 Jan 2017 05:09:57 GMT-08:00We Need to Talk about Depression and Dialysis: but What Questions Should We Ask, and Does Anyone Know the Answers?Hackett, Maree L.Jardine, Meg J.2017-01-26T05:09:57-08:00doi:10.2215/CJN.13031216hwp:resource-id:clinjasn;12/2/222American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepression, dialysis, randomized controlled trials, Depressive Disorder, Fluid Therapy, Knowledge, renal dialysis, SpeechEditorialsEditorialseditorial20172017-02-07February 07, 201710.2215/CJN.130312161555-90411555-905X2017-01-26T05:09:57-08:002017-02-07Clinical Journal of the American Society of NephrologyEditorials12222222280298224286303
- Long-Term Outcomes and Discard Rate of Kidneys by Decade of Extended Criteria Donor Age10.2215/CJN.06550616Thu, 15 Dec 2016 06:35:30 GMT-08:00Long-Term Outcomes and Discard Rate of Kidneys by Decade of Extended Criteria Donor AgeMessina, MariaDiena, DavideDellepiane, SergioGuzzo, GabriellaLo Sardo, LucaFop, FabrizioSegoloni, Giuseppe P.Amoroso, AntonioMagistroni, PaolaBiancone, Luigi2016-12-15T06:35:30-08:00doi:10.2215/CJN.06550616hwp:resource-id:clinjasn;12/2/323American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycadaver organ transplantation, organ allocation, graft survival, octogenarian donors, discard rate, elderly, Aged, 80 and over, Follow-Up Studies, Graft Survival, Health Resources, Humans, Incidence, kidney, kidney transplantation, Retrospective Studies, Tissue Donors, TransplantsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20172017-02-07February 07, 201710.2215/CJN.065506161555-90411555-905X2016-12-15T06:35:30-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122323331
- Acceptance of Antidepressant Treatment by Patients on Hemodialysis and Their Renal Providers10.2215/CJN.07720716Thu, 26 Jan 2017 05:09:58 GMT-08:00Acceptance of Antidepressant Treatment by Patients on Hemodialysis and Their Renal ProvidersPena-Polanco, Julio E.Mor, Maria K.Tohme, Fadi A.Fine, Michael J.Palevsky, Paul M.Weisbord, Steven D.2017-01-26T05:09:58-08:00doi:10.2215/CJN.07720716hwp:resource-id:clinjasn;12/2/298American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydepression, acceptance, treatment, anti-depressant therapy, quality of life, symptoms, hemodialysis, psychological, Chronic Disease, Depressive Disorder, Disease Management, Fluid Therapy, Humans, Nurses, renal dialysis, Surveys and QuestionnairesOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20172017-02-07February 07, 201710.2215/CJN.077207161555-90411555-905X2017-01-26T05:09:58-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1222298222303224
- Mortality, Hospitalization, and Quality of Life among Patients with Hepatitis C Infection on Hemodialysis10.2215/CJN.07940716Thu, 01 Dec 2016 05:08:29 GMT-08:00Mortality, Hospitalization, and Quality of Life among Patients with Hepatitis C Infection on HemodialysisGoodkin, David A.Bieber, BrianJadoul, MichelMartin, PaulKanda, EiichiroPisoni, Ronald L.2016-12-01T05:08:29-08:00doi:10.2215/CJN.07940716hwp:resource-id:clinjasn;12/2/287American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHepatitis C, mortality, quality of life, anemia, renal dialysis, Adult, Anorexia, Antiviral Agents, creatinine, depression, Epidemiologic Studies, Erythrocyte Transfusion, Follow-Up Studies, Hemoglobins, Hepacivirus, Hepatitis B, hospitalization, Humans, Incidence, Kidney Diseases, Mental, Health, Pain, Phosphorus, PrevalenceOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20172017-02-07February 07, 201710.2215/CJN.079407161555-90411555-905X2016-12-01T05:08:29-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles122287297
- Emergency Department Use among Patients with CKD: A Population-Based Analysis10.2215/CJN.06280616Tue, 24 Jan 2017 06:06:05 GMT-08:00Emergency Department Use among Patients with CKD: A Population-Based AnalysisRonksley, Paul E.Tonelli, MarcelloManns, Braden J.Weaver, Robert G.Thomas, Chandra M.MacRae, Jennifer M.Ravani, PietroQuinn, Robert R.James, Matthew T.Lewanczuk, RichardHemmelgarn, Brenda R.2017-01-24T06:06:05-08:00doi:10.2215/CJN.06280616hwp:resource-id:clinjasn;12/2/304American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, dialysis, Epidemiology and outcomes, Adult, Alberta, Ambulatory Care, Canada, Emergency Service, Hospital, Follow-Up Studies, heart failure, hospitalization, Humans, Hyperkalemia, Hypertension, Malignant, renal dialysis, Renal Insufficiency, ChronicOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20172017-02-07February 07, 201710.2215/CJN.062806161555-90411555-905X2017-01-24T06:06:05-08:002017-02-07Clinical Journal of the American Society of NephrologyOriginal Articles1222304225314227
- Serum Potassium and Cardiovascular Outcomes: The Highs and the Lows10.2215/CJN.00030117Tue, 31 Jan 2017 08:16:54 GMT-08:00Serum Potassium and Cardiovascular Outcomes: The Highs and the LowsToto, Robert D.2017-01-31T08:16:54-08:00doi:10.2215/CJN.00030117hwp:resource-id:clinjasn;12/2/220American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCardiovascular System, Hypnosis, PotassiumEditorialsEditorialseditorial20172017-02-07February 07, 201710.2215/CJN.000301171555-90411555-905X2017-01-31T08:16:54-08:002017-02-07Clinical Journal of the American Society of NephrologyEditorials1222220245221252
- Guiding Physician Decisions for Initiating Dialysis for AKI: Is Progress on the Horizon?10.2215/CJN.00020117Tue, 24 Jan 2017 06:06:05 GMT-08:00Guiding Physician Decisions for Initiating Dialysis for AKI: Is Progress on the Horizon?Macedo, EtienneMehta, Ravindra L.2017-01-24T06:06:05-08:00doi:10.2215/CJN.00020117hwp:resource-id:clinjasn;12/2/217American Society of NephrologyCopyright © 2017 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute Kidney Injury, Fluid Therapy, renal dialysisEditorialsEditorialseditorial20172017-02-07February 07, 201710.2215/CJN.000201171555-90411555-905X2017-01-24T06:06:05-08:002017-02-07Clinical Journal of the American Society of NephrologyEditorials1222217228219236
- Genetics of Diabetic Kidney Disease—From the Worst of Nightmares to the Light of Dawn?10.1681/ASN.2016091028Wed, 23 Nov 2016 09:30:59 GMT-08:00Genetics of Diabetic Kidney Disease—From the Worst of Nightmares to the Light of Dawn?Ma, Ronald C.W.Cooper, Mark E.2016-11-23T09:30:59-08:00doi:10.1681/ASN.2016091028hwp:resource-id:jnephrol;28/2/389American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologychronic diabetic complications, human genetics, diabetic nephropathy, molecular geneticsUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-02-01February 201710.1681/ASN.20160910281046-66731533-34502016-11-23T09:30:59-08:002017-02Journal of the American Society of NephrologyUp Front Matters2822389557393574
- Suppressor of Cytokine Signaling-1 Peptidomimetic Limits Progression of Diabetic NephropathyDiabetes is the main cause of CKD and ESRD worldwide. Chronic activation of Janus kinase and signal transducer and activator of transcription (STAT) signaling contributes to diabetic nephropathy by inducing genes involved in leukocyte infiltration, cell proliferation, and extracellular matrix accumulation. This study examined whether a cell-permeable peptide mimicking the kinase-inhibitory region of suppressor of cytokine signaling-1 (SOCS1) regulatory protein protects against nephropathy by suppressing STAT-mediated cell responses to diabetic conditions. In a mouse model combining hyperglycemia and hypercholesterolemia (streptozotocin diabetic, apoE-deficient mice), renal STAT activation status correlated with the severity of nephropathy. Notably, compared with administration of vehicle or mutant inactive peptide, administration of the SOCS1 peptidomimetic at either early or advanced stages of diabetes ameliorated STAT activity and resulted in reduced serum creatinine level, albuminuria, and renal histologic changes (mesangial expansion, tubular injury, and fibrosis) over time. Mice treated with the SOCS1 peptidomimetic also exhibited reduced kidney leukocyte recruitment (T lymphocytes and classic M1 proinflammatory macrophages) and decreased expression levels of proinflammatory and profibrotic markers that were independent of glycemic and lipid changes. In vitro, internalized peptide suppressed STAT activation and target gene expression induced by inflammatory and hyperglycemic conditions, reduced migration and proliferation in mesangial and tubuloepithelial cells, and altered the expression of cytokine-induced macrophage polarization markers. In conclusion, our study identifies SOCS1 mimicking as a feasible therapeutic strategy to halt the onset and progression of renal inflammation and fibrosis in diabetic kidney disease.10.1681/ASN.2016020237Thu, 08 Sep 2016 07:50:41 GMT-07:00Suppressor of Cytokine Signaling-1 Peptidomimetic Limits Progression of Diabetic NephropathyDiabetes is the main cause of CKD and ESRD worldwide. Chronic activation of Janus kinase and signal transducer and activator of transcription (STAT) signaling contributes to diabetic nephropathy by inducing genes involved in leukocyte infiltration, cell proliferation, and extracellular matrix accumulation. This study examined whether a cell-permeable peptide mimicking the kinase-inhibitory region of suppressor of cytokine signaling-1 (SOCS1) regulatory protein protects against nephropathy by suppressing STAT-mediated cell responses to diabetic conditions. In a mouse model combining hyperglycemia and hypercholesterolemia (streptozotocin diabetic, apoE-deficient mice), renal STAT activation status correlated with the severity of nephropathy. Notably, compared with administration of vehicle or mutant inactive peptide, administration of the SOCS1 peptidomimetic at either early or advanced stages of diabetes ameliorated STAT activity and resulted in reduced serum creatinine level, albuminuria, and renal histologic changes (mesangial expansion, tubular injury, and fibrosis) over time. Mice treated with the SOCS1 peptidomimetic also exhibited reduced kidney leukocyte recruitment (T lymphocytes and classic M1 proinflammatory macrophages) and decreased expression levels of proinflammatory and profibrotic markers that were independent of glycemic and lipid changes. In vitro, internalized peptide suppressed STAT activation and target gene expression induced by inflammatory and hyperglycemic conditions, reduced migration and proliferation in mesangial and tubuloepithelial cells, and altered the expression of cytokine-induced macrophage polarization markers. In conclusion, our study identifies SOCS1 mimicking as a feasible therapeutic strategy to halt the onset and progression of renal inflammation and fibrosis in diabetic kidney disease.Recio, CarlotaLazaro, IolandaOguiza, AinhoaLopez-Sanz, LauraBernal, SusanaBlanco, JuliaEgido, JesusGomez-Guerrero, Carmen2016-09-08T07:50:41-07:00doi:10.1681/ASN.2016020237hwp:resource-id:jnephrol;28/2/575American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyChronic inflammation, diabetic nephropathy, fibrosis, macrophages, transcription factors, apolipoprotein EBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160202371046-66731533-34502016-09-08T07:50:41-07:002017-02Journal of the American Society of NephrologyBasic Research282575585
- The Genetic Landscape of Renal Complications in Type 1 DiabetesDiabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10−3). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10−5) and the risk of type 2 diabetes (P=6.1×10−4) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10−4). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10−6), and pentose and glucuronate interconversions (P=3.0×10−6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.10.1681/ASN.2016020231Mon, 19 Sep 2016 10:04:56 GMT-07:00The Genetic Landscape of Renal Complications in Type 1 DiabetesDiabetes is the leading cause of ESRD. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2843 subjects, we estimated that the heritability of diabetic kidney disease was 35% (P=6.4×10−3). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole-exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index (P=2.2×10−5) and the risk of type 2 diabetes (P=6.1×10−4) associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation (P=1.1×10−4). Pathway analysis implicated ascorbate and aldarate metabolism (P=9.0×10−6), and pentose and glucuronate interconversions (P=3.0×10−6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.Sandholm, NiinaVan Zuydam, NatalieAhlqvist, EmmaJuliusdottir, ThorhildurDeshmukh, Harshal A.Rayner, N. WilliamDi Camillo, BarbaraForsblom, CarolFadista, JoaoZiemek, DanielSalem, Rany M.Hiraki, Linda T.Pezzolesi, MarcusTrégouët, DavidDahlström, EmmaValo, ErkkaOskolkov, NikolayLadenvall, ClaesMarcovecchio, M. LoredanaCooper, JasonSambo, FrancescoMalovini, AlbertoManfrini, MarcoMcKnight, Amy JayneLajer, MariaHarjutsalo, ValmaGordin, DanielParkkonen, Maija,Lyssenko, ValeriyaMcKeigue, Paul M.Rich, Stephen S.Brosnan, Mary JuliaFauman, EricBellazzi, RiccardoRossing, PeterHadjadj, SamyKrolewski, AndrzejPaterson, Andrew D.,Hirschhorn, Joel N.Maxwell, Alexander P.,Cobelli, ClaudioColhoun, Helen M.Groop, LeifMcCarthy, Mark I.Groop, Per-HenrikSandholm, N.Van Zuydam, N.Ahlqvist, E.Juliusdottir, T.Deshmukh, H.A.,Di Camillo, B.Forsblom, C.Fadista, J.Ziemek, D.Salem, R.M.Hiraki, L.T.Pezzolesi, M.Trégouët, D.Dahlström, E.Valo, E.Oskolkov, N.Ladenvall, C.Marcovecchio, M.L.Cooper, J.Sambo, F.Malovini, A.Manfrini, M.McKnight, A. J.Lajer, M.,Gordin, D.Parkkonen, M.Tuomilehto, J.,McKeigue, P.M.Rich, S.S.Brosnan, M.J.Fauman, E.Bellazzi, R.Rossing, P.Hadjadj, S.Krolewski, A.Paterson, A.D.Florez, J.C.Hirschhorn, J.N.Maxwell, A.P.Dunger, D.,,,,Cobelli, C.Colhoun, H.M.Groop, L.McCarthy, M.I.Groop, P.-H.2016-09-19T10:04:56-07:00doi:10.1681/ASN.2016020231hwp:resource-id:jnephrol;28/2/557American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic kidney disease, genetics and development, genome-wide association study, whole exome sequencingBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160202311046-66731533-34502016-09-19T10:04:56-07:002017-02Journal of the American Society of NephrologyBasic Research2822557389574393
- Renal Aging: Causes and ConsequencesIndividuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis—age–associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies.10.1681/ASN.2015121308Tue, 15 Nov 2016 03:21:30 GMT-08:00Renal Aging: Causes and ConsequencesIndividuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis—age–associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies.O’Sullivan, Eoin D.Hughes, JeremyFerenbach, David A.2016-11-15T15:21:30-08:00doi:10.1681/ASN.2015121308hwp:resource-id:jnephrol;28/2/407American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAging, glomerulosclerosis, kidney dysfunction, metabolism, molecular biology, progression of renal failureUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-02-01February 201710.1681/ASN.20151213081046-66731533-34502016-11-15T15:21:30-08:002017-02Journal of the American Society of NephrologyUp Front Matters282407420
- A Proposal for a Serology-Based Approach to Membranous NephropathyPrimary membranous nephropathy (MN) is an autoimmune disease mainly caused by autoantibodies against the recently discovered podocyte antigens: the M-type phospholipase A2 receptor 1 (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Assays for quantitative assessment of anti-PLA2R antibodies are commercially available, but a semiquantitative test to detect anti-THSD7A antibodies has been only recently developed. The presence or absence of anti-PLA2R and anti-THSD7A antibodies adds important information to clinical and immunopathologic data in discriminating between primary and secondary MN. Levels of anti-PLA2R antibodies and possibly, anti-THSD7A antibodies tightly correlate with disease activity. Low baseline and decreasing anti-PLA2R antibody levels strongly predict spontaneous remission, thus favoring conservative therapy. Conversely, high baseline or increasing anti-PLA2R antibody levels associate with nephrotic syndrome and progressive loss of kidney function, thereby encouraging prompt initiation of immunosuppressive therapy. Serum anti-PLA2R antibody profiles reliably predict response to therapy, and levels at completion of therapy may forecast long-term outcome. Re-emergence of or increase in antibody titers precedes a clinical relapse. Persistence or reappearance of anti-PLA2R antibodies after kidney transplant predicts development of recurrent disease. We propose that an individualized serology-based approach to MN, used to complement and refine the traditional proteinuria-driven approach, will improve the outcome in this disease.10.1681/ASN.2016070776Mon, 24 Oct 2016 08:09:45 GMT-07:00A Proposal for a Serology-Based Approach to Membranous NephropathyPrimary membranous nephropathy (MN) is an autoimmune disease mainly caused by autoantibodies against the recently discovered podocyte antigens: the M-type phospholipase A2 receptor 1 (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Assays for quantitative assessment of anti-PLA2R antibodies are commercially available, but a semiquantitative test to detect anti-THSD7A antibodies has been only recently developed. The presence or absence of anti-PLA2R and anti-THSD7A antibodies adds important information to clinical and immunopathologic data in discriminating between primary and secondary MN. Levels of anti-PLA2R antibodies and possibly, anti-THSD7A antibodies tightly correlate with disease activity. Low baseline and decreasing anti-PLA2R antibody levels strongly predict spontaneous remission, thus favoring conservative therapy. Conversely, high baseline or increasing anti-PLA2R antibody levels associate with nephrotic syndrome and progressive loss of kidney function, thereby encouraging prompt initiation of immunosuppressive therapy. Serum anti-PLA2R antibody profiles reliably predict response to therapy, and levels at completion of therapy may forecast long-term outcome. Re-emergence of or increase in antibody titers precedes a clinical relapse. Persistence or reappearance of anti-PLA2R antibodies after kidney transplant predicts development of recurrent disease. We propose that an individualized serology-based approach to MN, used to complement and refine the traditional proteinuria-driven approach, will improve the outcome in this disease.De Vriese, An S.Glassock, Richard J.Nath, Karl A.Sethi, SanjeevFervenza, Fernando C.2016-10-24T08:09:45-07:00doi:10.1681/ASN.2016070776hwp:resource-id:jnephrol;28/2/421American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, clinical nephrology, Immunology and pathology, PLA2R, THSD7AUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-02-01February 201710.1681/ASN.20160707761046-66731533-34502016-10-24T08:09:45-07:002017-02Journal of the American Society of NephrologyUp Front Matters282421430
- Stretching the Limits of Renal Transplantation in Elderly Recipients of Grafts from Elderly Deceased DonorsAn increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002–2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type. In multiple logistic regression analysis, elderly recipients of elderly DCD kidneys experienced more delayed graft function and acute rejection than did elderly recipients of young DBD kidneys (odds ratios 10.43 [95% confidence interval (95% CI), 5.75 to 18.91] and 2.78 [95% CI, 1.35 to 5.73], respectively). In Cox regression analysis, elderly recipients of elderly DCD kidneys had a 5-year mortality risk higher than that of elderly recipients of young DBD kidneys (hazard ratio, 1.86; 95% CI, 1.15 to 3.02). Elderly recipients of elderly kidneys had a 5-year mortality rate comparable to that of waitlisted elderly patients remaining on dialysis. Among elderly recipients, 63.8% of those who received elderly DCD kidneys, 45.5% of those who received elderly DBD kidneys, and approximately 26% of those who received young DBD or DCD kidneys had an eGFR<30 ml/min per 1.73 m2 (including primary nonfunction) after 1 year. In conclusion, improving donor selection and preservation is warranted if the allocation of elderly DCD grafts to elderly recipients is to be expanded.10.1681/ASN.2015080879Tue, 11 Oct 2016 06:07:39 GMT-07:00Stretching the Limits of Renal Transplantation in Elderly Recipients of Grafts from Elderly Deceased DonorsAn increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002–2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type. In multiple logistic regression analysis, elderly recipients of elderly DCD kidneys experienced more delayed graft function and acute rejection than did elderly recipients of young DBD kidneys (odds ratios 10.43 [95% confidence interval (95% CI), 5.75 to 18.91] and 2.78 [95% CI, 1.35 to 5.73], respectively). In Cox regression analysis, elderly recipients of elderly DCD kidneys had a 5-year mortality risk higher than that of elderly recipients of young DBD kidneys (hazard ratio, 1.86; 95% CI, 1.15 to 3.02). Elderly recipients of elderly kidneys had a 5-year mortality rate comparable to that of waitlisted elderly patients remaining on dialysis. Among elderly recipients, 63.8% of those who received elderly DCD kidneys, 45.5% of those who received elderly DBD kidneys, and approximately 26% of those who received young DBD or DCD kidneys had an eGFR<30 ml/min per 1.73 m2 (including primary nonfunction) after 1 year. In conclusion, improving donor selection and preservation is warranted if the allocation of elderly DCD grafts to elderly recipients is to be expanded.Peters-Sengers, HesselBerger, Stefan P.Heemskerk, Martin B.A.al Arashi, DoaaHoman van der Heide, Jaap J.Hemke, Aline C.ten Berge, Ineke J.M.Idu, Mirza M.Betjes, Michiel G.H.van Zuilen, Arjan D.Hilbrands, Luuk B.de Vries, Aiko P.J.Nurmohamed, Azam S.Christiaans, Maarten H.Ernest van Heurn, L.W.de Fijter, Johan W.Bemelman, Frederike J.2016-10-11T06:07:39-07:00doi:10.1681/ASN.2015080879hwp:resource-id:jnephrol;28/2/621American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, Donation after circulatory death, Donation after brain death, Elderly donors, Elderly recipients, Eurotransplant Senior ProgramClinical EpidemiologyClinical Epidemiologyresearch-article20172017-02-01February 201710.1681/ASN.20150808791046-66731533-34502016-10-11T06:07:39-07:002017-02Journal of the American Society of NephrologyClinical Epidemiology282621631
- The Emerging Importance of Non-HLA Autoantibodies in Kidney Transplant ComplicationsAntibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular injury, and/or rejection creates permissive conditions for the expression of cryptic autoantigens, allowing these autoantibodies to bind antigenic targets and further enhance vascular inflammation and renal dysfunction. Antiperlecan/LG3 antibodies and antiangiotensin II type 1 receptor antibodies have been found before transplant in patients with de novo transplants and portend negative long–term outcome in patients with renal transplants. Here, we review mounting evidence suggesting an important role for autoantibodies to cryptic antigens as novel accelerators of kidney dysfunction and acute or chronic allograft rejection.10.1681/ASN.2016070756Mon, 17 Oct 2016 09:47:38 GMT-07:00The Emerging Importance of Non-HLA Autoantibodies in Kidney Transplant ComplicationsAntibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular injury, and/or rejection creates permissive conditions for the expression of cryptic autoantigens, allowing these autoantibodies to bind antigenic targets and further enhance vascular inflammation and renal dysfunction. Antiperlecan/LG3 antibodies and antiangiotensin II type 1 receptor antibodies have been found before transplant in patients with de novo transplants and portend negative long–term outcome in patients with renal transplants. Here, we review mounting evidence suggesting an important role for autoantibodies to cryptic antigens as novel accelerators of kidney dysfunction and acute or chronic allograft rejection.Cardinal, HéloiseDieudé, MélanieHébert, Marie-Josée2016-10-17T09:47:38-07:00doi:10.1681/ASN.2016070756hwp:resource-id:jnephrol;28/2/400American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, acute renal failure, apoptosis, clinical immunology, endothelial cellsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20172017-02-01February 201710.1681/ASN.20160707561046-66731533-34502016-10-17T09:47:38-07:002017-02Journal of the American Society of NephrologyUp Front Matters282400406
- Kidney Transplantation Outcomes across GN Subtypes in the United StatesDifferences in kidney transplantation outcomes across GN subtypes have rarely been studied. From the US Renal Data System, we identified all adult (≥18 years) first kidney transplant recipients (1996–2011) with ESRD attributed to one of six GN subtypes or two comparator kidney diseases. We computed hazard ratios (HRs) for death, all-cause allograft failure, and allograft failure excluding death as a cause (competing risks framework) using Cox proportional hazards regression. Among the 32,131 patients with GN studied, patients with IgA nephropathy (IgAN) had the lowest mortality rates and patients with IgAN or vasculitis had the lowest allograft failure rates. After adjusting for patient- and transplant-related factors, compared with IgAN (referent), FSGS, membranous nephropathy, membranoproliferative GN, lupus nephritis, and vasculitis associated with HRs (95% confidence intervals) for death of 1.57 (1.43 to 1.72), 1.52 (1.34 to 1.72), 1.76 (1.55 to 2.01), 1.82 (1.63 to 2.02), and 1.56 (1.34 to 1.81), respectively, and with HRs for allograft failure excluding death as a cause of 1.20 (1.12 to 1.28), 1.27 (1.14 to 1.41), 1.50 (1.36 to 1.66), 1.11 (1.02 to 1.20), and 0.94 (0.81 to 1.09), respectively. Considering external comparator groups, and comparing with IgAN, autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy associated with higher HRs for mortality [1.22 (1.12 to 1.34) and 2.57 (2.35 to 2.82), respectively], but ADPKD associated with a lower HR for allograft failure excluding death as a cause [0.85 (0.79 to 0.91)]. Reasons for differential outcomes by GN subtype and cause of ESRD should be examined in future research.10.1681/ASN.2016020126Mon, 18 Jul 2016 07:17:49 GMT-07:00Kidney Transplantation Outcomes across GN Subtypes in the United StatesDifferences in kidney transplantation outcomes across GN subtypes have rarely been studied. From the US Renal Data System, we identified all adult (≥18 years) first kidney transplant recipients (1996–2011) with ESRD attributed to one of six GN subtypes or two comparator kidney diseases. We computed hazard ratios (HRs) for death, all-cause allograft failure, and allograft failure excluding death as a cause (competing risks framework) using Cox proportional hazards regression. Among the 32,131 patients with GN studied, patients with IgA nephropathy (IgAN) had the lowest mortality rates and patients with IgAN or vasculitis had the lowest allograft failure rates. After adjusting for patient- and transplant-related factors, compared with IgAN (referent), FSGS, membranous nephropathy, membranoproliferative GN, lupus nephritis, and vasculitis associated with HRs (95% confidence intervals) for death of 1.57 (1.43 to 1.72), 1.52 (1.34 to 1.72), 1.76 (1.55 to 2.01), 1.82 (1.63 to 2.02), and 1.56 (1.34 to 1.81), respectively, and with HRs for allograft failure excluding death as a cause of 1.20 (1.12 to 1.28), 1.27 (1.14 to 1.41), 1.50 (1.36 to 1.66), 1.11 (1.02 to 1.20), and 0.94 (0.81 to 1.09), respectively. Considering external comparator groups, and comparing with IgAN, autosomal dominant polycystic kidney disease (ADPKD) and diabetic nephropathy associated with higher HRs for mortality [1.22 (1.12 to 1.34) and 2.57 (2.35 to 2.82), respectively], but ADPKD associated with a lower HR for allograft failure excluding death as a cause [0.85 (0.79 to 0.91)]. Reasons for differential outcomes by GN subtype and cause of ESRD should be examined in future research.O’Shaughnessy, Michelle M.Liu, SaiMontez-Rath, Maria E.Lenihan, Colin R.Lafayette, Richard A.Winkelmayer, Wolfgang C.2016-07-18T07:17:49-07:00doi:10.1681/ASN.2016020126hwp:resource-id:jnephrol;28/2/632American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, kidney transplantation, chronic allograft failure, mortality, clinical epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20172017-02-01February 201710.1681/ASN.20160201261046-66731533-34502016-07-18T07:17:49-07:002017-02Journal of the American Society of NephrologyClinical Epidemiology282632644
- YKL-40 Associates with Renal Recovery in Deceased Donor Kidney TransplantationDeceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant.10.1681/ASN.2016010091Fri, 22 Jul 2016 07:17:28 GMT-07:00YKL-40 Associates with Renal Recovery in Deceased Donor Kidney TransplantationDeceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant.Puthumana, JeremyHall, Isaac E.Reese, Peter P.Schröppel, BerndWeng, Francis L.Thiessen-Philbrook, HeatherDoshi, Mona D.Rao, VeenaLee, Chun GeunElias, Jack A.Cantley, Lloyd G.Parikh, Chirag R.2016-07-22T07:17:28-07:00doi:10.1681/ASN.2016010091hwp:resource-id:jnephrol;28/2/661American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologydelayed graft function, renal transplantation, renal functionClinical ResearchClinical Researchresearch-article20172017-02-01February 201710.1681/ASN.20160100911046-66731533-34502016-07-22T07:17:28-07:002017-02Journal of the American Society of NephrologyClinical Research282661670
- This Month's Highlights10.1681/ASN.2016101156Tue, 31 Jan 2017 10:00:49 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2017-01-31T10:00:49-08:00doi:10.1681/ASN.2016101156hwp:resource-id:jnephrol;28/2/iAmerican Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20172017-02-01February 201710.1681/ASN.20161011561046-66731533-34502017-01-31T10:00:49-08:002017-02Journal of the American Society of NephrologyThis Month’s Highlights282ii
- Novel Type of Renal Amyloidosis Derived from Apolipoprotein-CIIAmyloidosis is characterized by extracellular deposition of misfolded proteins as insoluble fibrils. Most renal amyloidosis cases are Ig light chain, AA, or leukocyte chemotactic factor 2 amyloidosis, but rare hereditary forms can also involve the kidneys. Here, we describe the case of a 61-year-old woman who presented with nephrotic syndrome and renal impairment. Examination of the renal biopsy specimen revealed amyloidosis with predominant involvement of glomeruli and medullary interstitium. Proteomic analysis of Congo red–positive deposits detected large amounts of the Apo-CII protein. DNA sequencing of the APOC2 gene in the patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. We also detected the mutant peptide in the proband’s renal amyloid deposits. Using proteomics, we identified seven additional elderly patients with Apo-CII–rich amyloid deposits, all of whom had kidney involvement and histologically exhibited nodular glomerular involvement. Although prior in vitro studies have shown that Apo-CII can form amyloid fibrils and that certain mutations in this protein promote amyloid fibrillogenesis, there are no reports of this type of amyloidosis in humans. We propose that this study reveals a new form of hereditary amyloidosis (AApoCII) that is derived from the Apo-CII protein and appears to manifest in the elderly and preferentially affect the kidneys.10.1681/ASN.2015111228Mon, 13 Jun 2016 11:37:24 GMT-07:00Novel Type of Renal Amyloidosis Derived from Apolipoprotein-CIIAmyloidosis is characterized by extracellular deposition of misfolded proteins as insoluble fibrils. Most renal amyloidosis cases are Ig light chain, AA, or leukocyte chemotactic factor 2 amyloidosis, but rare hereditary forms can also involve the kidneys. Here, we describe the case of a 61-year-old woman who presented with nephrotic syndrome and renal impairment. Examination of the renal biopsy specimen revealed amyloidosis with predominant involvement of glomeruli and medullary interstitium. Proteomic analysis of Congo red–positive deposits detected large amounts of the Apo-CII protein. DNA sequencing of the APOC2 gene in the patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. We also detected the mutant peptide in the proband’s renal amyloid deposits. Using proteomics, we identified seven additional elderly patients with Apo-CII–rich amyloid deposits, all of whom had kidney involvement and histologically exhibited nodular glomerular involvement. Although prior in vitro studies have shown that Apo-CII can form amyloid fibrils and that certain mutations in this protein promote amyloid fibrillogenesis, there are no reports of this type of amyloidosis in humans. We propose that this study reveals a new form of hereditary amyloidosis (AApoCII) that is derived from the Apo-CII protein and appears to manifest in the elderly and preferentially affect the kidneys.Nasr, Samih H.Dasari, SurendraHasadsri, LindaTheis, Jason D.Vrana, Julie A.Gertz, Morie A.Muppa, PrasunaZimmermann, Michael T.Grogg, Karen L.Dispenzieri, AngelaSethi, SanjeevHighsmith, W. EdwardMerlini, GiampaoloLeung, NelsonKurtin, Paul J.2016-06-13T11:37:24-07:00doi:10.1681/ASN.2015111228hwp:resource-id:jnephrol;28/2/439American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyamyloidosis, renal amyloid, hereditary amyloidosis, apolipoprotein C-IIBrief CommunicationsBrief Communicationsbrief-report20172017-02-01February 201710.1681/ASN.20151112281046-66731533-34502016-06-13T11:37:24-07:002017-02Journal of the American Society of NephrologyBrief Communications282439445
- The Effect of Predialysis Fistula Attempt on Risk of All-Cause and Access-Related DeathWhether the lower risk of mortality associated with arteriovenous fistula use in hemodialysis patients is due to the avoidance of catheters or if healthier patients are simply more likely to have fistulas placed is unknown. To provide clarification, we determined the proportion of access-related deaths in a retrospective cohort study of patients aged ≥18 years who initiated hemodialysis between 2004 and 2012 at five Canadian dialysis programs. A total of 3168 patients initiated dialysis at the participating centers; 2300 met our inclusion criteria. Two investigators independently adjudicated cause of death using explicit criteria and determined whether a death was access-related. We observed significantly lower mortality in individuals who underwent a predialysis fistula attempt than in those without a predialysis fistula attempt in patients aged <65 years (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.29 to 0.82) and in the first 2 years of follow-up in those aged ≥65 years (HR0–24 months, 0.60; 95% CI, 0.43 to 0.84; HR24+ months, 1.83; 95% CI, 1.25 to 2.67). Sudden deaths that occurred out of hospital accounted for most of the deaths, followed by deaths due to cardiovascular disease and infectious complications. We found only 2.3% of deaths to be access-related. In conclusion, predialysis fistula attempt may associate with a lower risk of mortality. However, the excess mortality observed in patients treated with catheters does not appear to be due to direct, access-related complications but is likely the result of residual confounding, unmeasured comorbidity, or treatment selection bias.10.1681/ASN.2016020151Thu, 06 Oct 2016 07:08:12 GMT-07:00The Effect of Predialysis Fistula Attempt on Risk of All-Cause and Access-Related DeathWhether the lower risk of mortality associated with arteriovenous fistula use in hemodialysis patients is due to the avoidance of catheters or if healthier patients are simply more likely to have fistulas placed is unknown. To provide clarification, we determined the proportion of access-related deaths in a retrospective cohort study of patients aged ≥18 years who initiated hemodialysis between 2004 and 2012 at five Canadian dialysis programs. A total of 3168 patients initiated dialysis at the participating centers; 2300 met our inclusion criteria. Two investigators independently adjudicated cause of death using explicit criteria and determined whether a death was access-related. We observed significantly lower mortality in individuals who underwent a predialysis fistula attempt than in those without a predialysis fistula attempt in patients aged <65 years (hazard ratio [HR], 0.49; 95% confidence interval [95% CI], 0.29 to 0.82) and in the first 2 years of follow-up in those aged ≥65 years (HR0–24 months, 0.60; 95% CI, 0.43 to 0.84; HR24+ months, 1.83; 95% CI, 1.25 to 2.67). Sudden deaths that occurred out of hospital accounted for most of the deaths, followed by deaths due to cardiovascular disease and infectious complications. We found only 2.3% of deaths to be access-related. In conclusion, predialysis fistula attempt may associate with a lower risk of mortality. However, the excess mortality observed in patients treated with catheters does not appear to be due to direct, access-related complications but is likely the result of residual confounding, unmeasured comorbidity, or treatment selection bias.Quinn, Robert R.Oliver, Matthew J.Devoe, DanielPoinen, KrishnanKabani, RameezKamar, FareedMysore, PriyankaLewin, Adriane M.Hiremath, SwapnilMacRae, JenniferJames, Matthew T.Miller, LisaHemmelgarn, Brenda R.Moist, Louise M.Garg, Amit X.Chowdhury, Tanvir T.Ravani, Pietro2016-10-06T07:08:12-07:00doi:10.1681/ASN.2016020151hwp:resource-id:jnephrol;28/2/613American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis access, hemodialysis, arteriovenous fistulaClinical EpidemiologyClinical Epidemiologyresearch-article20172017-02-01February 201710.1681/ASN.20160201511046-66731533-34502016-10-06T07:08:12-07:002017-02Journal of the American Society of NephrologyClinical Epidemiology2822613395620397
- Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In VivoAcute tubular damage is a major cause of renal failure, especially at the early phase of kidney transplant when ischemia-reperfusion injury and cyclosporin A toxicity may coexist. The mechanisms of the latter are largely unknown. Using an mRNA microarray on microdissected tubules from a rat model of cyclosporin A toxicity to describe the related epithelial-specific transcriptional signature in vivo, we found that cyclosporin A induces pathways dependent on the transcription factor ATF4 and identified nuclear protein transcriptional regulator 1 (Nupr1), a stress response gene induced by ATF4, as the gene most strongly upregulated. Upon cyclosporin A treatment, Nupr1-deficient mice exhibited worse renal tubular lesions than wild-type mice. In primary cultures treated with cyclosporin A, renal tubular cells isolated from Nupr1-deficient mice exhibited more apoptosis and ATP depletion than cells from wild-type mice. Furthermore, cyclosporin A decreased protein synthesis and abolished proliferation in wild-type tubular cells, but only reduced proliferation in Nupr1-deficient cells. Compared with controls, mouse models of ischemia-reperfusion injury, urinary obstruction, and hypertension exhibited upregulated expression of renal NUPR1, and cyclosporin A induced Nupr1 expression in cultured human tubular epithelial cells. Finally, immunohistochemical analysis revealed strong expression of NUPR1 in the nuclei of renal proximal tubules of injured human kidney allografts, but not in those of stable allografts. Taken together, these results suggest that epithelial expression of NUPR1 has a protective role in response to injury after renal transplant and, presumably, in other forms of acute tubular damage.10.1681/ASN.2015080936Fri, 22 Jul 2016 07:17:27 GMT-07:00Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In VivoAcute tubular damage is a major cause of renal failure, especially at the early phase of kidney transplant when ischemia-reperfusion injury and cyclosporin A toxicity may coexist. The mechanisms of the latter are largely unknown. Using an mRNA microarray on microdissected tubules from a rat model of cyclosporin A toxicity to describe the related epithelial-specific transcriptional signature in vivo, we found that cyclosporin A induces pathways dependent on the transcription factor ATF4 and identified nuclear protein transcriptional regulator 1 (Nupr1), a stress response gene induced by ATF4, as the gene most strongly upregulated. Upon cyclosporin A treatment, Nupr1-deficient mice exhibited worse renal tubular lesions than wild-type mice. In primary cultures treated with cyclosporin A, renal tubular cells isolated from Nupr1-deficient mice exhibited more apoptosis and ATP depletion than cells from wild-type mice. Furthermore, cyclosporin A decreased protein synthesis and abolished proliferation in wild-type tubular cells, but only reduced proliferation in Nupr1-deficient cells. Compared with controls, mouse models of ischemia-reperfusion injury, urinary obstruction, and hypertension exhibited upregulated expression of renal NUPR1, and cyclosporin A induced Nupr1 expression in cultured human tubular epithelial cells. Finally, immunohistochemical analysis revealed strong expression of NUPR1 in the nuclei of renal proximal tubules of injured human kidney allografts, but not in those of stable allografts. Taken together, these results suggest that epithelial expression of NUPR1 has a protective role in response to injury after renal transplant and, presumably, in other forms of acute tubular damage.Galichon, PierreBataille, AurélienVandermeersch, SophieWetzstein, MorganeXu-Dubois, Yi-ChunLegouis, DavidHertig, AlexandreBuob, DavidPlacier, SandrineBigé, NaïkeLefevre, GuillaumeJouanneau, ChantalMartin, CarolineIovanna, Juan LucioRondeau, Eric2016-07-22T07:17:27-07:00doi:10.1681/ASN.2015080936hwp:resource-id:jnephrol;28/2/545American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologycell activation, cyclosporine nephrotoxicity, gene expression, renal proximal tubule cell, Pathophysiology of Renal Disease and ProgressionBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20150809361046-66731533-34502016-07-22T07:17:27-07:002017-02Journal of the American Society of NephrologyBasic Research282545556
- Fibroblast Growth Factor 23 Regulation by Systemic and Local Osteoblast-Synthesized 1,25-Dihydroxyvitamin DCirculating levels of fibroblast growth factor 23 (FGF23) increase during the early stages of kidney disease, but the underlying mechanism remains incompletely characterized. We investigated the role of vitamin D metabolites in regulating intact FGF23 production in genetically modified mice without and with adenine-induced uremia. Exogenous calcitriol (1,25-dihydroxyvitamin D) and high circulating levels of calcidiol (25-hydroxyvitamin D) each increased serum FGF23 levels in wild-type mice and in mice with global deficiency of the Cyp27b1 gene encoding 25-hydroxyvitamin D 1-α-hydroxylase, which produces 1,25-hydroxyvitamin D. Compared with wild-type mice, normal, or uremic mice lacking Cyp27b1 had lower levels of serum FGF23, despite having high concentrations of parathyroid hormone, but administration of exogenous 1,25-dihydroxyvitamin D increased FGF23 levels. Furthermore, raising serum calcium levels in Cyp27b1-depleted mice directly increased FGF23 levels and indirectly enhanced the action of ambient vitamin D metabolites via the vitamin D receptor. In chromatin immunoprecipitation assays, 25-hydroxyvitamin D promoted binding of the vitamin D receptor and retinoid X receptor to the promoters of osteoblastic target genes. Conditional osteoblastic deletion of Cyp27b1 caused lower serum FGF23 levels, despite normal circulating levels of vitamin D metabolites. In adenine-induced uremia, only a modest increase in serum FGF23 levels occurred in mice with osteoblastic deletion of Cyp27b1 (12-fold) compared with a large increase (58-fold) in wild-type mice. Therefore, in addition to the direct effect of high circulating concentrations of 25-hydroxyvitamin D, local osteoblastic conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D appears to be an important positive regulator of FGF23 production, particularly in uremia.10.1681/ASN.2016010066Wed, 17 Aug 2016 07:26:45 GMT-07:00Fibroblast Growth Factor 23 Regulation by Systemic and Local Osteoblast-Synthesized 1,25-Dihydroxyvitamin DCirculating levels of fibroblast growth factor 23 (FGF23) increase during the early stages of kidney disease, but the underlying mechanism remains incompletely characterized. We investigated the role of vitamin D metabolites in regulating intact FGF23 production in genetically modified mice without and with adenine-induced uremia. Exogenous calcitriol (1,25-dihydroxyvitamin D) and high circulating levels of calcidiol (25-hydroxyvitamin D) each increased serum FGF23 levels in wild-type mice and in mice with global deficiency of the Cyp27b1 gene encoding 25-hydroxyvitamin D 1-α-hydroxylase, which produces 1,25-hydroxyvitamin D. Compared with wild-type mice, normal, or uremic mice lacking Cyp27b1 had lower levels of serum FGF23, despite having high concentrations of parathyroid hormone, but administration of exogenous 1,25-dihydroxyvitamin D increased FGF23 levels. Furthermore, raising serum calcium levels in Cyp27b1-depleted mice directly increased FGF23 levels and indirectly enhanced the action of ambient vitamin D metabolites via the vitamin D receptor. In chromatin immunoprecipitation assays, 25-hydroxyvitamin D promoted binding of the vitamin D receptor and retinoid X receptor to the promoters of osteoblastic target genes. Conditional osteoblastic deletion of Cyp27b1 caused lower serum FGF23 levels, despite normal circulating levels of vitamin D metabolites. In adenine-induced uremia, only a modest increase in serum FGF23 levels occurred in mice with osteoblastic deletion of Cyp27b1 (12-fold) compared with a large increase (58-fold) in wild-type mice. Therefore, in addition to the direct effect of high circulating concentrations of 25-hydroxyvitamin D, local osteoblastic conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D appears to be an important positive regulator of FGF23 production, particularly in uremia.Nguyen-Yamamoto, LoanKaraplis, Andrew C.St–Arnaud, ReneGoltzman, David2016-08-17T07:26:45-07:00doi:10.1681/ASN.2016010066hwp:resource-id:jnephrol;28/2/586American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyVitamin D, FGF23, calcium, Activated Vitamin D, parathyroid hormoneBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160100661046-66731533-34502016-08-17T07:26:45-07:002017-02Journal of the American Society of NephrologyBasic Research2822586393597395
- Matrix Metalloproteinase-7 Is a Urinary Biomarker and Pathogenic Mediator of Kidney FibrosisMatrix metalloproteinase-7 (MMP-7), a secreted zinc– and calcium–dependent endopeptidase, is a transcriptional target of canonical Wnt/β-catenin signaling. Because Wnt/β-catenin is activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various kidney disorders had markedly elevated urinary levels of MMP-7. Furthermore, urinary MMP-7 levels closely correlated with renal fibrosis scores in patients. In mice, knockout of MMP-7 ameliorated the fibrotic lesions and expression of matrix genes induced by obstructive injury. Genetic ablation of MMP-7 also preserved E-cadherin protein expression and substantially reduced the expression of total and dephosphorylated β-catenin and the de novo expression of vimentin and fibroblast-specific protein 1 in renal tubules of obstructed kidneys. In vitro, MMP-7 proteolytically degraded E-cadherin in proximal tubular cells, leading to β-catenin liberation and nuclear translocation and induction of β-catenin target genes by a mechanism independent of Wnt ligands. Finally, pharmacologic inhibition of MMP-7 immediately after obstructive injury reduced renal fibrosis in vivo. These results suggest that MMP-7 not only can serve as a noninvasive biomarker but also is an important pathogenic mediator of kidney fibrosis.10.1681/ASN.2016030354Tue, 13 Sep 2016 07:22:26 GMT-07:00Matrix Metalloproteinase-7 Is a Urinary Biomarker and Pathogenic Mediator of Kidney FibrosisMatrix metalloproteinase-7 (MMP-7), a secreted zinc– and calcium–dependent endopeptidase, is a transcriptional target of canonical Wnt/β-catenin signaling. Because Wnt/β-catenin is activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various kidney disorders had markedly elevated urinary levels of MMP-7. Furthermore, urinary MMP-7 levels closely correlated with renal fibrosis scores in patients. In mice, knockout of MMP-7 ameliorated the fibrotic lesions and expression of matrix genes induced by obstructive injury. Genetic ablation of MMP-7 also preserved E-cadherin protein expression and substantially reduced the expression of total and dephosphorylated β-catenin and the de novo expression of vimentin and fibroblast-specific protein 1 in renal tubules of obstructed kidneys. In vitro, MMP-7 proteolytically degraded E-cadherin in proximal tubular cells, leading to β-catenin liberation and nuclear translocation and induction of β-catenin target genes by a mechanism independent of Wnt ligands. Finally, pharmacologic inhibition of MMP-7 immediately after obstructive injury reduced renal fibrosis in vivo. These results suggest that MMP-7 not only can serve as a noninvasive biomarker but also is an important pathogenic mediator of kidney fibrosis.Zhou, DongTian, YuanSun, LingZhou, LiliXiao, LiangxiangTan, Roderick J.Tian, JianweiFu, HaiyanHou, Fan FanLiu, Youhua2016-09-13T07:22:26-07:00doi:10.1681/ASN.2016030354hwp:resource-id:jnephrol;28/2/598American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, chronic kidney disease, nephropathy, Pathophysiology of Renal Disease and Progression, MMP-7, WntBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160303541046-66731533-34502016-09-13T07:22:26-07:002017-02Journal of the American Society of NephrologyBasic Research282598611
- An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary HyperoxaluriaPrimary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound.10.1681/ASN.2016030338Mon, 18 Jul 2016 07:17:50 GMT-07:00An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary HyperoxaluriaPrimary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk. In this report, we discuss the development of ALN-GO1, an investigational RNA interference (RNAi) therapeutic targeting glycolate oxidase, to deplete the substrate for oxalate synthesis. Subcutaneous administration of ALN-GO1 resulted in potent, dose-dependent, and durable silencing of the mRNA encoding glycolate oxidase and increased serum glycolate concentrations in wild-type mice, rats, and nonhuman primates. ALN-GO1 also increased urinary glycolate concentrations in normal nonhuman primates and in a genetic mouse model of PH1. Notably, ALN-GO1 reduced urinary oxalate concentration up to 50% after a single dose in the genetic mouse model of PH1, and up to 98% after multiple doses in a rat model of hyperoxaluria. These data demonstrate the ability of ALN-GO1 to reduce oxalate production in preclinical models of PH1 across multiple species and provide a clear rationale for clinical trials with this compound.Liebow, AbigailLi, XingshengRacie, TimothyHettinger, JuliaBettencourt, Brian R.Najafian, NaderHaslett, PatrickFitzgerald, KevinHolmes, Ross P.Erbe, DavidQuerbes, WilliamKnight, John2016-07-18T07:17:50-07:00doi:10.1681/ASN.2016030338hwp:resource-id:jnephrol;28/2/494American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, RNAi therapeutics, oxalate, primary hyperoxaluria type I, siRNABasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160303381046-66731533-34502016-07-18T07:17:50-07:002017-02Journal of the American Society of NephrologyBasic Research282494503
- Erratum10.1681/ASN.2016121275Tue, 31 Jan 2017 10:00:49 GMT-08:00ErratumAmerican Society of Nephrology2017-01-31T10:00:49-08:00doi:10.1681/ASN.2016121275hwp:resource-id:jnephrol;28/2/716American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20172017-02-01February 201710.1681/ASN.20161212751046-66731533-34502017-01-31T10:00:49-08:002017-02Journal of the American Society of NephrologyErratum2827210107163035303571630503050
- Toll-Like Receptors 2 and 4 Are Potential Therapeutic Targets in Peritoneal Dialysis–Associated FibrosisPeritoneal dialysis (PD) remains limited by dialysis failure due to peritoneal membrane fibrosis driven by inflammation caused by infections or sterile cellular stress. Given the fundamental role of Toll-like receptors (TLRs) and complement in inflammation, we assessed the potential of peritoneal TLR2, TLR4 and C5a receptors, C5aR and C5L2, as therapeutic targets in PD-associated fibrosis. We detected TLR2–, TLR4–, and C5aR–mediated proinflammatory and fibrotic responses to bacteria that were consistent with the expression of these receptors in peritoneal macrophages (TLR2/4, C5aR) and mesothelial cells (TLR2, C5aR). Experiments in knockout mice revealed a major role for TLR2, a lesser role for TLR4, a supplementary role for C5aR, and no apparent activity of C5L2 in infection–induced peritoneal fibrosis. Similarly, antibody blockade of TLR2, TLR4, or C5aR differentially inhibited bacteria–induced profibrotic and inflammatory mediator production by peritoneal leukocytes isolated from the peritoneal dialysis effluent (PDE) of noninfected uremic patients. Additionally, antibodies against TLR2, TLR4, or the coreceptor CD14 reduced the profibrotic responses of uremic leukocytes to endogenous components present in the PDE of noninfected patients. Enhancing TLR2-mediated inflammation increased fibrosis in vivo. Furthermore, soluble TLR2 (sTLR2), a negative modulator of TLRs that we detected in PDE, inhibited PDE–induced, TLR2– or TLR4–mediated profibrotic responses. Notably, sTLR2 treatment markedly reduced Gram–positive and –negative bacteria–induced fibrosis in vivo, inhibiting proinflammatory and fibrotic genes without affecting infection clearance. These findings reveal the influence of peritoneal TLR2 and TLR4 on PD-associated fibrosis and describe a therapeutic strategy against fibrosis.10.1681/ASN.2015080923Mon, 18 Jul 2016 07:17:48 GMT-07:00Toll-Like Receptors 2 and 4 Are Potential Therapeutic Targets in Peritoneal Dialysis–Associated FibrosisPeritoneal dialysis (PD) remains limited by dialysis failure due to peritoneal membrane fibrosis driven by inflammation caused by infections or sterile cellular stress. Given the fundamental role of Toll-like receptors (TLRs) and complement in inflammation, we assessed the potential of peritoneal TLR2, TLR4 and C5a receptors, C5aR and C5L2, as therapeutic targets in PD-associated fibrosis. We detected TLR2–, TLR4–, and C5aR–mediated proinflammatory and fibrotic responses to bacteria that were consistent with the expression of these receptors in peritoneal macrophages (TLR2/4, C5aR) and mesothelial cells (TLR2, C5aR). Experiments in knockout mice revealed a major role for TLR2, a lesser role for TLR4, a supplementary role for C5aR, and no apparent activity of C5L2 in infection–induced peritoneal fibrosis. Similarly, antibody blockade of TLR2, TLR4, or C5aR differentially inhibited bacteria–induced profibrotic and inflammatory mediator production by peritoneal leukocytes isolated from the peritoneal dialysis effluent (PDE) of noninfected uremic patients. Additionally, antibodies against TLR2, TLR4, or the coreceptor CD14 reduced the profibrotic responses of uremic leukocytes to endogenous components present in the PDE of noninfected patients. Enhancing TLR2-mediated inflammation increased fibrosis in vivo. Furthermore, soluble TLR2 (sTLR2), a negative modulator of TLRs that we detected in PDE, inhibited PDE–induced, TLR2– or TLR4–mediated profibrotic responses. Notably, sTLR2 treatment markedly reduced Gram–positive and –negative bacteria–induced fibrosis in vivo, inhibiting proinflammatory and fibrotic genes without affecting infection clearance. These findings reveal the influence of peritoneal TLR2 and TLR4 on PD-associated fibrosis and describe a therapeutic strategy against fibrosis.Raby, Anne-CatherineColmont, Chantal S.Kift-Morgan, AnnKöhl, JörgEberl, MatthiasFraser, DonaldTopley, NicholasLabéta, Mario O.2016-07-18T07:17:48-07:00doi:10.1681/ASN.2015080923hwp:resource-id:jnephrol;28/2/461American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, immunology and pathology, fibrosis, clinical immunologyBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20150809231046-66731533-34502016-07-18T07:17:48-07:002017-02Journal of the American Society of NephrologyBasic Research282461478
- The Pas de Trois of Vitamin D, FGF23, and PTH10.1681/ASN.2016090944Wed, 02 Nov 2016 01:07:15 GMT-07:00The Pas de Trois of Vitamin D, FGF23, and PTHNaveh-Many, TallySilver, Justin2016-11-02T13:07:15-07:00doi:10.1681/ASN.2016090944hwp:resource-id:jnephrol;28/2/393American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrology1,25(OH)2vitamin D, FGF23, PTHUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-02-01February 201710.1681/ASN.20160909441046-66731533-34502016-11-02T13:07:15-07:002017-02Journal of the American Society of NephrologyUp Front Matters2822393586395597
- Dynamin Autonomously Regulates Podocyte Focal Adhesion MaturationRho family GTPases, the prototypical members of which are Cdc42, Rac1, and RhoA, are molecular switches best known for regulating the actin cytoskeleton. In addition to the canonical small GTPases, the large GTPase dynamin has been implicated in regulating the actin cytoskeleton via direct dynamin-actin interactions. The physiologic role of dynamin in regulating the actin cytoskeleton has been linked to the maintenance of the kidney filtration barrier. Additionally, the small molecule Bis-T-23, which promotes actin–dependent dynamin oligomerization and thus, increases actin polymerization, improved renal health in diverse models of CKD, implicating dynamin as a potential therapeutic target for the treatment of CKD. Here, we show that treating cultured mouse podocytes with Bis-T-23 promoted stress fiber formation and focal adhesion maturation in a dynamin-dependent manner. Furthermore, Bis-T-23 induced the formation of focal adhesions and stress fibers in cells in which the RhoA signaling pathway was downregulated by multiple experimental approaches. Our study suggests that dynamin regulates focal adhesion maturation by a mechanism parallel to and synergistic with the RhoA signaling pathway. Identification of dynamin as one of the essential and autonomous regulators of focal adhesion maturation suggests a molecular mechanism that underlies the beneficial effect of Bis-T-23 on podocyte physiology.10.1681/ASN.2016010008Mon, 18 Jul 2016 07:17:47 GMT-07:00Dynamin Autonomously Regulates Podocyte Focal Adhesion MaturationRho family GTPases, the prototypical members of which are Cdc42, Rac1, and RhoA, are molecular switches best known for regulating the actin cytoskeleton. In addition to the canonical small GTPases, the large GTPase dynamin has been implicated in regulating the actin cytoskeleton via direct dynamin-actin interactions. The physiologic role of dynamin in regulating the actin cytoskeleton has been linked to the maintenance of the kidney filtration barrier. Additionally, the small molecule Bis-T-23, which promotes actin–dependent dynamin oligomerization and thus, increases actin polymerization, improved renal health in diverse models of CKD, implicating dynamin as a potential therapeutic target for the treatment of CKD. Here, we show that treating cultured mouse podocytes with Bis-T-23 promoted stress fiber formation and focal adhesion maturation in a dynamin-dependent manner. Furthermore, Bis-T-23 induced the formation of focal adhesions and stress fibers in cells in which the RhoA signaling pathway was downregulated by multiple experimental approaches. Our study suggests that dynamin regulates focal adhesion maturation by a mechanism parallel to and synergistic with the RhoA signaling pathway. Identification of dynamin as one of the essential and autonomous regulators of focal adhesion maturation suggests a molecular mechanism that underlies the beneficial effect of Bis-T-23 on podocyte physiology.Gu, ChangkyuLee, Ha WonGarborcauskas, GarrettReiser, JochenGupta, VineetSever, Sanja2016-07-18T07:17:47-07:00doi:10.1681/ASN.2016010008hwp:resource-id:jnephrol;28/2/446American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyactin, dynamin, RhoA, podocyteBrief CommunicationsBrief Communicationsbrief-report20172017-02-01February 201710.1681/ASN.20160100081046-66731533-34502016-07-18T07:17:47-07:002017-02Journal of the American Society of NephrologyBrief Communications282446451
- BP Control and Long-Term Risk of ESRD and MortalityWe recently showed an association between strict BP control and lower mortality risk during two decades of follow-up of prior participants in the Modification of Diet in Renal Disease (MDRD) trial. Here, we determined the risk of ESRD and mortality during extended follow-up of the African American Study of Kidney Disease and Hypertension (AASK) trial. We linked 1067 former AASK participants with CKD previously randomized to strict or usual BP control (mean arterial pressure ≤92 mmHg or 102–107 mmHg, respectively) to the US Renal Data System and Social Security Death Index; 397 patients had ESRD and 475 deaths occurred during a median follow-up of 14.4 years from 1995 to 2012. Compared with the usual BP arm, the strict BP arm had unadjusted and adjusted relative risks of ESRD of 0.92 (95% confidence interval [95% CI], 0.75 to 1.12) and 0.95 (95% CI, 0.78 to 1.16; P=0.64), respectively, and unadjusted and adjusted relative risks of death of 0.92 (95% CI, 0.77 to 1.10) and 0.81 (95% CI, 0.68 to 0.98; P=0.03), respectively. In meta-analyses of individual-level data from the MDRD and the AASK trials, unadjusted relative risk of ESRD was 0.88 (95% CI, 0.78 to 1.00) and unadjusted relative risk of death was 0.87 (95% CI, 0.76 to 0.99) for strict versus usual BP arms. Our findings suggest that, during long–term follow-up, strict BP control does not delay the onset of ESRD but may reduce the relative risk of death in CKD.10.1681/ASN.2016030326Thu, 11 Aug 2016 08:00:57 GMT-07:00BP Control and Long-Term Risk of ESRD and MortalityWe recently showed an association between strict BP control and lower mortality risk during two decades of follow-up of prior participants in the Modification of Diet in Renal Disease (MDRD) trial. Here, we determined the risk of ESRD and mortality during extended follow-up of the African American Study of Kidney Disease and Hypertension (AASK) trial. We linked 1067 former AASK participants with CKD previously randomized to strict or usual BP control (mean arterial pressure ≤92 mmHg or 102–107 mmHg, respectively) to the US Renal Data System and Social Security Death Index; 397 patients had ESRD and 475 deaths occurred during a median follow-up of 14.4 years from 1995 to 2012. Compared with the usual BP arm, the strict BP arm had unadjusted and adjusted relative risks of ESRD of 0.92 (95% confidence interval [95% CI], 0.75 to 1.12) and 0.95 (95% CI, 0.78 to 1.16; P=0.64), respectively, and unadjusted and adjusted relative risks of death of 0.92 (95% CI, 0.77 to 1.10) and 0.81 (95% CI, 0.68 to 0.98; P=0.03), respectively. In meta-analyses of individual-level data from the MDRD and the AASK trials, unadjusted relative risk of ESRD was 0.88 (95% CI, 0.78 to 1.00) and unadjusted relative risk of death was 0.87 (95% CI, 0.76 to 0.99) for strict versus usual BP arms. Our findings suggest that, during long–term follow-up, strict BP control does not delay the onset of ESRD but may reduce the relative risk of death in CKD.Ku, ElaineGassman, JenniferAppel, Lawrence J.Smogorzewski, MiroslawSarnak, Mark J.Glidden, David V.Bakris, GeorgeGutiérrez, Orlando M.Hebert, Lee A.Ix, Joachim H.Lea, JaniceLipkowitz, Michael S.Norris, KeithPloth, DavidPogue, Velvie A.Rostand, Stephen G.Siew, Edward D.Sika, MohammedTisher, C. CraigToto, RobertWright, Jackson T.Wyatt, ChristinaHsu, Chi-yuan2016-08-11T08:00:57-07:00doi:10.1681/ASN.2016030326hwp:resource-id:jnephrol;28/2/671American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, ckd, ESRDClinical ResearchClinical Researchresearch-article20172017-02-01February 201710.1681/ASN.20160303261046-66731533-34502016-08-11T08:00:57-07:002017-02Journal of the American Society of NephrologyClinical Research282671677
- The Survival Benefit of “Fistula First, Catheter Last” in Hemodialysis Is Primarily Due to Patient FactorsPatients needing hemodialysis are advised to have arteriovenous fistulas rather than catheters because of significantly lower mortality rates. However, disparities in fistula placement raise the possibility that patient factors have a role in this apparent mortality benefit. We derived a cohort of 115,425 patients on incident hemodialysis ≥67 years old from the US Renal Data System with linked Medicare claims to identify the first predialysis vascular access placed. We compared mortality outcomes in patients initiating hemodialysis with a fistula placed first, a catheter after a fistula placed first failed, or a catheter placed first (n=90,517; reference group). Of 21,436 patients with a fistula placed first, 9794 initiated hemodialysis with that fistula, and 8230 initiated dialysis with a catheter after failed fistula placement. The fistula group had the lowest mortality over 58 months (hazard ratio, 0.50; 95% confidence interval, 0.48 to 0.52; P<0.001), with mortality rates at 6, 12, and 24 months after initiation of 9%, 17%, and 31%, respectively, compared with 32%, 46%, and 62%, respectively, in the catheter group. However, the group initiating hemodialysis with a catheter after failed fistula placement also had significantly lower mortality rates than the catheter group had over 58 months (hazard ratio, 0.66; 95% confidence interval, 0.64 to 0.68; P<0.001), with mortality rates of 15%, 25%, and 42% at 6, 12, and 24 months, respectively. Thus, patient factors affecting fistula placement, even when patients are hemodialyzed with a catheter instead, may explain at least two thirds of the mortality benefit observed in patients with a fistula.10.1681/ASN.2016010019Wed, 07 Sep 2016 07:36:33 GMT-07:00The Survival Benefit of “Fistula First, Catheter Last” in Hemodialysis Is Primarily Due to Patient FactorsPatients needing hemodialysis are advised to have arteriovenous fistulas rather than catheters because of significantly lower mortality rates. However, disparities in fistula placement raise the possibility that patient factors have a role in this apparent mortality benefit. We derived a cohort of 115,425 patients on incident hemodialysis ≥67 years old from the US Renal Data System with linked Medicare claims to identify the first predialysis vascular access placed. We compared mortality outcomes in patients initiating hemodialysis with a fistula placed first, a catheter after a fistula placed first failed, or a catheter placed first (n=90,517; reference group). Of 21,436 patients with a fistula placed first, 9794 initiated hemodialysis with that fistula, and 8230 initiated dialysis with a catheter after failed fistula placement. The fistula group had the lowest mortality over 58 months (hazard ratio, 0.50; 95% confidence interval, 0.48 to 0.52; P<0.001), with mortality rates at 6, 12, and 24 months after initiation of 9%, 17%, and 31%, respectively, compared with 32%, 46%, and 62%, respectively, in the catheter group. However, the group initiating hemodialysis with a catheter after failed fistula placement also had significantly lower mortality rates than the catheter group had over 58 months (hazard ratio, 0.66; 95% confidence interval, 0.64 to 0.68; P<0.001), with mortality rates of 15%, 25%, and 42% at 6, 12, and 24 months, respectively. Thus, patient factors affecting fistula placement, even when patients are hemodialyzed with a catheter instead, may explain at least two thirds of the mortality benefit observed in patients with a fistula.Brown, Robert S.Patibandla, Bhanu K.Goldfarb-Rumyantzev, Alexander S.2016-09-07T07:36:33-07:00doi:10.1681/ASN.2016010019hwp:resource-id:jnephrol;28/2/645American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis access, mortality, mortality risk, arteriovenous fistula, dialysis, accessClinical EpidemiologyClinical Epidemiologyresearch-article20172017-02-01February 201710.1681/ASN.20160100191046-66731533-34502016-09-07T07:36:33-07:002017-02Journal of the American Society of NephrologyClinical Epidemiology2822645395652397
- Value of Donor–Specific Anti–HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft LossThe diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor–specific anti–HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic monitoring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post–transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post–transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post-transplant screening identified 186 (21.9%) DSA-positive patients. Post–transplant DSA monitoring improved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statistic from 0.67; 95% confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77). Addition of DSA IgG3 positivity or C1q binding capacity increased discrimination performance of the traditional model at transplant and post-transplant. Compared with DSA mean fluorescence intensity, DSA IgG3 positivity and C1q binding capacity adequately reclassified patients at lower or higher risk for allograft loss at transplant (category–free net reclassification index, 1.30; 95% CI, 0.94 to 1.67; P<0.001 and 0.93; 95% CI, 0.49 to 1.36; P<0.001, respectively) and post-transplant (category–free net reclassification index, 1.33; 95% CI, 1.03 to 1.62; P<0.001 and 0.95; 95% CI, 0.62 to 1.28; P<0.001, respectively). Thus, pre– and post–transplant DSA monitoring and characterization may improve individual risk stratification for kidney allograft loss.10.1681/ASN.2016030368Thu, 04 Aug 2016 05:44:09 GMT-07:00Value of Donor–Specific Anti–HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft LossThe diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor–specific anti–HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic monitoring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post–transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post–transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post-transplant screening identified 186 (21.9%) DSA-positive patients. Post–transplant DSA monitoring improved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statistic from 0.67; 95% confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77). Addition of DSA IgG3 positivity or C1q binding capacity increased discrimination performance of the traditional model at transplant and post-transplant. Compared with DSA mean fluorescence intensity, DSA IgG3 positivity and C1q binding capacity adequately reclassified patients at lower or higher risk for allograft loss at transplant (category–free net reclassification index, 1.30; 95% CI, 0.94 to 1.67; P<0.001 and 0.93; 95% CI, 0.49 to 1.36; P<0.001, respectively) and post-transplant (category–free net reclassification index, 1.33; 95% CI, 1.03 to 1.62; P<0.001 and 0.95; 95% CI, 0.62 to 1.28; P<0.001, respectively). Thus, pre– and post–transplant DSA monitoring and characterization may improve individual risk stratification for kidney allograft loss.Viglietti, DenisLoupy, AlexandreVernerey, DewiBentlejewski, CarolGosset, ClémentAubert, OlivierDuong van Huyen, Jean-PaulJouven, XavierLegendre, ChristopheGlotz, DenisZeevi, AdrianaLefaucheur, Carmen2016-08-04T05:44:09-07:00doi:10.1681/ASN.2016030368hwp:resource-id:jnephrol;28/2/702American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant outcomes, immunologyClinical ResearchClinical Researchresearch-article20172017-02-01February 201710.1681/ASN.20160303681046-66731533-34502016-08-04T05:44:09-07:002017-02Journal of the American Society of NephrologyClinical Research282702715
- Urinary Angiogenin Reflects the Magnitude of Kidney Injury at the Infrahistologic LevelThe ribonuclease angiogenin is a component of the mammalian stress response that is secreted by renal epithelial cells on activation of the inositol–requiring enzyme 1α (IRE1α)–active spliced X–box binding protein 1 (sXBP1) axis and instrumental to the adaptation to AKI associated with endoplasmic reticulum stress. To determine whether the amount of angiogenin in urine of individuals with a kidney injury reflects the magnitude of the lesions and provides information on the risk of organ failure, we examined individuals referred for a kidney injury and determined the biochemical characteristics of urinary angiogenin and its diagnostic and prognostic values. Urinary angiogenin did not correlate with the urinary concentrations of high molecular weight proteins and correlated only weakly with low molecular weight proteins, suggestive of tubular production. In a cohort of 242 kidney transplant recipients with acute allograft dysfunction, higher urinary angiogenin concentrations at the time of the biopsy associated with worse renal function and higher proteinuria but did not correlate with histologic lesions as defined in the Banff classification. Kidney transplant recipients with urinary angiogenin amounts in the highest 50% had a risk of graft failure 3.59 times as high (95% confidence interval, 1.12 to 15.94) as that of patients with amounts in the lowest 50%. Finally, the amount of urinary angiogenin reflected the activity of the IRE1α-XBP1 axis in allografts. Our approach identified urinary angiogenin as a noninvasive indicator of the extent of tissue damage, independent of the histologic lesions, and a risk predictor of kidney allograft failure.10.1681/ASN.2016020218Tue, 19 Jul 2016 08:11:47 GMT-07:00Urinary Angiogenin Reflects the Magnitude of Kidney Injury at the Infrahistologic LevelThe ribonuclease angiogenin is a component of the mammalian stress response that is secreted by renal epithelial cells on activation of the inositol–requiring enzyme 1α (IRE1α)–active spliced X–box binding protein 1 (sXBP1) axis and instrumental to the adaptation to AKI associated with endoplasmic reticulum stress. To determine whether the amount of angiogenin in urine of individuals with a kidney injury reflects the magnitude of the lesions and provides information on the risk of organ failure, we examined individuals referred for a kidney injury and determined the biochemical characteristics of urinary angiogenin and its diagnostic and prognostic values. Urinary angiogenin did not correlate with the urinary concentrations of high molecular weight proteins and correlated only weakly with low molecular weight proteins, suggestive of tubular production. In a cohort of 242 kidney transplant recipients with acute allograft dysfunction, higher urinary angiogenin concentrations at the time of the biopsy associated with worse renal function and higher proteinuria but did not correlate with histologic lesions as defined in the Banff classification. Kidney transplant recipients with urinary angiogenin amounts in the highest 50% had a risk of graft failure 3.59 times as high (95% confidence interval, 1.12 to 15.94) as that of patients with amounts in the lowest 50%. Finally, the amount of urinary angiogenin reflected the activity of the IRE1α-XBP1 axis in allografts. Our approach identified urinary angiogenin as a noninvasive indicator of the extent of tissue damage, independent of the histologic lesions, and a risk predictor of kidney allograft failure.Tavernier, QuentinMami, IadhRabant, MarionKarras, AlexandreLaurent-Puig, PierreChevet, EricThervet, EricAnglicheau, DanyPallet, Nicolas2016-07-19T08:11:47-07:00doi:10.1681/ASN.2016020218hwp:resource-id:jnephrol;28/2/678American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyCell Signaling, chronic allograft failure, epithelial, kidney biopsy, kidney transplantation, proteinuriaClinical ResearchClinical Researchresearch-article20172017-02-01February 201710.1681/ASN.20160202181046-66731533-34502016-07-19T08:11:47-07:002017-02Journal of the American Society of NephrologyClinical Research282678690
- Estimating the Risk of Radiocontrast-Associated NephropathyEstimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.10.1681/ASN.2016010021Thu, 29 Sep 2016 06:16:44 GMT-07:00Estimating the Risk of Radiocontrast-Associated NephropathyEstimates of the incidence of radiocontrast-associated nephropathy vary widely and suffer from misclassification of the cause of AKI and confounding. Using the Nationwide Inpatient Sample, we created multiple estimates of the risk of radiocontrast-associated nephropathy among adult patients hospitalized in the United States in 2009. First, we stratified patients according to the presence or absence of 12 relatively common diagnoses associated with AKI and evaluated the rate of AKI between strata. Next, we created a logistic regression model, controlling for comorbidity and acuity of illness, to estimate the risk of AKI associated with radiocontrast administration within each stratum. Finally, we performed an analysis stratified by the degree of preexisting comorbidity. In general, patients who received radiocontrast did not develop AKI at a clinically significant higher rate. Adjusted only for the complex survey design, patients to whom radiocontrast was and was not administered developed AKI at rates of 5.5% and 5.6%, respectively. After controlling for comorbidity and acuity of illness, radiocontrast administration associated with an odds ratio for AKI of 0.93 (95% confidence interval, 0.88 to 0.97). In conclusion, the risk of radiocontrast-associated nephropathy may be overstated in the literature and overestimated by clinicians. More accurate AKI risk estimates may improve clinical decision-making when attempting to balance the potential benefits of radiocontrast-enhanced imaging and the risk of AKI.Wilhelm-Leen, EmileeMontez-Rath, Maria E.Chertow, Glenn2016-09-29T06:16:44-07:00doi:10.1681/ASN.2016010021hwp:resource-id:jnephrol;28/2/653American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, outcomes, nephrotoxicityClinical EpidemiologyClinical Epidemiologyresearch-article20172017-02-01February 201710.1681/ASN.20160100211046-66731533-34502016-09-29T06:16:44-07:002017-02Journal of the American Society of NephrologyClinical Epidemiology2822653397659399
- A Multicenter Study of the Predictive Value of Crescents in IgA NephropathyThe Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7–2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in over one fourth of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.10.1681/ASN.2016040433Fri, 09 Sep 2016 09:59:10 GMT-07:00A Multicenter Study of the Predictive Value of Crescents in IgA NephropathyThe Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7–2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in over one fourth of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.Haas, MarkVerhave, Jacobien C.Liu, Zhi-HongAlpers, Charles E.Barratt, JonathanBecker, Jan U.Cattran, DanielCook, H. TerenceCoppo, RosannaFeehally, JohnPani, AntonelloPerkowska-Ptasinska, AgnieszkaRoberts, Ian S.D.Soares, Maria FernandaTrimarchi, HernanWang, SuxiaYuzawa, YukioZhang, HongTroyanov, StéphanKatafuchi, Ritsuko2016-09-09T09:59:10-07:00doi:10.1681/ASN.2016040433hwp:resource-id:jnephrol;28/2/691American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, glomerulonephritis, Renal pathology, Oxford classification, crescentsClinical ResearchClinical Researchresearch-article20172017-02-01February 201710.1681/ASN.20160404331046-66731533-34502016-09-09T09:59:10-07:002017-02Journal of the American Society of NephrologyClinical Research28282569116657011665
- Fully Automated Evaluation of Total Glomerular Number and Capillary Tuft Size in Nephritic Kidneys Using Lightsheet MicroscopyThe total number of glomeruli is a fundamental parameter of kidney function but very difficult to determine using standard methodology. Here, we counted all individual glomeruli in murine kidneys and sized the capillary tufts by combining in vivo fluorescence labeling of endothelial cells, a novel tissue–clearing technique, lightsheet microscopy, and automated registration by image analysis. Total hands–on time per organ was <1 hour, and automated counting/sizing was finished in <3 hours. We also investigated the novel use of ethyl-3-phenylprop-2-enoate (ethyl cinnamate) as a nontoxic solvent–based clearing reagent that can be handled without specific safety measures. Ethyl cinnamate rapidly cleared all tested organs, including calcified bone, but the fluorescence of proteins and immunohistochemical labels was maintained over weeks. Using ethyl cinnamate–cleared kidneys, we also quantified the average creatinine clearance rate per glomerulus. This parameter decreased in the first week of experimental nephrotoxic nephritis, whereas reduction in glomerular numbers occurred much later. Our approach delivers fundamental parameters of renal function, and because of its ease of use and speed, it is suitable for high-throughput analysis and could greatly facilitate studies of the effect of kidney diseases on whole-organ physiology.10.1681/ASN.2016020232Wed, 03 Aug 2016 05:46:49 GMT-07:00Fully Automated Evaluation of Total Glomerular Number and Capillary Tuft Size in Nephritic Kidneys Using Lightsheet MicroscopyThe total number of glomeruli is a fundamental parameter of kidney function but very difficult to determine using standard methodology. Here, we counted all individual glomeruli in murine kidneys and sized the capillary tufts by combining in vivo fluorescence labeling of endothelial cells, a novel tissue–clearing technique, lightsheet microscopy, and automated registration by image analysis. Total hands–on time per organ was <1 hour, and automated counting/sizing was finished in <3 hours. We also investigated the novel use of ethyl-3-phenylprop-2-enoate (ethyl cinnamate) as a nontoxic solvent–based clearing reagent that can be handled without specific safety measures. Ethyl cinnamate rapidly cleared all tested organs, including calcified bone, but the fluorescence of proteins and immunohistochemical labels was maintained over weeks. Using ethyl cinnamate–cleared kidneys, we also quantified the average creatinine clearance rate per glomerulus. This parameter decreased in the first week of experimental nephrotoxic nephritis, whereas reduction in glomerular numbers occurred much later. Our approach delivers fundamental parameters of renal function, and because of its ease of use and speed, it is suitable for high-throughput analysis and could greatly facilitate studies of the effect of kidney diseases on whole-organ physiology.Klingberg, AnikaHasenberg, AnjaLudwig-Portugall, IsisMedyukhina, AnnaMänn, LindaBrenzel, AlexandraEngel, Daniel R.Figge, Marc ThiloKurts, ChristianGunzer, Matthias2016-08-03T05:46:49-07:00doi:10.1681/ASN.2016020232hwp:resource-id:jnephrol;28/2/452American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular endothelial cells, glomerular filtration rate, glomerulonephritis, immune complexes, Immunology and pathology, kidney anatomyBrief CommunicationsBrief Communicationsbrief-report20172017-02-01February 201710.1681/ASN.20160202321046-66731533-34502016-08-03T05:46:49-07:002017-02Journal of the American Society of NephrologyBrief Communications282452459
- An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain–Containing 7A–Specific Antibodies in Membranous NephropathyThrombospondin type 1 domain–containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A2 receptor 1 (PLA2R1). The prevalence of THSD7A-Ab–positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLA2R1-Ab or THSD7A-Ab. We screened serum samples of 1276 patients with MN from three different cohorts for the presence of THSD7A-Ab by Western blot analysis and a newly developed indirect immunofluorescence test (IFT). Compared with Western blot analysis, the IFT had a 92% sensitivity and a 100% specificity. The prevalence of THSD7A-associated MN in a prospective cohort of 345 patients with MN was 2.6%, and most were women. In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA2R1-associated MN and malignant disease. In all cohorts, we identified 40 patients with THSD7A-associated MN, eight of whom developed a malignancy within a median time of 3 months from diagnosis of MN. In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis–infiltrated lymph node. We conclude that the IFT allows sensitive and specific measurement of circulating THSD7A-Ab in patients with MN. Patients with THSD7A-associated MN differ in their clinical characteristics from patients with PLA2R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN.10.1681/ASN.2016010050Tue, 19 Jul 2016 08:11:48 GMT-07:00An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain–Containing 7A–Specific Antibodies in Membranous NephropathyThrombospondin type 1 domain–containing 7A (THSD7A) is a target antigen identified in adult membranous nephropathy (MN) along with the major antigen phospholipase A2 receptor 1 (PLA2R1). The prevalence of THSD7A-Ab–positive patients is unknown, and it is unclear whether the clinical presentation differs between patients positive for PLA2R1-Ab or THSD7A-Ab. We screened serum samples of 1276 patients with MN from three different cohorts for the presence of THSD7A-Ab by Western blot analysis and a newly developed indirect immunofluorescence test (IFT). Compared with Western blot analysis, the IFT had a 92% sensitivity and a 100% specificity. The prevalence of THSD7A-associated MN in a prospective cohort of 345 patients with MN was 2.6%, and most were women. In this cohort, the percentage of patients with THSD7A-associated MN and malignant disease significantly exceeded that of patients with PLA2R1-associated MN and malignant disease. In all cohorts, we identified 40 patients with THSD7A-associated MN, eight of whom developed a malignancy within a median time of 3 months from diagnosis of MN. In one patient with THSD7A-associated MN and metastases of an endometrial carcinoma, immunohistochemistry showed THSD7A expression on the metastatic cells and within follicular dendritic cells of the metastasis–infiltrated lymph node. We conclude that the IFT allows sensitive and specific measurement of circulating THSD7A-Ab in patients with MN. Patients with THSD7A-associated MN differ in their clinical characteristics from patients with PLA2R1-associated MN, and more intensive screening for the presence of malignancies may be warranted in those with THSD7A-associated MN.Hoxha, ElionBeck, Laurence H.Wiech, ThorstenTomas, Nicola M.Probst, ChristianMindorf, SwantjeMeyer-Schwesinger, CatherineZahner, GuntherStahl, Phillip R.Schöpper, RuthPanzer, UlfHarendza, SigridHelmchen, UdoSalant, David J.Stahl, Rolf A.K.2016-07-19T08:11:48-07:00doi:10.1681/ASN.2016010050hwp:resource-id:jnephrol;28/2/520American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, THSD7A Antibodies, nephrotic syndromeBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160100501046-66731533-34502016-07-19T08:11:48-07:002017-02Journal of the American Society of NephrologyBasic Research282520531
- Inhibition of Bromodomain and Extraterminal Domain Family Proteins Ameliorates Experimental Renal DamageRenal inflammation has a key role in the onset and progression of immune– and nonimmune–mediated renal diseases. Therefore, the search for novel anti–inflammatory pharmacologic targets is of great interest in renal pathology. JQ1, a small molecule inhibitor of bromodomain and extraterminal (BET) proteins, was previously found to preserve renal function in experimental polycystic kidney disease. We report here that JQ1–induced BET inhibition modulated the in vitro expression of genes involved in several biologic processes, including inflammation and immune responses. Gene silencing of BRD4, an important BET protein, and chromatin immunoprecipitation assays showed that JQ1 alters the direct association of BRD4 with acetylated histone–packaged promoters and reduces the transcription of proinflammatory genes (IL-6, CCL-2, and CCL-5). In vivo, JQ1 abrogated experimental renal inflammation in murine models of unilateral ureteral obstruction, antimembrane basal GN, and infusion of Angiotensin II. Notably, JQ1 downregulated the expression of several genes controlled by the NF-κB pathway, a key inflammatory signaling pathway. The RelA NF-κB subunit is activated by acetylation of lysine 310. In damaged kidneys and cytokine–stimulated renal cells, JQ1 reduced the nuclear levels of RelA NF-κB. Additionally, JQ1 dampened the activation of the Th17 immune response in experimental renal damage. Our results show that inhibition of BET proteins reduces renal inflammation by several mechanisms: chromatin remodeling in promoter regions of specific genes, blockade of NF-κB pathway activation, and modulation of the Th17 immune response. These results suggest that inhibitors of BET proteins could have important therapeutic applications in inflammatory renal diseases.10.1681/ASN.2015080910Tue, 19 Jul 2016 08:11:46 GMT-07:00Inhibition of Bromodomain and Extraterminal Domain Family Proteins Ameliorates Experimental Renal DamageRenal inflammation has a key role in the onset and progression of immune– and nonimmune–mediated renal diseases. Therefore, the search for novel anti–inflammatory pharmacologic targets is of great interest in renal pathology. JQ1, a small molecule inhibitor of bromodomain and extraterminal (BET) proteins, was previously found to preserve renal function in experimental polycystic kidney disease. We report here that JQ1–induced BET inhibition modulated the in vitro expression of genes involved in several biologic processes, including inflammation and immune responses. Gene silencing of BRD4, an important BET protein, and chromatin immunoprecipitation assays showed that JQ1 alters the direct association of BRD4 with acetylated histone–packaged promoters and reduces the transcription of proinflammatory genes (IL-6, CCL-2, and CCL-5). In vivo, JQ1 abrogated experimental renal inflammation in murine models of unilateral ureteral obstruction, antimembrane basal GN, and infusion of Angiotensin II. Notably, JQ1 downregulated the expression of several genes controlled by the NF-κB pathway, a key inflammatory signaling pathway. The RelA NF-κB subunit is activated by acetylation of lysine 310. In damaged kidneys and cytokine–stimulated renal cells, JQ1 reduced the nuclear levels of RelA NF-κB. Additionally, JQ1 dampened the activation of the Th17 immune response in experimental renal damage. Our results show that inhibition of BET proteins reduces renal inflammation by several mechanisms: chromatin remodeling in promoter regions of specific genes, blockade of NF-κB pathway activation, and modulation of the Th17 immune response. These results suggest that inhibitors of BET proteins could have important therapeutic applications in inflammatory renal diseases.Suarez-Alvarez, BeatrizMorgado-Pascual, José LuisRayego-Mateos, SandraRodriguez, Ramon M.Rodrigues-Diez, RaulCannata-Ortiz, PabloSanz, Ana B.Egido, JesusTharaux, Pierre-LouisOrtiz, AlbertoLopez-Larrea, CarlosRuiz-Ortega, Marta2016-07-19T08:11:46-07:00doi:10.1681/ASN.2015080910hwp:resource-id:jnephrol;28/2/504American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologytranscription factors, Cell Signaling, chemokineBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20150809101046-66731533-34502016-07-19T08:11:46-07:002017-02Journal of the American Society of NephrologyBasic Research282504519
- Changing Paradigms in Contrast Nephropathy10.1681/ASN.2016121369Thu, 19 Jan 2017 06:14:46 GMT-08:00Changing Paradigms in Contrast NephropathyLopez-Ruiz, ArnaldoChandrashekar, KiranJuncos, Luis A.2017-01-19T06:14:46-08:00doi:10.1681/ASN.2016121369hwp:resource-id:jnephrol;28/2/397American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, contrast nephropathy, CKDUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-02-01February 201710.1681/ASN.20161213691046-66731533-34502017-01-19T06:14:46-08:002017-02Journal of the American Society of NephrologyUp Front Matters2822397653399659
- Transcription Factor Trps1 Promotes Tubular Cell Proliferation after Ischemia-Reperfusion Injury through cAMP–Specific 3′,5′-Cyclic Phosphodiesterase 4D and AKTTrichorhinophalangeal 1 (Trps1) is a transcription factor essential for epithelial cell morphogenesis during kidney development, but the role of Trps1 in AKI induced by ischemia-reperfusion (I/R) remains unclear. Our study investigated Trps1 expression during kidney repair after acute I/R in rats and explored the molecular mechanisms by which Trps1 promotes renal tubular epithelial cell proliferation. Trps1 expression positively associated with the extent of renal repair after I/R injury. Compared with wild-type rats, rats with knockdown of Trps1 exhibited significantly delayed renal repair in the moderate I/R model, with lower GFR levels and more severe morphologic injury, whereas rats overexpressing Trps1 exhibited significantly accelerated renal repair after severe I/R injury. Additionally, knockdown of Trps1 inhibited and overexpression of Trps1 enhanced the proliferation of renal tubular epithelial cells in rats. Chromatin immunoprecipitation sequencing assays and RT-PCR revealed that Trps1 regulated cAMP–specific 3′,5′-cyclic phosphodiesterase 4D (Pde4d) expression. Knockdown of Trps1 decreased the renal protein expression of Pde4d and phosphorylated Akt in rats, and dual luciferase analysis showed that Trps1 directly activated Pde4d transcription. Furthermore, knockdown of Pde4d or treatment with the phosphatidylinositol 3 kinase inhibitor wortmannin significantly inhibited Trps1–induced tubular cell proliferation in vitro. Trps1 may promote tubular cell proliferation through the Pde4d/phosphatidylinositol 3 kinase/AKT signaling pathway, suggesting Trps1 as a potential therapeutic target for kidney repair after I/R injury.10.1681/ASN.2016010009Wed, 27 Jul 2016 06:25:18 GMT-07:00Transcription Factor Trps1 Promotes Tubular Cell Proliferation after Ischemia-Reperfusion Injury through cAMP–Specific 3′,5′-Cyclic Phosphodiesterase 4D and AKTTrichorhinophalangeal 1 (Trps1) is a transcription factor essential for epithelial cell morphogenesis during kidney development, but the role of Trps1 in AKI induced by ischemia-reperfusion (I/R) remains unclear. Our study investigated Trps1 expression during kidney repair after acute I/R in rats and explored the molecular mechanisms by which Trps1 promotes renal tubular epithelial cell proliferation. Trps1 expression positively associated with the extent of renal repair after I/R injury. Compared with wild-type rats, rats with knockdown of Trps1 exhibited significantly delayed renal repair in the moderate I/R model, with lower GFR levels and more severe morphologic injury, whereas rats overexpressing Trps1 exhibited significantly accelerated renal repair after severe I/R injury. Additionally, knockdown of Trps1 inhibited and overexpression of Trps1 enhanced the proliferation of renal tubular epithelial cells in rats. Chromatin immunoprecipitation sequencing assays and RT-PCR revealed that Trps1 regulated cAMP–specific 3′,5′-cyclic phosphodiesterase 4D (Pde4d) expression. Knockdown of Trps1 decreased the renal protein expression of Pde4d and phosphorylated Akt in rats, and dual luciferase analysis showed that Trps1 directly activated Pde4d transcription. Furthermore, knockdown of Pde4d or treatment with the phosphatidylinositol 3 kinase inhibitor wortmannin significantly inhibited Trps1–induced tubular cell proliferation in vitro. Trps1 may promote tubular cell proliferation through the Pde4d/phosphatidylinositol 3 kinase/AKT signaling pathway, suggesting Trps1 as a potential therapeutic target for kidney repair after I/R injury.Ju-Rong, YangKe-Hong, ChenKun, HuangBi-Qiong, FuLi-Rong, LinJian-Guo, ZhangKai-Long, LiYa-Ni, He2016-07-27T06:25:18-07:00doi:10.1681/ASN.2016010009hwp:resource-id:jnephrol;28/2/532American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of NephrologyTrps1, Pde4d, proliferation, renal tubule epithelial cell, ischemia-reperfusion, injuryBasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160100091046-66731533-34502016-07-27T06:25:18-07:002017-02Journal of the American Society of NephrologyBasic Research282532544
- MicroRNA-146a in Human and Experimental Ischemic AKI: CXCL8-Dependent Mechanism of ActionAKI leads to tubular injury and interstitial inflammation that must be controlled to avoid the development of fibrosis. We hypothesized that microRNAs are involved in the regulation of the balance between lesion formation and adaptive repair. We found that, under proinflammatory conditions, microRNA-146a (miR-146a) is transcriptionally upregulated by ligands of IL-1 receptor/Toll–like receptor family members via the activation of NF-κB in cultured renal proximal tubular cells. In vivo, more severe renal ischemia-reperfusion injury (IRI) associated with increased expression of miR-146a in both allografts and urine of human kidney transplant recipients, and unilateral IRI in mice induced miR-146a expression in injured kidneys. After unilateral IRI, miR-146a−/− mice exhibited more extensive tubular injury, inflammatory infiltrates, and fibrosis than wild-type mice. In vitro, overexpression or downregulation of miR-146a diminished or enhanced, respectively, IL-1 receptor–associated kinase 1 expression and induced similar effects on C-X-C motif ligand 8 (CXCL8)/CXCL1 expression by injured tubular cells. Moreover, inhibition of CXCL8/CXCL1 signaling prevented the development of inflammation and fibrosis after IRI in miR-146a−/− mice. In conclusion, these results indicate that miR-146a is a key mediator of the renal tubular response to IRI that limits the consequences of inflammation, a key process in the development of AKI and CKD.10.1681/ASN.2016010045Thu, 21 Jul 2016 06:40:51 GMT-07:00MicroRNA-146a in Human and Experimental Ischemic AKI: CXCL8-Dependent Mechanism of ActionAKI leads to tubular injury and interstitial inflammation that must be controlled to avoid the development of fibrosis. We hypothesized that microRNAs are involved in the regulation of the balance between lesion formation and adaptive repair. We found that, under proinflammatory conditions, microRNA-146a (miR-146a) is transcriptionally upregulated by ligands of IL-1 receptor/Toll–like receptor family members via the activation of NF-κB in cultured renal proximal tubular cells. In vivo, more severe renal ischemia-reperfusion injury (IRI) associated with increased expression of miR-146a in both allografts and urine of human kidney transplant recipients, and unilateral IRI in mice induced miR-146a expression in injured kidneys. After unilateral IRI, miR-146a−/− mice exhibited more extensive tubular injury, inflammatory infiltrates, and fibrosis than wild-type mice. In vitro, overexpression or downregulation of miR-146a diminished or enhanced, respectively, IL-1 receptor–associated kinase 1 expression and induced similar effects on C-X-C motif ligand 8 (CXCL8)/CXCL1 expression by injured tubular cells. Moreover, inhibition of CXCL8/CXCL1 signaling prevented the development of inflammation and fibrosis after IRI in miR-146a−/− mice. In conclusion, these results indicate that miR-146a is a key mediator of the renal tubular response to IRI that limits the consequences of inflammation, a key process in the development of AKI and CKD.Amrouche, LucileDesbuissons, GeoffroyRabant, MarionSauvaget, VirginiaNguyen, ClémentBenon, AurélienBarre, PaulineRabaté, ClémentineLebreton, XavierGallazzini, MorganLegendre, ChristopheTerzi, FabiolaAnglicheau, Dany2016-07-21T06:40:51-07:00doi:10.1681/ASN.2016010045hwp:resource-id:jnephrol;28/2/479American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, Cell Signaling, delayed graft function, fibrosis, renal epithelial cell, mRNABasic ResearchBasic Researchresearch-article20172017-02-01February 201710.1681/ASN.20160100451046-66731533-34502016-07-21T06:40:51-07:002017-02Journal of the American Society of NephrologyBasic Research282479493
- Hereditary Lysozyme Amyloidosis Variant p.Leu102Ser Associates with Unique PhenotypeLysozyme amyloidosis (ALys) is a rare form of hereditary amyloidosis that typically manifests with renal impairment, gastrointestinal (GI) symptoms, and sicca syndrome, whereas cardiac involvement is exceedingly rare and neuropathy has not been reported. Here, we describe a 40-year-old man with renal impairment, cardiac and GI symptoms, and peripheral neuropathy. Renal biopsy specimen analysis revealed amyloidosis with extensive involvement of glomeruli, vessels, and medulla. Amyloid was also detected in the GI tract. Echocardiographic and electrocardiographic findings were consistent with cardiac involvement. Proteomic analysis of Congo red–positive renal and GI amyloid deposits detected abundant lysozyme C protein. DNA sequencing of the lysozyme gene in the patient and his mother detected a heterozygous c.305T>C alteration in exon 3, which causes a leucine to serine substitution at codon 102 (Human Genome Variation Society nomenclature: p.Leu102Ser; legacy designation: L84S). We also detected the mutant peptide in the proband’s renal and GI amyloid deposits. PolyPhen analysis predicted that the mutation damages the encoded protein. Molecular dynamics simulations suggested that the pathogenesis of ALys p.Leu102Ser is mediated by shifting the position of the central β-hairpin coordinated with an antiparallel motion of the C-terminal helix, which may alter the native-state structural ensemble of the molecule, leading to aggregation-prone intermediates.10.1681/ASN.2016090951Tue, 03 Jan 2017 06:06:01 GMT-08:00Hereditary Lysozyme Amyloidosis Variant p.Leu102Ser Associates with Unique PhenotypeLysozyme amyloidosis (ALys) is a rare form of hereditary amyloidosis that typically manifests with renal impairment, gastrointestinal (GI) symptoms, and sicca syndrome, whereas cardiac involvement is exceedingly rare and neuropathy has not been reported. Here, we describe a 40-year-old man with renal impairment, cardiac and GI symptoms, and peripheral neuropathy. Renal biopsy specimen analysis revealed amyloidosis with extensive involvement of glomeruli, vessels, and medulla. Amyloid was also detected in the GI tract. Echocardiographic and electrocardiographic findings were consistent with cardiac involvement. Proteomic analysis of Congo red–positive renal and GI amyloid deposits detected abundant lysozyme C protein. DNA sequencing of the lysozyme gene in the patient and his mother detected a heterozygous c.305T>C alteration in exon 3, which causes a leucine to serine substitution at codon 102 (Human Genome Variation Society nomenclature: p.Leu102Ser; legacy designation: L84S). We also detected the mutant peptide in the proband’s renal and GI amyloid deposits. PolyPhen analysis predicted that the mutation damages the encoded protein. Molecular dynamics simulations suggested that the pathogenesis of ALys p.Leu102Ser is mediated by shifting the position of the central β-hairpin coordinated with an antiparallel motion of the C-terminal helix, which may alter the native-state structural ensemble of the molecule, leading to aggregation-prone intermediates.Nasr, Samih H.Dasari, SurendraMills, John R.Theis, Jason D.Zimmermann, Michael T.Fonseca, RafaelVrana, Julie A.Lester, Steven J.McLaughlin, Brooke M.Gillespie, RobertHighsmith, W. EdwardLee, John J.Dispenzieri, AngelaKurtin, Paul J.2017-01-03T06:06:01-08:00doi:10.1681/ASN.2016090951hwp:resource-id:jnephrol;28/2/431American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyamyloidosis, lysozyme, hereditary amyloid, malfolding proteinsUp Front MattersRenal Biopsy with New InsightsUp Front MattersRenal Biopsy with New Insightsresearch-article20172017-02-01February 201710.1681/ASN.20160909511046-66731533-34502017-01-03T06:06:01-08:002017-02Journal of the American Society of NephrologyUp Front Matters282431438
- Vascular Access for Hemodialysis and Value-Based Purchasing for ESRD10.1681/ASN.2016070769Thu, 06 Oct 2016 07:08:12 GMT-07:00Vascular Access for Hemodialysis and Value-Based Purchasing for ESRDMehrotra, RajnishCheung, Alfred K.Meyer, TimothyNath, Karl A.2016-10-06T07:08:12-07:00doi:10.1681/ASN.2016070769hwp:resource-id:jnephrol;28/2/395American Society of NephrologyCopyright © 2017 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, arteriovenous graft, vascular access, mortality risk, hemodialysisUp Front MattersEditorialsUp Front MattersEditorialseditorial20172017-02-01February 201710.1681/ASN.20160707691046-66731533-34502016-10-06T07:08:12-07:002017-02Journal of the American Society of NephrologyUp Front Matters28222395613645397620652
- Early Steroid Withdrawal in Black Transplant Patients: A Selective Process10.2215/CJN.11731116Thu, 15 Dec 2016 06:35:30 GMT-08:00Early Steroid Withdrawal in Black Transplant Patients: A Selective ProcessAugustine, Joshua J.2016-12-15T06:35:30-08:00doi:10.2215/CJN.11731116hwp:resource-id:clinjasn;12/1/7American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAfrican-American, Transplant, Early Steroid Withdrawal, kidney transplantationEditorialsEditorialseditorial20162017-01-06January 06, 201710.2215/CJN.117311161555-90411555-905X2016-12-15T06:35:30-08:002017-01-06Clinical Journal of the American Society of NephrologyEditorials121171319139
- Dialysis Vintage and Outcomes after Kidney Transplantation: A Retrospective Cohort Study10.2215/CJN.04120416Mon, 28 Nov 2016 07:51:29 GMT-08:00Dialysis Vintage and Outcomes after Kidney Transplantation: A Retrospective Cohort StudyHaller, Maria C.Kainz, AlexanderBaer, HeatherOberbauer, Rainer2016-11-28T07:51:29-08:00doi:10.2215/CJN.04120416hwp:resource-id:clinjasn;12/1/122American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, transplantation, outcomes, allografts, cohort studies, death, follow-up studies, graft survival, humans, kidney transplantation, liver transplantation, registries, renal dialysis, renal replacement therapy, retrospective studies, tissue donorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162017-01-06January 06, 201710.2215/CJN.041204161555-90411555-905X2016-11-28T07:51:29-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles121122130
- A Comparative Effectiveness Analysis of Early Steroid Withdrawal in Black Kidney Transplant Recipients10.2215/CJN.04880516Thu, 15 Dec 2016 06:35:31 GMT-08:00A Comparative Effectiveness Analysis of Early Steroid Withdrawal in Black Kidney Transplant RecipientsTaber, David J.Hunt, Kelly J.Gebregziabher, MulugetaSrinivas, TitteChavin, Kenneth D.Baliga, Prabhakar K.Egede, Leonard E.2016-12-15T06:35:31-08:00doi:10.2215/CJN.04880516hwp:resource-id:clinjasn;12/1/131American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, acute allograft rejection, transplant outcomes, chronic allograft failure, adult, Blacks, Cohort Studies, delayed graft function, goals, humans, Immunosuppressive Agents, kidney, kidney transplantation, Propensity Score, tacrolimus, Transplant Recipients, United StatesOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162017-01-06January 06, 201710.2215/CJN.048805161555-90411555-905X2016-12-15T06:35:31-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles121113171399
- Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort10.2215/CJN.02700316Thu, 10 Nov 2016 08:52:33 GMT-08:00Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency CohortDubin, Ruth F.Deo, RajatBansal, NishaAnderson, Amanda H.Yang, PeterGo, Alan S.Keane, MartinTownsend, RayPorter, AnnaBudoff, MatthewMalik, ShaistaHe, JiangRahman, MahboobWright, JacksonCappola, ThomasKallem, RadhakrishnaRoy, JasonSha, DaohangShlipak, Michael G.,2016-11-10T08:52:33-08:00doi:10.2215/CJN.02700316hwp:resource-id:clinjasn;12/1/60American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, renal insufficiency, chronic, epidemiology, Biomarkers, Cardiovascular Diseases, echocardiography, Female, Follow-Up Studies, heart failure, Humans, Hypertrophy, Left Ventricular, Incidence, Male, Minerals, Renal Insufficiency, Chronic, risk factors, Troponin TOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162017-01-06January 06, 201710.2215/CJN.027003161555-90411555-905X2016-11-10T08:52:33-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1216068
- Filtration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-Analysis10.2215/CJN.03660316Thu, 10 Nov 2016 08:52:35 GMT-08:00Filtration Markers as Predictors of ESRD and Mortality: Individual Participant Data Meta-AnalysisInker, Lesley A.Coresh, JosefSang, YingyingHsu, Chi-yuanFoster, Meredith C.Eckfeldt, John H.Karger, Amy B.Nelson, Robert G.Liu, XunSarnak, MarkAppel, Lawrence J.Grams, MorganXie, DaweiKimmel, Paul L.Feldman, HaroldRamachandran, VasanLevey, Andrew S.,2016-11-10T08:52:35-08:00doi:10.2215/CJN.03660316hwp:resource-id:clinjasn;12/1/69American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, albuminuria, glomerular filtration rate, follow-up studies, humans, prostaglandin R2 D-isomerase, intramolecular oxidoreductases, kidney failure, chronic, lipocalins, renal insufficiency, chronic, risk factors, beta 2-microglobulinOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162017-01-06January 06, 201710.2215/CJN.036603161555-90411555-905X2016-11-10T08:52:35-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1216978
- Diet Soda Consumption and Risk of Incident End Stage Renal Disease10.2215/CJN.03390316Wed, 26 Oct 2016 05:29:36 GMT-07:00Diet Soda Consumption and Risk of Incident End Stage Renal DiseaseRebholz, Casey M.Grams, Morgan E.Steffen, Lyn M.Crews, Deidra C.Anderson, Cheryl A. M.Bazzano, Lydia A.Coresh, JosefAppel, Lawrence J.2016-10-26T05:29:36-07:00doi:10.2215/CJN.03390316hwp:resource-id:clinjasn;12/1/79American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyatherosclerosis, beverages, blood pressure, body mass index, diabetes, mellitus, diet, energy intake, female, follow-up studies, fructose, glomerular filtration rate, glucose, kidney failure, chronic, metabolic syndrome X, motor activity, obesity, overweight, phosphorus, dietary, smoking, sodium, dietary, surveys and questionnaires, sweetening agents, United States, uric acidOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162017-01-06January 06, 201710.2215/CJN.033903161555-90411555-905X2016-10-26T05:29:36-07:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1217986
- Patterns and Predictors of Screening for Breast and Cervical Cancer in Women with CKD10.2215/CJN.05990616Thu, 29 Dec 2016 04:46:06 GMT-08:00Patterns and Predictors of Screening for Breast and Cervical Cancer in Women with CKDWong, GermaineHayward, Jade S.McArthur, EricCraig, Jonathan C.Nash, Danielle M.Dixon, Stephanie N.Zimmerman, DeborahKitchlu, AbhijatGarg, Amit X.2016-12-29T04:46:06-08:00doi:10.2215/CJN.05990616hwp:resource-id:clinjasn;12/1/95American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, chronic kidney disease, dialysis, screening, chronic kidney failure, breast, Canada, Cohort Studies, Comorbidity, Early Detection of Cancer, Female, humans, incidence, Ontario, poverty, Prevalence, renal dialysis, renal insufficiency, chronic, uterine cervical neoplasmsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162017-01-06January 06, 201710.2215/CJN.059906161555-90411555-905X2016-12-29T04:46:06-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles12119551046
- Patient-Reported Outcomes in Glomerular DiseaseIncorporation of the patient perspective into research and clinical practice will enrich our understanding of the status and management of patients with glomerular disease and may result in therapies that better address patient needs. In recent years, the importance of the patient experience of glomerular disease has become clear, and significant efforts have been undertaken to systematically capture and describe the patient’s disease experience. Patient–reported outcome instruments provide a means to assess the patient’s experience in a quantitative manner, thus enabling for comparisons within and between patients. Patient–reported outcome assessments are solely on the basis of a patient report about the status of their health without amendment or interpretation by a clinician or others. Patient–reported outcome assessments provide an opportunity to incorporate the patient perspective into clinical care, research, and clinical trials. Our paper provides an overview of terminology and development methods for patient-reported outcomes and reviews (1) currently available patient–reported outcome instruments appropriate for use in glomerular disease, (2) existing patient–reported outcome data in glomerular disease, and (3) opportunities for incorporating patient–reported outcome instruments into clinical care and research.10.2215/CJN.13231215Fri, 03 Jun 2016 06:34:44 GMT-07:00Patient-Reported Outcomes in Glomerular DiseaseIncorporation of the patient perspective into research and clinical practice will enrich our understanding of the status and management of patients with glomerular disease and may result in therapies that better address patient needs. In recent years, the importance of the patient experience of glomerular disease has become clear, and significant efforts have been undertaken to systematically capture and describe the patient’s disease experience. Patient–reported outcome instruments provide a means to assess the patient’s experience in a quantitative manner, thus enabling for comparisons within and between patients. Patient–reported outcome assessments are solely on the basis of a patient report about the status of their health without amendment or interpretation by a clinician or others. Patient–reported outcome assessments provide an opportunity to incorporate the patient perspective into clinical care, research, and clinical trials. Our paper provides an overview of terminology and development methods for patient-reported outcomes and reviews (1) currently available patient–reported outcome instruments appropriate for use in glomerular disease, (2) existing patient–reported outcome data in glomerular disease, and (3) opportunities for incorporating patient–reported outcome instruments into clinical care and research.Selewski, David T.Thompson, AlizaKovacs, SarritPapadopoulos, Elektra J.Carlozzi, Noelle E.Trachtman, HowardTroost, Jonathan P.Merkel, Peter A.Gipson, Debbie S.2016-06-03T06:34:44-07:00doi:10.2215/CJN.13231215hwp:resource-id:clinjasn;12/1/140American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyquality of life, kidney disease, glomerulopathy, patient-centered outcomes, Disease Management, Humans, Patient Outcome Assessment, glomerulonephritisGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianreview-article20162017-01-06January 06, 201710.2215/CJN.132312151555-90411555-905X2016-06-03T06:34:44-07:002017-01-06Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician121140148
- ESRD Databases, Public Policy, and Quality of Care: Translational Medicine and NephrologyEfforts to improve care of patients with ESRD and the policies that guide those activities depend on evidence–based best practices derived from clinical trials and carefully conducted observational studies. Our review describes this process in the context of the translational research model (bench to bedside to populations), with a particular emphasis on bedside care. We illustrate some of its accomplishments and describe the limitations of the data and evidence supporting policy and practice.10.2215/CJN.02370316Wed, 16 Nov 2016 07:18:32 GMT-08:00ESRD Databases, Public Policy, and Quality of Care: Translational Medicine and NephrologyEfforts to improve care of patients with ESRD and the policies that guide those activities depend on evidence–based best practices derived from clinical trials and carefully conducted observational studies. Our review describes this process in the context of the translational research model (bench to bedside to populations), with a particular emphasis on bedside care. We illustrate some of its accomplishments and describe the limitations of the data and evidence supporting policy and practice.McClellan, William M.Plantinga, Laura C.Wilk, Adam S.Patzer, Rachel E.2016-11-16T07:18:32-08:00doi:10.2215/CJN.02370316hwp:resource-id:clinjasn;12/1/210American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyQuality improvement, Epidemiology and outcomes, surveillance, policy, guidelines, Translational epidemiology, Humans, Kidney Failure, Chronic, nephrology, Public Policy, Renal Insufficiency, Chronic, Translational, Medical ResearchPublic Policy SeriesPublic Policy Seriesresearch-article20162017-01-06January 06, 201710.2215/CJN.023703161555-90411555-905X2016-11-16T07:18:32-08:002017-01-06Clinical Journal of the American Society of NephrologyPublic Policy Series121210216
- Staphylococcus Infection–Associated GN – Spectrum of IgA Staining and Prevalence of ANCA in a Single-Center Cohort10.2215/CJN.05070516Mon, 07 Nov 2016 05:47:25 GMT-08:00Staphylococcus Infection–Associated GN – Spectrum of IgA Staining and Prevalence of ANCA in a Single-Center CohortSatoskar, Anjali A.Suleiman, SarahAyoub, IsabelleHemminger, JessicaParikh, SamirBrodsky, Sergey V.Bott, CherriCalomeni, EdwardNadasdy, Gyongyi M.Rovin, BradHebert, LeeNadasdy, Tibor2016-11-07T05:47:25-08:00doi:10.2215/CJN.05070516hwp:resource-id:clinjasn;12/1/39American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyantibodies, antineutrophil cytoplasmic, biopsy, electrons, endocarditis, fluorescent antibody technique, glomerulonephritis, glomerulonephritis, IGA, humans, immunoglobulin A, immunoglobulin G, kidney glomerulus, nephritis, prevalence, purpura, Schoenlein-Henoch, staining and labeling, StaphylococcusOriginal ArticlesClinical Immunology and PathologyOriginal ArticlesClinical Immunology and Pathologyresearch-article20162017-01-06January 06, 201710.2215/CJN.050705161555-90411555-905X2016-11-07T05:47:25-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1213949
- Predicting 5-Year Risk of RRT in Stage 3 or 4 CKD: Development and External Validation10.2215/CJN.01290216Tue, 27 Dec 2016 05:03:44 GMT-08:00Predicting 5-Year Risk of RRT in Stage 3 or 4 CKD: Development and External ValidationSchroeder, Emily B.Yang, XiuhaiThorp, Micah L.Arnold, Brent M.Tabano, David C.Petrik, Amanda F.Smith, David H.Platt, Robert W.Johnson, Eric S.2016-12-27T05:03:44-08:00doi:10.2215/CJN.01290216hwp:resource-id:clinjasn;12/1/87American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, renal failure, risk assessment, disease progression, prognosis, clinical prediction rule, albuminuria, Antihypertensive Agents, blood pressure, Calibration, Colorado, diabetes mellitus, Fistula, glomerular filtration rate, Hemoglobins, Humans, nephrology, Primary Health Care, proteinuria, Referral and Consultation, Renal Insufficiency, renal insufficiency, chronic, renal replacement therapy, retrospective studiesOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162017-01-06January 06, 201710.2215/CJN.012902161555-90411555-905X2016-12-27T05:03:44-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1211873944
- Association of Preoperative Urinary Uromodulin with AKI after Cardiac Surgery10.2215/CJN.02520316Wed, 26 Oct 2016 05:29:37 GMT-07:00Association of Preoperative Urinary Uromodulin with AKI after Cardiac SurgeryGarimella, Pranav S.Jaber, Bertrand L.Tighiouart, HocineLiangos, OrfeasBennett, Michael R.Devarajan, PrasadEl-Achkar, Tarek M.Sarnak, Mark J.2016-10-26T05:29:37-07:00doi:10.2215/CJN.02520316hwp:resource-id:clinjasn;12/1/10American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuromodulin, acute kidney injury, cardiac surgery, tubular function, adult, Animals, Cardiac Surgical Procedures, Cohort Studies, creatinine, Female, Humans, Kidney Function Tests, Models, Animal, Odds Ratio, Postoperative Period, Prospective Studies, Regression Analysis, renal dialysis, UromodulinOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162017-01-06January 06, 201710.2215/CJN.025203161555-90411555-905X2016-10-26T05:29:37-07:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1211018
- Biomarkers for the Early Detection and Prognosis of Acute Kidney InjuryAKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.10.2215/CJN.01300216Tue, 08 Nov 2016 11:03:47 GMT-08:00Biomarkers for the Early Detection and Prognosis of Acute Kidney InjuryAKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.Malhotra, RakeshSiew, Edward D.2016-11-08T11:03:47-08:00doi:10.2215/CJN.01300216hwp:resource-id:clinjasn;12/1/149American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, biomarkers, acute kidney injury, creatinine, Early Diagnosis, PrognosisEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20162017-01-06January 06, 201710.2215/CJN.013002161555-90411555-905X2016-11-08T11:03:47-08:002017-01-06Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology1211149174173175
- The Healthy People 2020 Objectives for Kidney Disease: How Far Have We Come, and Where Do We Need to Go?The Healthy People 2020 initiative established goals for patients with CKD and ESRD. We assessed United States progress toward some of these key goals. Using data from the Centers for Medicare and Medicaid Services ESRD database, we created yearly cohorts of patients on incident and prevalent dialysis from 2000 to 2013. Change in event rate or proportion change over the study years was modeled using Poisson regression with adjustment for age, race, sex, and primary cause of ESRD. For all-cause mortality in prevalent patients, Healthy People 2020 sought approximately 0.8% relative annual improvement; actual improvement was 2.7%. Improvement was greatest for patients ages 18–44 years old (3.8%; P<0.01 versus 2.8% for ages 65–74 years old) and 2.3% even for patients ages ≥75 years old. For mortality in incident patients, the relative annual decrease was 2.1% overall, a twofold improvement over the goal; mortality decreased nearly twice as much in black as in white patients (3.2% versus 1.8%; P<0.001). Geographic variation was substantial; the relative annual decrease was 0.6% in the Midwest and more than fourfold greater (2.7%) in the South. Cardiovascular mortality in prevalent patients decreased dramatically at 5.0% per year, far exceeding the annual goal of approximately 0.8%; the decrease was greatest in patients ages ≥75 years old (5.5%; P<0.001 versus ages 65–74 years old; 5.1%). The relative annual increase in percentages of patients with a fistula at dialysis initiation was 2.4%, roughly three times the goal; the increase was greater for black than white patients (3.2% versus 2.3%; P<0.01). Adjusted regional differences varied greater than twofold: 2.0% for the South versus 4.1% for the Midwest. Thus, although gains have been substantial, not all groups have benefitted equally. Goal development for Healthy People 2030 should consider changes in goal paradigms, such as tailoring by geographic region and incorporating patient-centered goals.10.2215/CJN.04210416Tue, 30 Aug 2016 06:16:52 GMT-07:00The Healthy People 2020 Objectives for Kidney Disease: How Far Have We Come, and Where Do We Need to Go?The Healthy People 2020 initiative established goals for patients with CKD and ESRD. We assessed United States progress toward some of these key goals. Using data from the Centers for Medicare and Medicaid Services ESRD database, we created yearly cohorts of patients on incident and prevalent dialysis from 2000 to 2013. Change in event rate or proportion change over the study years was modeled using Poisson regression with adjustment for age, race, sex, and primary cause of ESRD. For all-cause mortality in prevalent patients, Healthy People 2020 sought approximately 0.8% relative annual improvement; actual improvement was 2.7%. Improvement was greatest for patients ages 18–44 years old (3.8%; P<0.01 versus 2.8% for ages 65–74 years old) and 2.3% even for patients ages ≥75 years old. For mortality in incident patients, the relative annual decrease was 2.1% overall, a twofold improvement over the goal; mortality decreased nearly twice as much in black as in white patients (3.2% versus 1.8%; P<0.001). Geographic variation was substantial; the relative annual decrease was 0.6% in the Midwest and more than fourfold greater (2.7%) in the South. Cardiovascular mortality in prevalent patients decreased dramatically at 5.0% per year, far exceeding the annual goal of approximately 0.8%; the decrease was greatest in patients ages ≥75 years old (5.5%; P<0.001 versus ages 65–74 years old; 5.1%). The relative annual increase in percentages of patients with a fistula at dialysis initiation was 2.4%, roughly three times the goal; the increase was greater for black than white patients (3.2% versus 2.3%; P<0.01). Adjusted regional differences varied greater than twofold: 2.0% for the South versus 4.1% for the Midwest. Thus, although gains have been substantial, not all groups have benefitted equally. Goal development for Healthy People 2030 should consider changes in goal paradigms, such as tailoring by geographic region and incorporating patient-centered goals.Wetmore, James B.Liu, JiannongLi, SuyingHu, YanPeng, YiGilbertson, David T.Collins, Allan J.2016-08-30T06:16:52-07:00doi:10.2215/CJN.04210416hwp:resource-id:clinjasn;12/1/200American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, dialysis, Epidemiology and outcomes, ESRD, Healthy People 2020, public health, African Americans, African Continental Ancestry Group, European Continental Ancestry Group, Fistula, Goals, Humans, Kidney Failure, Chronic, Medicaid, Medicare, renal dialysis, Renal Insufficiency, Chronic, United StatesPublic Policy SeriesPublic Policy Seriesresearch-article20162017-01-06January 06, 201710.2215/CJN.042104161555-90411555-905X2016-08-30T06:16:52-07:002017-01-06Clinical Journal of the American Society of NephrologyPublic Policy Series121200209
- Facility Practice Variation to Help Understand the Effects of Public Policy: Insights from the Dialysis Outcomes and Practice Patterns Study (DOPPS)Recent Centers for Medicare & Medicaid Services policies have used dialysis facility practice variation to develop public ratings and adjust payments. In the Dialysis Facility Compare star rating system (DFC SRS), facility-relative rates of performance-based clinical measures varied nearly two-fold for mortality (standardized mortality ratio; 10th/90th percentiles: 0.71, 1.34) and hospitalization (standardized hospitalization ratio; 10th/90th percentiles: 0.64, 1.37), and nearly four-fold for transfusion (standardized transfusion ratio; 10th/90th percentiles: 0.43, 1.65). Medicare claims data (from July of 2014) demonstrate that facility variation for the proportions of patients on hemodialysis hospitalized (10th/90th percentiles: 27%, 50%) and transfused (10th/90th percentiles: 3%, 17%) within 6 months that far exceeds relatively modest recent overall longitudinal trends. DFC SRS–rated facility variation is also substantial for fistula (10th/90th percentiles: 50%, 78%) and catheter use >90 days (10th/90th percentiles: 3%, 19%). By contrast, DFC SRS–rated facility distributions for adult hemodialysis Kt/V>1.2 (10th/90th percentiles: 84%, 97%) and total serum calcium >10.2 mg/dl (median, 1%; 75th/90th percentiles: 3%, 5%) are quite narrow and may be of questionable value. Likewise, variation in the US Dialysis Outcomes and Practice Patterns Study is over two-fold for facility median serum parathyroid hormone (10th/90th percentiles: 290 pg/ml, 629 pg/ml) and ferritin (10th/90th percentiles: 469 ng/ml, 1143 ng/ml) levels, and facility mean treatment time varies by 30 minutes (10th/90th percentiles: 204 minutes, 234 minutes). Rising serum parathyroid hormone and ferritin levels, and generally short dialysis treatment time, represent areas unchecked by existing policy; both overall trends and facility variation in these values may reflect unintended consequences of policy or reimbursement pressures and therefore raise concern. Additionally, outcomes in the transition period from advanced CKD to dialysis remain poor, and policy initiatives and performance accountability in this area remain insufficient. Innovative models of comprehensive care in advanced CKD and the early dialysis period which are more amenable to policy oversight are needed. In summary, facility variation is typically larger than prevailing longitudinal trends, and should not be overlooked. The combination of nationally representative observational databases (e.g., the Dialysis Outcomes and Practice Patterns Study) and ESRD registries can provide policy makers with additional tools to evaluate facility variation, develop policies, and monitor unintended effects.10.2215/CJN.03930416Thu, 10 Nov 2016 08:52:34 GMT-08:00Facility Practice Variation to Help Understand the Effects of Public Policy: Insights from the Dialysis Outcomes and Practice Patterns Study (DOPPS)Recent Centers for Medicare & Medicaid Services policies have used dialysis facility practice variation to develop public ratings and adjust payments. In the Dialysis Facility Compare star rating system (DFC SRS), facility-relative rates of performance-based clinical measures varied nearly two-fold for mortality (standardized mortality ratio; 10th/90th percentiles: 0.71, 1.34) and hospitalization (standardized hospitalization ratio; 10th/90th percentiles: 0.64, 1.37), and nearly four-fold for transfusion (standardized transfusion ratio; 10th/90th percentiles: 0.43, 1.65). Medicare claims data (from July of 2014) demonstrate that facility variation for the proportions of patients on hemodialysis hospitalized (10th/90th percentiles: 27%, 50%) and transfused (10th/90th percentiles: 3%, 17%) within 6 months that far exceeds relatively modest recent overall longitudinal trends. DFC SRS–rated facility variation is also substantial for fistula (10th/90th percentiles: 50%, 78%) and catheter use >90 days (10th/90th percentiles: 3%, 19%). By contrast, DFC SRS–rated facility distributions for adult hemodialysis Kt/V>1.2 (10th/90th percentiles: 84%, 97%) and total serum calcium >10.2 mg/dl (median, 1%; 75th/90th percentiles: 3%, 5%) are quite narrow and may be of questionable value. Likewise, variation in the US Dialysis Outcomes and Practice Patterns Study is over two-fold for facility median serum parathyroid hormone (10th/90th percentiles: 290 pg/ml, 629 pg/ml) and ferritin (10th/90th percentiles: 469 ng/ml, 1143 ng/ml) levels, and facility mean treatment time varies by 30 minutes (10th/90th percentiles: 204 minutes, 234 minutes). Rising serum parathyroid hormone and ferritin levels, and generally short dialysis treatment time, represent areas unchecked by existing policy; both overall trends and facility variation in these values may reflect unintended consequences of policy or reimbursement pressures and therefore raise concern. Additionally, outcomes in the transition period from advanced CKD to dialysis remain poor, and policy initiatives and performance accountability in this area remain insufficient. Innovative models of comprehensive care in advanced CKD and the early dialysis period which are more amenable to policy oversight are needed. In summary, facility variation is typically larger than prevailing longitudinal trends, and should not be overlooked. The combination of nationally representative observational databases (e.g., the Dialysis Outcomes and Practice Patterns Study) and ESRD registries can provide policy makers with additional tools to evaluate facility variation, develop policies, and monitor unintended effects.Fuller, Douglas S.Robinson, Bruce M.2016-11-10T08:52:34-08:00doi:10.2215/CJN.03930416hwp:resource-id:clinjasn;12/1/190American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, dialysis access, hemodialysis adequacy, outcomes, adult, Calcium, Dietary, Centers for Medicare and Medicaid Services (U.S.), Ferritins, Fistula, Health Facilities, hospitalization, Humans, Kidney Failure, Chronic, Medicare, parathyroid hormone, peritoneal dialysis, Public Policy, Registries, renal dialysis, Social Responsibility, United StatesPublic Policy SeriesPublic Policy Seriesresearch-article20162017-01-06January 06, 201710.2215/CJN.039304161555-90411555-905X2016-11-10T08:52:34-08:002017-01-06Clinical Journal of the American Society of NephrologyPublic Policy Series121190199
- Screening Women with CKD for the Emperor of All Maladies10.2215/CJN.12151116Thu, 29 Dec 2016 04:46:06 GMT-08:00Screening Women with CKD for the Emperor of All MaladiesCrews, Deidra C.Khaliq, Waseem2016-12-29T04:46:06-08:00doi:10.2215/CJN.12151116hwp:resource-id:clinjasn;12/1/5American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycancer, chronic kidney disease, Epidemiology and outcomes, kidney transplantation, ESRD, Female, Humans, Mass Screening, Renal Insufficiency, Chronic, risk factorsEditorialsEditorialseditorial20162017-01-06January 06, 201710.2215/CJN.121511161555-90411555-905X2016-12-29T04:46:06-08:002017-01-06Clinical Journal of the American Society of NephrologyEditorials12115956104
- Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation10.2215/CJN.06440616Mon, 31 Oct 2016 09:24:25 GMT-07:00Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab DiscontinuationFakhouri, FadiFila, MarcProvôt, FrançoisDelmas, YahsouBarbet, ChristelleChâtelet, ValérieRafat, CédricCailliez, MathildeHogan, JulienServais, AudeKarras, AlexandreMakdassi, RaifahLouillet, FeriellCoindre, Jean-PhilippeRondeau, EricLoirat, ChantalFrémeaux-Bacchi, Véronique2016-10-31T09:24:25-07:00doi:10.2215/CJN.06440616hwp:resource-id:clinjasn;12/1/50American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemolytic uremic syndrome, complement, eculizumab, Adult, Antibodies, Monoclonal, Humanized, Antigens, CD46, Atypical Hemolytic Uremic Syndrome, Child, Complement Factor H, Complement Inactivating Agents, Complement System Proteins, creatinine, Follow-Up Studies, Hematologic Tests, Humans, Prospective Studies, Recurrence, Registries, renal dialysis, Retreatment, Retrospective StudiesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162017-01-06January 06, 201710.2215/CJN.064406161555-90411555-905X2016-10-31T09:24:25-07:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles1215059
- Monocyte Chemoattractant Protein-1 Levels and Postangioplasty Restenosis of Arteriovenous Fistulas10.2215/CJN.04030416Wed, 26 Oct 2016 05:29:37 GMT-07:00Monocyte Chemoattractant Protein-1 Levels and Postangioplasty Restenosis of Arteriovenous FistulasWu, Chih-ChengChen, Tsung-YanHsieh, Mu-YangLin, LinYang, Chung-WeiChuang, Shao-YuanTarng, Der-Cheng2016-10-26T05:29:37-07:00doi:10.2215/CJN.04030416hwp:resource-id:clinjasn;12/1/113American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyangioplasty, arterioveous fistula, hemodialysis, monocyte chemoattractant protein-1, stenosisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162017-01-06January 06, 201710.2215/CJN.040304161555-90411555-905X2016-10-26T05:29:37-07:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles121113121
- Peritoneal Dialysis Access Revision in Children: Causes, Interventions, and Outcomes10.2215/CJN.05270516Tue, 29 Nov 2016 05:19:01 GMT-08:00Peritoneal Dialysis Access Revision in Children: Causes, Interventions, and OutcomesBorzych-Duzalka, DagmaraAki, T. FazilAzocar, MartaWhite, ColinHarvey, ElizabethMir, SevgiAdragna, MartaSerdaroglu, ErkinSinha, RajivSamaille, CharlotteVanegas, Juan JoseKari, JameelaBarbosa, LorenaBagga, ArvindGalanti, MonicaYavascan, OnderLeozappa, GiovannaSzczepanska, MariaVondrak, KarelTse, Kei-ChiuSchaefer, FranzWarady, Bradley A.2016-11-29T05:19:01-08:00doi:10.2215/CJN.05270516hwp:resource-id:clinjasn;12/1/105American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychildren, dialysis access, catheter, Attention, Child, Follow-Up Studies, Humans, nephrology, Ostomy, peritoneal dialysis, Peritoneum, Peritonitis, Registries, risk factors, Surgeons, Survival Rate, vesico-ureteral refluxOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162017-01-06January 06, 201710.2215/CJN.052705161555-90411555-905X2016-11-29T05:19:01-08:002017-01-06Clinical Journal of the American Society of NephrologyOriginal Articles121105112
- Predicting Risk of RRT in Patients with CKD10.2215/CJN.11841116Tue, 27 Dec 2016 05:03:44 GMT-08:00Predicting Risk of RRT in Patients with CKDGrams, Morgan E.Coresh, Josef2016-12-27T05:03:44-08:00doi:10.2215/CJN.11841116hwp:resource-id:clinjasn;12/1/3American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, ESRD, Humans, Renal Insufficiency, Chronic, Renal Replacement Therapy, Risk, Prediction ModelEditorialsEditorialseditorial20162017-01-06January 06, 201710.2215/CJN.118411161555-90411555-905X2016-12-27T05:03:44-08:002017-01-06Clinical Journal of the American Society of NephrologyEditorials1211387494
- SGLT2 Inhibitors—Sweet Success for Diabetic Kidney Disease?10.1681/ASN.2016060650Thu, 18 Aug 2016 08:16:26 GMT-07:00SGLT2 Inhibitors—Sweet Success for Diabetic Kidney Disease?de Boer, Ian H.Kahn, Steven E.2016-08-18T08:16:26-07:00doi:10.1681/ASN.2016060650hwp:resource-id:jnephrol;28/1/7American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, diabetes mellitus, chronic kidney disease, clinical trialUp Front MattersEditorialsUp Front MattersEditorialseditorial20162017-01-01January 201710.1681/ASN.20160606501046-66731533-34502016-08-18T08:16:26-07:002017-01Journal of the American Society of NephrologyUp Front Matters2811736810375
- Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic NephropathyThe amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin–knockout mouse line, megalin(lox/lox);Ndrg1-CreERT2 (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild–type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol–binding protein. Furthermore, urinary albumin excretion increased to 175 μg/d (0.46 mg albumin/mg creatinine) in Tam-treated iMegKO mice, suggesting that this was the amount of total nephron albumin filtration. By comparing Tam-treated, streptozotocin-induced diabetic iMegKO mice with Tam-treated nondiabetic iMegKO mice, we estimated that the development of diabetes led to a 1.9-fold increase in total nephron albumin filtration, a 1.8-fold increase in reabsorption, and a significant reduction in reabsorption efficiency (86% efficiency versus 96% efficiency in nondiabetic mice). Insulin treatment normalized these abnormalities. Akita;iMegKO mice, another model of type 1 diabetes, showed equivalent results. Finally, nondiabetic iMegKO mice had a glomerular sieving coefficient of albumin of 1.7×10−5, which approximately doubled in diabetic iMegKO mice. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy in mice, bringing new insights to our understanding of renal albumin dynamics associated with the hyperfiltration status of diabetic nephropathy.10.1681/ASN.2015101168Wed, 06 Jul 2016 05:41:49 GMT-07:00Increase of Total Nephron Albumin Filtration and Reabsorption in Diabetic NephropathyThe amount of albumin filtered through the glomeruli and reabsorbed at the proximal tubules in normal and in diabetic kidneys is debated. The megalin/cubilin complex mediates protein reabsorption, but genetic knockout of megalin is perinatally lethal. To overcome current technical problems, we generated a drug-inducible megalin–knockout mouse line, megalin(lox/lox);Ndrg1-CreERT2 (iMegKO), in which megalin expression can be shut off at any time by administration of tamoxifen (Tam). Tam administration in adult iMegKO mice decreased the expression of renal megalin protein by 92% compared with that in wild–type C57BL/6J mice and almost completely abrogated renal reabsorption of intravenously injected retinol–binding protein. Furthermore, urinary albumin excretion increased to 175 μg/d (0.46 mg albumin/mg creatinine) in Tam-treated iMegKO mice, suggesting that this was the amount of total nephron albumin filtration. By comparing Tam-treated, streptozotocin-induced diabetic iMegKO mice with Tam-treated nondiabetic iMegKO mice, we estimated that the development of diabetes led to a 1.9-fold increase in total nephron albumin filtration, a 1.8-fold increase in reabsorption, and a significant reduction in reabsorption efficiency (86% efficiency versus 96% efficiency in nondiabetic mice). Insulin treatment normalized these abnormalities. Akita;iMegKO mice, another model of type 1 diabetes, showed equivalent results. Finally, nondiabetic iMegKO mice had a glomerular sieving coefficient of albumin of 1.7×10−5, which approximately doubled in diabetic iMegKO mice. This study reveals actual values and changes of albumin filtration and reabsorption in early diabetic nephropathy in mice, bringing new insights to our understanding of renal albumin dynamics associated with the hyperfiltration status of diabetic nephropathy.Mori, Keita P.Yokoi, HidekiKasahara, MasatoImamaki, HirotakaIshii, AkiraKuwabara, TakashigeKoga, KenichiKato, YukikoToda, NaohiroOhno, ShokoKuwahara, KoichiroEndo, TomomiNakao, KazuwaYanagita, MotokoMukoyama, MasashiMori, Kiyoshi2016-07-06T05:41:49-07:00doi:10.1681/ASN.2015101168hwp:resource-id:jnephrol;28/1/278American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, chronic kidney disease, diabetic nephropathy, glomerular hyperfiltration, endocytosisBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20151011681046-66731533-34502016-07-06T05:41:49-07:002017-01Journal of the American Society of NephrologyBasic Research281278289
- Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-UpRandomized trials of rituximab in primary membranous nephropathy (PMN) have not been conducted. We undertook a multicenter, randomized, controlled trial at 31 French hospitals (NCT01508468). Patients with biopsy-proven PMN and nephrotic syndrome after 6 months of nonimmunosuppressive antiproteinuric treatment (NIAT) were randomly assigned to 6-month therapy with NIAT and 375 mg/m2 intravenous rituximab on days 1 and 8 (n=37) or NIAT alone (n=38). Median times to last follow-up were 17.0 (interquartile range, 12.5–24.0) months and 17.0 (interquartile range, 13.0–23.0) months in NIAT-rituximab and NIAT groups, respectively. Primary outcome was a combined end point of complete or partial remission of proteinuria at 6 months. At month 6, 13 (35.1%; 95% confidence interval [95% CI], 19.7 to 50.5) patients in the NIAT-rituximab group and eight (21.1%; 95% CI, 8.1 to 34.0) patients in the NIAT group achieved remission (P=0.21). Rates of antiphospholipase A2 receptor antibody (anti–PLA2R-Ab) depletion in NIAT-rituximab and NIAT groups were 14 of 25 (56%) and one of 23 (4.3%) patients at month 3 (P<0.001) and 13 of 26 (50%) and three of 25 (12%) patients at month 6 (P=0.004), respectively. Eight serious adverse events occurred in each group. During the observational phase, remission rates before change of assigned treatment were 24 of 37 (64.9%) and 13 of 38 (34.2%) patients in NIAT-rituximab and NIAT groups, respectively (P<0.01). Positive effect of rituximab on proteinuria remission occurred after 6 months. These data suggest that PLA2R-Ab levels are early markers of rituximab effect and that addition of rituximab to NIAT does not affect safety.10.1681/ASN.2016040449Mon, 27 Jun 2016 08:30:52 GMT-07:00Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-UpRandomized trials of rituximab in primary membranous nephropathy (PMN) have not been conducted. We undertook a multicenter, randomized, controlled trial at 31 French hospitals (NCT01508468). Patients with biopsy-proven PMN and nephrotic syndrome after 6 months of nonimmunosuppressive antiproteinuric treatment (NIAT) were randomly assigned to 6-month therapy with NIAT and 375 mg/m2 intravenous rituximab on days 1 and 8 (n=37) or NIAT alone (n=38). Median times to last follow-up were 17.0 (interquartile range, 12.5–24.0) months and 17.0 (interquartile range, 13.0–23.0) months in NIAT-rituximab and NIAT groups, respectively. Primary outcome was a combined end point of complete or partial remission of proteinuria at 6 months. At month 6, 13 (35.1%; 95% confidence interval [95% CI], 19.7 to 50.5) patients in the NIAT-rituximab group and eight (21.1%; 95% CI, 8.1 to 34.0) patients in the NIAT group achieved remission (P=0.21). Rates of antiphospholipase A2 receptor antibody (anti–PLA2R-Ab) depletion in NIAT-rituximab and NIAT groups were 14 of 25 (56%) and one of 23 (4.3%) patients at month 3 (P<0.001) and 13 of 26 (50%) and three of 25 (12%) patients at month 6 (P=0.004), respectively. Eight serious adverse events occurred in each group. During the observational phase, remission rates before change of assigned treatment were 24 of 37 (64.9%) and 13 of 38 (34.2%) patients in NIAT-rituximab and NIAT groups, respectively (P<0.01). Positive effect of rituximab on proteinuria remission occurred after 6 months. These data suggest that PLA2R-Ab levels are early markers of rituximab effect and that addition of rituximab to NIAT does not affect safety.Dahan, KarineDebiec, HannaPlaisier, EmmanuelleCachanado, MarineRousseau, AlexandraWakselman, LauraMichel, Pierre-AntoineMihout, FabriceDussol, BertrandMatignon, MarieMousson, ChristianeSimon, TabassomeRonco, Pierre,Audard, VincentBataille, PierreBerland, YvonBoffa, Jean-JacquesBouvier, NicolasBraun, LauraBridoux, FrankBurtey, StéphaneChaintreuil, DéborahCastrale, CindyChoukroun, GabrielCombe, ChristianDaugas, EricDelahousse, MichelDuval-Sabatier, ArianeEssig, MarieEtienne, IsabelleFrançois, HélèneFouque, DenisGlotz, DenisGodin, MichelGondouin, BertrandGosselin, MorganeHourmant, MaryvonneHummel, AurélieIsnard-Bagnis, CorinneJouzel, CharlotteHurault de Ligny, BrunoKarras, AlexandreKofman, ThomasLang, PhilippeLemoine, SandrineVerhoeven, Anne-Sophie LibrezMesbah, RafikMesnard, LaurentMoulin, BrunoOttavioli, Jean-NoëlPéraldi, Marie-NoellePillebout, EvangelinePouteil-Noble, ClaireRieu, PhilippeRigothier, ClaireRyckelynck, Jean-PhilippeSahali, DjillaliSoltani, ZaaraSouid, MarcStehlé, ThomasTouzot, MaximeTrolliet, PierreVanhille, PhilippeLebas, CélineVerhelst, DavidVigneau, CecileVrigneaud, LaurenceVrtosvnik, François2016-06-27T08:30:52-07:00doi:10.1681/ASN.2016040449hwp:resource-id:jnephrol;28/1/348American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrituximab, idiopathic membranous nephropathy, randomized controlled trial, severe adverse event, anti-PLA2R antibody, anti-THSD7A antibodyClinical ResearchClinical Researchresearch-article20162017-01-01January 201710.1681/ASN.20160404491046-66731533-34502016-06-27T08:30:52-07:002017-01Journal of the American Society of NephrologyClinical Research281348358
- mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular CellsRenal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR–dependent regulatory network for nutrient transport in renal proximal tubular cells.10.1681/ASN.2015111224Mon, 13 Jun 2016 11:37:24 GMT-07:00mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular CellsRenal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR–dependent regulatory network for nutrient transport in renal proximal tubular cells.Grahammer, FlorianRamakrishnan, Suresh K.Rinschen, Markus M.Larionov, Alexey A.Syed, MaryamKhatib, HazimRoerden, MalteSass, Jörn OliverHelmstaedter, MartinOsenberg, DorotheaKühne, LucasKretz, OliverWanner, NicolaJouret, FrancoisBenzing, ThomasArtunc, FerruhHuber, Tobias B.Theilig, Franziska2016-06-13T11:37:24-07:00doi:10.1681/ASN.2015111224hwp:resource-id:jnephrol;28/1/230American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, endocytosis, epithelial transport, mTOR, albuminuria, proteomicsBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20151112241046-66731533-34502016-06-13T11:37:24-07:002017-01Journal of the American Society of NephrologyBasic Research281123032415
- High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKDHigh levels of proenkephalin-A (pro-ENK) have been associated with decreased eGFR in an acute setting. Here, we examined whether pro-ENK levels predict CKD and decline of renal function in a prospective cohort of 2568 participants without CKD (eGFR>60 ml/min per 1.73 m2) at baseline. During a mean follow-up of 16.6 years, 31.7% of participants developed CKD. Participants with baseline pro-ENK levels in the highest tertile had significantly greater yearly mean decline of eGFR (Ptrend<0.001) and rise of cystatin C (Ptrend=0.01) and creatinine (Ptrend<0.001) levels. Furthermore, compared with participants in the lowest tertile, participants in the highest tertile of baseline pro-ENK concentration had increased CKD incidence (odds ratio, 1.51; 95% confidence interval, 1.18 to 1.94) when adjusted for multiple factors. Adding pro-ENK to a model of conventional risk factors in net reclassification improvement analysis resulted in reclassification of 14.14% of participants. Genome-wide association analysis in 4150 participants of the same cohort revealed the strongest association of pro-ENK levels with rs1012178 near the PENK gene, where the minor T-allele associated with a 0.057 pmol/L higher pro-ENK level per allele (P=4.67x10−21). Furthermore, the T-allele associated with a 19% increased risk of CKD per allele (P=0.03) and a significant decrease in the instrumental variable estimator for eGFR (P<0.01) in a Mendelian randomization analysis. In conclusion, circulating plasma pro-ENK level predicts incident CKD and may aid in identifying subjects in need of primary preventive regimens. Additionally, the Mendelian randomization analysis suggests a causal relationship between pro-ENK level and deterioration of kidney function over time.10.1681/ASN.2015101177Fri, 08 Jul 2016 06:48:42 GMT-07:00High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKDHigh levels of proenkephalin-A (pro-ENK) have been associated with decreased eGFR in an acute setting. Here, we examined whether pro-ENK levels predict CKD and decline of renal function in a prospective cohort of 2568 participants without CKD (eGFR>60 ml/min per 1.73 m2) at baseline. During a mean follow-up of 16.6 years, 31.7% of participants developed CKD. Participants with baseline pro-ENK levels in the highest tertile had significantly greater yearly mean decline of eGFR (Ptrend<0.001) and rise of cystatin C (Ptrend=0.01) and creatinine (Ptrend<0.001) levels. Furthermore, compared with participants in the lowest tertile, participants in the highest tertile of baseline pro-ENK concentration had increased CKD incidence (odds ratio, 1.51; 95% confidence interval, 1.18 to 1.94) when adjusted for multiple factors. Adding pro-ENK to a model of conventional risk factors in net reclassification improvement analysis resulted in reclassification of 14.14% of participants. Genome-wide association analysis in 4150 participants of the same cohort revealed the strongest association of pro-ENK levels with rs1012178 near the PENK gene, where the minor T-allele associated with a 0.057 pmol/L higher pro-ENK level per allele (P=4.67x10−21). Furthermore, the T-allele associated with a 19% increased risk of CKD per allele (P=0.03) and a significant decrease in the instrumental variable estimator for eGFR (P<0.01) in a Mendelian randomization analysis. In conclusion, circulating plasma pro-ENK level predicts incident CKD and may aid in identifying subjects in need of primary preventive regimens. Additionally, the Mendelian randomization analysis suggests a causal relationship between pro-ENK level and deterioration of kidney function over time.Schulz, Christina-AlexandraChristensson, AndersEricson, UlrikaAlmgren, PeterHindy, GeorgeNilsson, Peter M.Struck, JoachimBergmann, AndreasMelander, OlleOrho-Melander, Marju2016-07-08T06:48:42-07:00doi:10.1681/ASN.2015101177hwp:resource-id:jnephrol;28/1/291American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycreatinine, glomerular filtration rate, chronic kidney disease, proenkephalin, cystatin C, PENKClinical EpidemiologyClinical Epidemiologyresearch-article20162017-01-01January 201710.1681/ASN.20151011771046-66731533-34502016-07-08T06:48:42-07:002017-01Journal of the American Society of NephrologyClinical Epidemiology281291303
- Double Knockout of the Na+-Driven Cl−/HCO3− Exchanger and Na+/Cl− Cotransporter Induces Hypokalemia and Volume DepletionWe recently described a novel thiazide–sensitive electroneutral NaCl transport mechanism resulting from the parallel operation of the Cl−/HCO3− exchanger pendrin and the Na+–driven Cl−/2HCO3− exchanger (NDCBE) in β-intercalated cells of the collecting duct. Although a role for pendrin in maintaining Na+ balance, intravascular volume, and BP is well supported, there is no in vivo evidence for the role of NDCBE in maintaining Na+ balance. Here, we show that deletion of NDCBE in mice caused only subtle perturbations of Na+ homeostasis and provide evidence that the Na+/Cl− cotransporter (NCC) compensated for the inactivation of NDCBE. To unmask the role of NDCBE, we generated Ndcbe/Ncc double–knockout (dKO) mice. On a normal salt diet, dKO and single-knockout mice exhibited similar activation of the renin-angiotensin-aldosterone system, whereas only dKO mice displayed a lower blood K+ concentration. Furthermore, dKO mice displayed upregulation of the epithelial sodium channel (ENaC) and the Ca2+–activated K+ channel BKCa. During NaCl depletion, only dKO mice developed marked intravascular volume contraction, despite dramatically increased renin activity. Notably, the increase in aldosterone levels expected on NaCl depletion was attenuated in dKO mice, and single-knockout and dKO mice had similar blood K+ concentrations under this condition. In conclusion, NDCBE is necessary for maintaining sodium balance and intravascular volume during salt depletion or NCC inactivation in mice. Furthermore, NDCBE has an important role in the prevention of hypokalemia. Because NCC and NDCBE are both thiazide targets, the combined inhibition of NCC and the NDCBE/pendrin system may explain thiazide-induced hypokalemia in some patients.10.1681/ASN.2015070734Thu, 05 May 2016 07:03:11 GMT-07:00Double Knockout of the Na+-Driven Cl−/HCO3− Exchanger and Na+/Cl− Cotransporter Induces Hypokalemia and Volume DepletionWe recently described a novel thiazide–sensitive electroneutral NaCl transport mechanism resulting from the parallel operation of the Cl−/HCO3− exchanger pendrin and the Na+–driven Cl−/2HCO3− exchanger (NDCBE) in β-intercalated cells of the collecting duct. Although a role for pendrin in maintaining Na+ balance, intravascular volume, and BP is well supported, there is no in vivo evidence for the role of NDCBE in maintaining Na+ balance. Here, we show that deletion of NDCBE in mice caused only subtle perturbations of Na+ homeostasis and provide evidence that the Na+/Cl− cotransporter (NCC) compensated for the inactivation of NDCBE. To unmask the role of NDCBE, we generated Ndcbe/Ncc double–knockout (dKO) mice. On a normal salt diet, dKO and single-knockout mice exhibited similar activation of the renin-angiotensin-aldosterone system, whereas only dKO mice displayed a lower blood K+ concentration. Furthermore, dKO mice displayed upregulation of the epithelial sodium channel (ENaC) and the Ca2+–activated K+ channel BKCa. During NaCl depletion, only dKO mice developed marked intravascular volume contraction, despite dramatically increased renin activity. Notably, the increase in aldosterone levels expected on NaCl depletion was attenuated in dKO mice, and single-knockout and dKO mice had similar blood K+ concentrations under this condition. In conclusion, NDCBE is necessary for maintaining sodium balance and intravascular volume during salt depletion or NCC inactivation in mice. Furthermore, NDCBE has an important role in the prevention of hypokalemia. Because NCC and NDCBE are both thiazide targets, the combined inhibition of NCC and the NDCBE/pendrin system may explain thiazide-induced hypokalemia in some patients.Sinning, AnneRadionov, NikitaTrepiccione, FrancescoLópez-Cayuqueo, Karen I.Jayat, MaximilienBaron, StéphanieCornière, NicolasAlexander, R. ToddHadchouel, JulietteEladari, DominiqueHübner, Christian A.Chambrey, Régine2016-05-05T07:03:11-07:00doi:10.1681/ASN.2015070734hwp:resource-id:jnephrol;28/1/130American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiuretics, hypertension, hypokalemiaBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150707341046-66731533-34502016-05-05T07:03:11-07:002017-01Journal of the American Society of NephrologyBasic Research281130139
- CD8+ T Cells Effect Glomerular Injury in Experimental Anti-Myeloperoxidase GNObservations in patients with ANCA-associated vasculitis suggest that CD8+ T cells participate in disease, but there is no experimental functional evidence of pathologic involvement for these cells. Myeloperoxidase (MPO) is a well defined autoantigen in ANCA-associated vasculitis. Studies in experimental models of anti-MPO GN suggest that, after ANCA–induced neutrophil localization, deposited MPO within glomeruli is recognized by autoreactive T cells that contribute to injury. We tested the hypothesis that CD8+ T cells mediate disease in experimental ANCA–associated vasculitis. CD8+ T cell depletion in the effector phase of disease attenuated injury in murine anti–MPO GN. This protection associated with decreased levels of intrarenal IFN-γ, TNF, and inflammatory chemokines and fewer glomerular macrophages. Moreover, we identified a pathogenic CD8+ T cell MPO epitope (MPO431–439) and found that cotransfer of MPO431–439–specific CD8+ T cell clones exacerbated disease mediated by MPO–specific CD4+ cells in Rag1−/− mice. Transfer of MPO431–439–specific CD8+ cells without CD4+ cells mediated glomerular injury when MPO was planted in glomeruli. These results show a pathogenic role for MPO–specific CD8+ T cells, provide evidence that CD8+ cells are a therapeutic target in ANCA-associated vasculitis, and suggest that a molecular hotspot within the MPO molecule contains important CD8+, CD4+, and B cell epitopes.10.1681/ASN.2015121356Fri, 10 Jun 2016 06:45:18 GMT-07:00CD8+ T Cells Effect Glomerular Injury in Experimental Anti-Myeloperoxidase GNObservations in patients with ANCA-associated vasculitis suggest that CD8+ T cells participate in disease, but there is no experimental functional evidence of pathologic involvement for these cells. Myeloperoxidase (MPO) is a well defined autoantigen in ANCA-associated vasculitis. Studies in experimental models of anti-MPO GN suggest that, after ANCA–induced neutrophil localization, deposited MPO within glomeruli is recognized by autoreactive T cells that contribute to injury. We tested the hypothesis that CD8+ T cells mediate disease in experimental ANCA–associated vasculitis. CD8+ T cell depletion in the effector phase of disease attenuated injury in murine anti–MPO GN. This protection associated with decreased levels of intrarenal IFN-γ, TNF, and inflammatory chemokines and fewer glomerular macrophages. Moreover, we identified a pathogenic CD8+ T cell MPO epitope (MPO431–439) and found that cotransfer of MPO431–439–specific CD8+ T cell clones exacerbated disease mediated by MPO–specific CD4+ cells in Rag1−/− mice. Transfer of MPO431–439–specific CD8+ cells without CD4+ cells mediated glomerular injury when MPO was planted in glomeruli. These results show a pathogenic role for MPO–specific CD8+ T cells, provide evidence that CD8+ cells are a therapeutic target in ANCA-associated vasculitis, and suggest that a molecular hotspot within the MPO molecule contains important CD8+, CD4+, and B cell epitopes.Chang, JanetEggenhuizen, PeterO’Sullivan, Kim M.Alikhan, Maliha A.Holdsworth, Stephen R.Ooi, Joshua D.Kitching, A. Richard2016-06-10T06:45:18-07:00doi:10.1681/ASN.2015121356hwp:resource-id:jnephrol;28/1/47American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, glomerulonephritis, vasculitis, immunologyBrief CommunicationsBrief Communicationsbrief-report20162017-01-01January 201710.1681/ASN.20151213561046-66731533-34502016-06-10T06:45:18-07:002017-01Journal of the American Society of NephrologyBrief Communications2814755
- MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na+-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17–SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na+/H+ exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters.10.1681/ASN.2015111282Fri, 10 Jun 2016 06:45:19 GMT-07:00MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na+-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17–SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na+/H+ exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters.Coady, Michael J.El Tarazi, AbdulahSanter, RenéBissonnette, PierreSasseville, Louis J.Calado, JoaquimLussier, YoannDumayne, ChristopherBichet, Daniel G.Lapointe, Jean-Yves2016-06-10T06:45:19-07:00doi:10.1681/ASN.2015111282hwp:resource-id:jnephrol;28/1/85American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell & transport physiology, diabetes, ion transport, Na transport, glucose reabsorptionBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20151112821046-66731533-34502016-06-10T06:45:19-07:002017-01Journal of the American Society of NephrologyBasic Research2818593
- Understanding and Communicating Medical Risks for Living Kidney Donors: A Matter of PerspectiveCommunicating the current knowledge of medical outcomes after live kidney donation necessary to support donor candidates in well informed decision-making requires grounding in perspectives of comparison. Baseline risk (without donating), risk attributable to donation, and absolute risk (after donating) need to be considered. Severe perioperative complications and death are rare, but vary by demographic, clinical, and procedure factors. Innovative capture of “healthy” controls designed to simulate donor selection processes has identified higher risk of ESRD attributable to donation in two studies; importantly, however, the absolute 15-year ESRD incidence in donors remains very low (0.3%). In the first decade after donation, the risk of all-cause mortality and cardiovascular events is no higher than in healthy nondonors. Pregnancies in donors may incur attributable risk of gestational hypertension or preeclampsia (11% versus 5% incidence in one study). A modest rise in uric acid levels beginning early after donation, and a small (1.4%) increase in the 8-year incidence of gout, have also been reported in comparisons to healthy nondonors. As in the general population, postdonation outcomes vary by race, sex, and age. Efforts to improve the counseling and selection of living donors should focus on developing tools for tailored risk prediction according to donor characteristics, and ideally, compared with similar healthy nondonors.10.1681/ASN.2016050571Fri, 02 Sep 2016 04:31:23 GMT-07:00Understanding and Communicating Medical Risks for Living Kidney Donors: A Matter of PerspectiveCommunicating the current knowledge of medical outcomes after live kidney donation necessary to support donor candidates in well informed decision-making requires grounding in perspectives of comparison. Baseline risk (without donating), risk attributable to donation, and absolute risk (after donating) need to be considered. Severe perioperative complications and death are rare, but vary by demographic, clinical, and procedure factors. Innovative capture of “healthy” controls designed to simulate donor selection processes has identified higher risk of ESRD attributable to donation in two studies; importantly, however, the absolute 15-year ESRD incidence in donors remains very low (0.3%). In the first decade after donation, the risk of all-cause mortality and cardiovascular events is no higher than in healthy nondonors. Pregnancies in donors may incur attributable risk of gestational hypertension or preeclampsia (11% versus 5% incidence in one study). A modest rise in uric acid levels beginning early after donation, and a small (1.4%) increase in the 8-year incidence of gout, have also been reported in comparisons to healthy nondonors. As in the general population, postdonation outcomes vary by race, sex, and age. Efforts to improve the counseling and selection of living donors should focus on developing tools for tailored risk prediction according to donor characteristics, and ideally, compared with similar healthy nondonors.Lentine, Krista L.Segev, Dorry L.2016-09-02T04:31:23-07:00doi:10.1681/ASN.2016050571hwp:resource-id:jnephrol;28/1/12American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney donation, transplantation, donorsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162017-01-01January 201710.1681/ASN.20160505711046-66731533-34502016-09-02T04:31:23-07:002017-01Journal of the American Society of NephrologyUp Front Matters2811224
- Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal FunctionThe cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels.10.1681/ASN.2015070731Fri, 06 May 2016 08:56:00 GMT-07:00Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal FunctionThe cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels.Staffel, JaninaValletta, DanielaFederlein, AnnaEhm, KatharinaVolkmann, RegineFüchsl, Andrea M.Witzgall, RalphKuhn, MichaelaSchweda, Frank2016-05-06T08:56:00-07:00doi:10.1681/ASN.2015070731hwp:resource-id:jnephrol;28/1/260American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycardiac natriuretic peptides, podocyte, albuminuria, progression of renal failureBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150707311046-66731533-34502016-05-06T08:56:00-07:002017-01Journal of the American Society of NephrologyBasic Research281260277
- Does Renal Repair Recapitulate Kidney Development?Over a decade ago, it was proposed that the regulation of tubular repair in the kidney might involve the recapitulation of developmental pathways. Although the kidney cannot generate new nephrons after birth, suggesting a low level of regenerative competence, the tubular epithelial cells of the nephrons can proliferate to repair the damage after AKI. However, the debate continues over whether this repair involves a persistent progenitor population or any mature epithelial cell remaining after injury. Recent reports have highlighted the expression of Sox9, a transcription factor critical for normal kidney development, during postnatal epithelial repair in the kidney. Indeed, the proliferative response of the epithelium involves expression of several pathways previously described as being involved in kidney development. In some instances, these pathways are also apparently involved in the maladaptive responses observed after repeated injury. Whether development and repair in the kidney are the same processes or we are misinterpreting the similar expression of genes under different circumstances remains unknown. Here, we review the evidence for this link, concluding that such parallels in expression may more correctly represent the use of the same pathways in a distinct context, likely triggered by similar stressors.10.1681/ASN.2016070748Wed, 26 Oct 2016 05:20:37 GMT-07:00Does Renal Repair Recapitulate Kidney Development?Over a decade ago, it was proposed that the regulation of tubular repair in the kidney might involve the recapitulation of developmental pathways. Although the kidney cannot generate new nephrons after birth, suggesting a low level of regenerative competence, the tubular epithelial cells of the nephrons can proliferate to repair the damage after AKI. However, the debate continues over whether this repair involves a persistent progenitor population or any mature epithelial cell remaining after injury. Recent reports have highlighted the expression of Sox9, a transcription factor critical for normal kidney development, during postnatal epithelial repair in the kidney. Indeed, the proliferative response of the epithelium involves expression of several pathways previously described as being involved in kidney development. In some instances, these pathways are also apparently involved in the maladaptive responses observed after repeated injury. Whether development and repair in the kidney are the same processes or we are misinterpreting the similar expression of genes under different circumstances remains unknown. Here, we review the evidence for this link, concluding that such parallels in expression may more correctly represent the use of the same pathways in a distinct context, likely triggered by similar stressors.Little, Melissa HelenKairath, Pamela2016-10-26T05:20:37-07:00doi:10.1681/ASN.2016070748hwp:resource-id:jnephrol;28/1/34American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, kidney development, transcriptional profiling, tubular repair, acute tubular injury, Maladaptive repairUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162017-01-01January 201710.1681/ASN.20160707481046-66731533-34502016-10-26T05:20:37-07:002017-01Journal of the American Society of NephrologyUp Front Matters2813446
- AKI and Long-Term Risk for Cardiovascular Events and MortalityAKI associates with increased long-term risk of mortality, but the prognostic significance of AKI in terms of long-term cardiovascular disease remains unconfirmed. We conducted a systematic review and meta-analysis to assess whether AKI associates with long-term cardiovascular disease. We included cohort studies that examined adults with and without AKI and reported a multivariable-adjusted relative risk (RR) for the association between AKI and cardiovascular mortality, major cardiovascular events, and disease-specific events: congestive heart failure, acute myocardial infarction, and stroke. Twenty-five studies involving 254,408 adults (55,150 with AKI) were included. AKI associated with an 86% and a 38% increased risk of cardiovascular mortality and major cardiovascular events, respectively ([RR 1.86; 95% confidence interval (95% CI), 1.72 to 2.01] and [RR 1.38; 95% CI, 1.23 to 1.55], respectively). For disease-specific events, AKI associated with a 58% increased risk of heart failure (RR 1.58; 95% CI, 1.46 to 1.72) and a 40% increased risk of acute myocardial infarction (RR 1.40; 95% CI, 1.23 to 1.59). The elevated risk of heart failure and acute myocardial infarction persisted in subgroup analyses on the basis of AKI severity and the proportion of adults with baseline ischemic heart disease. Finally, AKI was associated with a 15% increased risk of stroke (RR 1.15; 95% CI, 1.03 to 1.28). In conclusion, AKI associates with an elevated risk of cardiovascular mortality and major cardiovascular events, particularly heart failure and acute myocardial infarction.10.1681/ASN.2016010105Mon, 13 Jun 2016 11:37:25 GMT-07:00AKI and Long-Term Risk for Cardiovascular Events and MortalityAKI associates with increased long-term risk of mortality, but the prognostic significance of AKI in terms of long-term cardiovascular disease remains unconfirmed. We conducted a systematic review and meta-analysis to assess whether AKI associates with long-term cardiovascular disease. We included cohort studies that examined adults with and without AKI and reported a multivariable-adjusted relative risk (RR) for the association between AKI and cardiovascular mortality, major cardiovascular events, and disease-specific events: congestive heart failure, acute myocardial infarction, and stroke. Twenty-five studies involving 254,408 adults (55,150 with AKI) were included. AKI associated with an 86% and a 38% increased risk of cardiovascular mortality and major cardiovascular events, respectively ([RR 1.86; 95% confidence interval (95% CI), 1.72 to 2.01] and [RR 1.38; 95% CI, 1.23 to 1.55], respectively). For disease-specific events, AKI associated with a 58% increased risk of heart failure (RR 1.58; 95% CI, 1.46 to 1.72) and a 40% increased risk of acute myocardial infarction (RR 1.40; 95% CI, 1.23 to 1.59). The elevated risk of heart failure and acute myocardial infarction persisted in subgroup analyses on the basis of AKI severity and the proportion of adults with baseline ischemic heart disease. Finally, AKI was associated with a 15% increased risk of stroke (RR 1.15; 95% CI, 1.03 to 1.28). In conclusion, AKI associates with an elevated risk of cardiovascular mortality and major cardiovascular events, particularly heart failure and acute myocardial infarction.Odutayo, AyodeleWong, Christopher X.Farkouh, MichaelAltman, Douglas G.Hopewell, SallyEmdin, Connor A.Hunn, Benjamin H.2016-06-13T11:37:25-07:00doi:10.1681/ASN.2016010105hwp:resource-id:jnephrol;28/1/377American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cardiovascular disease, Stroke, congestive heart failure, Ischemic Heart DiseaseMeta-AnalysisMeta-Analysisresearch-article20162017-01-01January 201710.1681/ASN.20160101051046-66731533-34502016-06-13T11:37:25-07:002017-01Journal of the American Society of NephrologyMeta-Analysis281377387
- Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary TractCongenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management.10.1681/ASN.2015080962Thu, 05 May 2016 07:03:12 GMT-07:00Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary TractCongenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management.Vivante, AsafHwang, Daw-YangKohl, StefanChen, JingShril, ShirleeSchulz, Julianvan der Ven, AmelieDaouk, GhalebSoliman, Neveen A.Kumar, Aravind SelvinSenguttuvan, PrabhaKehinde, Elijah O.Tasic, VeliborHildebrandt, Friedhelm2016-05-05T07:03:12-07:00doi:10.1681/ASN.2015080962hwp:resource-id:jnephrol;28/1/69American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCAKUT, monogenic disease, WESBrief CommunicationsBrief Communicationsbrief-report20162017-01-01January 201710.1681/ASN.20150809621046-66731533-34502016-05-05T07:03:12-07:002017-01Journal of the American Society of NephrologyBrief Communications2816975
- In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter AbundanceDistal tubular sodium retention is a potent driver of hypertension, and the thiazide–sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1–related, proline alanine–rich kinase (SPAK) in human urinary exosomes. We isolated exosomes from daily urine samples in 25 patients undergoing fludrocortisone suppression testing (100 μg every 6 hours for 4 days) to diagnose or exclude primary aldosteronism. Over the course of the test, NCC levels increased 3.68-fold (P<0.01) and pNCC levels increased 2.73-fold (P<0.01) relative to baseline. The ratio of pNCC/NCC dropped by 48% (P<0.01). The abundance of WNK4 increased 3.23-fold (P<0.01), but SPAK abundance did not change significantly (P=0.14). Plasma potassium concentration strongly and negatively correlated with pNCC, NCC, and WNK4 abundance (P<0.001 for all). This study shows that, in humans, mineralocorticoid administration is associated with a rapid increase in abundance of NCC and pNCC, possibly via the WNK pathway. These effects may be driven by changes in plasma potassium.10.1681/ASN.2015111221Tue, 05 Jul 2016 08:11:17 GMT-07:00In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter AbundanceDistal tubular sodium retention is a potent driver of hypertension, and the thiazide–sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1–related, proline alanine–rich kinase (SPAK) in human urinary exosomes. We isolated exosomes from daily urine samples in 25 patients undergoing fludrocortisone suppression testing (100 μg every 6 hours for 4 days) to diagnose or exclude primary aldosteronism. Over the course of the test, NCC levels increased 3.68-fold (P<0.01) and pNCC levels increased 2.73-fold (P<0.01) relative to baseline. The ratio of pNCC/NCC dropped by 48% (P<0.01). The abundance of WNK4 increased 3.23-fold (P<0.01), but SPAK abundance did not change significantly (P=0.14). Plasma potassium concentration strongly and negatively correlated with pNCC, NCC, and WNK4 abundance (P<0.001 for all). This study shows that, in humans, mineralocorticoid administration is associated with a rapid increase in abundance of NCC and pNCC, possibly via the WNK pathway. These effects may be driven by changes in plasma potassium.Wolley, Martin J.Wu, AihuaXu, ShengxinGordon, Richard D.Fenton, Robert A.Stowasser, Michael2016-07-05T08:11:17-07:00doi:10.1681/ASN.2015111221hwp:resource-id:jnephrol;28/1/56American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyNCC, aldosterone, Na transport, ExosomesBrief CommunicationsBrief Communicationsbrief-report20162017-01-01January 201710.1681/ASN.20151112211046-66731533-34502016-07-05T08:11:17-07:002017-01Journal of the American Society of NephrologyBrief Communications2815663
- Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD–Related Systemic InflammationCKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3–deficient mice with Alport syndrome–related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen–presenting cells, CD4 and CD8 T cells, and Th17– or IFNγ–producing T cells in the spleen as well as regulatory T cell suppression. CKD–related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD–related systemic inflammation and its consequences.10.1681/ASN.2015111285Thu, 05 May 2016 07:03:13 GMT-07:00Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD–Related Systemic InflammationCKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3–deficient mice with Alport syndrome–related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen–presenting cells, CD4 and CD8 T cells, and Th17– or IFNγ–producing T cells in the spleen as well as regulatory T cell suppression. CKD–related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD–related systemic inflammation and its consequences.Andersen, KirstinKesper, Marie SophieMarschner, Julian A.Konrad, LukasRyu, MiKumar VR, SanthoshKulkarni, Onkar P.Mulay, Shrikant R.Romoli, SimoneDemleitner, JanaSchiller, PatrickDietrich, AlexanderMüller, SusannaGross, OliverRuscheweyh, Hans-JoachimHuson, Daniel H.Stecher, BärbelAnders, Hans-Joachim2016-05-05T07:03:13-07:00doi:10.1681/ASN.2015111285hwp:resource-id:jnephrol;28/1/76American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyinflammation, chronic kidney disease, microbiotaBrief CommunicationsBrief Communicationsbrief-report20162017-01-01January 201710.1681/ASN.20151112851046-66731533-34502016-05-05T07:03:13-07:002017-01Journal of the American Society of NephrologyBrief Communications2817683
- Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate SecretionPatients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6–mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr−/− mice in Ussing chambers and measured transcellular secretion of [14C]oxalate. Intestinal tissue isolated from Cftr−/− mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr−/− tissue. Compared with wild-type mice, Cftr−/− mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6–mediated Cl−–oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr−/− mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis.10.1681/ASN.2016030279Thu, 16 Jun 2016 07:16:32 GMT-07:00Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate SecretionPatients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6–mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr−/− mice in Ussing chambers and measured transcellular secretion of [14C]oxalate. Intestinal tissue isolated from Cftr−/− mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr−/− tissue. Compared with wild-type mice, Cftr−/− mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6–mediated Cl−–oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr−/− mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis.Knauf, FelixThomson, Robert B.Heneghan, John F.Jiang, ZhirongAdebamiro, AdedotunThomson, Claire L.Barone, ChristinaAsplin, John R.Egan, Marie E.Alper, Seth L.Aronson, Peter S.2016-06-16T07:16:32-07:00doi:10.1681/ASN.2016030279hwp:resource-id:jnephrol;28/1/242American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney stones, Cystic fibrosis, Cell & Transport PhysiologyBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20160302791046-66731533-34502016-06-16T07:16:32-07:002017-01Journal of the American Society of NephrologyBasic Research281242249
- IgA1 Glycosylation Is Heritable in Healthy TwinsIgA nephropathy (IgAN) is the most common form of primary GN and an important cause of kidney failure. Characteristically, patients with IgAN have increased serum levels of undergalactosylated IgA1 (gd-IgA1). To assess the degree to which serum gd-IgA1 levels are genetically determined in healthy individuals, we determined serum IgA and gd-IgA1 levels by ELISA in a sample of 148 healthy female twins, including 27 monozygotic and 47 dizygotic pairs. Using the classic twin model, we found the heritability of serum gd-IgA1 and IgA levels to be 80% (95% confidence interval, 66% to 89%) and 46% (95% confidence interval, 15% to 69%), respectively. These data indicate that serum gd-IgA1 levels are highly heritable. Elucidating the genetic basis of this heritability will be important in understanding the pathogenesis of IgAN.10.1681/ASN.2016020184Thu, 16 Jun 2016 07:16:32 GMT-07:00IgA1 Glycosylation Is Heritable in Healthy TwinsIgA nephropathy (IgAN) is the most common form of primary GN and an important cause of kidney failure. Characteristically, patients with IgAN have increased serum levels of undergalactosylated IgA1 (gd-IgA1). To assess the degree to which serum gd-IgA1 levels are genetically determined in healthy individuals, we determined serum IgA and gd-IgA1 levels by ELISA in a sample of 148 healthy female twins, including 27 monozygotic and 47 dizygotic pairs. Using the classic twin model, we found the heritability of serum gd-IgA1 and IgA levels to be 80% (95% confidence interval, 66% to 89%) and 46% (95% confidence interval, 15% to 69%), respectively. These data indicate that serum gd-IgA1 levels are highly heritable. Elucidating the genetic basis of this heritability will be important in understanding the pathogenesis of IgAN.Lomax-Browne, Hannah J.Visconti, AlessiaPusey, Charles D.Cook, H. TerenceSpector, Tim D.Pickering, Matthew C.Falchi, Mario2016-06-16T07:16:32-07:00doi:10.1681/ASN.2016020184hwp:resource-id:jnephrol;28/1/64American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, human genetics, gd-IgA1, glycosylationBrief CommunicationsBrief Communicationsbrief-report20162017-01-01January 201710.1681/ASN.20160201841046-66731533-34502016-06-16T07:16:32-07:002017-01Journal of the American Society of NephrologyBrief Communications2816468
- Krüppel–Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation MarkersPodocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores podocyte differentiation markers and normal ultrastructure and improves cell survival in murine podocytes. We previously determined that Krüppel–like factor 15 (KLF15), a kidney–enriched zinc finger transcription factor, is required for restoring podocyte differentiation markers in mice and human podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15. In three independent proteinuric murine models, podocyte-specific loss of Klf15 abrogated dexamethasone–induced podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human podocytes. Finally, the level of KLF15 expression in the podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the podocyte.10.1681/ASN.2015060672Fri, 10 Jun 2016 06:45:18 GMT-07:00Krüppel–Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation MarkersPodocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores podocyte differentiation markers and normal ultrastructure and improves cell survival in murine podocytes. We previously determined that Krüppel–like factor 15 (KLF15), a kidney–enriched zinc finger transcription factor, is required for restoring podocyte differentiation markers in mice and human podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15. In three independent proteinuric murine models, podocyte-specific loss of Klf15 abrogated dexamethasone–induced podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human podocytes. Finally, the level of KLF15 expression in the podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the podocyte.Mallipattu, Sandeep K.Guo, YiqingRevelo, Monica P.Roa-Peña, LuciaMiller, TimothyLing, JasonShankland, Stuart J.Bialkowska, Agnieszka B.Ly, VictoriaEstrada, ChelseaJain, Mukesh K.Lu, YuanMa’ayan, AviMehrotra, AnitaYacoub, RabiNord, Edward P.Woroniecki, Robert P.Yang, Vincent W.He, John C.2016-06-10T06:45:18-07:00doi:10.1681/ASN.2015060672hwp:resource-id:jnephrol;28/1/166American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, glucocorticoid, focal segmental glomerulosclerosis, minimal change diseaseBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150606721046-66731533-34502016-06-10T06:45:18-07:002017-01Journal of the American Society of NephrologyBasic Research281166184
- Corticosteroids in IgA Nephropathy: Lessons from Recent StudiesIgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to ESRD. The immune and autoimmune responses that characterize IgAN indicate a potential benefit for corticosteroids. The 2012 Kidney Disease Improving Global Outcome (KDIGO) guidelines suggest giving corticosteroids to patients with rather preserved renal function (GFR>50 ml/min per 1.73 m2) and persistent proteinuria >1 g/d, despite 3–6 months of optimized supportive care with renin-angiotensin system blockers. However, the evidence supporting this guideline was considered of low quality. More recent results from large cohort studies and randomized, controlled trials have provided conflicting messages about the benefits of corticosteroid treatment over supportive care alone, mostly involving optimized renin-angiotensin system blockade, which might generate further uncertainty in the therapeutic choice. Overall, these results indicate that corticosteroids are a powerful tool for treating patients with IgAN; however, treatment success is not universal and mostly occurs in patients who are highly proteinuric with early CKD. In patients with advanced CKD, the side effects of corticosteroids increase, and the renal protection decreases. This brief review aimed at integrating the findings of these recently published reports to provide balanced advice for clinicians as well as suggestions for future trials.10.1681/ASN.2016060647Mon, 26 Sep 2016 07:21:16 GMT-07:00Corticosteroids in IgA Nephropathy: Lessons from Recent StudiesIgA nephropathy (IgAN) is a common chronic glomerular disease that, in most patients, slowly progresses to ESRD. The immune and autoimmune responses that characterize IgAN indicate a potential benefit for corticosteroids. The 2012 Kidney Disease Improving Global Outcome (KDIGO) guidelines suggest giving corticosteroids to patients with rather preserved renal function (GFR>50 ml/min per 1.73 m2) and persistent proteinuria >1 g/d, despite 3–6 months of optimized supportive care with renin-angiotensin system blockers. However, the evidence supporting this guideline was considered of low quality. More recent results from large cohort studies and randomized, controlled trials have provided conflicting messages about the benefits of corticosteroid treatment over supportive care alone, mostly involving optimized renin-angiotensin system blockade, which might generate further uncertainty in the therapeutic choice. Overall, these results indicate that corticosteroids are a powerful tool for treating patients with IgAN; however, treatment success is not universal and mostly occurs in patients who are highly proteinuric with early CKD. In patients with advanced CKD, the side effects of corticosteroids increase, and the renal protection decreases. This brief review aimed at integrating the findings of these recently published reports to provide balanced advice for clinicians as well as suggestions for future trials.Coppo, Rosanna2016-09-26T07:21:16-07:00doi:10.1681/ASN.2016060647hwp:resource-id:jnephrol;28/1/25American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, progression of chronic renal failure, glomerular disease, immunosuppression, risk factorsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162017-01-01January 201710.1681/ASN.20160606471046-66731533-34502016-09-26T07:21:16-07:002017-01Journal of the American Society of NephrologyUp Front Matters2812533
- The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal NephronChloride transport by the renal tubule is critical for blood pressure (BP), acid-base, and potassium homeostasis. Chloride uptake from the urinary fluid is mediated by various apical transporters, whereas basolateral chloride exit is thought to be mediated by ClC-Ka/K1 and ClC-Kb/K2, two chloride channels from the ClC family, or by KCl cotransporters from the SLC12 gene family. Nevertheless, the localization and role of ClC-K channels is not fully resolved. Because inactivating mutations in ClC-Kb/K2 cause Bartter syndrome, a disease that mimics the effects of the loop diuretic furosemide, ClC-Kb/K2 is assumed to have a critical role in salt handling by the thick ascending limb. To dissect the role of this channel in detail, we generated a mouse model with a targeted disruption of the murine ortholog ClC-K2. Mutant mice developed a Bartter syndrome phenotype, characterized by renal salt loss, marked hypokalemia, and metabolic alkalosis. Patch-clamp analysis of tubules isolated from knockout (KO) mice suggested that ClC-K2 is the main basolateral chloride channel in the thick ascending limb and in the aldosterone-sensitive distal nephron. Accordingly, ClC-K2 KO mice did not exhibit the natriuretic response to furosemide and exhibited a severely blunted response to thiazide. We conclude that ClC-Kb/K2 is critical for salt absorption not only by the thick ascending limb, but also by the distal convoluted tubule.10.1681/ASN.2016010085Wed, 22 Jun 2016 07:02:42 GMT-07:00The ClC-K2 Chloride Channel Is Critical for Salt Handling in the Distal NephronChloride transport by the renal tubule is critical for blood pressure (BP), acid-base, and potassium homeostasis. Chloride uptake from the urinary fluid is mediated by various apical transporters, whereas basolateral chloride exit is thought to be mediated by ClC-Ka/K1 and ClC-Kb/K2, two chloride channels from the ClC family, or by KCl cotransporters from the SLC12 gene family. Nevertheless, the localization and role of ClC-K channels is not fully resolved. Because inactivating mutations in ClC-Kb/K2 cause Bartter syndrome, a disease that mimics the effects of the loop diuretic furosemide, ClC-Kb/K2 is assumed to have a critical role in salt handling by the thick ascending limb. To dissect the role of this channel in detail, we generated a mouse model with a targeted disruption of the murine ortholog ClC-K2. Mutant mice developed a Bartter syndrome phenotype, characterized by renal salt loss, marked hypokalemia, and metabolic alkalosis. Patch-clamp analysis of tubules isolated from knockout (KO) mice suggested that ClC-K2 is the main basolateral chloride channel in the thick ascending limb and in the aldosterone-sensitive distal nephron. Accordingly, ClC-K2 KO mice did not exhibit the natriuretic response to furosemide and exhibited a severely blunted response to thiazide. We conclude that ClC-Kb/K2 is critical for salt absorption not only by the thick ascending limb, but also by the distal convoluted tubule.Hennings, J. ChristopherAndrini, OlgaPicard, NicolasPaulais, MarcHuebner, Antje K.Cayuqueo, Irma Karen LopezBignon, YohanKeck, MathildeCornière, NicolasBöhm, DavidJentsch, Thomas J.Chambrey, RégineTeulon, JacquesHübner, Christian A.Eladari, Dominique2016-06-22T07:02:42-07:00doi:10.1681/ASN.2016010085hwp:resource-id:jnephrol;28/1/209American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychloride channels, Bartter-s syndrome, ion transport, transgenic mouseBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20160100851046-66731533-34502016-06-22T07:02:42-07:002017-01Journal of the American Society of NephrologyBasic Research281209217
- Specialized Regulatory T Cells for Optimal Suppression of T Cell Responses in GN10.1681/ASN.2016070785Wed, 28 Sep 2016 11:23:23 GMT-07:00Specialized Regulatory T Cells for Optimal Suppression of T Cell Responses in GNEller, KathrinRosenkranz, Alexander R.2016-09-28T11:23:23-07:00doi:10.1681/ASN.2016070785hwp:resource-id:jnephrol;28/1/1American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, Immunology and pathology, Cell transferUp Front MattersEditorialsUp Front MattersEditorialseditorial20162017-01-01January 201710.1681/ASN.20160707851046-66731533-34502016-09-28T11:23:23-07:002017-01Journal of the American Society of NephrologyUp Front Matters281111852196
- mTOR: Pumping Nutrients into Tubules10.1681/ASN.2016080924Thu, 27 Oct 2016 07:42:49 GMT-07:00mTOR: Pumping Nutrients into TubulesInoki, Ken2016-10-27T07:42:49-07:00doi:10.1681/ASN.2016080924hwp:resource-id:jnephrol;28/1/3American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyendocytosis, kidney tubule, renal proximal tubule cell, albuminuria, tubule cells, signalingUp Front MattersEditorialsUp Front MattersEditorialseditorial20162017-01-01January 201710.1681/ASN.20160809241046-66731533-34502016-10-27T07:42:49-07:002017-01Journal of the American Society of NephrologyUp Front Matters281132305241
- Is Dietary Red Meat Kidney Toxic?10.1681/ASN.2016060664Mon, 22 Aug 2016 05:33:23 GMT-07:00Is Dietary Red Meat Kidney Toxic?Goraya, NimritWesson, Donald E.2016-08-22T05:33:23-07:00doi:10.1681/ASN.2016060664hwp:resource-id:jnephrol;28/1/5American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiet, CKD, ESRDUp Front MattersEditorialsUp Front MattersEditorialseditorial20162017-01-01January 201710.1681/ASN.20160606641046-66731533-34502016-08-22T05:33:23-07:002017-01Journal of the American Society of NephrologyUp Front Matters281153047312
- Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis PatientsCardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3–6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 μM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.10.1681/ASN.2016030374Tue, 19 Jul 2016 08:11:46 GMT-07:00Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis PatientsCardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3–6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 μM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.Shafi, TariqPowe, Neil R.Meyer, Timothy W.Hwang, SeungyoungHai, XinMelamed, Michal L.Banerjee, TanushreeCoresh, JosefHostetter, Thomas H.2016-07-19T08:11:46-07:00doi:10.1681/ASN.2016030374hwp:resource-id:jnephrol;28/1/321American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular events, hemodialysis, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20162017-01-01January 201710.1681/ASN.20160303741046-66731533-34502016-07-19T08:11:46-07:002017-01Journal of the American Society of NephrologyClinical Epidemiology281321331
- Red Meat Intake and Risk of ESRDRandomized controlled trials suggest that protein restriction may retard the progression of CKD toward ESRD. However, the effects of dietary protein intake level and the food sources of dietary protein on the risk of ESRD in the general population remain unclear. We investigated these effects in the Singapore Chinese Health Study, a prospective population-based cohort that recruited 63,257 Chinese adults aged 45–74 years from 1993 to 1998. We collected habitual diet information via a validated semiquantitative food frequency questionnaire and identified ESRD via record linkage with a nationwide registry. In all, 951 cases of ESRD occurred over a mean follow-up of 15.5 years. Regarding total protein intake, compared with the lowest quartile, the three higher quartiles combined had a hazard ratio for ESRD of 1.24 (95% confidence interval [95% CI], 1.05 to 1.46), but the dose-dependent association across the quartiles was not statistically significant (Ptrend=0.16). Red meat intake strongly associated with ESRD risk in a dose-dependent manner (hazard ratio for highest quartile versus lowest quartile,1.40 [95% CI, 1.15 to 1.71; Ptrend<0.001]). Intake of poultry, fish, eggs, or dairy products did not associate with risk of ESRD. In substitution analysis, replacing one serving of red meat with other food sources of protein associated with a maximum relative risk reduction of 62.4% (95% CI, 33.1 to 78.9; P<0.01). Our study shows that red meat intake may increase the risk of ESRD in the general population and substituting alternative sources of protein may reduce the incidence of ESRD.10.1681/ASN.2016030248Thu, 14 Jul 2016 05:46:36 GMT-07:00Red Meat Intake and Risk of ESRDRandomized controlled trials suggest that protein restriction may retard the progression of CKD toward ESRD. However, the effects of dietary protein intake level and the food sources of dietary protein on the risk of ESRD in the general population remain unclear. We investigated these effects in the Singapore Chinese Health Study, a prospective population-based cohort that recruited 63,257 Chinese adults aged 45–74 years from 1993 to 1998. We collected habitual diet information via a validated semiquantitative food frequency questionnaire and identified ESRD via record linkage with a nationwide registry. In all, 951 cases of ESRD occurred over a mean follow-up of 15.5 years. Regarding total protein intake, compared with the lowest quartile, the three higher quartiles combined had a hazard ratio for ESRD of 1.24 (95% confidence interval [95% CI], 1.05 to 1.46), but the dose-dependent association across the quartiles was not statistically significant (Ptrend=0.16). Red meat intake strongly associated with ESRD risk in a dose-dependent manner (hazard ratio for highest quartile versus lowest quartile,1.40 [95% CI, 1.15 to 1.71; Ptrend<0.001]). Intake of poultry, fish, eggs, or dairy products did not associate with risk of ESRD. In substitution analysis, replacing one serving of red meat with other food sources of protein associated with a maximum relative risk reduction of 62.4% (95% CI, 33.1 to 78.9; P<0.01). Our study shows that red meat intake may increase the risk of ESRD in the general population and substituting alternative sources of protein may reduce the incidence of ESRD.Lew, Quan-Lan JasmineJafar, Tazeen HasanKoh, Hiromi Wai LingJin, AizhenChow, Khuan YewYuan, Jian-MinKoh, Woon-Puay2016-07-14T05:46:36-07:00doi:10.1681/ASN.2016030248hwp:resource-id:jnephrol;28/1/304American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, diet, red meat, protein, population-based studyClinical EpidemiologyClinical Epidemiologyresearch-article20162017-01-01January 201710.1681/ASN.20160302481046-66731533-34502016-07-14T05:46:36-07:002017-01Journal of the American Society of NephrologyClinical Epidemiology281130453127
- σ1-Receptor Agonism Protects against Renal Ischemia-Reperfusion InjuryMechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role of σ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high–affinity σ1–receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused the σ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked by σ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney, σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time– and isoform–specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two–photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by the σ1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury, σ1-receptor agonists improved postischemic survival and renal function via activation of Akt–mediated nitric oxide signaling in the kidney. Thus, σ1-receptor activation might provide a therapeutic option for renoprotective therapy.10.1681/ASN.2015070772Thu, 07 Apr 2016 06:41:14 GMT-07:00σ1-Receptor Agonism Protects against Renal Ischemia-Reperfusion InjuryMechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role of σ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high–affinity σ1–receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused the σ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked by σ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney, σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time– and isoform–specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two–photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by the σ1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury, σ1-receptor agonists improved postischemic survival and renal function via activation of Akt–mediated nitric oxide signaling in the kidney. Thus, σ1-receptor activation might provide a therapeutic option for renoprotective therapy.Hosszu, AdamAntal, ZsuzsannaLenart, LillaHodrea, JuditKoszegi, SandorBalogh, Dora B.Banki, Nora F.Wagner, LaszloDenes, AdamHamar, PeterDegrell, PeterVannay, AdamSzabo, Attila J.Fekete, Andrea2016-04-07T06:41:14-07:00doi:10.1681/ASN.2015070772hwp:resource-id:jnephrol;28/1/152American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney, ischemia-reperfusion, nitric oxide, Sigma-1 receptorBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150707721046-66731533-34502016-04-07T06:41:14-07:002017-01Journal of the American Society of NephrologyBasic Research281152165
- Inducible Expression of Claudin-1 in Glomerular Podocytes Generates Aberrant Tight Junctions and Proteinuria through Slit Diaphragm DestabilizationThe tight junction (TJ) has a key role in regulating paracellular permeability to water and solutes in the kidney. However, the functional role of the TJ in the glomerular podocyte is unclear. In diabetic nephropathy, the gene expression of claudins, in particular claudin-1, is markedly upregulated in the podocyte, accompanied by a tighter filtration slit and the appearance of TJ-like structures between the foot processes. However, there is no definitive evidence to show slit diaphragm (SD) to TJ transition in vivo. Here, we report the generation of a claudin-1 transgenic mouse model with doxycycline-inducible transgene expression specifically in the glomerular podocyte. We found that induction of claudin-1 gene expression in mature podocytes caused profound proteinuria, and with deep-etching freeze-fracture electron microscopy, we resolved the ultrastructural change in the claudin-1–induced SD-TJ transition. Notably, immunolabeling of kidney proteins revealed that claudin-1 induction destabilized the SD protein complex in podocytes, with significantly reduced expression and altered localization of nephrin and podocin proteins. Mechanistically, claudin-1 interacted with both nephrin and podocin through cis- and trans-associations in cultured cells. Furthermore, the rat puromycin aminonucleoside nephrosis model, previously suspected of undergoing SD-TJ transition, exhibited upregulated expression levels of claudin-1 mRNA and protein in podocytes. Together, our data attest to the novel concept that claudins and the TJ have essential roles in podocyte pathophysiology and that claudin interactions with SD components may facilitate SD-TJ transition that appears to be common to many nephrotic conditions.10.1681/ASN.2015121324Thu, 05 May 2016 07:03:11 GMT-07:00Inducible Expression of Claudin-1 in Glomerular Podocytes Generates Aberrant Tight Junctions and Proteinuria through Slit Diaphragm DestabilizationThe tight junction (TJ) has a key role in regulating paracellular permeability to water and solutes in the kidney. However, the functional role of the TJ in the glomerular podocyte is unclear. In diabetic nephropathy, the gene expression of claudins, in particular claudin-1, is markedly upregulated in the podocyte, accompanied by a tighter filtration slit and the appearance of TJ-like structures between the foot processes. However, there is no definitive evidence to show slit diaphragm (SD) to TJ transition in vivo. Here, we report the generation of a claudin-1 transgenic mouse model with doxycycline-inducible transgene expression specifically in the glomerular podocyte. We found that induction of claudin-1 gene expression in mature podocytes caused profound proteinuria, and with deep-etching freeze-fracture electron microscopy, we resolved the ultrastructural change in the claudin-1–induced SD-TJ transition. Notably, immunolabeling of kidney proteins revealed that claudin-1 induction destabilized the SD protein complex in podocytes, with significantly reduced expression and altered localization of nephrin and podocin proteins. Mechanistically, claudin-1 interacted with both nephrin and podocin through cis- and trans-associations in cultured cells. Furthermore, the rat puromycin aminonucleoside nephrosis model, previously suspected of undergoing SD-TJ transition, exhibited upregulated expression levels of claudin-1 mRNA and protein in podocytes. Together, our data attest to the novel concept that claudins and the TJ have essential roles in podocyte pathophysiology and that claudin interactions with SD components may facilitate SD-TJ transition that appears to be common to many nephrotic conditions.Gong, YongfengSunq, AbbyRoth, Robyn A.Hou, Jianghui2016-05-05T07:03:11-07:00doi:10.1681/ASN.2015121324hwp:resource-id:jnephrol;28/1/106American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytight junction, slit diaphragm, claudin, proteinuria, protein interaction, podocyteBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20151213241046-66731533-34502016-05-05T07:03:11-07:002017-01Journal of the American Society of NephrologyBasic Research281106117
- Genome-Wide Gene Expression Profiling of Randall’s Plaques in Calcium Oxalate Stone FormersRandall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.10.1681/ASN.2015111271Mon, 13 Jun 2016 11:37:26 GMT-07:00Genome-Wide Gene Expression Profiling of Randall’s Plaques in Calcium Oxalate Stone FormersRandall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.Taguchi, KazumiHamamoto, ShuzoOkada, AtsushiUnno, ReiKamisawa, HideyukiNaiki, TakuAndo, RyosukeMizuno, KentaroKawai, NoriyasuTozawa, KeiichiKohri, KenjiroYasui, Takahiro2016-06-13T11:37:26-07:00doi:10.1681/ASN.2015111271hwp:resource-id:jnephrol;28/1/333American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney stone disease, renal papilla, Randall’s plaque, calcium oxalate, microarray, ingenuity pathway analysisClinical ResearchClinical Researchresearch-article20162017-01-01January 201710.1681/ASN.20151112711046-66731533-34502016-06-13T11:37:26-07:002017-01Journal of the American Society of NephrologyClinical Research281333347
- The Joubert Syndrome Protein Inpp5e Controls Ciliogenesis by Regulating Phosphoinositides at the Apical MembranePhosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear. Here, we utilized an in vivo vertebrate model of renal cystogenesis to show that Inpp5e enzymatic activity at the apical membrane directs apical docking of basal bodies in renal epithelia. Knockdown or knockout of inpp5e led to ciliogenesis defects and cystic kidneys in zebrafish. Furthermore, knockdown of inpp5e in embryos led to defects in cell polarity, cortical organization of F-actin, and apical segregation of PtdIns(4,5)P2 and PtdIns(3,4,5)P3. Knockdown of the ezrin gene, which encodes an ezrin/radixin/moesin (ERM) protein that crosslinks PtdIns(4,5)P2 and F-actin, phenocopied inpp5e knockdowns. Notably, overexpression of the ezrin gene rescued inpp5e morphants. Finally, treatment with the PI 3-kinase inhibitor LY294002, which decreases PtdIns(3,4,5)P3 levels, rescued the cellular, phenotypic, and renal functional defects in inpp5e-knockdown embryos. Together, our data indicate that Inpp5e functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns(3,4,5)P3 and subsequently stabilizing PtdIns(4,5)P2 and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies.10.1681/ASN.2015080906Fri, 08 Jul 2016 06:48:41 GMT-07:00The Joubert Syndrome Protein Inpp5e Controls Ciliogenesis by Regulating Phosphoinositides at the Apical MembranePhosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear. Here, we utilized an in vivo vertebrate model of renal cystogenesis to show that Inpp5e enzymatic activity at the apical membrane directs apical docking of basal bodies in renal epithelia. Knockdown or knockout of inpp5e led to ciliogenesis defects and cystic kidneys in zebrafish. Furthermore, knockdown of inpp5e in embryos led to defects in cell polarity, cortical organization of F-actin, and apical segregation of PtdIns(4,5)P2 and PtdIns(3,4,5)P3. Knockdown of the ezrin gene, which encodes an ezrin/radixin/moesin (ERM) protein that crosslinks PtdIns(4,5)P2 and F-actin, phenocopied inpp5e knockdowns. Notably, overexpression of the ezrin gene rescued inpp5e morphants. Finally, treatment with the PI 3-kinase inhibitor LY294002, which decreases PtdIns(3,4,5)P3 levels, rescued the cellular, phenotypic, and renal functional defects in inpp5e-knockdown embryos. Together, our data indicate that Inpp5e functions as a key regulator of cell polarity in the renal epithelia, by inhibiting PtdIns(3,4,5)P3 and subsequently stabilizing PtdIns(4,5)P2 and recruiting Ezrin, F-actin, and basal bodies to the apical membrane, and suggest a possible novel approach for treating human ciliopathies.Xu, WenyanJin, MiaomiaoHu, RuikunWang, HongZhang, FanYuan, ShiaulouCao, Ying2016-07-08T06:48:41-07:00doi:10.1681/ASN.2015080906hwp:resource-id:jnephrol;28/1/118American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycilia, phosphoinositides, polycystic kidney disease, Inpp5eBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150809061046-66731533-34502016-07-08T06:48:41-07:002017-01Journal of the American Society of NephrologyBasic Research281118129
- The Substantial Loss of Nephrons in Healthy Human Kidneys with AgingNephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18–29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70–75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.10.1681/ASN.2016020154Fri, 08 Jul 2016 06:48:43 GMT-07:00The Substantial Loss of Nephrons in Healthy Human Kidneys with AgingNephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18–29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70–75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons.Denic, AleksandarLieske, John C.Chakkera, Harini A.Poggio, Emilio D.Alexander, Mariam P.Singh, PrinceKremers, Walter K.Lerman, Lilach O.Rule, Andrew D.2016-07-08T06:48:43-07:00doi:10.1681/ASN.2016020154hwp:resource-id:jnephrol;28/1/313American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyNephron number, Nephron loss, Aging, kidneyClinical EpidemiologyClinical Epidemiologyresearch-article20162017-01-01January 201710.1681/ASN.20160201541046-66731533-34502016-07-08T06:48:43-07:002017-01Journal of the American Society of NephrologyClinical Epidemiology281313320
- Premature T Cell Senescence in Pediatric CKDAn individual’s immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+ T cells, reduction in the proportion of naïve T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation.10.1681/ASN.2016010053Wed, 13 Jul 2016 05:41:07 GMT-07:00Premature T Cell Senescence in Pediatric CKDAn individual’s immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+ T cells, reduction in the proportion of naïve T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation.George, Roshan P.Mehta, Aneesh K.Perez, Sebastian D.Winterberg, PamelaCheeseman, JenniferJohnson, BrandiKwun, JeanMonday, StephanieStempora, LindaWarshaw, BarryKirk, Allan D.2016-07-13T05:41:07-07:00doi:10.1681/ASN.2016010053hwp:resource-id:jnephrol;28/1/359American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyT cell maturation, Chronic Kidney Disease, Dialysis, pediatric kidney transplantationClinical ResearchClinical Researchresearch-article20162017-01-01January 201710.1681/ASN.20160100531046-66731533-34502016-07-13T05:41:07-07:002017-01Journal of the American Society of NephrologyClinical Research281359367
- Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid–Induced AKIAKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)–induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor–interacting protein kinase 3 (RIPK3) and mixed lineage domain–like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI.10.1681/ASN.2015121376Mon, 27 Jun 2016 08:30:52 GMT-07:00Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid–Induced AKIAKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)–induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor–interacting protein kinase 3 (RIPK3) and mixed lineage domain–like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI.Martin-Sanchez, DiegoRuiz-Andres, OlgaPoveda, JonayCarrasco, SusanaCannata-Ortiz, PabloSanchez-Niño, Maria D.Ruiz Ortega, MartaEgido, JesusLinkermann, AndreasOrtiz, AlbertoSanz, Ana B.2016-06-27T08:30:52-07:00doi:10.1681/ASN.2015121376hwp:resource-id:jnephrol;28/1/218American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, renal proximal tubule cell, inflammation, cell death, ferroptosis, IL-33Basic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20151213761046-66731533-34502016-06-27T08:30:52-07:002017-01Journal of the American Society of NephrologyBasic Research281218229
- Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic EffectsSodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6–8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 ml/min per 1.73 m2 per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m2 per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m2 per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P<0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.10.1681/ASN.2016030278Thu, 18 Aug 2016 08:16:26 GMT-07:00Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic EffectsSodium-glucose cotransporter 2 inhibition with canagliflozin decreases HbA1c, body weight, BP, and albuminuria, implying that canagliflozin confers renoprotection. We determined whether canagliflozin decreases albuminuria and reduces renal function decline independently of its glycemic effects in a secondary analysis of a clinical trial in 1450 patients with type 2 diabetes receiving metformin and randomly assigned to either once-daily canagliflozin 100 mg, canagliflozin 300 mg, or glimepiride uptitrated to 6–8 mg. End points were annual change in eGFR and albuminuria over 2 years of follow-up. Glimepiride, canagliflozin 100 mg, and canagliflozin 300 mg groups had eGFR declines of 3.3 ml/min per 1.73 m2 per year (95% confidence interval [95% CI], 2.8 to 3.8), 0.5 ml/min per 1.73 m2 per year (95% CI, 0.0 to 1.0), and 0.9 ml/min per 1.73 m2 per year (95% CI, 0.4 to 1.4), respectively (P<0.01 for each canagliflozin group versus glimepiride). In the subgroup of patients with baseline urinary albumin-to-creatinine ratio ≥30 mg/g, urinary albumin-to-creatinine ratio decreased more with canagliflozin 100 mg (31.7%; 95% CI, 8.6% to 48.9%; P=0.01) or canagliflozin 300 mg (49.3%; 95% CI, 31.9% to 62.2%; P<0.001) than with glimepiride. Patients receiving glimepiride, canagliflozin 100 mg, or canagliflozin 300 mg had reductions in HbA1c of 0.81%, 0.82%, and 0.93%, respectively, at 1 year and 0.55%, 0.65%, and 0.74%, respectively, at 2 years. In conclusion, canagliflozin 100 or 300 mg/d, compared with glimepiride, slowed the progression of renal disease over 2 years in patients with type 2 diabetes, and canagliflozin may confer renoprotective effects independently of its glycemic effects.Heerspink, Hiddo J. L.Desai, MehulJardine, MegBalis, DainiusMeininger, GaryPerkovic, Vlado2016-08-18T08:16:26-07:00doi:10.1681/ASN.2016030278hwp:resource-id:jnephrol;28/1/368American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologySGLT2, canagliflozin, renal function, diabetic nephropathyClinical ResearchClinical Researchresearch-article20162017-01-01January 201710.1681/ASN.20160302781046-66731533-34502016-08-18T08:16:26-07:002017-01Journal of the American Society of NephrologyClinical Research2811368737510
- IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKDPatients with CKD requiring dialysis have a higher risk of sepsis and a 100-fold higher mortality rate than the general population with sepsis. The severity of cardiac dysfunction predicts mortality in patients with sepsis. Here, we investigated the effect of preexisting CKD on cardiac function in mice with sepsis and whether inhibition of IκB kinase (IKK) reduces the cardiac dysfunction in CKD sepsis. Male C57BL/6 mice underwent 5/6 nephrectomy, and 8 weeks later, they were subjected to LPS (2 mg/kg) or sepsis by cecal ligation and puncture (CLP). Compared with sham operation, nephrectomy resulted in significant increases in urea and creatinine levels, a small (P<0.05) reduction in ejection fraction (echocardiography), and increases in the cardiac levels of phosphorylated IκBα, Akt, and extracellular signal–regulated kinase 1/2; nuclear translocation of the NF-κB subunit p65; and inducible nitric oxide synthase (iNOS) expression. When subjected to LPS or CLP, compared with sham-operated controls, CKD mice exhibited exacerbation of cardiac dysfunction and lung inflammation, greater increases in levels of plasma cytokines (TNF-α, IL-1β, IL-6, and IL-10), and greater increases in the cardiac levels of phosphorylated IKKα/β and IκBα, nuclear translocation of p65, and iNOS expression. Treatment of CKD mice with an IKK inhibitor (IKK 16; 1 mg/kg) 1 hour after CLP or LPS administration attenuated these effects. Thus, preexisting CKD aggravates the cardiac dysfunction caused by sepsis or endotoxemia in mice; this effect may be caused by increased cardiac NF-κB activation and iNOS expression.10.1681/ASN.2015060670Fri, 06 May 2016 08:56:01 GMT-07:00IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKDPatients with CKD requiring dialysis have a higher risk of sepsis and a 100-fold higher mortality rate than the general population with sepsis. The severity of cardiac dysfunction predicts mortality in patients with sepsis. Here, we investigated the effect of preexisting CKD on cardiac function in mice with sepsis and whether inhibition of IκB kinase (IKK) reduces the cardiac dysfunction in CKD sepsis. Male C57BL/6 mice underwent 5/6 nephrectomy, and 8 weeks later, they were subjected to LPS (2 mg/kg) or sepsis by cecal ligation and puncture (CLP). Compared with sham operation, nephrectomy resulted in significant increases in urea and creatinine levels, a small (P<0.05) reduction in ejection fraction (echocardiography), and increases in the cardiac levels of phosphorylated IκBα, Akt, and extracellular signal–regulated kinase 1/2; nuclear translocation of the NF-κB subunit p65; and inducible nitric oxide synthase (iNOS) expression. When subjected to LPS or CLP, compared with sham-operated controls, CKD mice exhibited exacerbation of cardiac dysfunction and lung inflammation, greater increases in levels of plasma cytokines (TNF-α, IL-1β, IL-6, and IL-10), and greater increases in the cardiac levels of phosphorylated IKKα/β and IκBα, nuclear translocation of p65, and iNOS expression. Treatment of CKD mice with an IKK inhibitor (IKK 16; 1 mg/kg) 1 hour after CLP or LPS administration attenuated these effects. Thus, preexisting CKD aggravates the cardiac dysfunction caused by sepsis or endotoxemia in mice; this effect may be caused by increased cardiac NF-κB activation and iNOS expression.Chen, JianminKieswich, Julius E.Chiazza, FaustoMoyes, Amie J.Gobbetti, ThomasPurvis, Gareth S.D.Salvatori, Daniela C.F.Patel, Nimesh S.A.Perretti, MauroHobbs, Adrian J.Collino, MassimoYaqoob, Muhammad M.Thiemermann, Christoph2016-05-06T08:56:01-07:00doi:10.1681/ASN.2015060670hwp:resource-id:jnephrol;28/1/94American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, sepsis, cardiac dysfunctionBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150606701046-66731533-34502016-05-06T08:56:01-07:002017-01Journal of the American Society of NephrologyBasic Research28194105
- T-Bet Enhances Regulatory T Cell Fitness and Directs Control of Th1 Responses in Crescentic GNTh1 cells are central pathogenic mediators of crescentic GN (cGN). Mechanisms responsible for Th1 cell downregulation, however, remain widely unknown. Recently, it was proposed that activation of the Th1–characteristic transcription factor T-bet optimizes Foxp3+ regulatory T (Treg) cells to counteract Th1-type inflammation. Because very little is known about the role of T-bet+ Treg1 cells in inflammatory diseases, we studied the function of these cells in the nephrotoxic nephritis (NTN) model of cGN. The percentage of Treg1 cells progressively increased in kidneys of nephritic wild–type mice during the course of NTN, indicating their functional importance. Notably, naïve Foxp3CrexT-betfl/fl mice, lacking Treg1 cells, showed spontaneous skewing toward Th1 immunity. Furthermore, absence of Treg1 cells resulted in aggravated NTN with selectively dysregulated renal and systemic Th1 responses. Detailed analyses of Treg cells from Foxp3CrexT-betfl/fl mice revealed unaltered cytokine production and suppressive capacity. However, in competitive cotransfer experiments, wild–type Treg cells outcompeted T-bet–deficient Treg cells in terms of population expansion and expression levels of Foxp3, indicating that T-bet expression is crucial for general Treg fitness. Additionally, T-bet–deficient Treg cells lacked expression of the Th1–characteristic trafficking receptor CXCR3, which correlated with significant impairment of renal Treg infiltration. In summary, our data indicate a new subtype of Treg cells in cGN. These Treg1 cells are characterized by activation of the transcription factor T-bet, which enhances the overall fitness of these cells and optimizes their capacity to downregulate Th1 responses by inducing chemokine receptor CXCR3 expression.10.1681/ASN.2015070820Mon, 13 Jun 2016 11:37:27 GMT-07:00T-Bet Enhances Regulatory T Cell Fitness and Directs Control of Th1 Responses in Crescentic GNTh1 cells are central pathogenic mediators of crescentic GN (cGN). Mechanisms responsible for Th1 cell downregulation, however, remain widely unknown. Recently, it was proposed that activation of the Th1–characteristic transcription factor T-bet optimizes Foxp3+ regulatory T (Treg) cells to counteract Th1-type inflammation. Because very little is known about the role of T-bet+ Treg1 cells in inflammatory diseases, we studied the function of these cells in the nephrotoxic nephritis (NTN) model of cGN. The percentage of Treg1 cells progressively increased in kidneys of nephritic wild–type mice during the course of NTN, indicating their functional importance. Notably, naïve Foxp3CrexT-betfl/fl mice, lacking Treg1 cells, showed spontaneous skewing toward Th1 immunity. Furthermore, absence of Treg1 cells resulted in aggravated NTN with selectively dysregulated renal and systemic Th1 responses. Detailed analyses of Treg cells from Foxp3CrexT-betfl/fl mice revealed unaltered cytokine production and suppressive capacity. However, in competitive cotransfer experiments, wild–type Treg cells outcompeted T-bet–deficient Treg cells in terms of population expansion and expression levels of Foxp3, indicating that T-bet expression is crucial for general Treg fitness. Additionally, T-bet–deficient Treg cells lacked expression of the Th1–characteristic trafficking receptor CXCR3, which correlated with significant impairment of renal Treg infiltration. In summary, our data indicate a new subtype of Treg cells in cGN. These Treg1 cells are characterized by activation of the transcription factor T-bet, which enhances the overall fitness of these cells and optimizes their capacity to downregulate Th1 responses by inducing chemokine receptor CXCR3 expression.Nosko, AnnaKluger, Malte A.Diefenhardt, PaulMelderis, SimonWegscheid, ClaudiaTiegs, GisaStahl, Rolf A.K.Panzer, UlfSteinmetz, Oliver M.2016-06-13T11:37:27-07:00doi:10.1681/ASN.2015070820hwp:resource-id:jnephrol;28/1/185American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyTreg, CXCR3, immunology, Treg1, cytokines, inflammationBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150708201046-66731533-34502016-06-13T11:37:27-07:002017-01Journal of the American Society of NephrologyBasic Research281118511962
- Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in PodocytesKlotho is a type-1 membrane protein predominantly produced in the kidney, the extracellular domain of which is secreted into the systemic circulation. Membranous and secreted Klotho protect organs, including the kidney, but whether and how Klotho directly protects the glomerular filter is unknown. Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca2+ influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel. Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells. Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria. Notably, immunofluorescence and in situ hybridization revealed Klotho expression in podocytes of mouse and human kidney. Heterozygous Klotho-deficient CKD mice had aggravated albuminuria compared with that in wild-type CKD mice with a similar degree of hypertension and reduced clearance function. Finally, disrupting the integrity of glomerular filter by saline infusion-mediated extracellular fluid volume expansion increased urinary Klotho excretion. These results reveal a potential novel function of Klotho in protecting the glomerular filter, and may offer a new therapeutic strategy for treatment of proteinuria.10.1681/ASN.2015080888Thu, 05 May 2016 07:03:14 GMT-07:00Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in PodocytesKlotho is a type-1 membrane protein predominantly produced in the kidney, the extracellular domain of which is secreted into the systemic circulation. Membranous and secreted Klotho protect organs, including the kidney, but whether and how Klotho directly protects the glomerular filter is unknown. Here, we report that secreted Klotho suppressed transient receptor potential channel 6 (TRPC6)-mediated Ca2+ influx in cultured mouse podocytes by inhibiting phosphoinositide 3-kinase-dependent exocytosis of the channel. Furthermore, soluble Klotho reduced ATP-stimulated actin cytoskeletal remodeling and transepithelial albumin leakage in these cells. Overexpression of TRPC6 by gene delivery in mice induced albuminuria, and exogenous administration of Klotho ameliorated the albuminuria. Notably, immunofluorescence and in situ hybridization revealed Klotho expression in podocytes of mouse and human kidney. Heterozygous Klotho-deficient CKD mice had aggravated albuminuria compared with that in wild-type CKD mice with a similar degree of hypertension and reduced clearance function. Finally, disrupting the integrity of glomerular filter by saline infusion-mediated extracellular fluid volume expansion increased urinary Klotho excretion. These results reveal a potential novel function of Klotho in protecting the glomerular filter, and may offer a new therapeutic strategy for treatment of proteinuria.Kim, Ji-HeeXie, JianHwang, Kyu-HeeWu, Yueh-LinOliver, NoelynnEom, MinseobPark, Kyu-SangBarrezueta, NestorKong, In-DeokFracasso, R. PaulHuang, Chou-LongCha, Seung-Kuy2016-05-05T07:03:14-07:00doi:10.1681/ASN.2015080888hwp:resource-id:jnephrol;28/1/140American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyKlotho, podocyte, TRPC6Basic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150808881046-66731533-34502016-05-05T07:03:14-07:002017-01Journal of the American Society of NephrologyBasic Research281140151
- Wnt7b Signaling from the Ureteric Bud Epithelium Regulates Medullary Capillary DevelopmentThe renal vasculature is integral to the physiologic function of the kidneys in regulating hemodynamics of the body and maintaining organ health. The close inter-relationship of capillaries and the renal epithelium is key to renal physiology, but how renal tubules regulate capillary development remains unclear. Our previous work showed that Wnt7b is expressed in the ureteric trunk epithelium and activates canonical Wnt signaling in the surrounding medullary interstitium, where the capillaries reside. In this study, we showed by immunofluorescence that the target interstitial cells of Wnt7b/canonical Wnt signaling are mural cells of periureteric bud capillaries in the nascent renal medulla of embryonic mice. Genetic ablation of Wnt7b enhanced the proliferation of Wnt7b target mural cells, an effect that associated with decreased expression of PDGFRβ and p57kip2, a cyclin–dependent kinase inhibitor, in these cells. Furthermore, Wnt7b regulated lumen formation of the capillary endothelium in the renal medulla. In the absence of Wnt7b signaling, the periureteric bud medullary capillaries displayed narrower lumens lined with less flattened endothelial cells and a significantly increased presence of luminal endothelial cell-cell junctions, a transient configuration in the forming blood vessels in the controls. Moreover, the absence of Wnt7b led to greatly diminished levels of vascular endothelial (VE)-cadherin at the cell surface in these blood vessels. VE-cadherin is essential for blood vessel lumen formation; thus, Wnt7b may regulate lumen formation through modulation of VE-cadherin localization. Overall, these results indicate a novel role of Wnt7b signaling and the ureteric bud epithelium in renal medullary capillary development.10.1681/ASN.2015111205Mon, 18 Jul 2016 07:17:48 GMT-07:00Wnt7b Signaling from the Ureteric Bud Epithelium Regulates Medullary Capillary DevelopmentThe renal vasculature is integral to the physiologic function of the kidneys in regulating hemodynamics of the body and maintaining organ health. The close inter-relationship of capillaries and the renal epithelium is key to renal physiology, but how renal tubules regulate capillary development remains unclear. Our previous work showed that Wnt7b is expressed in the ureteric trunk epithelium and activates canonical Wnt signaling in the surrounding medullary interstitium, where the capillaries reside. In this study, we showed by immunofluorescence that the target interstitial cells of Wnt7b/canonical Wnt signaling are mural cells of periureteric bud capillaries in the nascent renal medulla of embryonic mice. Genetic ablation of Wnt7b enhanced the proliferation of Wnt7b target mural cells, an effect that associated with decreased expression of PDGFRβ and p57kip2, a cyclin–dependent kinase inhibitor, in these cells. Furthermore, Wnt7b regulated lumen formation of the capillary endothelium in the renal medulla. In the absence of Wnt7b signaling, the periureteric bud medullary capillaries displayed narrower lumens lined with less flattened endothelial cells and a significantly increased presence of luminal endothelial cell-cell junctions, a transient configuration in the forming blood vessels in the controls. Moreover, the absence of Wnt7b led to greatly diminished levels of vascular endothelial (VE)-cadherin at the cell surface in these blood vessels. VE-cadherin is essential for blood vessel lumen formation; thus, Wnt7b may regulate lumen formation through modulation of VE-cadherin localization. Overall, these results indicate a novel role of Wnt7b signaling and the ureteric bud epithelium in renal medullary capillary development.Roker, LaToya AnnNemri, KatrinaYu, Jing2016-07-18T07:17:48-07:00doi:10.1681/ASN.2015111205hwp:resource-id:jnephrol;28/1/250American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal development, ureteric bud, vascular, signalingBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20151112051046-66731533-34502016-07-18T07:17:48-07:002017-01Journal of the American Society of NephrologyBasic Research281250259
- G Protein–Coupled Receptor-G–Protein βγ–Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart FailureDevelopment of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein–coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G–protein βγ–subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR–Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR–Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor–Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI.10.1681/ASN.2015080852Mon, 13 Jun 2016 11:37:25 GMT-07:00G Protein–Coupled Receptor-G–Protein βγ–Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart FailureDevelopment of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein–coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G–protein βγ–subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR–Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR–Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor–Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI.Kamal, Fadia A.Travers, Joshua G.Schafer, Allison E.Ma, QingDevarajan, PrasadBlaxall, Burns C.2016-06-13T11:37:25-07:00doi:10.1681/ASN.2015080852hwp:resource-id:jnephrol;28/1/197American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic heart failure, chronic kidney disease, acute renal failure, GPCR-g protein signaling, renal fibrosisBasic ResearchBasic Researchresearch-article20162017-01-01January 201710.1681/ASN.20150808521046-66731533-34502016-06-13T11:37:25-07:002017-01Journal of the American Society of NephrologyBasic Research281197208
- A Concept–Wide Association Study of Clinical Notes to Discover New Predictors of Kidney Failure10.2215/CJN.02420316Mon, 10 Oct 2016 04:58:33 GMT-07:00A Concept–Wide Association Study of Clinical Notes to Discover New Predictors of Kidney FailureSingh, KarandeepBetensky, Rebecca A.Wright, AdamCurhan, Gary C.Bates, David W.Waikar, Sushrut S.2016-10-10T04:58:33-07:00doi:10.2215/CJN.02420316hwp:resource-id:clinjasn;11/12/2150American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, natural language processing, informatics, electronic health record, adult, Ascorbic Acid, Cohort Studies, creatinine, Disease Progression, Electronic Health Records, fast foods, Follow-Up Studies, humans, kidney, Kidney Diseases, Kidney Failure, Chronic, Natural Language Processing, nephrology, Outpatients, Renal Insufficiency, Retrospective Studies, risk factors, Tertiary Care CentersOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-12-07December 07, 201610.2215/CJN.024203161555-90411555-905X2016-10-10T04:58:33-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221502158
- Progression of Interstitial Fibrosis during the First Year after Deceased Donor Kidney Transplantation among Patients with and without Delayed Graft Function10.2215/CJN.05060516Mon, 24 Oct 2016 08:02:50 GMT-07:00Progression of Interstitial Fibrosis during the First Year after Deceased Donor Kidney Transplantation among Patients with and without Delayed Graft FunctionHeilman, Raymond L.Smith, Maxwell L.Smith, Byron H.Qaqish, IbrahimKhamash, HasanSinger, Andrew L.Kaplan, BruceReddy, Kunam S.2016-10-24T08:02:50-07:00doi:10.2215/CJN.05060516hwp:resource-id:clinjasn;11/12/2225American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydelayed graft function after kidney transplant, interstitial fibrosis, ischemia reperfusion injury and kidney transplant, acute kidney injury, biopsy, Control Groups, delayed graft function, fibrosis, Humans, kidney, kidney transplantation, Reperfusion Injury, Retrospective Studies, Tissue DonorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-12-07December 07, 201610.2215/CJN.050605161555-90411555-905X2016-10-24T08:02:50-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles11121211222521101969223221121977
- Progression of Interstitial Fibrosis in Kidney Transplantation10.2215/CJN.09770916Mon, 24 Oct 2016 08:02:49 GMT-07:00Progression of Interstitial Fibrosis in Kidney TransplantationOberbauer, Rainer2016-10-24T08:02:49-07:00doi:10.2215/CJN.09770916hwp:resource-id:clinjasn;11/12/2110American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplantation, fibrosis, renal biopsy, Disease Progression, kidney, kidney transplantation, Lung Diseases, InterstitialEditorialsEditorialseditorial20162016-12-07December 07, 201610.2215/CJN.097709161555-90411555-905X2016-10-24T08:02:49-07:002016-12-07Clinical Journal of the American Society of NephrologyEditorials1112122110222521122232
- Association of Increasing GFR with Change in Albuminuria in the General Population10.2215/CJN.04940516Wed, 28 Sep 2016 11:21:28 GMT-07:00Association of Increasing GFR with Change in Albuminuria in the General PopulationMelsom, ToralfStefansson, VidarSchei, JørgenSolbu, MaritJenssen, TrondWilsgaard, TomEriksen, Bjørn O.2016-09-28T11:21:28-07:00doi:10.2215/CJN.04940516hwp:resource-id:clinjasn;11/12/2186American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbumin creatinine ratio, albuminuria, hyperfiltration, glomerular filtration rate, glomerular filtration rate OR GFR or “incident CKD”, clinical epidemiology, general population, glomerular hyperfiltration, ACR, iohexol clearance, Albumins, cardiovascular disease, creatinine, diabetes mellitus, follow-up studies, humans, Iohexol, Kidney Diseases, Kidney Function Tests, Linear Models, Nephrons, Norway, Odds Ratio, risk factorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-12-07December 07, 201610.2215/CJN.049405161555-90411555-905X2016-09-28T11:21:28-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221862194
- Acute Kidney Injury in the Era of the AKI E-Alert10.2215/CJN.05170516Fri, 28 Oct 2016 05:09:45 GMT-07:00Acute Kidney Injury in the Era of the AKI E-AlertHolmes, JenniferRainer, TimothyGeen, JohnRoberts, GethinMay, KateWilson, NickWilliams, John D.Phillips, Aled O.2016-10-28T05:09:45-07:00doi:10.2215/CJN.05170516hwp:resource-id:clinjasn;11/12/2123American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, clinical epidemiology, clinical nephrology, Epidemiology and outcomes, acute kidney injury, adult, cohort studies, humans, Incidence, Intelligence, kidney, Prospective Studies, Receptor, Epidermal Growth Factor, Surveys and Questionnaires, EGFR protein, humanOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-12-07December 07, 201610.2215/CJN.051705161555-90411555-905X2016-10-28T05:09:45-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221232131
- Achieving Procedural Competence during Nephrology Fellowship Training: Current Requirements and Educational ResearchConcerns have previously been raised as to whether training programs are ensuring that nephrology fellows achieve competence in the procedural skills required for independent practice. We sought to review the current requirements for procedural training as well as educational research pertaining to achieving competence in the core nephrology procedures of nontunneled (temporary) hemodialysis catheter insertion and percutaneous kidney biopsy. At this time, there is no universal approach to procedural training and assessment during nephrology fellowship. Nonetheless, simulation–based mastery learning programs have been shown to be effective in improving fellows’ skills in nontunneled (temporary) hemodialysis catheter insertion and should be provided by all nephrology training programs. For percutaneous kidney biopsy, the development and evaluation of inexpensive simulators are a promising starting point for future study. Current practice with respect to procedural training during nephrology fellowship remains imperfect; however, the ongoing shift toward competency-based evaluation provides opportunities to refocus on improvement.10.2215/CJN.08940815Tue, 07 Jun 2016 07:13:33 GMT-07:00Achieving Procedural Competence during Nephrology Fellowship Training: Current Requirements and Educational ResearchConcerns have previously been raised as to whether training programs are ensuring that nephrology fellows achieve competence in the procedural skills required for independent practice. We sought to review the current requirements for procedural training as well as educational research pertaining to achieving competence in the core nephrology procedures of nontunneled (temporary) hemodialysis catheter insertion and percutaneous kidney biopsy. At this time, there is no universal approach to procedural training and assessment during nephrology fellowship. Nonetheless, simulation–based mastery learning programs have been shown to be effective in improving fellows’ skills in nontunneled (temporary) hemodialysis catheter insertion and should be provided by all nephrology training programs. For percutaneous kidney biopsy, the development and evaluation of inexpensive simulators are a promising starting point for future study. Current practice with respect to procedural training during nephrology fellowship remains imperfect; however, the ongoing shift toward competency-based evaluation provides opportunities to refocus on improvement.Clark, EdwardBarsuk, Jeffrey H.Karpinski, JolantaMcQuillan, Rory2016-06-07T07:13:33-07:00doi:10.2215/CJN.08940815hwp:resource-id:clinjasn;11/12/2244American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymedical education, procedures, non-tunneled hemodialysis catheter, kidney biopsy, Catheterization, Fellowships and Scholarships, nephrology, renal dialysis, ResearchEducation SeriesEducation Seriesresearch-article20162016-12-07December 07, 201610.2215/CJN.089408151555-90411555-905X2016-06-07T07:13:33-07:002016-12-07Clinical Journal of the American Society of NephrologyEducation Series111222442249
- Sex and the Risk of AKI Following Cardio-thoracic Surgery: A Meta-Analysis10.2215/CJN.03340316Thu, 20 Oct 2016 06:35:04 GMT-07:00Sex and the Risk of AKI Following Cardio-thoracic Surgery: A Meta-AnalysisNeugarten, JoelSandilya, SandipaniSingh, BeenuGolestaneh, Ladan2016-10-20T06:35:04-07:00doi:10.2215/CJN.03340316hwp:resource-id:clinjasn;11/12/2113American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, cardiac surgery, sex, acute kidney injury, Cardiac Surgical Procedures, Consensus, female, humans, Incidence, male, Multivariate Analysis, risk factors, Specialties, Surgical, Thoracic SurgeryOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-12-07December 07, 201610.2215/CJN.033403161555-90411555-905X2016-10-20T06:35:04-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221132122
- Conservative Management and End-of-Life Care in an Australian Cohort with ESRD10.2215/CJN.11861115Mon, 03 Oct 2016 08:49:30 GMT-07:00Conservative Management and End-of-Life Care in an Australian Cohort with ESRDMorton, Rachael L.Webster, Angela C.McGeechan, KevinHoward, KirstenMurtagh, Fliss E.M.Gray, Nicholas A.Kerr, Peter G.Germain, Michael J.Snelling, Paul2016-10-03T08:49:30-07:00doi:10.2215/CJN.11861115hwp:resource-id:clinjasn;11/12/2195American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypalliative medicine, advance directives, hospices, kidney failure, chronic, Australia, Cohort Studies, Death, Follow-Up Studies, Hospices, Humans, Kidney Failure, Chronic, Palliative Care, renal dialysis, Renal Insufficiency, Chronic, Renal Replacement Therapy, Serum Albumin, Terminal CareOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-12-07December 07, 201610.2215/CJN.118611151555-90411555-905X2016-10-03T08:49:30-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221952203
- Paraprotein–Related Kidney Disease: Glomerular Diseases Associated with ParaproteinemiasParaproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein–related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.10.2215/CJN.02980316Mon, 15 Aug 2016 04:05:38 GMT-07:00Paraprotein–Related Kidney Disease: Glomerular Diseases Associated with ParaproteinemiasParaproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein–related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.Motwani, Shveta S.Herlitz, LealMonga, DivyaJhaveri, Kenar D.Lam, Albert Q.2016-08-15T04:05:38-07:00doi:10.2215/CJN.02980316hwp:resource-id:clinjasn;11/12/2260American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, cancer, multiple myeloma, nephrotic syndrome, amyloidosis, light chain deposition disease, fibrillary glomerulonephritis, immunotactoid glomerulopathy, cryoglobulinemia, Amyloidosis, glomerulonephritis, Immunoglobulin G, Kidney Glomerulus, Paraproteinemias, Paraproteins, Thrombotic MicroangiopathiesMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-12-07December 07, 201610.2215/CJN.029803161555-90411555-905X2016-08-15T04:05:38-07:002016-12-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111222602272
- Glomerular Diseases: Registries and Clinical TrialsNephrology has conducted few high–quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty–specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.10.2215/CJN.00540116Mon, 26 Sep 2016 07:34:50 GMT-07:00Glomerular Diseases: Registries and Clinical TrialsNephrology has conducted few high–quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty–specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases.Moxey-Mims, Marva M.Flessner, Michael F.Holzman, LawrenceKaskel, FrederickSedor, John R.Smoyer, William E.Thompson, Aliza M.Yao, Lynne2016-09-26T07:34:50-07:00doi:10.2215/CJN.00540116hwp:resource-id:clinjasn;11/12/2234American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, glomerular disease, registries, Cooperative Behavior, Electronic Health Records, Foundations, Government, Humans, kidney, Kidney Failure, Chronic, Kidney Glomerulus, nephrology, Patient Advocacy, Phenotype, Prevalence, Registries, Research, Science, SpecializationGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20162016-12-07December 07, 201610.2215/CJN.005401161555-90411555-905X2016-09-26T07:34:50-07:002016-12-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician111222342243
- Vancomycin and the Risk of AKI: A Systematic Review and Meta-Analysis10.2215/CJN.05920616Mon, 28 Nov 2016 07:51:28 GMT-08:00Vancomycin and the Risk of AKI: A Systematic Review and Meta-AnalysisSinha Ray, AbhisekhHaikal, AmmarHammoud, Kassem A.Yu, Alan S.L.2016-11-28T07:51:28-08:00doi:10.2215/CJN.05920616hwp:resource-id:clinjasn;11/12/2132American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGlycopeptides, chronic renal insufficiency, meta-analysis, acute kidney injury, Anti-Bacterial Agents, Cohort Studies, Control Groups, Cross Infection, Humans, Libraries, Linezolid, Pneumonia, PubMed, Randomized Controlled Trials as Topic, Risk Assessment, Soft Tissue Infections, VancomycinOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-12-07December 07, 201610.2215/CJN.059206161555-90411555-905X2016-11-28T07:51:28-08:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1112122132210121402103
- Association of Nondisease-Specific Problems with Mortality, Long-Term Care, and Functional Impairment among Older Adults Who Require Skilled Nursing Care after Dialysis Initiation10.2215/CJN.01260216Wed, 12 Oct 2016 08:52:56 GMT-07:00Association of Nondisease-Specific Problems with Mortality, Long-Term Care, and Functional Impairment among Older Adults Who Require Skilled Nursing Care after Dialysis InitiationBowling, C. BarrettPlantinga, LauraHall, Rasheeda K.Mirk, AnnaZhang, RebeccaKutner, Nancy2016-10-12T08:52:56-07:00doi:10.2215/CJN.01260216hwp:resource-id:clinjasn;11/12/2218American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygeriatric nephrology, dialysis, mortality, Accidental Falls, Activities of Daily Living, Cognition Disorders, depression, hospitalization, Humans, Long-Term Care, Medicare, Patient Discharge, Polypharmacy, Registries, renal dialysis, Skilled Nursing Facilities, United StatesOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20162016-12-07December 07, 201610.2215/CJN.012602161555-90411555-905X2016-10-12T08:52:56-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111222182224
- The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase–Associated Lipocalin with Progression from CKD to ESRD10.2215/CJN.02670316Wed, 16 Nov 2016 07:18:31 GMT-08:00The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase–Associated Lipocalin with Progression from CKD to ESRDAlderson, Helen V.Ritchie, James P.Pagano, SabrinaMiddleton, Rachel J.Pruijm, MennoVuilleumier, NicolasKalra, Philip A.2016-11-16T07:18:31-08:00doi:10.2215/CJN.02670316hwp:resource-id:clinjasn;11/12/2141American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyKIM-1, NGAL, biomarkers, risk prediction, clinical outcomes, Acute-Phase Proteins, Adult, Biomarkers, follow-up studies, humans, Kidney Failure, Chronic, Lipocalins, Proto-Oncogene Proteins, ROC Curve, renal dialysis, renal insufficiency, chronic, risk factors, LCN2 protein, humanOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-12-07December 07, 201610.2215/CJN.026703161555-90411555-905X2016-11-16T07:18:31-08:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221412149
- Vancomycin and the Risk of AKI: Now Clearer than Mississippi Mud10.2215/CJN.11011016Mon, 28 Nov 2016 07:51:28 GMT-08:00Vancomycin and the Risk of AKI: Now Clearer than Mississippi MudNolin, Thomas D.2016-11-28T07:51:28-08:00doi:10.2215/CJN.11011016hwp:resource-id:clinjasn;11/12/2101American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvancomycin, acute renal failure, nephrotoxicity, drug nephrotoxicity, Acute Kidney Injury, Mississippi, Risk, VancomycinEditorialsEditorialseditorial20162016-12-07December 07, 201610.2215/CJN.110110161555-90411555-905X2016-11-28T07:51:28-08:002016-12-07Clinical Journal of the American Society of NephrologyEditorials1112122101213221032140
- With Gratitude to the CJASN Community10.2215/CJN.11041016Wed, 07 Dec 2016 10:00:36 GMT-08:00With Gratitude to the CJASN CommunityCurhan, Gary2016-12-07T10:00:36-08:00doi:10.2215/CJN.11041016hwp:resource-id:clinjasn;11/12/2099American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEditorialsEditorialseditorial20162016-12-07December 07, 201610.2215/CJN.110410161555-90411555-905X2016-12-07T10:00:36-08:002016-12-07Clinical Journal of the American Society of NephrologyEditorials111220992100
- Comparative Effectiveness of Second-Line Agents for the Treatment of Diabetes Type 2 in Preventing Kidney Function Decline10.2215/CJN.02630316Tue, 08 Nov 2016 11:03:48 GMT-08:00Comparative Effectiveness of Second-Line Agents for the Treatment of Diabetes Type 2 in Preventing Kidney Function DeclineHung, Adriana M.Roumie, Christianne L.Greevy, Robert A.Grijalva, Carlos G.Liu, XuleiMurff, Harvey J.Ikizler, T. AlpGriffin, Marie R.2016-11-08T11:03:48-08:00doi:10.2215/CJN.02630316hwp:resource-id:clinjasn;11/12/2177American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, comparative effectiveness, treatment intensification, diabetic nephropathy, diabetes management, Confidence Intervals, creatinine, Diabetes Mellitus, Type 2, Glucose, humans, insulin, kidney, Kidney Failure, Chronic, Metformin, Propensity Score, Retrospective Studies, Sulfonylurea Compounds, VeteransOriginal ArticlesDiabetes and The kidneyOriginal ArticlesDiabetes and The kidneyresearch-article20162016-12-07December 07, 201610.2215/CJN.026303161555-90411555-905X2016-11-08T11:03:48-08:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1112122177210421852106
- Second-Line Agents for the Treatment of Type 2 Diabetes and Prevention of CKD10.2215/CJN.10361016Tue, 08 Nov 2016 11:03:46 GMT-08:00Second-Line Agents for the Treatment of Type 2 Diabetes and Prevention of CKDYu, Margaret K.Kim, Sun H.2016-11-08T11:03:46-08:00doi:10.2215/CJN.10361016hwp:resource-id:clinjasn;11/12/2104American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, Diabetes Mellitus, Type 2, Kidney Failure, Chronic, Renal Insufficiency, ChronicEditorialsEditorialseditorial20162016-12-07December 07, 201610.2215/CJN.103610161555-90411555-905X2016-11-08T11:03:46-08:002016-12-07Clinical Journal of the American Society of NephrologyEditorials1112122104217721062185
- Prevalence and Contents of Advance Directives of Patients with ESRD Receiving Dialysis10.2215/CJN.12131115Thu, 17 Nov 2016 07:19:05 GMT-08:00Prevalence and Contents of Advance Directives of Patients with ESRD Receiving DialysisFeely, Molly A.Hildebrandt, DanielEdakkanambeth Varayil, JithinrajMueller, Paul S.2016-11-17T07:19:05-08:00doi:10.2215/CJN.12131115hwp:resource-id:clinjasn;11/12/2204American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyadvance directives, dialysis, advance care planning, kidney failure, chronic, terminal care, Academic Medical Centers, Advance Directives, Cardiopulmonary Resuscitation, Clinical Decision-Making, Cognition Disorders, Death, Documentation, Goals, Humans, Kidney Failure, Chronic, Male, Medical Records, Pain Management, Prevalence, renal dialysis, Respiration, Artificial, Retrospective Studies, Terminal CareOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-12-07December 07, 201610.2215/CJN.121311151555-90411555-905X2016-11-17T07:19:05-08:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1112122204210722092109
- Paraprotein–Related Kidney Disease: Attack of the Killer M ProteinsParaproteins are monoclonal Igs or their components (light or heavy chains) that are produced by a clonal population of mature B cells, most commonly plasma cells. These paraproteins or monoclonal proteins are secreted into the blood and subsequently filtered by the glomerulus before entering into urine, where they can cause various types of kidney disease, including both glomerular and tubulointerstitial injuries. Furthermore, a monoclonal protein that causes a specific glomerular or tubulointerstitial lesion in a human can reproducibly cause the same pathology when injected into an animal, supporting unique paraprotein characteristics. This Moving Points in Nephrology will provide an update for the Clinical Journal of the American Society of Nephrology readership on some of the clinically relevant kidney lesions associated with monoclonal paraprotein production and the pathophysiology underlying these kidney lesions.10.2215/CJN.02960316Wed, 07 Dec 2016 10:00:36 GMT-08:00Paraprotein–Related Kidney Disease: Attack of the Killer M ProteinsParaproteins are monoclonal Igs or their components (light or heavy chains) that are produced by a clonal population of mature B cells, most commonly plasma cells. These paraproteins or monoclonal proteins are secreted into the blood and subsequently filtered by the glomerulus before entering into urine, where they can cause various types of kidney disease, including both glomerular and tubulointerstitial injuries. Furthermore, a monoclonal protein that causes a specific glomerular or tubulointerstitial lesion in a human can reproducibly cause the same pathology when injected into an animal, supporting unique paraprotein characteristics. This Moving Points in Nephrology will provide an update for the Clinical Journal of the American Society of Nephrology readership on some of the clinically relevant kidney lesions associated with monoclonal paraprotein production and the pathophysiology underlying these kidney lesions.Perazella, Mark A.Finkel, Kevin W.2016-12-07T10:00:36-08:00doi:10.2215/CJN.02960316hwp:resource-id:clinjasn;11/12/2256American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymonoclonal paraprotein, kidney, amyloidosis, light chains, cast nephropathy, Kidney Diseases, Myeloma Proteins, Paraproteins, Social Behavior, multiple myeloma M-proteinsMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-12-07December 07, 201610.2215/CJN.029603161555-90411555-905X2016-12-07T10:00:36-08:002016-12-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111222562259
- Prognostic Value of Histologic Classification of ANCA-Associated Glomerulonephritis10.2215/CJN.04800516Tue, 18 Oct 2016 05:20:34 GMT-07:00Prognostic Value of Histologic Classification of ANCA-Associated GlomerulonephritisBjørneklett, RuneSriskandarajah, SanjeevanBostad, Leif2016-10-18T05:20:34-07:00doi:10.2215/CJN.04800516hwp:resource-id:clinjasn;11/12/2159American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, classification, vasculitis, renal pathology, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, Biopsy, Follow-Up Studies, glomerulonephritis, Humans, kidney, Kidney Failure, Chronic, Kidney Glomerulus, Prognosis, ROC Curve, Registries, Regression AnalysisOriginal ArticlesClinical Immunology and PathologyOriginal ArticlesClinical Immunology and Pathologyresearch-article20162016-12-07December 07, 201610.2215/CJN.048005161555-90411555-905X2016-10-18T05:20:34-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221592167
- Glomerular Pathology in Dent Disease and Its Association with Kidney Function10.2215/CJN.03710416Mon, 03 Oct 2016 08:49:29 GMT-07:00Glomerular Pathology in Dent Disease and Its Association with Kidney FunctionWang, XianglingAnglani, FrancaBeara-Lasic, LadaMehta, Anila J.Vaughan, Lisa E.Herrera Hernandez, LorenCogal, AndreaScheinman, Steven J.Ariceta, GemaIsom, RobertCopelovitch, LawrenceEnders, Felicity T.Del Prete, DorellaVezzoli, GiuseppePaglialonga, FabioHarris, Peter C.Lieske, John C.2016-10-03T08:49:29-07:00doi:10.2215/CJN.03710416hwp:resource-id:clinjasn;11/12/2168American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyDent disease, glomerulosclerosis, podocyte, interstitial fibrosis, biopsy, Disease Progression, glomerular filtration rate, Glomerulosclerosis, Focal Segmental, Humans, Inflammation, kidney, Kidney Glomerulus, Male, Molecular Weight, Podocytes, proteinuriaOriginal ArticlesClinical Immunology and PathologyOriginal ArticlesClinical Immunology and Pathologyresearch-article20162016-12-07December 07, 201610.2215/CJN.037104161555-90411555-905X2016-10-03T08:49:29-07:002016-12-07Clinical Journal of the American Society of NephrologyOriginal Articles111221682176
- Paraprotein–Related Kidney Disease: Evaluation and Treatment of Myeloma Cast NephropathyNearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm–Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high–cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high–cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care.10.2215/CJN.01640216Mon, 15 Aug 2016 04:05:38 GMT-07:00Paraprotein–Related Kidney Disease: Evaluation and Treatment of Myeloma Cast NephropathyNearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm–Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high–cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high–cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care.Finkel, Kevin W.Cohen, Eric P.Shirali, AnushreeAbudayyeh, Ala2016-08-15T04:05:38-07:00doi:10.2215/CJN.01640216hwp:resource-id:clinjasn;11/12/2273American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, multiple myeloma, cast nephropathy, free light chains, HCO dialysis, Humans, Immunoglobulin Light Chains, Molecular Weight, Myeloma Proteins, Plasma Exchange, Randomized Controlled Trials as Topic, renal dialysis, Standard of Care, Uromodulin, multiple myeloma M-proteinsMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-12-07December 07, 201610.2215/CJN.016402161555-90411555-905X2016-08-15T04:05:38-07:002016-12-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111222732279
- Paraprotein–Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal SignificanceParaprotein–related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders.10.2215/CJN.02920316Mon, 15 Aug 2016 04:05:37 GMT-07:00Paraprotein–Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal SignificanceParaprotein–related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders.Rosner, Mitchell H.Edeani, AmakaYanagita, MotokoGlezerman, Ilya G.Leung, Nelson2016-08-15T04:05:37-07:00doi:10.2215/CJN.02920316hwp:resource-id:clinjasn;11/12/2280American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney disease, multiple myeloma, paraproteinemia, monoclonal gammopathy, Aged, B-Lymphocytes, Biopsy, Fanconi Syndrome, Humans, kidney, Kidney Diseases, Paraproteins, Prognosis, proteinuria, Stem Cell TransplantationMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-12-07December 07, 201610.2215/CJN.029203161555-90411555-905X2016-08-15T04:05:37-07:002016-12-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111222802287
- Paraprotein–Related Kidney Disease: Kidney Injury from Paraproteins—What Determines the Site of Injury?Disorders of plasma and B cells leading to paraproteinemias are associated with a variety of renal diseases. Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. Glomerular diseases that may be associated with paraproteinemias include amyloid deposition, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, C3 glomerulopathy caused by alterations in the complement pathway, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemia. Tubular lesions include the classic Fanconi syndrome, light–chain proximal tubulopathy, interstitial fibrosis, and cast nephropathy. These paraproteinemic renal diseases are distinct in their pathogenesis as well as their urinary and kidney biopsy findings. Renal pathology is usually initiated by deposition and direct involvement of the intact monoclonal Ig or Ig fragments with resident cells of the nephron. Our review summarizes current insights into the underlying molecular pathogenesis of these interesting kidney lesions.10.2215/CJN.02560316Mon, 15 Aug 2016 04:05:38 GMT-07:00Paraprotein–Related Kidney Disease: Kidney Injury from Paraproteins—What Determines the Site of Injury?Disorders of plasma and B cells leading to paraproteinemias are associated with a variety of renal diseases. Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. Glomerular diseases that may be associated with paraproteinemias include amyloid deposition, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, C3 glomerulopathy caused by alterations in the complement pathway, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemia. Tubular lesions include the classic Fanconi syndrome, light–chain proximal tubulopathy, interstitial fibrosis, and cast nephropathy. These paraproteinemic renal diseases are distinct in their pathogenesis as well as their urinary and kidney biopsy findings. Renal pathology is usually initiated by deposition and direct involvement of the intact monoclonal Ig or Ig fragments with resident cells of the nephron. Our review summarizes current insights into the underlying molecular pathogenesis of these interesting kidney lesions.Doshi, MonaLahoti, AmitDanesh, Farhad R.Batuman, VecihiSanders, Paul W.2016-08-15T04:05:38-07:00doi:10.2215/CJN.02560316hwp:resource-id:clinjasn;11/12/2288American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyparaproteins, multiple myeloma, amyloidosis, immunoglobulins, immunoglobulin free light chains, glomerular disease, tubular epithelium, kidney, Kidney Diseases, Myeloma Proteins, Paraproteins, multiple myeloma M-proteinsMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-12-07December 07, 201610.2215/CJN.025603161555-90411555-905X2016-08-15T04:05:38-07:002016-12-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111222882294
- Working Toward More Effective Advance Care Planning in Patients with ESRD10.2215/CJN.10511016Thu, 17 Nov 2016 07:19:05 GMT-08:00Working Toward More Effective Advance Care Planning in Patients with ESRDCombs, Sara Ann2016-11-17T07:19:05-08:00doi:10.2215/CJN.10511016hwp:resource-id:clinjasn;11/12/2107American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAdvance Care Planning, end-stage renal disease, decision-making, Humans, Kidney Failure, Chronic, Renal Insufficiency, ChronicEditorialsEditorialseditorial20162016-12-07December 07, 201610.2215/CJN.105110161555-90411555-905X2016-11-17T07:19:05-08:002016-12-07Clinical Journal of the American Society of NephrologyEditorials1112122107220421092209
- Inhibition of Activin Signaling Slows Progression of Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD), characterized by the formation of numerous kidney cysts, is caused by PKD1 or PKD2 mutations and affects 0.1% of the population. Although recent clinical studies indicate that reduction of cAMP levels slows progression of PKD, this finding has not led to an established safe and effective therapy for patients, indicating the need to find new therapeutic targets. The role of TGF-β in PKD is not clearly understood, but nuclear accumulation of phosphorylated SMAD2/3 in cyst-lining cells suggests the involvement of TGF-β signaling in this disease. In this study, we ablated the TGF-β type 1 receptor (also termed activin receptor–like kinase 5) in renal epithelial cells of PKD mice, which had little to no effect on the expression of SMAD2/3 target genes or the progression of PKD. Therefore, we investigated whether alternative TGF-β superfamily ligands account for SMAD2/3 activation in cystic epithelial cells. Activins are members of the TGF-β superfamily and drive SMAD2/3 phosphorylation via activin receptors, but activins have not been studied in the context of PKD. Mice with PKD had increased expression of activin ligands, even at early stages of disease. In addition, treatment with a soluble activin receptor IIB fusion (sActRIIB-Fc) protein, which acts as a soluble trap to sequester activin ligands, effectively inhibited cyst formation in three distinct mouse models of PKD. These data point to activin signaling as a key pathway in PKD and a promising target for therapy.10.1681/ASN.2015030287Mon, 28 Mar 2016 06:04:43 GMT-07:00Inhibition of Activin Signaling Slows Progression of Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD), characterized by the formation of numerous kidney cysts, is caused by PKD1 or PKD2 mutations and affects 0.1% of the population. Although recent clinical studies indicate that reduction of cAMP levels slows progression of PKD, this finding has not led to an established safe and effective therapy for patients, indicating the need to find new therapeutic targets. The role of TGF-β in PKD is not clearly understood, but nuclear accumulation of phosphorylated SMAD2/3 in cyst-lining cells suggests the involvement of TGF-β signaling in this disease. In this study, we ablated the TGF-β type 1 receptor (also termed activin receptor–like kinase 5) in renal epithelial cells of PKD mice, which had little to no effect on the expression of SMAD2/3 target genes or the progression of PKD. Therefore, we investigated whether alternative TGF-β superfamily ligands account for SMAD2/3 activation in cystic epithelial cells. Activins are members of the TGF-β superfamily and drive SMAD2/3 phosphorylation via activin receptors, but activins have not been studied in the context of PKD. Mice with PKD had increased expression of activin ligands, even at early stages of disease. In addition, treatment with a soluble activin receptor IIB fusion (sActRIIB-Fc) protein, which acts as a soluble trap to sequester activin ligands, effectively inhibited cyst formation in three distinct mouse models of PKD. These data point to activin signaling as a key pathway in PKD and a promising target for therapy.Leonhard, Wouter N.Kunnen, Steven J.Plugge, Anna J.Pasternack, ArjaJianu, Sebastian B.T.Veraar, Kimberleyel Bouazzaoui, FatihaHoogaars, Willem M.H.ten Dijke, PeterBreuning, Martijn H.De Heer, EmileRitvos, OlliPeters, Dorien J.M.2016-03-28T06:04:43-07:00doi:10.1681/ASN.2015030287hwp:resource-id:jnephrol;27/12/3589American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, ADPKD, TGF-beta, genetic renal disease, Activin, inhbBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150302871046-66731533-34502016-03-28T06:04:43-07:002016-12Journal of the American Society of NephrologyBasic Research271235893599
- A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial NephritisKaryomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy characterized by tubulointerstitial nephritis and formation of enlarged nuclei in the kidneys and other tissues. We recently reported that recessive mutations in the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans. FAN1 is a major component of the Fanconi anemia–related pathway of DNA damage response (DDR) signaling. To study the pathogenesis of KIN, we generated a Fan1 knockout mouse model, with abrogation of Fan1 expression confirmed by quantitative RT-PCR. Challenging Fan1−/− and wild-type mice with 20 mg/kg cisplatin caused AKI in both genotypes. In contrast, chronic injection of cisplatin at 2 mg/kg induced KIN that led to renal failure within 5 weeks in Fan1−/− mice but not in wild-type mice. Cell culture studies showed decreased survival and reduced colony formation of Fan1−/− mouse embryonic fibroblasts and bone marrow mesenchymal stem cells compared with wild-type counterparts in response to treatment with genotoxic agents, suggesting that FAN1 mutations cause chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in the physiologic response of kidney tubular cells to DNA damage, which contributes to the pathogenesis of CKD. Moreover, Fan1−/− mice provide a new model with which to study the pathomechanisms of CKD.10.1681/ASN.2015101108Tue, 29 Mar 2016 07:00:05 GMT-07:00A FANCD2/FANCI-Associated Nuclease 1-Knockout Model Develops Karyomegalic Interstitial NephritisKaryomegalic interstitial nephritis (KIN) is a chronic interstitial nephropathy characterized by tubulointerstitial nephritis and formation of enlarged nuclei in the kidneys and other tissues. We recently reported that recessive mutations in the gene encoding FANCD2/FANCI-associated nuclease 1 (FAN1) cause KIN in humans. FAN1 is a major component of the Fanconi anemia–related pathway of DNA damage response (DDR) signaling. To study the pathogenesis of KIN, we generated a Fan1 knockout mouse model, with abrogation of Fan1 expression confirmed by quantitative RT-PCR. Challenging Fan1−/− and wild-type mice with 20 mg/kg cisplatin caused AKI in both genotypes. In contrast, chronic injection of cisplatin at 2 mg/kg induced KIN that led to renal failure within 5 weeks in Fan1−/− mice but not in wild-type mice. Cell culture studies showed decreased survival and reduced colony formation of Fan1−/− mouse embryonic fibroblasts and bone marrow mesenchymal stem cells compared with wild-type counterparts in response to treatment with genotoxic agents, suggesting that FAN1 mutations cause chemosensitivity and bone marrow failure. Our data show that Fan1 is involved in the physiologic response of kidney tubular cells to DNA damage, which contributes to the pathogenesis of CKD. Moreover, Fan1−/− mice provide a new model with which to study the pathomechanisms of CKD.Airik, RannarSchueler, MarkusAirik, MerlinCho, JangPorath, Jonathan D.Mukherjee, ElinaSims-Lucas, SunderHildebrandt, Friedhelm2016-03-29T07:00:05-07:00doi:10.1681/ASN.2015101108hwp:resource-id:jnephrol;27/12/3552American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyFAN1, karyomegalic interstitial nephritis, DNA damage response signaling, chronic kidney disease, genetic renal diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-12-01December 201610.1681/ASN.20151011081046-66731533-34502016-03-29T07:00:05-07:002016-12Journal of the American Society of NephrologyBrief Communications271235523559
- Capillary Rarefaction Associates with Albuminuria: The Maastricht StudyAlbuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria.10.1681/ASN.2015111219Mon, 09 May 2016 06:33:56 GMT-07:00Capillary Rarefaction Associates with Albuminuria: The Maastricht StudyAlbuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria.Martens, Remy J.H.Henry, Ronald M.A.Houben, Alfons J.H.M.van der Kallen, Carla J.H.Kroon, Abraham A.Schalkwijk, Casper G.Schram, Miranda T.Sep, Simone J.S.Schaper, Nicolaas C.Dagnelie, Pieter C.Muris, Dennis M.J.Gronenschild, Ed H.B.M.van der Sande, Frank M.Leunissen, Karel M.L.Kooman, Jeroen P.Stehouwer, Coen D.A.2016-05-09T06:33:56-07:00doi:10.1681/ASN.2015111219hwp:resource-id:jnephrol;27/12/3748American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, diabetic nephropathy, microalbuminuria, endotheliumClinical EpidemiologyClinical Epidemiologyresearch-article20162016-12-01December 201610.1681/ASN.20151112191046-66731533-34502016-05-09T06:33:56-07:002016-12Journal of the American Society of NephrologyClinical Epidemiology271237483757
- Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disruption of the Glomerular GlycocalyxDiabetic nephropathy (DN) is the leading cause of CKD in the Western world. Endothelin receptor antagonists have emerged as a novel treatment for DN, but the mechanisms underlying the protective effect remain unknown. We previously showed that both heparanase and endothelin-1 are essential for the development of DN. Here, we further investigated the role of these proteins in DN, and demonstrated that endothelin-1 activates podocytes to release heparanase. Furthermore, conditioned podocyte culture medium increased glomerular transendothelial albumin passage in a heparanase-dependent manner. In mice, podocyte-specific knockout of the endothelin receptor prevented the diabetes-induced increase in glomerular heparanase expression, consequent reduction in heparan sulfate expression and endothelial glycocalyx thickness, and development of proteinuria observed in wild-type counterparts. Our data suggest that in diabetes, endothelin-1 signaling, as occurs in endothelial activation, induces heparanase expression in the podocyte, damage to the glycocalyx, proteinuria, and renal failure. Thus, prevention of these effects may constitute the mechanism of action of endothelin receptor blockers in DN.10.1681/ASN.2015091070Tue, 29 Mar 2016 07:00:04 GMT-07:00Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disruption of the Glomerular GlycocalyxDiabetic nephropathy (DN) is the leading cause of CKD in the Western world. Endothelin receptor antagonists have emerged as a novel treatment for DN, but the mechanisms underlying the protective effect remain unknown. We previously showed that both heparanase and endothelin-1 are essential for the development of DN. Here, we further investigated the role of these proteins in DN, and demonstrated that endothelin-1 activates podocytes to release heparanase. Furthermore, conditioned podocyte culture medium increased glomerular transendothelial albumin passage in a heparanase-dependent manner. In mice, podocyte-specific knockout of the endothelin receptor prevented the diabetes-induced increase in glomerular heparanase expression, consequent reduction in heparan sulfate expression and endothelial glycocalyx thickness, and development of proteinuria observed in wild-type counterparts. Our data suggest that in diabetes, endothelin-1 signaling, as occurs in endothelial activation, induces heparanase expression in the podocyte, damage to the glycocalyx, proteinuria, and renal failure. Thus, prevention of these effects may constitute the mechanism of action of endothelin receptor blockers in DN.Garsen, MarjoleinLenoir, OliviaRops, Angelique L.W.M.M.Dijkman, Henry B.Willemsen, Brigithvan Kuppevelt, Toin H.Rabelink, Ton J.Berden, Jo H.M.Tharaux, Pierre-Louisvan der Vlag, Johan2016-03-29T07:00:04-07:00doi:10.1681/ASN.2015091070hwp:resource-id:jnephrol;27/12/3545American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, diabetic nephropathy, glomerular filtration barrier, glomerular endothelial cells, podocyteBrief CommunicationsBrief Communicationsbrief-report20162016-12-01December 201610.1681/ASN.20150910701046-66731533-34502016-03-29T07:00:04-07:002016-12Journal of the American Society of NephrologyBrief Communications271235453551
- Coronary Revascularization in Patients with CKD Stage 5D: Pragmatic ConsiderationsCoronary revascularization decisions for patients with CKD stage 5D present a dilemma for clinicians because of high baseline risks of mortality and future cardiovascular events. This population differs from the general population regarding characteristics of coronary plaque composition and behavior, accuracy of noninvasive testing, and response to surgical and percutaneous revascularization, such that findings from the general population cannot be automatically extrapolated. However, this high-risk population has been excluded from all randomized trials evaluating outcomes of revascularization. Observational studies have attempted to address long-term outcomes after surgical versus percutaneous revascularization strategies, but inherent selection bias may limit accuracy. Compared with percutaneous strategies, surgical revascularization seems to have long–term survival benefit on the basis of observational data but associates with substantially higher short–term mortality rates. Percutaneous revascularization with drug-eluting and bare metal stents associates with a high risk of in-stent restenosis and need for future revascularization, perhaps contributing to the higher long–term mortality hazard. Off–pump coronary bypass surgery and the newest generation of drug–eluting stent platforms offer no definitive benefits. In this review, we address the nuances, complexities, and tradeoffs that clinicians face in determining the optimal method of coronary revascularization for this high-risk population.10.1681/ASN.2016030345Thu, 04 Aug 2016 05:44:09 GMT-07:00Coronary Revascularization in Patients with CKD Stage 5D: Pragmatic ConsiderationsCoronary revascularization decisions for patients with CKD stage 5D present a dilemma for clinicians because of high baseline risks of mortality and future cardiovascular events. This population differs from the general population regarding characteristics of coronary plaque composition and behavior, accuracy of noninvasive testing, and response to surgical and percutaneous revascularization, such that findings from the general population cannot be automatically extrapolated. However, this high-risk population has been excluded from all randomized trials evaluating outcomes of revascularization. Observational studies have attempted to address long-term outcomes after surgical versus percutaneous revascularization strategies, but inherent selection bias may limit accuracy. Compared with percutaneous strategies, surgical revascularization seems to have long–term survival benefit on the basis of observational data but associates with substantially higher short–term mortality rates. Percutaneous revascularization with drug-eluting and bare metal stents associates with a high risk of in-stent restenosis and need for future revascularization, perhaps contributing to the higher long–term mortality hazard. Off–pump coronary bypass surgery and the newest generation of drug–eluting stent platforms offer no definitive benefits. In this review, we address the nuances, complexities, and tradeoffs that clinicians face in determining the optimal method of coronary revascularization for this high-risk population.Shroff, Gautam R.Herzog, Charles A.2016-08-04T05:44:09-07:00doi:10.1681/ASN.2016030345hwp:resource-id:jnephrol;27/12/3521American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycoronary revascularization, chronic kidney disease, cardiovascular diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-12-01December 201610.1681/ASN.20160303451046-66731533-34502016-08-04T05:44:09-07:002016-12Journal of the American Society of NephrologyUp Front Matters271235213529
- Acidosis and Urinary Calcium Excretion: Insights from Genetic DisordersMetabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.10.1681/ASN.2016030305Thu, 28 Jul 2016 05:44:08 GMT-07:00Acidosis and Urinary Calcium Excretion: Insights from Genetic DisordersMetabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport in the renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis.Alexander, R. ToddCordat, EmmanuelleChambrey, RégineDimke, HenrikEladari, Dominique2016-07-28T05:44:08-07:00doi:10.1681/ASN.2016030305hwp:resource-id:jnephrol;27/12/3511American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal tubular acidosis, chronic metabolic acidosis, calcium, hypercalciuriaUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-12-01December 201610.1681/ASN.20160303051046-66731533-34502016-07-28T05:44:08-07:002016-12Journal of the American Society of NephrologyUp Front Matters271235113520
- Association between Preoperative Vascular Function and Postoperative Arteriovenous Fistula DevelopmentArteriovenous fistula (AVF) maturation failure is the primary cause of dialysis vascular access dysfunction. To evaluate whether preoperative vascular functional properties predict postoperative AVF measurements, patients enrolled in the Hemodialysis Fistula Maturation Study underwent up to five preoperative vascular function tests (VFTs): flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, and venous occlusion plethysmography. We used mixed effects multiple regression analyses to relate each preoperative VFT to ultrasound measurements of AVF blood flow rate and venous diameter at 1 day, 2 weeks, and 6 weeks after AVF placement. After controlling for AVF location, preoperative ultrasound measurements, and demographic factors (age, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence interval [95% CI], 3.7% to 25.3%; P<0.01; change in diameter =0.45 mm; 95% CI, 0.25 to 0.65 mm; P<0.001). Greater FMD also associated with greater increases in 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in FMD: change in blood flow rate =11.6%; 95% CI, 0.6% to 23.9%; P=0.04; change in diameter =0.31 mm; 95% CI, 0.05 to 0.57 mm; P=0.02). None of the remaining VFT parameters exhibited consistent statistically significant relationships with both postoperative AVF blood flow rate and diameter. In conclusion, preoperative NMD and FMD positively associated with changes in 6-week AVF blood flow rate and diameter, suggesting that native functional arterial properties affect AVF development.10.1681/ASN.2015020141Mon, 09 May 2016 06:33:55 GMT-07:00Association between Preoperative Vascular Function and Postoperative Arteriovenous Fistula DevelopmentArteriovenous fistula (AVF) maturation failure is the primary cause of dialysis vascular access dysfunction. To evaluate whether preoperative vascular functional properties predict postoperative AVF measurements, patients enrolled in the Hemodialysis Fistula Maturation Study underwent up to five preoperative vascular function tests (VFTs): flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, and venous occlusion plethysmography. We used mixed effects multiple regression analyses to relate each preoperative VFT to ultrasound measurements of AVF blood flow rate and venous diameter at 1 day, 2 weeks, and 6 weeks after AVF placement. After controlling for AVF location, preoperative ultrasound measurements, and demographic factors (age, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence interval [95% CI], 3.7% to 25.3%; P<0.01; change in diameter =0.45 mm; 95% CI, 0.25 to 0.65 mm; P<0.001). Greater FMD also associated with greater increases in 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in FMD: change in blood flow rate =11.6%; 95% CI, 0.6% to 23.9%; P=0.04; change in diameter =0.31 mm; 95% CI, 0.05 to 0.57 mm; P=0.02). None of the remaining VFT parameters exhibited consistent statistically significant relationships with both postoperative AVF blood flow rate and diameter. In conclusion, preoperative NMD and FMD positively associated with changes in 6-week AVF blood flow rate and diameter, suggesting that native functional arterial properties affect AVF development.Allon, MichaelGreene, TomDember, Laura M.Vita, Joseph A.Cheung, Alfred K.Hamburg, Naomi M.Imrey, Peter B.Kaufman, James S.Robbin, Michelle L.Shiu, Yan-TingTerry, Christi M.Umphrey, Heidi R.Feldman, Harold I.,2016-05-09T06:33:55-07:00doi:10.1681/ASN.2015020141hwp:resource-id:jnephrol;27/12/3788American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriovenous fistula, arteriovenous access, vascular accessClinical ResearchClinical Researchresearch-article20162016-12-01December 201610.1681/ASN.20150201411046-66731533-34502016-05-09T06:33:55-07:002016-12Journal of the American Society of NephrologyClinical Research2712123788350837953510
- This Month's Highlights10.1681/ASN.2016080834Wed, 30 Nov 2016 10:00:46 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2016-11-30T10:00:46-08:00doi:10.1681/ASN.2016080834hwp:resource-id:jnephrol;27/12/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-12-01December 201610.1681/ASN.20160808341046-66731533-34502016-11-30T10:00:46-08:002016-12Journal of the American Society of NephrologyThis Month's Highlights2712ii
- Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The Biologic ContextPatients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys. However, the large intrafamilial variation in the progression rate of ADPKD suggests involvement of additional factors other than the type of mutation. The identification of these factors will increase our understanding of ADPKD and could ultimately help in the development of a clinically relevant therapy. Our review addresses the mechanisms by which various biologic processes influence cyst formation and cyst growth, thereby explaining an important part of the inter- and intrafamilial variability in ADPKD. Numerous studies from many laboratories provide compelling evidence for the influence on cyst formation by spatiotemporal gene inactivation, the genetic context, the metabolic status, the presence of existing cysts, and whether the kidneys were challenged by renal injury. Collectively, a solid basis is provided for the concept that the probability of cyst formation is determined by functional PKD protein levels and the biologic context. We model these findings in a graphic representation called the cystic probability landscape, providing a robust conceptual understanding of why cells sometimes do or do not form cysts.10.1681/ASN.2016040425Thu, 04 Aug 2016 05:44:10 GMT-07:00Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The Biologic ContextPatients with autosomal dominant polycystic kidney disease (ADPKD) typically carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst formation in both kidneys. However, the large intrafamilial variation in the progression rate of ADPKD suggests involvement of additional factors other than the type of mutation. The identification of these factors will increase our understanding of ADPKD and could ultimately help in the development of a clinically relevant therapy. Our review addresses the mechanisms by which various biologic processes influence cyst formation and cyst growth, thereby explaining an important part of the inter- and intrafamilial variability in ADPKD. Numerous studies from many laboratories provide compelling evidence for the influence on cyst formation by spatiotemporal gene inactivation, the genetic context, the metabolic status, the presence of existing cysts, and whether the kidneys were challenged by renal injury. Collectively, a solid basis is provided for the concept that the probability of cyst formation is determined by functional PKD protein levels and the biologic context. We model these findings in a graphic representation called the cystic probability landscape, providing a robust conceptual understanding of why cells sometimes do or do not form cysts.Leonhard, Wouter N.Happe, HesterPeters, Dorien J.M.2016-08-04T05:44:10-07:00doi:10.1681/ASN.2016040425hwp:resource-id:jnephrol;27/12/3530American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, Probability Landscape, Biological Context, ADPKD, PKD1, PolycystinUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-12-01December 201610.1681/ASN.20160404251046-66731533-34502016-08-04T05:44:10-07:002016-12Journal of the American Society of NephrologyUp Front Matters271235303538
- Phospholipase A2 Receptor–Related Membranous Nephropathy and Mannan-Binding Lectin DeficiencyMost patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL deficiency. Genotyping revealed a heterozygous (A/C) polymorphism in codon 57 of MBL2 exon 1 associated with homozygous and heterozygous variations in the promoter region at −550 (L/L) and −221 (X/Y), respectively, suggesting that the patient harbored the LXA/LYC haplotypes linked to MBL deficiency. Genetic sequencing in 77 consecutive patients with IMN identified four patients with MBL2 promoter and coding region variations associated with MBL deficiency and the same complement pattern in immune deposits as the index patient. In contrast, patients with wild-type MBL2 had immune deposits with intense Cd4 staining. Thus, IMN can develop in patients with complete MBL deficiency, with complement activated mainly by the alternative pathway, whereas the lectin pathway is also activated in those with wild-type MBL2.10.1681/ASN.2015101155Fri, 06 May 2016 08:56:02 GMT-07:00Phospholipase A2 Receptor–Related Membranous Nephropathy and Mannan-Binding Lectin DeficiencyMost patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL deficiency. Genotyping revealed a heterozygous (A/C) polymorphism in codon 57 of MBL2 exon 1 associated with homozygous and heterozygous variations in the promoter region at −550 (L/L) and −221 (X/Y), respectively, suggesting that the patient harbored the LXA/LYC haplotypes linked to MBL deficiency. Genetic sequencing in 77 consecutive patients with IMN identified four patients with MBL2 promoter and coding region variations associated with MBL deficiency and the same complement pattern in immune deposits as the index patient. In contrast, patients with wild-type MBL2 had immune deposits with intense Cd4 staining. Thus, IMN can develop in patients with complete MBL deficiency, with complement activated mainly by the alternative pathway, whereas the lectin pathway is also activated in those with wild-type MBL2.Bally, StéphaneDebiec, HannaPonard, DeniseDijoud, FrédériqueRendu, JohnFauré, JulienRonco, PierreDumestre-Perard, Chantal2016-05-06T08:56:02-07:00doi:10.1681/ASN.2015101155hwp:resource-id:jnephrol;27/12/3539American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, complement, glomerular disease, immunohistochemistryBrief CommunicationsBrief Communicationsbrief-report20162016-12-01December 201610.1681/ASN.20151011551046-66731533-34502016-05-06T08:56:02-07:002016-12Journal of the American Society of NephrologyBrief Communications271235393544
- Renin-Angiotensin-Aldosterone System Inhibition Increases Podocyte Derivation from Cells of Renin LineageBecause adult podocytes cannot proliferate and are therefore unable to self-renew, replacement of these cells depends on stem/progenitor cells. Although podocyte number is higher after renin-angiotensin-aldosterone system (RAAS) inhibition in glomerular diseases, the events explaining this increase are unclear. Cells of renin lineage (CoRL) have marked plasticity, including the ability to acquire a podocyte phenotype. To test the hypothesis that RAAS inhibition partially replenishes adult podocytes by increasing CoRL number, migration, and/or transdifferentiation, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R CoRL reporter mice to induce permanent labeling of CoRL with red fluorescent protein variant tdTomato. We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody. RAAS inhibition by enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin-receptor blocker) in FSGS mice stimulated the proliferation of CoRL, increasing the reservoir of these cells in the juxtaglomerular compartment (JGC). Compared with water or hydralazine, RAAS inhibition significantly increased the migration of CoRL from the JGC to the intraglomerular compartment (IGC), with more glomeruli containing RFP+CoRL and, within these glomeruli, more RFP+CoRL. Moreover, RAAS inhibition in FSGS mice increased RFP+CoRL transdifferentiation in the IGC to phenotypes, consistent with those of podocytes (coexpression of synaptopodin and Wilms tumor protein), parietal epithelial cells (PAX 8), and mesangial cells (α8 integrin). These results show that in the context of podocyte depletion in FSGS, RAAS inhibition augments CoRL proliferation and plasticity toward three different glomerular cell lineages.10.1681/ASN.2015080877Thu, 14 Apr 2016 08:01:57 GMT-07:00Renin-Angiotensin-Aldosterone System Inhibition Increases Podocyte Derivation from Cells of Renin LineageBecause adult podocytes cannot proliferate and are therefore unable to self-renew, replacement of these cells depends on stem/progenitor cells. Although podocyte number is higher after renin-angiotensin-aldosterone system (RAAS) inhibition in glomerular diseases, the events explaining this increase are unclear. Cells of renin lineage (CoRL) have marked plasticity, including the ability to acquire a podocyte phenotype. To test the hypothesis that RAAS inhibition partially replenishes adult podocytes by increasing CoRL number, migration, and/or transdifferentiation, we administered tamoxifen to Ren1cCreERxRs-tdTomato-R CoRL reporter mice to induce permanent labeling of CoRL with red fluorescent protein variant tdTomato. We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody. RAAS inhibition by enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin-receptor blocker) in FSGS mice stimulated the proliferation of CoRL, increasing the reservoir of these cells in the juxtaglomerular compartment (JGC). Compared with water or hydralazine, RAAS inhibition significantly increased the migration of CoRL from the JGC to the intraglomerular compartment (IGC), with more glomeruli containing RFP+CoRL and, within these glomeruli, more RFP+CoRL. Moreover, RAAS inhibition in FSGS mice increased RFP+CoRL transdifferentiation in the IGC to phenotypes, consistent with those of podocytes (coexpression of synaptopodin and Wilms tumor protein), parietal epithelial cells (PAX 8), and mesangial cells (α8 integrin). These results show that in the context of podocyte depletion in FSGS, RAAS inhibition augments CoRL proliferation and plasticity toward three different glomerular cell lineages.Lichtnekert, JuliaKaverina, Natalya V.Eng, Diana G.Gross, Kenneth W.Kutz, J. NathanPippin, Jeffrey W.Shankland, Stuart J.2016-04-14T08:01:57-07:00doi:10.1681/ASN.2015080877hwp:resource-id:jnephrol;27/12/3611American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyACE inhibitors, focal segmental glomerulosclerosis, podocyteBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150808771046-66731533-34502016-04-14T08:01:57-07:002016-12Journal of the American Society of NephrologyBasic Research271236113627
- Low–Energy Shockwave Therapy Improves Ischemic Kidney MicrocirculationMicrovascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low–energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low–energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low–energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β1-integrin) ex vivo. A 3-week low–energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low–energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low–energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.10.1681/ASN.2015060704Mon, 13 Jun 2016 11:37:23 GMT-07:00Low–Energy Shockwave Therapy Improves Ischemic Kidney MicrocirculationMicrovascular rarefaction distal to renal artery stenosis is linked to renal dysfunction and poor outcomes. Low–energy shockwave therapy stimulates angiogenesis, but the effect on the kidney microvasculature is unknown. We hypothesized that low–energy shockwave therapy would restore the microcirculation and alleviate renal dysfunction in renovascular disease. Normal pigs and pigs subjected to 3 weeks of renal artery stenosis were treated with six sessions of low–energy shockwave (biweekly for 3 consecutive weeks) or left untreated. We assessed BP, urinary protein, stenotic renal blood flow, GFR, microvascular structure, and oxygenation in vivo 4 weeks after completion of treatment, and then, we assessed expression of angiogenic factors and mechanotransducers (focal adhesion kinase and β1-integrin) ex vivo. A 3-week low–energy shockwave regimen attenuated renovascular hypertension, normalized stenotic kidney microvascular density and oxygenation, stabilized function, and alleviated fibrosis in pigs subjected to renal artery stenosis. These effects associated with elevated renal expression of angiogenic factors and mechanotransducers, particularly in proximal tubular cells. In additional pigs with prolonged (6 weeks) renal artery stenosis, shockwave therapy also decreased BP and improved GFR, microvascular density, and oxygenation in the stenotic kidney. This shockwave regimen did not cause detectable kidney injury in normal pigs. In conclusion, low–energy shockwave therapy improves stenotic kidney function, likely in part by mechanotransduction-mediated expression of angiogenic factors in proximal tubular cells, and it may ameliorate renovascular hypertension. Low–energy shockwave therapy may serve as a novel noninvasive intervention in the management of renovascular disease.Zhang, XinKrier, James D.Amador Carrascal, CarolinaGreenleaf, James F.Ebrahimi, BehzadHedayat, Ahmad F.Textor, Stephen C.Lerman, AmirLerman, Lilach O.2016-06-13T11:37:23-07:00doi:10.1681/ASN.2015060704hwp:resource-id:jnephrol;27/12/3715American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal artery stenosis, chronic kidney disease, kidney dysfunctionBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150607041046-66731533-34502016-06-13T11:37:23-07:002016-12Journal of the American Society of NephrologyBasic Research271237153724
- Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule DevelopmentThe kidney is a highly polarized epithelial organ that develops from undifferentiated mesenchyme, although the mechanisms that regulate the development of renal epithelial polarity are incompletely understood. Partitioning-defective 1 (Par1) proteins have been implicated in cell polarity and epithelial morphogenesis; however, the role of these proteins in the developing kidney has not been established. Therefore, we studied the contribution of Par1a/b to renal epithelial development. We examined the renal phenotype of newborn compound mutant mice carrying only one allele of Par1a or Par1b. Loss of three out of four Par1a/b alleles resulted in severe renal hypoplasia, associated with impaired ureteric bud branching. Compared with kidneys of newborn control littermates, kidneys of newborn mutant mice exhibited dilated proximal tubules and immature glomeruli, and the renal proximal tubular epithelia lacked proper localization of adhesion complexes. Furthermore, Par1a/b mutants expressed low levels of renal Notch ligand Jag1, activated Notch2, and Notch effecter Hes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling.10.1681/ASN.2014111124Mon, 16 May 2016 08:22:22 GMT-07:00Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule DevelopmentThe kidney is a highly polarized epithelial organ that develops from undifferentiated mesenchyme, although the mechanisms that regulate the development of renal epithelial polarity are incompletely understood. Partitioning-defective 1 (Par1) proteins have been implicated in cell polarity and epithelial morphogenesis; however, the role of these proteins in the developing kidney has not been established. Therefore, we studied the contribution of Par1a/b to renal epithelial development. We examined the renal phenotype of newborn compound mutant mice carrying only one allele of Par1a or Par1b. Loss of three out of four Par1a/b alleles resulted in severe renal hypoplasia, associated with impaired ureteric bud branching. Compared with kidneys of newborn control littermates, kidneys of newborn mutant mice exhibited dilated proximal tubules and immature glomeruli, and the renal proximal tubular epithelia lacked proper localization of adhesion complexes. Furthermore, Par1a/b mutants expressed low levels of renal Notch ligand Jag1, activated Notch2, and Notch effecter Hes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling.Akchurin, OlehDu, ZhongfangRamkellawan, NadiraDalal, VidhiHan, Seung HyeokPullman, JamesMüsch, AnneSusztak, KatalinReidy, Kimberly J.2016-05-16T08:22:22-07:00doi:10.1681/ASN.2014111124hwp:resource-id:jnephrol;27/12/3725American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, proximal tubule, cell adhesion, renal epithelial cell, ureteric bud, podocyteBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20141111241046-66731533-34502016-05-16T08:22:22-07:002016-12Journal of the American Society of NephrologyBasic Research271237253737
- Residual Kidney Function Decline and Mortality in Incident Hemodialysis PatientsIn patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9–5.0) and −1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of −6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix–adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: −1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.10.1681/ASN.2015101142Wed, 11 May 2016 05:46:37 GMT-07:00Residual Kidney Function Decline and Mortality in Incident Hemodialysis PatientsIn patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9–5.0) and −1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of −6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix–adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: −1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.Obi, YoshitsuguRhee, Connie M.Mathew, Anna T.Shah, GaurangStreja, ElaniBrunelli, Steven M.Kovesdy, Csaba P.Mehrotra, RajnishKalantar-Zadeh, Kamyar2016-05-11T05:46:37-07:00doi:10.1681/ASN.2015101142hwp:resource-id:jnephrol;27/12/3758American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis adequacy, hemodialysis, chronic hemodialysis, end stage kidney disease, end-stage renal disease, renal function declineClinical EpidemiologyClinical Epidemiologyresearch-article20162016-12-01December 201610.1681/ASN.20151011421046-66731533-34502016-05-11T05:46:37-07:002016-12Journal of the American Society of NephrologyClinical Epidemiology2712123758350437683507
- Metabolic Profiling of Impaired Cognitive Function in Patients Receiving DialysisRetention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites—4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline—were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.10.1681/ASN.2016010039Thu, 21 Jul 2016 06:40:51 GMT-07:00Metabolic Profiling of Impaired Cognitive Function in Patients Receiving DialysisRetention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites—4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline—were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.Kurella Tamura, ManjulaChertow, Glenn M.Depner, Thomas A.Nissenson, Allen R.Schiller, BrigitteMehta, Ravindra L.Liu, SaiSirich, Tammy L.2016-07-21T06:40:51-07:00doi:10.1681/ASN.2016010039hwp:resource-id:jnephrol;27/12/3780American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, ESRD, metabolism, cognitive functionClinical ResearchClinical Researchresearch-article20162016-12-01December 201610.1681/ASN.20160100391046-66731533-34502016-07-21T06:40:51-07:002016-12Journal of the American Society of NephrologyClinical Research271237803787
- Immune-Regulatory Molecule CD69 Controls Peritoneal FibrosisPatients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.10.1681/ASN.2015080909Thu, 05 May 2016 07:03:10 GMT-07:00Immune-Regulatory Molecule CD69 Controls Peritoneal FibrosisPatients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.Liappas, GeorgiosGonzález-Mateo, Guadalupe TirmaSánchez-Díaz, RaquelLazcano, Juan JoséLasarte, SandraMatesanz-Marín, AdelaZur, RafalFerrantelli, EvelinaRamírez, Laura GarcíaAguilera, AbelardoFernández-Ruiz, ElenaBeelen, Robert H.J.Selgas, RafaelSánchez-Madrid, FranciscoMartín, PilarLópez-Cabrera, Manuel2016-05-05T07:03:10-07:00doi:10.1681/ASN.2015080909hwp:resource-id:jnephrol;27/12/3561American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyChronic inflammation, dialysis, fibrosis, Immunology and pathologyBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150809091046-66731533-34502016-05-05T07:03:10-07:002016-12Journal of the American Society of NephrologyBasic Research271235613576
- Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in ChinaThe effect of air pollution on the changing pattern of glomerulopathy has not been studied. We estimated the profile of and temporal change in glomerular diseases in an 11-year renal biopsy series including 71,151 native biopsies at 938 hospitals spanning 282 cities in China from 2004 to 2014, and examined the association of long-term exposure to fine particulate matter of <2.5 μm (PM2.5) with glomerulopathy. After age and region standardization, we identified IgA nephropathy as the leading type of glomerulopathy, with a frequency of 28.1%, followed by membranous nephropathy (MN), with a frequency of 23.4%. Notably, the adjusted odds for MN increased 13% annually over the 11-year study period, whereas the proportions of other major glomerulopathies remained stable. During the study period, 3-year average PM2.5 exposure varied among the 282 cities, ranging from 6 to 114 μg/m3 (mean, 52.6 μg/m3). Each 10 μg/m3 increase in PM2.5 concentration associated with 14% higher odds for MN (odds ratio, 1.14; 95% confidence interval, 1.10 to 1.18) in regions with PM2.5 concentration >70 μg/m3. We also found that higher 3-year average air quality index was associated with increased risk of MN. In conclusion, in this large renal biopsy series, the frequency of MN increased over the study period, and long-term exposure to high levels of PM2.5 was associated with an increased risk of MN.10.1681/ASN.2016010093Thu, 30 Jun 2016 07:40:48 GMT-07:00Long-Term Exposure to Air Pollution and Increased Risk of Membranous Nephropathy in ChinaThe effect of air pollution on the changing pattern of glomerulopathy has not been studied. We estimated the profile of and temporal change in glomerular diseases in an 11-year renal biopsy series including 71,151 native biopsies at 938 hospitals spanning 282 cities in China from 2004 to 2014, and examined the association of long-term exposure to fine particulate matter of <2.5 μm (PM2.5) with glomerulopathy. After age and region standardization, we identified IgA nephropathy as the leading type of glomerulopathy, with a frequency of 28.1%, followed by membranous nephropathy (MN), with a frequency of 23.4%. Notably, the adjusted odds for MN increased 13% annually over the 11-year study period, whereas the proportions of other major glomerulopathies remained stable. During the study period, 3-year average PM2.5 exposure varied among the 282 cities, ranging from 6 to 114 μg/m3 (mean, 52.6 μg/m3). Each 10 μg/m3 increase in PM2.5 concentration associated with 14% higher odds for MN (odds ratio, 1.14; 95% confidence interval, 1.10 to 1.18) in regions with PM2.5 concentration >70 μg/m3. We also found that higher 3-year average air quality index was associated with increased risk of MN. In conclusion, in this large renal biopsy series, the frequency of MN increased over the study period, and long-term exposure to high levels of PM2.5 was associated with an increased risk of MN.Xu, XinWang, GuobaoChen, NanLu, TaoNie, ShengXu, GangZhang, PingLuo, YangWang, YongpingWang, XiaobinSchwartz, JoelGeng, JianHou, Fan Fan2016-06-30T07:40:48-07:00doi:10.1681/ASN.2016010093hwp:resource-id:jnephrol;27/12/3739American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal biopsy, membranous nephropathy, air pollutionClinical EpidemiologyClinical Epidemiologyresearch-article20162016-12-01December 201610.1681/ASN.20160100931046-66731533-34502016-06-30T07:40:48-07:002016-12Journal of the American Society of NephrologyClinical Epidemiology271237393746
- Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft RejectionBelatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 and its alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesting that blocking CTLA-4 is deleterious. We performed a head to head assessment of FR104 (n=5), a selective pegylated Fab′ antibody fragment antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboons. The biologics were supplemented with an initial 1-month treatment with low-dose tacrolimus. In cases of acute rejection, animals also received steroids. In the belatacept group, four of five recipients developed severe, steroid–resistant acute cellular rejection, whereas FR104-treated animals did not. Assessment of regulatory T cell–specific demethylated region methylation status in 1-month biopsy samples revealed a nonsignificant trend for higher regulatory T cell frequencies in FR104-treated animals. Transcriptional analysis did not reveal significant differences in Th17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals. In vitro, FR104 controlled the proliferative response of human preexisting Tfh cells more efficiently than belatacept. In mice, selective CD28 blockade also controlled Tfh memory cell responses to KLH stimulation more efficiently than CD80/86 blockade. Our data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of renal allograft rejection, particularly at the level of Tfh cell stimulation.10.1681/ASN.2015070774Mon, 09 May 2016 06:33:57 GMT-07:00Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft RejectionBelatacept is a biologic that targets CD80/86 and prevents its interaction with CD28 and its alternative ligand, cytotoxic T lymphocyte antigen 4 (CTLA-4). Clinical experience in kidney transplantation has revealed a high incidence of rejection with belatacept, especially with intensive regimens, suggesting that blocking CTLA-4 is deleterious. We performed a head to head assessment of FR104 (n=5), a selective pegylated Fab′ antibody fragment antagonist of CD28 that does not block the CTLA-4 pathway, and belatacept (n=5) in kidney allotransplantation in baboons. The biologics were supplemented with an initial 1-month treatment with low-dose tacrolimus. In cases of acute rejection, animals also received steroids. In the belatacept group, four of five recipients developed severe, steroid–resistant acute cellular rejection, whereas FR104-treated animals did not. Assessment of regulatory T cell–specific demethylated region methylation status in 1-month biopsy samples revealed a nonsignificant trend for higher regulatory T cell frequencies in FR104-treated animals. Transcriptional analysis did not reveal significant differences in Th17 cytokines but did reveal higher levels of IL-21, the main cytokine secreted by CD4 T follicular helper (Tfh) cells, in belatacept-treated animals. In vitro, FR104 controlled the proliferative response of human preexisting Tfh cells more efficiently than belatacept. In mice, selective CD28 blockade also controlled Tfh memory cell responses to KLH stimulation more efficiently than CD80/86 blockade. Our data reveal that selective CD28 blockade and belatacept exert different effects on mechanisms of renal allograft rejection, particularly at the level of Tfh cell stimulation.Ville, SimonPoirier, NicolasBranchereau, JulienCharpy, VianneyPengam, SabrinaNerriere-Daguin, VéroniqueLe Bas-Bernardet, StéphanieCoulon, FloraMary, CarolineChenouard, AlexisHervouet, JeremyMinault, DavidNedellec, StevenRenaudin, KarineVanhove, BernardBlancho, Gilles2016-05-09T06:33:57-07:00doi:10.1681/ASN.2015070774hwp:resource-id:jnephrol;27/12/3577American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, immunology, immunosuppression, lymphocytes, acute rejectionBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150707741046-66731533-34502016-05-09T06:33:57-07:002016-12Journal of the American Society of NephrologyBasic Research271235773588
- APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney DiseaseAPOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.10.1681/ASN.2015111220Tue, 29 Mar 2016 07:00:06 GMT-07:00APOL1-G0 or APOL1-G2 Transgenic Models Develop Preeclampsia but Not Kidney DiseaseAPOL1 risk variants are associated with kidney disease in blacks, but the mechanisms of renal injury associated with APOL1 risk variants are unknown. Because APOL1 is unique to humans and some primates, we created transgenic (Tg) mice using the promoter of nephrin-encoding Nphs1 to express the APOL1 reference sequence (G0) or the G2 risk variant in podocytes, establishing Tg lines with a spectrum of APOL1 expression levels. Podocytes from Tg-G0 and Tg-G2 mice did not undergo necrosis, apoptosis, or autophagic cell death in vivo, even in lines with highly expressed transgenes. Further, Tg-G0 and Tg-G2 mice did not develop kidney pathology, proteinuria, or azotemia as of 300 days of age. However, by 200 days of age, Tg-G2 mice had significantly lower podocyte density than age-matched WT and Tg-G0 mice had, a difference that was not evident at weaning. Notably, a pregnancy-associated phenotype that encompassed eclampsia, preeclampsia, fetal/neonatal deaths, and small litter sizes occurred in some Tg-G0 mice and more severely in Tg-G2 mice. Similar to human placenta, placentas of Tg mice expressed APOL1. Overall, these results suggest podocyte depletion could predispose individuals with APOL1 risk genotypes to kidney disease in response to a second stressor, and add to other published evidence associating APOL1 expression with preeclampsia.Bruggeman, Leslie A.Wu, ZhenzhenLuo, LipingMadhavan, Sethu M.Konieczkowski, MarthaDrawz, Paul E.Thomas, David B.Barisoni, LauraSedor, John R.O'Toole, John F.2016-03-29T07:00:06-07:00doi:10.1681/ASN.2015111220hwp:resource-id:jnephrol;27/12/3600American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, podocyte, transgenic mouse, focal segmental glomerulosclerosis, chronic kidney diseaseBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20151112201046-66731533-34502016-03-29T07:00:06-07:002016-12Journal of the American Society of NephrologyBasic Research271236003610
- Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney CystsThe gene for ADP ribosylation factor–like GTPase 13B (Arl13b) encodes a small GTPase essential for cilia biogenesis in multiple model organisms. Inactivation of arl13b in zebrafish leads to a number of phenotypes indicative of defective cilia, including cystic kidneys. In mouse, null mutation in Arl13b results in severe patterning defects in the neural tube and defective Hedgehog signaling. Human mutations of ARL13B lead to Joubert syndrome, a ciliopathy. However, patients with mutated ARL13B do not develop kidney cysts. To investigate whether Arl13b has a role in ciliogenesis in mammalian kidney and whether loss of function of Arl13b leads to cystic kidneys in mammals, we generated a mouse model with kidney–specific conditional knockout of Arl13b. Deletion of Arl13b in the distal nephron at the perinatal stage led to a cilia biogenesis defect and rapid kidney cyst formation. Additionally, we detected misregulation of multiple pathways in the cystic kidneys of this model. Moreover, valproic acid, a histone deacetylase inhibitor that we previously showed slows cyst progression in a mouse cystic kidney model with neonatal inactivation of Pkd1, inhibited the early rise of Wnt7a expression, ameliorated fibrosis, slowed cyst progression, and improved kidney function in the Arl13b mutant mouse. Finally, in rescue experiments in zebrafish, all ARL13B allele combinations identified in patients with Joubert syndrome provided residual Arl13b function, supporting the idea that the lack of cystic kidney phenotype in human patients with ARL13B mutations is explained by the hypomorphic nature of the mutations.10.1681/ASN.2015091004Fri, 06 May 2016 08:56:00 GMT-07:00Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney CystsThe gene for ADP ribosylation factor–like GTPase 13B (Arl13b) encodes a small GTPase essential for cilia biogenesis in multiple model organisms. Inactivation of arl13b in zebrafish leads to a number of phenotypes indicative of defective cilia, including cystic kidneys. In mouse, null mutation in Arl13b results in severe patterning defects in the neural tube and defective Hedgehog signaling. Human mutations of ARL13B lead to Joubert syndrome, a ciliopathy. However, patients with mutated ARL13B do not develop kidney cysts. To investigate whether Arl13b has a role in ciliogenesis in mammalian kidney and whether loss of function of Arl13b leads to cystic kidneys in mammals, we generated a mouse model with kidney–specific conditional knockout of Arl13b. Deletion of Arl13b in the distal nephron at the perinatal stage led to a cilia biogenesis defect and rapid kidney cyst formation. Additionally, we detected misregulation of multiple pathways in the cystic kidneys of this model. Moreover, valproic acid, a histone deacetylase inhibitor that we previously showed slows cyst progression in a mouse cystic kidney model with neonatal inactivation of Pkd1, inhibited the early rise of Wnt7a expression, ameliorated fibrosis, slowed cyst progression, and improved kidney function in the Arl13b mutant mouse. Finally, in rescue experiments in zebrafish, all ARL13B allele combinations identified in patients with Joubert syndrome provided residual Arl13b function, supporting the idea that the lack of cystic kidney phenotype in human patients with ARL13B mutations is explained by the hypomorphic nature of the mutations.Li, YuanyuanTian, XinMa, MingJerman, StephanieKong, ShanshanSomlo, StefanSun, Zhaoxia2016-05-06T08:56:00-07:00doi:10.1681/ASN.2015091004hwp:resource-id:jnephrol;27/12/3628American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, renal fibrosis, signalingBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150910041046-66731533-34502016-05-06T08:56:00-07:002016-12Journal of the American Society of NephrologyBasic Research271236283638
- TWEAK-Fn14 Signaling Activates Myofibroblasts to Drive Progression of Fibrotic Kidney DiseaseThe identification of the cellular origins of myofibroblasts has led to the discovery of novel pathways that potentially drive myofibroblast perpetuation in disease. Here, we further investigated the role of innate immune signaling pathways in this process. In mice, renal injury-induced activation of pericytes, which are myofibroblast precursors attached to endothelial cells, led to upregulated expression of TNF receptor superfamily member 12a, also known as fibroblast growth factor-inducible 14 (Fn14), by these cells. In live rat kidney slices, administration of the Fn14 ligand, TNF-related weak inducer of apoptosis (TWEAK), promoted pericyte-dependent vasoconstriction followed by pericyte detachment from capillaries. In vitro, administration of TWEAK activated and differentiated pericytes into cytokine-producing myofibroblasts, and further activated established myofibroblasts in a manner requiring canonical and noncanonical NF-κB signaling pathways. Deficiency of Fn14 protected mouse kidneys from fibrogenesis, inflammation, and associated vascular instability after in vivo injury, and was associated with loss of NF-κB signaling. In a genetic model of spontaneous CKD, therapeutic delivery of anti-TWEAK blocking antibodies attenuated disease progression, preserved organ function, and increased survival. These results identify the TWEAK-Fn14 signaling pathway as an important factor in myofibroblast perpetuation, fibrogenesis, and chronic disease progression.10.1681/ASN.2015111227Tue, 29 Mar 2016 07:00:03 GMT-07:00TWEAK-Fn14 Signaling Activates Myofibroblasts to Drive Progression of Fibrotic Kidney DiseaseThe identification of the cellular origins of myofibroblasts has led to the discovery of novel pathways that potentially drive myofibroblast perpetuation in disease. Here, we further investigated the role of innate immune signaling pathways in this process. In mice, renal injury-induced activation of pericytes, which are myofibroblast precursors attached to endothelial cells, led to upregulated expression of TNF receptor superfamily member 12a, also known as fibroblast growth factor-inducible 14 (Fn14), by these cells. In live rat kidney slices, administration of the Fn14 ligand, TNF-related weak inducer of apoptosis (TWEAK), promoted pericyte-dependent vasoconstriction followed by pericyte detachment from capillaries. In vitro, administration of TWEAK activated and differentiated pericytes into cytokine-producing myofibroblasts, and further activated established myofibroblasts in a manner requiring canonical and noncanonical NF-κB signaling pathways. Deficiency of Fn14 protected mouse kidneys from fibrogenesis, inflammation, and associated vascular instability after in vivo injury, and was associated with loss of NF-κB signaling. In a genetic model of spontaneous CKD, therapeutic delivery of anti-TWEAK blocking antibodies attenuated disease progression, preserved organ function, and increased survival. These results identify the TWEAK-Fn14 signaling pathway as an important factor in myofibroblast perpetuation, fibrogenesis, and chronic disease progression.Gomez, Ivan G.Roach, Allie M.Nakagawa, NaokiAmatucci, AldoJohnson, Bryce G.Dunn, KadeshiaKelly, Mark C.Karaca, GamzeZheng, Timothy S.Szak, SuzannePeppiatt-Wildman, Claire M.Burkly, Linda C.Duffield, Jeremy S.2016-03-29T07:00:03-07:00doi:10.1681/ASN.2015111227hwp:resource-id:jnephrol;27/12/3639American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypericyte, myofibroblast, vascular biology, Alport nephropathy, chronic, kidney diseaseBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20151112271046-66731533-34502016-03-29T07:00:03-07:002016-12Journal of the American Society of NephrologyBasic Research2712123639350236523504
- Role of Ragulator in the Regulation of Mechanistic Target of Rapamycin Signaling in Podocytes and Glomerular FunctionAberrant activation of mechanistic target of rapamycin complex 1 (mTORC1) in glomerular podocytes leads to glomerular insufficiency and may contribute to the development of glomerular diseases, including diabetic nephropathy. Thus, an approach for preventing mTORC1 activation may allow circumvention of the onset and progression of mTORC1-dependent podocyte injury and glomerular diseases. mTORC1 activation requires inputs from both growth factors and nutrients that inactivate the tuberous sclerosis complex (TSC), a key suppressor of mTORC1, on the lysosome. Previous studies in mice revealed that the growth factor-phosphatidylinositol 3-kinase pathway and mTORC1 are essential for maintaining normal podocyte function, suggesting that direct inhibition of the phosphatidylinositol 3-kinase pathway or mTORC1 may not be an ideal approach to sustaining physiologic podocyte functions under certain disease conditions. Here, we report the role of the Ragulator complex, which recruits mTORC1 to lysosomes in response to nutrient availability in podocytes. Notably, podocytes lacking Ragulator maintain basal mTORC1 activity. Unlike podocyte-specific mTORC1-knockout mice, mice lacking functional Ragulator in podocytes did not show abnormalities in podocyte or glomerular function. However, aberrant mTORC1 activation induced by active Rheb in podocyte-specific TSC1-knockout (podo-TSC1 KO) mice did require Ragulator. Moreover, ablation of Ragulator in the podocytes of podo-TSC1 KO mice or streptozotocin-induced diabetic mice significantly blocked the development of pathologic renal phenotypes. These observations suggest that the blockade of mTORC1 recruitment to lysosomes may be a useful clinical approach to attenuate aberrant mTORC1 activation under certain disease conditions.10.1681/ASN.2015010032Thu, 31 Mar 2016 07:21:59 GMT-07:00Role of Ragulator in the Regulation of Mechanistic Target of Rapamycin Signaling in Podocytes and Glomerular FunctionAberrant activation of mechanistic target of rapamycin complex 1 (mTORC1) in glomerular podocytes leads to glomerular insufficiency and may contribute to the development of glomerular diseases, including diabetic nephropathy. Thus, an approach for preventing mTORC1 activation may allow circumvention of the onset and progression of mTORC1-dependent podocyte injury and glomerular diseases. mTORC1 activation requires inputs from both growth factors and nutrients that inactivate the tuberous sclerosis complex (TSC), a key suppressor of mTORC1, on the lysosome. Previous studies in mice revealed that the growth factor-phosphatidylinositol 3-kinase pathway and mTORC1 are essential for maintaining normal podocyte function, suggesting that direct inhibition of the phosphatidylinositol 3-kinase pathway or mTORC1 may not be an ideal approach to sustaining physiologic podocyte functions under certain disease conditions. Here, we report the role of the Ragulator complex, which recruits mTORC1 to lysosomes in response to nutrient availability in podocytes. Notably, podocytes lacking Ragulator maintain basal mTORC1 activity. Unlike podocyte-specific mTORC1-knockout mice, mice lacking functional Ragulator in podocytes did not show abnormalities in podocyte or glomerular function. However, aberrant mTORC1 activation induced by active Rheb in podocyte-specific TSC1-knockout (podo-TSC1 KO) mice did require Ragulator. Moreover, ablation of Ragulator in the podocytes of podo-TSC1 KO mice or streptozotocin-induced diabetic mice significantly blocked the development of pathologic renal phenotypes. These observations suggest that the blockade of mTORC1 recruitment to lysosomes may be a useful clinical approach to attenuate aberrant mTORC1 activation under certain disease conditions.Yao, YaoWang, JunyingYoshida, SeiNada, ShigeyukiOkada, MasatoInoki, Ken2016-03-31T07:21:59-07:00doi:10.1681/ASN.2015010032hwp:resource-id:jnephrol;27/12/3653American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynutrition, podocyte, renal cell biology, signaling, diabetic glomerulopathy, glomerulopathyBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150100321046-66731533-34502016-03-31T07:21:59-07:002016-12Journal of the American Society of NephrologyBasic Research271236533665
- IL-17F Promotes Tissue Injury in Autoimmune Kidney DiseasesThe TH17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional TH17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4+ T cells and γδ T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene–deficient mice, IL-17F–neutralizing antibodies, and adoptive transfer experiments into Rag1−/− mice demonstrated that CD4+ T cell–derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F–deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F–deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F–deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti–IL-17 cytokine therapies in TH17-mediated human autoimmune diseases.10.1681/ASN.2015101077Wed, 30 Mar 2016 06:21:53 GMT-07:00IL-17F Promotes Tissue Injury in Autoimmune Kidney DiseasesThe TH17 immune response has a central role in the pathogenesis of autoimmune diseases, implicating the TH17 master cytokine, IL-17A, as the critical mediator of diseases such as human and experimental crescentic GN. However, the relative importance of additional TH17 effector cytokines, including IL-17F, in immune-mediated tissue injury remains to be fully elucidated. Here, using a mouse model of acute crescentic GN (nephrotoxic nephritis), we identified CD4+ T cells and γδ T cells as the major cellular source of IL-17F in the inflamed kidney. Interventional studies using IL-17F gene–deficient mice, IL-17F–neutralizing antibodies, and adoptive transfer experiments into Rag1−/− mice demonstrated that CD4+ T cell–derived IL-17F drives renal tissue injury in acute crescentic GN. Notably, IL-17F–deficient nephritic mice had fewer renal infiltrating neutrophils than wild-type nephritic mice, and neutrophil depletion did not affect the course of GN in IL-17F–deficient mice. Moreover, in the chronic model of pristane-induced SLE, IL-17F–deficient mice developed less severe disease than wild-type mice, with respect to survival and renal injury. Finally, we show that IL-17F induced expression of the neutrophil-attracting chemokines CXCL1 and CXCL5 in kidney cells. The finding that IL-17F has a nonredundant function in the development of renal tissue injury in experimental GN might be of great importance for the development of anti–IL-17 cytokine therapies in TH17-mediated human autoimmune diseases.Riedel, Jan-HendrikPaust, Hans-JoachimKrohn, SonjaTurner, Jan-EricKluger, Malte A.Steinmetz, Oliver M.Krebs, Christian F.Stahl, Rolf A.K.Panzer, Ulf2016-03-30T06:21:53-07:00doi:10.1681/ASN.2015101077hwp:resource-id:jnephrol;27/12/3666American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologylymphocytes, cytokines, glomerulonephritis, immunology, systemic lupus erythematosusBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20151010771046-66731533-34502016-03-30T06:21:53-07:002016-12Journal of the American Society of NephrologyBasic Research271236663677
- Stat3 Controls Tubulointerstitial Communication during CKDIn CKD, tubular cells may be involved in the induction of interstitial fibrosis, which in turn, leads to loss of renal function. However, the molecular mechanisms that link tubular cells to the interstitial compartment are not clear. Activation of the Stat3 transcription factor has been reported in tubular cells after renal damage, and Stat3 has been implicated in CKD progression. Here, we combined an experimental model of nephron reduction in mice from different genetic backgrounds and genetically modified animals with in silico and in vitro experiments to determine whether the selective activation of Stat3 in tubular cells is involved in the development of interstitial fibrosis. Nephron reduction caused Stat3 phosphorylation in tubular cells of lesion-prone mice but not in resistant mice. Furthermore, specific deletion of Stat3 in tubular cells significantly reduced the extent of interstitial fibrosis, which correlated with reduced fibroblast proliferation and matrix synthesis, after nephron reduction. Mechanistically, in vitro tubular Stat3 activation triggered the expression of a specific subset of paracrine profibrotic factors, including Lcn2, Pdgfb, and Timp1. Together, our results provide a molecular link between tubular and interstitial cells during CKD progression and identify Stat3 as a central regulator of this link and a promising therapeutic target.10.1681/ASN.2015091014Fri, 06 May 2016 08:56:03 GMT-07:00Stat3 Controls Tubulointerstitial Communication during CKDIn CKD, tubular cells may be involved in the induction of interstitial fibrosis, which in turn, leads to loss of renal function. However, the molecular mechanisms that link tubular cells to the interstitial compartment are not clear. Activation of the Stat3 transcription factor has been reported in tubular cells after renal damage, and Stat3 has been implicated in CKD progression. Here, we combined an experimental model of nephron reduction in mice from different genetic backgrounds and genetically modified animals with in silico and in vitro experiments to determine whether the selective activation of Stat3 in tubular cells is involved in the development of interstitial fibrosis. Nephron reduction caused Stat3 phosphorylation in tubular cells of lesion-prone mice but not in resistant mice. Furthermore, specific deletion of Stat3 in tubular cells significantly reduced the extent of interstitial fibrosis, which correlated with reduced fibroblast proliferation and matrix synthesis, after nephron reduction. Mechanistically, in vitro tubular Stat3 activation triggered the expression of a specific subset of paracrine profibrotic factors, including Lcn2, Pdgfb, and Timp1. Together, our results provide a molecular link between tubular and interstitial cells during CKD progression and identify Stat3 as a central regulator of this link and a promising therapeutic target.Bienaimé, FrankMuorah, MordiYammine, LucieBurtin, MartineNguyen, ClémentBaron, WillianGarbay, SergeViau, AmandineBroueilh, MélanieBlanc, ThomasPeters, DorienPoli, ValeriaAnglicheau, DanyFriedlander, GérardPontoglio, MarcoGallazzini, MorganTerzi, Fabiola2016-05-06T08:56:03-07:00doi:10.1681/ASN.2015091014hwp:resource-id:jnephrol;27/12/3690American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Cell Signaling, Pathophysiology of Renal Disease and Progression, renal tubular epithelial cells, renal fibrosis, transcriptional profilingBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20150910141046-66731533-34502016-05-06T08:56:03-07:002016-12Journal of the American Society of NephrologyBasic Research2712123690350237053504
- Small-Molecule Inhibitors of Pendrin Potentiate the Diuretic Action of FurosemidePendrin is a Cl−/HCO3− exchanger expressed in type B and non-A, non-B intercalated cells in the distal nephron, where it facilitates Cl− absorption and is involved in Na+ absorption and acid-base balance. Pendrin-knockout mice show no fluid-electrolyte abnormalities under baseline conditions, although mice with double knockout of pendrin and the Na+/Cl− cotransporter (NCC) manifest profound salt wasting. Thus, pendrin may attenuate diuretic-induced salt loss, but this function remains unconfirmed. To clarify the physiologic role of pendrin under conditions not confounded by gene knockout, and to test the potential utility of pendrin inhibitors for diuretic therapy, we tested in mice a small-molecule pendrin inhibitor identified from a high-throughput screen. In vitro, a pyrazole-thiophenesulfonamide, PDSinh-C01, inhibited Cl−/anion exchange mediated by mouse pendrin with a 50% inhibitory concentration of 1–3 µM, without affecting other major kidney tubule transporters. Administration of PDSinh-C01 to mice at predicted therapeutic doses, determined from serum and urine pharmacokinetics, did not affect urine output, osmolality, salt excretion, or acid-base balance. However, in mice treated acutely with furosemide, administration of PDSinh-C01 produced a 30% increase in urine output, with increased Na+ and Cl− excretion. In mice treated long term with furosemide, in which renal pendrin is upregulated, PDSinh-C01 produced a 60% increase in urine output. Our findings clarify the role of pendrin in kidney function and suggest pendrin inhibition as a novel approach to potentiate the action of loop diuretics. Such combination therapy might enhance diuresis and salt excretion for treatment of hypertension and edema, perhaps including diuretic-resistant edema.10.1681/ASN.2015121312Fri, 06 May 2016 08:55:59 GMT-07:00Small-Molecule Inhibitors of Pendrin Potentiate the Diuretic Action of FurosemidePendrin is a Cl−/HCO3− exchanger expressed in type B and non-A, non-B intercalated cells in the distal nephron, where it facilitates Cl− absorption and is involved in Na+ absorption and acid-base balance. Pendrin-knockout mice show no fluid-electrolyte abnormalities under baseline conditions, although mice with double knockout of pendrin and the Na+/Cl− cotransporter (NCC) manifest profound salt wasting. Thus, pendrin may attenuate diuretic-induced salt loss, but this function remains unconfirmed. To clarify the physiologic role of pendrin under conditions not confounded by gene knockout, and to test the potential utility of pendrin inhibitors for diuretic therapy, we tested in mice a small-molecule pendrin inhibitor identified from a high-throughput screen. In vitro, a pyrazole-thiophenesulfonamide, PDSinh-C01, inhibited Cl−/anion exchange mediated by mouse pendrin with a 50% inhibitory concentration of 1–3 µM, without affecting other major kidney tubule transporters. Administration of PDSinh-C01 to mice at predicted therapeutic doses, determined from serum and urine pharmacokinetics, did not affect urine output, osmolality, salt excretion, or acid-base balance. However, in mice treated acutely with furosemide, administration of PDSinh-C01 produced a 30% increase in urine output, with increased Na+ and Cl− excretion. In mice treated long term with furosemide, in which renal pendrin is upregulated, PDSinh-C01 produced a 60% increase in urine output. Our findings clarify the role of pendrin in kidney function and suggest pendrin inhibition as a novel approach to potentiate the action of loop diuretics. Such combination therapy might enhance diuresis and salt excretion for treatment of hypertension and edema, perhaps including diuretic-resistant edema.Cil, OnurHaggie, Peter M.Phuan, Puay-wahTan, Joseph-AnthonyVerkman, Alan S.2016-05-06T08:55:59-07:00doi:10.1681/ASN.2015121312hwp:resource-id:jnephrol;27/12/3706American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiuretics, cell & transport physiology, collecting ducts, water-electrolyte balanceBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20151213121046-66731533-34502016-05-06T08:55:59-07:002016-12Journal of the American Society of NephrologyBasic Research2712123706349937143501
- Predicting the Functionality and Form of a Dialysis Fistula10.1681/ASN.2016050569Thu, 04 Aug 2016 05:44:08 GMT-07:00Predicting the Functionality and Form of a Dialysis FistulaNath, Karl A.Katusic, Zvonimir S.2016-08-04T05:44:08-07:00doi:10.1681/ASN.2016050569hwp:resource-id:jnephrol;27/12/3508American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, vascular access, vasculopathy, uremia, nitric oxideUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-12-01December 201610.1681/ASN.20160505691046-66731533-34502016-08-04T05:44:08-07:002016-12Journal of the American Society of NephrologyUp Front Matters2712123508378835103795
- Beyond EMT: Epithelial STAT3 as a Central Regulator of Fibrogenesis10.1681/ASN.2016060603Fri, 01 Jul 2016 05:43:27 GMT-07:00Beyond EMT: Epithelial STAT3 as a Central Regulator of FibrogenesisDuffield, Jeremy S.2016-07-01T05:43:27-07:00doi:10.1681/ASN.2016060603hwp:resource-id:jnephrol;27/12/3502American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyinterstitial fibrosis, STAT3, fibroblastUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-12-01December 201610.1681/ASN.20160606031046-66731533-34502016-07-01T05:43:27-07:002016-12Journal of the American Society of NephrologyUp Front Matters27121212350236393690350436523705
- Pendrin—A New Target for Diuretic Therapy?10.1681/ASN.2016070720Thu, 11 Aug 2016 08:00:57 GMT-07:00Pendrin—A New Target for Diuretic Therapy?Wagner, Carsten A.2016-08-11T08:00:57-07:00doi:10.1681/ASN.2016070720hwp:resource-id:jnephrol;27/12/3499American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyblood pressure, Cell & Transport Physiology, distal tubule, diureticsUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-12-01December 201610.1681/ASN.20160707201046-66731533-34502016-08-11T08:00:57-07:002016-12Journal of the American Society of NephrologyUp Front Matters2712123499370635013714
- Preserving Residual Kidney Function in Hemodialysis Patients—Back in the Spotlight10.1681/ASN.2016060693Thu, 04 Aug 2016 05:44:09 GMT-07:00Preserving Residual Kidney Function in Hemodialysis Patients—Back in the SpotlightWang, Angela Yee-Moon2016-08-04T05:44:09-07:00doi:10.1681/ASN.2016060693hwp:resource-id:jnephrol;27/12/3504American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyresidual kidney function, survival, hemodialysisUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-12-01December 201610.1681/ASN.20160606931046-66731533-34502016-08-04T05:44:09-07:002016-12Journal of the American Society of NephrologyUp Front Matters2712123504375835073768
- Neither Hematocrit Normalization nor Exercise Training Restores Oxygen Consumption to Normal Levels in Hemodialysis PatientsPatients treated with hemodialysis develop severely reduced functional capacity, which can be partially ameliorated by correcting anemia and through exercise training. In this study, we determined perturbations of an erythroid-stimulating agent and exercise training to examine if and where limitation to oxygen transport exists in patients on hemodialysis. Twenty-seven patients on hemodialysis completed a crossover study consisting of two exercise training phases at two hematocrit (Hct) values: 30% (anemic) and 42% (physiologic; normalized by treatment with erythroid-stimulating agent). To determine primary outcome measures of peak power and oxygen consumption (VO2) and secondary measures related to components of oxygen transport and utilization, all patients underwent numerous tests at five time points: baseline, untrained at Hct of 30%, after training at Hct of 30%, untrained at Hct of 42%, and after training at Hct of 42%. Hct normalization, exercise training, or the combination thereof significantly improved peak power and VO2 relative to values in the untrained anemic phase. Hct normalization increased peak arterial oxygen and arteriovenous oxygen difference, whereas exercise training improved cardiac output, citrate synthase activity, and peak tissue diffusing capacity. However, although the increase in arterial oxygen observed in the combination phase reached a value similar to that in healthy sedentary controls, the increase in peak arteriovenous oxygen difference did not. Muscle biopsy specimens showed markedly thickened endothelium and electron–dense interstitial deposits. In conclusion, exercise and Hct normalization had positive effects but failed to normalize exercise capacity in patients on hemodialysis. This effect may be caused by abnormalities identified within skeletal muscle.10.1681/ASN.2015091034Fri, 06 May 2016 08:56:03 GMT-07:00Neither Hematocrit Normalization nor Exercise Training Restores Oxygen Consumption to Normal Levels in Hemodialysis PatientsPatients treated with hemodialysis develop severely reduced functional capacity, which can be partially ameliorated by correcting anemia and through exercise training. In this study, we determined perturbations of an erythroid-stimulating agent and exercise training to examine if and where limitation to oxygen transport exists in patients on hemodialysis. Twenty-seven patients on hemodialysis completed a crossover study consisting of two exercise training phases at two hematocrit (Hct) values: 30% (anemic) and 42% (physiologic; normalized by treatment with erythroid-stimulating agent). To determine primary outcome measures of peak power and oxygen consumption (VO2) and secondary measures related to components of oxygen transport and utilization, all patients underwent numerous tests at five time points: baseline, untrained at Hct of 30%, after training at Hct of 30%, untrained at Hct of 42%, and after training at Hct of 42%. Hct normalization, exercise training, or the combination thereof significantly improved peak power and VO2 relative to values in the untrained anemic phase. Hct normalization increased peak arterial oxygen and arteriovenous oxygen difference, whereas exercise training improved cardiac output, citrate synthase activity, and peak tissue diffusing capacity. However, although the increase in arterial oxygen observed in the combination phase reached a value similar to that in healthy sedentary controls, the increase in peak arteriovenous oxygen difference did not. Muscle biopsy specimens showed markedly thickened endothelium and electron–dense interstitial deposits. In conclusion, exercise and Hct normalization had positive effects but failed to normalize exercise capacity in patients on hemodialysis. This effect may be caused by abnormalities identified within skeletal muscle.Stray-Gundersen, JamesHowden, Erin J.Parsons, Dora BethThompson, Jeffrey R.2016-05-06T08:56:03-07:00doi:10.1681/ASN.2015091034hwp:resource-id:jnephrol;27/12/3769American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, erythropoietin, physical activity, end stage kidney disease, citrate synthase, VO2 peakClinical ResearchClinical Researchresearch-article20162016-12-01December 201610.1681/ASN.20150910341046-66731533-34502016-05-06T08:56:03-07:002016-12Journal of the American Society of NephrologyClinical Research271237693779
- Cold Shock Proteins Mediate GN with MesangioproliferationDNA binding protein A (DbpA) is a member of the human cold shock domain–containing protein superfamily, with known functions in cell proliferation, differentiation, and stress responses. DbpA mediates tight junction–associated activities in tubular epithelial cells, but the function of DbpA in mesangial cells is unknown. Here, we found DbpA protein expression restricted to vascular smooth muscle cells in healthy human kidney tissue but profound induction of DbpA protein expression within the glomerular mesangial compartment in mesangioproliferative nephritis. In vitro, depletion or overexpression of DbpA using lentiviral constructs led to inhibition or promotion, respectively, of mesangial cell proliferation. Because platelet–derived growth factor B (PDGF-B) signaling has a pivotal role in mesangial cell proliferation, we examined the regulatory effect of PDGF-B on DbpA. In vitro studies of human and rat mesangial cells confirmed a stimulatory effect of PDGF-B on DbpA transcript numbers and protein levels. Additional in vivo investigations showed DbpA upregulation in experimental rat anti–Thy1.1 nephritis and murine mesangioproliferative nephritis models. To interfere with PDGF-B signaling, we injected nephritic rats with PDGF-B neutralizing aptamers or the MEK/ERK inhibitor U0126. Both interventions markedly decreased DbpA protein expression. Conversely, continuous PDGF-B infusion in healthy rats induced DbpA expression predominantly within the mesangial compartment. Taken together, these results indicate that DbpA is a novel target of PDGF-B signaling and a key mediator of mesangial cell proliferation.10.1681/ASN.2015121367Thu, 05 May 2016 07:03:12 GMT-07:00Cold Shock Proteins Mediate GN with MesangioproliferationDNA binding protein A (DbpA) is a member of the human cold shock domain–containing protein superfamily, with known functions in cell proliferation, differentiation, and stress responses. DbpA mediates tight junction–associated activities in tubular epithelial cells, but the function of DbpA in mesangial cells is unknown. Here, we found DbpA protein expression restricted to vascular smooth muscle cells in healthy human kidney tissue but profound induction of DbpA protein expression within the glomerular mesangial compartment in mesangioproliferative nephritis. In vitro, depletion or overexpression of DbpA using lentiviral constructs led to inhibition or promotion, respectively, of mesangial cell proliferation. Because platelet–derived growth factor B (PDGF-B) signaling has a pivotal role in mesangial cell proliferation, we examined the regulatory effect of PDGF-B on DbpA. In vitro studies of human and rat mesangial cells confirmed a stimulatory effect of PDGF-B on DbpA transcript numbers and protein levels. Additional in vivo investigations showed DbpA upregulation in experimental rat anti–Thy1.1 nephritis and murine mesangioproliferative nephritis models. To interfere with PDGF-B signaling, we injected nephritic rats with PDGF-B neutralizing aptamers or the MEK/ERK inhibitor U0126. Both interventions markedly decreased DbpA protein expression. Conversely, continuous PDGF-B infusion in healthy rats induced DbpA expression predominantly within the mesangial compartment. Taken together, these results indicate that DbpA is a novel target of PDGF-B signaling and a key mediator of mesangial cell proliferation.Zhu, ChengSauter, EvaSchreiter, Anjavan Roeyen, Claudia R.C.Ostendorf, TammoFloege, JürgenGembardt, FlorianHugo, Christian P.Isermann, BerendLindquist, Jonathan A.Mertens, Peter R.2016-05-05T07:03:12-07:00doi:10.1681/ASN.2015121367hwp:resource-id:jnephrol;27/12/3678American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymesangial cells, Proliferation, cell activation, cold shock proteins, mesangioproliferative glomerulonephritis, platelet derived growth factor-BBasic ResearchBasic Researchresearch-article20162016-12-01December 201610.1681/ASN.20151213671046-66731533-34502016-05-05T07:03:12-07:002016-12Journal of the American Society of NephrologyBasic Research271236783689
- Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney DiseaseNovel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs from healthy controls and patients with ADPKD using a labeled approach and then used a label-free approach with uEVs of different subjects (healthy controls versus patients with ADPKD versus patients with non-ADPKD CKD). In both experiments, 30 proteins were consistently more abundant (by two-fold or greater) in ADPKD-uEVs than in healthy- and CKD-uEVs. Of these proteins, we selected periplakin, envoplakin, villin-1, and complement C3 and C9 for confirmation because they were also significantly overrepresented in pathway analysis and were previously implicated in ADPKD pathogenesis. Immunoblotting confirmed higher abundances of the selected proteins in uEVs from three independent groups of patients with ADPKD. Whereas uEVs of young patients with ADPKD and preserved kidney function already had higher levels of complement, only uEVs of patients with advanced stages of ADPKD had increased levels of villin-1, periplakin, and envoplakin. Furthermore, all five proteins correlated positively with total kidney volume. Analysis in kidney tissue from mice with kidney-specific, tamoxifen-inducible Pkd1 deletion demonstrated higher expression in more severe stages of the disease and correlation with kidney weight for each protein of interest. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.10.1681/ASN.2015090994Thu, 03 Mar 2016 10:59:04 GMT-08:00Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney DiseaseNovel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs from healthy controls and patients with ADPKD using a labeled approach and then used a label-free approach with uEVs of different subjects (healthy controls versus patients with ADPKD versus patients with non-ADPKD CKD). In both experiments, 30 proteins were consistently more abundant (by two-fold or greater) in ADPKD-uEVs than in healthy- and CKD-uEVs. Of these proteins, we selected periplakin, envoplakin, villin-1, and complement C3 and C9 for confirmation because they were also significantly overrepresented in pathway analysis and were previously implicated in ADPKD pathogenesis. Immunoblotting confirmed higher abundances of the selected proteins in uEVs from three independent groups of patients with ADPKD. Whereas uEVs of young patients with ADPKD and preserved kidney function already had higher levels of complement, only uEVs of patients with advanced stages of ADPKD had increased levels of villin-1, periplakin, and envoplakin. Furthermore, all five proteins correlated positively with total kidney volume. Analysis in kidney tissue from mice with kidney-specific, tamoxifen-inducible Pkd1 deletion demonstrated higher expression in more severe stages of the disease and correlation with kidney weight for each protein of interest. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.Salih, MahdiDemmers, Jeroen A.Bezstarosti, KarelLeonhard, Wouter N.Losekoot, Moniquevan Kooten, CeesGansevoort, Ron T.Peters, Dorien J.M.Zietse, RobertHoorn, Ewout J.2016-03-03T10:59:04-08:00doi:10.1681/ASN.2015090994hwp:resource-id:jnephrol;27/10/3079American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, complement, cytoskeleton, genetic renal diseaseBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150909941046-66731533-34502016-03-03T10:59:04-08:002016-10Journal of the American Society of NephrologyBasic Research271030793092
- Plasma Levels of Risk-Variant APOL1 Do Not Associate with Renal Disease in a Population-Based CohortTwo common missense variants in APOL1 (G1 and G2) have been definitively linked to CKD in black Americans. However, not all individuals with the renal-risk genotype develop CKD, and little is known about how APOL1 variants drive disease. Given the association of APOL1 with HDL particles, which are cleared by the kidney, differences in the level or quality of mutant APOL1‑HDL particles could be causal for disease and might serve as a useful risk stratification marker. We measured plasma levels of G0 (low risk), G1, and G2 APOL1 in 3450 individuals in the Dallas Heart Study using a liquid chromatography-MS method that enabled quantitation of the different variants. Additionally, we characterized native APOL1‑HDL from donors with no or two APOL1 risk alleles by size-exclusion chromatography and analysis of immunopurified APOL1‑HDL particles. Finally, we identified genetic loci associated with plasma APOL1 levels and tested for APOL1-dependent association with renal function. Although we replicated the previous association between APOL1 variant status and renal function in nondiabetic individuals, levels of circulating APOL1 did not associate with microalbuminuria or GFR. Furthermore, the size or known components of APOL1‑HDL did not consistently differ in subjects with the renal-risk genotype. Genetic association studies implicated variants in loci harboring haptoglobin-related protein (HPR), APOL1, and ubiquitin D (UBD) in the regulation of plasma APOL1 levels, but these variants did not associate with renal function. Collectively, these data demonstrate that the risk of renal disease associated with APOL1 is probably not related to circulating levels of the mutant protein.10.1681/ASN.2015101121Tue, 22 Mar 2016 05:24:27 GMT-07:00Plasma Levels of Risk-Variant APOL1 Do Not Associate with Renal Disease in a Population-Based CohortTwo common missense variants in APOL1 (G1 and G2) have been definitively linked to CKD in black Americans. However, not all individuals with the renal-risk genotype develop CKD, and little is known about how APOL1 variants drive disease. Given the association of APOL1 with HDL particles, which are cleared by the kidney, differences in the level or quality of mutant APOL1‑HDL particles could be causal for disease and might serve as a useful risk stratification marker. We measured plasma levels of G0 (low risk), G1, and G2 APOL1 in 3450 individuals in the Dallas Heart Study using a liquid chromatography-MS method that enabled quantitation of the different variants. Additionally, we characterized native APOL1‑HDL from donors with no or two APOL1 risk alleles by size-exclusion chromatography and analysis of immunopurified APOL1‑HDL particles. Finally, we identified genetic loci associated with plasma APOL1 levels and tested for APOL1-dependent association with renal function. Although we replicated the previous association between APOL1 variant status and renal function in nondiabetic individuals, levels of circulating APOL1 did not associate with microalbuminuria or GFR. Furthermore, the size or known components of APOL1‑HDL did not consistently differ in subjects with the renal-risk genotype. Genetic association studies implicated variants in loci harboring haptoglobin-related protein (HPR), APOL1, and ubiquitin D (UBD) in the regulation of plasma APOL1 levels, but these variants did not associate with renal function. Collectively, these data demonstrate that the risk of renal disease associated with APOL1 is probably not related to circulating levels of the mutant protein.Kozlitina, JuliaZhou, HaihongBrown, Patricia N.Rohm, Rory J.Pan, YiAyanoglu, GulesiDu, XiaoyanRimmer, EricReilly, Dermot F.Roddy, Thomas P.Cully, Doris F.Vogt, Thomas F.Blom, DanielHoek, Maarten2016-03-22T05:24:27-07:00doi:10.1681/ASN.2015101121hwp:resource-id:jnephrol;27/10/3204American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Epidemiology and outcomes, genetic renal disease, human genetics, Pathophysiology of Renal Disease and Progression, risk factorsClinical ResearchClinical Researchresearch-article20162016-10-01October 201610.1681/ASN.20151011211046-66731533-34502016-03-22T05:24:27-07:002016-10Journal of the American Society of NephrologyClinical Research271032043219
- Gene Editing: Powerful New Tools for Nephrology Research and TherapyBiologic research is experiencing a transformation brought about by the ability of programmable nucleases to manipulate the genome. In the recently developed CRISPR/Cas system, short RNA sequences guide the endonuclease Cas9 to any location in the genome, causing a DNA double–strand break (DSB). Repair of DSBs allows the introduction of targeted genetic manipulations with high precision. Cas9–mediated gene editing is simple, scalable, and rapid, and it can be applied to virtually any organism. Here, we summarize the development of modern gene editing techniques and the biology of DSB repair on which these techniques are based. We discuss technical points in applying this technology and review its use in model organisms. Finally, we describe prospects for the use of gene editing to treat human genetic diseases. This technology offers tremendous promise for equipping the nephrology research community to better model and ultimately, treat kidney diseases.10.1681/ASN.2016020146Wed, 29 Jun 2016 06:49:36 GMT-07:00Gene Editing: Powerful New Tools for Nephrology Research and TherapyBiologic research is experiencing a transformation brought about by the ability of programmable nucleases to manipulate the genome. In the recently developed CRISPR/Cas system, short RNA sequences guide the endonuclease Cas9 to any location in the genome, causing a DNA double–strand break (DSB). Repair of DSBs allows the introduction of targeted genetic manipulations with high precision. Cas9–mediated gene editing is simple, scalable, and rapid, and it can be applied to virtually any organism. Here, we summarize the development of modern gene editing techniques and the biology of DSB repair on which these techniques are based. We discuss technical points in applying this technology and review its use in model organisms. Finally, we describe prospects for the use of gene editing to treat human genetic diseases. This technology offers tremendous promise for equipping the nephrology research community to better model and ultimately, treat kidney diseases.Miyagi, AyanoLu, AiwuHumphreys, Benjamin D.2016-06-29T06:49:36-07:00doi:10.1681/ASN.2016020146hwp:resource-id:jnephrol;27/10/2940American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymolecular genetics, gene therapy, transgenic mouseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-10-01October 201610.1681/ASN.20160201461046-66731533-34502016-06-29T06:49:36-07:002016-10Journal of the American Society of NephrologyUp Front Matters271029402947
- The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human EvolutionCommon variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.10.1681/ASN.2015070830Thu, 10 Mar 2016 07:57:46 GMT-08:00The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human EvolutionCommon variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.Ghirotto, SilviaTassi, FrancescaBarbujani, GuidoPattini, LindaHayward, CarolineVollenweider, PeterBochud, MurielleRampoldi, LucaDevuyst, Olivier2016-03-10T07:57:46-08:00doi:10.1681/ASN.2015070830hwp:resource-id:jnephrol;27/10/2983American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, chronic kidney disease, kidney tubule, tubular epithelium, Urinary tract infectionBrief CommunicationsBrief Communicationsbrief-report20162016-10-01October 201610.1681/ASN.20150708301046-66731533-34502016-03-10T07:57:46-08:002016-10Journal of the American Society of NephrologyBrief Communications271029832996
- Sex Differences in Renal Proximal Tubular Cell HomeostasisStudies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase–α. Additionally, we quantified urinary excretion of blood plasma proteins α1–microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase–α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1–microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ–derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.10.1681/ASN.2015080886Thu, 28 Apr 2016 06:19:55 GMT-07:00Sex Differences in Renal Proximal Tubular Cell HomeostasisStudies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase–α. Additionally, we quantified urinary excretion of blood plasma proteins α1–microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase–α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1–microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ–derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.Seppi, ThomasPrajczer, SinikkaDörler, Maria-MagdalenaEiter, OliverHekl, DanielNevinny-Stickel, MeinhardSkvortsova, IraidaGstraunthaler, GerhardLukas, PeterLechner, Judith2016-04-28T06:19:55-07:00doi:10.1681/ASN.2015080886hwp:resource-id:jnephrol;27/10/3051American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal proximal tubule cell, sex and gender difference, sex hormones, nonreproductive functions, urinary marker proteins, Fructose-1,6-bisphosphatase, menstrual cycleBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150808861046-66731533-34502016-04-28T06:19:55-07:002016-10Journal of the American Society of NephrologyBasic Research2710103051292130622924
- This Month's Highlights10.1681/ASN.2016060634Fri, 30 Sep 2016 10:00:56 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-09-30T10:00:56-07:00doi:10.1681/ASN.2016060634hwp:resource-id:jnephrol;27/10/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-10-01October 201610.1681/ASN.20160606341046-66731533-34502016-09-30T10:00:56-07:002016-10Journal of the American Society of NephrologyThis Month's Highlights2710ii
- Developmental Origins for Kidney Disease Due to Shroom3 DeficiencyCKD is a significant health concern with an underlying genetic component. Multiple genome–wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman’s capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho–kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.10.1681/ASN.2015060621Thu, 03 Mar 2016 10:59:08 GMT-08:00Developmental Origins for Kidney Disease Due to Shroom3 DeficiencyCKD is a significant health concern with an underlying genetic component. Multiple genome–wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman’s capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho–kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.Khalili, HadisehSull, AlexandraSarin, SanjayBoivin, Felix J.Halabi, RamiSvajger, BrunoLi, AihuaCui, Valerie WencheDrysdale, ThomasBridgewater, Darren2016-03-03T10:59:08-08:00doi:10.1681/ASN.2015060621hwp:resource-id:jnephrol;27/10/2965American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, podocyte, kidney development, chronic kidney disease, Shroom3Brief CommunicationsBrief Communicationsbrief-report20162016-10-01October 201610.1681/ASN.20150606211046-66731533-34502016-03-03T10:59:08-08:002016-10Journal of the American Society of NephrologyBrief Communications271029652973
- Autoantibodies Targeting a Collecting Duct–Specific Water Channel in Tubulointerstitial NephritisTubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct–specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.10.1681/ASN.2015101126Wed, 16 Mar 2016 10:09:03 GMT-07:00Autoantibodies Targeting a Collecting Duct–Specific Water Channel in Tubulointerstitial NephritisTubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct–specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.Landegren, NilsPourmousa Lindberg, MinaSkov, JakobHallgren, ÅsaEriksson, DanielLisberg Toft-Bertelsen, TrineMacAulay, NannaHagforsen, EvaRäisänen-Sokolowski, AnneSaha, HeikkiNilsson, ThomasNordmark, GunnelOhlsson, SophieGustafsson, JanHusebye, Eystein S.Larsson, ErikAnderson, Mark S.Perheentupa, JaakkoRorsman, FredrikFenton, Robert A.Kämpe, Olle2016-03-16T10:09:03-07:00doi:10.1681/ASN.2015101126hwp:resource-id:jnephrol;27/10/3220American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend stage kidney disease, Immunology and pathology, interstitial fibrosisClinical ResearchClinical Researchresearch-article20162016-10-01October 201610.1681/ASN.20151011261046-66731533-34502016-03-16T10:09:03-07:002016-10Journal of the American Society of NephrologyClinical Research271032203228
- Mesencephalic Astrocyte–Derived Neurotrophic Factor as a Urine Biomarker for Endoplasmic Reticulum Stress–Related Kidney DiseasesEndoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte–derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin β2 protein–induced podocyte ER stress and AKI triggered by tunicamycin– or ischemia-reperfusion–induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells. ER stress upregulated MANF expression in podocytes and tubular cells. Notably, urinary MANF excretion concurrent with podocyte or tubular cell ER stress preceded clinical or histologic manifestations of the corresponding disease. Thus, MANF can potentially serve as a urine diagnostic or prognostic biomarker in ER stress–related kidney diseases to help stratify disease risk, predict disease progression, monitor treatment response, and identify subgroups of patients who can be treated with ER stress modulators in a highly targeted manner.10.1681/ASN.2014100986Thu, 03 Mar 2016 10:58:57 GMT-08:00Mesencephalic Astrocyte–Derived Neurotrophic Factor as a Urine Biomarker for Endoplasmic Reticulum Stress–Related Kidney DiseasesEndoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte–derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin β2 protein–induced podocyte ER stress and AKI triggered by tunicamycin– or ischemia-reperfusion–induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells. ER stress upregulated MANF expression in podocytes and tubular cells. Notably, urinary MANF excretion concurrent with podocyte or tubular cell ER stress preceded clinical or histologic manifestations of the corresponding disease. Thus, MANF can potentially serve as a urine diagnostic or prognostic biomarker in ER stress–related kidney diseases to help stratify disease risk, predict disease progression, monitor treatment response, and identify subgroups of patients who can be treated with ER stress modulators in a highly targeted manner.Kim, YeawonLee, HeedooManson, Scott R.Lindahl, MariaEvans, BradleyMiner, Jeffrey H.Urano, FumihikoChen, Ying Maggie2016-03-03T10:58:57-08:00doi:10.1681/ASN.2014100986hwp:resource-id:jnephrol;27/10/2974American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, acute renal failure, endoplasmic reticulumBrief CommunicationsBrief Communicationsbrief-report20162016-10-01October 201610.1681/ASN.20141009861046-66731533-34502016-03-03T10:58:57-08:002016-10Journal of the American Society of NephrologyBrief Communications271029742982
- Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health InitiativePragmatic clinical trials are conducted under the real-world conditions of clinical care delivery. As a result, these trials yield findings that are highly generalizable to the nonresearch setting, identify interventions that are readily translatable into clinical practice, and cost less than trials that require extensive research infrastructures. Maintenance dialysis is a setting especially well suited for pragmatic trials because of inherently frequent and predictable patient encounters, highly granular and uniform data collection, use of electronic data systems, and delivery of care by a small number of provider organizations to approximately 90% of patients nationally. Recognizing the potential for pragmatic trials to generate much needed evidence to guide the care of patients receiving maintenance dialysis, the Kidney Health Initiative assembled a group of individuals with relevant expertise from academia, industry, and government to provide the nephrology community with information about the design and conduct of such trials, with a specific focus on the dialysis setting. Here, we review this information, and where applicable, use experience from the ongoing Time to Reduce Mortality in End Stage Renal Disease Trial, a large cluster-randomized, pragmatic trial evaluating hemodialysis session duration, to illustrate challenges and solutions to operational, ethical, and regulatory issues.10.1681/ASN.2016030340Mon, 11 Jul 2016 03:56:24 GMT-07:00Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health InitiativePragmatic clinical trials are conducted under the real-world conditions of clinical care delivery. As a result, these trials yield findings that are highly generalizable to the nonresearch setting, identify interventions that are readily translatable into clinical practice, and cost less than trials that require extensive research infrastructures. Maintenance dialysis is a setting especially well suited for pragmatic trials because of inherently frequent and predictable patient encounters, highly granular and uniform data collection, use of electronic data systems, and delivery of care by a small number of provider organizations to approximately 90% of patients nationally. Recognizing the potential for pragmatic trials to generate much needed evidence to guide the care of patients receiving maintenance dialysis, the Kidney Health Initiative assembled a group of individuals with relevant expertise from academia, industry, and government to provide the nephrology community with information about the design and conduct of such trials, with a specific focus on the dialysis setting. Here, we review this information, and where applicable, use experience from the ongoing Time to Reduce Mortality in End Stage Renal Disease Trial, a large cluster-randomized, pragmatic trial evaluating hemodialysis session duration, to illustrate challenges and solutions to operational, ethical, and regulatory issues.Dember, Laura M.Archdeacon, PatrickKrishnan, MaheshLacson, EduardoLing, Shari M.Roy-Chaudhury, PrabirSmith, Kimberly A.Flessner, Michael F.2016-07-11T15:56:24-07:00doi:10.1681/ASN.2016030340hwp:resource-id:jnephrol;27/10/2955American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycluster randomization, health systems, informed consent, electronic medical record, ethical and regulatory issuesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-10-01October 201610.1681/ASN.20160303401046-66731533-34502016-07-11T15:56:24-07:002016-10Journal of the American Society of NephrologyUp Front Matters271029552963
- Current and Emerging Therapies for Lupus NephritisThe introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments.10.1681/ASN.2016040415Thu, 09 Jun 2016 07:35:15 GMT-07:00Current and Emerging Therapies for Lupus NephritisThe introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments.Parikh, Samir V.Rovin, Brad H.2016-06-09T07:35:15-07:00doi:10.1681/ASN.2016040415hwp:resource-id:jnephrol;27/10/2929American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologylupus nephritis, systemic lupus erythematosus, clinical trial, glomerular disease, immunosuppressionUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-10-01October 201610.1681/ASN.20160404151046-66731533-34502016-06-09T07:35:15-07:002016-10Journal of the American Society of NephrologyUp Front Matters271029292939
- EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water ReabsorptionNephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high–throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output. Erlotinib, a selective EGFR inhibitor, enhanced AQP2 apical membrane expression in collecting duct principal cells and reduced urine volume by 45% after 5 days of treatment in mice with lithium-induced NDI. Similar to VP, erlotinib increased exocytosis and decreased endocytosis in LLC-PK1 cells, resulting in a significant increase in AQP2 membrane accumulation. Erlotinib increased phosphorylation of AQP2 at Ser-256 and Ser-269 and decreased phosphorylation at Ser-261 in a dose-dependent manner. However, unlike VP, the effect of erlotinib was independent of cAMP, cGMP, and protein kinase A. Conversely, EGF reduced VP–induced AQP2 Ser-256 phosphorylation, suggesting crosstalk between VP and EGF in AQP2 trafficking and a role of EGF in water homeostasis. These results reveal a novel pathway that contributes to the regulation of AQP2–mediated water reabsorption and suggest new potential therapeutic strategies for NDI treatment.10.1681/ASN.2015080903Wed, 09 Mar 2016 09:59:04 GMT-08:00EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water ReabsorptionNephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high–throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output. Erlotinib, a selective EGFR inhibitor, enhanced AQP2 apical membrane expression in collecting duct principal cells and reduced urine volume by 45% after 5 days of treatment in mice with lithium-induced NDI. Similar to VP, erlotinib increased exocytosis and decreased endocytosis in LLC-PK1 cells, resulting in a significant increase in AQP2 membrane accumulation. Erlotinib increased phosphorylation of AQP2 at Ser-256 and Ser-269 and decreased phosphorylation at Ser-261 in a dose-dependent manner. However, unlike VP, the effect of erlotinib was independent of cAMP, cGMP, and protein kinase A. Conversely, EGF reduced VP–induced AQP2 Ser-256 phosphorylation, suggesting crosstalk between VP and EGF in AQP2 trafficking and a role of EGF in water homeostasis. These results reveal a novel pathway that contributes to the regulation of AQP2–mediated water reabsorption and suggest new potential therapeutic strategies for NDI treatment.Cheung, Pui W.Nomura, NaohiroNair, Anil V.Pathomthongtaweechai, NutthapoomUeberdiek, LarsLu, Hua A. JennyBrown, DennisBouley, Richard2016-03-09T09:59:04-08:00doi:10.1681/ASN.2015080903hwp:resource-id:jnephrol;27/10/3105American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologywater channels, diabetes insipidus, Cell SignalingBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150809031046-66731533-34502016-03-09T09:59:04-08:002016-10Journal of the American Society of NephrologyBasic Research271031053116
- Pragmatic Clinical Trials in CKD: Opportunities and ChallengesRandomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney disease and the exorbitant costs of their health care. Observational studies of CKD frequently yield seemingly paradoxic associations of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials conducted in people with normal kidney function to patients with CKD. However, many completed trials in CKD have been limited by intermediate outcomes of unclear clinical significance or narrow eligibility criteria that limit external validity, and implementation of proven therapies remains a challenge. It is therefore imperative that the nephrology community capitalize on recent interest in novel approaches to trial design, such as pragmatic clinical trials. These trials are meant to promote research within real world settings to yield clinically relevant results with greater applicability than those of traditional trials, while maintaining many advantages, such as controlling for potential sources of bias. We provide a description of pragmatic clinical trials and a discussion of advantages, disadvantages, and practical challenges inherent to this study design, in the context of specific scientific questions relevant to patients with CKD.10.1681/ASN.2015111264Thu, 09 Jun 2016 07:35:20 GMT-07:00Pragmatic Clinical Trials in CKD: Opportunities and ChallengesRandomized controlled trials in CKD lag in number behind those of other chronic diseases, despite the high morbidity and mortality experienced by patients with kidney disease and the exorbitant costs of their health care. Observational studies of CKD frequently yield seemingly paradoxic associations of traditional risk factors with outcomes, making it difficult to extrapolate the results of trials conducted in people with normal kidney function to patients with CKD. However, many completed trials in CKD have been limited by intermediate outcomes of unclear clinical significance or narrow eligibility criteria that limit external validity, and implementation of proven therapies remains a challenge. It is therefore imperative that the nephrology community capitalize on recent interest in novel approaches to trial design, such as pragmatic clinical trials. These trials are meant to promote research within real world settings to yield clinically relevant results with greater applicability than those of traditional trials, while maintaining many advantages, such as controlling for potential sources of bias. We provide a description of pragmatic clinical trials and a discussion of advantages, disadvantages, and practical challenges inherent to this study design, in the context of specific scientific questions relevant to patients with CKD.de Boer, Ian H.Kovesdy, Csaba P.Navaneethan, Sankar D.Peralta, Carmen A.Tuot, Delphine S.Vazquez, Miguel A.Crews, Deidra C.de Boer, Ian H.Kovesdy, Csaba P.Navaneethan, Sankar D.Peralta, Carmen A.Tuot, Delphine S.Vazquez, Miguel A.Crews, Deidra C.2016-06-09T07:35:20-07:00doi:10.1681/ASN.2015111264hwp:resource-id:jnephrol;27/10/2948American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical trial, outcomesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-10-01October 201610.1681/ASN.20151112641046-66731533-34502016-06-09T07:35:20-07:002016-10Journal of the American Society of NephrologyUp Front Matters271029482954
- Trabecular Bone Score and Incident Fragility Fracture Risk in Adults with Reduced Kidney Function10.2215/CJN.00720116Mon, 24 Oct 2016 08:02:49 GMT-07:00Trabecular Bone Score and Incident Fragility Fracture Risk in Adults with Reduced Kidney FunctionNaylor, Kyla L.Prior, JerilynnGarg, Amit X.Berger, ClaudieLangsetmo, LisaAdachi, Jonathan D.Goltzman, DavidKovacs, Christopher S.Josse, Robert G.Leslie, William D.2016-10-24T08:02:49-07:00doi:10.2215/CJN.00720116hwp:resource-id:clinjasn;11/11/2032American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytrabecular bone score, chronic kidney disease, fragility fracture, reduced kidney function, Absorptiometry, Photon, adult, Bone Density, Bone and Bones, Canada, Confidence Intervals, Follow-Up Studies, glomerular filtration rate, humans, Lumbar Vertebrae, minerals, Osteoporosis, risk factorsOriginal ArticlesMineral Metabolism/Bone DiseaseOriginal ArticlesMineral Metabolism/Bone Diseaseresearch-article20162016-11-07November 07, 201610.2215/CJN.007201161555-90411555-905X2016-10-24T08:02:49-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1111112032192920401931
- Use of Electronic Health Data to Estimate Heart Failure Events in a Population-Based Cohort with CKD10.2215/CJN.03900416Tue, 09 Aug 2016 05:44:44 GMT-07:00Use of Electronic Health Data to Estimate Heart Failure Events in a Population-Based Cohort with CKDFloyd, James S.Wellman, RobertFuller, SharonBansal, NishaPsaty, Bruce M.de Boer, Ian H.Scholes, Delia2016-08-09T05:44:44-07:00doi:10.2215/CJN.03900416hwp:resource-id:clinjasn;11/11/1954American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, epidemiology and outcomes, electronic health records, adult, algorithms, follow-up studies, heart failure, hospitalization, humans, medical records, outpatients, receptor, epidermal growth factor, EGFR protein, humanOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-11-07November 07, 201610.2215/CJN.039004161555-90411555-905X2016-08-09T05:44:44-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119541961
- Cardiovascular Disease Risk Factors and Left Ventricular Hypertrophy in Girls and Boys With CKD10.2215/CJN.01270216Wed, 14 Sep 2016 07:17:54 GMT-07:00Cardiovascular Disease Risk Factors and Left Ventricular Hypertrophy in Girls and Boys With CKDRuebner, Rebecca L.Ng, DerekMitsnefes, MarkFoster, Bethany J.Meyers, KevinWarady, BradleyFurth, Susan L.2016-09-14T07:17:54-07:00doi:10.2215/CJN.01270216hwp:resource-id:clinjasn;11/11/1962American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, left ventricular hypertrophy, pediatric nephrology, cardiovascular disease, Body Size, Body Weight, child, female, Humans, hypertension, Hypertrophy, Left Ventricular, Male, Prevalence, Renal Insufficiency, Chronic, risk factors, Sex Characteristics, TriglyceridesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-11-07November 07, 201610.2215/CJN.012702161555-90411555-905X2016-09-14T07:17:54-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119621968
- Recurrent FSGS Postkidney Transplant: Moving the Needle Forward10.2215/CJN.09520916Thu, 20 Oct 2016 06:35:04 GMT-07:00Recurrent FSGS Postkidney Transplant: Moving the Needle ForwardAmaral, SandraNeu, Alicia2016-10-20T06:35:04-07:00doi:10.2215/CJN.09520916hwp:resource-id:clinjasn;11/11/1932American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfocal segmental glomerulosclerosis, transplantation, outcomesEditorialsEditorialsresearch-article20162016-11-07November 07, 201610.2215/CJN.095209161555-90411555-905X2016-10-20T06:35:04-07:002016-11-07Clinical Journal of the American Society of NephrologyEditorials1111111932204119342046
- Long-Term Outcome of Kidney Transplantation in Recipients with Focal Segmental Glomerulosclerosis10.2215/CJN.03060316Thu, 20 Oct 2016 06:35:05 GMT-07:00Long-Term Outcome of Kidney Transplantation in Recipients with Focal Segmental GlomerulosclerosisFrancis, AnnaTrnka, PeterMcTaggart, Steven J.2016-10-20T06:35:05-07:00doi:10.2215/CJN.03060316hwp:resource-id:clinjasn;11/11/2041American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfocal segmental glomerulosclerosis, living donor, deceased donor, graft survival, Adult, Australia, Biopsy, Child, Glomerulosclerosis, Focal, Graft Survival, Humans, Incidence, kidney, Kidney Failure, Chronic, kidney transplantation, Living Donors, Logistic Models, New Zealand, Registries, renal dialysis, risk factorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-11-07November 07, 201610.2215/CJN.030603161555-90411555-905X2016-10-20T06:35:05-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1111112041193220461934
- Delays in Prior Living Kidney Donors Receiving Priority on the Transplant Waiting List10.2215/CJN.01360216Fri, 02 Sep 2016 04:14:18 GMT-07:00Delays in Prior Living Kidney Donors Receiving Priority on the Transplant Waiting ListWainright, Jennifer L.Klassen, David K.Kucheryavaya, Anna Y.Stewart, Darren E.2016-09-02T04:14:18-07:00doi:10.2215/CJN.01360216hwp:resource-id:clinjasn;11/11/2047American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyliving donors, chronic kidney failure, kidney transplantation, Centers for Medicare and Medicaid Services (U.S.), Death, kidney, Living Donors, renal dialysis, Transplants, United States, 1-dodecylpyridoxalOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-11-07November 07, 201610.2215/CJN.013602161555-90411555-905X2016-09-02T04:14:18-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111120472052
- Fibroblast Growth Factor 23 and Risk of CKD Progression in Children10.2215/CJN.02110216Thu, 25 Aug 2016 05:48:41 GMT-07:00Fibroblast Growth Factor 23 and Risk of CKD Progression in ChildrenPortale, Anthony A.Wolf, Myles S.Messinger, ShariPerwad, FarzanaJüppner, HaraldWarady, Bradley A.Furth, Susan L.Salusky, Isidro B.2016-08-25T05:48:41-07:00doi:10.2215/CJN.02110216hwp:resource-id:clinjasn;11/11/1989American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, progression of chronic renal failure, fibroblast growth factor 23, CKiD, parathyroid hormone, mineral metabolism, adult, child, cohort studies, Confidence Intervals, Demography, Fibroblast Growth Factors, Follow-Up Studies, glomerular filtration rate, humans, iohexol, kidney, kidney transplantation, Minerals, Phosphorus, proteinuria, renal dialysis, Renal Insufficiency, Chronic, risk factors, Vitamin DOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-11-07November 07, 201610.2215/CJN.021102161555-90411555-905X2016-08-25T05:48:41-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119891998
- NT-proBNP and Echocardiographic Parameters for Prediction of Cardiovascular Outcomes in Patients with CKD Stages G2–G410.2215/CJN.01660216Thu, 11 Aug 2016 08:21:50 GMT-07:00NT-proBNP and Echocardiographic Parameters for Prediction of Cardiovascular Outcomes in Patients with CKD Stages G2–G4Untersteller, KathrinGirerd, NicolasDuarte, KevinRogacev, Kyrill S.Seiler-Mussler, SarahFliser, DaniloRossignol, PatrickHeine, Gunnar H.2016-08-11T08:21:50-07:00doi:10.2215/CJN.01660216hwp:resource-id:clinjasn;11/11/1978American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, natriuretic peptides, renal insufficiency, chronic, Diastole, echocardiography, Follow-Up Studies, heart failure, Humans, Multivariate Analysis, Natriuretic Peptide, Brain, Peptide Fragments, Proportional Hazards Models, Renal Insufficiency, Chronic, Ventricular Function, Left, pro-brain natriuretic peptide (1–76)Original ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-11-07November 07, 201610.2215/CJN.016602161555-90411555-905X2016-08-11T08:21:50-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119781988
- Development of a Multicenter Ward–Based AKI Prediction Model10.2215/CJN.00280116Thu, 15 Sep 2016 06:02:45 GMT-07:00Development of a Multicenter Ward–Based AKI Prediction ModelKoyner, Jay L.Adhikari, RichaEdelson, Dana P.Churpek, Matthew M.2016-09-15T06:02:45-07:00doi:10.2215/CJN.00280116hwp:resource-id:clinjasn;11/11/1935American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, clinical nephrology, hospitalization, electronic health records, acute kidney injury, biomarker, risk assessment, vitals signs, Acute Kidney Injury, Algorithms, Area Under Curve, creatinine, Demography, Early Intervention (Education), Electronic Health Records, Humans, Inpatients, Patients’ Rooms, Probability, ROC Curve, Risk, Sensitivity and SpecificityOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-11-07November 07, 201610.2215/CJN.002801161555-90411555-905X2016-09-15T06:02:45-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119351943
- Incidence, Severity, and Outcomes of AKI Associated with Dual Renin-Angiotensin System Blockade10.2215/CJN.03470316Tue, 27 Sep 2016 07:05:57 GMT-07:00Incidence, Severity, and Outcomes of AKI Associated with Dual Renin-Angiotensin System BlockadePalevsky, Paul M.Zhang, Jane H.Seliger, Stephen L.Emanuele, NicholasFried, Linda F.2016-09-27T07:05:57-07:00doi:10.2215/CJN.03470316hwp:resource-id:clinjasn;11/11/1944American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, chronic kidney disease, renin angiotensin system, angiotensin receptor blocker, angiotensin converting enzyme inhibitor, proteinuria, diabetes mellitus, diabetic nephropathy, Albumins, Ambulatory Care, Arm, creatinine, Diabetes Mellitus, Type 2, Follow-Up Studies, glomerular filtration rate, Humans, Incidence, Kidney Failure, Chronic, Lisinopril, Losartan, Nephrons, Renin-Angiotensin System, risk factors, VeteransOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-11-07November 07, 201610.2215/CJN.034703161555-90411555-905X2016-09-27T07:05:57-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119441953
- Defining Glomerular Disease in Mechanistic Terms: Implementing an Integrative Biology Approach in NephrologyAdvances in biomedical research allow for the capture of an unprecedented level of genetic, molecular, and clinical information from large patient cohorts, where the quest for precision medicine can be pursued. An overarching goal of precision medicine is to integrate the large–scale genetic and molecular data with deep phenotypic information to identify a new mechanistic disease classification. This classification can ideally be used to meet the clinical goal of the right medication for the right patient at the right time. Glomerular disease presents a formidable challenge for precision medicine. Patients present with similar signs and symptoms, which cross the current disease categories. The diseases are grouped by shared histopathologic features, but individual patients have dramatic variability in presentation, progression, and response to therapy, reflecting the underlying biologic heterogeneity within each glomerular disease category. Despite the clinical challenge, glomerular disease has several unique advantages to building multilayered datasets connecting genetic, molecular, and structural information needed to address the goals of precision medicine in this population. Kidney biopsy tissue, obtained during routine clinical care, provides a direct window into the molecular mechanisms active in the affected organ. In addition, urine is a biofluid ideally suited for repeated measurement from the diseased organ as a liquid biopsy with potential to reflect the dynamic state of renal tissue. In our review, current approaches for large–scale data generation and integration along the genotype-phenotype continuum in glomerular disease will be summarized. Several successful examples of this integrative biology approach within glomerular disease will be highlighted along with an outlook on how achieving a mechanistic disease classification could help to shape glomerular disease research and care in the future.10.2215/CJN.13651215Wed, 14 Sep 2016 07:17:53 GMT-07:00Defining Glomerular Disease in Mechanistic Terms: Implementing an Integrative Biology Approach in NephrologyAdvances in biomedical research allow for the capture of an unprecedented level of genetic, molecular, and clinical information from large patient cohorts, where the quest for precision medicine can be pursued. An overarching goal of precision medicine is to integrate the large–scale genetic and molecular data with deep phenotypic information to identify a new mechanistic disease classification. This classification can ideally be used to meet the clinical goal of the right medication for the right patient at the right time. Glomerular disease presents a formidable challenge for precision medicine. Patients present with similar signs and symptoms, which cross the current disease categories. The diseases are grouped by shared histopathologic features, but individual patients have dramatic variability in presentation, progression, and response to therapy, reflecting the underlying biologic heterogeneity within each glomerular disease category. Despite the clinical challenge, glomerular disease has several unique advantages to building multilayered datasets connecting genetic, molecular, and structural information needed to address the goals of precision medicine in this population. Kidney biopsy tissue, obtained during routine clinical care, provides a direct window into the molecular mechanisms active in the affected organ. In addition, urine is a biofluid ideally suited for repeated measurement from the diseased organ as a liquid biopsy with potential to reflect the dynamic state of renal tissue. In our review, current approaches for large–scale data generation and integration along the genotype-phenotype continuum in glomerular disease will be summarized. Several successful examples of this integrative biology approach within glomerular disease will be highlighted along with an outlook on how achieving a mechanistic disease classification could help to shape glomerular disease research and care in the future.Mariani, Laura H.Pendergraft, William F.Kretzler, Matthias2016-09-14T07:17:53-07:00doi:10.2215/CJN.13651215hwp:resource-id:clinjasn;11/11/2054American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetics and development, glomerular disease, glomerulonephritis, glomerulopathy, molecular genetics, transcriptional profiling, Biological Products, Biology, Biomedical Research, Biopsy, Genotype, Goals, Humans, Kidney Glomerulus, nephrology, Phenotype, Precision MedicineGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20162016-11-07November 07, 201610.2215/CJN.136512151555-90411555-905X2016-09-14T07:17:53-07:002016-11-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician111120542060
- Introducing the Evidence-Based Nephrology Series10.2215/CJN.06570616Mon, 07 Nov 2016 10:00:33 GMT-08:00Introducing the Evidence-Based Nephrology SeriesKestenbaum, BryanSeliger, Stephen L.2016-11-07T10:00:33-08:00doi:10.2215/CJN.06570616hwp:resource-id:clinjasn;11/11/2061American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyBiomedical Research, Caregivers, Chronic Disease, Evidence-Based Medicine, Humans, nephrology, Patient Care, Physicians, Renal Insufficiency, Chronic, risk factorsEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20162016-11-07November 07, 201610.2215/CJN.065706161555-90411555-905X2016-11-07T10:00:33-08:002016-11-07Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology111120612061
- Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Introduction10.2215/CJN.09700916Mon, 07 Nov 2016 10:00:33 GMT-08:00Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: IntroductionPalevsky, Paul M.2016-11-07T10:00:33-08:00doi:10.2215/CJN.09700916hwp:resource-id:clinjasn;11/11/2078American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnticoagulants, Atrial Fibrillation, Blood Coagulation, Disease Management, Humans, Kidney Failure, ChronicControversies in NephrologyControversies in Nephrologyresearch-article20162016-11-07November 07, 201610.2215/CJN.097009161555-90411555-905X2016-11-07T10:00:33-08:002016-11-07Clinical Journal of the American Society of NephrologyControversies in Nephrology111120782078
- Prevalence of Barriers and Facilitators to Enhancing Conservative Kidney Management for Older Adults in the Primary Care Setting10.2215/CJN.04510416Mon, 22 Aug 2016 05:32:57 GMT-07:00Prevalence of Barriers and Facilitators to Enhancing Conservative Kidney Management for Older Adults in the Primary Care SettingTam-Tham, HelenKing-Shier, Kathryn M.Thomas, Chandra M.Quinn, Robert R.Fruetel, KarenDavison, Sara N.Hemmelgarn, Brenda R.2016-08-22T05:32:57-07:00doi:10.2215/CJN.04510416hwp:resource-id:clinjasn;11/11/2012American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyKidney Failure, Chronic, Therapeutics, Geriatrics, nephrology, Physicians, Primary Care, Surveys and Questionnaires, Conservative Care, Non-dialysis Care, geriatric nephrology, Adult, Alberta, Canada, Cross-Sectional Studies, Empathy, Humans, Male, Postal Service, Prevalence, Primary Health Care, renal dialysis, Renal Insufficiency, Chronic, Specialization, Telefacsimile, TelephoneOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20162016-11-07November 07, 201610.2215/CJN.045104161555-90411555-905X2016-08-22T05:32:57-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111120122021
- Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Verdict 210.2215/CJN.09470916Tue, 25 Oct 2016 04:28:27 GMT-07:00Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Verdict 2Herzog, Charles A.2016-10-25T04:28:27-07:00doi:10.2215/CJN.09470916hwp:resource-id:clinjasn;11/11/2095American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAtrial fibrillation, end-stage renal disease, Anticoagulants, Blood Coagulation, Disease Management, Humans, Kidney Failure, ChronicCommentariesCommentariesresearch-article20162016-11-07November 07, 201610.2215/CJN.094709161555-90411555-905X2016-10-25T04:28:27-07:002016-11-07Clinical Journal of the American Society of NephrologyCommentaries111120952096
- Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Study10.2215/CJN.02870316Mon, 24 Oct 2016 08:02:52 GMT-07:00Albuminuria Changes and Cardiovascular and Renal Outcomes in Type 1 Diabetes: The DCCT/EDIC Studyde Boer, Ian H.Gao, XiaoyuCleary, Patricia A.Bebu, IonutLachin, John M.Molitch, Mark E.Orchard, TrevorPaterson, Andrew D.Perkins, Bruce A.Steffes, Michael W.Zinman, Bernard2016-10-24T08:02:52-07:00doi:10.2215/CJN.02870316hwp:resource-id:clinjasn;11/11/1969American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes, albuminuria, cardiovascular disease, chronic kidney disease, progression of chronic renal failure, albumins, cardiovascular diseases, carotid intima-media thickness, coronary vessels, diabetes mellitus, type 1, diabetes mellitus, type 2, disease progression, kidney, renin-angiotensin system, riskOriginal ArticlesDiabetes and the kidneyOriginal ArticlesDiabetes and the kidneyresearch-article20162016-11-07November 07, 201610.2215/CJN.028703161555-90411555-905X2016-10-24T08:02:52-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles11111112196919212225197719232232
- Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Verdict 310.2215/CJN.09230816Tue, 25 Oct 2016 04:28:27 GMT-07:00Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Verdict 3Rigatto, Claudio2016-10-25T04:28:27-07:00doi:10.2215/CJN.09230816hwp:resource-id:clinjasn;11/11/2097American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic dialysis, kidney failure, Oral Anticoagulation, ESRD, Atrial FibrillationCommentariesCommentariesresearch-article20162016-11-07November 07, 201610.2215/CJN.092308161555-90411555-905X2016-10-25T04:28:27-07:002016-11-07Clinical Journal of the American Society of NephrologyCommentaries111120972097
- Association of Peritonitis with Hemodialysis Catheter Dependence after Modality Switch10.2215/CJN.04970516Tue, 30 Aug 2016 06:16:50 GMT-07:00Association of Peritonitis with Hemodialysis Catheter Dependence after Modality SwitchLee, TimmyThamer, MaeZhang, YiZhang, QianAllon, Michael2016-08-30T06:16:50-07:00doi:10.2215/CJN.04970516hwp:resource-id:clinjasn;11/11/1999American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, arteriovenous graft, hemodialysis catheter, ESRD, Adult, Humans, Medicare, peritoneal dialysis, Peritonitis, renal dialysis, United StatesOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-11-07November 07, 201610.2215/CJN.049705161555-90411555-905X2016-08-30T06:16:50-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles111119992004
- Crackles and Comets: Lung Ultrasound to Detect Pulmonary Congestion in Patients on Dialysis is Coming of Age10.2215/CJN.09140816Thu, 22 Sep 2016 06:35:07 GMT-07:00Crackles and Comets: Lung Ultrasound to Detect Pulmonary Congestion in Patients on Dialysis is Coming of AgeSherman, Richard A.2016-09-22T06:35:07-07:00doi:10.2215/CJN.09140816hwp:resource-id:clinjasn;11/11/1924American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfluid overload, dialysis volume, lung ultrasound, lung crackles, edema, uremic lung, High-Energy Shock Waves, humans, lung, Pulmonary Circulation, Pulmonary Edema, renal dialysisEditorialsEditorialseditorial20162016-11-07November 07, 201610.2215/CJN.091408161555-90411555-905X2016-09-22T06:35:07-07:002016-11-07Clinical Journal of the American Society of NephrologyEditorials1111111924200519262011
- Are Ambulatory Care–Sensitive Conditions the Fulcrum of Hospitalizations for CKD Patients?10.2215/CJN.09160816Thu, 06 Oct 2016 07:01:30 GMT-07:00Are Ambulatory Care–Sensitive Conditions the Fulcrum of Hospitalizations for CKD Patients?Fink, Jeffrey C.2016-10-06T07:01:30-07:00doi:10.2215/CJN.09160816hwp:resource-id:clinjasn;11/11/1927American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAmbulatory Care-Sensitive Conditions, CKD, hospitalization, Adverse, events, Ambulatory Care, HumansEditorialsEditorialseditorial20162016-11-07November 07, 201610.2215/CJN.091608161555-90411555-905X2016-10-06T07:01:30-07:002016-11-07Clinical Journal of the American Society of NephrologyEditorials1111111927202219282031
- Pharmacotherapy of Hypertension in Chronic Dialysis PatientsAmong patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.10.2215/CJN.00870116Mon, 24 Oct 2016 08:02:52 GMT-07:00Pharmacotherapy of Hypertension in Chronic Dialysis PatientsAmong patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis (i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.Georgianos, Panagiotis I.Agarwal, Rajiv2016-10-24T08:02:52-07:00doi:10.2215/CJN.00870116hwp:resource-id:clinjasn;11/11/2062American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, pharmacotherapy, cardiovascular disease, Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, blood pressure, Humans, Mineralocorticoid Receptor Antagonists, renal dialysis, SodiumEvidence-Based NephrologyEvidence-Based Nephrologyresearch-article20162016-11-07November 07, 201610.2215/CJN.008701161555-90411555-905X2016-10-24T08:02:52-07:002016-11-07Clinical Journal of the American Society of NephrologyEvidence-Based Nephrology111120622075
- Commentary on Pharmacotherapy of Hypertension in Patients on Chronic Dialysis10.2215/CJN.07740716Mon, 24 Oct 2016 08:02:51 GMT-07:00Commentary on Pharmacotherapy of Hypertension in Patients on Chronic DialysisSeliger, Stephen L.Kestenbaum, Bryan2016-10-24T08:02:51-07:00doi:10.2215/CJN.07740716hwp:resource-id:clinjasn;11/11/2076American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPharmacotherapy, evidence-based, hypertension, chronic dialysis, Humans, renal dialysisCommentaryCommentaryarticle-commentary20162016-11-07November 07, 201610.2215/CJN.077407161555-90411555-905X2016-10-24T08:02:51-07:002016-11-07Clinical Journal of the American Society of NephrologyCommentary111120762077
- Correction10.2215/CJN.09490916Fri, 21 Oct 2016 08:25:28 GMT-07:00CorrectionAmerican Society of Nephrology2016-10-21T08:25:28-07:00doi:10.2215/CJN.09490916hwp:resource-id:clinjasn;11/11/2053American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGFR, creatinine, pediatric nephrology, sex, β-trace proteinErratumErratumcorrection20162016-11-07November 07, 201610.2215/CJN.094909161555-90411555-905X2016-10-21T08:25:28-07:002016-11-07Clinical Journal of the American Society of NephrologyErratum111011320534012053409
- Potentially Preventable Hospitalization among Patients with CKD and High Inpatient Use10.2215/CJN.04690416Thu, 06 Oct 2016 07:01:31 GMT-07:00Potentially Preventable Hospitalization among Patients with CKD and High Inpatient UseRonksley, Paul E.Hemmelgarn, Brenda R.Manns, Braden J.Wick, JamesJames, Matthew T.Ravani, PietroQuinn, Robert R.Scott-Douglas, NairneLewanczuk, RichardTonelli, Marcello2016-10-06T07:01:31-07:00doi:10.2215/CJN.04690416hwp:resource-id:clinjasn;11/11/2022American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal insufficiency, heart failure, adult, Alberta, Ambulatory Care, Canada, follow-up studies, hospitalization, humans, Hyperkalemia, Hypertension, Malignant, Inpatients, Primary Health Care, renal dialysis, renal insufficiency, chronic, Residence CharacteristicsOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20162016-11-07November 07, 201610.2215/CJN.046904161555-90411555-905X2016-10-06T07:01:31-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1111112022192720311928
- Use of Oral Anticoagulation for Patients with ESRD on Hemodialysis with Atrial Fibrillation: Verdict 110.2215/CJN.08610816Tue, 25 Oct 2016 04:28:28 GMT-07:00Use of Oral Anticoagulation for Patients with ESRD on Hemodialysis with Atrial Fibrillation: Verdict 1Bansal, Nisha2016-10-25T04:28:28-07:00doi:10.2215/CJN.08610816hwp:resource-id:clinjasn;11/11/2093American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, cardiovascular disease, dialysis, Anticoagulants, Atrial Fibrillation, Blood Coagulation, Disease Management, Humans, Kidney Failure, ChronicCommentariesCommentariesresearch-article20162016-11-07November 07, 201610.2215/CJN.086108161555-90411555-905X2016-10-25T04:28:28-07:002016-11-07Clinical Journal of the American Society of NephrologyCommentaries111120932094
- The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study10.2215/CJN.03890416Thu, 22 Sep 2016 06:35:08 GMT-07:00The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST StudyTorino, ClaudiaGargani, LunaSicari, RosaLetachowicz, KrzysztofEkart, RobertFliser, DaniloCovic, AdrianSiamopoulos, KostasStavroulopoulos, AristeidisMassy, Ziad A.Fiaccadori, EnricoCaiazza, AlbertoBachelet, ThomasSlotki, ItzchakMartinez-Castelao, AlbertoCoudert-Krier, Marie-JeanneRossignol, PatrickGueler, FaikahHannedouche, ThierryPanichi, VincenzoWiecek, AndrzejPontoriero, GiuseppeSarafidis, PantelisKlinger, MarianHojs, RadovanSeiler-Mussler, SarahLizzi, FabioSiriopol, DimitrieBalafa, OlgaShavit, LindaTripepi, RoccoMallamaci, FrancescaTripepi, GiovanniPicano, EugenioLondon, Gérard MichelZoccali, Carmine2016-09-22T06:35:08-07:00doi:10.2215/CJN.03890416hwp:resource-id:clinjasn;11/11/2005American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, chronic kidney disease, hemodialysis, clinical epidemiology, Auscultation, Cardiomyopathies, Edema, Humans, Kidney Failure, Chronic, Pulmonary Edema, Regression Analysis, renal dialysis, Reproducibility of Results, Respiratory Sounds, Sound, ultrafiltration, WaterOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-11-07November 07, 201610.2215/CJN.038904161555-90411555-905X2016-09-22T06:35:08-07:002016-11-07Clinical Journal of the American Society of NephrologyOriginal Articles1111112005192420111926
- Is Change in Albuminuria a Surrogate Marker for Cardiovascular and Renal Outcomes in Type 1 Diabetes?10.2215/CJN.09540916Mon, 24 Oct 2016 08:02:51 GMT-07:00Is Change in Albuminuria a Surrogate Marker for Cardiovascular and Renal Outcomes in Type 1 Diabetes?Dixon, Bradley S.2016-10-24T08:02:51-07:00doi:10.2215/CJN.09540916hwp:resource-id:clinjasn;11/11/1921American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, diabetic nephropathy, microalbuminuria, cardiovascular disease, Epidemiology and outcomes, albuminuria, Biomarkers, Cardiovascular System, Diabetes Mellitus, Type 1, kidneyEditorialsEditorialseditorial20162016-11-07November 07, 201610.2215/CJN.095409161555-90411555-905X2016-10-24T08:02:51-07:002016-11-07Clinical Journal of the American Society of NephrologyEditorials1111111921196919231977
- Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: ConAmong patients with atrial fibrillation, prophylaxis for stroke prevention with the use of anticoagulation is well established in the general population. A number of randomized controlled trials and evidence-based risk prediction tools clearly delineate the benefit and risks of therapy. Despite the high incidence of atrial fibrillation in the late stage CKD and ESRD populations, little high quality evidence exists in these populations. Is it appropriate then to extrapolate findings from the general population to those with CKD/ESRD? In our view, too much uncertainty exists regarding proof of efficacy with clear signals of harm. Routine anticoagulation for stroke prevention in atrial fibrillation is not recommended for the majority of CKD and ESRD patients.10.2215/CJN.03200316Tue, 25 Oct 2016 04:28:28 GMT-07:00Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: ConAmong patients with atrial fibrillation, prophylaxis for stroke prevention with the use of anticoagulation is well established in the general population. A number of randomized controlled trials and evidence-based risk prediction tools clearly delineate the benefit and risks of therapy. Despite the high incidence of atrial fibrillation in the late stage CKD and ESRD populations, little high quality evidence exists in these populations. Is it appropriate then to extrapolate findings from the general population to those with CKD/ESRD? In our view, too much uncertainty exists regarding proof of efficacy with clear signals of harm. Routine anticoagulation for stroke prevention in atrial fibrillation is not recommended for the majority of CKD and ESRD patients.Keskar, VaibhavSood, Manish M.2016-10-25T04:28:28-07:00doi:10.2215/CJN.03200316hwp:resource-id:clinjasn;11/11/2085American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAnticoagulation, chronic kidney disease, stroke, hemorrhage, atrial fibrillation, warfarin, Blood Coagulation, Humans, Incidence, Kidney Failure, Chronic, Renal Insufficiency, Chronic, Risk, UncertaintyControversies in NephrologyControversies in Nephrologyresearch-article20162016-11-07November 07, 201610.2215/CJN.032003161555-90411555-905X2016-10-25T04:28:28-07:002016-11-07Clinical Journal of the American Society of NephrologyControversies in Nephrology111120852092
- Fractures in Patients with CKD: Time for Action10.2215/CJN.09500916Mon, 24 Oct 2016 08:02:51 GMT-07:00Fractures in Patients with CKD: Time for ActionMoe, Sharon M.Nickolas, Thomas L.2016-10-24T08:02:51-07:00doi:10.2215/CJN.09500916hwp:resource-id:clinjasn;11/11/1929American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, fracture, bone quality, renal osteodystrophy, CKDEditorialsEditorialseditorial20162016-11-07November 07, 201610.2215/CJN.095009161555-90411555-905X2016-10-24T08:02:51-07:002016-11-07Clinical Journal of the American Society of NephrologyEditorials1111111929203219312040
- Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: ProWarfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.10.2215/CJN.02680316Tue, 25 Oct 2016 04:28:28 GMT-07:00Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: ProWarfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.McCullough, Peter A.Ball, TimothyCox, Katy MathewsAssar, Manish D.2016-10-25T04:28:28-07:00doi:10.2215/CJN.02680316hwp:resource-id:clinjasn;11/11/2079American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyoral anticoagulation, atrial fibrillation, end-stage renal disease, stroke, Anticoagulants, Embolism, Hemorrhage, Humans, Kidney Failure, Chronic, renal dialysis, Warfarin, apixabanControversies in NephrologyControversies in Nephrologyarticle-commentary20162016-11-07November 07, 201610.2215/CJN.026803161555-90411555-905X2016-10-25T04:28:28-07:002016-11-07Clinical Journal of the American Society of NephrologyControversies in Nephrology111120792084
- Genetic African Ancestry and Markers of Mineral Metabolism in CKD10.2215/CJN.08020715Mon, 08 Feb 2016 06:50:45 GMT-08:00Genetic African Ancestry and Markers of Mineral Metabolism in CKDGutiérrez, Orlando M.Parsa, AfshinIsakova, TamaraScialla, Julia J.Chen, JingFlack, John M.Nessel, Lisa C.Gupta, JayantaBellovich, Keith A.Steigerwalt, SusanSondheimer, James H.Wright, Jackson T.Feldman, Harold I.Kusek, John W.Lash, James P.Wolf, Myles2016-02-08T06:50:45-08:00doi:10.2215/CJN.08020715hwp:resource-id:clinjasn;11/4/653American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, mineral metabolism, African Americans, Cohort Studies, Fibroblast Growth Factors, Humans, parathyroid hormone, Phosphorus, Renal Insufficiency, ChronicOriginal ArticlesMineral Metabolism/Bone DiseaseOriginal ArticlesMineral Metabolism/Bone Diseaseresearch-article20162016-04-07April 07, 201610.2215/CJN.080207151555-90411555-905X2016-02-08T06:50:45-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114653662
- A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction10.2215/CJN.12011214Tue, 09 Feb 2016 08:37:43 GMT-08:00A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal DysfunctionCha, Ran-huiKang, Shin WookPark, Cheol WheeCha, Dae RyongNa, Ki YoungKim, Sung GyunYoon, Sun AeHan, Sang YoubChang, Jae HyunPark, Sue K.Lim, Chun SooKim, Yon Su2016-02-09T08:37:43-08:00doi:10.2215/CJN.12011214hwp:resource-id:clinjasn;11/4/559American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRandomized trial, uremic toxin, disease progression, glomerular filtration rate, hospitalization, humans, kidney, kidney function tests, proteinuria, renal insufficiency, chronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-04-07April 07, 201610.2215/CJN.120112141555-90411555-905X2016-02-09T08:37:43-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114559567
- Association of Performance-Based and Self–Reported Function–Based Definitions of Frailty with Mortality among Patients Receiving Hemodialysis10.2215/CJN.03710415Wed, 20 Jan 2016 07:24:35 GMT-08:00Association of Performance-Based and Self–Reported Function–Based Definitions of Frailty with Mortality among Patients Receiving HemodialysisJohansen, Kirsten L.Dalrymple, Lorien S.Glidden, DavidDelgado, CynthiaKaysen, George A.Grimes, BarbaraChertow, Glenn M.2016-01-20T07:24:35-08:00doi:10.2215/CJN.03710415hwp:resource-id:clinjasn;11/4/626American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, hemodialysis, survival, geriatric nephrology, physical fitness, health status indicators, fatigue, follow-up studies, gait, hand strength, humansOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-04-07April 07, 201610.2215/CJN.037104151555-90411555-905X2016-01-20T07:24:35-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114626632
- Peripheral Edema, Central Venous Pressure, and Risk of AKI in Critical Illness10.2215/CJN.08080715Tue, 19 Jan 2016 06:59:06 GMT-08:00Peripheral Edema, Central Venous Pressure, and Risk of AKI in Critical IllnessChen, Kenneth P.Cavender, SusanLee, JoonFeng, MenglingMark, Roger G.Celi, Leo AnthonyMukamal, Kenneth J.Danziger, John2016-01-19T06:59:06-08:00doi:10.2215/CJN.08080715hwp:resource-id:clinjasn;11/4/602American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, renal function, acute kidney injury, central venous pressure, comorbidity, critical illness, edema, heart failure, humans, pulmonary edemaOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-04-07April 07, 201610.2215/CJN.080807151555-90411555-905X2016-01-19T06:59:06-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114602608
- External Validation of the Kidney Failure Risk Equation and Re-Calibration with Addition of Ultrasound Parameters10.2215/CJN.08110715Tue, 19 Jan 2016 06:59:07 GMT-08:00External Validation of the Kidney Failure Risk Equation and Re-Calibration with Addition of Ultrasound ParametersLennartz, Claudia S.Pickering, John WilliamSeiler-Mußler, SarahBauer, LucieUntersteller, KathrinEmrich, Insa EZawada, Adam M.Radermacher, JörgTangri, NavdeepFliser, DaniloHeine, Gunnar H.2016-01-19T06:59:07-08:00doi:10.2215/CJN.08110715hwp:resource-id:clinjasn;11/4/609American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney failure, ultrasonography, Doppler, calibration, humans, prospective studies, renal insufficiency, chronic, survivors, tertiary care centersOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-04-07April 07, 201610.2215/CJN.081107151555-90411555-905X2016-01-19T06:59:07-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114609615
- Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis10.2215/CJN.08510815Wed, 02 Mar 2016 06:43:30 GMT-08:00Intradialytic Hypoxemia and Clinical Outcomes in Patients on HemodialysisMeyring-Wösten, AnnaZhang, HanjieYe, XiaolingFuertinger, Doris H.Chan, LiliKappel, FranzArtemyev, MikhailGinsberg, NancyWang, YuedongThijssen, StephanKotanko, Peter2016-03-02T06:43:30-08:00doi:10.2215/CJN.08510815hwp:resource-id:clinjasn;11/4/616American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypoxia, mortality, hospitalization, erythropoietin, oxygen saturation, prolonged intradialytic hypoxemia, inflammation, Cohort Studies, Humans, renal dialysisOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-04-07April 07, 201610.2215/CJN.085108151555-90411555-905X2016-03-02T06:43:30-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1144616549625551
- Approach to the Highly Sensitized Kidney Transplant CandidateFor patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist.10.2215/CJN.05930615Thu, 25 Feb 2016 07:14:57 GMT-08:00Approach to the Highly Sensitized Kidney Transplant CandidateFor patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist.Keith, Douglas S.Vranic, Gayle M.2016-02-25T07:14:57-08:00doi:10.2215/CJN.05930615hwp:resource-id:clinjasn;11/4/684American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, immunology, allografts, HLA antigens, humans, kidney, kidney failure, chronic’ living donors, quality of life, renal dialysisAttending RoundsAttending Roundsresearch-article20162016-04-07April 07, 201610.2215/CJN.059306151555-90411555-905X2016-02-25T07:14:57-08:002016-04-07Clinical Journal of the American Society of NephrologyAttending Rounds114684693
- Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in ChildrenRituximab, a chimeric anti-CD20 monoclonal antibody originally licensed for lymphoma, is emerging as a novel steroid-sparing agent for idiopathic nephrotic syndrome in children. The potential use of anti-CD20 monoclonal antibodies in idiopathic nephrotic syndrome has contributed to shifting the view of podocytopathies from T cell–mediated to more complex immunomediated disorders that can benefit from targeting B cells and other mediators of the early immune response. Clinical data on the use of rituximab also have implications on disease management and classification. In this review, we present results of clinical studies that support rituximab as an effective steroid-sparing agent in steroid-dependent idiopathic nephrotic syndrome. Recent randomized controlled trials suggest that potential benefits of rituximab therapy in steroid-dependent forms of idiopathic nephrotic syndrome vary depending on whether children are dependent on steroids alone or on both steroids and calcineurin inhibitors, with greater probabilities to achieve drug-free remission in the former group. Multiple-drug dependence may identify a different disease state with different prognosis and treatment options. Insufficient data are available on optimal use of rituximab as a maintenance steroid-sparing agent in these steroid-sensitive forms of the disease, including how often and for how long rituximab infusions should be repeated to maximize expected benefits and minimize potential harms. Finally, one randomized controlled trial in children with steroid-resistant idiopathic nephrotic syndrome yielded negative results. New anti-CD20 antibodies are under study in this patient population.10.2215/CJN.08500815Thu, 19 Nov 2015 06:12:14 GMT-08:00Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in ChildrenRituximab, a chimeric anti-CD20 monoclonal antibody originally licensed for lymphoma, is emerging as a novel steroid-sparing agent for idiopathic nephrotic syndrome in children. The potential use of anti-CD20 monoclonal antibodies in idiopathic nephrotic syndrome has contributed to shifting the view of podocytopathies from T cell–mediated to more complex immunomediated disorders that can benefit from targeting B cells and other mediators of the early immune response. Clinical data on the use of rituximab also have implications on disease management and classification. In this review, we present results of clinical studies that support rituximab as an effective steroid-sparing agent in steroid-dependent idiopathic nephrotic syndrome. Recent randomized controlled trials suggest that potential benefits of rituximab therapy in steroid-dependent forms of idiopathic nephrotic syndrome vary depending on whether children are dependent on steroids alone or on both steroids and calcineurin inhibitors, with greater probabilities to achieve drug-free remission in the former group. Multiple-drug dependence may identify a different disease state with different prognosis and treatment options. Insufficient data are available on optimal use of rituximab as a maintenance steroid-sparing agent in these steroid-sensitive forms of the disease, including how often and for how long rituximab infusions should be repeated to maximize expected benefits and minimize potential harms. Finally, one randomized controlled trial in children with steroid-resistant idiopathic nephrotic syndrome yielded negative results. New anti-CD20 antibodies are under study in this patient population.Ravani, PietroBonanni, AliceRossi, RobertaCaridi, GianlucaGhiggeri, Gian Marco2015-11-19T06:12:14-08:00doi:10.2215/CJN.08500815hwp:resource-id:clinjasn;11/4/710American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, proteinuria, anti-CD20 monoclonal antibodies, glomerular disease, antibodies, monoclonal, child, humans, immunosuppressive agents, T-lymphocytes, rituximabMini-ReviewMini-Reviewreview-article20162016-04-07April 07, 201610.2215/CJN.085008151555-90411555-905X2015-11-19T06:12:14-08:002016-04-07Clinical Journal of the American Society of NephrologyMini-Review114710720
- Lupus Podocytopathy: A Distinct Entity10.2215/CJN.01880216Wed, 16 Mar 2016 10:16:15 GMT-07:00Lupus Podocytopathy: A Distinct EntityBomback, Andrew S.Markowitz, Glen S.2016-03-16T10:16:15-07:00doi:10.2215/CJN.01880216hwp:resource-id:clinjasn;11/4/547American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, systemic lupus erythematosus, nephrotic syndrome, PodocytesEditorialsEditorialseditorial20162016-04-07April 07, 201610.2215/CJN.018802161555-90411555-905X2016-03-16T10:16:15-07:002016-04-07Clinical Journal of the American Society of NephrologyEditorials1144547585548592
- Emergency Department Visits after Kidney Transplantation10.2215/CJN.07950715Thu, 24 Mar 2016 06:41:23 GMT-07:00Emergency Department Visits after Kidney TransplantationSchold, Jesse D.Elfadawy, NissreenBuccini, Laura D.Goldfarb, David A.Flechner, Stuart M.P. Phelan, MichaelPoggio, Emilio D.2016-03-24T06:41:23-07:00doi:10.2215/CJN.07950715hwp:resource-id:clinjasn;11/4/674American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, hospitalization, ethnicity, transplant outcomes, diabetes mellitus, Emergency Service, Hospital, Follow-Up Studies, Health Care Costs, Humans, Transplant RecipientsOriginal ArticlesRenal transplantationOriginal ArticlesRenal transplantationresearch-article20162016-04-07April 07, 201610.2215/CJN.079507151555-90411555-905X2016-03-24T06:41:23-07:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1144674555683557
- Emergency Department Visits after Kidney Transplantation10.2215/CJN.02040216Thu, 24 Mar 2016 06:41:23 GMT-07:00Emergency Department Visits after Kidney TransplantationDalrymple, Lorien S.Romano, Patrick S.2016-03-24T06:41:23-07:00doi:10.2215/CJN.02040216hwp:resource-id:clinjasn;11/4/555American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyemergency department, transplant outcomes, kidney transplantation, utilization, Emergency Service, Hospital, kidney, Transplant RecipientsEditorialsEditorialseditorial20162016-04-07April 07, 201610.2215/CJN.020402161555-90411555-905X2016-03-24T06:41:23-07:002016-04-07Clinical Journal of the American Society of NephrologyEditorials1144555674557683
- American Society of Nephrology Quiz and Questionnaire 2015: Electrolytes and Acid–Base DisordersThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. During the 2015 meeting the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid–base disorders, glomerular disease, end-stage renal disease and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single-best-answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cell-phone app containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for the Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.10.2215/CJN.12801215Fri, 29 Jan 2016 06:46:12 GMT-08:00American Society of Nephrology Quiz and Questionnaire 2015: Electrolytes and Acid–Base DisordersThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. During the 2015 meeting the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid–base disorders, glomerular disease, end-stage renal disease and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single-best-answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cell-phone app containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for the Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.Rosner, Mitchell H.Perazella, Mark A.Choi, Michael J.2016-01-29T06:46:12-08:00doi:10.2215/CJN.12801215hwp:resource-id:clinjasn;11/4/735American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, hyponatremia, vasopressin, WNK kinases, calcineurin inhibitor, electrolytes, kidney, Kidney Diseases, Kidney Failure, Chronic, kidney transplantationSpecial FeatureSpecial Featureresearch-article20162016-04-07April 07, 201610.2215/CJN.128012151555-90411555-905X2016-01-29T06:46:12-08:002016-04-07Clinical Journal of the American Society of NephrologySpecial Feature114735744
- Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin SystemATPase H+-transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H+-ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na+-K+-2Cl− cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity.10.1681/ASN.2015080915Mon, 04 Apr 2016 07:51:20 GMT-07:00Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin SystemATPase H+-transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H+-ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na+-K+-2Cl− cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity.Trepiccione, FrancescoGerber, Simon D.Grahammer, FlorianLópez-Cayuqueo, Karen I.Baudrie, VéroniquePăunescu, Teodor G.Capen, Diane E.Picard, NicolasAlexander, R. ToddHuber, Tobias B.Chambrey, RegineBrown, DennisHouillier, PascalEladari, DominiqueSimons, Matias2016-04-04T07:51:20-07:00doi:10.1681/ASN.2015080915hwp:resource-id:jnephrol;27/11/3320American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCell & Transport Physiology, cell biology and structure, acidosis, water-electrolyte, balanceBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150809151046-66731533-34502016-04-04T07:51:20-07:002016-11Journal of the American Society of NephrologyBasic Research271133203330
- Relationship between eGFR Decline and Hard Outcomes after Kidney TransplantsTrials designed to assess the effect of interventions on death and graft failure in kidney transplant recipients are not feasible, because these are predominantly late events. Here, we examined the potential of percentage decline in eGFR as a surrogate for hard outcomes. We obtained deidentified data from the Australia and New Zealand Dialysis and Transplant Registry and studied 7949 transplants performed from 1995 to 2009, including 71,845 patient-years of follow-up, 1121 graft losses, and 1192 deaths. We used adjusted Cox proportional hazards models to determine risks of death or death–censored graft failure related to percentage change in eGFR between years 1 and 3 after transplant. Percentage change in eGFR was modeled as a restricted cubic spline. Rate of eGFR decline associated with exponentially increased risks of graft failure and death. Compared with stable eGFR, a ≥30% decline in eGFR, detected in 10% of patients, strongly associated with subsequent death (hazard ratio, 2.20; 95% confidence interval, 1.87 to 2.60) and death–censored graft failure (hazard ratio, 5.14; 95% confidence interval, 4.44 to 5.95). Decline in eGFR was superior to other surrogates, including acute rejection, doubling of serum creatinine level, and eGFR at year 1 or year 2. We conclude that 30% decline in eGFR between years 1 and 3 after kidney transplant is common and strongly associated with risks of subsequent death and death–censored graft failure, which mirrors findings in CKD. Percentage decline in eGFR should be considered for use as a surrogate outcome in kidney transplant trials.10.1681/ASN.2015050524Fri, 08 Apr 2016 05:34:15 GMT-07:00Relationship between eGFR Decline and Hard Outcomes after Kidney TransplantsTrials designed to assess the effect of interventions on death and graft failure in kidney transplant recipients are not feasible, because these are predominantly late events. Here, we examined the potential of percentage decline in eGFR as a surrogate for hard outcomes. We obtained deidentified data from the Australia and New Zealand Dialysis and Transplant Registry and studied 7949 transplants performed from 1995 to 2009, including 71,845 patient-years of follow-up, 1121 graft losses, and 1192 deaths. We used adjusted Cox proportional hazards models to determine risks of death or death–censored graft failure related to percentage change in eGFR between years 1 and 3 after transplant. Percentage change in eGFR was modeled as a restricted cubic spline. Rate of eGFR decline associated with exponentially increased risks of graft failure and death. Compared with stable eGFR, a ≥30% decline in eGFR, detected in 10% of patients, strongly associated with subsequent death (hazard ratio, 2.20; 95% confidence interval, 1.87 to 2.60) and death–censored graft failure (hazard ratio, 5.14; 95% confidence interval, 4.44 to 5.95). Decline in eGFR was superior to other surrogates, including acute rejection, doubling of serum creatinine level, and eGFR at year 1 or year 2. We conclude that 30% decline in eGFR between years 1 and 3 after kidney transplant is common and strongly associated with risks of subsequent death and death–censored graft failure, which mirrors findings in CKD. Percentage decline in eGFR should be considered for use as a surrogate outcome in kidney transplant trials.Clayton, Philip A.Lim, Wai H.Wong, GermaineChadban, Steven J.2016-04-08T05:34:15-07:00doi:10.1681/ASN.2015050524hwp:resource-id:jnephrol;27/11/3440American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular filtration rate, mortality, renal transplantation, transplant outcomesClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20150505241046-66731533-34502016-04-08T05:34:15-07:002016-11Journal of the American Society of NephrologyClinical Research271134403446
- Bad Memory: CD4 T Cell Presensitization Fosters Antibody-Mediated Kidney Transplant Rejection10.1681/ASN.2016040470Wed, 25 May 2016 06:24:09 GMT-07:00Bad Memory: CD4 T Cell Presensitization Fosters Antibody-Mediated Kidney Transplant RejectionDean, Patrick G.Griffin, Matthew D.2016-05-25T06:24:09-07:00doi:10.1681/ASN.2016040470hwp:resource-id:jnephrol;27/11/3231American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, immunology, acute rejection, chronic allograft rejection, transplant pathology, Cell transferUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-11-01November 201610.1681/ASN.20160404701046-66731533-34502016-05-25T06:24:09-07:002016-11Journal of the American Society of NephrologyUp Front Matters2711113231329932333307
- Electrophysiologic Substrate and Risk of Mortality in Incident HemodialysisThe single leading cause of mortality on hemodialysis is sudden cardiac death. Whether measures of electrophysiologic substrate independently associate with mortality is unknown. We examined measures of electrophysiologic substrate in a prospective cohort of 571 patients on incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease Study. A total of 358 participants completed both baseline 5-minute and 12-lead electrocardiogram recordings on a nondialysis day. Measures of electrophysiologic substrate included ventricular late potentials by the signal-averaged electrocardiogram and spatial mean QRS-T angle measured on the averaged beat recorded within a median of 106 days (interquartile range, 78–151 days) from dialysis initiation. The cohort was 59% men, and 73% were black, with a mean±SD age of 55±13 years. Transthoracic echocardiography revealed a mean±SD ejection fraction of 65.5%±12.0% and a mean±SD left ventricular mass index of 66.6±22.3 g/m2.7. During 864.6 person-years of follow-up, 77 patients died; 35 died from cardiovascular causes, of which 15 were sudden cardiac deaths. By Cox regression analysis, QRS-T angle ≥75° significantly associated with increased risk of cardiovascular mortality (hazard ratio, 2.99; 95% confidence interval, 1.31 to 6.82) and sudden cardiac death (hazard ratio, 4.52; 95% confidence interval, 1.17 to 17.40) after multivariable adjustment for demographic, cardiovascular, and dialysis factors. Abnormal signal–averaged electrocardiogram measures did not associate with mortality. In conclusion, spatial QRS-T angle but not abnormal signal–averaged electrocardiogram significantly associates with cardiovascular mortality and sudden cardiac death independent of traditional risk factors in patients starting hemodialysis.10.1681/ASN.2015080916Fri, 29 Apr 2016 06:40:10 GMT-07:00Electrophysiologic Substrate and Risk of Mortality in Incident HemodialysisThe single leading cause of mortality on hemodialysis is sudden cardiac death. Whether measures of electrophysiologic substrate independently associate with mortality is unknown. We examined measures of electrophysiologic substrate in a prospective cohort of 571 patients on incident hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease Study. A total of 358 participants completed both baseline 5-minute and 12-lead electrocardiogram recordings on a nondialysis day. Measures of electrophysiologic substrate included ventricular late potentials by the signal-averaged electrocardiogram and spatial mean QRS-T angle measured on the averaged beat recorded within a median of 106 days (interquartile range, 78–151 days) from dialysis initiation. The cohort was 59% men, and 73% were black, with a mean±SD age of 55±13 years. Transthoracic echocardiography revealed a mean±SD ejection fraction of 65.5%±12.0% and a mean±SD left ventricular mass index of 66.6±22.3 g/m2.7. During 864.6 person-years of follow-up, 77 patients died; 35 died from cardiovascular causes, of which 15 were sudden cardiac deaths. By Cox regression analysis, QRS-T angle ≥75° significantly associated with increased risk of cardiovascular mortality (hazard ratio, 2.99; 95% confidence interval, 1.31 to 6.82) and sudden cardiac death (hazard ratio, 4.52; 95% confidence interval, 1.17 to 17.40) after multivariable adjustment for demographic, cardiovascular, and dialysis factors. Abnormal signal–averaged electrocardiogram measures did not associate with mortality. In conclusion, spatial QRS-T angle but not abnormal signal–averaged electrocardiogram significantly associates with cardiovascular mortality and sudden cardiac death independent of traditional risk factors in patients starting hemodialysis.Tereshchenko, Larisa G.Kim, Esther D.Oehler, AndrewMeoni, Lucy A.Ghafoori, ElyarRami, TejalMaly, MaggieKabir, MuammarHawkins, LaurenTomaselli, Gordon F.Lima, Joao A.Jaar, Bernard G.Sozio, Stephen M.Estrella, MichelleKao, W.H. LindaParekh, Rulan S.2016-04-29T06:40:10-07:00doi:10.1681/ASN.2015080916hwp:resource-id:jnephrol;27/11/3413American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyElectrocardiogram, QRS-T angle, Arrhythmia, mortality, End stage renal disease, Sudden cardiac deathClinical EpidemiologyClinical Epidemiologyresearch-article20162016-11-01November 201610.1681/ASN.20150809161046-66731533-34502016-04-29T06:40:10-07:002016-11Journal of the American Society of NephrologyClinical Epidemiology271134133420
- Intravital and Kidney Slice Imaging of Podocyte Membrane DynamicsIn glomerular disease, podocyte injury results in a dramatic change in cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through the activity of small GTPases was identified as a key mechanism in effacement, with increased membrane activity and motility in vitro. However, whether podocytes are stationary or actively moving cells in vivo remains debated. Using intravital and kidney slice two–photon imaging of the three-dimensional structure of mouse podocytes, we found that uninjured podocytes remained nonmotile and maintained a canopy-shaped structure over time. On expression of constitutively active Rac1, however, podocytes changed shape by retracting processes and clearly exhibited domains of increased membrane activity. Constitutive activation of Rac1 also led to podocyte detachment from the glomerular basement membrane, and we detected detached podocytes crawling on the surface of the tubular epithelium and occasionally, in contact with peritubular capillaries. Podocyte membrane activity also increased in the inflammatory environment of immune complex–mediated GN. Our results provide evidence that podocytes transition from a static to a dynamic state in vivo, shedding new light on mechanisms in foot process effacement.10.1681/ASN.2015121303Fri, 01 Apr 2016 07:44:02 GMT-07:00Intravital and Kidney Slice Imaging of Podocyte Membrane DynamicsIn glomerular disease, podocyte injury results in a dramatic change in cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through the activity of small GTPases was identified as a key mechanism in effacement, with increased membrane activity and motility in vitro. However, whether podocytes are stationary or actively moving cells in vivo remains debated. Using intravital and kidney slice two–photon imaging of the three-dimensional structure of mouse podocytes, we found that uninjured podocytes remained nonmotile and maintained a canopy-shaped structure over time. On expression of constitutively active Rac1, however, podocytes changed shape by retracting processes and clearly exhibited domains of increased membrane activity. Constitutive activation of Rac1 also led to podocyte detachment from the glomerular basement membrane, and we detected detached podocytes crawling on the surface of the tubular epithelium and occasionally, in contact with peritubular capillaries. Podocyte membrane activity also increased in the inflammatory environment of immune complex–mediated GN. Our results provide evidence that podocytes transition from a static to a dynamic state in vivo, shedding new light on mechanisms in foot process effacement.Brähler, SebastianYu, HaiyangSuleiman, HaniKrishnan, Gokul M.Saunders, Brian T.Kopp, Jeffrey B.Miner, Jeffrey H.Zinselmeyer, Bernd H.Shaw, Andrey S.2016-04-01T07:44:02-07:00doi:10.1681/ASN.2015121303hwp:resource-id:jnephrol;27/11/3285American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, cytoskeleton, glomerular diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-11-01November 201610.1681/ASN.20151213031046-66731533-34502016-04-01T07:44:02-07:002016-11Journal of the American Society of NephrologyBrief Communications271132853290
- The Current State of Peritoneal DialysisTechnical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.10.1681/ASN.2016010112Thu, 23 Jun 2016 07:48:49 GMT-07:00The Current State of Peritoneal DialysisTechnical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.Mehrotra, RajnishDevuyst, OlivierDavies, Simon J.Johnson, David W.2016-06-23T07:48:49-07:00doi:10.1681/ASN.2016010112hwp:resource-id:jnephrol;27/11/3238American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal membrane, peritoneal dialysis, end-stage renal disease, cardiovascular disease, Life-threatening dialysis complicationsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-11-01November 201610.1681/ASN.20160101121046-66731533-34502016-06-23T07:48:49-07:002016-11Journal of the American Society of NephrologyUp Front Matters271132383252
- Loss of Kynurenine 3-Mono-oxygenase Causes ProteinuriaChanges in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes.10.1681/ASN.2015070835Mon, 28 Mar 2016 06:04:46 GMT-07:00Loss of Kynurenine 3-Mono-oxygenase Causes ProteinuriaChanges in metabolite levels of the kynurenine pathway have been observed in patients with CKD, suggesting involvement of this pathway in disease pathogenesis. Our recent genetic analysis in the mouse identified the kynurenine 3-mono-oxygenase (KMO) gene (Kmo) as a candidate gene associated with albuminuria. This study investigated this association in more detail. We compared KMO abundance in the glomeruli of mice and humans under normal and diabetic conditions, observing a decrease in glomerular KMO expression with diabetes. Knockdown of kmo expression in zebrafish and genetic deletion of Kmo in mice each led to a proteinuria phenotype. We observed pronounced podocyte foot process effacement on long stretches of the filtration barrier in the zebrafish knockdown model and mild podocyte foot process effacement in the mouse model, whereas all other structures within the kidney remained unremarkable. These data establish the candidacy of KMO as a causal factor for changes in the kidney leading to proteinuria and indicate a functional role for KMO and metabolites of the tryptophan pathway in podocytes.Korstanje, RonDeutsch, KonstantinBolanos-Palmieri, PatriciaHanke, NilsSchroder, PatriciaStaggs, LynneBräsen, Jan H.Roberts, Ian S.D.Sheehan, SusanSavage, HollyHaller, HermannSchiffer, Mario2016-03-28T06:04:46-07:00doi:10.1681/ASN.2015070835hwp:resource-id:jnephrol;27/11/3271American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, proteinuria, genetic renal diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-11-01November 201610.1681/ASN.20150708351046-66731533-34502016-03-28T06:04:46-07:002016-11Journal of the American Society of NephrologyBrief Communications271132713277
- 2015 Homer W. Smith Award: The Podocyte from Periphery to Center StageThis overview summarizes selected major developments over the last 40 years in understanding podocyte biology and its involvement in glomerular disease subjectively from my perspective. Serendipity has played a major role in my contributions to investigative nephrology that range from basic mechanisms of immune deposit formation in experimental membranous nephropathy to the role of a microRNA in FSGS. This review emphasizes the importance of continuous reality checks of experimental results obtained in vitro or with genetically modified animals with human disease.10.1681/ASN.2016040490Mon, 20 Jun 2016 06:00:04 GMT-07:002015 Homer W. Smith Award: The Podocyte from Periphery to Center StageThis overview summarizes selected major developments over the last 40 years in understanding podocyte biology and its involvement in glomerular disease subjectively from my perspective. Serendipity has played a major role in my contributions to investigative nephrology that range from basic mechanisms of immune deposit formation in experimental membranous nephropathy to the role of a microRNA in FSGS. This review emphasizes the importance of continuous reality checks of experimental results obtained in vitro or with genetically modified animals with human disease.Kerjaschki, Dontscho2016-06-20T06:00:04-07:00doi:10.1681/ASN.2016040490hwp:resource-id:jnephrol;27/11/3266American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, Homer Smith, kidney disease, microRNAs, focal segmental glomerulosclerosis, nephrologyUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-11-01November 201610.1681/ASN.20160404901046-66731533-34502016-06-20T06:00:04-07:002016-11Journal of the American Society of NephrologyUp Front Matters271132663270
- This Month's Highlights10.1681/ASN.2016070772Mon, 31 Oct 2016 10:00:44 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-10-31T10:00:44-07:00doi:10.1681/ASN.2016070772hwp:resource-id:jnephrol;27/11/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20162016-11-01November 201610.1681/ASN.20160707721046-66731533-34502016-10-31T10:00:44-07:002016-11Journal of the American Society of NephrologyThis Month’s Highlights2711ii
- Mendelian Randomization as an Approach to Assess Causality Using Observational DataMendelian randomization refers to an analytic approach to assess the causality of an observed association between a modifiable exposure or risk factor and a clinically relevant outcome. It presents a valuable tool, especially when randomized controlled trials to examine causality are not feasible and observational studies provide biased associations because of confounding or reverse causality. These issues are addressed by using genetic variants as instrumental variables for the tested exposure: the alleles of this exposure–associated genetic variant are randomly allocated and not subject to reverse causation. This, together with the wide availability of published genetic associations to screen for suitable genetic instrumental variables make Mendelian randomization a time- and cost-efficient approach and contribute to its increasing popularity for assessing and screening for potentially causal associations. An observed association between the genetic instrumental variable and the outcome supports the hypothesis that the exposure in question is causally related to the outcome. This review provides an overview of the Mendelian randomization method, addresses assumptions and implications, and includes illustrative examples. We also discuss special issues in nephrology, such as inverse risk factor associations in advanced disease, and outline opportunities to design Mendelian randomization studies around kidney function and disease.10.1681/ASN.2016010098Tue, 02 Aug 2016 06:05:11 GMT-07:00Mendelian Randomization as an Approach to Assess Causality Using Observational DataMendelian randomization refers to an analytic approach to assess the causality of an observed association between a modifiable exposure or risk factor and a clinically relevant outcome. It presents a valuable tool, especially when randomized controlled trials to examine causality are not feasible and observational studies provide biased associations because of confounding or reverse causality. These issues are addressed by using genetic variants as instrumental variables for the tested exposure: the alleles of this exposure–associated genetic variant are randomly allocated and not subject to reverse causation. This, together with the wide availability of published genetic associations to screen for suitable genetic instrumental variables make Mendelian randomization a time- and cost-efficient approach and contribute to its increasing popularity for assessing and screening for potentially causal associations. An observed association between the genetic instrumental variable and the outcome supports the hypothesis that the exposure in question is causally related to the outcome. This review provides an overview of the Mendelian randomization method, addresses assumptions and implications, and includes illustrative examples. We also discuss special issues in nephrology, such as inverse risk factor associations in advanced disease, and outline opportunities to design Mendelian randomization studies around kidney function and disease.Sekula, PeggyDel Greco M, FabiolaPattaro, CristianKöttgen, Anna2016-08-02T06:05:11-07:00doi:10.1681/ASN.2016010098hwp:resource-id:jnephrol;27/11/3253American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycausality, mendelian randomization, statistical methodUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-11-01November 201610.1681/ASN.20160100981046-66731533-34502016-08-02T06:05:11-07:002016-11Journal of the American Society of NephrologyUp Front Matters271132533265
- Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac SurgeryHeme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ≥27 GT repeats), and defined AKI as an increase in serum creatinine ≥0.3 mg/dl within 48 hours or ≥50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.10.1681/ASN.2016010038Thu, 02 Jun 2016 05:35:03 GMT-07:00Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac SurgeryHeme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; ≥27 GT repeats), and defined AKI as an increase in serum creatinine ≥0.3 mg/dl within 48 hours or ≥50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.Leaf, David E.Body, Simon C.Muehlschlegel, Jochen D.McMahon, Gearoid M.Lichtner, PeterCollard, Charles D.Shernan, Stanton K.Fox, Amanda A.Waikar, Sushrut S.2016-06-02T05:35:03-07:00doi:10.1681/ASN.2016010038hwp:resource-id:jnephrol;27/11/3291American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, heme oxygenase, human geneticsBrief CommunicationsBrief Communicationsbrief-report20162016-11-01November 201610.1681/ASN.20160100381046-66731533-34502016-06-02T05:35:03-07:002016-11Journal of the American Society of NephrologyBrief Communications2711113291322932973231
- Heme Oxygenase-1 Gene Polymorphisms—Toward Precision Medicine for AKI10.1681/ASN.2016060699Thu, 04 Aug 2016 05:44:09 GMT-07:00Heme Oxygenase-1 Gene Polymorphisms—Toward Precision Medicine for AKICurtis, Lisa M.Agarwal, Anupam2016-08-04T05:44:09-07:00doi:10.1681/ASN.2016060699hwp:resource-id:jnephrol;27/11/3229American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, heme oxygenase, gene transcription, ischemia-reperfusion, polymorphisms, reactive oxygen speciesUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-11-01November 201610.1681/ASN.20160606991046-66731533-34502016-08-04T05:44:09-07:002016-11Journal of the American Society of NephrologyUp Front Matters2711113229329132313297
- Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA NephropathyAutoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactose-deficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y1CS3, in the complementarity-determining region 3 of the heavy chain variable region compared with a Y1CA3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls from whom we had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y1C(A/V)3 amino-acid sequence. Thus, the A/V>S substitution in the complementarity-determining region 3 of anti-galactose–deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent β-sheet and stem structure, important features for effective binding to galactose-deficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy.10.1681/ASN.2014101044Thu, 10 Mar 2016 07:57:44 GMT-08:00Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA NephropathyAutoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactose-deficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y1CS3, in the complementarity-determining region 3 of the heavy chain variable region compared with a Y1CA3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls from whom we had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y1C(A/V)3 amino-acid sequence. Thus, the A/V>S substitution in the complementarity-determining region 3 of anti-galactose–deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent β-sheet and stem structure, important features for effective binding to galactose-deficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy.Huang, Zhi QiangRaska, MilanStewart, Tyler J.Reily, ColinKing, R. GlennCrossman, David K.Crowley, Michael R.Hargett, AudraZhang, ZhixinSuzuki, HitoshiHall, StacyWyatt, Robert J.Julian, Bruce A.Renfrow, Matthew B.Gharavi, Ali G.Novak, Jan2016-03-10T07:57:44-08:00doi:10.1681/ASN.2014101044hwp:resource-id:jnephrol;27/11/3278American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, immune complexes, immunologyBrief CommunicationsBrief Communicationsbrief-report20162016-11-01November 201610.1681/ASN.20141010441046-66731533-34502016-03-10T07:57:44-08:002016-11Journal of the American Society of NephrologyBrief Communications271132783284
- Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates with Calcium Nephrolithiasis in PatientsHypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole–cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2– and caveolin-1–mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan–deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.10.1681/ASN.2015101100Fri, 01 Apr 2016 07:44:03 GMT-07:00Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates with Calcium Nephrolithiasis in PatientsHypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 (MUC1) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls (n=12), patients (n=12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole–cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2– and caveolin-1–mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N-glycan–deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N-glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.Nie, MingzhuBal, Manjot S.Yang, ZhufengLiu, JieRivera, CarolinaWenzel, AndreaBeck, Bodo B.Sakhaee, KhashayarMarciano, Denise K.Wolf, Matthias T.F.2016-04-01T07:44:03-07:00doi:10.1681/ASN.2015101100hwp:resource-id:jnephrol;27/11/3447American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, kidney stones, ion channel, hypercalciuria, endocytosis, electrophysiologyClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20151011001046-66731533-34502016-04-01T07:44:03-07:002016-11Journal of the American Society of NephrologyClinical Research271134473458
- Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis StudyThe Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (−9%; 95% confidence interval [95% CI], −2% to −15%), indoxyl sulfate (−11%; 95% CI, −6% to −15%), and methylguanidine (−22%; 95% CI, −18% to −27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea. In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy.10.1681/ASN.2015091035Tue, 29 Mar 2016 07:00:02 GMT-07:00Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis StudyThe Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (−9%; 95% confidence interval [95% CI], −2% to −15%), indoxyl sulfate (−11%; 95% CI, −6% to −15%), and methylguanidine (−22%; 95% CI, −18% to −27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea. In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy.Meyer, Timothy W.Sirich, Tammy L.Fong, Kara D.Plummer, Natalie S.Shafi, TariqHwang, SeungyoungBanerjee, TanushreeZhu, YunnuoPowe, Neil R.Hai, XinHostetter, Thomas H.2016-03-29T07:00:02-07:00doi:10.1681/ASN.2015091035hwp:resource-id:jnephrol;27/11/3469American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, uremia, hemodialysis adequacyClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20150910351046-66731533-34502016-03-29T07:00:02-07:002016-11Journal of the American Society of NephrologyClinical Research2711113469323534783237
- Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKDColonic microbial metabolism substantially contributes to uremic solute production. p-Cresyl sulfate and indoxyl sulfate are the main representatives of solutes of microbial origin and also, protein-bound solutes, exhibiting high protein-binding affinity and dependence on tubular secretion. Phenylacetylglutamine is another microbial metabolite with high dependence on tubular secretion but low protein-binding affinity. The relevance of such solutes is unknown. Therefore, we prospectively followed 488 patients with CKD stages 1–5 and a measurement of serum phenylacetylglutamine by liquid chromatography-mass spectrometry. In a subgroup, we determined 24-hour urinary excretion as a surrogate of intestinal uptake as well as renal clearance of phenylacetylglutamine. We performed outcome analysis for mortality (51 events) and cardiovascular disease (75 events). Serum phenylacetylglutamine level correlated with 24-hour urinary excretion (rho=0.55; P<0.001) and clearance of phenylacetylglutamine (rho=−0.76; P<0.001). Phenylacetylglutamine clearance also correlated with eGFR (rho=0.84; P<0.001). Furthermore, serum phenylacetylglutamine level associated with mortality (hazard ratio per 1-SD increase, 1.77; 95% confidence interval, 1.22 to 2.57; P=0.003) and cardiovascular disease (hazard ratio, 1.79; 95% confidence interval, 1.32 to 2.41; P<0.001) after adjustment for age, sex, presence of diabetes mellitus, prior cardiovascular disease, and eGFR. Thus, serum phenylacetylglutamine level is elevated in patients with more advanced CKD and determined by intestinal uptake and renal clearance, and it is not fully accounted for by differences in eGFR. High serum phenylacetylglutamine level is a strong and independent risk factor for mortality and cardiovascular disease, suggesting the relevance of microbial metabolism and/or tubular dysfunction in CKD, irrespective of protein binding.10.1681/ASN.2015121302Thu, 26 May 2016 06:16:23 GMT-07:00Microbiota-Derived Phenylacetylglutamine Associates with Overall Mortality and Cardiovascular Disease in Patients with CKDColonic microbial metabolism substantially contributes to uremic solute production. p-Cresyl sulfate and indoxyl sulfate are the main representatives of solutes of microbial origin and also, protein-bound solutes, exhibiting high protein-binding affinity and dependence on tubular secretion. Phenylacetylglutamine is another microbial metabolite with high dependence on tubular secretion but low protein-binding affinity. The relevance of such solutes is unknown. Therefore, we prospectively followed 488 patients with CKD stages 1–5 and a measurement of serum phenylacetylglutamine by liquid chromatography-mass spectrometry. In a subgroup, we determined 24-hour urinary excretion as a surrogate of intestinal uptake as well as renal clearance of phenylacetylglutamine. We performed outcome analysis for mortality (51 events) and cardiovascular disease (75 events). Serum phenylacetylglutamine level correlated with 24-hour urinary excretion (rho=0.55; P<0.001) and clearance of phenylacetylglutamine (rho=−0.76; P<0.001). Phenylacetylglutamine clearance also correlated with eGFR (rho=0.84; P<0.001). Furthermore, serum phenylacetylglutamine level associated with mortality (hazard ratio per 1-SD increase, 1.77; 95% confidence interval, 1.22 to 2.57; P=0.003) and cardiovascular disease (hazard ratio, 1.79; 95% confidence interval, 1.32 to 2.41; P<0.001) after adjustment for age, sex, presence of diabetes mellitus, prior cardiovascular disease, and eGFR. Thus, serum phenylacetylglutamine level is elevated in patients with more advanced CKD and determined by intestinal uptake and renal clearance, and it is not fully accounted for by differences in eGFR. High serum phenylacetylglutamine level is a strong and independent risk factor for mortality and cardiovascular disease, suggesting the relevance of microbial metabolism and/or tubular dysfunction in CKD, irrespective of protein binding.Poesen, RubenClaes, KathleenEvenepoel, Pieterde Loor, HenrietteAugustijns, PatrickKuypers, DirkMeijers, Björn2016-05-26T06:16:23-07:00doi:10.1681/ASN.2015121302hwp:resource-id:jnephrol;27/11/3479American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, uremia, intestine, tubular epitheliumClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20151213021046-66731533-34502016-05-26T06:16:23-07:002016-11Journal of the American Society of NephrologyClinical Research271134793487
- CKD Progression and Mortality among Hispanics and Non-HispanicsAlthough recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes.10.1681/ASN.2015050570Thu, 05 May 2016 07:03:13 GMT-07:00CKD Progression and Mortality among Hispanics and Non-HispanicsAlthough recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes.Fischer, Michael J.Hsu, Jesse Y.Lora, Claudia M.Ricardo, Ana C.Anderson, Amanda H.Bazzano, LydiaCuevas, Magdalena M.Hsu, Chi-yuanKusek, John W.Renteria, AmadaOjo, Akinlolu O.Raj, Dominic S.Rosas, Sylvia E.Pan, QiangYaffe, KristineGo, Alan S.Lash, James P.,Appel, Lawrence J.Feldman, Harold I.He, JiangRahman, MahboobTownsend, Raymond R.2016-05-05T07:03:13-07:00doi:10.1681/ASN.2015050570hwp:resource-id:jnephrol;27/11/3488American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, ethnicity, mortalityClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20150505701046-66731533-34502016-05-05T07:03:13-07:002016-11Journal of the American Society of NephrologyClinical Research271134883497
- Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer PropertiesCisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced increase in BUN and serum creatinine levels, renal tubular apoptosis, and oxidative stress. Additionally, pretreatment with dichloroacetate accelerated tubular regeneration after cisplatin-induced renal damage. Whole transcriptome sequencing revealed that dichloroacetate prevented mitochondrial dysfunction and preserved the energy-generating capacity of the kidneys by preventing the cisplatin-induced downregulation of fatty acid and glucose oxidation, and of genes involved in the Krebs cycle and oxidative phosphorylation. Notably, dichloroacetate did not interfere with the anticancer activity of cisplatin in vivo. These data provide strong evidence that dichloroacetate preserves renal function when used in conjunction with cisplatin.10.1681/ASN.2015070827Wed, 09 Mar 2016 09:59:02 GMT-08:00Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer PropertiesCisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced increase in BUN and serum creatinine levels, renal tubular apoptosis, and oxidative stress. Additionally, pretreatment with dichloroacetate accelerated tubular regeneration after cisplatin-induced renal damage. Whole transcriptome sequencing revealed that dichloroacetate prevented mitochondrial dysfunction and preserved the energy-generating capacity of the kidneys by preventing the cisplatin-induced downregulation of fatty acid and glucose oxidation, and of genes involved in the Krebs cycle and oxidative phosphorylation. Notably, dichloroacetate did not interfere with the anticancer activity of cisplatin in vivo. These data provide strong evidence that dichloroacetate preserves renal function when used in conjunction with cisplatin.Galgamuwa, RamindhuHardy, KristineDahlstrom, Jane E.Blackburn, Anneke C.Wium, ElizeRooke, MelissaCappello, Jean Y.Tummala, PadmajaPatel, Hardip R.Chuah, AaronTian, LuyangMcMorrow, LindaBoard, Philip G.Theodoratos, Angelo2016-03-09T09:59:02-08:00doi:10.1681/ASN.2015070827hwp:resource-id:jnephrol;27/11/3331American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cisplatin nephrotoxicity, renal protectionBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150708271046-66731533-34502016-03-09T09:59:02-08:002016-11Journal of the American Society of NephrologyBasic Research271133313344
- Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct CellsExtracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCDC11 cells required cAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo. We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease.10.1681/ASN.2015050568Mon, 28 Mar 2016 06:04:45 GMT-07:00Vasopressin Regulates Extracellular Vesicle Uptake by Kidney Collecting Duct CellsExtracellular vesicles (ECVs) facilitate intercellular communication along the nephron, with the potential to change the function of the recipient cell. However, it is not known whether this is a regulated process analogous to other signaling systems. We investigated the potential hormonal regulation of ECV transfer and report that desmopressin, a vasopressin analogue, stimulated the uptake of fluorescently loaded ECVs into a kidney collecting duct cell line (mCCDC11) and into primary cells. Exposure of mCCDC11 cells to ECVs isolated from cells overexpressing microRNA-503 led to downregulated expression of microRNA-503 target genes, but only in the presence of desmopressin. Mechanistically, ECV entry into mCCDC11 cells required cAMP production, was reduced by inhibiting dynamin, and was selective for ECVs from kidney tubular cells. In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan. In control-treated mice, we recovered 2.5% of administered ECVs in the urine; tolvaptan increased recovery five-fold and reduced ECV deposition in kidney tissue. Furthermore, in a patient with central diabetes insipidus, desmopressin reduced the excretion of ECVs derived from glomerular and proximal tubular cells. These data are consistent with vasopressin-regulated uptake of ECVs in vivo. We conclude that ECV uptake is a specific and regulated process. Physiologically, ECVs are a new mechanism of intercellular communication; therapeutically, ECVs may be a vehicle by which RNA therapy could be targeted to specific cells for the treatment of kidney disease.Oosthuyzen, WilnaScullion, Kathleen M.Ivy, Jessica R.Morrison, Emma E.Hunter, Robert W.Starkey Lewis, Philip J.O'Duibhir, EoghanStreet, Jonathan M.Caporali, AndreaGregory, Christopher D.Forbes, Stuart J.Webb, David J.Bailey, Matthew A.Dear, James W.2016-03-28T06:04:45-07:00doi:10.1681/ASN.2015050568hwp:resource-id:jnephrol;27/11/3345American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyexosomes, vasopressin, vesiclesBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150505681046-66731533-34502016-03-28T06:04:45-07:002016-11Journal of the American Society of NephrologyBasic Research271133453355
- Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates ProteinuriaGain-of-function mutations of classic transient receptor potential channel 6 (TRPC6) were identified in familial FSGS, and increased expression of wild-type TRPC6 in glomeruli is observed in several human acquired proteinuric diseases. Synaptopodin, an actin binding protein that is important in maintaining podocyte function, is downregulated in various glomerular diseases. Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6. We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes. Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it. Mechanistically, synaptopodin–dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons. Overexpression of wild–type or FSGS–inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6–mediated calcium influx and induced apoptosis. In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6. Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice. Furthermore, administration of cyclosporin A reversed the LPS-induced increase in podocyte surface expression of TRPC6 in wild-type mice. Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction. Reducing TRPC6 surface levels may be a new approach to restoring podocyte function.10.1681/ASN.2015080896Mon, 28 Mar 2016 06:04:45 GMT-07:00Synaptopodin Limits TRPC6 Podocyte Surface Expression and Attenuates ProteinuriaGain-of-function mutations of classic transient receptor potential channel 6 (TRPC6) were identified in familial FSGS, and increased expression of wild-type TRPC6 in glomeruli is observed in several human acquired proteinuric diseases. Synaptopodin, an actin binding protein that is important in maintaining podocyte function, is downregulated in various glomerular diseases. Here, we investigated whether synaptopodin maintains podocyte function by regulating podocyte surface expression and activity of TRPC6. We show indirect interaction and nonrandom association of synaptopodin and TRPC6 in podocytes. Knockdown of synaptopodin in cultured mouse podocytes increased the expression of TRPC6 at the plasma membrane, whereas overexpression of synaptopodin decreased it. Mechanistically, synaptopodin–dependent TRPC6 surface expression required functional actin and microtubule cytoskeletons. Overexpression of wild–type or FSGS–inducing mutant TRPC6 in synaptopodin-depleted podocytes enhanced TRPC6–mediated calcium influx and induced apoptosis. In vivo, knockdown of synaptopodin also caused increased podocyte surface expression of TRPC6. Administration of cyclosporin A, which stabilizes synaptopodin, reduced LPS-induced proteinuria significantly in wild-type mice but to a lesser extent in TRPC6 knockout mice. Furthermore, administration of cyclosporin A reversed the LPS-induced increase in podocyte surface expression of TRPC6 in wild-type mice. Our findings suggest that alteration in synaptopodin levels under disease conditions may modify intracellular TRPC6 channel localization and activity, which further contribute to podocyte dysfunction. Reducing TRPC6 surface levels may be a new approach to restoring podocyte function.Yu, HaoKistler, AndreasFaridi, Mohd HafeezMeyer, James OttoTryniszewska, BeataMehta, DollyYue, LixiaDryer, StuartReiser, Jochen2016-03-28T06:04:45-07:00doi:10.1681/ASN.2015080896hwp:resource-id:jnephrol;27/11/3308American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, TRPC6, synaptopodin, surface expression, calcium, proteinuriaBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150808961046-66731533-34502016-03-28T06:04:45-07:002016-11Journal of the American Society of NephrologyBasic Research271133083319
- Mitochondrial Pathology and Glycolytic Shift during Proximal Tubule Atrophy after Ischemic AKIDuring recovery by regeneration after AKI, proximal tubule cells can fail to redifferentiate, undergo premature growth arrest, and become atrophic. The atrophic tubules display pathologically persistent signaling increases that trigger production of profibrotic peptides, proliferation of interstitial fibroblasts, and fibrosis. We studied proximal tubules after ischemia-reperfusion injury (IRI) to characterize possible mitochondrial pathologies and alterations of critical enzymes that govern energy metabolism. In rat kidneys, tubules undergoing atrophy late after IRI but not normally recovering tubules showed greatly reduced mitochondrial number, with rounded profiles, and large autophagolysosomes. Studies after IRI of kidneys in mice, done in parallel, showed large scale loss of the oxidant–sensitive mitochondrial protein Mpv17L. Renal expression of hypoxia markers also increased after IRI. During early and late reperfusion after IRI, kidneys exhibited increased lactate and pyruvate content and hexokinase activity, which are indicators of glycolysis. Furthermore, normally regenerating tubules as well as tubules undergoing atrophy exhibited increased glycolytic enzyme expression and inhibitory phosphorylation of pyruvate dehydrogenase. TGF-β antagonism prevented these effects. Our data show that the metabolic switch occurred early during regeneration after injury and was reversed during normal tubule recovery but persisted and became progressively more severe in tubule cells that failed to redifferentiate. In conclusion, irreversibility of the metabolic switch, taking place in the context of hypoxia, high TGF-β signaling and depletion of mitochondria characterizes the development of atrophy in proximal tubule cells and may contribute to the renal pathology after AKI.10.1681/ASN.2015020177Mon, 21 Mar 2016 09:47:59 GMT-07:00Mitochondrial Pathology and Glycolytic Shift during Proximal Tubule Atrophy after Ischemic AKIDuring recovery by regeneration after AKI, proximal tubule cells can fail to redifferentiate, undergo premature growth arrest, and become atrophic. The atrophic tubules display pathologically persistent signaling increases that trigger production of profibrotic peptides, proliferation of interstitial fibroblasts, and fibrosis. We studied proximal tubules after ischemia-reperfusion injury (IRI) to characterize possible mitochondrial pathologies and alterations of critical enzymes that govern energy metabolism. In rat kidneys, tubules undergoing atrophy late after IRI but not normally recovering tubules showed greatly reduced mitochondrial number, with rounded profiles, and large autophagolysosomes. Studies after IRI of kidneys in mice, done in parallel, showed large scale loss of the oxidant–sensitive mitochondrial protein Mpv17L. Renal expression of hypoxia markers also increased after IRI. During early and late reperfusion after IRI, kidneys exhibited increased lactate and pyruvate content and hexokinase activity, which are indicators of glycolysis. Furthermore, normally regenerating tubules as well as tubules undergoing atrophy exhibited increased glycolytic enzyme expression and inhibitory phosphorylation of pyruvate dehydrogenase. TGF-β antagonism prevented these effects. Our data show that the metabolic switch occurred early during regeneration after injury and was reversed during normal tubule recovery but persisted and became progressively more severe in tubule cells that failed to redifferentiate. In conclusion, irreversibility of the metabolic switch, taking place in the context of hypoxia, high TGF-β signaling and depletion of mitochondria characterizes the development of atrophy in proximal tubule cells and may contribute to the renal pathology after AKI.Lan, RongpeiGeng, HuiSingha, Prajjal K.Saikumar, PothanaBottinger, Erwin P.Weinberg, Joel M.Venkatachalam, Manjeri A.2016-03-21T09:47:59-07:00doi:10.1681/ASN.2015020177hwp:resource-id:jnephrol;27/11/3356American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolism, pathology, proximal tubule, ischemia-reperfusion, mitochondriaBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150201771046-66731533-34502016-03-21T09:47:59-07:002016-11Journal of the American Society of NephrologyBasic Research271133563367
- CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10–Producing Regulatory T CellsKidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3−/− mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN.10.1681/ASN.2015080873Fri, 01 Apr 2016 07:44:02 GMT-07:00CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10–Producing Regulatory T CellsKidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3−/− mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN.Evers, Beatrix D.G.Engel, Daniel R.Böhner, Alexander M.C.Tittel, André P.Krause, Torsten A.Heuser, ChristophGarbi, NatalioKastenmüller, WolfgangMack, MatthiasTiegs, GisaPanzer, UlfBoor, PeterLudwig-Portugall, IsisKurts, Christian2016-04-01T07:44:02-07:00doi:10.1681/ASN.2015080873hwp:resource-id:jnephrol;27/11/3368American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, immunology, lymphocytes, regulatory T cells, dendritic cellsBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150808731046-66731533-34502016-04-01T07:44:02-07:002016-11Journal of the American Society of NephrologyBasic Research271133683382
- Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic NephropathyDiabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.10.1681/ASN.2015050473Mon, 25 Apr 2016 05:34:35 GMT-07:00Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic NephropathyDiabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.Scheele, WimDiamond, SusanGale, JeremyClerin, ValerieTamimi, NihadLe, VuWalley, RosalindGrover-Páez, FernandoPerros-Huguet, ChristelleRolph, TimothyEl Nahas, Meguid2016-04-25T05:34:35-07:00doi:10.1681/ASN.2015050473hwp:resource-id:jnephrol;27/11/3459American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, randomized controlled trials, diabetic nephropathy, nitric oxideClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20150504731046-66731533-34502016-04-25T05:34:35-07:002016-11Journal of the American Society of NephrologyClinical Research271134593468
- The Role of TNF Superfamily Member 13 in the Progression of IgA NephropathyTNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.10.1681/ASN.2015060677Mon, 11 Apr 2016 05:50:19 GMT-07:00The Role of TNF Superfamily Member 13 in the Progression of IgA NephropathyTNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.Han, Seung SeokYang, Seung HeeChoi, MurimKim, Hang-RaeKim, KwangsooLee, SangmoonMoon, Kyung ChulKim, Joo YoungLee, HajeongLee, Jung PyoJung, Ji YongKim, SejoongJoo, Kwon WookLim, Chun SooKang, Shin-WookKim, Yon SuKim, Dong Ki2016-04-11T05:50:19-07:00doi:10.1681/ASN.2015060677hwp:resource-id:jnephrol;27/11/3430American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, outcomes, lymphocytes, glomerulonephritisClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20150606771046-66731533-34502016-04-11T05:50:19-07:002016-11Journal of the American Society of NephrologyClinical Research271134303439
- Endothelial Sphingosine 1‑Phosphate Receptor‑1 Mediates Protection and Recovery from Acute Kidney InjuryEpithelial and endothelial injury and a cascade of immune and interstitial cell activation in the kidney lead to AKI. After mild to moderate AKI, the epithelium can regenerate and restore kidney function, yet little is known about the endothelium during these repair processes. Sphingosine 1-phosphate receptor 1 (S1P1), a G protein–coupled receptor, is necessary for vascular homeostasis. Here, we used an inducible genetic approach in a mouse model of AKI, ischemia–reperfusion injury (IRI), to determine the temporal effects of endothelial S1P1 during AKI. Deletion of endothelial S1P1 before IRI exacerbated kidney injury and inflammation, and the delayed deletion of S1P1 after IRI prevented kidney recovery, resulting in chronic inflammation and progressive fibrosis. Specifically, S1P1 directly suppressed endothelial activation of leukocyte adhesion molecule expression and inflammation. Altogether, the data indicate activation of endothelial S1P1 is necessary to protect from IRI and permit recovery from AKI. Endothelial S1P1 may be a therapeutic target for the prevention of early injury as well as prevention of progressive kidney fibrosis after AKI.10.1681/ASN.2015080922Wed, 09 Mar 2016 09:59:05 GMT-08:00Endothelial Sphingosine 1‑Phosphate Receptor‑1 Mediates Protection and Recovery from Acute Kidney InjuryEpithelial and endothelial injury and a cascade of immune and interstitial cell activation in the kidney lead to AKI. After mild to moderate AKI, the epithelium can regenerate and restore kidney function, yet little is known about the endothelium during these repair processes. Sphingosine 1-phosphate receptor 1 (S1P1), a G protein–coupled receptor, is necessary for vascular homeostasis. Here, we used an inducible genetic approach in a mouse model of AKI, ischemia–reperfusion injury (IRI), to determine the temporal effects of endothelial S1P1 during AKI. Deletion of endothelial S1P1 before IRI exacerbated kidney injury and inflammation, and the delayed deletion of S1P1 after IRI prevented kidney recovery, resulting in chronic inflammation and progressive fibrosis. Specifically, S1P1 directly suppressed endothelial activation of leukocyte adhesion molecule expression and inflammation. Altogether, the data indicate activation of endothelial S1P1 is necessary to protect from IRI and permit recovery from AKI. Endothelial S1P1 may be a therapeutic target for the prevention of early injury as well as prevention of progressive kidney fibrosis after AKI.Perry, Heather M.Huang, LipingYe, HongLiu, ChongSung, Sun-sang J.Lynch, Kevin R.Rosin, Diane L.Bajwa, AmandeepOkusa, Mark D.2016-03-09T09:59:05-08:00doi:10.1681/ASN.2015080922hwp:resource-id:jnephrol;27/11/3383American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, fibrosis, endothelium, inflammationBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150809221046-66731533-34502016-03-09T09:59:05-08:002016-11Journal of the American Society of NephrologyBasic Research271133833393
- Carbamylated Erythropoietin Outperforms Erythropoietin in the Treatment of AKI-on-CKD and Other AKI ModelsErythropoietin (EPO) may be a beneficial tissue–protective cytokine. However, high doses of EPO are associate with adverse effects, including thrombosis, tumor growth, and hypertension. Carbamylated erythropoietin (CEPO) lacks both erythropoietic and vasoconstrictive actions. In this study, we compared the renoprotective, hemodynamic, and hematologic activities and survival effects of identical EPO and CEPO doses in rat models of clinically relevant AKI presentations, including ischemia-reperfusion–induced AKI superimposed on CKD (5000 U/kg EPO or CEPO; three subcutaneous injections) and ischemia-reperfusion–induced AKI in old versus young animals and male versus female animals (1000 U/kg EPO or CEPO; three subcutaneous injections). Compared with EPO therapy, CEPO therapy induced greater improvements in renal function and body weight in AKI on CKD animals, with smaller increases in hematocrit levels and similarly improved survival. Compared with EPO therapy in the other AKI groups, CEPO therapy induced greater improvements in protection and recovery of renal function and survival, with smaller increases in systolic BP and hematocrit levels. Overall, old or male animals had more severe loss in kidney function and higher mortality rates than young or female animals, respectively. Notably, mRNA and protein expression analyses confirmed the renal expression of the heterodimeric EPO receptor/CD131 complex, which is required for the tissue-protective effects of CEPO signaling. In conclusion, CEPO improves renal function, body and kidney weight, and survival in AKI models without raising hematocrit levels and BP as substantially as EPO. Thus, CEPO therapy may be superior to EPO in improving outcomes in common forms of clinical AKI.10.1681/ASN.2015091059Wed, 16 Mar 2016 10:09:03 GMT-07:00Carbamylated Erythropoietin Outperforms Erythropoietin in the Treatment of AKI-on-CKD and Other AKI ModelsErythropoietin (EPO) may be a beneficial tissue–protective cytokine. However, high doses of EPO are associate with adverse effects, including thrombosis, tumor growth, and hypertension. Carbamylated erythropoietin (CEPO) lacks both erythropoietic and vasoconstrictive actions. In this study, we compared the renoprotective, hemodynamic, and hematologic activities and survival effects of identical EPO and CEPO doses in rat models of clinically relevant AKI presentations, including ischemia-reperfusion–induced AKI superimposed on CKD (5000 U/kg EPO or CEPO; three subcutaneous injections) and ischemia-reperfusion–induced AKI in old versus young animals and male versus female animals (1000 U/kg EPO or CEPO; three subcutaneous injections). Compared with EPO therapy, CEPO therapy induced greater improvements in renal function and body weight in AKI on CKD animals, with smaller increases in hematocrit levels and similarly improved survival. Compared with EPO therapy in the other AKI groups, CEPO therapy induced greater improvements in protection and recovery of renal function and survival, with smaller increases in systolic BP and hematocrit levels. Overall, old or male animals had more severe loss in kidney function and higher mortality rates than young or female animals, respectively. Notably, mRNA and protein expression analyses confirmed the renal expression of the heterodimeric EPO receptor/CD131 complex, which is required for the tissue-protective effects of CEPO signaling. In conclusion, CEPO improves renal function, body and kidney weight, and survival in AKI models without raising hematocrit levels and BP as substantially as EPO. Thus, CEPO therapy may be superior to EPO in improving outcomes in common forms of clinical AKI.Tögel, Florian E.Ahlstrom, Jon D.Yang, YingHu, ZhumaZhang, PingWestenfelder, Christof2016-03-16T10:09:03-07:00doi:10.1681/ASN.2015091059hwp:resource-id:jnephrol;27/11/3394American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, chronic kidney disease, erythropoietinBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150910591046-66731533-34502016-03-16T10:09:03-07:002016-11Journal of the American Society of NephrologyBasic Research271133943404
- Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney DiseaseAlbuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions used in the other trials by the number (one, two, or three) of consecutively collected urine samples at each study visit, the time interval between study visits, the requirement of an additional visit to confirm the class transition, and the requirement of a percentage increase in albuminuria from baseline in addition to the class transition. In Cox regression analysis, neither increasing the number of urine samples collected at a single study visit nor differences in the other variables used to define albuminuria class transition altered the average drug effect. However, the SEM of the treatment effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per study visit. A confirmation of the end point or a requirement of a minimal percentage change in albuminuria from baseline seems unnecessary.10.1681/ASN.2015101150Thu, 07 Apr 2016 06:41:13 GMT-07:00Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney DiseaseAlbuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions used in the other trials by the number (one, two, or three) of consecutively collected urine samples at each study visit, the time interval between study visits, the requirement of an additional visit to confirm the class transition, and the requirement of a percentage increase in albuminuria from baseline in addition to the class transition. In Cox regression analysis, neither increasing the number of urine samples collected at a single study visit nor differences in the other variables used to define albuminuria class transition altered the average drug effect. However, the SEM of the treatment effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per study visit. A confirmation of the end point or a requirement of a minimal percentage change in albuminuria from baseline seems unnecessary.Kröpelin, Tobias F.de Zeeuw, DickRemuzzi, GiuseppeBilous, RudyParving, Hans-HenrikHeerspink, Hiddo J.L.2016-04-07T06:41:13-07:00doi:10.1681/ASN.2015101150hwp:resource-id:jnephrol;27/11/3405American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, diabetes mellitus, microalbuminuria, randomized controlled trialsClinical EpidemiologyClinical Epidemiologyresearch-article20162016-11-01November 201610.1681/ASN.20151011501046-66731533-34502016-04-07T06:41:13-07:002016-11Journal of the American Society of NephrologyClinical Epidemiology271134053412
- A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk FactorsAccurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273–2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.10.1681/ASN.2015091065Thu, 14 Apr 2016 08:01:55 GMT-07:00A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk FactorsAccurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273–2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.Nigwekar, Sagar U.Zhao, SophiaWenger, JuliaHymes, Jeffrey L.Maddux, Franklin W.Thadhani, Ravi I.Chan, Kevin E.2016-04-14T08:01:55-07:00doi:10.1681/ASN.2015091065hwp:resource-id:jnephrol;27/11/3421American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, end stage kidney disease, clinical epidemiology, diabetes mellitus, obesity, vascular calcificationClinical ResearchClinical Researchresearch-article20162016-11-01November 201610.1681/ASN.20150910651046-66731533-34502016-04-14T08:01:55-07:002016-11Journal of the American Society of NephrologyClinical Research2711113421323334293235
- Calcific Uremic Arteriolopathy Revisited10.1681/ASN.2016040480Wed, 25 May 2016 06:24:10 GMT-07:00Calcific Uremic Arteriolopathy RevisitedJovanovich, AnnaChonchol, Michel2016-05-25T06:24:10-07:00doi:10.1681/ASN.2016040480hwp:resource-id:jnephrol;27/11/3233American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, chronic dialysis, coronary calcification, Epidemiology and outcomesUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-11-01November 201610.1681/ASN.20160404801046-66731533-34502016-05-25T06:24:10-07:002016-11Journal of the American Society of NephrologyUp Front Matters2711113233342132353429
- HEMO Revisited: Why Kt/Vurea Only Tells Part of the Story10.1681/ASN.2016040417Tue, 07 Jun 2016 07:46:17 GMT-07:00HEMO Revisited: Why Kt/Vurea Only Tells Part of the StoryMeijers, BjörnVanholder, Raymond2016-06-07T07:46:17-07:00doi:10.1681/ASN.2016040417hwp:resource-id:jnephrol;27/11/3235American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis adequacy, urea modeling, uremiaUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-11-01November 201610.1681/ASN.20160404171046-66731533-34502016-06-07T07:46:17-07:002016-11Journal of the American Society of NephrologyUp Front Matters2711113235346932373478
- Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal AllograftsDespite advances in immunosuppression, antibody-mediated rejection is a serious threat to allograft survival. Alloreactive memory helper T cells can induce potent alloantibody responses and often associate with poor graft outcome. Nevertheless, the ability of memory T cells to elicit well characterized manifestations of antibody-mediated rejection has not been tested. We investigated helper functions of memory CD4 T cells in a mouse model of renal transplantation. Whereas the majority of unsensitized C57Bl/6 recipients spontaneously accepted fully MHC–mismatched A/J renal allografts, recipients containing donor–reactive memory CD4 T cells rapidly lost allograft function. Increased serum creatinine levels, high serum titers of donor-specific alloantibody, minimal T cell infiltration, and intense C4d deposition in the grafts of sensitized recipients fulfilled all diagnostic criteria for acute renal antibody–mediated rejection in humans. IFNγ neutralization did not prevent the renal allograft rejection induced by memory helper T cells, and CD8 T cell depletion at the time of transplantation or depletion of both CD4 and CD8 T cells also did not prevent the renal allograft rejection induced by memory helper T cells starting at day 4 after transplantation. However, B cell depletion inhibited alloantibody generation and significantly extended allograft survival, indicating that donor-specific alloantibodies (not T cells) were the critical effector mechanism of renal allograft rejection induced by memory CD4 T cells. Our studies provide direct evidence that recipient T cell sensitization may result in antibody-mediated rejection of renal allografts and introduce a physiologically relevant animal model with which to investigate mechanisms of antibody-mediated rejection and novel therapeutic approaches for its prevention and treatment.10.1681/ASN.2015080848Mon, 28 Mar 2016 06:04:44 GMT-07:00Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal AllograftsDespite advances in immunosuppression, antibody-mediated rejection is a serious threat to allograft survival. Alloreactive memory helper T cells can induce potent alloantibody responses and often associate with poor graft outcome. Nevertheless, the ability of memory T cells to elicit well characterized manifestations of antibody-mediated rejection has not been tested. We investigated helper functions of memory CD4 T cells in a mouse model of renal transplantation. Whereas the majority of unsensitized C57Bl/6 recipients spontaneously accepted fully MHC–mismatched A/J renal allografts, recipients containing donor–reactive memory CD4 T cells rapidly lost allograft function. Increased serum creatinine levels, high serum titers of donor-specific alloantibody, minimal T cell infiltration, and intense C4d deposition in the grafts of sensitized recipients fulfilled all diagnostic criteria for acute renal antibody–mediated rejection in humans. IFNγ neutralization did not prevent the renal allograft rejection induced by memory helper T cells, and CD8 T cell depletion at the time of transplantation or depletion of both CD4 and CD8 T cells also did not prevent the renal allograft rejection induced by memory helper T cells starting at day 4 after transplantation. However, B cell depletion inhibited alloantibody generation and significantly extended allograft survival, indicating that donor-specific alloantibodies (not T cells) were the critical effector mechanism of renal allograft rejection induced by memory CD4 T cells. Our studies provide direct evidence that recipient T cell sensitization may result in antibody-mediated rejection of renal allografts and introduce a physiologically relevant animal model with which to investigate mechanisms of antibody-mediated rejection and novel therapeutic approaches for its prevention and treatment.Gorbacheva, VictoriaFan, RanFairchild, Robert L.Baldwin, William M.Valujskikh, Anna2016-03-28T06:04:44-07:00doi:10.1681/ASN.2015080848hwp:resource-id:jnephrol;27/11/3299American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, immunology, lymphocytesBasic ResearchBasic Researchresearch-article20162016-11-01November 201610.1681/ASN.20150808481046-66731533-34502016-03-28T06:04:44-07:002016-11Journal of the American Society of NephrologyBasic Research2711113299323133073233
- Mammalian Target of Rapamycin Inhibitors and Clinical Outcomes in Adult Kidney Transplant Recipients10.2215/CJN.00190116Thu, 21 Jul 2016 06:25:39 GMT-07:00Mammalian Target of Rapamycin Inhibitors and Clinical Outcomes in Adult Kidney Transplant RecipientsBadve, Sunil V.Pascoe, Elaine M.Burke, MichaelClayton, Philip A.Campbell, Scott B.Hawley, Carmel M.Lim, Wai H.McDonald, Stephen P.Wong, GermaineJohnson, David W.2016-07-21T06:25:39-07:00doi:10.2215/CJN.00190116hwp:resource-id:clinjasn;11/10/1845American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymortality, immunosuppression, cohort studies, graft survival, humans, Allografts, kidney transplantation, Longitudinal Studies, risk factors, Skin Neoplasms, Transplant Recipients, Transplantation, HomologousOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-10-07October 07, 201610.2215/CJN.001901161555-90411555-905X2016-07-21T06:25:39-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111018451855
- Effect of Processing Delay and Storage Conditions on Urine Albumin-to-Creatinine Ratio10.2215/CJN.13341215Wed, 21 Sep 2016 10:03:54 GMT-07:00Effect of Processing Delay and Storage Conditions on Urine Albumin-to-Creatinine RatioHerrington, WilliamIllingworth, NicolaStaplin, NatalieKumar, AishwaryaStorey, BenHrusecka, RenataJudge, ParminderMahmood, MariaParish, SarahLandray, MartinHaynes, RichardBaigent, ColinHill, MichaelClark, Sarah2016-09-21T10:03:54-07:00doi:10.2215/CJN.13341215hwp:resource-id:clinjasn;11/10/1794American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, randomized controlled trials, microalbuminuria, proteinuria, Albumins, Boric Acids, Confidence Intervals, creatinine, Freezing, Humans, Kidney Diseases, Randomized Controlled Trials as Topic, Specimen Handling, Temperature, Urinalysis, boric acidOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-10-07October 07, 201610.2215/CJN.133412151555-90411555-905X2016-09-21T10:03:54-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1110101794172618011728
- High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S. Veterans10.2215/CJN.00730116Thu, 11 Aug 2016 08:21:49 GMT-07:00High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S. VeteransBowe, BenjaminXie, YanXian, HongBalasubramanian, SumitraZayed, Mohamed A.Al-Aly, Ziyad2016-08-11T08:21:49-07:00doi:10.2215/CJN.00730116hwp:resource-id:clinjasn;11/10/1784American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypercholesterolemia, mortality risk, chronic kidney disease, lipids, mortality, Epidemiology and outcomes, Cardiovascular Diseases, Cholesterol, HDL, coronary artery disease, Humans, United States, VeteransOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-10-07October 07, 201610.2215/CJN.007301161555-90411555-905X2016-08-11T08:21:49-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111017841793
- Supportive Care: Integration of Patient-Centered Kidney Care to Manage Symptoms and Geriatric SyndromesDialysis care is often associated with poor outcomes including low quality of life (QOL). To improve patient-reported outcomes, incorporation of the patient’s needs and perspective into the medical care they receive is essential. This article provides a framework to help clinicians integrate symptom assessment and other measures such as QOL and frailty scores into a clinical approach to the contemporary supportive care of patients with advanced CKD. This approach involves (1) defining our understanding of kidney supportive care, patient-centered dialysis, and palliative dialysis; (2) understanding and recognizing common symptoms associated with advanced CKD; (3) discussing the concepts of physical function, frailty, and QOL and their role in CKD; and (4) identifying the structural and process barriers that may arise when patient-centered dialysis is being introduced into clinical practice.10.2215/CJN.01050116Wed, 10 Aug 2016 06:57:42 GMT-07:00Supportive Care: Integration of Patient-Centered Kidney Care to Manage Symptoms and Geriatric SyndromesDialysis care is often associated with poor outcomes including low quality of life (QOL). To improve patient-reported outcomes, incorporation of the patient’s needs and perspective into the medical care they receive is essential. This article provides a framework to help clinicians integrate symptom assessment and other measures such as QOL and frailty scores into a clinical approach to the contemporary supportive care of patients with advanced CKD. This approach involves (1) defining our understanding of kidney supportive care, patient-centered dialysis, and palliative dialysis; (2) understanding and recognizing common symptoms associated with advanced CKD; (3) discussing the concepts of physical function, frailty, and QOL and their role in CKD; and (4) identifying the structural and process barriers that may arise when patient-centered dialysis is being introduced into clinical practice.Davison, Sara N.Jassal, Sarbjit Vanita2016-08-10T06:57:42-07:00doi:10.2215/CJN.01050116hwp:resource-id:clinjasn;11/10/1882American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysupportive care, symptoms, quality of life, frailty, Disease Management, Humans, kidney, Patient Outcome Assessment, Patient-Centered Care, renal dialysis, Renal Insufficiency, Chronic, Symptom AssessmentMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.010501161555-90411555-905X2016-08-10T06:57:42-07:002016-10-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111018821891
- Chronic Kidney Disease and Risk for Gastrointestinal Bleeding in the Community: The Atherosclerosis Risk in Communities (ARIC) Study10.2215/CJN.02170216Thu, 11 Aug 2016 08:21:50 GMT-07:00Chronic Kidney Disease and Risk for Gastrointestinal Bleeding in the Community: The Atherosclerosis Risk in Communities (ARIC) StudyIshigami, JunichiGrams, Morgan E.Naik, Rakhi P.Coresh, JosefMatsushita, Kunihiro2016-08-11T08:21:50-07:00doi:10.2215/CJN.02170216hwp:resource-id:clinjasn;11/10/1735American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, albuminuria, gastrointestinal complications, chronic kidney failure, proteinuria, chronic renal failure, Albumins, Atherosclerosis, Attention, creatinine, Follow-Up Studies, glomerular filtration rate, hospitalization, Humans, Incidence, kidney, Proportional Hazards Models, renal dialysis, Renal Insufficiency, Chronic, RiskOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-10-07October 07, 201610.2215/CJN.021702161555-90411555-905X2016-08-11T08:21:50-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111017351743
- All Things ComplementThe complement (C) cascade is an ancient system of proteins whose primary role is to initiate and modulate immune responses. During C activation, circulating proteins are cleaved and nascent cleavage fragments participate in a broad range of downstream innate and adaptive immune functions. Although the majority of these functions are either homeostatic or protective, a large body of experimental and clinical evidence also highlights a central role for the C system in the pathogenesis of many types of glomerular disease. From classic pathway activation in lupus nephritis to alternative pathway dysregulation in C3 glomerulopathy, our understanding of the spectrum of C involvement in kidney disease has expanded greatly in recent years. However, the characteristics that make the glomerulus so uniquely susceptible to C-mediated injury are not fully understood, and this remains an area of ongoing investigation. Several C inhibitors have been approved for clinical use, and additional C inhibitory drugs are in development. The use of these drugs in patients with kidney disease will expand our understanding of the benefits and limitations of C inhibition.10.2215/CJN.01710216Thu, 23 Jun 2016 08:13:32 GMT-07:00All Things ComplementThe complement (C) cascade is an ancient system of proteins whose primary role is to initiate and modulate immune responses. During C activation, circulating proteins are cleaved and nascent cleavage fragments participate in a broad range of downstream innate and adaptive immune functions. Although the majority of these functions are either homeostatic or protective, a large body of experimental and clinical evidence also highlights a central role for the C system in the pathogenesis of many types of glomerular disease. From classic pathway activation in lupus nephritis to alternative pathway dysregulation in C3 glomerulopathy, our understanding of the spectrum of C involvement in kidney disease has expanded greatly in recent years. However, the characteristics that make the glomerulus so uniquely susceptible to C-mediated injury are not fully understood, and this remains an area of ongoing investigation. Several C inhibitors have been approved for clinical use, and additional C inhibitory drugs are in development. The use of these drugs in patients with kidney disease will expand our understanding of the benefits and limitations of C inhibition.Thurman, Joshua M.Nester, Carla M.2016-06-23T08:13:32-07:00doi:10.2215/CJN.01710216hwp:resource-id:clinjasn;11/10/1856American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, complement, immune complexes, clinical immunology, glomerulonephritis, Complement Activation, Complement Inactivating Agents, Complement System Proteins, Humans, Kidney Diseases, Kidney Glomerulus, lupus nephritisGlomerular Diseases: Update for the ClinicianGlomerular Diseases: Update for the Clinicianresearch-article20162016-10-07October 07, 201610.2215/CJN.017102161555-90411555-905X2016-06-23T08:13:32-07:002016-10-07Clinical Journal of the American Society of NephrologyGlomerular Diseases: Update for the Clinician111018561866
- Supportive Care: Economic Considerations in Advanced Kidney DiseaseKidney supportive care describes multiple interventions for patients with advanced CKD that focus on improving the quality of life and addressing what matters most to patients. This includes shared decision making and aligning treatment plans with patient goals through advance care planning and providing relief from pain and other distressing symptoms. Kidney supportive care is an essential component of quality care throughout the illness trajectory. However, in the context of limited health care resources, evidence of its cost-effectiveness is required to support decisions regarding appropriate resource allocation. We review the literature and outline the evidence gaps and particular issues associated with measuring the costs, benefits, and cost-effectiveness of kidney supportive care. We find evidence that the dominant evaluative framework of a cost per quality–adjusted life year may not be suitable for evaluations in this context and that relevant outcomes may include broader measures of patient wellbeing, having care aligned with treatment preferences, and family satisfaction with the end of life care experience. To improve the evidence base for the cost-effectiveness of kidney supportive care, large prospective cohort studies are recommended to collect data on both resource use and health outcomes and should include patients who receive conservative kidney management without dialysis. Linkage to administrative datasets, such as Medicare, Hospital Episode Statistics, and the Pharmaceutical Benefits Scheme for prescribed medicines, can provide a detailed estimate of publicly funded resource use and reduce the burden of data collection for patients and families. Longitudinal collection of quality of life and functional status should be added to existing cohort or kidney registry studies. Interventions that improve health outcomes for people with advanced CKD, such as kidney supportive care, not only have the potential to improve quality of life, but also may reduce the high costs associated with unwanted hospitalization and intensive medical treatments.10.2215/CJN.12651115Wed, 10 Aug 2016 06:57:42 GMT-07:00Supportive Care: Economic Considerations in Advanced Kidney DiseaseKidney supportive care describes multiple interventions for patients with advanced CKD that focus on improving the quality of life and addressing what matters most to patients. This includes shared decision making and aligning treatment plans with patient goals through advance care planning and providing relief from pain and other distressing symptoms. Kidney supportive care is an essential component of quality care throughout the illness trajectory. However, in the context of limited health care resources, evidence of its cost-effectiveness is required to support decisions regarding appropriate resource allocation. We review the literature and outline the evidence gaps and particular issues associated with measuring the costs, benefits, and cost-effectiveness of kidney supportive care. We find evidence that the dominant evaluative framework of a cost per quality–adjusted life year may not be suitable for evaluations in this context and that relevant outcomes may include broader measures of patient wellbeing, having care aligned with treatment preferences, and family satisfaction with the end of life care experience. To improve the evidence base for the cost-effectiveness of kidney supportive care, large prospective cohort studies are recommended to collect data on both resource use and health outcomes and should include patients who receive conservative kidney management without dialysis. Linkage to administrative datasets, such as Medicare, Hospital Episode Statistics, and the Pharmaceutical Benefits Scheme for prescribed medicines, can provide a detailed estimate of publicly funded resource use and reduce the burden of data collection for patients and families. Longitudinal collection of quality of life and functional status should be added to existing cohort or kidney registry studies. Interventions that improve health outcomes for people with advanced CKD, such as kidney supportive care, not only have the potential to improve quality of life, but also may reduce the high costs associated with unwanted hospitalization and intensive medical treatments.Morton, Rachael L.Kurella Tamura, ManjulaCoast, JoannaDavison, Sara N.2016-08-10T06:57:42-07:00doi:10.2215/CJN.12651115hwp:resource-id:clinjasn;11/10/1915American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhealth economics, palliative care, conservative care, quality of life, supportive care, Cost-Benefit Analysis, Humans, Personal Satisfaction, Prospective Studies, Quality-Adjusted Life Years, renal dialysis, Renal Insufficiency, ChronicMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.126511151555-90411555-905X2016-08-10T06:57:42-07:002016-10-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111019151920
- Renal Survival in Patients with Collapsing Compared with Not Otherwise Specified FSGS10.2215/CJN.13091215Thu, 21 Jul 2016 06:25:40 GMT-07:00Renal Survival in Patients with Collapsing Compared with Not Otherwise Specified FSGSLaurin, Louis-PhilippeGasim, Adil M.Derebail, Vimal K.McGregor, JulieAnne G.Kidd, Jason M.Hogan, Susan L.Poulton, Caroline J.Detwiler, Randal K.Jennette, J. CharlesFalk, Ronald J.Nachman, Patrick H.2016-07-21T06:25:40-07:00doi:10.2215/CJN.13091215hwp:resource-id:clinjasn;11/10/1752American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfocal segmental glomerulosclerosis, nephrotic syndrome, glomerulonephritis, Follow-Up Studies, glomerular filtration rate, Humans, immunosuppression, Kidney Failure, Chronic, Prognosis, Proportional Hazards Models, proteinuria, renal dialysisOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.130912151555-90411555-905X2016-07-21T06:25:40-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111017521759
- Predictors of Initiation for Predialysis Arteriovenous Fistula10.2215/CJN.00700116Wed, 14 Sep 2016 07:17:53 GMT-07:00Predictors of Initiation for Predialysis Arteriovenous FistulaAl-Balas, AlianLee, TimmyYoung, Carlton J.Barker-Finkel, JillAllon, Michael2016-09-14T07:17:53-07:00doi:10.2215/CJN.00700116hwp:resource-id:clinjasn;11/10/1802American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous access, arteriovenous fistula, glomerular filtration rate, Area Under Curve, creatinine, diabetes mellitus, Humans, Logistic Models, Probability, proteinuria, ROC Curve, renal dialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-10-07October 07, 201610.2215/CJN.007001161555-90411555-905X2016-09-14T07:17:53-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1110101802172918081731
- Effect of Patiromer on Urinary Ion Excretion in Healthy Adults10.2215/CJN.01170216Tue, 27 Sep 2016 07:05:56 GMT-07:00Effect of Patiromer on Urinary Ion Excretion in Healthy AdultsBushinsky, David A.Spiegel, David M.Gross, ColemanBenton, Wade W.Fogli, JeaneneHill Gallant, Kathleen M.Du Mond, CharlesBlock, Geoffrey A.Weir, Matthew R.Pitt, Bertram2016-09-27T07:05:56-07:00doi:10.2215/CJN.01170216hwp:resource-id:clinjasn;11/10/1769American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatiromer, hyperkalemia, electrolytes, urinary excretion, cation exchange, Animals, Brachyura, calcium, Calcium, Dietary, Cations, Cross-Over Studies, Diet, Gastrointestinal Absorption, Intestinal Absorption, Magnesium, Phosphates, Polymers, Potassium, SodiumOriginal ArticlesClinical PharmacologyOriginal ArticlesClinical Pharmacologyresearch-article20162016-10-07October 07, 201610.2215/CJN.011702161555-90411555-905X2016-09-27T07:05:56-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1110101769172317761725
- Supportive Care: Meeting the Needs of Patients with Advanced Chronic Kidney Disease10.2215/CJN.06800616Fri, 07 Oct 2016 10:00:31 GMT-07:00Supportive Care: Meeting the Needs of Patients with Advanced Chronic Kidney DiseaseDavison, Sara N.Moss, Alvin H.2016-10-07T10:00:31-07:00doi:10.2215/CJN.06800616hwp:resource-id:clinjasn;11/10/1879American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-centered care, supportive care, palliative care, symptoms, quality of life, Humans, Renal Insufficiency, ChronicMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.068006161555-90411555-905X2016-10-07T10:00:31-07:002016-10-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111018791880
- The Influence of Processing and Storage Conditions on Renal Protein Biomarkers10.2215/CJN.08800816Wed, 21 Sep 2016 10:03:54 GMT-07:00The Influence of Processing and Storage Conditions on Renal Protein BiomarkersGiesen, CallenLieske, John C.2016-09-21T10:03:54-07:00doi:10.2215/CJN.08800816hwp:resource-id:clinjasn;11/10/1726American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyurine, kidney, renal biomarker, urine biomarker, biomarkers, leadershipEditorialsEditorialseditorial20162016-10-07October 07, 201610.2215/CJN.088008161555-90411555-905X2016-09-21T10:03:54-07:002016-10-07Clinical Journal of the American Society of NephrologyEditorials1110101726179417281801
- Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome10.2215/CJN.00380116Thu, 21 Jul 2016 06:25:40 GMT-07:00Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic SyndromeBanh, Tonny H.M.Hussain-Shamsy, NeeshaPatel, ViralVasilevska-Ristovska, JovankaBorges, KarlotaSibbald, CathrynLipszyc, DeborahBrooke, JosefinaGeary, DenisLanglois, ValerieReddon, MichelePearl, RachelLevin, LeoPiekut, MonicaLicht, Christoph P.B.Radhakrishnan, SeethaAitken-Menezes, KimberlyHarvey, ElizabethHebert, DianePiscione, Tino D.Parekh, Rulan S.2016-07-21T06:25:40-07:00doi:10.2215/CJN.00380116hwp:resource-id:clinjasn;11/10/1760American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, ethnicity, children, steroids, cyclophosphamide, Asian Continental Ancestry Group, Ethnic Groups, European Continental Ancestry Group, Humans, Incidence, Longitudinal Studies, RecurrenceOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.003801161555-90411555-905X2016-07-21T06:25:40-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111017601768
- A Prospective, Randomized Trial of Routine Duplex Ultrasound Surveillance on Arteriovenous Fistula Maturation10.2215/CJN.00620116Wed, 24 Aug 2016 04:42:02 GMT-07:00A Prospective, Randomized Trial of Routine Duplex Ultrasound Surveillance on Arteriovenous Fistula MaturationHan, AhramMin, Seung-KeeKim, Mi-SookJoo, Kwon WookKim, JungsunHa, JongwonLee, JoongyubMin, Sang-il2016-08-24T04:42:02-07:00doi:10.2215/CJN.00620116hwp:resource-id:clinjasn;11/10/1817American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysurgical arteriovenous shunt, doppler duplex ultrasonography, hemodialysis, arteriovenous fistula, Confidence Intervals, coronary artery disease, diabetes mellitus, Female, Humans, Odds Ratio, Physical Examination, Prospective Studies, renal dialysis, Ultrasonography, Doppler, DuplexOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-10-07October 07, 201610.2215/CJN.006201161555-90411555-905X2016-08-24T04:42:02-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111018171824
- Longitudinal Changes in Protein Carbamylation and Mortality Risk after Initiation of Hemodialysis10.2215/CJN.02390316Thu, 21 Jul 2016 06:25:38 GMT-07:00Longitudinal Changes in Protein Carbamylation and Mortality Risk after Initiation of HemodialysisKalim, SahirTrottier, Caitlin A.Wenger, Julia B.Wibecan, JoshAhmed, RayhnumaAnkers, ElizabethKarumanchi, S. AnanthThadhani, RaviBerg, Anders H.2016-07-21T06:25:38-07:00doi:10.2215/CJN.02390316hwp:resource-id:clinjasn;11/10/1809American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, ESRD, mortality risk, uremia, protein carbamylation, Albumins, Blood Urea Nitrogen, Case-Control Studies, Demography, Fluid Therapy, Humans, Kidney Failure, Chronic, Protein Processing, Post-Translational, renal dialysis, Risk, ureaOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-10-07October 07, 201610.2215/CJN.023903161555-90411555-905X2016-07-21T06:25:38-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111018091816
- Can We Predict the Unpredictable after Vascular Access Creation?10.2215/CJN.08930816Wed, 14 Sep 2016 07:17:53 GMT-07:00Can We Predict the Unpredictable after Vascular Access Creation?Polkinghorne, Kevan R.Lok, Charmaine E.2016-09-14T07:17:53-07:00doi:10.2215/CJN.08930816hwp:resource-id:clinjasn;11/10/1729American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, dialysis, hemodialysis access, eGFR trajectory, Kidney function decline, Arteriovenous Shunt, Surgical, renal dialysisEditorialsEditorialseditorial20162016-10-07October 07, 201610.2215/CJN.089308161555-90411555-905X2016-09-14T07:17:53-07:002016-10-07Clinical Journal of the American Society of NephrologyEditorials1110101729180217311808
- Supportive Care: Comprehensive Conservative Care in End-Stage Kidney DiseaseComprehensive conservative (nondialytic) kidney care is widely recognized and delivered but until recently, has not been clearly defined. We provide a clear definition of comprehensive conservative care. This includes interventions to delay progression of kidney disease and minimize complications as well as detailed communication, shared decision making, advance care planning, and psychologic and family support. It does not include dialysis. Limited epidemiologic evidence from Australia and Canada indicates that, for every new person diagnosed with ESRD who receives dialysis or transplant, there is one new person who is managed conservatively (either actively or not). For older patients (those >75 or 80 years old) who have higher levels of comorbidity (such as diabetes and heart disease) and poorer functional status, the survival advantage of dialysis may be limited, and comprehensive conservative management may be considered; however, robust comparative evidence remains limited. Considerations of symptoms, quality of life, and hospital-free days are as or sometimes more important for patients and families than survival. There is some evidence that communication about possible conservative management options is generally insufficient, even where comprehensive conservative care pathways are already established. Symptom control and the cost-effectiveness of interventions are addressed in the companion papers within this Moving Points in Nephrology series. There is almost no evidence about which models of care and which interventions might be most beneficial in this population; future research on these areas is much needed. Meanwhile, consistency in definition of comprehensive conservative care and basing interventions on existing evidence about survival, symptoms, quality of life, and experience will maximize patient-centered and holistic care.10.2215/CJN.04840516Wed, 10 Aug 2016 06:57:42 GMT-07:00Supportive Care: Comprehensive Conservative Care in End-Stage Kidney DiseaseComprehensive conservative (nondialytic) kidney care is widely recognized and delivered but until recently, has not been clearly defined. We provide a clear definition of comprehensive conservative care. This includes interventions to delay progression of kidney disease and minimize complications as well as detailed communication, shared decision making, advance care planning, and psychologic and family support. It does not include dialysis. Limited epidemiologic evidence from Australia and Canada indicates that, for every new person diagnosed with ESRD who receives dialysis or transplant, there is one new person who is managed conservatively (either actively or not). For older patients (those >75 or 80 years old) who have higher levels of comorbidity (such as diabetes and heart disease) and poorer functional status, the survival advantage of dialysis may be limited, and comprehensive conservative management may be considered; however, robust comparative evidence remains limited. Considerations of symptoms, quality of life, and hospital-free days are as or sometimes more important for patients and families than survival. There is some evidence that communication about possible conservative management options is generally insufficient, even where comprehensive conservative care pathways are already established. Symptom control and the cost-effectiveness of interventions are addressed in the companion papers within this Moving Points in Nephrology series. There is almost no evidence about which models of care and which interventions might be most beneficial in this population; future research on these areas is much needed. Meanwhile, consistency in definition of comprehensive conservative care and basing interventions on existing evidence about survival, symptoms, quality of life, and experience will maximize patient-centered and holistic care.Murtagh, Fliss E.M.Burns, AineMoranne, OlivierMorton, Rachael L.Naicker, Saraladevi2016-08-10T06:57:42-07:00doi:10.2215/CJN.04840516hwp:resource-id:clinjasn;11/10/1909American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient-centered care, chronic kidney disease, conservative care, palliative care, supportive care, Advance Care Planning, Australia, Canada, Comorbidity, diabetes mellitus, Heart Diseases, Humans, Kidney Failure, Chronic, Prevalence, quality of life, renal dialysis, Renal Insufficiency, ChronicMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.048405161555-90411555-905X2016-08-10T06:57:42-07:002016-10-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111019091914
- The Role of RRT in Hyperammonemic PatientsHyperammonemia is an important cause of cerebral edema in both adults with liver failure and children with inborn errors of metabolism. There are few studies that have analyzed the role of extracorporeal dialysis in reducing blood ammonia levels in the adult population. Furthermore, there are no firm guidelines about when to implement RRT, because many of the conditions that are characterized by hyperammonemia are extremely rare. In this review of existing literature on RRT, we present the body’s own mechanisms for clearing ammonia as well as the dialytic properties of ammonia. We review the available literature on the use of continuous venovenous hemofiltration, peritoneal dialysis, and hemodialysis in neonates and adults with conditions characterized by hyperammonemia and discuss some of the controversies that exist over selecting one modality over another.10.2215/CJN.01320216Thu, 19 May 2016 06:54:28 GMT-07:00The Role of RRT in Hyperammonemic PatientsHyperammonemia is an important cause of cerebral edema in both adults with liver failure and children with inborn errors of metabolism. There are few studies that have analyzed the role of extracorporeal dialysis in reducing blood ammonia levels in the adult population. Furthermore, there are no firm guidelines about when to implement RRT, because many of the conditions that are characterized by hyperammonemia are extremely rare. In this review of existing literature on RRT, we present the body’s own mechanisms for clearing ammonia as well as the dialytic properties of ammonia. We review the available literature on the use of continuous venovenous hemofiltration, peritoneal dialysis, and hemodialysis in neonates and adults with conditions characterized by hyperammonemia and discuss some of the controversies that exist over selecting one modality over another.Gupta, ShrutiFenves, Andrew Z.Hootkins, Robert2016-05-19T06:54:28-07:00doi:10.2215/CJN.01320216hwp:resource-id:clinjasn;11/10/1872American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyelectrolytes, liver failure, outcomes, Ammonia, Hemofiltration, Humans, Hyperammonemia, peritoneal dialysis, renal dialysis, Renal Replacement TherapyIn-Depth ReviewIn-Depth Reviewreview-article20162016-10-07October 07, 201610.2215/CJN.013202161555-90411555-905X2016-05-19T06:54:28-07:002016-10-07Clinical Journal of the American Society of NephrologyIn-Depth Review111018721878
- Patiromer–an Oral Calcium-Loaded Potassium Binder: Kalirrhea with Calciuresis10.2215/CJN.08910816Tue, 27 Sep 2016 07:05:57 GMT-07:00Patiromer–an Oral Calcium-Loaded Potassium Binder: Kalirrhea with CalciuresisEmmett, MichaelMehta, Ankit2016-09-27T07:05:57-07:00doi:10.2215/CJN.08910816hwp:resource-id:clinjasn;11/10/1723American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypotassium channels, calcium, chronic kidney disease, electrolytes, phosphate uptake, Calcium, Dietary, Polymers, Potassium, patiromerEditorialsEditorialseditorial20162016-10-07October 07, 201610.2215/CJN.089108161555-90411555-905X2016-09-27T07:05:57-07:002016-10-07Clinical Journal of the American Society of NephrologyEditorials1110101723176917251776
- Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome10.2215/CJN.00320116Thu, 21 Jul 2016 06:25:38 GMT-07:00Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic SyndromeTellier, StéphanieDallocchio, AymericGuigonis, VincentSaint-Marcoux, FrankLlanas, BrigitteIchay, LydiaBandin, FlavioGodron, AstridMorin, DenisBrochard, KarineGandia, PeggyBouchet, StéphaneMarquet, PierreDecramer, StéphaneHarambat, Jérôme2016-07-21T06:25:38-07:00doi:10.2215/CJN.00320116hwp:resource-id:clinjasn;11/10/1777American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyPharmacokinetics, mycophenolate mofetil, children, Area Under Curve, Drug Monitoring, Humans, Immunosuppressive Agents, Mycophenolic Acid, nephrotic syndrome, Prednisone, RecurrenceOriginal ArticlesClinical PharmacologyOriginal ArticlesClinical Pharmacologyresearch-article20162016-10-07October 07, 201610.2215/CJN.003201161555-90411555-905X2016-07-21T06:25:38-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111017771782
- RRT in AKI: Start Early or Wait?10.2215/CJN.06690616Mon, 26 Sep 2016 07:34:50 GMT-07:00RRT in AKI: Start Early or Wait?Liu, Kathleen D.Palevsky, Paul M.2016-09-26T07:34:50-07:00doi:10.2215/CJN.06690616hwp:resource-id:clinjasn;11/10/1867American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute kidney injury, Renal replacement therapy, dialysis, hemodialysis, acute renal failureCommentaryCommentaryarticle-commentary20162016-10-07October 07, 201610.2215/CJN.066906161555-90411555-905X2016-09-26T07:34:50-07:002016-10-07Clinical Journal of the American Society of NephrologyCommentary111018671871
- Practice Change Is Needed for Dialysis Decision Making with Older Adults with Advanced Kidney Disease10.2215/CJN.08770816Thu, 22 Sep 2016 06:35:09 GMT-07:00Practice Change Is Needed for Dialysis Decision Making with Older Adults with Advanced Kidney DiseaseScherer, Jennifer S.Moss, Alvin H.2016-09-22T06:35:09-07:00doi:10.2215/CJN.08770816hwp:resource-id:clinjasn;11/10/1732American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysupportive care, older patients, conservative care, shared decision-making, chronic dialysis, Decision Making, fluid therapy, humans, kidney, kidney diseases, renal dialysisEditorialsEditorialseditorial20162016-10-07October 07, 201610.2215/CJN.087708161555-90411555-905X2016-09-22T06:35:09-07:002016-10-07Clinical Journal of the American Society of NephrologyEditorials1110101732182517341833
- Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US Department of Veterans Affairs, 2000–201110.2215/CJN.03760416Thu, 22 Sep 2016 06:35:09 GMT-07:00Decisions about Renal Replacement Therapy in Patients with Advanced Kidney Disease in the US Department of Veterans Affairs, 2000–2011Wong, Susan P.Y.Hebert, Paul L.Laundry, Ryan J.Hammond, Kenric W.Liu, Chuan-FenBurrows, Nilka R.O’Hare, Ann M.2016-09-22T06:35:09-07:00doi:10.2215/CJN.03760416hwp:resource-id:clinjasn;11/10/1825American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, dialysis, end-stage renal disease, Adult, Comorbidity, Developed Countries, Electronic Health Records, Follow-Up Studies, glomerular filtration rate, Humans, kidney, Medicare, renal dialysis, Renal Insufficiency, Chronic, Renal Replacement Therapy, Retrospective Studies, United States, VeteransOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-10-07October 07, 201610.2215/CJN.037604161555-90411555-905X2016-09-22T06:35:09-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1110101825173218331734
- Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney Stones10.2215/CJN.01520216Thu, 21 Jul 2016 06:25:40 GMT-07:00Dietary Protein and Potassium, Diet–Dependent Net Acid Load, and Risk of Incident Kidney StonesFerraro, Pietro ManuelMandel, Ernest I.Curhan, Gary C.Gambaro, GiovanniTaylor, Eric N.2016-07-21T06:25:40-07:00doi:10.2215/CJN.01520216hwp:resource-id:clinjasn;11/10/1834American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacid load, nutrition, potassium, protein, urolithiasis, NEAP, kidney stones, Body Mass Index, Citrates, Citric Acid, Cross-Sectional Studies, Diet, Dietary Proteins, Epidemiologic Studies, Follow-Up Studies, Kidney Calculi, Potassium, Dietary, Risk, VegetablesOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20162016-10-07October 07, 201610.2215/CJN.015202161555-90411555-905X2016-07-21T06:25:40-07:002016-10-07Clinical Journal of the American Society of NephrologyOriginal Articles111018341844
- Supportive Care: Communication Strategies to Improve Cultural Competence in Shared Decision MakingHistoric migration and the ever–increasing current migration into Western countries have greatly changed the ethnic and cultural patterns of patient populations. Because health care beliefs of minority groups may follow their religion and country of origin, inevitable conflict can arise with decision making at the end of life. The principles of truth telling and patient autonomy are embedded in the framework of Anglo–American medical ethics. In contrast, in many parts of the world, the cultural norm is protection of the patient from the truth, decision making by the family, and a tradition of familial piety, where it is dishonorable not to do as much as possible for parents. The challenge for health care professionals is to understand how culture has enormous potential to influence patients’ responses to medical issues, such as healing and suffering, as well as the physician-patient relationship. Our paper provides a framework of communication strategies that enhance crosscultural competency within nephrology teams. Shared decision making also enables clinicians to be culturally competent communicators by providing a model where clinicians and patients jointly consider best clinical evidence in light of a patient’s specific health characteristics and values when choosing health care. The development of decision aids to include cultural awareness could avoid conflict proactively, more productively address it when it occurs, and enable decision making within the framework of the patient and family cultural beliefs.10.2215/CJN.13661215Wed, 10 Aug 2016 06:57:43 GMT-07:00Supportive Care: Communication Strategies to Improve Cultural Competence in Shared Decision MakingHistoric migration and the ever–increasing current migration into Western countries have greatly changed the ethnic and cultural patterns of patient populations. Because health care beliefs of minority groups may follow their religion and country of origin, inevitable conflict can arise with decision making at the end of life. The principles of truth telling and patient autonomy are embedded in the framework of Anglo–American medical ethics. In contrast, in many parts of the world, the cultural norm is protection of the patient from the truth, decision making by the family, and a tradition of familial piety, where it is dishonorable not to do as much as possible for parents. The challenge for health care professionals is to understand how culture has enormous potential to influence patients’ responses to medical issues, such as healing and suffering, as well as the physician-patient relationship. Our paper provides a framework of communication strategies that enhance crosscultural competency within nephrology teams. Shared decision making also enables clinicians to be culturally competent communicators by providing a model where clinicians and patients jointly consider best clinical evidence in light of a patient’s specific health characteristics and values when choosing health care. The development of decision aids to include cultural awareness could avoid conflict proactively, more productively address it when it occurs, and enable decision making within the framework of the patient and family cultural beliefs.Brown, Edwina A.Bekker, Hilary L.Davison, Sara N.Koffman, JonathanSchell, Jane O.2016-08-10T06:57:43-07:00doi:10.2215/CJN.13661215hwp:resource-id:clinjasn;11/10/1902American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend of life, advanced kidney disease, decision-making, Communication, Cultural Competency, Decision Support Techniques, Ethics, Medical, Ethnic Groups, Humans, Minority Groups, chronic kidney disease, Physician-Patient RelationsMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.136612151555-90411555-905X2016-08-10T06:57:43-07:002016-10-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111019021908
- Supportive Care: Time to Change Our Prognostic Tools and Their Use in CKDIn using a patient-centered approach, neither a clinician nor a prognostic score can predict with absolute certainty how well a patient will do or how long he will live; however, validated prognostic scores may improve accuracy of prognostic estimates, thereby enhancing the ability of the clinicians to appreciate the individual burden of disease and the prognosis of their patients and inform them accordingly. They may also facilitate nephrologist’s recommendation of dialysis services to those who may benefit and proposal of alternative care pathways that might better respect patients’ values and goals to those who are unlikely to benefit. The purpose of this article is to discuss the use as well as the limits and deficiencies of currently available prognostic tools. It will describe new predictors that could be integrated in future scores and the role of patients’ priorities in development of new scores. Delivering patient-centered care requires an understanding of patients’ priorities that are important and relevant to them. Because of limits of available scores, the contribution of new prognostic tools with specific markers of the trajectories for patients with CKD and patients’ health reports should be evaluated in relation to their transportability to different clinical and cultural contexts and their potential for integration into the decision-making processes. The benefit of their use then needs to be quantified in clinical practice by outcome studies including health–related quality of life, patient and caregiver satisfaction, or utility for improving clinical management pathways and tailoring individualized patient–centered strategies of care. Future research also needs to incorporate qualitative methods involving patients and their caregivers to better understand the barriers and facilitators to use of these tools in the clinical setting. Information given to patients should be supported by a more realistic approach to what dialysis is likely to entail for the individual patient in terms of likely quality and quantity of life according to the patient’s values and goals and not just the possibility of life prolongation.10.2215/CJN.12631115Wed, 10 Aug 2016 06:57:41 GMT-07:00Supportive Care: Time to Change Our Prognostic Tools and Their Use in CKDIn using a patient-centered approach, neither a clinician nor a prognostic score can predict with absolute certainty how well a patient will do or how long he will live; however, validated prognostic scores may improve accuracy of prognostic estimates, thereby enhancing the ability of the clinicians to appreciate the individual burden of disease and the prognosis of their patients and inform them accordingly. They may also facilitate nephrologist’s recommendation of dialysis services to those who may benefit and proposal of alternative care pathways that might better respect patients’ values and goals to those who are unlikely to benefit. The purpose of this article is to discuss the use as well as the limits and deficiencies of currently available prognostic tools. It will describe new predictors that could be integrated in future scores and the role of patients’ priorities in development of new scores. Delivering patient-centered care requires an understanding of patients’ priorities that are important and relevant to them. Because of limits of available scores, the contribution of new prognostic tools with specific markers of the trajectories for patients with CKD and patients’ health reports should be evaluated in relation to their transportability to different clinical and cultural contexts and their potential for integration into the decision-making processes. The benefit of their use then needs to be quantified in clinical practice by outcome studies including health–related quality of life, patient and caregiver satisfaction, or utility for improving clinical management pathways and tailoring individualized patient–centered strategies of care. Future research also needs to incorporate qualitative methods involving patients and their caregivers to better understand the barriers and facilitators to use of these tools in the clinical setting. Information given to patients should be supported by a more realistic approach to what dialysis is likely to entail for the individual patient in terms of likely quality and quantity of life according to the patient’s values and goals and not just the possibility of life prolongation.Couchoud, CécileHemmelgarn, BrendaKotanko, PeterGermain, Michael J.Moranne, OlivierDavison, Sara N.2016-08-10T06:57:41-07:00doi:10.2215/CJN.12631115hwp:resource-id:clinjasn;11/10/1892American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysupportive care, chronic kidney disease, survival, Epidemiology and outcomes, Caregivers, Decision Making, Humans, Patient-Centered Care, Personal Satisfaction, Prognosis, quality of life, renal dialysisMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-10-07October 07, 201610.2215/CJN.126311151555-90411555-905X2016-08-10T06:57:41-07:002016-10-07Clinical Journal of the American Society of NephrologyMoving Points in Nephrology111018921901
- Measurement Error as Alternative Explanation for the Observation that CrCl/GFR Ratio is Higher at Lower GFR10.2215/CJN.12821215Wed, 03 Aug 2016 05:54:00 GMT-07:00Measurement Error as Alternative Explanation for the Observation that CrCl/GFR Ratio is Higher at Lower GFRZhang, XuehanMcCulloch, Charles E.Lin, FengLin, Yen-chungAllen, Isabel ElaineBansal, NishaGo, Alan S.Hsu, Chi-yuan2016-08-03T05:54:00-07:00doi:10.2215/CJN.12821215hwp:resource-id:clinjasn;11/9/1574American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-09-07September 07, 201610.2215/CJN.128212151555-90411555-905X2016-08-03T05:54:00-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11991574151815811521
- Silent Cerebral Microbleeds and Longitudinal Risk of Renal and Cardiovascular Events in Patients with CKD10.2215/CJN.13481215Mon, 27 Jun 2016 06:49:04 GMT-07:00Silent Cerebral Microbleeds and Longitudinal Risk of Renal and Cardiovascular Events in Patients with CKDShima, HideakiMori, TatsuhikoOoi, MasayukiSonoda, MikaShoji, TetsuoIshimura, EijiOkamura, MikioIshizaka, NobukazuInaba, Masaaki2016-06-27T06:49:04-07:00doi:10.2215/CJN.13481215hwp:resource-id:clinjasn;11/9/1557American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, cardiovascular disease, microbleeds, magnetic resonance imaging, cerebrovascular disorders, blood pressure, Cohort Studies, Humans, Kidney Failure, Chronic, Peripheral Arterial Disease, Renal Insufficiency, Chronic, StrokeOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-09-07September 07, 201610.2215/CJN.134812151555-90411555-905X2016-06-27T06:49:04-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915571565
- Risk Factors for and Outcomes of Catheter-Associated Peritonitis in Children: The SCOPE Collaborative10.2215/CJN.02540316Thu, 23 Jun 2016 08:13:30 GMT-07:00Risk Factors for and Outcomes of Catheter-Associated Peritonitis in Children: The SCOPE CollaborativeSethna, Christine B.Bryant, KristinaMunshi, RajWarady, Bradley A.Richardson, TroyLawlor, JohnNewland, Jason G.Neu, Alicia2016-06-23T08:13:30-07:00doi:10.2215/CJN.02540316hwp:resource-id:clinjasn;11/9/1590American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, children, peritonitis, catheter-related infections, Follow-Up Studies, Humans, Kidney Failure, Chronic, Patient Care Bundles, Quality Improvement, renal dialysis, risk factorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-09-07September 07, 201610.2215/CJN.025403161555-90411555-905X2016-06-23T08:13:30-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915901596
- Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants10.2215/CJN.13381215Thu, 28 Jul 2016 05:59:10 GMT-07:00Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight InfantsAskenazi, David J.Koralkar, RajeshPatil, NehaHalloran, BrianAmbalavanan, NamasivayamGriffin, Russell2016-07-28T05:59:10-07:00doi:10.2215/CJN.13381215hwp:resource-id:clinjasn;11/9/1527American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNGAL, KIM-1, cystatin c, beta-2 microglobulin, child, acute kidney injury, biomarkers, creatinine, humans, infant, very low birth weight, intensive care units, neonatal, prospective studiesOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-09-07September 07, 201610.2215/CJN.133812151555-90411555-905X2016-07-28T05:59:10-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915271535
- Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome10.2215/CJN.00910116Thu, 18 Aug 2016 08:15:53 GMT-07:00Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal SyndromeChen, ChunboYang, XiaobingLei, YingZha, YanLiu, HuafengMa, ChangshengTian, JianweiChen, PingyanYang, TiechengHou, Fan Fan2016-08-18T08:15:53-07:00doi:10.2215/CJN.00910116hwp:resource-id:clinjasn;11/9/1536American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, biomarkers, prediction, outcomes, Adult, Angiotensinogen, Area Under Curve, Cardio-Renal Syndrome, creatinine, Humans, Prospective StudiesOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-09-07September 07, 201610.2215/CJN.009101161555-90411555-905X2016-08-18T08:15:53-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11991536151515441517
- Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis10.2215/CJN.01190216Thu, 23 Jun 2016 08:13:33 GMT-07:00Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental GlomerulosclerosisZhang, Yi-miaoGu, Qiu-huaHuang, JingQu, ZhenWang, XinMeng, Li-qiangWang, FangLiu, GangCui, ZhaoZhao, Ming-hui2016-06-23T08:13:33-07:00doi:10.2215/CJN.01190216hwp:resource-id:clinjasn;11/9/1582American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfocal segmental glomerulosclerosis, complement, outcomes, Biopsy, Complement Activation, creatinine, Disease Progression, Follow-Up Studies, Humans, Immunoglobulin M, Prevalence, risk factorsOriginal ArticlesClinical Immunology and PathologyOriginal ArticlesClinical Immunology and Pathologyresearch-article20162016-09-07September 07, 201610.2215/CJN.011902161555-90411555-905X2016-06-23T08:13:33-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915821589
- Inflammation and Progression of CKD: The CRIC Study10.2215/CJN.13121215Thu, 23 Jun 2016 08:13:32 GMT-07:00Inflammation and Progression of CKD: The CRIC StudyAmdur, Richard L.Feldman, Harold I.Gupta, JayantaYang, WeiKanetsky, PeterShlipak, MichaelRahman, MahboobLash, James P.Townsend, Raymond R.Ojo, AkinloluRoy-Chaudhury, AkshayGo, Alan S.Joffe, MarshallHe, JiangBalakrishnan, Vaidyanathapuram S.Kimmel, Paul L.Kusek, John W.Raj, Dominic S.,2016-06-23T08:13:32-07:00doi:10.2215/CJN.13121215hwp:resource-id:clinjasn;11/9/1546American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cytokines, glomerular filtration rate, end-stage renal disease, albuminuria, C-Reactive Protein, Follow-Up Studies, Humans, Inflammation, Interleukin-6, Renal Insufficiency, Chronic, Tumor Necrosis Factor-alphaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-09-07September 07, 201610.2215/CJN.131212151555-90411555-905X2016-06-23T08:13:32-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915461556
- Creatinine–Based and Cystatin C–Based GFR Estimating Equations and Their Non-GFR Determinants in Kidney Transplant Recipients10.2215/CJN.11741115Thu, 23 Jun 2016 08:13:30 GMT-07:00Creatinine–Based and Cystatin C–Based GFR Estimating Equations and Their Non-GFR Determinants in Kidney Transplant RecipientsKeddis, Mira T.Amer, HatemVoskoboev, NikolayKremers, Walter K.Rule, Andrew D.Lieske, John C.2016-06-23T08:13:30-07:00doi:10.2215/CJN.11741115hwp:resource-id:clinjasn;11/9/1640American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCardiovascular Diseases, Creatinine, Cystatin C, diabetes mellitus, glomerular filtration rate, Iothalamic Acid, kidney transplantation, obesity, proteinuria, risk factors, Smoking, TriglyceridesOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-09-07September 07, 201610.2215/CJN.117411151555-90411555-905X2016-06-23T08:13:30-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11916401649
- The Players: Cells Involved in Glomerular DiseaseGlomerular diseases are common and important. They can arise from systemic inflammatory or metabolic diseases that affect the kidney. Alternately, they are caused primarily by local glomerular abnormalities, including genetic diseases. Both intrinsic glomerular cells and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease. Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells within the glomerulus all play unique and specialized roles. Although a specific disease often primarily affects a particular cell type, the close proximity, and interdependent functions and interactions between cells mean that even diseases affecting one cell type usually indirectly influence others. In addition to those cells intrinsic to the glomerulus, leukocytes patrol the glomerulus in health and mediate injury in disease. Distinct leukocyte types and subsets are present, with some being involved in different ways in an individual glomerular disease. Cells of the innate and adaptive immune systems are important, directing systemic immune and inflammatory responses, locally mediating injury, and potentially dampening inflammation and facilitating repair. The advent of new genetic and molecular techniques, and new disease models means that we better understand both the basic biology of the glomerulus and the pathogenesis of glomerular disease. This understanding should lead to better diagnostic techniques, biomarkers, and predictors of prognosis, disease severity, and relapse. With this knowledge comes the promise of better therapies in the future, directed toward halting pathways of injury and fibrosis, or interrupting the underlying pathophysiology of the individual diseases that lead to significant and progressive glomerular disease.10.2215/CJN.13791215Tue, 12 Apr 2016 08:25:44 GMT-07:00The Players: Cells Involved in Glomerular DiseaseGlomerular diseases are common and important. They can arise from systemic inflammatory or metabolic diseases that affect the kidney. Alternately, they are caused primarily by local glomerular abnormalities, including genetic diseases. Both intrinsic glomerular cells and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease. Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells within the glomerulus all play unique and specialized roles. Although a specific disease often primarily affects a particular cell type, the close proximity, and interdependent functions and interactions between cells mean that even diseases affecting one cell type usually indirectly influence others. In addition to those cells intrinsic to the glomerulus, leukocytes patrol the glomerulus in health and mediate injury in disease. Distinct leukocyte types and subsets are present, with some being involved in different ways in an individual glomerular disease. Cells of the innate and adaptive immune systems are important, directing systemic immune and inflammatory responses, locally mediating injury, and potentially dampening inflammation and facilitating repair. The advent of new genetic and molecular techniques, and new disease models means that we better understand both the basic biology of the glomerulus and the pathogenesis of glomerular disease. This understanding should lead to better diagnostic techniques, biomarkers, and predictors of prognosis, disease severity, and relapse. With this knowledge comes the promise of better therapies in the future, directed toward halting pathways of injury and fibrosis, or interrupting the underlying pathophysiology of the individual diseases that lead to significant and progressive glomerular disease.Kitching, A. RichardHutton, Holly L.2016-04-12T08:25:44-07:00doi:10.2215/CJN.13791215hwp:resource-id:clinjasn;11/9/1664American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGlomerulus, Immunology and pathology, endothelial cells, fibrosis, Inflammation, kidney, Leukocytes, mesangial cells, Podocytes, PrognosisGlomerular Disease Update for the ClinicianGlomerular Disease Update for the Clinicianresearch-article20162016-09-07September 07, 201610.2215/CJN.137912151555-90411555-905X2016-04-12T08:25:44-07:002016-09-07Clinical Journal of the American Society of NephrologyGlomerular Disease Update for the Clinician11916641674
- Assisted Peritoneal Dialysis as an Alternative to In-Center Hemodialysis10.2215/CJN.07040716Wed, 27 Jul 2016 06:04:24 GMT-07:00Assisted Peritoneal Dialysis as an Alternative to In-Center HemodialysisBrown, Edwina A.Wilkie, Martin2016-07-27T06:04:24-07:00doi:10.2215/CJN.07040716hwp:resource-id:clinjasn;11/9/1522American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hemodialysis, geriatric nephrology, renal dialysisEditorialsEditorialseditorial20162016-09-07September 07, 201610.2215/CJN.070407161555-90411555-905X2016-07-27T06:04:24-07:002016-09-07Clinical Journal of the American Society of NephrologyEditorials11991522160615241614
- Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal SignificanceThe monoclonal gammopathies of renal significance (MGRS) are a group of disorders characterized by monoclonal Ig deposition in the kidney, but are not associated with systemic lymphoma or overt multiple myeloma. The prevailing hypothesis is that the pathogenic paraproteins in MGRS are produced by underlying B cell or plasma cell clones. However, in the MGRS literature, the yield of detecting a clone has been variable, and progression to ESRD is common. Here, we present an “onco-nephrologic” approach to the MGRS disorders by highlighting recent advances in lymphoma and multiple myeloma that can be used in the evaluation and management of these patients.10.2215/CJN.03160316Thu, 14 Jul 2016 06:32:39 GMT-07:00Bridging the Divide: An Onco-Nephrologic Approach to the Monoclonal Gammopathies of Renal SignificanceThe monoclonal gammopathies of renal significance (MGRS) are a group of disorders characterized by monoclonal Ig deposition in the kidney, but are not associated with systemic lymphoma or overt multiple myeloma. The prevailing hypothesis is that the pathogenic paraproteins in MGRS are produced by underlying B cell or plasma cell clones. However, in the MGRS literature, the yield of detecting a clone has been variable, and progression to ESRD is common. Here, we present an “onco-nephrologic” approach to the MGRS disorders by highlighting recent advances in lymphoma and multiple myeloma that can be used in the evaluation and management of these patients.Hogan, Jonathan J.Weiss, Brendan M.2016-07-14T06:32:39-07:00doi:10.2215/CJN.03160316hwp:resource-id:clinjasn;11/9/1681American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, proteinuria, B-Lymphocytes, Humans, kidney, Kidney Failure, Chronic, Lymphoma, multiple myeloma, Myeloma Proteins, Paraproteinemias, Paraproteins, Plasma Cells, multiple myeloma M-proteinsMini-ReviewsMini-Reviewsreview-article20162016-09-07September 07, 201610.2215/CJN.031603161555-90411555-905X2016-07-14T06:32:39-07:002016-09-07Clinical Journal of the American Society of NephrologyMini-Reviews11916811691
- Variation in Patients’ Awareness of CKD according to How They Are Asked10.2215/CJN.00490116Thu, 23 Jun 2016 08:13:34 GMT-07:00Variation in Patients’ Awareness of CKD according to How They Are AskedTuot, Delphine S.Zhu, YunnuoVelasquez, AlexandraEspinoza, JuanMendez, C. DamarisBanerjee, TanushreeHsu, Chi-yuanPowe, Neil R.2016-06-23T08:13:34-07:00doi:10.2215/CJN.00490116hwp:resource-id:clinjasn;11/9/1566American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, awareness, diabetes mellitus, Health Literacy, Humans, hypertension, kidney, Kidney Calculi, Language, Medical Records, Patient Participation, Renal Insufficiency, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-09-07September 07, 201610.2215/CJN.004901161555-90411555-905X2016-06-23T08:13:34-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915661573
- Introduction: Glomerular Disease Update for the Clinician10.2215/CJN.07430716Wed, 07 Sep 2016 10:00:36 GMT-07:00Introduction: Glomerular Disease Update for the ClinicianNester, Carla M.J. Falk, Ronald2016-09-07T10:00:36-07:00doi:10.2215/CJN.07430716hwp:resource-id:clinjasn;11/9/1662American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, review, education, Kidney Diseases, Kidney GlomerulusGlomerular Disease Update for the ClinicianGlomerular Disease Update for the Clinicianresearch-article20162016-09-07September 07, 201610.2215/CJN.074307161555-90411555-905X2016-09-07T10:00:36-07:002016-09-07Clinical Journal of the American Society of NephrologyGlomerular Disease Update for the Clinician11916621663
- Lower Extremity Permanent Dialysis Vascular AccessHemodialysis remains the most commonly used RRT option around the world. Technological advances, superior access to care, and better quality of care have led to overall improvement in survival of patients on long-term hemodialysis. Maintaining a functioning upper extremity vascular access for a prolonged duration continues to remain a challenge for dialysis providers. Frequently encountered difficulties in clinical practice include (1) a high incidence of central venous catheter–related central vein stenosis and (2) limited options for creating a functioning upper extremity permanent arteriovenous access. Lack of surgical skills, fear of complications, and limited involvement of the treating nephrologists in the decision-making process are some of the reasons why lower extremity permanent dialysis access remains an infrequently used option. Similar to upper extremity vascular access options, lower extremity arteriovenous fistula remains a preferred access over arteriovenous synthetic graft. The use of femoral tunneled catheter as a long-term access should be avoided as far as possible, especially with the availability of newer graft-catheter hybrid devices. Our review provides a summary of clinical evidence published in surgical, radiology, and nephrology literature highlighting the pros and cons of different types of lower extremity permanent dialysis access.10.2215/CJN.01780216Fri, 27 May 2016 06:24:11 GMT-07:00Lower Extremity Permanent Dialysis Vascular AccessHemodialysis remains the most commonly used RRT option around the world. Technological advances, superior access to care, and better quality of care have led to overall improvement in survival of patients on long-term hemodialysis. Maintaining a functioning upper extremity vascular access for a prolonged duration continues to remain a challenge for dialysis providers. Frequently encountered difficulties in clinical practice include (1) a high incidence of central venous catheter–related central vein stenosis and (2) limited options for creating a functioning upper extremity permanent arteriovenous access. Lack of surgical skills, fear of complications, and limited involvement of the treating nephrologists in the decision-making process are some of the reasons why lower extremity permanent dialysis access remains an infrequently used option. Similar to upper extremity vascular access options, lower extremity arteriovenous fistula remains a preferred access over arteriovenous synthetic graft. The use of femoral tunneled catheter as a long-term access should be avoided as far as possible, especially with the availability of newer graft-catheter hybrid devices. Our review provides a summary of clinical evidence published in surgical, radiology, and nephrology literature highlighting the pros and cons of different types of lower extremity permanent dialysis access.Parekh, Vishal B.Niyyar, Vandana D.Vachharajani, Tushar J.2016-05-27T06:24:11-07:00doi:10.2215/CJN.01780216hwp:resource-id:clinjasn;11/9/1693American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, lower extremity access, vascular access, tunneled dialysis catheter, arteriovenous graft, femoral catheter, dialysis access, Central Venous Catheters, Constriction, Pathologic, Humans, Lower Extremity, nephrologyMini-ReviewsMini-Reviewsreview-article20162016-09-07September 07, 201610.2215/CJN.017802161555-90411555-905X2016-05-27T06:24:11-07:002016-09-07Clinical Journal of the American Society of NephrologyMini-Reviews11916931702
- Adjusting the 17β–Estradiol-to-Androgen Ratio Ameliorates Diabetic NephropathyDiabetes is manifested predominantly in males in experimental models, and compelling evidence suggests that 17β-estradiol (E2) supplementation improves hyperglycemia in humans. We previously generated a severely diabetic transgenic (Tg) mouse model by β-cell–specific overexpression of inducible cAMP early repressor (ICER) and found that male but not female ICER-Tg mice exhibit sustained hyperglycemia and develop major clinical and pathologic features of human diabetic nephropathy (DN). Thus, we hypothesized that differences in circulating hormone levels have a key role in determining susceptibility to diabetes. Here, we examined whether DN in male ICER-Tg mice is rescued by adjusting the androgen-to-E2 ratio to approximate that in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX), E2 pellet implantation, or both. E2 pellet implantation at an early stage of DN with or without ORX caused a rapid drop in blood glucose and a dramatic increase in β-cell number, and it markedly inhibited DN progression [namely, E2 reduced glomerulosclerosis, collagen IV deposition and albuminuria, and prevented hyperfiltration]. Furthermore, E2 pellet implantation was more effective than ORX alone and induced a remarkable improvement, even when initiated at advanced-stage DN. In contrast, induction of normoglycemia by islet transplant in ICER-Tg mice eliminated albuminuria but was less effective than E2+ORX in reducing glomerulosclerosis or collagen IV deposition and hyperfiltration. These findings indicate that E2 treatment is effective, even after establishment of DN, whereas glucose normalization alone does not improve sclerotic lesions. We propose that E2 intervention is a potential therapeutic option for DN.10.1681/ASN.2015070741Thu, 03 Mar 2016 10:59:05 GMT-08:00Adjusting the 17β–Estradiol-to-Androgen Ratio Ameliorates Diabetic NephropathyDiabetes is manifested predominantly in males in experimental models, and compelling evidence suggests that 17β-estradiol (E2) supplementation improves hyperglycemia in humans. We previously generated a severely diabetic transgenic (Tg) mouse model by β-cell–specific overexpression of inducible cAMP early repressor (ICER) and found that male but not female ICER-Tg mice exhibit sustained hyperglycemia and develop major clinical and pathologic features of human diabetic nephropathy (DN). Thus, we hypothesized that differences in circulating hormone levels have a key role in determining susceptibility to diabetes. Here, we examined whether DN in male ICER-Tg mice is rescued by adjusting the androgen-to-E2 ratio to approximate that in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX), E2 pellet implantation, or both. E2 pellet implantation at an early stage of DN with or without ORX caused a rapid drop in blood glucose and a dramatic increase in β-cell number, and it markedly inhibited DN progression [namely, E2 reduced glomerulosclerosis, collagen IV deposition and albuminuria, and prevented hyperfiltration]. Furthermore, E2 pellet implantation was more effective than ORX alone and induced a remarkable improvement, even when initiated at advanced-stage DN. In contrast, induction of normoglycemia by islet transplant in ICER-Tg mice eliminated albuminuria but was less effective than E2+ORX in reducing glomerulosclerosis or collagen IV deposition and hyperfiltration. These findings indicate that E2 treatment is effective, even after establishment of DN, whereas glucose normalization alone does not improve sclerotic lesions. We propose that E2 intervention is a potential therapeutic option for DN.Inada, AkariInada, OogiFujii, Nobuharu L.Nagafuchi, SeihoKatsuta, HitoshiYasunami, YohichiMatsubara, TakeshiArai, HidenoriFukatsu, AtsushiNabeshima, Yo-ichi2016-03-03T10:59:05-08:00doi:10.1681/ASN.2015070741hwp:resource-id:jnephrol;27/10/3035American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes mellitus, diabetic nephropathy, diabetes, islet beta-cells, hyperglycemiaBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150707411046-66731533-34502016-03-03T10:59:05-08:002016-10Journal of the American Society of NephrologyBasic Research27281010223035292171671630502924716716
- Prorenin Receptor, a Necessary Component in Urine Concentration Mechanism10.1681/ASN.2016030344Wed, 20 Apr 2016 06:42:31 GMT-07:00Prorenin Receptor, a Necessary Component in Urine Concentration MechanismJensen, Boye L.2016-04-20T06:42:31-07:00doi:10.1681/ASN.2016030344hwp:resource-id:jnephrol;27/10/2919American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyaquaporin, diabetes insipidus, prorenin, prostaglandin, vasopressinUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-10-01October 201610.1681/ASN.20160303441046-66731533-34502016-04-20T06:42:31-07:002016-10Journal of the American Society of NephrologyUp Front Matters2710102919302229213034
- Sex Differences and Renal Protection: Keeping in Touch with Your Feminine Side10.1681/ASN.2016040454Tue, 17 May 2016 07:14:26 GMT-07:00Sex Differences and Renal Protection: Keeping in Touch with Your Feminine SideGarovic, Vesna D.August, Phyllis2016-05-17T07:14:26-07:00doi:10.1681/ASN.2016040454hwp:resource-id:jnephrol;27/10/2921American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, hormones, renalUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-10-01October 201610.1681/ASN.20160404541046-66731533-34502016-05-17T07:14:26-07:002016-10Journal of the American Society of NephrologyUp Front Matters27101010292130353051292430503062
- ESRD Payment Reform: First Do No Harm10.1681/ASN.2016020153Tue, 29 Mar 2016 07:00:05 GMT-07:00ESRD Payment Reform: First Do No HarmShen, Jenny I.Norris, Keith C.2016-03-29T07:00:05-07:00doi:10.1681/ASN.2016020153hwp:resource-id:jnephrol;27/10/2924American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, end-stage renal disease, Medicare, Payment ReformUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-10-01October 201610.1681/ASN.20160201531046-66731533-34502016-03-29T07:00:05-07:002016-10Journal of the American Society of NephrologyUp Front Matters2710102924312929263138
- Proton Pump Inhibitors and CKD10.1681/ASN.2016020192Thu, 14 Apr 2016 08:01:56 GMT-07:00Proton Pump Inhibitors and CKDMoledina, Dennis G.Perazella, Mark A.2016-04-14T08:01:56-07:00doi:10.1681/ASN.2016020192hwp:resource-id:jnephrol;27/10/2926American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, acute interstitial nephritis, proton pump inhibitorsUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-10-01October 201610.1681/ASN.20160201921046-66731533-34502016-04-14T08:01:56-07:002016-10Journal of the American Society of NephrologyUp Front Matters2710102926315329283163
- Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug DispositionThe circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question, we performed a combined functional, transcriptomic, and metabolomic analysis in mice with inducible conditional knockout (cKO) of BMAL1, which is critically involved in the circadian clock system, in renal tubular cells (Bmal1lox/lox/Pax8-rtTA/LC1 mice). Induction of cKO in adult mice did not produce obvious abnormalities in renal sodium, potassium, or water handling. Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport in cKO mice compared with control littermates. Furthermore, kidneys from cKO mice exhibited a significant decrease in the NAD+-to-NADH ratio, which reflects the oxidative phosphorylation-to-glycolysis ratio and/or the status of mitochondrial function. Metabolome profiling showed significant changes in plasma levels of amino acids, biogenic amines, acylcarnitines, and lipids. In-depth analysis of two selected pathways revealed a significant increase in plasma urea level correlating with increased renal Arginase II activity, hyperargininemia, and increased kidney arginine content as well as a significant increase in plasma creatinine concentration and a reduced capacity of the kidney to secrete anionic drugs (furosemide) paralleled by an approximate 80% decrease in the expression level of organic anion transporter 3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at the intrarenal and systemic levels and are involved in drug disposition.10.1681/ASN.2015091055Thu, 07 Apr 2016 06:41:15 GMT-07:00Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug DispositionThe circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question, we performed a combined functional, transcriptomic, and metabolomic analysis in mice with inducible conditional knockout (cKO) of BMAL1, which is critically involved in the circadian clock system, in renal tubular cells (Bmal1lox/lox/Pax8-rtTA/LC1 mice). Induction of cKO in adult mice did not produce obvious abnormalities in renal sodium, potassium, or water handling. Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport in cKO mice compared with control littermates. Furthermore, kidneys from cKO mice exhibited a significant decrease in the NAD+-to-NADH ratio, which reflects the oxidative phosphorylation-to-glycolysis ratio and/or the status of mitochondrial function. Metabolome profiling showed significant changes in plasma levels of amino acids, biogenic amines, acylcarnitines, and lipids. In-depth analysis of two selected pathways revealed a significant increase in plasma urea level correlating with increased renal Arginase II activity, hyperargininemia, and increased kidney arginine content as well as a significant increase in plasma creatinine concentration and a reduced capacity of the kidney to secrete anionic drugs (furosemide) paralleled by an approximate 80% decrease in the expression level of organic anion transporter 3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at the intrarenal and systemic levels and are involved in drug disposition.Nikolaeva, SvetlanaAnsermet, CamilleCenteno, GabrielPradervand, SylvainBize, VincentMordasini, DavidHenry, HuguesKoesters, RobertMaillard, MarcBonny, OlivierTokonami, NatsukoFirsov, Dmitri2016-04-07T06:41:15-07:00doi:10.1681/ASN.2015091055hwp:resource-id:jnephrol;27/10/2997American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycircadian clock, organic anion transporter, kidney excretory rhythms, metabolome, arginaseBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150910551046-66731533-34502016-04-07T06:41:15-07:002016-10Journal of the American Society of NephrologyBasic Research271029973004
- MicroRNA-196a/b Mitigate Renal Fibrosis by Targeting TGF-β Receptor 2Organ-specific microRNAs have essential roles in maintaining normal organ function. However, the microRNA profile of the kidney and the role of microRNAs in modulating renal function remain undefined. We performed an unbiased assessment of the genome-wide microRNA expression profile in 14 mouse organs using Solexa deep sequencing and found that microRNA-196a (miR-196a) and miR-196b are selectively expressed in kidney, with 74.37% of mouse total miR-196a and 73.19% of mouse total miR-196b distributed in the kidneys. We confirmed the predominant expression of miR-196a/b in mouse and human kidney, particularly in the glomeruli and tubular epithelium, by quantitative RT-PCR and in situ hybridization assays. During unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis, renal miR-196a/b levels rapidly decreased. Elevation of renal miR-196a/b expression by hydrodynamic-based delivery of a miR-196a/b–expressing plasmid before or shortly after UUO significantly downregulated profibrotic proteins, including collagen 1 and α-smooth muscle actin, and mitigated UUO-induced renal fibrosis. In contrast, depletion of renal miR-196a/b by miR-196a/b antagomirs substantially aggravated UUO-induced renal fibrosis. Mechanistic studies further identified transforming growth factor beta receptor II (TGFβR2) as a common target of miR-196a and miR-196b. Decreasing miR-196a/b expression in human HK2 cells strongly activated TGF-β–Smad signaling and cell fibrosis; whereas increasing miR-196a/b levels in mouse primary cultured tubular epithelial cells inhibited TGF-β–Smad signaling. In the UUO model, miR-196a/b silenced TGF-β–Smad signaling, decreased the expression of collagen 1 and α-smooth muscle actin, and attenuated renal fibrosis. Our findings suggest that elevating renal miR-196a/b levels may be a novel therapeutic strategy for treating renal fibrosis.10.1681/ASN.2015040422Thu, 03 Mar 2016 10:59:03 GMT-08:00MicroRNA-196a/b Mitigate Renal Fibrosis by Targeting TGF-β Receptor 2Organ-specific microRNAs have essential roles in maintaining normal organ function. However, the microRNA profile of the kidney and the role of microRNAs in modulating renal function remain undefined. We performed an unbiased assessment of the genome-wide microRNA expression profile in 14 mouse organs using Solexa deep sequencing and found that microRNA-196a (miR-196a) and miR-196b are selectively expressed in kidney, with 74.37% of mouse total miR-196a and 73.19% of mouse total miR-196b distributed in the kidneys. We confirmed the predominant expression of miR-196a/b in mouse and human kidney, particularly in the glomeruli and tubular epithelium, by quantitative RT-PCR and in situ hybridization assays. During unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis, renal miR-196a/b levels rapidly decreased. Elevation of renal miR-196a/b expression by hydrodynamic-based delivery of a miR-196a/b–expressing plasmid before or shortly after UUO significantly downregulated profibrotic proteins, including collagen 1 and α-smooth muscle actin, and mitigated UUO-induced renal fibrosis. In contrast, depletion of renal miR-196a/b by miR-196a/b antagomirs substantially aggravated UUO-induced renal fibrosis. Mechanistic studies further identified transforming growth factor beta receptor II (TGFβR2) as a common target of miR-196a and miR-196b. Decreasing miR-196a/b expression in human HK2 cells strongly activated TGF-β–Smad signaling and cell fibrosis; whereas increasing miR-196a/b levels in mouse primary cultured tubular epithelial cells inhibited TGF-β–Smad signaling. In the UUO model, miR-196a/b silenced TGF-β–Smad signaling, decreased the expression of collagen 1 and α-smooth muscle actin, and attenuated renal fibrosis. Our findings suggest that elevating renal miR-196a/b levels may be a novel therapeutic strategy for treating renal fibrosis.Meng, JiaoLi, LiminZhao, YueZhou, ZhenZhang, MingchaoLi, DonghaiZhang, Chen-YuZen, KeLiu, Zhihong2016-03-03T10:59:03-08:00doi:10.1681/ASN.2015040422hwp:resource-id:jnephrol;27/10/3006American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologymicroRNA, renal fibrosis, TGFβR2Basic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150404221046-66731533-34502016-03-03T10:59:03-08:002016-10Journal of the American Society of NephrologyBasic Research271030063021
- Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4. Notably, EP4 also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4 and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4 antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4 receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.10.1681/ASN.2015050592Mon, 21 Mar 2016 09:47:58 GMT-07:00Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE2 receptor EP4. Notably, EP4 also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP4 and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP4 antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP4 receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE2/EP4/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.Wang, FeiLu, XiaohanPeng, KexinFang, HuiZhou, LiSu, JiahuiNau, AdamYang, Kevin T.Ichihara, AtsuhiroLu, AihuaZhou, Shu-FengYang, Tianxin2016-03-21T09:47:58-07:00doi:10.1681/ASN.2015050592hwp:resource-id:jnephrol;27/10/3022American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrology(Pro)renin receptor, aquaporin-2, nephrogenic diabetes insipidus, vasopressin, prostaglandin EP4 receptorBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150505921046-66731533-34502016-03-21T09:47:58-07:002016-10Journal of the American Society of NephrologyBasic Research2710103022291930342921
- Blockade of Orai1 Store-Operated Calcium Entry Protects against Renal FibrosisEvidence supports an important role of Ca2+ release-activated Ca2+ channel protein 1 (Orai1)-mediated Ca2+ entry in the development of renal fibrosis, a common pathologic feature of CKDs that lead to ESRD, but the molecular mechanisms remain unclear. We determined the role of Orai1 calcium channel in renal fibrosis induced by high-fat diet and by unilateral ureteral obstruction. Mouse kidneys with fibrosis had higher levels of Orai1 protein expression than did kidneys without fibrosis. In vivo knockdown of Orai1 with adenovirus harboring Orai1–short hairpin RNA or inhibition of Orai1 with SKF96365 dramatically prevented renal fibrosis and significantly decreased protein expression of fibronectin, α‑smooth muscle actin, and TGF‑β1 in the kidney cortex of ApoE–/– mice on a high-fat diet and in the obstructed kidneys of mice with unilateral ureteral obstruction. Compared with kidney biopsy specimens of patients with glomerular minimal change disease, those of patients with fibrotic nephropathy had higher expression levels of Orai1. In cultured human proximal tubule epithelial cells (HK2), knockdown of Orai1 Ca2+ channel with adenovirus–Orai1–short hairpin RNA markedly inhibited TGF-β1–induced intracellular Ca2+ influx and phosphorylation of smad2/3. Knockdown or blockade of the Orai1 Ca2+ channel in HK2 cells also prevented epithelial-to-mesenchymal transition induced by TGF‑β1. In conclusion, blockade of the Orai1 Ca2+ channel prevented progression of renal fibrosis in mice, likely by suppressing smad2/3 phosphorylation and TGF-β1–induced epithelial-to-mesenchymal transition. These results render the Orai1 Ca2+ channel a potential therapeutic target against renal fibrosis.10.1681/ASN.2015080889Thu, 03 Mar 2016 10:59:07 GMT-08:00Blockade of Orai1 Store-Operated Calcium Entry Protects against Renal FibrosisEvidence supports an important role of Ca2+ release-activated Ca2+ channel protein 1 (Orai1)-mediated Ca2+ entry in the development of renal fibrosis, a common pathologic feature of CKDs that lead to ESRD, but the molecular mechanisms remain unclear. We determined the role of Orai1 calcium channel in renal fibrosis induced by high-fat diet and by unilateral ureteral obstruction. Mouse kidneys with fibrosis had higher levels of Orai1 protein expression than did kidneys without fibrosis. In vivo knockdown of Orai1 with adenovirus harboring Orai1–short hairpin RNA or inhibition of Orai1 with SKF96365 dramatically prevented renal fibrosis and significantly decreased protein expression of fibronectin, α‑smooth muscle actin, and TGF‑β1 in the kidney cortex of ApoE–/– mice on a high-fat diet and in the obstructed kidneys of mice with unilateral ureteral obstruction. Compared with kidney biopsy specimens of patients with glomerular minimal change disease, those of patients with fibrotic nephropathy had higher expression levels of Orai1. In cultured human proximal tubule epithelial cells (HK2), knockdown of Orai1 Ca2+ channel with adenovirus–Orai1–short hairpin RNA markedly inhibited TGF-β1–induced intracellular Ca2+ influx and phosphorylation of smad2/3. Knockdown or blockade of the Orai1 Ca2+ channel in HK2 cells also prevented epithelial-to-mesenchymal transition induced by TGF‑β1. In conclusion, blockade of the Orai1 Ca2+ channel prevented progression of renal fibrosis in mice, likely by suppressing smad2/3 phosphorylation and TGF-β1–induced epithelial-to-mesenchymal transition. These results render the Orai1 Ca2+ channel a potential therapeutic target against renal fibrosis.Mai, XiaoyiShang, JinyanLiang, SijiaYu, BeixinYuan, JianiLin, YuLuo, RenfeiZhang, FeiranLiu, YingyingLv, XiaofeiLi, ChunlingLiang, XinlingWang, WeidongZhou, Jiaguo2016-03-03T10:59:07-08:00doi:10.1681/ASN.2015080889hwp:resource-id:jnephrol;27/10/3063American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyOrai1, EMT, renal fibrosisBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150808891046-66731533-34502016-03-03T10:59:07-08:002016-10Journal of the American Society of NephrologyBasic Research271030633078
- Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole GlomeruliPodocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.10.1681/ASN.2015121340Mon, 14 Mar 2016 06:33:06 GMT-07:00Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole GlomeruliPodocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli.Puelles, Victor G.van der Wolde, James W.Schulze, Keith E.Short, Kieran M.Wong, Milagros N.Bensley, Jonathan G.Cullen-McEwen, Luise A.Caruana, GeorginaHokke, Stacey N.Li, JinhuaFirth, Stephen D.Harper, Ian S.Nikolic-Paterson, David J.Bertram, John F.2016-03-14T06:33:06-07:00doi:10.1681/ASN.2015121340hwp:resource-id:jnephrol;27/10/3093American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, renal morphology, glomerular diseaseBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20151213401046-66731533-34502016-03-14T06:33:06-07:002016-10Journal of the American Society of NephrologyBasic Research271030933104
- Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRDThe association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2 blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2 blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31–90, 91–180, 181–360, and 361–720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.10.1681/ASN.2015121377Thu, 14 Apr 2016 08:01:55 GMT-07:00Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRDThe association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (n=173,321) and new users of histamine H2-receptor antagonists (H2 blockers; n=20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H2 blockers group, had an increased risk of incident eGFR<60 ml/min per 1.73 m2 and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline >30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31–90, 91–180, 181–360, and 361–720 days compared with those exposed for ≤30 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H2 blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.Xie, YanBowe, BenjaminLi, TingtingXian, HongBalasubramanian, SumitraAl-Aly, Ziyad2016-04-14T08:01:55-07:00doi:10.1681/ASN.2015121377hwp:resource-id:jnephrol;27/10/3153American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, chronic kidney disease, renal progression, progression of chronic renal failure, Epidemiology and outcomes, clinical epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20162016-10-01October 201610.1681/ASN.20151213771046-66731533-34502016-04-14T08:01:55-07:002016-10Journal of the American Society of NephrologyClinical Epidemiology2710103153292631632928
- Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension TrialApolipoprotein L-1 (APOL1) high–risk alleles and the glutathione-S-transferase-μ1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high–risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high– or low–risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.73 m2 decline), incident ESRD, death, or composite outcomes. The groups differed significantly in event-free survival for incident ESRD and composite outcomes (P≤0.001 by log-rank test). Compared with the reference GSTM1 active/APOL1 low–risk group, other groups had these hazard ratios for the composite outcome of incident ESRD and change in GFR: GSTM1 active/APOL1 high–risk hazard ratio, 2.13; 95% confidence interval, 0.76 to 5.90 (P=0.15); GSTM1 null/APOL1 low–risk hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.88 (P=0.03); and GSTM1 null/APOL1 high–risk hazard ratio, 3.0; 95% confidence interval, 1.51 to 5.96 (P=0.002). In conclusion, GSTM1 null and APOL1 high–risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high–risk genotypes had highest risk of adverse renal outcomes. Larger cohorts are needed to fully explore interactions of GSTM1 and APOL1 genotypes in other subgroups.10.1681/ASN.2015050487Thu, 03 Mar 2016 10:58:59 GMT-08:00Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension TrialApolipoprotein L-1 (APOL1) high–risk alleles and the glutathione-S-transferase-μ1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high–risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high– or low–risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.73 m2 decline), incident ESRD, death, or composite outcomes. The groups differed significantly in event-free survival for incident ESRD and composite outcomes (P≤0.001 by log-rank test). Compared with the reference GSTM1 active/APOL1 low–risk group, other groups had these hazard ratios for the composite outcome of incident ESRD and change in GFR: GSTM1 active/APOL1 high–risk hazard ratio, 2.13; 95% confidence interval, 0.76 to 5.90 (P=0.15); GSTM1 null/APOL1 low–risk hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.88 (P=0.03); and GSTM1 null/APOL1 high–risk hazard ratio, 3.0; 95% confidence interval, 1.51 to 5.96 (P=0.002). In conclusion, GSTM1 null and APOL1 high–risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high–risk genotypes had highest risk of adverse renal outcomes. Larger cohorts are needed to fully explore interactions of GSTM1 and APOL1 genotypes in other subgroups.Bodonyi-Kovacs, GaborMa, Jennie Z.Chang, JamisonLipkowitz, Michael S.Kopp, Jeffrey B.Winkler, Cheryl AnnLe, Thu H.2016-03-03T10:58:59-08:00doi:10.1681/ASN.2015050487hwp:resource-id:jnephrol;27/10/3140American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), genetic renal disease, kidney diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20162016-10-01October 201610.1681/ASN.20150504871046-66731533-34502016-03-03T10:58:59-08:002016-10Journal of the American Society of NephrologyClinical Epidemiology271031403152
- Predicting Individual Renal Allograft Outcomes Using Risk Models with 1-Year Surveillance Biopsy and Alloantibody DataThe ability to predict outcomes for individual patients would be a significant advance for not only counseling, but also identifying those for whom interventions may be needed. The goals of this study were to validate an existing risk prediction score that incorporates easily obtainable clinical factors and determine if histologic findings at 1-year surveillance biopsy and/or serum donor–specific alloantibody status could improve predictability of graft loss by 5 years. We retrospectively studied 1465 adults who received a solitary kidney transplant between January of 1999 and December of 2008 and had sufficiently detailed 5-year follow-up data for modeling. In this cohort, the Birmingham risk model (incorporating recipient factors at 1 year, including age, sex, ethnicity, renal function, proteinuria, and prior acute rejection) predicted death–censored and overall graft survival (c statistics =0.84 and 0.78, respectively). The presence of glomerulitis or chronic interstitial fibrosis (g and ci scores by Banff, respectively) on 1-year biopsy specimens independently correlated with graft loss by 5 years. Adding these variables to the model for death–censored graft loss increased predictability (c statistic =0.90), improved calibration (ability to stratify risk from high to low), and reclassified risk of failure in 29% of patients. Adding the presence of donor-specific alloantibody at 1 year did not improve predictability or reclassification but did improve calibration marginally. We conclude that, at 1 year after kidney transplant, a risk model of graft survival that incorporates clinical factors and histologic findings at surveillance biopsy is highly predictive of individual risk and well calibrated.10.1681/ASN.2015070811Wed, 09 Mar 2016 09:59:01 GMT-08:00Predicting Individual Renal Allograft Outcomes Using Risk Models with 1-Year Surveillance Biopsy and Alloantibody DataThe ability to predict outcomes for individual patients would be a significant advance for not only counseling, but also identifying those for whom interventions may be needed. The goals of this study were to validate an existing risk prediction score that incorporates easily obtainable clinical factors and determine if histologic findings at 1-year surveillance biopsy and/or serum donor–specific alloantibody status could improve predictability of graft loss by 5 years. We retrospectively studied 1465 adults who received a solitary kidney transplant between January of 1999 and December of 2008 and had sufficiently detailed 5-year follow-up data for modeling. In this cohort, the Birmingham risk model (incorporating recipient factors at 1 year, including age, sex, ethnicity, renal function, proteinuria, and prior acute rejection) predicted death–censored and overall graft survival (c statistics =0.84 and 0.78, respectively). The presence of glomerulitis or chronic interstitial fibrosis (g and ci scores by Banff, respectively) on 1-year biopsy specimens independently correlated with graft loss by 5 years. Adding these variables to the model for death–censored graft loss increased predictability (c statistic =0.90), improved calibration (ability to stratify risk from high to low), and reclassified risk of failure in 29% of patients. Adding the presence of donor-specific alloantibody at 1 year did not improve predictability or reclassification but did improve calibration marginally. We conclude that, at 1 year after kidney transplant, a risk model of graft survival that incorporates clinical factors and histologic findings at surveillance biopsy is highly predictive of individual risk and well calibrated.Gonzales, Manuel MorenoBentall, AndrewKremers, Walter K.Stegall, Mark D.Borrows, Richard2016-03-09T09:59:01-08:00doi:10.1681/ASN.2015070811hwp:resource-id:jnephrol;27/10/3165American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant outcomes, albuminuria, chronic allograft failure, renal, transplantation, kidney biopsy, mortality riskClinical ResearchClinical Researchresearch-article20162016-10-01October 201610.1681/ASN.20150708111046-66731533-34502016-03-09T09:59:01-08:002016-10Journal of the American Society of NephrologyClinical Research271031653174
- Polymorphisms in α-Defensin–Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral RefluxThe contribution of genetic variation to urinary tract infection (UTI) risk in children with vesicoureteral reflux is largely unknown. The innate immune system, which includes antimicrobial peptides, such as the α-defensins, encoded by DEFA1A3, is important in preventing UTIs but has not been investigated in the vesicoureteral reflux population. We used quantitative real–time PCR to determine DEFA1A3 DNA copy numbers in 298 individuals with confirmed UTIs and vesicoureteral reflux from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Study and 295 controls, and we correlated copy numbers with outcomes. Outcomes studied included reflux grade, UTIs during the study on placebo or antibiotics, bowel and bladder dysfunction, and renal scarring. Overall, 29% of patients and 16% of controls had less than or equal to five copies of DEFA1A3 (odds ratio, 2.09; 95% confidence interval, 1.40 to 3.11; P<0.001). For each additional copy of DEFA1A3, the odds of recurrent UTI in patients receiving antibiotic prophylaxis decreased by 47% when adjusting for vesicoureteral reflux grade and bowel and bladder dysfunction. In patients receiving placebo, DEFA1A3 copy number did not associate with risk of recurrent UTI. Notably, we found that DEFA1A3 is expressed in renal epithelium and not restricted to myeloid-derived cells, such as neutrophils. In conclusion, low DEFA1A3 copy number associated with recurrent UTIs in subjects in the RIVUR Study randomized to prophylactic antibiotics, providing evidence that copy number polymorphisms in an antimicrobial peptide associate with UTI risk.10.1681/ASN.2015060700Thu, 03 Mar 2016 10:59:01 GMT-08:00Polymorphisms in α-Defensin–Encoding DEFA1A3 Associate with Urinary Tract Infection Risk in Children with Vesicoureteral RefluxThe contribution of genetic variation to urinary tract infection (UTI) risk in children with vesicoureteral reflux is largely unknown. The innate immune system, which includes antimicrobial peptides, such as the α-defensins, encoded by DEFA1A3, is important in preventing UTIs but has not been investigated in the vesicoureteral reflux population. We used quantitative real–time PCR to determine DEFA1A3 DNA copy numbers in 298 individuals with confirmed UTIs and vesicoureteral reflux from the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Study and 295 controls, and we correlated copy numbers with outcomes. Outcomes studied included reflux grade, UTIs during the study on placebo or antibiotics, bowel and bladder dysfunction, and renal scarring. Overall, 29% of patients and 16% of controls had less than or equal to five copies of DEFA1A3 (odds ratio, 2.09; 95% confidence interval, 1.40 to 3.11; P<0.001). For each additional copy of DEFA1A3, the odds of recurrent UTI in patients receiving antibiotic prophylaxis decreased by 47% when adjusting for vesicoureteral reflux grade and bowel and bladder dysfunction. In patients receiving placebo, DEFA1A3 copy number did not associate with risk of recurrent UTI. Notably, we found that DEFA1A3 is expressed in renal epithelium and not restricted to myeloid-derived cells, such as neutrophils. In conclusion, low DEFA1A3 copy number associated with recurrent UTIs in subjects in the RIVUR Study randomized to prophylactic antibiotics, providing evidence that copy number polymorphisms in an antimicrobial peptide associate with UTI risk.Schwaderer, Andrew L.Wang, HuanyuKim, SungHwanKline, Jennifer M.Liang, DongBrophy, Pat D.McHugh, Kirk M.Tseng, George C.Saxena, VijayBarr-Beare, EvanPierce, Keith R.Shaikh, NaderManak, J. RobertCohen, Daniel M.Becknell, BrianSpencer, John D.Baker, Peter B.Yu, Chack-YungHains, David S.2016-03-03T10:59:01-08:00doi:10.1681/ASN.2015060700hwp:resource-id:jnephrol;27/10/3175American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvesico-ureteral reflux, genetics and development, pyelonephritisClinical ResearchClinical Researchresearch-article20162016-10-01October 201610.1681/ASN.20150607001046-66731533-34502016-03-03T10:59:01-08:002016-10Journal of the American Society of NephrologyClinical Research271031753186
- Fine Mapping Implicates a Deletion of CFHR1 and CFHR3 in Protection from IgA Nephropathy in Han ChineseAn intronic variant at the complement factor H (CFH) gene on chromosome 1q32 (rs6677604) associates with risk of IgA nephropathy (IgAN), but the association signal has not been uniformly replicated in Han Chinese populations. We investigated whether the causal sequence variant resides in the CFH gene or the neighboring complement factor H–related 1 (CFHR1) gene and CFHR3, which harbor an 84-kb combined deletion (CFHR3,1Δ) in linkage disequilibrium with rs6677604. Imputation of 1000 Genomes Project data did not suggest new causal single–nucleotide variants within the CFH cluster. We next performed copy number analysis across the CFH locus in two independent Han Chinese case-control cohorts (combined n=3581). The CFHR3,1Δ and rs6677604-A alleles were rare (4.4% in patients and 7.1% in controls) and in strong linkage disequilibrium with each other (r2=0.95); of these alleles, CFHR3,1Δ associated more significantly with decreased risk of IgAN (odds ratio [OR], 0.56; 95% confidence interval [95% CI], 0.46 to 0.70; P=8.5 × 10−8 versus OR, 0.61; 95% CI, 0.50 to 0.75; P=1.6 × 10−6 for rs6677604-A). Moreover, CFHR3,1Δ explained all of the association signal at rs6677604 and remained significant after conditioning on rs6677604 genotype (P=0.01). Exploratory analyses of clinical and histopathologic parameters using the Oxford classification criteria revealed a suggestive association of CFHR3,1Δ with reduced tubulointerstitial injury (OR, 0.46; 95% CI, 0.25 to 0.79). These data indicate that dysregulated activity of the alternative complement pathway contributes to IgAN pathogenesis in both Asians and Europeans and implicate CFHR3,1Δ as the functional allele at this locus.10.1681/ASN.2015111210Thu, 03 Mar 2016 10:59:06 GMT-08:00Fine Mapping Implicates a Deletion of CFHR1 and CFHR3 in Protection from IgA Nephropathy in Han ChineseAn intronic variant at the complement factor H (CFH) gene on chromosome 1q32 (rs6677604) associates with risk of IgA nephropathy (IgAN), but the association signal has not been uniformly replicated in Han Chinese populations. We investigated whether the causal sequence variant resides in the CFH gene or the neighboring complement factor H–related 1 (CFHR1) gene and CFHR3, which harbor an 84-kb combined deletion (CFHR3,1Δ) in linkage disequilibrium with rs6677604. Imputation of 1000 Genomes Project data did not suggest new causal single–nucleotide variants within the CFH cluster. We next performed copy number analysis across the CFH locus in two independent Han Chinese case-control cohorts (combined n=3581). The CFHR3,1Δ and rs6677604-A alleles were rare (4.4% in patients and 7.1% in controls) and in strong linkage disequilibrium with each other (r2=0.95); of these alleles, CFHR3,1Δ associated more significantly with decreased risk of IgAN (odds ratio [OR], 0.56; 95% confidence interval [95% CI], 0.46 to 0.70; P=8.5 × 10−8 versus OR, 0.61; 95% CI, 0.50 to 0.75; P=1.6 × 10−6 for rs6677604-A). Moreover, CFHR3,1Δ explained all of the association signal at rs6677604 and remained significant after conditioning on rs6677604 genotype (P=0.01). Exploratory analyses of clinical and histopathologic parameters using the Oxford classification criteria revealed a suggestive association of CFHR3,1Δ with reduced tubulointerstitial injury (OR, 0.46; 95% CI, 0.25 to 0.79). These data indicate that dysregulated activity of the alternative complement pathway contributes to IgAN pathogenesis in both Asians and Europeans and implicate CFHR3,1Δ as the functional allele at this locus.Xie, JingyuanKiryluk, KrzysztofLi, YifuMladkova, NikolZhu, LiHou, PingRen, HongWang, WeimingZhang, HongChen, NanGharavi, Ali G.2016-03-03T10:59:06-08:00doi:10.1681/ASN.2015111210hwp:resource-id:jnephrol;27/10/3187American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, IgA nephropathy, complement, human geneticsClinical ResearchClinical Researchresearch-article20162016-10-01October 201610.1681/ASN.20151112101046-66731533-34502016-03-03T10:59:06-08:002016-10Journal of the American Society of NephrologyClinical Research271031873194
- Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous NephropathySerum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb− (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb−/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.10.1681/ASN.2015080953Thu, 17 Mar 2016 07:24:37 GMT-07:00Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous NephropathySerum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb− (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb−/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.Qin, Hua-ZhangZhang, Ming-ChaoLe, Wei-BoRen, QiangChen, Da-ChengZeng, Cai-HongLiu, LeiZuo, KeXu, FengLiu, Zhi-Hong2016-03-17T07:24:37-07:00doi:10.1681/ASN.2015080953hwp:resource-id:jnephrol;27/10/3195American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, membranous nephropathy, primary glomerulonephritisClinical ResearchClinical Researchresearch-article20162016-10-01October 201610.1681/ASN.20150809531046-66731533-34502016-03-17T07:24:37-07:002016-10Journal of the American Society of NephrologyClinical Research271031953203
- YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal FibrogenesisLike many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-β responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-β. In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-β–induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-β stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-β to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-β/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-β signaling and renal fibrogenesis.10.1681/ASN.2015050499Wed, 09 Mar 2016 09:59:00 GMT-08:00YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal FibrogenesisLike many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-β responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-β. In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-β–induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-β stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-β to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-β/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-β signaling and renal fibrogenesis.Szeto, Stephen G.Narimatsu, MasahiroLu, MingliangHe, XiaolinSidiqi, Ahmad M.Tolosa, Monica F.Chan, LaurenDe Freitas, KrystaleBialik, Janne FolkeMajumder, SyamantakBoo, StellarHinz, BorisDan, QinghongAdvani, AndrewJohn, RohanWrana, Jeffrey L.Kapus, AndrasYuen, Darren A.2016-03-09T09:59:00-08:00doi:10.1681/ASN.2015050499hwp:resource-id:jnephrol;27/10/3117American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, extracellular matrix, fibrosis, TGF-beta, YAP, TAZBasic ResearchBasic Researchresearch-article20162016-10-01October 201610.1681/ASN.20150504991046-66731533-34502016-03-09T09:59:00-08:002016-10Journal of the American Society of NephrologyBasic Research271031173128
- Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment ReformErythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005–2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: −0.24 [−0.08 to −0.37] for stroke, −2.43 [−1.35 to −3.70] for VTE, and −0.77 [−0.28 to −1.27] for heart failure), although non–ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.10.1681/ASN.2015111232Thu, 25 Feb 2016 01:28:07 GMT-08:00Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment ReformErythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005–2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: −0.24 [−0.08 to −0.37] for stroke, −2.43 [−1.35 to −3.70] for VTE, and −0.77 [−0.28 to −1.27] for heart failure), although non–ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.Chertow, Glenn M.Liu, JiannongMonda, Keri L.Gilbertson, David T.Brookhart, M. AlanBeaubrun, Anne C.Winkelmayer, Wolfgang C.Pollock, AllanHerzog, Charles A.Ashfaq, AkhtarSturmer, TilRothman, Kenneth J.Bradbury, Brian D.Collins, Allan J.2016-02-25T13:28:07-08:00doi:10.1681/ASN.2015111232hwp:resource-id:jnephrol;27/10/3129American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, health policy, erythropoietin, cardiovascular events, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20162016-10-01October 201610.1681/ASN.20151112321046-66731533-34502016-02-25T13:28:07-08:002016-10Journal of the American Society of NephrologyClinical Epidemiology2710103129292431382926
- Pragmatic, Precision Medicine Approaches for Dialysis Vascular Access Dysfunction: Challenges and Opportunities10.2215/CJN.08160816Tue, 30 Aug 2016 06:16:50 GMT-07:00Pragmatic, Precision Medicine Approaches for Dialysis Vascular Access Dysfunction: Challenges and OpportunitiesRoy-Chaudhury, Prabir2016-08-30T06:16:50-07:00doi:10.2215/CJN.08160816hwp:resource-id:clinjasn;11/9/1525American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, dialysis, arteriovenous fistula, Arteriovenous Shunt, Surgical, Communication, Fluid Therapy, Precision Medicine, renal dialysisEditorialsEditorialseditorial20162016-09-07September 07, 201610.2215/CJN.081608161555-90411555-905X2016-08-30T06:16:50-07:002016-09-07Clinical Journal of the American Society of NephrologyEditorials11991525161515261623
- What Is the Correct Approach for Comparing GFR by Different Methods across Levels of GFR?10.2215/CJN.07530716Wed, 03 Aug 2016 05:53:59 GMT-07:00What Is the Correct Approach for Comparing GFR by Different Methods across Levels of GFR?Rule, Andrew D.Kremers, Walter K.2016-08-03T05:53:59-07:00doi:10.2215/CJN.07530716hwp:resource-id:clinjasn;11/9/1518American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular filtration rate, creatinine clearance, renal functionEditorialsEditorialseditorial20162016-09-07September 07, 201610.2215/CJN.075307161555-90411555-905X2016-08-03T05:53:59-07:002016-09-07Clinical Journal of the American Society of NephrologyEditorials11991518157415211581
- Urinary Angiotensinogen: A Promising Biomarker of AKI Progression in Acute Decompensated Heart Failure: What Does It Mean?10.2215/CJN.07780716Thu, 18 Aug 2016 08:15:53 GMT-07:00Urinary Angiotensinogen: A Promising Biomarker of AKI Progression in Acute Decompensated Heart Failure: What Does It Mean?Wysocki, JanBatlle, Daniel2016-08-18T08:15:53-07:00doi:10.2215/CJN.07780716hwp:resource-id:clinjasn;11/9/1515American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyserum creatinine, AKI, GFR, angiotensinogen, Acute Disease, Biomarkers, Disease Progression, heart failureEditorialsEditorialseditorial20162016-09-07September 07, 201610.2215/CJN.077807161555-90411555-905X2016-08-18T08:15:53-07:002016-09-07Clinical Journal of the American Society of NephrologyEditorials11991515153615171544
- Correction10.2215/CJN.07690716Mon, 15 Aug 2016 04:05:39 GMT-07:00CorrectionAmerican Society of Nephrology2016-08-15T04:05:39-07:00doi:10.2215/CJN.07690716hwp:resource-id:clinjasn;11/9/1721American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyErratum, correction, proteinuria, Corticosteroids, Azathioprine, nephropathyErratumErratumcorrection20162016-09-07September 07, 201610.2215/CJN.076907161555-90411555-905X2016-08-15T04:05:39-07:002016-09-07Clinical Journal of the American Society of NephrologyErratum111196617219739731721981981
- Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate10.2215/CJN.13171215Thu, 30 Jun 2016 07:01:42 GMT-07:00Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and MycophenolateTanriover, BekirJaikaransingh, VishalMacConmara, Malcolm P.Parekh, Justin R.Levea, Swee-LingAriyamuthu, Venkatesh K.Zhang, SongGao, AngAyvaci, Mehmet U.S.Sandikci, BurhaneddinRajora, NilumAhmed, VaqarLu, Christopher Y.Mohan, SumitVazquez, Miguel A.2016-06-30T07:01:42-07:00doi:10.2215/CJN.13171215hwp:resource-id:clinjasn;11/9/1650American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyImmunosuppression, kidney transplantation, rejection, Antibodies, Monoclonal, Humanized, Antilymphocyte Serum, Follow-Up Studies, Graft Survival, Humans, Immunosuppressive Agents, Mycophenolic Acid, tacrolimus, Tissue DonorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-09-07September 07, 201610.2215/CJN.131712151555-90411555-905X2016-06-30T07:01:42-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11916501661
- Effect of Tenapanor on Interdialytic Weight Gain in Patients on Hemodialysis10.2215/CJN.09050815Thu, 23 Jun 2016 08:13:29 GMT-07:00Effect of Tenapanor on Interdialytic Weight Gain in Patients on HemodialysisBlock, Geoffrey A.Rosenbaum, David P.Leonsson-Zachrisson, MariaStefansson, Bergur V.Rydén-Bergsten, TinaGreasley, Peter J.Johansson, Susanne A.Knutsson, MikaelCarlsson, Björn C.2016-06-23T08:13:29-07:00doi:10.2215/CJN.09050815hwp:resource-id:clinjasn;11/9/1597American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytenapanor, sodium/hydrogen antiporter, end-stage renal disease, chronic kidney disease stage 5D, Body Weight, Humans, Renal Dialysis, Renal Insufficiency, Chronic, Sodium, Sodium-Hydrogen Antiporter, Weight GainOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-09-07September 07, 201610.2215/CJN.090508151555-90411555-905X2016-06-23T08:13:29-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11915971605
- Alport Syndrome in Women and GirlsAlport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%–30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The “Expert guidelines for the diagnosis and management of Alport syndrome” recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling, informed of their reproductive options, and monitored closely during pregnancy for the development of hypertension.10.2215/CJN.00580116Fri, 10 Jun 2016 06:44:56 GMT-07:00Alport Syndrome in Women and GirlsAlport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%–30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The “Expert guidelines for the diagnosis and management of Alport syndrome” recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling, informed of their reproductive options, and monitored closely during pregnancy for the development of hypertension.Savige, JudyColville, DebRheault, MichelleGear, SusieLennon, RachelLagas, SharonFinlay, MoiraFlinter, Frances2016-06-10T06:44:56-07:00doi:10.2215/CJN.00580116hwp:resource-id:clinjasn;11/9/1713American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, genetic renal disease, ACE inhibitors, albuminuria, Deafness, Female, Genetic Testing, Hearing Loss, Humans, Kidney Failure, Chronic, Mutation, Nephritis, HereditarySpecial FeaturesSpecial Featuresresearch-article20162016-09-07September 07, 201610.2215/CJN.005801161555-90411555-905X2016-06-10T06:44:56-07:002016-09-07Clinical Journal of the American Society of NephrologySpecial Features11917131720
- Preoperative Vascular Medial Fibrosis and Arteriovenous Fistula Development10.2215/CJN.00500116Tue, 30 Aug 2016 06:16:51 GMT-07:00Preoperative Vascular Medial Fibrosis and Arteriovenous Fistula DevelopmentShiu, Yan-TingLitovsky, Silvio H.Cheung, Alfred K.Pike, Daniel B.Tey, Jason Chieh ShengZhang, YingyingYoung, Carlton J.Robbin, MichelleHoyt, KennethAllon, Michael2016-08-30T06:16:51-07:00doi:10.2215/CJN.00500116hwp:resource-id:clinjasn;11/9/1615American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, hemodialysis, fibrosis, arteries, Arteriovenous Shunt, Surgical, Collagen, Demography, Humans, Odds Ratio, Tunica Media, VeinsOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-09-07September 07, 201610.2215/CJN.005001161555-90411555-905X2016-08-30T06:16:51-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11991615152516231526
- Chemistry Testing on Plasma Versus Serum Samples in Dialysis Patients: Clinical and Quality Improvement ImplicationsPlasma samples collected in tubes containing separator gels have replaced serum samples for most chemistry tests in many hospital and commercial laboratories. Use of plasma samples for blood tests in the dialysis population eliminates delays in sample processing while waiting for clotting to complete, laboratory technical issues associated with fibrin formation, repeat sample collection, and patient care issues caused by delay of results because of incompletely clotted specimens. Additionally, a larger volume of plasma is produced than serum for the same amount of blood collected. Plasma samples are also acceptable for most chemical tests involved in the care of patients with ESRD. This information becomes very important when United States regulatory requirements for ESRD inadvertently limit the type of sample that can be used for government reporting, quality assessment, and value–based payment initiatives. In this narrative, we summarize the renal community experience and how the subsequent resolution of the acceptability of phosphorus levels measured from serum and plasma samples may have significant implications in the country’s continued development of a value–based Medicare ESRD Quality Incentive Program.10.2215/CJN.09310915Mon, 16 May 2016 08:36:54 GMT-07:00Chemistry Testing on Plasma Versus Serum Samples in Dialysis Patients: Clinical and Quality Improvement ImplicationsPlasma samples collected in tubes containing separator gels have replaced serum samples for most chemistry tests in many hospital and commercial laboratories. Use of plasma samples for blood tests in the dialysis population eliminates delays in sample processing while waiting for clotting to complete, laboratory technical issues associated with fibrin formation, repeat sample collection, and patient care issues caused by delay of results because of incompletely clotted specimens. Additionally, a larger volume of plasma is produced than serum for the same amount of blood collected. Plasma samples are also acceptable for most chemical tests involved in the care of patients with ESRD. This information becomes very important when United States regulatory requirements for ESRD inadvertently limit the type of sample that can be used for government reporting, quality assessment, and value–based payment initiatives. In this narrative, we summarize the renal community experience and how the subsequent resolution of the acceptability of phosphorus levels measured from serum and plasma samples may have significant implications in the country’s continued development of a value–based Medicare ESRD Quality Incentive Program.Carey, Roger NeillJani, ChinuJohnson, CurtisPearce, JimHui-Ng, PatriciaLacson, Eduardo2016-05-16T08:36:54-07:00doi:10.2215/CJN.09310915hwp:resource-id:clinjasn;11/9/1675American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCMS, National Quality Forum, Hematologic Tests, Humans, Kidney Failure, Chronic, Medicare, Phosphorus, Plasma, Quality Improvement, renal dialysisCommentaryCommentaryarticle-commentary20162016-09-07September 07, 201610.2215/CJN.093109151555-90411555-905X2016-05-16T08:36:54-07:002016-09-07Clinical Journal of the American Society of NephrologyCommentary11916751679
- Hospitalization Rates for Patients on Assisted Peritoneal Dialysis Compared with In-Center Hemodialysis10.2215/CJN.10130915Wed, 27 Jul 2016 06:04:24 GMT-07:00Hospitalization Rates for Patients on Assisted Peritoneal Dialysis Compared with In-Center HemodialysisOliver, Matthew J.Al-Jaishi, Ahmed A.Dixon, Stephanie N.Perl, JeffreyJain, Arsh K.Lavoie, Susan D.Nash, Danielle M.Paterson, J. MichaelLok, Charmaine E.Quinn, Robert R.2016-07-27T06:04:24-07:00doi:10.2215/CJN.10130915hwp:resource-id:clinjasn;11/9/1606American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hospitalization, social support, family, Cohort Studies, Humans, Outpatients, Peritonitis, Propensity Score, renal dialysis, Self CareOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-09-07September 07, 201610.2215/CJN.101309151555-90411555-905X2016-07-27T06:04:24-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11991606152216141524
- Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney DiseasesIncluding target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is “Patient Centered-Research”, in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases.10.2215/CJN.09780915Thu, 19 May 2016 06:54:28 GMT-07:00Patient and Other Stakeholder Engagement in Patient-Centered Outcomes Research Institute Funded Studies of Patients with Kidney DiseasesIncluding target populations in the design and implementation of research trials has been one response to the growing health disparities endemic to our health care system, as well as an aid to study generalizability. One type of community-based participatory research is “Patient Centered-Research”, in which patient perspectives on the germane research questions and methodologies are incorporated into the study. The Patient-Centered Outcomes Research Institute (PCORI) has mandated that meaningful patient and stakeholder engagement be incorporated into all applications. As of March 2015, PCORI funded seven clinically-focused studies of patients with kidney disease. The goal of this paper is to synthesize the experiences of these studies to gain an understanding of how meaningful patient and stakeholder engagement can occur in clinical research of kidney diseases, and what the key barriers are to its implementation. Our collective experience suggests that successful implementation of a patient- and stakeholder-engaged research paradigm involves: (1) defining the roles and process for the incorporation of input; (2) identifying the particular patients and other stakeholders; (3) engaging patients and other stakeholders so they appreciate the value of their own participation and have personal investment in the research process; and (4) overcoming barriers and challenges that arise and threaten the productivity of the collaboration. It is our hope that the experiences of these studies will further interest and capacity for incorporating patient and stakeholder perspectives in research of kidney diseases.Cukor, DanielCohen, Lewis M.Cope, Elizabeth L.Ghahramani, NasrollahHedayati, S. SusanHynes, Denise M.Shah, Vallabh O.Tentori, FrancescaUnruh, MarkBobelu, JeanetteCohen, ScottDember, Laura M.Faber, ThomasFischer, Michael J.Gallardo, RaniGermain, Michael J.Ghahate, DonicaGrote, NancyHartwell, LoriHeagerty, PatrickKimmel, Paul L.Kutner, NancyLawson, SusanMarr, LisaNelson, Robert G.Porter, Anna C.Sandy, PhillipStruminger, Bruce B.Subramanian, LalitaWeisbord, SteveYoung, BessieMehrotra, Rajnish2016-05-19T06:54:28-07:00doi:10.2215/CJN.09780915hwp:resource-id:clinjasn;11/9/1703American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical nephrology, randomized controlled trials, depression, diabetic nephropathy, dialysis, end-stage renal disease, nephrotic syndrome, kidney disease, Community-Based Participatory Research, Humans, Patient Outcome AssessmentSpecial FeaturesSpecial Featuresresearch-article20162016-09-07September 07, 201610.2215/CJN.097809151555-90411555-905X2016-05-19T06:54:28-07:002016-09-07Clinical Journal of the American Society of NephrologySpecial Features11917031712
- Functional and Cognitive Impairment, Frailty, and Adverse Health Outcomes in Older Patients Reaching ESRD—A Systematic Review10.2215/CJN.13611215Fri, 24 Jun 2016 06:51:08 GMT-07:00Functional and Cognitive Impairment, Frailty, and Adverse Health Outcomes in Older Patients Reaching ESRD—A Systematic ReviewKallenberg, Marije H.Kleinveld, Hilda A.Dekker, Friedo W.van Munster, Barbara C.Rabelink, Ton J.van Buren, MarjolijnMooijaart, Simon P.2016-06-24T06:51:08-07:00doi:10.2215/CJN.13611215hwp:resource-id:clinjasn;11/9/1624American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage renal disease, dialysis, functional impairment, cognitive impairment, frail elderly, Cognition Disorders, Follow-Up Studies, Humans, Kidney Failure, Chronic, Outcome Assessment (Health Care), renal dialysis, Renal Replacement TherapyOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20162016-09-07September 07, 201610.2215/CJN.136112151555-90411555-905X2016-06-24T06:51:08-07:002016-09-07Clinical Journal of the American Society of NephrologyOriginal Articles11916241639
- Urinary Soluble CD163 in Active Renal VasculitisA specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.10.1681/ASN.2015050511Thu, 03 Mar 2016 10:58:59 GMT-08:00Urinary Soluble CD163 in Active Renal VasculitisA specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV.O’Reilly, Vincent P.Wong, LimyKennedy, ClaireElliot, Louise A.O’Meachair, ShaneCoughlan, Alice MarieO’Brien, Eoin C.Ryan, Michelle M.Sandoval, DiegoConnolly, EmmaDekkema, Gerjan J.Lau, JiayingAbdulahad, Wayel H.Sanders, Jan-Stephan F.Heeringa, PeterBuckley, ColmO’Brien, CathalFinn, StephenCohen, Clemens D.Lindemeyer, Maja T.Hickey, Fionnuala B.O’Hara, Paul V.Feighery, ConlethMoran, Sarah M.Mellotte, GeorgeClarkson, Michael R.Dorman, Anthony J.Murray, Patrick T.Little, Mark A.2016-03-03T10:58:59-08:00doi:10.1681/ASN.2015050511hwp:resource-id:jnephrol;27/9/2906American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, ANCA, glomerulonephritis, nephrology, renal injury, vasculitisClinical ResearchClinical Researchresearch-article20162016-09-01September 201610.1681/ASN.20150505111046-66731533-34502016-03-03T10:58:59-08:002016-09Journal of the American Society of NephrologyClinical Research2729998290625512255291625532255
- IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial DepositionIgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch–Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen–free environment had less IgA deposition. However, serum IgA of specific pathogen–free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α1KI, and even J chain–deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post–translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.10.1681/ASN.2015080911Fri, 29 Jan 2016 09:12:17 GMT-08:00IgA Structure Variations Associate with Immune Stimulations and IgA Mesangial DepositionIgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch–Schönlein purpura, the onset of which often follows infections. Deposited IgA has been reported as polymeric, J chain associated, and often, hypogalactosylated but with no information concerning the influence of the IgA repertoire or the link between immune stimuli and IgA structure. We explored these issues in the α1KI mouse model, which produces polyclonal human IgA1 prone to mesangial deposition. Compared with mice challenged by a conventional environment, mice in a specific pathogen–free environment had less IgA deposition. However, serum IgA of specific pathogen–free mice showed more galactosylation and much lower polymerization. Notably, wild-type, α1KI, and even J chain–deficient mice showed increased polymeric serum IgA on exposure to pathogens. Strict germfree conditions delayed but did not completely prevent deposition; mice housed in these conditions had very low serum IgA levels and produced essentially monomeric IgA. Finally, comparing monoclonal IgA1 that had different variable regions and mesangial deposition patterns indicated that, independently of glycosylation and polymerization, deposition might also depend on IgA carrying specific variable domains. Together with IgA quantities and constant region post–translational modifications, repertoire changes during immune responses might, thus, modulate IgA propensity to deposition. These IgA features are not associated with circulating immune complexes and C3 deposition and are more pertinent to an initial IgA deposition step preceding overt clinical symptoms in patients.Oruc, ZelihaOblet, ChristelleBoumediene, AhmedDruilhe, AnnePascal, VirginieLe Rumeur, ElisabethCuvillier, ArmelleEl Hamel, ChahrazedLecardeur, SandrineLeanderson, TomasMorelle, WillyDemengeot, JocelyneAldigier, Jean-ClaudeCogné, Michel2016-01-29T09:12:17-08:00doi:10.1681/ASN.2015080911hwp:resource-id:jnephrol;27/9/2748American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, IgA deposition, IgA, transgenic mouse, Immunology and pathologyBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150809111046-66731533-34502016-01-29T09:12:17-08:002016-09Journal of the American Society of NephrologyBasic Research27927482761
- TRPC6 G757D Loss-of-Function Mutation Associates with FSGSFSGS is a CKD with heavy proteinuria that eventually progresses to ESRD. Hereditary forms of FSGS have been linked to mutations in the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene encoding a nonselective cation channel. Most of these TRPC6 mutations cause a gain-of-function phenotype, leading to calcium–triggered podocyte cell death, but the underlying molecular mechanisms are unclear. We studied the molecular effect of disease-related mutations using tridimensional in silico modeling of tetrameric TRPC6. Our results indicated that G757 is localized in a domain forming a TRPC6-TRPC6 interface and predicted that the amino acid exchange G757D causes local steric hindrance and disruption of the channel complex. Notably, functional characterization of model interface domain mutants suggested a loss-of-function phenotype. We then characterized 19 human FSGS–related TRPC6 mutations, the majority of which caused gain-of-function mutations. However, five mutations (N125S, L395A, G757D, L780P, and R895L) caused a loss-of-function phenotype. Coexpression of wild-type TRPC6 and TRPC6 G757D, mimicking heterozygosity observed in patients, revealed a dominant negative effect of TRPC6 G757D. Our comprehensive analysis of human disease–causing TRPC6 mutations reveals loss of TRPC6 function as an additional concept of hereditary FSGS and provides molecular insights into the mechanism responsible for the loss-of-function phenotype of TRPC6 G757D in humans.10.1681/ASN.2015030318Thu, 18 Feb 2016 07:35:11 GMT-08:00TRPC6 G757D Loss-of-Function Mutation Associates with FSGSFSGS is a CKD with heavy proteinuria that eventually progresses to ESRD. Hereditary forms of FSGS have been linked to mutations in the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene encoding a nonselective cation channel. Most of these TRPC6 mutations cause a gain-of-function phenotype, leading to calcium–triggered podocyte cell death, but the underlying molecular mechanisms are unclear. We studied the molecular effect of disease-related mutations using tridimensional in silico modeling of tetrameric TRPC6. Our results indicated that G757 is localized in a domain forming a TRPC6-TRPC6 interface and predicted that the amino acid exchange G757D causes local steric hindrance and disruption of the channel complex. Notably, functional characterization of model interface domain mutants suggested a loss-of-function phenotype. We then characterized 19 human FSGS–related TRPC6 mutations, the majority of which caused gain-of-function mutations. However, five mutations (N125S, L395A, G757D, L780P, and R895L) caused a loss-of-function phenotype. Coexpression of wild-type TRPC6 and TRPC6 G757D, mimicking heterozygosity observed in patients, revealed a dominant negative effect of TRPC6 G757D. Our comprehensive analysis of human disease–causing TRPC6 mutations reveals loss of TRPC6 function as an additional concept of hereditary FSGS and provides molecular insights into the mechanism responsible for the loss-of-function phenotype of TRPC6 G757D in humans.Riehle, MarcBüscher, Anja K.Gohlke, Björn-OliverKaßmann, MarioKolatsi-Joannou, MariaBräsen, Jan H.Nagel, MatoBecker, Jan U.Winyard, PaulHoyer, Peter F.Preissner, RobertKrautwurst, DietmarGollasch, MaikWeber, StefanieHarteneck, Christian2016-02-18T07:35:11-08:00doi:10.1681/ASN.2015030318hwp:resource-id:jnephrol;27/9/2771American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, glomerulosclerosis, ion channel, calcium, kidney diseaseBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150303181046-66731533-34502016-02-18T07:35:11-08:002016-09Journal of the American Society of NephrologyBasic Research27927712783
- Re-Examining Risk of Repeated HLA Mismatch in Kidney TransplantationKidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all–cause or death–censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death–censored graft loss, particularly in patients with detectable panel–reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all–cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death–censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients.10.1681/ASN.2015060626Wed, 17 Feb 2016 07:14:32 GMT-08:00Re-Examining Risk of Repeated HLA Mismatch in Kidney TransplantationKidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all–cause or death–censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death–censored graft loss, particularly in patients with detectable panel–reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all–cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death–censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients.Tinckam, Kathryn J.Rose, CarenHariharan, SundaramGill, John2016-02-17T07:14:32-08:00doi:10.1681/ASN.2015060626hwp:resource-id:jnephrol;27/9/2833American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant nephrectomy, chronic allograft failure, transplant outcomes, kidney transplantation, renal transplantation, transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20162016-09-01September 201610.1681/ASN.20150606261046-66731533-34502016-02-17T07:14:32-08:002016-09Journal of the American Society of NephrologyClinical Epidemiology27928332841
- The Search for a Biomarker of Relapse in ANCA-Associated Vasculitis10.1681/ASN.2016030347Mon, 09 May 2016 06:33:55 GMT-07:00The Search for a Biomarker of Relapse in ANCA-Associated VasculitisFree, Meghan E.Falk, Ronald J.2016-05-09T06:33:55-07:00doi:10.1681/ASN.2016030347hwp:resource-id:jnephrol;27/9/2551American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyANCA vasculitis, biomarker, relapse, remissionUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-09-01September 201610.1681/ASN.20160303471046-66731533-34502016-05-09T06:33:55-07:002016-09Journal of the American Society of NephrologyUp Front Matters27992551290625532916
- MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic NephropathyDiabetic nephropathy (DN) is a frequent and severe complication of diabetes that is structurally characterized by glomerular basement membrane thickening, extracellular matrix accumulation, and destabilization of podocyte foot processes. MicroRNAs (miRNAs) are dysregulated in DN, but identification of the specific miRs involved remains incomplete. Here, we confirm that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of miR-23b compared with those of their nondiabetic counterparts. Furthermore, exposure to high glucose downregulated miR-23b in cultured kidney cells. In contrast, renal expression of Ras GTPase-activating protein SH3 domain-binding protein 2 (G3BP2), a putative miR-23b target, increased in DN. In vitro, overexpression of miR-23b decreased, and inhibition of miR-23b increased, G3BP2 expression levels. Bioinformatics analysis also revealed p53 binding sites in the miR-23b promoter; in vitro inhibition of p53 or the upstream p38 mitogen-activated protein kinase (p38MAPK) upregulated miR-23b expression in high-glucose conditions. In turn, inhibition of G3BP2 or overexpression of miR-23b downregulated p53 and p38MAPK expression in high-glucose conditions. In vivo, overexpression of miR-23b or inhibition of p53 in db/db mice reversed hyperalbuminuria and kidney fibrosis, whereas miR-23b antagomir treatment promoted renal fibrosis and increased albuminuria in wild-type mice. These data suggest that hyperglycemia regulates pathogenic processes in DN through an miR-23b/G3BP2 feedback circuit involving p38MAPK and p53. In conclusion, these results reveal a role for miR-23b in DN and indicate a novel potential therapeutic target.10.1681/ASN.2015030300Tue, 02 Feb 2016 06:15:34 GMT-08:00MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic NephropathyDiabetic nephropathy (DN) is a frequent and severe complication of diabetes that is structurally characterized by glomerular basement membrane thickening, extracellular matrix accumulation, and destabilization of podocyte foot processes. MicroRNAs (miRNAs) are dysregulated in DN, but identification of the specific miRs involved remains incomplete. Here, we confirm that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of miR-23b compared with those of their nondiabetic counterparts. Furthermore, exposure to high glucose downregulated miR-23b in cultured kidney cells. In contrast, renal expression of Ras GTPase-activating protein SH3 domain-binding protein 2 (G3BP2), a putative miR-23b target, increased in DN. In vitro, overexpression of miR-23b decreased, and inhibition of miR-23b increased, G3BP2 expression levels. Bioinformatics analysis also revealed p53 binding sites in the miR-23b promoter; in vitro inhibition of p53 or the upstream p38 mitogen-activated protein kinase (p38MAPK) upregulated miR-23b expression in high-glucose conditions. In turn, inhibition of G3BP2 or overexpression of miR-23b downregulated p53 and p38MAPK expression in high-glucose conditions. In vivo, overexpression of miR-23b or inhibition of p53 in db/db mice reversed hyperalbuminuria and kidney fibrosis, whereas miR-23b antagomir treatment promoted renal fibrosis and increased albuminuria in wild-type mice. These data suggest that hyperglycemia regulates pathogenic processes in DN through an miR-23b/G3BP2 feedback circuit involving p38MAPK and p53. In conclusion, these results reveal a role for miR-23b in DN and indicate a novel potential therapeutic target.Zhao, BinghaiLi, HongzhiLiu, JietingHan, PengfeiZhang, ChunleiBai, HeYuan, XiaohuanWang, XiaoliLi, LiMa, HongchuangJin, XiudongChu, Yanhui2016-02-02T06:15:34-08:00doi:10.1681/ASN.2015030300hwp:resource-id:jnephrol;27/9/2597American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, diabetes, diabetic nephropathyBrief CommunicationsBrief Communicationsbrief-report20162016-09-01September 201610.1681/ASN.20150303001046-66731533-34502016-02-02T06:15:34-08:002016-09Journal of the American Society of NephrologyBrief Communications27925972608
- Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype-Phenotype Correlations in Autosomal Dominant Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height–adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 [MSG2]) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype.10.1681/ASN.2015050583Thu, 28 Jan 2016 09:48:39 GMT-08:00Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype-Phenotype Correlations in Autosomal Dominant Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height–adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 [MSG2]) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype.Heyer, Christina M.Sundsbak, Jamie L.Abebe, Kaleab Z.Chapman, Arlene B.Torres, Vicente E.Grantham, Jared J.Bae, Kyongtae T.Schrier, Robert W.Perrone, Ronald D.Braun, William E.Steinman, Theodore I.Mrug, MichalYu, Alan S.L.Brosnahan, GodelaHopp, KatharinaIrazabal, Maria V.Bennett, William M.Flessner, Michael F.Moore, Charity G.Landsittel, DouglasHarris, Peter C.,2016-01-28T09:48:39-08:00doi:10.1681/ASN.2015050583hwp:resource-id:jnephrol;27/9/2872American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, Genotype/phenotype, Prognostic studiesClinical ResearchClinical Researchresearch-article20162016-09-01September 201610.1681/ASN.20150505831046-66731533-34502016-01-28T09:48:39-08:002016-09Journal of the American Society of NephrologyClinical Research27928722884
- Coordinated Control of ENaC and Na+,K+-ATPase in Renal Collecting DuctTubular reabsorption of filtered sodium is tightly controlled to maintain body volume homeostasis. The rate of sodium transport by collecting duct (CD) cells varies widely in response to dietary sodium intake, GFR, circulating hormones, neural signals, and local regulatory factors. Reabsorption of filtered sodium by CD cells occurs via a two-step process. First, luminal sodium crosses the apical plasma membrane along its electrochemical gradient through epithelial sodium channels (ENaC). Intracellular sodium is then actively extruded into the interstitial space by the Na+,K+-ATPase located along the basolateral membrane. Mismatch between sodium entry and exit induces variations in sodium intracellular concentration and cell volume that must be maintained within narrow ranges for control of vital cell functions. Therefore, renal epithelial cells display highly coordinated apical and basolateral sodium transport rates. We review evidence from experiments conducted in vivo and in cultured cells that indicates aldosterone and vasopressin, the two major hormones regulating sodium reabsorption by CD, generate a coordinated stimulation of apical ENaC and basolateral Na+,K+-ATPase. Moreover, we discuss evidence suggesting that variations in sodium entry per se induce a coordinated change in Na+,K+-ATPase activity through the signaling of protein kinases such as protein kinase A and p38 mitogen-activated protein kinase.10.1681/ASN.2016020124Tue, 17 May 2016 07:14:27 GMT-07:00Coordinated Control of ENaC and Na+,K+-ATPase in Renal Collecting DuctTubular reabsorption of filtered sodium is tightly controlled to maintain body volume homeostasis. The rate of sodium transport by collecting duct (CD) cells varies widely in response to dietary sodium intake, GFR, circulating hormones, neural signals, and local regulatory factors. Reabsorption of filtered sodium by CD cells occurs via a two-step process. First, luminal sodium crosses the apical plasma membrane along its electrochemical gradient through epithelial sodium channels (ENaC). Intracellular sodium is then actively extruded into the interstitial space by the Na+,K+-ATPase located along the basolateral membrane. Mismatch between sodium entry and exit induces variations in sodium intracellular concentration and cell volume that must be maintained within narrow ranges for control of vital cell functions. Therefore, renal epithelial cells display highly coordinated apical and basolateral sodium transport rates. We review evidence from experiments conducted in vivo and in cultured cells that indicates aldosterone and vasopressin, the two major hormones regulating sodium reabsorption by CD, generate a coordinated stimulation of apical ENaC and basolateral Na+,K+-ATPase. Moreover, we discuss evidence suggesting that variations in sodium entry per se induce a coordinated change in Na+,K+-ATPase activity through the signaling of protein kinases such as protein kinase A and p38 mitogen-activated protein kinase.Feraille, EricDizin, Eva2016-05-17T07:14:27-07:00doi:10.1681/ASN.2016020124hwp:resource-id:jnephrol;27/9/2554American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyaldosterone, epithelial sodium channel, collecting ducts, ENaC, Na transport, p38 mitogen-activated protein kinaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-09-01September 201610.1681/ASN.20160201241046-66731533-34502016-05-17T07:14:27-07:002016-09Journal of the American Society of NephrologyUp Front Matters27925542563
- Social Determinants of Racial Disparities in CKDSignificant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.10.1681/ASN.2016010027Fri, 13 May 2016 09:11:45 GMT-07:00Social Determinants of Racial Disparities in CKDSignificant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.Norton, Jenna M.Moxey-Mims, Marva M.Eggers, Paul W.Narva, Andrew S.Star, Robert A.Kimmel, Paul L.Rodgers, Griffin P.2016-05-13T09:11:45-07:00doi:10.1681/ASN.2016010027hwp:resource-id:jnephrol;27/9/2576American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, social determinants, racial disparities, socioeconomic status, psychosocial factors, end stage kidney diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-09-01September 201610.1681/ASN.20160100271046-66731533-34502016-05-13T09:11:45-07:002016-09Journal of the American Society of NephrologyUp Front Matters27925762595
- This Month's Highlights10.1681/ASN.2016050579Wed, 31 Aug 2016 10:01:11 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-08-31T10:01:11-07:00doi:10.1681/ASN.2016050579hwp:resource-id:jnephrol;27/9/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-09-01September 201610.1681/ASN.20160505791046-66731533-34502016-08-31T10:01:11-07:002016-09Journal of the American Society of NephrologyThis Month's Highlights279ii
- Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney DiseaseKidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1β and of the alarmin IL-1α. Dying cells release IL-1α also, independently of the inflammasome. Both IL-1α and IL-1β ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1α/IL-β-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1α/β regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1α/IL-β-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency–approved IL-1–neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1α/IL-β-IL-1R system in kidney disease should be further explored.10.1681/ASN.2016020177Thu, 11 Aug 2016 08:00:58 GMT-07:00Of Inflammasomes and Alarmins: IL-1β and IL-1α in Kidney DiseaseKidney injury implies danger signaling and a response by the immune system. The inflammasome is a central danger recognition platform that triggers local and systemic inflammation. In immune cells, inflammasome activation causes the release of mature IL-1β and of the alarmin IL-1α. Dying cells release IL-1α also, independently of the inflammasome. Both IL-1α and IL-1β ligate the same IL-1 receptor (IL-1R) that is present on nearly all cells inside and outside the kidney, further amplifying cytokine and chemokine release. Thus, the inflammasome-IL-1α/IL-β-IL-1R system is a central element of kidney inflammation and the systemic consequences. Seminal discoveries of recent years have expanded this central paradigm of inflammation. This review gives an overview of arising concepts of inflammasome and IL-1α/β regulation in renal cells and in experimental kidney disease models. There is a pipeline of compounds that can interfere with the inflammasome-IL-1α/IL-β-IL-1R system, ranging from recently described small molecule inhibitors of NLRP3, a component of the inflammasome complex, to regulatory agency–approved IL-1–neutralizing biologic drugs. Based on strong theoretic and experimental rationale, the potential therapeutic benefits of using such compounds to block the inflammasome-IL-1α/IL-β-IL-1R system in kidney disease should be further explored.Anders, Hans-Joachim2016-08-11T08:00:58-07:00doi:10.1681/ASN.2016020177hwp:resource-id:jnephrol;27/9/2564American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyinflammation, glomerulonephritis, acute kidney injury, chronic kidney disease, innate immunityUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-09-01September 201610.1681/ASN.20160201771046-66731533-34502016-08-11T08:00:58-07:002016-09Journal of the American Society of NephrologyUp Front Matters27925642575
- Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA NephropathyA recent genome–wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H–related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants. The distribution of rare variants in CFHR5 in patients with IgAN differed significantly from that in controls (P=0.002). Among the rare variants, in silico programs predicted nine as potential functional variants, which we then assessed in functional assays. Compared with wild-type CFHR5, three recombinant CFHR5 proteins, CFHR5-M (c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D (c.822A>T/p.Glu274Asp), showed significantly higher C3b binding capacity (CFHR5-M: 109.67%±3.54%; P=0.02; CFHR5-S: 174.27%±9.78%; P<0.001; CFHR5-D: 127.25%±1.75%; P<0.001), whereas another recombinant CFHR5 (c.776T>A/p.Leu259Termination) showed less C3b binding (56.89%±0.57%; P<0.001). Our study found that rare variants in CFHR5 may contribute to the genetic susceptibility to IgAN, which suggests that CFHR5 is an IgAN susceptibility gene.10.1681/ASN.2015010012Fri, 29 Jan 2016 09:12:12 GMT-08:00Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA NephropathyA recent genome–wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H–related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants. The distribution of rare variants in CFHR5 in patients with IgAN differed significantly from that in controls (P=0.002). Among the rare variants, in silico programs predicted nine as potential functional variants, which we then assessed in functional assays. Compared with wild-type CFHR5, three recombinant CFHR5 proteins, CFHR5-M (c.508G>A/p.Val170Met), CFHR5-S (c.533A>G/p.Asn178Ser), and CFHR5-D (c.822A>T/p.Glu274Asp), showed significantly higher C3b binding capacity (CFHR5-M: 109.67%±3.54%; P=0.02; CFHR5-S: 174.27%±9.78%; P<0.001; CFHR5-D: 127.25%±1.75%; P<0.001), whereas another recombinant CFHR5 (c.776T>A/p.Leu259Termination) showed less C3b binding (56.89%±0.57%; P<0.001). Our study found that rare variants in CFHR5 may contribute to the genetic susceptibility to IgAN, which suggests that CFHR5 is an IgAN susceptibility gene.Zhai, Ya-LingMeng, Si-JunZhu, LiShi, Su-FangWang, Su-XiaLiu, Li-JunLv, Ji-ChengYu, FengZhao, Ming-HuiZhang, Hong2016-01-29T09:12:12-08:00doi:10.1681/ASN.2015010012hwp:resource-id:jnephrol;27/9/2894American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCFHR5, IgA nephropathy, genetic analysisClinical ResearchClinical Researchresearch-article20162016-09-01September 201610.1681/ASN.20150100121046-66731533-34502016-01-29T09:12:12-08:002016-09Journal of the American Society of NephrologyClinical Research27992894254729052551
- IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA NephropathyIgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti–hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the α1KI‑CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1‑P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1‑P (1–10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1–sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b+ infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1‑P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1‑P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN.10.1681/ASN.2015080856Fri, 05 Feb 2016 06:25:47 GMT-08:00IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA NephropathyIgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti–hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the α1KI‑CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1‑P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1‑P (1–10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1–sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b+ infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1‑P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1‑P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN.Lechner, Sebastian M.Abbad, LiliaBoedec, ErwanPapista, ChristinaLe Stang, Marie-BénédicteMoal, ChristelleMaillard, JulienJamin, AgnèsBex-Coudrat, JulieWang, YongLi, AiqunMartini, Paolo G.V.Monteiro, Renato C.Berthelot, Laureline2016-02-05T06:25:47-08:00doi:10.1681/ASN.2015080856hwp:resource-id:jnephrol;27/9/2622American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, immune complexes, glomerulonephritis, immunology, pathologyBrief CommunicationsBrief Communicationsbrief-report20162016-09-01September 201610.1681/ASN.20150808561046-66731533-34502016-02-05T06:25:47-08:002016-09Journal of the American Society of NephrologyBrief Communications27926222629
- Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3−Regulation of blood pH—critical for virtually every facet of life—requires that the renal proximal tubule (PT) adjust its rate of H+ secretion (nearly the same as the rate of HCO3− reabsorption, JHCO3) in response to changes in blood [CO2] and [HCO3−]. Yet CO2/HCO3− sensing mechanisms remain poorly characterized. Because receptor tyrosine kinase inhibitors render JHCO3 in the PT insensitive to changes in CO2 concentration, we hypothesized that the structural features of receptor protein tyrosine phosphatase-γ (RPTPγ) that are consistent with binding of extracellular CO2 or HCO3− facilitate monitoring of blood CO2/HCO3− concentrations. We now report that PTs express RPTPγ on blood-facing membranes. Moreover, RPTPγ deletion in mice eliminated the CO2 and HCO3− sensitivities of JHCO3 as well as the normal defense of blood pH during whole-body acidosis. Thus, RPTPγ appears to be a novel extracellular CO2/HCO3− sensor critical for pH homeostasis.10.1681/ASN.2015040439Tue, 02 Feb 2016 06:15:34 GMT-08:00Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3−Regulation of blood pH—critical for virtually every facet of life—requires that the renal proximal tubule (PT) adjust its rate of H+ secretion (nearly the same as the rate of HCO3− reabsorption, JHCO3) in response to changes in blood [CO2] and [HCO3−]. Yet CO2/HCO3− sensing mechanisms remain poorly characterized. Because receptor tyrosine kinase inhibitors render JHCO3 in the PT insensitive to changes in CO2 concentration, we hypothesized that the structural features of receptor protein tyrosine phosphatase-γ (RPTPγ) that are consistent with binding of extracellular CO2 or HCO3− facilitate monitoring of blood CO2/HCO3− concentrations. We now report that PTs express RPTPγ on blood-facing membranes. Moreover, RPTPγ deletion in mice eliminated the CO2 and HCO3− sensitivities of JHCO3 as well as the normal defense of blood pH during whole-body acidosis. Thus, RPTPγ appears to be a novel extracellular CO2/HCO3− sensor critical for pH homeostasis.Zhou, YuehanSkelton, Lara A.Xu, LumeiChandler, Margaret P.Berthiaume, Jessica M.Boron, Walter F.2016-02-02T06:15:34-08:00doi:10.1681/ASN.2015040439hwp:resource-id:jnephrol;27/9/2616American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymetabolic acidosis, pH, bicarbonate transport, proximal tubule, receptor protein tyrosine phosphatase, kidneyBrief CommunicationsBrief Communicationsbrief-report20162016-09-01September 201610.1681/ASN.20150404391046-66731533-34502016-02-02T06:15:34-08:002016-09Journal of the American Society of NephrologyBrief Communications27992616254326212545
- Recombinant N–Terminal Slit2 Inhibits TGF-β–Induced Fibroblast Activation and Renal FibrosisFibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF-β. Here, we examined whether Slit2 also controls TGF-β–induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N–terminal fragment of Slit2 inhibited TGF-β–induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C–terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis.10.1681/ASN.2015040356Thu, 11 Feb 2016 05:52:03 GMT-08:00Recombinant N–Terminal Slit2 Inhibits TGF-β–Induced Fibroblast Activation and Renal FibrosisFibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF-β. Here, we examined whether Slit2 also controls TGF-β–induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N–terminal fragment of Slit2 inhibited TGF-β–induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C–terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis.Yuen, Darren A.Huang, Yi-WeiLiu, Guang-YingPatel, SajedabanuFang, FeiZhou, JoyceThai, KerriSidiqi, AhmadSzeto, Stephen G.Chan, LaurenLu, MingliangHe, XiaolinJohn, RohanGilbert, Richard E.Scholey, James W.Robinson, Lisa A.2016-02-11T05:52:03-08:00doi:10.1681/ASN.2015040356hwp:resource-id:jnephrol;27/9/2609American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, Slit2, Robo, Transforming growth factor-betaBrief CommunicationsBrief Communicationsbrief-report20162016-09-01September 201610.1681/ASN.20150403561046-66731533-34502016-02-11T05:52:03-08:002016-09Journal of the American Society of NephrologyBrief Communications27926092615
- Glucocorticoid-Regulated Kinase: Linking Azotemia and Muscle Wasting in CKD10.1681/ASN.2016030284Fri, 08 Apr 2016 05:34:14 GMT-07:00Glucocorticoid-Regulated Kinase: Linking Azotemia and Muscle Wasting in CKDMenon, Madhav C.He, John Cijiang2016-04-08T05:34:14-07:00doi:10.1681/ASN.2016030284hwp:resource-id:jnephrol;27/9/2545American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyGlucocorticoid-related kinase-1, CKD-induced myopathy, Azotemia, knockout miceUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-09-01September 201610.1681/ASN.20160302841046-66731533-34502016-04-08T05:34:14-07:002016-09Journal of the American Society of NephrologyUp Front Matters27992545279725472808
- Candidate Surrogate End Points for ESRD after AKIAKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%–40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.10.1681/ASN.2015070829Mon, 08 Feb 2016 06:17:30 GMT-08:00Candidate Surrogate End Points for ESRD after AKIAKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%–40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.Grams, Morgan E.Sang, YingyingCoresh, JosefBallew, Shoshana H.Matsushita, KunihiroLevey, Andrew S.Greene, Tom H.Molnar, Miklos Z.Szabo, ZoltanKalantar-Zadeh, KamyarKovesdy, Csaba P.2016-02-08T06:17:30-08:00doi:10.1681/ASN.2015070829hwp:resource-id:jnephrol;27/9/2851American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, end stage kidney disease, glomerular filtration rateClinical EpidemiologyClinical Epidemiologyresearch-article20162016-09-01September 201610.1681/ASN.20150708291046-66731533-34502016-02-08T06:17:30-08:002016-09Journal of the American Society of NephrologyClinical Epidemiology27928512859
- Inhibition of EGF Receptor Blocks the Development and Progression of Peritoneal FibrosisInhibitors of EGF receptor (EGFR) have antifibrotic effects in several organs, but the effect of these inhibitors on the development of peritoneal fibrosis is unknown. Here, we explored the therapeutic effect of gefitinib, a specific inhibitor of EGFR, on the development and progression of peritoneal fibrosis in a rat model. Daily intraperitoneal injections of chlorhexidine gluconate induced peritoneal fibrosis, indicated by thickening of the submesothelial area with an accumulation of collagen fibrils and activation of myofibroblasts, accompanied by time-dependent phosphorylation of EGFR. Administration of gefitinib immediately after injury prevented the onset of peritoneal fibrosis and delayed administration after the onset of peritoneal fibrosis halted fibrosis progression. Gefitinib treatment abrogated the increased phosphorylation of EGFR, Smad3, signal transducer and activator of transcription 3, and NF-κB during peritoneal fibrosis; it also inhibited the accompanying overproduction of TGF-β1 and proinflammatory cytokines and the infiltration of macrophages to the injured peritoneum. Moreover, gefitinib significantly reduced the peritoneal increase of CD31-positive blood vessels and vascular EGF-positive cells after injury. Finally, gefitinib also attenuated high glucose–induced peritoneal fibrosis in rats and abrogated TGF-β1–induced phosphorylation of Smad3 and the epithelial-to-mesenchymal transition of cultured human peritoneal mesothelial cells. These results demonstrate that EGFR contributes to peritoneal fibrosis, inflammation, and angiogenesis, suggesting that EGFR inhibitors may have therapeutic potential in attenuating peritoneal fibrosis.10.1681/ASN.2015030299Thu, 17 Dec 2015 07:44:13 GMT-08:00Inhibition of EGF Receptor Blocks the Development and Progression of Peritoneal FibrosisInhibitors of EGF receptor (EGFR) have antifibrotic effects in several organs, but the effect of these inhibitors on the development of peritoneal fibrosis is unknown. Here, we explored the therapeutic effect of gefitinib, a specific inhibitor of EGFR, on the development and progression of peritoneal fibrosis in a rat model. Daily intraperitoneal injections of chlorhexidine gluconate induced peritoneal fibrosis, indicated by thickening of the submesothelial area with an accumulation of collagen fibrils and activation of myofibroblasts, accompanied by time-dependent phosphorylation of EGFR. Administration of gefitinib immediately after injury prevented the onset of peritoneal fibrosis and delayed administration after the onset of peritoneal fibrosis halted fibrosis progression. Gefitinib treatment abrogated the increased phosphorylation of EGFR, Smad3, signal transducer and activator of transcription 3, and NF-κB during peritoneal fibrosis; it also inhibited the accompanying overproduction of TGF-β1 and proinflammatory cytokines and the infiltration of macrophages to the injured peritoneum. Moreover, gefitinib significantly reduced the peritoneal increase of CD31-positive blood vessels and vascular EGF-positive cells after injury. Finally, gefitinib also attenuated high glucose–induced peritoneal fibrosis in rats and abrogated TGF-β1–induced phosphorylation of Smad3 and the epithelial-to-mesenchymal transition of cultured human peritoneal mesothelial cells. These results demonstrate that EGFR contributes to peritoneal fibrosis, inflammation, and angiogenesis, suggesting that EGFR inhibitors may have therapeutic potential in attenuating peritoneal fibrosis.Wang, LiLiu, NaXiong, ChongxiangXu, LiuqingShi, YingfengQiu, AndongZang, XiujuanMao, HaipingZhuang, Shougang2015-12-17T07:44:13-08:00doi:10.1681/ASN.2015030299hwp:resource-id:jnephrol;27/9/2631American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyepidermal growth factor, fibrosis, peritoneal dialysis, TGF-beta, VEGF, signalingBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150302991046-66731533-34502015-12-17T07:44:13-08:002016-09Journal of the American Society of NephrologyBasic Research2728972631224926442251
- Erratum10.1681/ASN.2016030339Wed, 31 Aug 2016 10:01:11 GMT-07:00ErratumAmerican Society of Nephrology2016-08-31T10:01:11-07:00doi:10.1681/ASN.2016030339hwp:resource-id:jnephrol;27/9/2917American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20162016-09-01September 201610.1681/ASN.20160303391046-66731533-34502016-08-31T10:01:11-07:002016-09Journal of the American Society of NephrologyErrata2726982917198229171989
- Erratum10.1681/ASN.2016060616Wed, 31 Aug 2016 10:01:11 GMT-07:00ErratumAmerican Society of Nephrology2016-08-31T10:01:11-07:00doi:10.1681/ASN.2016060616hwp:resource-id:jnephrol;27/9/2918American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20162016-09-01September 201610.1681/ASN.20160606161046-66731533-34502016-08-31T10:01:11-07:002016-09Journal of the American Society of NephrologyErrata27199129181822918187
- Receptor Protein Tyrosine Phosphatase γ, CO2 Sensing in Proximal Tubule and Acid Base Homeostasis10.1681/ASN.2016030332Mon, 18 Apr 2016 07:55:56 GMT-07:00Receptor Protein Tyrosine Phosphatase γ, CO2 Sensing in Proximal Tubule and Acid Base HomeostasisSoleimani, Manoocher2016-04-18T07:55:56-07:00doi:10.1681/ASN.2016030332hwp:resource-id:jnephrol;27/9/2543American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, Na+/H+ exchanger isoform 3, Na+:HCO3- cotransporter, NBC-e1 (NBC1, SLC4A4), HCO3- reabsorption, CO2/HCO3- sensingUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-09-01September 201610.1681/ASN.20160303321046-66731533-34502016-04-18T07:55:56-07:002016-09Journal of the American Society of NephrologyUp Front Matters27992543261625452621
- Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKDKidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m2) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per µU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, −0.7; 95% confidence interval, −1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, −85; 95% confidence interval, −160 to −10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.10.1681/ASN.2015070756Thu, 28 Jan 2016 09:48:37 GMT-08:00Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKDKidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m2) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per µU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, −0.7; 95% confidence interval, −1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, −85; 95% confidence interval, −160 to −10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.de Boer, Ian H.Zelnick, LeilaAfkarian, MaryamAyers, ErnestCurtin, LauraHimmelfarb, JonathanIkizler, T. AlpKahn, Steven E.Kestenbaum, BryanUtzschneider, Kristina2016-01-28T09:48:37-08:00doi:10.1681/ASN.2015070756hwp:resource-id:jnephrol;27/9/2861American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, metabolism, obesity, renal insulin resistance, insulin resistanceClinical ResearchClinical Researchresearch-article20162016-09-01September 201610.1681/ASN.20150707561046-66731533-34502016-01-28T09:48:37-08:002016-09Journal of the American Society of NephrologyClinical Research27928612871
- Race, APOL1 Risk, and eGFR Decline in the General PopulationThe APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987–1989 (baseline) to 2011–2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th–90th percentile) unadjusted eGFR decline was 1.5 (1.0–2.2) ml/min per 1.73 m2 per year for whites, 2.1 (1.4–3.1) ml/min per 1.73 m2 per year for blacks with APOL1 low-risk status, and 2.3 (1.5–3.5) ml/min per 1.73 m2 per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.10.1681/ASN.2015070763Thu, 10 Mar 2016 07:57:45 GMT-08:00Race, APOL1 Risk, and eGFR Decline in the General PopulationThe APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987–1989 (baseline) to 2011–2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th–90th percentile) unadjusted eGFR decline was 1.5 (1.0–2.2) ml/min per 1.73 m2 per year for whites, 2.1 (1.4–3.1) ml/min per 1.73 m2 per year for blacks with APOL1 low-risk status, and 2.3 (1.5–3.5) ml/min per 1.73 m2 per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.Grams, Morgan E.Rebholz, Casey M.Chen, YuanRawlings, Andreea M.Estrella, Michelle M.Selvin, ElizabethAppel, Lawrence J.Tin, AdrienneCoresh, Josef2016-03-10T07:57:45-08:00doi:10.1681/ASN.2015070763hwp:resource-id:jnephrol;27/9/2842American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, glomerular filtration rate, ethnicityClinical EpidemiologyClinical Epidemiologyresearch-article20162016-09-01September 201610.1681/ASN.20150707631046-66731533-34502016-03-10T07:57:45-08:002016-09Journal of the American Society of NephrologyClinical Epidemiology27928422850
- Challenges in Rare Variant Association Studies for Complex Kidney Traits: CFHR5 and IgA Nephropathy10.1681/ASN.2016040383Tue, 17 May 2016 07:14:26 GMT-07:00Challenges in Rare Variant Association Studies for Complex Kidney Traits: CFHR5 and IgA NephropathyKiryluk, Krzysztof2016-05-17T07:14:26-07:00doi:10.1681/ASN.2016040383hwp:resource-id:jnephrol;27/9/2547American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyIgA nephropathy, Rare variants, CFHR5, GWAS, Sequencing, Genetic associationUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-09-01September 201610.1681/ASN.20160403831046-66731533-34502016-05-17T07:14:26-07:002016-09Journal of the American Society of NephrologyUp Front Matters27992547289425512905
- Renal Function Profile in White Kidney Donors: The First 4 DecadesPrevious studies reported the risk of ESRD after kidney donation, but not the renal outcomes that precede ESRD. Here, we estimated the risk of proteinuria, reduced GFR, and ESRD in 3956 white kidney donors, assessed the contribution of postdonation hypertension and diabetes to these outcomes, and developed a risk calculator. After a mean±SD follow-up of 16.6±11.9 years, 215 (6.1%) donors developed proteinuria. Men had a higher risk of proteinuria (hazard ratio [HR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) as did those with higher body mass index (HR, 1.10; 95% CI, 1.06 to 1.13; P<0.001). In all, 1410 (36%) donors reached an eGFR<60 ml/min per 1.73 m2, and 112 (2.8%) donors had either an eGFR<30 ml/min per 1.73 m2 or ESRD (28 donors developed ESRD). An eGFR<30 ml/min per 1.73 m2 or ESRD associated with older age (HR, 1.07; 95% CI, 1.05 to 1.09; P<0.001), higher body mass index (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01) at donation. Postdonation diabetes and hypertension associated with a fourfold higher risk of proteinuria and a >2-fold higher risk of ESRD. Models predicting proteinuria and reduced eGFR performed well (C-index 0.77–1.00). In conclusion, severe reduction in GFR and ESRD after kidney donation were uncommon and were highly associated with postdonation diabetes and hypertension. Furthermore, information available before donation may predict long-term renal outcomes in white living kidney donors.10.1681/ASN.2015091018Wed, 17 Feb 2016 07:14:33 GMT-08:00Renal Function Profile in White Kidney Donors: The First 4 DecadesPrevious studies reported the risk of ESRD after kidney donation, but not the renal outcomes that precede ESRD. Here, we estimated the risk of proteinuria, reduced GFR, and ESRD in 3956 white kidney donors, assessed the contribution of postdonation hypertension and diabetes to these outcomes, and developed a risk calculator. After a mean±SD follow-up of 16.6±11.9 years, 215 (6.1%) donors developed proteinuria. Men had a higher risk of proteinuria (hazard ratio [HR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) as did those with higher body mass index (HR, 1.10; 95% CI, 1.06 to 1.13; P<0.001). In all, 1410 (36%) donors reached an eGFR<60 ml/min per 1.73 m2, and 112 (2.8%) donors had either an eGFR<30 ml/min per 1.73 m2 or ESRD (28 donors developed ESRD). An eGFR<30 ml/min per 1.73 m2 or ESRD associated with older age (HR, 1.07; 95% CI, 1.05 to 1.09; P<0.001), higher body mass index (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01) at donation. Postdonation diabetes and hypertension associated with a fourfold higher risk of proteinuria and a >2-fold higher risk of ESRD. Models predicting proteinuria and reduced eGFR performed well (C-index 0.77–1.00). In conclusion, severe reduction in GFR and ESRD after kidney donation were uncommon and were highly associated with postdonation diabetes and hypertension. Furthermore, information available before donation may predict long-term renal outcomes in white living kidney donors.Ibrahim, Hassan N.Foley, Robert N.Reule, Scott A.Spong, RichardKukla, AleksandraIssa, NaimBerglund, Danielle M.Sieger, Gretchen K.Matas, Arthur J.2016-02-17T07:14:33-08:00doi:10.1681/ASN.2015091018hwp:resource-id:jnephrol;27/9/2885American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyoutcomes, kidney donation, renal dysfunctionClinical ResearchClinical Researchresearch-article20162016-09-01September 201610.1681/ASN.20150910181046-66731533-34502016-02-17T07:14:33-08:002016-09Journal of the American Society of NephrologyClinical Research279122885296828932969
- Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin–Mediated Kidney InjuryUrinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma. Moreover, hepcidin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion of injected hhep25 and no hepcidin staining in proximal tubules that lack megalin. This indicates that hepcidin is reaborbed in the proximal tubules by megalin dependent endocytosis. Administration of hhep25 concomitant with or 4 hours after a single intravenous dose of hemoglobin abolished hemoglobin-induced upregulation of urinary kidney injury markers (NGAL and KIM-1) and renal Interleukin-6 and Ngal mRNA observed 24 hours after administration but did not affect renal ferroportin expression at this point. Notably, coadministration of hhep25 and hemoglobin but not administration of either alone greatly increased renal mRNA expression of hepcidin-encoding Hamp1 and hepcidin staining in distal tubules. These findings suggest a role for locally synthesized hepcidin in renal protection. Our observations did not support a role for ferroportin in hhep25-mediated protection against hemoglobin–induced early injury, but other mechanisms of cellular iron handling may be involved. In conclusion, our data suggest that both systemically delivered and locally produced hepcidin protect against hemoglobin-induced AKI.10.1681/ASN.2015040461Fri, 29 Jan 2016 09:12:14 GMT-08:00Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin–Mediated Kidney InjuryUrinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma. Moreover, hepcidin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion of injected hhep25 and no hepcidin staining in proximal tubules that lack megalin. This indicates that hepcidin is reaborbed in the proximal tubules by megalin dependent endocytosis. Administration of hhep25 concomitant with or 4 hours after a single intravenous dose of hemoglobin abolished hemoglobin-induced upregulation of urinary kidney injury markers (NGAL and KIM-1) and renal Interleukin-6 and Ngal mRNA observed 24 hours after administration but did not affect renal ferroportin expression at this point. Notably, coadministration of hhep25 and hemoglobin but not administration of either alone greatly increased renal mRNA expression of hepcidin-encoding Hamp1 and hepcidin staining in distal tubules. These findings suggest a role for locally synthesized hepcidin in renal protection. Our observations did not support a role for ferroportin in hhep25-mediated protection against hemoglobin–induced early injury, but other mechanisms of cellular iron handling may be involved. In conclusion, our data suggest that both systemically delivered and locally produced hepcidin protect against hemoglobin-induced AKI.van Swelm, Rachel P.L.Wetzels, Jack F.M.Verweij, Vivienne G.M.Laarakkers, Coby M.M.Pertijs, Jeanne C.L.M.van der Wijst, JennyThévenod, FrankMasereeuw, RosalindeSwinkels, Dorine W.2016-01-29T09:12:14-08:00doi:10.1681/ASN.2015040461hwp:resource-id:jnephrol;27/9/2720American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhepcidin, iron, megalin, hemoglobin, acute kidney injuryBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150404611046-66731533-34502016-01-29T09:12:14-08:002016-09Journal of the American Society of NephrologyBasic Research27927202732
- Dynamin–Related Protein 1 Deficiency Improves Mitochondrial Fitness and Protects against Progression of Diabetic NephropathyMitochondrial fission has been linked to the pathogenesis of diabetic nephropathy (DN). However, how mitochondrial fission affects progression of DN in vivo is unknown. Here, we report the effect of conditional podocyte–specific deletion of dynamin-related protein 1 (Drp1), an essential component of mitochondrial fission, on the pathogenesis and progression of DN. Inducible podocyte–specific deletion of Drp1 in diabetic mice decreased albuminuria and improved mesangial matrix expansion and podocyte morphology. Ultrastructure analysis revealed a significant increase in fragmented mitochondria in the podocytes of wild–type diabetic mice but a marked improvement in mitochondrial structure in Drp1-null podocytes of diabetic mice. When isolated from diabetic mice and cultured in high glucose, Drp1-null podocytes had more elongated mitochondria and better mitochondrial fitness associated with enhanced oxygen consumption and ATP production than wild-type podocytes. Furthermore, administration of a pharmacologic inhibitor of Drp1, Mdivi1, significantly blunted mitochondrial fission and rescued key pathologic features of DN in mice. Taken together, these results provide novel correlations between mitochondrial morphology and the progression of DN and point to Drp1 as a potential therapeutic target in DN.10.1681/ASN.2015101096Fri, 29 Jan 2016 09:12:13 GMT-08:00Dynamin–Related Protein 1 Deficiency Improves Mitochondrial Fitness and Protects against Progression of Diabetic NephropathyMitochondrial fission has been linked to the pathogenesis of diabetic nephropathy (DN). However, how mitochondrial fission affects progression of DN in vivo is unknown. Here, we report the effect of conditional podocyte–specific deletion of dynamin-related protein 1 (Drp1), an essential component of mitochondrial fission, on the pathogenesis and progression of DN. Inducible podocyte–specific deletion of Drp1 in diabetic mice decreased albuminuria and improved mesangial matrix expansion and podocyte morphology. Ultrastructure analysis revealed a significant increase in fragmented mitochondria in the podocytes of wild–type diabetic mice but a marked improvement in mitochondrial structure in Drp1-null podocytes of diabetic mice. When isolated from diabetic mice and cultured in high glucose, Drp1-null podocytes had more elongated mitochondria and better mitochondrial fitness associated with enhanced oxygen consumption and ATP production than wild-type podocytes. Furthermore, administration of a pharmacologic inhibitor of Drp1, Mdivi1, significantly blunted mitochondrial fission and rescued key pathologic features of DN in mice. Taken together, these results provide novel correlations between mitochondrial morphology and the progression of DN and point to Drp1 as a potential therapeutic target in DN.Ayanga, Bernard A.Badal, Shawn S.Wang, YinGalvan, Daniel L.Chang, Benny H.Schumacker, Paul T.Danesh, Farhad R.2016-01-29T09:12:13-08:00doi:10.1681/ASN.2015101096hwp:resource-id:jnephrol;27/9/2733American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, mitochondria, diabetic nephropathyBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20151010961046-66731533-34502016-01-29T09:12:13-08:002016-09Journal of the American Society of NephrologyBasic Research27927332747
- Urine of Preterm Neonates as a Novel Source of Kidney Progenitor CellsIn humans, nephrogenesis is completed prenatally, with nephrons formed until 34 weeks of gestational age. We hypothesized that urine of preterm neonates born before the completion of nephrogenesis is a noninvasive source of highly potent stem/progenitor cells. To test this hypothesis, we collected freshly voided urine at day 1 after birth from neonates born at 31–36 weeks of gestational age and characterized isolated cells using a single–cell RT-PCR strategy for gene expression analysis and flow cytometry and immunofluorescence for protein expression analysis. Neonatal stem/progenitor cells expressed markers of nephron progenitors but also, stromal progenitors, with many single cells coexpressing these markers. Furthermore, these cells presented mesenchymal stem cell features and protected cocultured tubule cells from cisplatin-induced apoptosis. Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte–specific transient receptor potential cation channel, subfamily C, member 6. Differentiated proximal tubule cells showed upregulation of specific genes and significantly elevated p-glycoprotein activity. We conclude that urine of preterm neonates is a novel noninvasive source of kidney progenitors that are capable of differentiation into mature kidney cells and have high potential for regenerative kidney repair.10.1681/ASN.2015060664Thu, 03 Mar 2016 10:58:58 GMT-08:00Urine of Preterm Neonates as a Novel Source of Kidney Progenitor CellsIn humans, nephrogenesis is completed prenatally, with nephrons formed until 34 weeks of gestational age. We hypothesized that urine of preterm neonates born before the completion of nephrogenesis is a noninvasive source of highly potent stem/progenitor cells. To test this hypothesis, we collected freshly voided urine at day 1 after birth from neonates born at 31–36 weeks of gestational age and characterized isolated cells using a single–cell RT-PCR strategy for gene expression analysis and flow cytometry and immunofluorescence for protein expression analysis. Neonatal stem/progenitor cells expressed markers of nephron progenitors but also, stromal progenitors, with many single cells coexpressing these markers. Furthermore, these cells presented mesenchymal stem cell features and protected cocultured tubule cells from cisplatin-induced apoptosis. Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte–specific transient receptor potential cation channel, subfamily C, member 6. Differentiated proximal tubule cells showed upregulation of specific genes and significantly elevated p-glycoprotein activity. We conclude that urine of preterm neonates is a novel noninvasive source of kidney progenitors that are capable of differentiation into mature kidney cells and have high potential for regenerative kidney repair.Arcolino, Fanny OliveiraZia, SilviaHeld, KatharinaPapadimitriou, ElliTheunis, KoenBussolati, BenedettaRaaijmakers, AnkeAllegaert, KarelVoet, ThierryDeprest, JanVriens, JorisToelen, Jaanvan den Heuvel, LambertusLevtchenko, Elena2016-03-03T10:58:58-08:00doi:10.1681/ASN.2015060664hwp:resource-id:jnephrol;27/9/2762American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologystem cell, preterm, urineBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150606641046-66731533-34502016-03-03T10:58:58-08:002016-09Journal of the American Society of NephrologyBasic Research27927622770
- MicroRNA-489 Induction by Hypoxia–Inducible Factor–1 Protects against Ischemic Kidney InjuryMicroRNAs have been implicated in ischemic AKI. However, the specific microRNA species that regulates ischemic kidney injury remains unidentified. Our previous microarray analysis revealed microRNA-489 induction in kidneys of mice subjected to renal ischemia-reperfusion. In this study, we verified the induction of microRNA-489 during ischemic AKI in mice and further examined the underlying mechanisms. Hypoxia–inducible factor–1α deficiency associated with diminished microRNA-489 induction in cultured rat proximal tubular cells subjected to hypoxia and kidney tissues of mice after renal ischemia-reperfusion injury. Moreover, genomic analysis revealed that microRNA-489 is intronic in the calcitonin receptor gene, and chromatin immunoprecipitation assays showed increased binding of hypoxia–inducible factor–1 to a specific site in the calcitonin receptor gene promoter after hypoxia. Inhibition of microRNA-489 increased apoptosis in renal tubular cells after ATP depletion injury in vitro, whereas microRNA-489 mimics mediated protection. In mice, inhibition of microRNA-489 enhanced tubular cell death and ischemic AKI without significantly affecting tubular cell proliferation. Deep sequencing identified 417 mRNAs that were recruited to the RNA–induced silencing complex by microRNA-489. Of the identified mRNAs, 127 contain microRNA-489 targeting sites, and of those, 18 are involved in the cellular stress response, including the poly(ADP-ribose) polymerase 1 gene implicated in ischemic kidney injury. Sequence analysis and in vitro studies validated poly(ADP-ribose) polymerase 1 as a microRNA-489 target. Together, these results suggest that microRNA-489 is induced via hypoxia–inducible factor–1 during ischemic AKI to protect kidneys by targeting relevant genes.10.1681/ASN.2015080870Mon, 14 Mar 2016 06:33:08 GMT-07:00MicroRNA-489 Induction by Hypoxia–Inducible Factor–1 Protects against Ischemic Kidney InjuryMicroRNAs have been implicated in ischemic AKI. However, the specific microRNA species that regulates ischemic kidney injury remains unidentified. Our previous microarray analysis revealed microRNA-489 induction in kidneys of mice subjected to renal ischemia-reperfusion. In this study, we verified the induction of microRNA-489 during ischemic AKI in mice and further examined the underlying mechanisms. Hypoxia–inducible factor–1α deficiency associated with diminished microRNA-489 induction in cultured rat proximal tubular cells subjected to hypoxia and kidney tissues of mice after renal ischemia-reperfusion injury. Moreover, genomic analysis revealed that microRNA-489 is intronic in the calcitonin receptor gene, and chromatin immunoprecipitation assays showed increased binding of hypoxia–inducible factor–1 to a specific site in the calcitonin receptor gene promoter after hypoxia. Inhibition of microRNA-489 increased apoptosis in renal tubular cells after ATP depletion injury in vitro, whereas microRNA-489 mimics mediated protection. In mice, inhibition of microRNA-489 enhanced tubular cell death and ischemic AKI without significantly affecting tubular cell proliferation. Deep sequencing identified 417 mRNAs that were recruited to the RNA–induced silencing complex by microRNA-489. Of the identified mRNAs, 127 contain microRNA-489 targeting sites, and of those, 18 are involved in the cellular stress response, including the poly(ADP-ribose) polymerase 1 gene implicated in ischemic kidney injury. Sequence analysis and in vitro studies validated poly(ADP-ribose) polymerase 1 as a microRNA-489 target. Together, these results suggest that microRNA-489 is induced via hypoxia–inducible factor–1 during ischemic AKI to protect kidneys by targeting relevant genes.Wei, QingqingLiu, YongLiu, PengyuanHao, JieluLiang, MingyuMi, Qing-shengChen, Jian-KangDong, Zheng2016-03-14T06:33:08-07:00doi:10.1681/ASN.2015080870hwp:resource-id:jnephrol;27/9/2784American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, gene expression, hypoxia, apoptosisBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150808701046-66731533-34502016-03-14T06:33:08-07:002016-09Journal of the American Society of NephrologyBasic Research27927842796
- Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid–regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKD–induced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK-1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N-myc downstream–regulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD–induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD.10.1681/ASN.2015080867Mon, 15 Feb 2016 06:04:51 GMT-08:00Serum Glucocorticoid–Regulated Kinase 1 Blocks CKD–Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid–regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKD–induced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK-1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N-myc downstream–regulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD–induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD.Luo, JinlongLiang, AnlinLiang, MingXia, RuohanRizvi, YasmeenWang, YunCheng, Jizhong2016-02-15T06:04:51-08:00doi:10.1681/ASN.2015080867hwp:resource-id:jnephrol;27/9/2797American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, Cell Signaling, nutrition, SGK-1Basic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150808671046-66731533-34502016-02-15T06:04:51-08:002016-09Journal of the American Society of NephrologyBasic Research27992797254528082547
- Inorganic Phosphate Activates the AKT/mTORC1 Pathway and Shortens the Life Span of an α‑Klotho–Deficient ModelInorganic phosphate (Pi) has been implicated in the pathogenesis of accelerated aging; however, the underlying mechanisms remain elusive. Herein, we demonstrated in cultured cells and in vivo that increased levels of extracellular Pi activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway by suppressing membrane-bound phosphatase and tensin homolog (PTEN) levels in a manner requiring the sodium-dependent Pi transporter PiT‑1. High levels of extracellular Pi also led to phosphorylation of Ser/Thr clusters in the C‑terminal tail of PTEN, which has been shown to dissociate PTEN from the membrane. Notably, blockade of mTORC1 activity by rapamycin treatment prolonged the life span of hyperphosphatemic α‑Klotho–deficient (Kl−/−) mice. Dietary correction of hyperphosphatemia or treatment with rapamycin also rescued the brown adipose tissue dysfunction and oxidative damage observed in Kl−/− mice. Furthermore, rapamycin treatment partially rescued these effects and extended the life span when Kl−/− mice were maintained on a high-phosphate diet. Finally, rapamycin reduced circulating Pi levels in Kl−/− mice, apparently by decreasing the localization of sodium-dependent Pi transport protein 2a at the renal brush border membrane. Therefore, the activation of mTORC1 may create a vicious loop that exacerbates the retention of Pi, which in turn may enhance oxidative damage and ultimately shorten the life span of Kl−/− mice. These results demonstrate that Pi has important roles in the aging process, and the blockade of mTORC1 may have therapeutic potential for premature aging-like symptoms associated with hyperphosphatemia.10.1681/ASN.2015040446Fri, 12 Feb 2016 08:26:53 GMT-08:00Inorganic Phosphate Activates the AKT/mTORC1 Pathway and Shortens the Life Span of an α‑Klotho–Deficient ModelInorganic phosphate (Pi) has been implicated in the pathogenesis of accelerated aging; however, the underlying mechanisms remain elusive. Herein, we demonstrated in cultured cells and in vivo that increased levels of extracellular Pi activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway by suppressing membrane-bound phosphatase and tensin homolog (PTEN) levels in a manner requiring the sodium-dependent Pi transporter PiT‑1. High levels of extracellular Pi also led to phosphorylation of Ser/Thr clusters in the C‑terminal tail of PTEN, which has been shown to dissociate PTEN from the membrane. Notably, blockade of mTORC1 activity by rapamycin treatment prolonged the life span of hyperphosphatemic α‑Klotho–deficient (Kl−/−) mice. Dietary correction of hyperphosphatemia or treatment with rapamycin also rescued the brown adipose tissue dysfunction and oxidative damage observed in Kl−/− mice. Furthermore, rapamycin treatment partially rescued these effects and extended the life span when Kl−/− mice were maintained on a high-phosphate diet. Finally, rapamycin reduced circulating Pi levels in Kl−/− mice, apparently by decreasing the localization of sodium-dependent Pi transport protein 2a at the renal brush border membrane. Therefore, the activation of mTORC1 may create a vicious loop that exacerbates the retention of Pi, which in turn may enhance oxidative damage and ultimately shorten the life span of Kl−/− mice. These results demonstrate that Pi has important roles in the aging process, and the blockade of mTORC1 may have therapeutic potential for premature aging-like symptoms associated with hyperphosphatemia.Kawai, MasanobuKinoshita, SaoriOzono, KeiichiMichigami, Toshimi2016-02-12T08:26:53-08:00doi:10.1681/ASN.2015040446hwp:resource-id:jnephrol;27/9/2810American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyaging, phosphate metabolism, Klotho, PTEN, oxidative stress, brown adipose tissueBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150404461046-66731533-34502016-02-12T08:26:53-08:002016-09Journal of the American Society of NephrologyBasic Research27928102824
- The Risk of Major Hemorrhage with CKDNew staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002–2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m2) and urine albumin-to-creatinine ratio (ACR; >300, 30–300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m2 had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted.10.1681/ASN.2015050535Thu, 28 Jan 2016 09:48:40 GMT-08:00The Risk of Major Hemorrhage with CKDNew staging systems for CKD account for both reduced eGFR and albuminuria; whether each measure associates with greater risk of hemorrhage is unclear. In this retrospective cohort study (2002–2010), we grouped 516,197 adults ≥40 years old by eGFR (≥90, 60 to <90, 45 to <60, 30 to <45, 15 to <30, or <15 ml/min per 1.73 m2) and urine albumin-to-creatinine ratio (ACR; >300, 30–300, or <30 mg/g) to examine incidence of hemorrhage. The 3-year cumulative incidence of hemorrhage increased 20-fold across declining eGFR and increasing urine ACR groupings (highest eGFR/lowest ACR: 0.5%; lowest eGFR/highest ACR: 10.1%). Urine ACR altered the association of eGFR with hemorrhage (P<0.001). In adjusted models using the highest eGFR/lowest ACR grouping as the referent, patients with eGFR=15 to <30 ml/min per 1.73 m2 had adjusted relative risks of hemorrhage of 1.9 (95% confidence interval [95% CI], 1.5 to 2.4) with the lowest ACR and 3.7 (95% CI, 3.0 to 4.5) with the highest ACR. Patients with the highest eGFR/highest ACR had an adjusted relative risk of hemorrhage of 2.3 (95% CI, 1.8 to 2.9), comparable with the risk for patients with the lowest eGFR/lowest ACR. The associations attenuated but remained significant after adjustment for anticoagulant and antiplatelet use in patients ≥66 years old. The risk of hemorrhage differed by urine ACR in high risk subgroups. Our data show that declining eGFR and increasing albuminuria each independently increase hemorrhage risk. Strategies to reduce hemorrhage events among patients with CKD are warranted.Molnar, Amber O.Bota, Sarah E.Garg, Amit X.Harel, ZivLam, NganMcArthur, EricNesrallah, GihadPerl, JeffreySood, Manish M.2016-01-28T09:48:40-08:00doi:10.1681/ASN.2015050535hwp:resource-id:jnephrol;27/9/2825American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, vascular disease, albuminuria, hemorrhage, bleeding riskClinical EpidemiologyClinical Epidemiologyresearch-article20162016-09-01September 201610.1681/ASN.20150505351046-66731533-34502016-01-28T09:48:40-08:002016-09Journal of the American Society of NephrologyClinical Epidemiology27928252832
- Far Upstream Element-Binding Protein 1 Binds the 3′ Untranslated Region of PKD2 and Suppresses Its TranslationAutosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3′ untranslated region (3′UTR) of PKD2 mRNA inhibits luciferase protein expression. We then identified nucleotides 691–1044, which we called 3FI, as the 3′UTR fragment necessary for repressing the expression of luciferase or PKD2 in this system. Using a pull-down assay and mass spectrometry we identified far upstream element-binding protein 1 (FUBP1) as a 3FI-binding protein. In vitro overexpression of FUBP1 inhibited the expression of PKD2 protein but not mRNA. In embryonic zebrafish, FUBP1 knockdown (KD) by morpholino injection increased PKD2 expression and alleviated fish tail curling caused by morpholino-mediated KD of PKD2. Conversely, FUBP1 overexpression by mRNA injection significantly increased pronephric cyst occurrence and tail curling in zebrafish embryos. Furthermore, FUBP1 binds directly to eukaryotic translation initiation factor 4E-binding protein 1, indicating a link to the translation initiation complex. These results show that FUBP1 binds 3FI in the PKD2 3′UTR to inhibit PKD2 translation, regulating zebrafish disease phenotypes associated with PKD2 KD.10.1681/ASN.2015070836Tue, 02 Feb 2016 06:15:35 GMT-08:00Far Upstream Element-Binding Protein 1 Binds the 3′ Untranslated Region of PKD2 and Suppresses Its TranslationAutosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3′ untranslated region (3′UTR) of PKD2 mRNA inhibits luciferase protein expression. We then identified nucleotides 691–1044, which we called 3FI, as the 3′UTR fragment necessary for repressing the expression of luciferase or PKD2 in this system. Using a pull-down assay and mass spectrometry we identified far upstream element-binding protein 1 (FUBP1) as a 3FI-binding protein. In vitro overexpression of FUBP1 inhibited the expression of PKD2 protein but not mRNA. In embryonic zebrafish, FUBP1 knockdown (KD) by morpholino injection increased PKD2 expression and alleviated fish tail curling caused by morpholino-mediated KD of PKD2. Conversely, FUBP1 overexpression by mRNA injection significantly increased pronephric cyst occurrence and tail curling in zebrafish embryos. Furthermore, FUBP1 binds directly to eukaryotic translation initiation factor 4E-binding protein 1, indicating a link to the translation initiation complex. These results show that FUBP1 binds 3FI in the PKD2 3′UTR to inhibit PKD2 translation, regulating zebrafish disease phenotypes associated with PKD2 KD.Zheng, WangShen, FanHu, RuikunRoy, BirbickramYang, JungWooWang, QianZhang, FanKing, Jennifer C.Sergi, ConsolatoLiu, Song-MeiCordat, EmmanuelleTang, JingfengCao, YingAli, DeclanChen, Xing-Zhen2016-02-02T06:15:35-08:00doi:10.1681/ASN.2015070836hwp:resource-id:jnephrol;27/9/2645American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, 3'UTR, RNA-binding protein, translational regulation, zebrafishBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150708361046-66731533-34502016-02-02T06:15:35-08:002016-09Journal of the American Society of NephrologyBasic Research27926452657
- Tubular Epithelial NF-κB Activity Regulates Ischemic AKINF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of AKI. The cell type–specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)–induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed that IRI induced widespread NF-κB activation in renal tubular epithelia and in interstitial cells that peaked 2–3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBαΔN in renal proximal, distal, and collecting duct epithelial cells. Compared with control mice, these mice exhibited improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration after IRI-induced AKI. Furthermore, tubular NF-κB–dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBαΔN-expressing mice and exposed to hypoxia-mimetic agent cobalt chloride exhibited less apoptosis and expressed lower levels of chemokines than cells from control mice did. Our results indicate that postischemic NF-κB activation in renal tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.10.1681/ASN.2015070748Thu, 28 Jan 2016 09:48:42 GMT-08:00Tubular Epithelial NF-κB Activity Regulates Ischemic AKINF-κB is a key regulator of innate and adaptive immunity and is implicated in the pathogenesis of AKI. The cell type–specific functions of NF-κB in the kidney are unknown; however, the pathway serves distinct functions in immune and tissue parenchymal cells. We analyzed tubular epithelial-specific NF-κB signaling in a mouse model of ischemia-reperfusion injury (IRI)–induced AKI. NF-κB reporter activity and nuclear localization of phosphorylated NF-κB subunit p65 analyses in mice revealed that IRI induced widespread NF-κB activation in renal tubular epithelia and in interstitial cells that peaked 2–3 days after injury. To genetically antagonize tubular epithelial NF-κB activity, we generated mice expressing the human NF-κB super-repressor IκBαΔN in renal proximal, distal, and collecting duct epithelial cells. Compared with control mice, these mice exhibited improved renal function, reduced tubular apoptosis, and attenuated neutrophil and macrophage infiltration after IRI-induced AKI. Furthermore, tubular NF-κB–dependent gene expression profiles revealed temporally distinct functional gene clusters for apoptosis, chemotaxis, and morphogenesis. Primary proximal tubular cells isolated from IκBαΔN-expressing mice and exposed to hypoxia-mimetic agent cobalt chloride exhibited less apoptosis and expressed lower levels of chemokines than cells from control mice did. Our results indicate that postischemic NF-κB activation in renal tubular epithelia aggravates tubular injury and exacerbates a maladaptive inflammatory response.Markó, LajosVigolo, EmiliaHinze, ChristianPark, Joon-KeunRoël, GiuliettaBalogh, AndrásChoi, MiraWübken, AnneCording, JimmiBlasig, Ingolf E.Luft, Friedrich C.Scheidereit, ClausSchmidt-Ott, Kai M.Schmidt-Ullrich, RuthMüller, Dominik N.2016-01-28T09:48:42-08:00doi:10.1681/ASN.2015070748hwp:resource-id:jnephrol;27/9/2658American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, ischemia-reperfusion, chemokine, renal tubular, epithelial cells, apoptosis, NF-kappaBBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150707481046-66731533-34502016-01-28T09:48:42-08:002016-09Journal of the American Society of NephrologyBasic Research27926582669
- A Novel Extrinsic Pathway for the Unfolded Protein Response in the KidneyThe ribonuclease angiogenin is a component of the mammalian stress response, and functions in both cell-autonomous and non-cell-autonomous ways to promote tissue adaptation to injury. We recently showed that angiogenin regulates tissue homeostasis during AKI associated with endoplasmic reticulum (ER) stress through the production of transfer RNA fragments that interfere with translation initiation and thereby alleviate ER stress. However, whether the paracrine signaling mediated by angiogenin secretion is a genuine component of the ER stress response to kidney injury is unknown. Here, we explored the molecular mechanisms by which angiogenin is secreted upon ER stress, and determined how it modulates the inflammatory microenvironment. In cultured renal epithelial cells, ER stress specifically induced angiogenin secretion under the selective control of inositol-requiring enzyme 1α, a key activator of the unfolded protein response. The transcription factors spliced X-box–binding protein 1 and p65, which are activated by inositol-requiring enzyme 1α upon ER stress, each bound the angiogenin promoter and controlled the amount of angiogenin secreted. Furthermore, p65 promoted angiogenin transcription in an ER stress-dependent manner. Similar to secretion of the ER stress-induced proinflammatory cytokine IL-6, secretion of angiogenin required the ER-Golgi pathway. Notably, incubation of human macrophages with angiogenin promoted macrophage reprogramming toward an activated and proinflammatory phenotype. In patients, angiogenin expression increased upon renal inflammation, and the urinary concentration of angiogenin correlated with the extent of immune-mediated kidney injury. Collectively, our data identify angiogenin as a mediator of the ER stress-dependent inflammatory response and as a potential noninvasive biomarker of AKI.10.1681/ASN.2015060703Thu, 28 Jan 2016 09:48:41 GMT-08:00A Novel Extrinsic Pathway for the Unfolded Protein Response in the KidneyThe ribonuclease angiogenin is a component of the mammalian stress response, and functions in both cell-autonomous and non-cell-autonomous ways to promote tissue adaptation to injury. We recently showed that angiogenin regulates tissue homeostasis during AKI associated with endoplasmic reticulum (ER) stress through the production of transfer RNA fragments that interfere with translation initiation and thereby alleviate ER stress. However, whether the paracrine signaling mediated by angiogenin secretion is a genuine component of the ER stress response to kidney injury is unknown. Here, we explored the molecular mechanisms by which angiogenin is secreted upon ER stress, and determined how it modulates the inflammatory microenvironment. In cultured renal epithelial cells, ER stress specifically induced angiogenin secretion under the selective control of inositol-requiring enzyme 1α, a key activator of the unfolded protein response. The transcription factors spliced X-box–binding protein 1 and p65, which are activated by inositol-requiring enzyme 1α upon ER stress, each bound the angiogenin promoter and controlled the amount of angiogenin secreted. Furthermore, p65 promoted angiogenin transcription in an ER stress-dependent manner. Similar to secretion of the ER stress-induced proinflammatory cytokine IL-6, secretion of angiogenin required the ER-Golgi pathway. Notably, incubation of human macrophages with angiogenin promoted macrophage reprogramming toward an activated and proinflammatory phenotype. In patients, angiogenin expression increased upon renal inflammation, and the urinary concentration of angiogenin correlated with the extent of immune-mediated kidney injury. Collectively, our data identify angiogenin as a mediator of the ER stress-dependent inflammatory response and as a potential noninvasive biomarker of AKI.Mami, IadhTavernier, QuentinBouvier, NicolasAboukamis, RimDesbuissons, GeoffroyRabant, MarionPoindessous, VirginieLaurent-Puig, PierreBeaune, PhilippeTharaux, Pierre-LouisThervet, EricChevet, EricAnglicheau, DanyPallet, Nicolas2016-01-28T09:48:41-08:00doi:10.1681/ASN.2015060703hwp:resource-id:jnephrol;27/9/2670American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute rejection, cytokines, macrophages, renal tubular epithelial cells, cell activationBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150607031046-66731533-34502016-01-28T09:48:41-08:002016-09Journal of the American Society of NephrologyBasic Research27926702683
- Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKDStudies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte–specific CD–knockout mice that developed proteinuria at 5 months of age and ESRD by 20–22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CD-deficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7– and lysosome–associated membrane glycoprotein 1–positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte–specific CD–knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c–positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death.10.1681/ASN.2015040366Thu, 28 Jan 2016 09:48:43 GMT-08:00Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKDStudies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte–specific CD–knockout mice that developed proteinuria at 5 months of age and ESRD by 20–22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CD-deficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7– and lysosome–associated membrane glycoprotein 1–positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte–specific CD–knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c–positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death.Yamamoto-Nonaka, KanaeKoike, MasatoAsanuma, KatsuhikoTakagi, MiyukiOliva Trejo, Juan AlejandroSeki, TakutoHidaka, TeruoIchimura, KoichiroSakai, TatsuoTada, NorihiroUeno, TakashiUchiyama, YasuoTomino, Yasuhiko2016-01-28T09:48:43-08:00doi:10.1681/ASN.2015040366hwp:resource-id:jnephrol;27/9/2685American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, Cathepsin D, Autophagy, Lysosome, subunit c of mitochondrial ATP synthase, glomerulosclerosisBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150403661046-66731533-34502016-01-28T09:48:43-08:002016-09Journal of the American Society of NephrologyBasic Research27926852700
- Distinct Requirements for Vacuolar Protein Sorting 34 Downstream Effector Phosphatidylinositol 3-Phosphate 5-Kinase in Podocytes Versus Proximal Tubular CellsThe mechanisms by which the glomerular filtration barrier prevents the loss of large macromolecules and simultaneously, maintains the filter remain poorly understood. Recent studies proposed that podocytes have an active role in both the endocytosis of filtered macromolecules and the maintenance of the filtration barrier. Deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. We recently showed that the vacuolation phenotype in cultured Vps34–deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase (PIKfyve), which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2. PIKfyve perturbation and PtdIns(3,5)P2 reduction result in massive membrane vacuolation along the endosomal system, but the cell-specific functions of PIKfyve in vivo remain unclear. We show here that the genetic deletion of PIKfyve in endocytically active proximal tubular cells resulted in the development of large cytoplasmic vacuoles caused by arrested endocytic traffic progression at a late-endosome stage. In contrast, deletion of PIKfyve in glomerular podocytes did not significantly alter the endosomal morphology, even in age 18-month-old mice. However, on culturing, the PIKfyve-deleted podocytes developed massive cytoplasmic vacuoles. In summary, these data suggest that glomerular podocytes and proximal tubules have different requirements for PIKfyve function, likely related to distinct in vivo needs for endocytic flux.10.1681/ASN.2015050555Fri, 29 Jan 2016 09:12:15 GMT-08:00Distinct Requirements for Vacuolar Protein Sorting 34 Downstream Effector Phosphatidylinositol 3-Phosphate 5-Kinase in Podocytes Versus Proximal Tubular CellsThe mechanisms by which the glomerular filtration barrier prevents the loss of large macromolecules and simultaneously, maintains the filter remain poorly understood. Recent studies proposed that podocytes have an active role in both the endocytosis of filtered macromolecules and the maintenance of the filtration barrier. Deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. We recently showed that the vacuolation phenotype in cultured Vps34–deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase (PIKfyve), which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2. PIKfyve perturbation and PtdIns(3,5)P2 reduction result in massive membrane vacuolation along the endosomal system, but the cell-specific functions of PIKfyve in vivo remain unclear. We show here that the genetic deletion of PIKfyve in endocytically active proximal tubular cells resulted in the development of large cytoplasmic vacuoles caused by arrested endocytic traffic progression at a late-endosome stage. In contrast, deletion of PIKfyve in glomerular podocytes did not significantly alter the endosomal morphology, even in age 18-month-old mice. However, on culturing, the PIKfyve-deleted podocytes developed massive cytoplasmic vacuoles. In summary, these data suggest that glomerular podocytes and proximal tubules have different requirements for PIKfyve function, likely related to distinct in vivo needs for endocytic flux.Venkatareddy, MadhusudanVerma, RakeshKalinowski, AnnePatel, Sanjeevkumar R.Shisheva, AssiaGarg, Puneet2016-01-29T09:12:15-08:00doi:10.1681/ASN.2015050555hwp:resource-id:jnephrol;27/9/2702American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, glomerulus, proteinuriaBasic ResearchBasic Researchresearch-article20162016-09-01September 201610.1681/ASN.20150505551046-66731533-34502016-01-29T09:12:15-08:002016-09Journal of the American Society of NephrologyBasic Research27927022719
- T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS10.2215/CJN.11941115Tue, 07 Jun 2016 07:13:32 GMT-07:00T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGSChan, Chang-YienLiu, Isaac DeshengResontoc, Lourdes PaulaNg, Kar-HuiChan, Yiong-HuakLau, Perry Yew-WengThan, MyaJordan, Stanley C.Lam, Kong-PengYeo, Wee-SongYap, Hui-Kim2016-06-07T07:13:32-07:00doi:10.2215/CJN.11941115hwp:resource-id:clinjasn;11/8/1360American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGlomerulosclerosis, Focal Segmental, Lymphocyte Activation, Rituximab, Humans, Immunosuppressive Agents, nephrotic syndrome, Prednisolone, proteinuria, ROC Curve, T-Lymphocyte SubsetsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-08-08August 08, 201610.2215/CJN.119411151555-90411555-905X2016-06-07T07:13:32-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11813601368
- Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial10.2215/CJN.12051115Tue, 17 May 2016 06:53:02 GMT-07:00Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD TrialNadkarni, Girish N.Rao, VeenaIsmail-Beigi, FaramarzFonseca, Vivian A.Shah, Sudhir V.Simonson, Michael S.Cantley, LloydDevarajan, PrasadParikh, Chirag R.Coca, Steven G.2016-05-17T06:53:02-07:00doi:10.2215/CJN.12051115hwp:resource-id:clinjasn;11/8/1343American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, renal injury, renal fibrosis, chronic kidney disease, Biomarkers, Diabetes Mellitus, Type 2, Follow-Up Studies, Inflammation, CCL2 protein, human, CHI3L1 protein, humanOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-08-08August 08, 201610.2215/CJN.120511151555-90411555-905X2016-05-17T06:53:02-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11813431352
- Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson Heart Study10.2215/CJN.13111215Thu, 23 Jun 2016 08:13:31 GMT-07:00Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson Heart StudyAfkarian, MaryamKatz, RonitBansal, NishaCorrea, AdolfoKestenbaum, BryanHimmelfarb, Jonathande Boer, Ian H.Young, Bessie2016-06-23T08:13:31-07:00doi:10.2215/CJN.13111215hwp:resource-id:clinjasn;11/8/1384American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, chronic kidney disease, stroke, cardiovascular disease, cardiovascular mortality, African Americans, Albumins, coronary artery disease, creatinine, Follow-Up Studies, Humans, Renal Insufficiency, ChronicOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-08-08August 08, 201610.2215/CJN.131112151555-90411555-905X2016-06-23T08:13:31-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11813841391
- Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease10.2215/CJN.13591215Mon, 11 Jul 2016 10:26:42 GMT-07:00Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane DiseaseCanney, MarkO’Hara, Paul V.McEvoy, Caitriona M.Medani, SamarConnaughton, Dervla M.Abdalla, Ahad A.Doyle, RossStack, Austin G.O’Seaghdha, Conall M.Clarkson, Michael R.Griffin, Matthew D.Holian, JohnDorman, Anthony M.Niland, AileenKeogan, MaryWallace, Eleanor M.Conlon, Niall P.Walsh, CathalKelly, AlanLittle, Mark A.2016-07-11T10:26:42-07:00doi:10.2215/CJN.13591215hwp:resource-id:clinjasn;11/8/1392American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanti-glomerular basement membrane disease, epidemiology, cluster analysis, incidence, ANCA, autoantibodies, follow-up studies, humans, kidney, kidney failure, chronicOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-08-08August 08, 201610.2215/CJN.135912151555-90411555-905X2016-07-11T10:26:42-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11881392132413991326
- Antihypertensive Medication Use in Older Patients Transitioning from Chronic Kidney Disease to End-Stage Renal Disease on Dialysis10.2215/CJN.10611015Mon, 27 Jun 2016 06:49:03 GMT-07:00Antihypertensive Medication Use in Older Patients Transitioning from Chronic Kidney Disease to End-Stage Renal Disease on DialysisChang, Tara I.Zheng, YuanchaoMontez-Rath, Maria E.Winkelmayer, Wolfgang C.2016-06-27T06:49:03-07:00doi:10.2215/CJN.10611015hwp:resource-id:clinjasn;11/8/1401American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyACE inhibitors, cardiovascular disease, blood pressure, coronary artery disease, acute kidney injury, antihypertensive agents, hospitalization, humans, hyperkalemia, kidney failure, chronic, renal dialysisOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-08-08August 08, 201610.2215/CJN.106110151555-90411555-905X2016-06-27T06:49:03-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11881401132714121329
- Geovariation in Fracture Risk among Patients Receiving Hemodialysis10.2215/CJN.11651115Tue, 07 Jun 2016 07:13:32 GMT-07:00Geovariation in Fracture Risk among Patients Receiving HemodialysisWetmore, James B.Liu, JiannongWirtz, Heidi S.Gilbertson, David T.Cooper, KerryNieman, Kimberly M.Collins, Allan J.Bradbury, Brian D.2016-06-07T07:13:32-07:00doi:10.2215/CJN.11651115hwp:resource-id:clinjasn;11/8/1413American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, Fracture, geographic variation, hemodialysis, Follow-Up Studies, Humans, Medicaid, Medicare, Morbidity, PrevalenceOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-08-08August 08, 201610.2215/CJN.116511151555-90411555-905X2016-06-07T07:13:32-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11814131421
- Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network Study10.2215/CJN.10991015Fri, 22 Jul 2016 06:30:48 GMT-07:00Comparison of Urine Output among Patients Treated with More Intensive Versus Less Intensive RRT: Results from the Acute Renal Failure Trial Network StudyMc Causland, Finnian R.Asafu-Adjei, JosephineBetensky, Rebecca A.Palevsky, Paul M.Waikar, Sushrut S.2016-07-22T06:30:48-07:00doi:10.2215/CJN.10991015hwp:resource-id:clinjasn;11/8/1335American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, Acute kidney injury, critical illness, Humans, Randomized trials as topic, renal dialysis, renal replacement therapyOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-08-08August 08, 201610.2215/CJN.109910151555-90411555-905X2016-07-22T06:30:48-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11881335132113421323
- New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access OutcomesVascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.10.2215/CJN.02030216Mon, 11 Jul 2016 10:26:43 GMT-07:00New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access OutcomesVascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.Lee, TimmyMisra, Sanjay2016-07-11T10:26:43-07:00doi:10.2215/CJN.02030216hwp:resource-id:clinjasn;11/8/1504American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyArteriovenous access, Arteriovenous fistula, Arteriovenous graftMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-08-08August 08, 201610.2215/CJN.020302161555-90411555-905X2016-07-11T10:26:43-07:002016-08-08Clinical Journal of the American Society of NephrologyMoving Points in Nephrology11815041512
- Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK10.2215/CJN.12221115Thu, 26 May 2016 06:28:31 GMT-07:00Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASKTin, AdrienneGrams, Morgan E.Estrella, MichelleLipkowitz, MichaelGreene, Tom H.Kao, Wen Hong LindaLi, LiangAppel, Lawrence J.2016-05-26T06:28:31-07:00doi:10.2215/CJN.12221115hwp:resource-id:clinjasn;11/8/1353American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, Epidemiology and outcomes, genetic renal disease, African Americans, Alleles, Follow-Up Studies, Genotype, glomerular filtration rate, Humans, hypertension, Kidney DiseasesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-08-08August 08, 201610.2215/CJN.122211151555-90411555-905X2016-05-26T06:28:31-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11813531359
- New Insights into Dialysis Vascular Access: Introduction10.2215/CJN.01610216Mon, 08 Aug 2016 10:00:40 GMT-07:00New Insights into Dialysis Vascular Access: IntroductionAllon, Michael2016-08-08T10:00:40-07:00doi:10.2215/CJN.01610216hwp:resource-id:clinjasn;11/8/1484American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous access, arteriovenous fistula, arteriovenous graft, Arteriovenous Shunt, Surgical, Fluid Therapy, Problem Solving, renal dialysisMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-08-08August 08, 201610.2215/CJN.016102161555-90411555-905X2016-08-08T10:00:40-07:002016-08-08Clinical Journal of the American Society of NephrologyMoving Points in Nephrology11814841486
- New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG OutcomesDespite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.10.2215/CJN.01860216Mon, 11 Jul 2016 10:26:42 GMT-07:00New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG OutcomesDespite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it.Vazquez-Padron, Roberto I.Allon, Michael2016-07-11T10:26:42-07:00doi:10.2215/CJN.01860216hwp:resource-id:clinjasn;11/8/1495American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous fistula, arteriovenous graft, pre-existing pathologies, vascular calcification, vascular fibrosis, intimal hyperplasia, arteries, Humans, Hyperplasia, renal dialysis, Renal Insufficiency, Chronic, VeinsMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-08-08August 08, 201610.2215/CJN.018602161555-90411555-905X2016-07-11T10:26:42-07:002016-08-08Clinical Journal of the American Society of NephrologyMoving Points in Nephrology11814951503
- Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress NephropathyClimate change has led to significant rise of 0.8°C–0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves (extreme heat events). Climate change has also been increasingly connected to detrimental human health. One of the consequences of climate-related extreme heat exposure is dehydration and volume loss, leading to acute mortality from exacerbations of pre-existing chronic disease, as well as from outright heat exhaustion and heat stroke. Recent studies have also shown that recurrent heat exposure with physical exertion and inadequate hydration can lead to CKD that is distinct from that caused by diabetes, hypertension, or GN. Epidemics of CKD consistent with heat stress nephropathy are now occurring across the world. Here, we describe this disease, discuss the locations where it appears to be manifesting, link it with increasing temperatures, and discuss ongoing attempts to prevent the disease. Heat stress nephropathy may represent one of the first epidemics due to global warming. Government, industry, and health policy makers in the impacted regions should place greater emphasis on occupational and community interventions.10.2215/CJN.13841215Thu, 05 May 2016 06:45:48 GMT-07:00Climate Change and the Emergent Epidemic of CKD from Heat Stress in Rural Communities: The Case for Heat Stress NephropathyClimate change has led to significant rise of 0.8°C–0.9°C in global mean temperature over the last century and has been linked with significant increases in the frequency and severity of heat waves (extreme heat events). Climate change has also been increasingly connected to detrimental human health. One of the consequences of climate-related extreme heat exposure is dehydration and volume loss, leading to acute mortality from exacerbations of pre-existing chronic disease, as well as from outright heat exhaustion and heat stroke. Recent studies have also shown that recurrent heat exposure with physical exertion and inadequate hydration can lead to CKD that is distinct from that caused by diabetes, hypertension, or GN. Epidemics of CKD consistent with heat stress nephropathy are now occurring across the world. Here, we describe this disease, discuss the locations where it appears to be manifesting, link it with increasing temperatures, and discuss ongoing attempts to prevent the disease. Heat stress nephropathy may represent one of the first epidemics due to global warming. Government, industry, and health policy makers in the impacted regions should place greater emphasis on occupational and community interventions.Glaser, JasonLemery, JayRajagopalan, BalajiDiaz, Henry F.García-Trabanino, RamónTaduri, GangadharMadero, MagdalenaAmarasinghe, MalaAbraham, GeorgiAnutrakulchai, SiriratJha, VivekanandStenvinkel, PeterRoncal-Jimenez, CarlosLanaspa, Miguel A.Correa-Rotter, RicardoSheikh-Hamad, DavidBurdmann, Emmanuel A.Andres-Hernando, AnaMilagres, TamaraWeiss, IlanaKanbay, MehmetWesseling, CatharinaSánchez-Lozada, Laura GabrielaJohnson, Richard J.2016-05-05T06:45:48-07:00doi:10.2215/CJN.13841215hwp:resource-id:clinjasn;11/8/1472American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, Climate, Climate Change, Dehydration, Health Policy, Heat Exhaustion, Hot Temperature, Physical Exertion, Renal Insufficiency, Chronic, Rural PopulationSpecial FeatureSpecial Featureresearch-article20162016-08-08August 08, 201610.2215/CJN.138412151555-90411555-905X2016-05-05T06:45:48-07:002016-08-08Clinical Journal of the American Society of NephrologySpecial Feature11814721483
- Update on Ethical Issues in Pediatric Dialysis: Has Pediatric Dialysis Become Morally Obligatory?Improvements in pediatric dialysis over the past 50 years have made the decision to proceed with dialysis straightforward for the majority of pediatric patients. For certain groups, however, such as children with multiple comorbid conditions, children and families with few social and economic resources, and neonates and infants, the decision of whether to proceed with dialysis remains much more controversial. In this review, we will examine the best available data regarding the outcomes of dialysis in these populations and analyze the important ethical considerations that should guide decisions regarding dialysis for these patients. We conclude that providers must continue to follow a nuanced and individualized approach in decision making for each child and to recognize that, regardless of the decision reached about dialysis, there is a continued duty to care for patients and families to maximize the remaining quality of their lives.10.2215/CJN.12741215Fri, 01 Apr 2016 06:30:13 GMT-07:00Update on Ethical Issues in Pediatric Dialysis: Has Pediatric Dialysis Become Morally Obligatory?Improvements in pediatric dialysis over the past 50 years have made the decision to proceed with dialysis straightforward for the majority of pediatric patients. For certain groups, however, such as children with multiple comorbid conditions, children and families with few social and economic resources, and neonates and infants, the decision of whether to proceed with dialysis remains much more controversial. In this review, we will examine the best available data regarding the outcomes of dialysis in these populations and analyze the important ethical considerations that should guide decisions regarding dialysis for these patients. We conclude that providers must continue to follow a nuanced and individualized approach in decision making for each child and to recognize that, regardless of the decision reached about dialysis, there is a continued duty to care for patients and families to maximize the remaining quality of their lives.Wightman, Aaron G.Freeman, Michael A.2016-04-01T06:30:13-07:00doi:10.2215/CJN.12741215hwp:resource-id:clinjasn;11/8/1456American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis withholding, pediatric nephrology, mortality, Economic Impact, Child, Decision Making, Humans, Moral Obligations, pediatrics, renal dialysisEthics SeriesEthics Seriesresearch-article20162016-08-08August 08, 201610.2215/CJN.127412151555-90411555-905X2016-04-01T06:30:13-07:002016-08-08Clinical Journal of the American Society of NephrologyEthics Series11814561462
- Correction10.2215/CJN.05620516Mon, 27 Jun 2016 06:49:04 GMT-07:00CorrectionAmerican Society of Nephrology2016-06-27T06:49:04-07:00doi:10.2215/CJN.05620516hwp:resource-id:clinjasn;11/8/1513American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, nephrology quiz and questionnaire, Kidney WeekErratumErratumcorrection20162016-08-08August 08, 201610.2215/CJN.056205161555-90411555-905X2016-06-27T06:49:04-07:002016-08-08Clinical Journal of the American Society of NephrologyErratum11118515138841513890
- Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney Stones10.2215/CJN.10360915Thu, 09 Jun 2016 07:34:38 GMT-07:00Intestinal Calcium Absorption among Hypercalciuric Patients with or without Calcium Kidney StonesVezzoli, GiuseppeMacrina, LorenzaRubinacci, AlessandroSpotti, DonatellaArcidiacono, Teresa2016-06-09T07:34:38-07:00doi:10.2215/CJN.10360915hwp:resource-id:clinjasn;11/8/1450American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypercalciuria, calcium metabolism disorders, kidney stones, Bone Density, Bone Diseases, Metabolic, Calcium, Dietary, Humans, Intestinal Absorption, Regression Analysis, StrontiumOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20162016-08-08August 08, 201610.2215/CJN.103609151555-90411555-905X2016-06-09T07:34:38-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11814501455
- Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome10.2215/CJN.01000116Wed, 08 Jun 2016 06:36:35 GMT-07:00Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport SyndromeKamiyoshi, NaohiroNozu, KandaiFu, Xue JunMorisada, NaoyaNozu, YoshimiYe, Ming JuanImafuku, AyaMiura, KenichiroYamamura, TomohikoMinamikawa, ShogoShono, AkemiNinchoji, TakeshiMorioka, IchiroNakanishi, KoichiYoshikawa, NorishigeKaito, HiroshiIijima, Kazumoto2016-06-08T06:36:35-07:00doi:10.2215/CJN.01000116hwp:resource-id:clinjasn;11/8/1441American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAlport syndrome, COL4A4, Autosomal dominant, COL4A3, Glomerular Basement Membrane, Hearing Loss, Humans, Japan, kidney, Phenotype, proteinuria, Renal Insufficiency, ChronicOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20162016-08-08August 08, 201610.2215/CJN.010001161555-90411555-905X2016-06-08T06:36:35-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11814411449
- New Insights into Dialysis Vascular Access: What Is the Optimal Vascular Access Type and Timing of Access Creation in CKD and Dialysis Patients?Optimal vascular access planning begins when the patient is in the predialysis stages of CKD. The choice of optimal vascular access for an individual patient and determining timing of access creation are dependent on a multitude of factors that can vary widely with each patient, including demographics, comorbidities, anatomy, and personal preferences. It is important to consider every patient’s ESRD life plan (hence, their overall dialysis access life plan for every vascular access creation or placement). Optimal access type and timing of access creation are also influenced by factors external to the patient, such as surgeon experience and processes of care. In this review, we will discuss the key determinants in optimal access type and timing of access creation for upper extremity arteriovenous fistulas and grafts.10.2215/CJN.02190216Mon, 11 Jul 2016 10:26:42 GMT-07:00New Insights into Dialysis Vascular Access: What Is the Optimal Vascular Access Type and Timing of Access Creation in CKD and Dialysis Patients?Optimal vascular access planning begins when the patient is in the predialysis stages of CKD. The choice of optimal vascular access for an individual patient and determining timing of access creation are dependent on a multitude of factors that can vary widely with each patient, including demographics, comorbidities, anatomy, and personal preferences. It is important to consider every patient’s ESRD life plan (hence, their overall dialysis access life plan for every vascular access creation or placement). Optimal access type and timing of access creation are also influenced by factors external to the patient, such as surgeon experience and processes of care. In this review, we will discuss the key determinants in optimal access type and timing of access creation for upper extremity arteriovenous fistulas and grafts.Woo, KarenLok, Charmaine E.2016-07-11T10:26:42-07:00doi:10.2215/CJN.02190216hwp:resource-id:clinjasn;11/8/1487American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis access, arteriovenous fistula, arteriovenous graft, timing of creation, Arteriovenous Shunt, Surgical, Fluid Therapy, Humans, renal dialysisMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-08-08August 08, 201610.2215/CJN.021902161555-90411555-905X2016-07-11T10:26:42-07:002016-08-08Clinical Journal of the American Society of NephrologyMoving Points in Nephrology11814871494
- Peripherally Inserted Central Catheters and Hemodialysis Outcomes10.2215/CJN.01980216Thu, 23 Jun 2016 08:13:28 GMT-07:00Peripherally Inserted Central Catheters and Hemodialysis OutcomesMcGill, Rita L.Ruthazer, RobinMeyer, Klemens B.Miskulin, Dana C.Weiner, Daniel E.2016-06-23T08:13:28-07:00doi:10.2215/CJN.01980216hwp:resource-id:clinjasn;11/8/1434American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic hemodialysis, vascular access, arteriovenous fistula, arteriovenous graft, United States Renal Data System, Catheterization, Peripheral, Central Venous Catheters, Follow-Up Studies, Humans, kidney, renal dialysis, Renal Insufficiency, ChronicOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-08-08August 08, 201610.2215/CJN.019802161555-90411555-905X2016-06-23T08:13:28-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11881434133314401334
- Does Changing the Volume Matter? The Relationship of Urine Volume and Dialysis Intensity10.2215/CJN.06420616Fri, 22 Jul 2016 06:30:48 GMT-07:00Does Changing the Volume Matter? The Relationship of Urine Volume and Dialysis IntensityFederspiel, Christine K.Liu, Kathleen D.2016-07-22T06:30:48-07:00doi:10.2215/CJN.06420616hwp:resource-id:clinjasn;11/8/1321American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAcute kidney injury, dialysis, urine volume, blood pressure, fluid therapy, renal dialysisEditorialsEditorialseditorial20162016-08-08August 08, 201610.2215/CJN.064206161555-90411555-905X2016-07-22T06:30:48-07:002016-08-08Clinical Journal of the American Society of NephrologyEditorials11881321133513231342
- Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors10.2215/CJN.12731215Tue, 17 May 2016 06:53:01 GMT-07:00Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney DonorsCourbebaisse, MarieGaillard, FrançoisTissier, Anne-MarieFournier, CatherineLe Nestour, AlexisCorréas, Jean-MichelSlimani-Thevenet, HindMartinez, FrankLéon, CarineEladari, DominiqueTimsit, Marc-OlivierOtal, PhilippeHignette, ChantalFriedlander, GérardMéjean, ArnaudHouillier, PascalKamar, NassimLegendre, Christophe2016-05-17T06:53:01-07:00doi:10.2215/CJN.12731215hwp:resource-id:clinjasn;11/8/1369American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, glomerular filtration rate, chronic renal disease, kidney volume, renal function decline, blood pressure, albuminuria, Humans, kidney, Living DonorsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-08-08August 08, 201610.2215/CJN.127312151555-90411555-905X2016-05-17T06:53:01-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11813691376
- Clustering of Anti-GBM Disease: Clues to an Environmental Trigger?10.2215/CJN.05580516Mon, 11 Jul 2016 10:26:43 GMT-07:00Clustering of Anti-GBM Disease: Clues to an Environmental Trigger?McAdoo, Stephen P.Pusey, Charles D.2016-07-11T10:26:43-07:00doi:10.2215/CJN.05580516hwp:resource-id:clinjasn;11/8/1324American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanti-GBM disease, Goodpasture-s syndrome, ANCA, Epidemiology and outcomes, Glomerular Basement Membrane, Anti-Glomerular Basement Membrane Disease, Cluster Analysis, EnvironmentEditorialsEditorialseditorial20162016-08-08August 08, 201610.2215/CJN.055805161555-90411555-905X2016-07-11T10:26:43-07:002016-08-08Clinical Journal of the American Society of NephrologyEditorials11881324139213261399
- Antihypertensive Medication in Patients Pre- and Postdialysis: Still Hazy After All These Years10.2215/CJN.06130616Mon, 27 Jun 2016 06:49:03 GMT-07:00Antihypertensive Medication in Patients Pre- and Postdialysis: Still Hazy After All These YearsCohen, Jordana B.Townsend, Raymond R.2016-06-27T06:49:03-07:00doi:10.2215/CJN.06130616hwp:resource-id:clinjasn;11/8/1327American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAntihypertensive Agents, Blood Pressure, Humas, Hypertension, Renal DialysisEditorialsEditorialseditorial20162016-08-08August 08, 201610.2215/CJN.061306161555-90411555-905X2016-06-27T06:49:03-07:002016-08-08Clinical Journal of the American Society of NephrologyEditorials11881327140113291412
- Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT10.2215/CJN.10260915Thu, 19 May 2016 06:54:26 GMT-07:00Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRTShotwell, Matthew S.Nesbitt, RossMadonia, Phillip N.Gould, Edward R.Connor, Michael J.Salem, CharbelAduroja, Olufemi A.Amde, MilenGroszek, Joseph J.Wei, PeilinTaylor, Maria E.Tolwani, Ashita J.Fissell, William H.2016-05-19T06:54:26-07:00doi:10.2215/CJN.10260915hwp:resource-id:clinjasn;11/8/1377American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypharmacokinetics, Acute Kidney Injury, piperacillin, extended-infusion, Anti-Bacterial Agents, Critical Illness, Dialysis Solutions, Humans, Microbial Sensitivity Tests, Renal Replacement TherapyOriginal ArticlesCritical Care NephrologyOriginal ArticlesCritical Care Nephrologyresearch-article20162016-08-08August 08, 201610.2215/CJN.102609151555-90411555-905X2016-05-19T06:54:26-07:002016-08-08Clinical Journal of the American Society of NephrologyOriginal Articles11813771383
- Nephrologists Versus Peripherally Inserted Central Catheters: Are the PICCs Winning?10.2215/CJN.05750516Thu, 23 Jun 2016 08:13:34 GMT-07:00Nephrologists Versus Peripherally Inserted Central Catheters: Are the PICCs Winning?Kalloo, SeanWish, Jay B.2016-06-23T08:13:34-07:00doi:10.2215/CJN.05750516hwp:resource-id:clinjasn;11/8/1333American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, chronic kidney disease, end stage kidney disease, hemodialysis, Catheterization, Central Venous, Catheterization, Peripheral, PhysiciansEditorialsEditorialseditorial20162016-08-08August 08, 201610.2215/CJN.057505161555-90411555-905X2016-06-23T08:13:34-07:002016-08-08Clinical Journal of the American Society of NephrologyEditorials11881333143413341440
- Metabolic and Kidney Diseases in the Setting of Climate Change, Water Shortage, and Survival FactorsClimate change (global warming) is leading to an increase in heat extremes and coupled with increasing water shortage, provides a perfect storm for a new era of environmental crises and potentially, new diseases. We use a comparative physiologic approach to show that one of the primary mechanisms by which animals protect themselves against water shortage is to increase fat mass as a means for providing metabolic water. Strong evidence suggests that certain hormones (vasopressin), foods (fructose), and metabolic products (uric acid) function as survival signals to help reduce water loss and store fat (which also provides a source of metabolic water). These mechanisms are intricately linked with each other and stimulated by dehydration and hyperosmolarity. Although these mechanisms were protective in the setting of low sugar and low salt intake in our past, today, the combination of diets high in fructose and salty foods, increasing temperatures, and decreasing available water places these survival signals in overdrive and may be accelerating the obesity and diabetes epidemics. The recent discovery of multiple epidemics of CKD occurring in agricultural workers in hot and humid environments may represent harbingers of the detrimental consequences of the combination of climate change and overactivation of survival pathways.10.1681/ASN.2015121314Thu, 09 Jun 2016 07:35:14 GMT-07:00Metabolic and Kidney Diseases in the Setting of Climate Change, Water Shortage, and Survival FactorsClimate change (global warming) is leading to an increase in heat extremes and coupled with increasing water shortage, provides a perfect storm for a new era of environmental crises and potentially, new diseases. We use a comparative physiologic approach to show that one of the primary mechanisms by which animals protect themselves against water shortage is to increase fat mass as a means for providing metabolic water. Strong evidence suggests that certain hormones (vasopressin), foods (fructose), and metabolic products (uric acid) function as survival signals to help reduce water loss and store fat (which also provides a source of metabolic water). These mechanisms are intricately linked with each other and stimulated by dehydration and hyperosmolarity. Although these mechanisms were protective in the setting of low sugar and low salt intake in our past, today, the combination of diets high in fructose and salty foods, increasing temperatures, and decreasing available water places these survival signals in overdrive and may be accelerating the obesity and diabetes epidemics. The recent discovery of multiple epidemics of CKD occurring in agricultural workers in hot and humid environments may represent harbingers of the detrimental consequences of the combination of climate change and overactivation of survival pathways.Johnson, Richard J.Stenvinkel, PeterJensen, ThomasLanaspa, Miguel A.Roncal, CarlosSong, ZhilinBankir, LiseSánchez-Lozada, Laura G.2016-06-09T07:35:14-07:00doi:10.1681/ASN.2015121314hwp:resource-id:jnephrol;27/8/2247American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvasopressin, osmolality, obesity, metabolism, chronic kidney diseaseUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-08-01August 201610.1681/ASN.20151213141046-66731533-34502016-06-09T07:35:14-07:002016-08Journal of the American Society of NephrologyUp Front Matters27822472256
- Parathyroidectomy or Calcimimetic to Treat Hypercalcemia after Kidney Transplantation?10.1681/ASN.2015121349Fri, 15 Jan 2016 06:30:47 GMT-08:00Parathyroidectomy or Calcimimetic to Treat Hypercalcemia after Kidney Transplantation?Fukagawa, MasafumiDrüeke, Tilman B.2016-01-15T06:30:47-08:00doi:10.1681/ASN.2015121349hwp:resource-id:jnephrol;27/8/2221American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperparathyroidism, parathyroid hormone, kidney transplantation, calcium, calcium receptorUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-08-01August 201610.1681/ASN.20151213491046-66731533-34502016-01-15T06:30:47-08:002016-08Journal of the American Society of NephrologyUp Front Matters27882221248722242494
- The End of Racial Disparities in Kidney Transplantation? Not So Fast!10.1681/ASN.2016010005Mon, 07 Mar 2016 06:35:45 GMT-08:00The End of Racial Disparities in Kidney Transplantation? Not So Fast!Williams, Winfred W.Delmonico, Francis L.2016-03-07T06:35:45-08:00doi:10.1681/ASN.2016010005hwp:resource-id:jnephrol;27/8/2224American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, kidney transplantation, transplant outcomes, Ethnic minorityUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-08-01August 201610.1681/ASN.20160100051046-66731533-34502016-03-07T06:35:45-08:002016-08Journal of the American Society of NephrologyUp Front Matters27888222423572511222623692518
- B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGSFSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7–1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7–1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7–1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7–1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7–1 blockade did not induce FSGS remission after transplant in our study.10.1681/ASN.2015091002Wed, 23 Dec 2015 06:57:21 GMT-08:00B7–1 Blockade Does Not Improve Post–Transplant Nephrotic Syndrome Caused by Recurrent FSGSFSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7–1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7–1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7–1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7–1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7–1 blockade did not induce FSGS remission after transplant in our study.Delville, MarianneBaye, EmilieDurrbach, AntoineAudard, VincentKofman, TomekBraun, LauraOlagne, JérômeNguyen, ClémentDeschênes, GeorgesMoulin, BrunoDelahousse, MichelKesler-Roussey, GwenaëlleBeaudreuil, SéverineMartinez, FrankRabant, MarionGrimbert, PhilippeGallazzini, MorganTerzi, FabiolaLegendre, ChristopheCanaud, Guillaume2015-12-23T06:57:21-08:00doi:10.1681/ASN.2015091002hwp:resource-id:jnephrol;27/8/2520American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, podocyte, transplantation, signalingClinical ResearchClinical Researchresearch-article20162016-08-01August 201610.1681/ASN.20150910021046-66731533-34502015-12-23T06:57:21-08:002016-08Journal of the American Society of NephrologyClinical Research27825202527
- Reduced Racial Disparity in Kidney Transplant Outcomes in the United States from 1990 to 2012Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990–2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P<0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P=0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P<0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P<0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community.10.1681/ASN.2015030293Thu, 04 Feb 2016 06:57:28 GMT-08:00Reduced Racial Disparity in Kidney Transplant Outcomes in the United States from 1990 to 2012Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990–2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P<0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P=0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P<0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P<0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community.Purnell, Tanjala S.Luo, XunKucirka, Lauren M.Cooper, Lisa A.Crews, Deidra C.Massie, Allan B.Boulware, L. EbonySegev, Dorry L.2016-02-04T06:57:28-08:00doi:10.1681/ASN.2015030293hwp:resource-id:jnephrol;27/8/2511American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, ethnicity, kidney transplantation, Epidemiology, and outcomes, transplant outcomesClinical ResearchClinical Researchresearch-article20162016-08-01August 201610.1681/ASN.20150302931046-66731533-34502016-02-04T06:57:28-08:002016-08Journal of the American Society of NephrologyClinical Research27882511222425182226
- Caspase-1, but Not Caspase-3, Promotes Diabetic NephropathyGlomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity. Accordingly, analysis of gene expression data in the Nephromine database revealed persistently elevated glomerular expression of inflammasome markers (NLRP3, CASP1, PYCARD, IL-18, IL-1β), but not of apoptosis markers (CASP3, CASP7, PARP1), in patients with and murine models of dNP. In vitro, increased levels of markers of inflammasome activation (Nlrp3, caspase-1 cleavage) preceded those of markers of apoptosis activation (caspase-3 and -7, PARP1 cleavage) in glucose-stressed podocytes. Finally, caspase-3 deficiency did not protect mice from dNP, whereas both homozygous and hemizygous caspase-1 deficiency did. Hence, these results suggest caspase-3-dependent cell death has a negligible effect, whereas caspase-1-dependent inflammasome activation has a crucial function in the establishment of dNP. Furthermore, small molecules targeting caspase-1 or inflammasome activation may be a feasible therapeutic approach in dNP.10.1681/ASN.2015060676Mon, 01 Feb 2016 01:53:27 GMT-08:00Caspase-1, but Not Caspase-3, Promotes Diabetic NephropathyGlomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity. Accordingly, analysis of gene expression data in the Nephromine database revealed persistently elevated glomerular expression of inflammasome markers (NLRP3, CASP1, PYCARD, IL-18, IL-1β), but not of apoptosis markers (CASP3, CASP7, PARP1), in patients with and murine models of dNP. In vitro, increased levels of markers of inflammasome activation (Nlrp3, caspase-1 cleavage) preceded those of markers of apoptosis activation (caspase-3 and -7, PARP1 cleavage) in glucose-stressed podocytes. Finally, caspase-3 deficiency did not protect mice from dNP, whereas both homozygous and hemizygous caspase-1 deficiency did. Hence, these results suggest caspase-3-dependent cell death has a negligible effect, whereas caspase-1-dependent inflammasome activation has a crucial function in the establishment of dNP. Furthermore, small molecules targeting caspase-1 or inflammasome activation may be a feasible therapeutic approach in dNP.Shahzad, KhurrumBock, FabianAl-Dabet, Moh’d MohanadGadi, IhsanKohli, ShreyNazir, SumraGhosh, SanchitaRanjan, SatishWang, HongjieMadhusudhan, ThatiNawroth, Peter P.Isermann, Berend2016-02-01T13:53:27-08:00doi:10.1681/ASN.2015060676hwp:resource-id:jnephrol;27/8/2270American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, apoptosis, immunology, renal protectionBrief CommunicationsBrief Communicationsbrief-report20162016-08-01August 201610.1681/ASN.20150606761046-66731533-34502016-02-01T13:53:27-08:002016-08Journal of the American Society of NephrologyBrief Communications27822702275
- This Month's Highlights10.1681/ASN.2016050506Fri, 29 Jul 2016 10:00:54 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-07-29T10:00:54-07:00doi:10.1681/ASN.2016050506hwp:resource-id:jnephrol;27/8/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20162016-08-01August 201610.1681/ASN.20160505061046-66731533-34502016-07-29T10:00:54-07:002016-08Journal of the American Society of NephrologyThis Month’s Highlights278ii
- IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKILow cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan–IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan–IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.10.1681/ASN.2015050578Thu, 11 Feb 2016 05:52:02 GMT-08:00IGF-1 C Domain–Modified Hydrogel Enhances Cell Therapy for AKILow cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan–IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan–IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.Feng, GuoweiZhang, JiminLi, YangNie, YanZhu, DashuaiWang, RanLiu, JianfengGao, JieLiu, NaHe, NingningDu, WeiTao, HongyanChe, YongzheXu, YongKong, DelingZhao, QiangLi, Zongjin2016-02-11T05:52:02-08:00doi:10.1681/ASN.2015050578hwp:resource-id:jnephrol;27/8/2357American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, apoptosis, cell survival, transplantation, stem cell, survivalBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150505781046-66731533-34502016-02-11T05:52:02-08:002016-08Journal of the American Society of NephrologyBasic Research27888235722192224236922212226
- αKlotho Mitigates Progression of AKI to CKD through Activation of AutophagyAKI confers increased risk of progression to CKD. αKlotho is a cytoprotective protein, the expression of which is reduced in AKI, but the relationship of αKlotho expression level to AKI progression to CKD has not been studied. We altered systemic αKlotho levels by genetic manipulation, phosphate loading, or aging and examined the effect on long-term outcome after AKI in two models: bilateral ischemia-reperfusion injury and unilateral nephrectomy plus contralateral ischemia-reperfusion injury. Despite apparent initial complete recovery of renal function, both types of AKI eventually progressed to CKD, with decreased creatinine clearance, hyperphosphatemia, and renal fibrosis. Compared with wild-type mice, heterozygous αKlotho–hypomorphic mice (αKlotho haploinsufficiency) progressed to CKD much faster, whereas αKlotho-overexpressing mice had better preserved renal function after AKI. High phosphate diet exacerbated αKlotho deficiency after AKI, dramatically increased renal fibrosis, and accelerated CKD progression. Recombinant αKlotho administration after AKI accelerated renal recovery and reduced renal fibrosis. Compared with wild-type conditions, αKlotho deficiency and overexpression are associated with lower and higher autophagic flux in the kidney, respectively. Upregulation of autophagy protected kidney cells in culture from oxidative stress and reduced collagen 1 accumulation. We propose that αKlotho upregulates autophagy, attenuates ischemic injury, mitigates renal fibrosis, and retards AKI progression to CKD.10.1681/ASN.2015060613Wed, 23 Dec 2015 06:57:20 GMT-08:00αKlotho Mitigates Progression of AKI to CKD through Activation of AutophagyAKI confers increased risk of progression to CKD. αKlotho is a cytoprotective protein, the expression of which is reduced in AKI, but the relationship of αKlotho expression level to AKI progression to CKD has not been studied. We altered systemic αKlotho levels by genetic manipulation, phosphate loading, or aging and examined the effect on long-term outcome after AKI in two models: bilateral ischemia-reperfusion injury and unilateral nephrectomy plus contralateral ischemia-reperfusion injury. Despite apparent initial complete recovery of renal function, both types of AKI eventually progressed to CKD, with decreased creatinine clearance, hyperphosphatemia, and renal fibrosis. Compared with wild-type mice, heterozygous αKlotho–hypomorphic mice (αKlotho haploinsufficiency) progressed to CKD much faster, whereas αKlotho-overexpressing mice had better preserved renal function after AKI. High phosphate diet exacerbated αKlotho deficiency after AKI, dramatically increased renal fibrosis, and accelerated CKD progression. Recombinant αKlotho administration after AKI accelerated renal recovery and reduced renal fibrosis. Compared with wild-type conditions, αKlotho deficiency and overexpression are associated with lower and higher autophagic flux in the kidney, respectively. Upregulation of autophagy protected kidney cells in culture from oxidative stress and reduced collagen 1 accumulation. We propose that αKlotho upregulates autophagy, attenuates ischemic injury, mitigates renal fibrosis, and retards AKI progression to CKD.Shi, MingjunFlores, BriannaGillings, NancyBian, AoCho, Han JunYan, ShirleyLiu, YangLevine, BethMoe, Orson W.Hu, Ming Chang2015-12-23T06:57:20-08:00doi:10.1681/ASN.2015060613hwp:resource-id:jnephrol;27/8/2331American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, chronic kidney disease, autophagy, renal fibrosis, ischemia-reperfusion injury, αKlothoBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150606131046-66731533-34502015-12-23T06:57:20-08:002016-08Journal of the American Society of NephrologyBasic Research27823312345
- Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3β Reinforces the Nrf2 Antioxidant Defense against PodocytopathyEvidence suggests that the glycogen synthase kinase 3 (GSK3)–dictated nuclear exclusion and degradation of Nrf2 is pivotal in switching off the self-protective antioxidant stress response after injury. Here, we examined the mechanisms underlying this regulation in glomerular disease. In primary podocytes, doxorubicin elicited cell death and actin cytoskeleton disorganization, concomitant with overactivation of GSK3β (the predominant GSK3 isoform expressed in glomerular podocytes) and minimal Nrf2 activation. SB216763, a highly selective small molecule inhibitor of GSK3, exerted a protective effect that depended on the potentiated Nrf2 antioxidant response, marked by increased Nrf2 expression and nuclear accumulation and augmented production of the Nrf2 target heme oxygenase-1. Ectopic expression of the kinase-dead mutant of GSK3β in cultured podocytes reinforced the doxorubicin-induced Nrf2 activation and prevented podocyte injury. Conversely, a constitutively active GSK3β mutant blunted the doxorubicin-induced Nrf2 response and exacerbated podocyte injury, which could be abolished by treatment with SB216763. In murine models of doxorubicin nephropathy or nephrotoxic serum nephritis, genetic targeting of GSK3β by doxycycline-inducible podocyte-specific knockout or pharmacologic targeting by SB216763 significantly attenuated albuminuria and ameliorated histologic signs of podocyte injury, including podocytopenia, loss of podocyte markers, podocyte de novo expression of desmin, and ultrastructural lesions of podocytopathy (such as foot process effacement). This beneficial outcome was likely attributable to an enhanced Nrf2 antioxidant response in glomerular podocytes because the selective Nrf2 antagonist trigonelline abolished the proteinuria-reducing and podocyte-protective effect. Collectively, our results suggest the GSK3β-regulated Nrf2 antioxidant response as a novel therapeutic target for protecting podocytes and treating proteinuric glomerulopathies.10.1681/ASN.2015050565Tue, 08 Dec 2015 01:27:46 GMT-08:00Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3β Reinforces the Nrf2 Antioxidant Defense against PodocytopathyEvidence suggests that the glycogen synthase kinase 3 (GSK3)–dictated nuclear exclusion and degradation of Nrf2 is pivotal in switching off the self-protective antioxidant stress response after injury. Here, we examined the mechanisms underlying this regulation in glomerular disease. In primary podocytes, doxorubicin elicited cell death and actin cytoskeleton disorganization, concomitant with overactivation of GSK3β (the predominant GSK3 isoform expressed in glomerular podocytes) and minimal Nrf2 activation. SB216763, a highly selective small molecule inhibitor of GSK3, exerted a protective effect that depended on the potentiated Nrf2 antioxidant response, marked by increased Nrf2 expression and nuclear accumulation and augmented production of the Nrf2 target heme oxygenase-1. Ectopic expression of the kinase-dead mutant of GSK3β in cultured podocytes reinforced the doxorubicin-induced Nrf2 activation and prevented podocyte injury. Conversely, a constitutively active GSK3β mutant blunted the doxorubicin-induced Nrf2 response and exacerbated podocyte injury, which could be abolished by treatment with SB216763. In murine models of doxorubicin nephropathy or nephrotoxic serum nephritis, genetic targeting of GSK3β by doxycycline-inducible podocyte-specific knockout or pharmacologic targeting by SB216763 significantly attenuated albuminuria and ameliorated histologic signs of podocyte injury, including podocytopenia, loss of podocyte markers, podocyte de novo expression of desmin, and ultrastructural lesions of podocytopathy (such as foot process effacement). This beneficial outcome was likely attributable to an enhanced Nrf2 antioxidant response in glomerular podocytes because the selective Nrf2 antagonist trigonelline abolished the proteinuria-reducing and podocyte-protective effect. Collectively, our results suggest the GSK3β-regulated Nrf2 antioxidant response as a novel therapeutic target for protecting podocytes and treating proteinuric glomerulopathies.Zhou, SijieWang, PeiQiao, YingjinGe, YanWang, YingziQuan, SongxiaYao, RickyZhuang, ShougangWang, Li JuanDu, YongLiu, ZhangsuoGong, Rujun2015-12-08T13:27:46-08:00doi:10.1681/ASN.2015050565hwp:resource-id:jnephrol;27/8/2289American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, reactive oxygen species, glomerulopathy, Nrf2 antioxidant, response, glycogen synthase kinase, conditional knockoutBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150505651046-66731533-34502015-12-08T13:27:46-08:002016-08Journal of the American Society of NephrologyBasic Research27822892308
- Nephrin Tyrosine Phosphorylation Is Required to Stabilize and Restore Podocyte Foot Process ArchitecturePodocytes are specialized epithelial cells of the kidney blood filtration barrier that contribute to permselectivity via a series of interdigitating actin–rich foot processes. Positioned between adjacent projections is a unique cell junction known as the slit diaphragm, which is physically connected to the actin cytoskeleton via the transmembrane protein nephrin. Evidence indicates that tyrosine phosphorylation of the intracellular tail of nephrin initiates signaling events, including recruitment of cytoplasmic adaptor proteins Nck1 and Nck2 that regulate actin cytoskeletal dynamics. Nephrin tyrosine phosphorylation is altered in human and experimental renal diseases characterized by pathologic foot process remodeling, prompting the hypothesis that phosphonephrin signaling directly influences podocyte morphology. To explore this possibility, we generated and analyzed knockin mice with mutations that disrupt nephrin tyrosine phosphorylation and Nck1/2 binding (nephrinY3F/Y3F mice). Homozygous nephrinY3F/Y3F mice developed progressive proteinuria accompanied by structural changes in the filtration barrier, including podocyte foot process effacement, irregular thickening of the glomerular basement membrane, and dilated capillary loops, with a similar but later onset phenotype in heterozygous animals. Furthermore, compared with wild-type mice, nephrinY3F/Y3F mice displayed delayed recovery in podocyte injury models. Profiling of nephrin tyrosine phosphorylation dynamics in wild-type mice subjected to podocyte injury indicated site-specific differences in phosphorylation at baseline, injury, and recovery, which correlated with loss of nephrin-Nck1/2 association during foot process effacement. Our results define an essential requirement for nephrin tyrosine phosphorylation in stabilizing podocyte morphology and suggest a model in which dynamic changes in phosphotyrosine-based signaling confer plasticity to the podocyte actin cytoskeleton.10.1681/ASN.2015091048Fri, 22 Jan 2016 07:55:46 GMT-08:00Nephrin Tyrosine Phosphorylation Is Required to Stabilize and Restore Podocyte Foot Process ArchitecturePodocytes are specialized epithelial cells of the kidney blood filtration barrier that contribute to permselectivity via a series of interdigitating actin–rich foot processes. Positioned between adjacent projections is a unique cell junction known as the slit diaphragm, which is physically connected to the actin cytoskeleton via the transmembrane protein nephrin. Evidence indicates that tyrosine phosphorylation of the intracellular tail of nephrin initiates signaling events, including recruitment of cytoplasmic adaptor proteins Nck1 and Nck2 that regulate actin cytoskeletal dynamics. Nephrin tyrosine phosphorylation is altered in human and experimental renal diseases characterized by pathologic foot process remodeling, prompting the hypothesis that phosphonephrin signaling directly influences podocyte morphology. To explore this possibility, we generated and analyzed knockin mice with mutations that disrupt nephrin tyrosine phosphorylation and Nck1/2 binding (nephrinY3F/Y3F mice). Homozygous nephrinY3F/Y3F mice developed progressive proteinuria accompanied by structural changes in the filtration barrier, including podocyte foot process effacement, irregular thickening of the glomerular basement membrane, and dilated capillary loops, with a similar but later onset phenotype in heterozygous animals. Furthermore, compared with wild-type mice, nephrinY3F/Y3F mice displayed delayed recovery in podocyte injury models. Profiling of nephrin tyrosine phosphorylation dynamics in wild-type mice subjected to podocyte injury indicated site-specific differences in phosphorylation at baseline, injury, and recovery, which correlated with loss of nephrin-Nck1/2 association during foot process effacement. Our results define an essential requirement for nephrin tyrosine phosphorylation in stabilizing podocyte morphology and suggest a model in which dynamic changes in phosphotyrosine-based signaling confer plasticity to the podocyte actin cytoskeleton.New, Laura A.Martin, Claire E.Scott, Rizaldy P.Platt, Mathew J.Keyvani Chahi, AvaStringer, Colin D.Lu, PeihuaSamborska, BozenaEremina, VeraTakano, TomokoSimpson, Jeremy A.Quaggin, Susan E.Jones, Nina2016-01-22T07:55:46-08:00doi:10.1681/ASN.2015091048hwp:resource-id:jnephrol;27/8/2422American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynephrin, cell signaling, cytoskeleton, glomerular disease, cell biology and structure, podocyteBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150910481046-66731533-34502016-01-22T07:55:46-08:002016-08Journal of the American Society of NephrologyBasic Research27824222435
- Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKIInappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue–specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.10.1681/ASN.2015060683Thu, 07 Jan 2016 06:07:30 GMT-08:00Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKIInappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue–specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.Zhang, JiandongRudemiller, Nathan P.Patel, Mehul B.Wei, QingQingKarlovich, Norah S.Jeffs, Alexander D.Wu, MinSparks, Matthew A.Privratsky, Jamie R.Herrera, MarcelaGurley, Susan B.Nedospasov, Sergei A.Crowley, Steven D.2016-01-07T06:07:30-08:00doi:10.1681/ASN.2015060683hwp:resource-id:jnephrol;27/8/2257American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin, acute renal failure, angiotensinBrief CommunicationsBrief Communicationsbrief-report20162016-08-01August 201610.1681/ASN.20150606831046-66731533-34502016-01-07T06:07:30-08:002016-08Journal of the American Society of NephrologyBrief Communications27822572264
- The Nephrologist’s Tumor: Basic Biology and Management of Renal Cell CarcinomaKidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel–Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist’s tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist’s tumor.10.1681/ASN.2015121335Wed, 09 Mar 2016 09:58:59 GMT-08:00The Nephrologist’s Tumor: Basic Biology and Management of Renal Cell CarcinomaKidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel–Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist’s tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist’s tumor.Hu, Susie L.Chang, AnthonyPerazella, Mark A.Okusa, Mark D.Jaimes, Edgar A.Weiss, Robert H.2016-03-09T09:58:59-08:00doi:10.1681/ASN.2015121335hwp:resource-id:jnephrol;27/8/2227American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycancer, renal carcinoma, chronic renal diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-08-01August 201610.1681/ASN.20151213351046-66731533-34502016-03-09T09:58:59-08:002016-08Journal of the American Society of NephrologyUp Front Matters27822272237
- Increased Synthesis of Liver Erythropoietin with CKDAnemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0–20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6–9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.10.1681/ASN.2015050508Tue, 12 Jan 2016 06:13:50 GMT-08:00Increased Synthesis of Liver Erythropoietin with CKDAnemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0–20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6–9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.de Seigneux, SophieLundby, Anne-Kristine MeinildBerchtold, LenaBerg, Anders H.Saudan, PatrickLundby, Carsten2016-01-12T06:13:50-08:00doi:10.1681/ASN.2015050508hwp:resource-id:jnephrol;27/8/2265American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic kidney disease, erythropoietinBrief CommunicationsBrief Communicationsbrief-report20162016-08-01August 201610.1681/ASN.20150505081046-66731533-34502016-01-12T06:13:50-08:002016-08Journal of the American Society of NephrologyBrief Communications27822652269
- Hepatitis C Virus Infection in Chronic Kidney DiseaseSoon after the hepatitis C virus (HCV) was identified in 1989, it was recognized that the prevalence of infection in patients with ESRD far exceeded that in the general population. Infection with HCV predisposes to the hepatic complications of cirrhosis and hepatocellular carcinoma. However, important extrahepatic manifestations include immune complex glomerular disease, accelerated progression of CKD, increases in cardiovascular event risk, and lymphoproliferative disorders. Advances in understanding the molecular biology of HCV have ushered in a new era in the treatment of this infection. Second generation direct–acting antiviral agents have revolutionized therapy, with sustained virologic response rates (undetectable viral load 12 weeks after completing therapy) of >90% in most patients. Studies using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. In this context, it is imperative that nephrologists become familiar with this literature, reviewed here, so that the important decisions, including which patients should be treated and the optimal timing to initiate therapy, are vetted in association with the compounding issues of CKD, ESRD, and kidney transplantation.10.1681/ASN.2016010030Tue, 19 Apr 2016 05:54:06 GMT-07:00Hepatitis C Virus Infection in Chronic Kidney DiseaseSoon after the hepatitis C virus (HCV) was identified in 1989, it was recognized that the prevalence of infection in patients with ESRD far exceeded that in the general population. Infection with HCV predisposes to the hepatic complications of cirrhosis and hepatocellular carcinoma. However, important extrahepatic manifestations include immune complex glomerular disease, accelerated progression of CKD, increases in cardiovascular event risk, and lymphoproliferative disorders. Advances in understanding the molecular biology of HCV have ushered in a new era in the treatment of this infection. Second generation direct–acting antiviral agents have revolutionized therapy, with sustained virologic response rates (undetectable viral load 12 weeks after completing therapy) of >90% in most patients. Studies using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. In this context, it is imperative that nephrologists become familiar with this literature, reviewed here, so that the important decisions, including which patients should be treated and the optimal timing to initiate therapy, are vetted in association with the compounding issues of CKD, ESRD, and kidney transplantation.Ladino, MarcoPedraza, FernandoRoth, David2016-04-19T05:54:06-07:00doi:10.1681/ASN.2016010030hwp:resource-id:jnephrol;27/8/2238American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhepatitis, kidney transplantation, chronic kidney diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-08-01August 201610.1681/ASN.20160100301046-66731533-34502016-04-19T05:54:06-07:002016-08Journal of the American Society of NephrologyUp Front Matters27822382246
- Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical TrialsObservational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.10.1681/ASN.2015060642Mon, 28 Dec 2015 06:30:33 GMT-08:00Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical TrialsObservational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short–term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between–group differences in CKD and/or mortality rate ≥3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo–controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.Coca, Steven G.Zabetian, AzadehFerket, Bart S.Zhou, JingTestani, Jeffrey M.Garg, Amit X.Parikh, Chirag R.2015-12-28T06:30:33-08:00doi:10.1681/ASN.2015060642hwp:resource-id:jnephrol;27/8/2529American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, chronic kidney disease, chronic kidney failureMeta-AnalysisMeta-Analysisresearch-article20162016-08-01August 201610.1681/ASN.20150606421046-66731533-34502015-12-28T06:30:33-08:002016-08Journal of the American Society of NephrologyMeta-Analysis27825292542
- MicroRNA-21 Aggravates Cyst Growth in a Model of Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated in numerous diseases, but the role of these noncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death 4. Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD.10.1681/ASN.2015060634Thu, 17 Dec 2015 07:44:14 GMT-08:00MicroRNA-21 Aggravates Cyst Growth in a Model of Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated in numerous diseases, but the role of these noncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likely through direct repression of its target gene programmed cell death 4. Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD.Lakhia, RonakHajarnis, SachinWilliams, DarrenAboudehen, KaramYheskel, MatanelXing, ChaoHatley, Mark E.Torres, Vicente E.Wallace, Darren P.Patel, Vishal2015-12-17T07:44:14-08:00doi:10.1681/ASN.2015060634hwp:resource-id:jnephrol;27/8/2319American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, microRNAs, cell death, miR-21Basic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150606341046-66731533-34502015-12-17T07:44:14-08:002016-08Journal of the American Society of NephrologyBasic Research27823192330
- Severity and Frequency of Proximal Tubule Injury Determines Renal PrognosisAKI increases the risk of developing CKD, but the mechanisms linking AKI to CKD remain unclear. Because proximal tubule injury is the mainstay of AKI, we postulated that proximal tubule injury triggers features of CKD. We generated a novel mouse model to induce proximal tubule–specific adjustable injury by inducing the expression of diphtheria toxin (DT) receptor with variable prevalence in proximal tubules. Administration of high-dose DT in mice expressing the DT receptor consistently caused severe proximal tubule–specific injury associated with interstitial fibrosis and reduction of erythropoietin production. Mild proximal tubule injury from a single injection of low-dose DT triggered reversible fibrosis, whereas repeated mild injuries caused sustained interstitial fibrosis, inflammation, glomerulosclerosis, and atubular glomeruli. DT–induced proximal tubule–specific injury also triggered distal tubule injury. Furthermore, injured tubular cells cocultured with fibroblasts stimulated induction of extracellular matrix and inflammatory genes. These results support the existence of proximal-distal tubule crosstalk and crosstalk between tubular cells and fibroblasts. Overall, our data provide evidence that proximal tubule injury triggers several features of CKD and that the severity and frequency of proximal tubule injury determines the progression to CKD.10.1681/ASN.2015060647Wed, 23 Dec 2015 06:57:24 GMT-08:00Severity and Frequency of Proximal Tubule Injury Determines Renal PrognosisAKI increases the risk of developing CKD, but the mechanisms linking AKI to CKD remain unclear. Because proximal tubule injury is the mainstay of AKI, we postulated that proximal tubule injury triggers features of CKD. We generated a novel mouse model to induce proximal tubule–specific adjustable injury by inducing the expression of diphtheria toxin (DT) receptor with variable prevalence in proximal tubules. Administration of high-dose DT in mice expressing the DT receptor consistently caused severe proximal tubule–specific injury associated with interstitial fibrosis and reduction of erythropoietin production. Mild proximal tubule injury from a single injection of low-dose DT triggered reversible fibrosis, whereas repeated mild injuries caused sustained interstitial fibrosis, inflammation, glomerulosclerosis, and atubular glomeruli. DT–induced proximal tubule–specific injury also triggered distal tubule injury. Furthermore, injured tubular cells cocultured with fibroblasts stimulated induction of extracellular matrix and inflammatory genes. These results support the existence of proximal-distal tubule crosstalk and crosstalk between tubular cells and fibroblasts. Overall, our data provide evidence that proximal tubule injury triggers several features of CKD and that the severity and frequency of proximal tubule injury determines the progression to CKD.Takaori, KojiNakamura, JinYamamoto, ShinyaNakata, HirosukeSato, YukiTakase, MasayukiNameta, MasaakiYamamoto, TadashiEconomides, Aris N.Kohno, KenjiHaga, HironoriSharma, KumarYanagita, Motoko2015-12-23T06:57:24-08:00doi:10.1681/ASN.2015060647hwp:resource-id:jnephrol;27/8/2393American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, chronic kidney disease, proximal tubuleBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150606471046-66731533-34502015-12-23T06:57:24-08:002016-08Journal of the American Society of NephrologyBasic Research27823932406
- A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with HyperparathyroidismTertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open–label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.10.1681/ASN.2015060622Tue, 08 Dec 2015 01:27:44 GMT-08:00A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with HyperparathyroidismTertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open–label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant ≥6 months before the study and had an eGFR>30 ml/min per 1.73 m2. The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.Cruzado, Josep M.Moreno, PabloTorregrosa, José V.Taco, OmarMast, RichardGómez-Vaquero, CarmenPolo, CarolinaRevuelta, IgnacioFrancos, JoséTorras, JoanGarcía-Barrasa, ArantxaBestard, OriolGrinyó, Josep M.2015-12-08T13:27:44-08:00doi:10.1681/ASN.2015060622hwp:resource-id:jnephrol;27/8/2487American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhyperparathyroidism, renal transplantation, calciumClinical ResearchClinical Researchresearch-article20162016-08-01August 201610.1681/ASN.20150606221046-66731533-34502015-12-08T13:27:44-08:002016-08Journal of the American Society of NephrologyClinical Research27882487222124942224
- Transcription Factor Hepatocyte Nuclear Factor–1β Regulates Renal Cholesterol MetabolismHNF-1β is a tissue–specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β–regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin–like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism.10.1681/ASN.2015060607Mon, 28 Dec 2015 06:30:34 GMT-08:00Transcription Factor Hepatocyte Nuclear Factor–1β Regulates Renal Cholesterol MetabolismHNF-1β is a tissue–specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β–regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin–like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism.Aboudehen, KaramKim, Min SooMitsche, MatthewGarland, KristinaAnderson, NormaNoureddine, LamaPontoglio, MarcoPatel, VishalXie, YangDeBose-Boyd, RussellIgarashi, Peter2015-12-28T06:30:34-08:00doi:10.1681/ASN.2015060607hwp:resource-id:jnephrol;27/8/2408American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, lipids, transcription factorsBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150606071046-66731533-34502015-12-28T06:30:34-08:002016-08Journal of the American Society of NephrologyBasic Research27824082421
- Direct and Indirect Mineralocorticoid Effects Determine Distal Salt TransportExcess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide–sensitive Na+-Cl− cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney–specific MR–knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.10.1681/ASN.2015070815Mon, 28 Dec 2015 06:30:35 GMT-08:00Direct and Indirect Mineralocorticoid Effects Determine Distal Salt TransportExcess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide–sensitive Na+-Cl− cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney–specific MR–knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.Terker, Andrew S.Yarbrough, BethzaidaFerdaus, Mohammed Z.Lazelle, Rebecca A.Erspamer, Kayla J.Meermeier, Nicholas P.Park, Hae J.McCormick, James A.Yang, Chao-LingEllison, David H.2015-12-28T06:30:35-08:00doi:10.1681/ASN.2015070815hwp:resource-id:jnephrol;27/8/2436American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyaldosterone, cell signaling, ENaC, epithelial sodium transport, hypokalemiaBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150708151046-66731533-34502015-12-28T06:30:35-08:002016-08Journal of the American Society of NephrologyBasic Research27824362445
- Past Decline Versus Current eGFR and Subsequent ESRD RiskeGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta–analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of −6 versus 0 ml/min per 1.73 m2 per year over the previous 3 years (a decline of 18 ml/min per 1.73 m2 versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m2 (a difference of 20 ml/min per 1.73 m2) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m2.10.1681/ASN.2015060687Fri, 11 Dec 2015 08:20:59 GMT-08:00Past Decline Versus Current eGFR and Subsequent ESRD RiskeGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta–analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of −6 versus 0 ml/min per 1.73 m2 per year over the previous 3 years (a decline of 18 ml/min per 1.73 m2 versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m2 (a difference of 20 ml/min per 1.73 m2) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m2.Kovesdy, Csaba P.Coresh, JosefBallew, Shoshana H.Woodward, MarkLevin, AdeeraNaimark, David M.J.Nally, JosephRothenbacher, DietrichStengel, BenedicteIseki, KunitoshiMatsushita, KunihiroLevey, Andrew S.2015-12-11T08:20:59-08:00doi:10.1681/ASN.2015060687hwp:resource-id:jnephrol;27/8/2447American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyprogression of chronic renal failure, glomerular filtration rate, epidemiology and outcomes, end-stage renal diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20162016-08-01August 201610.1681/ASN.20150606871046-66731533-34502015-12-11T08:20:59-08:002016-08Journal of the American Society of NephrologyClinical Epidemiology27824472455
- Past Decline Versus Current eGFR and Subsequent Mortality RiskA single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual–level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <−5 ml/min per 1.73 m2 per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m2 per year, a slope of −6 ml/min per 1.73 m2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m2 per year also associated with higher all–cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.10.1681/ASN.2015060688Fri, 11 Dec 2015 08:20:58 GMT-08:00Past Decline Versus Current eGFR and Subsequent Mortality RiskA single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual–level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <−5 ml/min per 1.73 m2 per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m2 per year, a slope of −6 ml/min per 1.73 m2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m2 per year also associated with higher all–cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.Naimark, David M.J.Grams, Morgan E.Matsushita, KunihiroBlack, CorriDrion, IefkeFox, Caroline S.Inker, Lesley A.Ishani, AreefJee, Sun HaKitamura, AkihikoLea, Janice P.Nally, JosephPeralta, Carmen AliciaRothenbacher, DietrichRyu, SeunghoTonelli, MarcelloYatsuya, HiroshiCoresh, JosefGansevoort, Ron T.Warnock, David G.Woodward, Markde Jong, Paul E.2015-12-11T08:20:58-08:00doi:10.1681/ASN.2015060688hwp:resource-id:jnephrol;27/8/2456American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, mortality, epidemiology, outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20162016-08-01August 201610.1681/ASN.20150606881046-66731533-34502015-12-11T08:20:58-08:002016-08Journal of the American Society of NephrologyClinical Epidemiology27824562466
- Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities StudyMitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P<0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P<0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.10.1681/ASN.2015060661Thu, 21 Jan 2016 05:59:20 GMT-08:00Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities StudyMitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD. Mitochondrial DNA (mtDNA) copy number is a surrogate measure of mitochondrial function, and higher mtDNA copy number in peripheral blood has been associated with lower risk of two important risk factors for CKD progression, diabetes and microalbuminuria. We evaluated whether mtDNA copy number in peripheral blood associates with incident CKD in a population-based cohort of middle-aged adults. We estimated mtDNA copy number using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Among 9058 participants, those with higher mtDNA copy number had a lower rate of prevalent diabetes and lower C-reactive protein levels and white blood cell counts. Baseline eGFR did not differ significantly by mtDNA copy number. Over a median follow-up of 19.6 years, 1490 participants developed CKD. Higher mtDNA copy number associated with lower risk of incident CKD (highest versus lowest quartile: hazard ratio 0.65; 95% confidence interval, 0.56 to 0.75; P<0.001) after adjusting for age, sex, and race. After adjusting for additional risk factors of CKD, including prevalent diabetes, hypertension, C-reactive protein level, and white blood cell count, this association remained significant (highest versus lowest quartile: hazard ratio 0.75; 95% confidence interval, 0.64 to 0.87; P<0.001). In conclusion, higher mtDNA copy number associated with lower incidence of CKD independent of traditional risk factors and inflammation biomarker levels in this cohort. Further research on modifiable factors influencing mtDNA copy number may lead to improvement in the prevention and treatment of CKD.Tin, AdrienneGrams, Morgan E.Ashar, Foram N.Lane, John A.Rosenberg, Avi Z.Grove, Megan L.Boerwinkle, EricSelvin, ElizabethCoresh, JosefPankratz, NathanArking, Dan E.2016-01-21T05:59:20-08:00doi:10.1681/ASN.2015060661hwp:resource-id:jnephrol;27/8/2467American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, mitochondria, epidemiology and outcomes, renal function declineClinical EpidemiologyClinical Epidemiologyresearch-article20162016-08-01August 201610.1681/ASN.20150606611046-66731533-34502016-01-21T05:59:20-08:002016-08Journal of the American Society of NephrologyClinical Epidemiology27824672473
- Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on HemodialysisExposure to high Ca concentrations may influence the development of low–turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.10.1681/ASN.2015030268Wed, 23 Dec 2015 06:57:20 GMT-08:00Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on HemodialysisExposure to high Ca concentrations may influence the development of low–turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.Ok, ErcanAsci, GulayBayraktaroglu, SelenToz, HuseyinOzkahya, MehmetYilmaz, MumtazKircelli, FatihSevinc Ok, EbruCeylan, NaimDuman, SonerCirit, MustafaMonier-Faugere, Marie-ClaudeMalluche, Hartmut H.2015-12-23T06:57:20-08:00doi:10.1681/ASN.2015030268hwp:resource-id:jnephrol;27/8/2475American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, mineral metabolism, vascular calcificationClinical ResearchClinical Researchresearch-article20162016-08-01August 201610.1681/ASN.20150302681046-66731533-34502015-12-23T06:57:20-08:002016-08Journal of the American Society of NephrologyClinical Research27824752486
- Early Changes in Kidney Distribution under the New Allocation SystemThe Kidney Allocation System (KAS), a major change to deceased donor kidney allocation, was implemented in December 2014. Goals of KAS included directing the highest-quality organs to younger/healthier recipients and increasing access to deceased donor kidney transplantation (DDKT) for highly sensitized patients and racial/ethnic minorities. Using national registry data, we compared kidney distribution, DDKT rates for waitlist registrants, and recipient characteristics between January 1, 2013, and December 3, 2014 (pre-KAS) with those between December 4, 2014, and August 31, 2015 (post-KAS). Regional imports increased from 8.8% pre-KAS to 12.5% post-KAS; national imports increased from 12.7% pre-KAS to 19.1% post-KAS (P<0.001). The proportion of recipients >30 years older than their donor decreased from 19.4% to 15.0% (P<0.001). The proportion of recipients with calculated panel-reactive antibody =100 increased from 1.0% to 10.3% (P<0.001). Overall DDKT rate did not change as modeled using exponential regression adjusting for candidate characteristics (P=0.07). However, DDKT rate (incidence rate ratio, 95% confidence interval) increased for black (1.19; 1.13 to 1.25) and Hispanic (1.13; 1.05 to 1.20) candidates and for candidates aged 18–40 (1.47; 1.38 to 1.57), but declined for candidates aged >50 (0.93; 0.87 to 0.98 for aged 51–60 and 0.90; 0.85 to 0.96 for aged >70). Delayed graft function in transplant recipients increased from 24.8% pre-KAS to 29.9% post-KAS (P<0.001). Thus, in the first 9 months under KAS, access to DDKT improved for minorities, younger candidates, and highly sensitized patients, but declined for older candidates. Delayed graft function increased substantially, possibly suggesting poorer long-term outcomes.10.1681/ASN.2015080934Thu, 17 Dec 2015 07:44:15 GMT-08:00Early Changes in Kidney Distribution under the New Allocation SystemThe Kidney Allocation System (KAS), a major change to deceased donor kidney allocation, was implemented in December 2014. Goals of KAS included directing the highest-quality organs to younger/healthier recipients and increasing access to deceased donor kidney transplantation (DDKT) for highly sensitized patients and racial/ethnic minorities. Using national registry data, we compared kidney distribution, DDKT rates for waitlist registrants, and recipient characteristics between January 1, 2013, and December 3, 2014 (pre-KAS) with those between December 4, 2014, and August 31, 2015 (post-KAS). Regional imports increased from 8.8% pre-KAS to 12.5% post-KAS; national imports increased from 12.7% pre-KAS to 19.1% post-KAS (P<0.001). The proportion of recipients >30 years older than their donor decreased from 19.4% to 15.0% (P<0.001). The proportion of recipients with calculated panel-reactive antibody =100 increased from 1.0% to 10.3% (P<0.001). Overall DDKT rate did not change as modeled using exponential regression adjusting for candidate characteristics (P=0.07). However, DDKT rate (incidence rate ratio, 95% confidence interval) increased for black (1.19; 1.13 to 1.25) and Hispanic (1.13; 1.05 to 1.20) candidates and for candidates aged 18–40 (1.47; 1.38 to 1.57), but declined for candidates aged >50 (0.93; 0.87 to 0.98 for aged 51–60 and 0.90; 0.85 to 0.96 for aged >70). Delayed graft function in transplant recipients increased from 24.8% pre-KAS to 29.9% post-KAS (P<0.001). Thus, in the first 9 months under KAS, access to DDKT improved for minorities, younger candidates, and highly sensitized patients, but declined for older candidates. Delayed graft function increased substantially, possibly suggesting poorer long-term outcomes.Massie, Allan B.Luo, XunLonze, Bonnie E.Desai, Niraj M.Bingaman, Adam W.Cooper, MatthewSegev, Dorry L.2015-12-17T07:44:15-08:00doi:10.1681/ASN.2015080934hwp:resource-id:jnephrol;27/8/2495American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, transplant outcomes, chronic kidney diseaseClinical ResearchClinical Researchresearch-article20162016-08-01August 201610.1681/ASN.20150809341046-66731533-34502015-12-17T07:44:15-08:002016-08Journal of the American Society of NephrologyClinical Research27824952501
- Intragraft Blood Dendritic Cell Antigen-1–Positive Myeloid Dendritic Cells Increase during BK Polyomavirus–Associated NephropathyAlthough both polyomavirus infection and T cell–mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus–associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1+ (BDCA-1+) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P=0.04) than during TCMR. Double immunostaining for SV40 and BDCA-1 showed that, during BKPyVAN, BDCA-1+ mDCs localized in proximity to the polyomavirus–infected tubular epithelial cells. We ensured that time of biopsy after transplantation was not a confounding factor by including additional specimens with late TCMR and protocol biopsy specimens matched for biopsy time. These additional specimens showed amounts of BDCA-1+ mDCs comparable with amounts in the early TCMR specimens. These results suggest that BDCA-1+ mDCs, known to be involved in the antiviral immune response during various viral infections, might have a pivotal role during BKPyVAN infection in the grafted kidney.10.1681/ASN.2015040442Wed, 23 Dec 2015 06:57:22 GMT-08:00Intragraft Blood Dendritic Cell Antigen-1–Positive Myeloid Dendritic Cells Increase during BK Polyomavirus–Associated NephropathyAlthough both polyomavirus infection and T cell–mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus–associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1+ (BDCA-1+) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P=0.04) than during TCMR. Double immunostaining for SV40 and BDCA-1 showed that, during BKPyVAN, BDCA-1+ mDCs localized in proximity to the polyomavirus–infected tubular epithelial cells. We ensured that time of biopsy after transplantation was not a confounding factor by including additional specimens with late TCMR and protocol biopsy specimens matched for biopsy time. These additional specimens showed amounts of BDCA-1+ mDCs comparable with amounts in the early TCMR specimens. These results suggest that BDCA-1+ mDCs, known to be involved in the antiviral immune response during various viral infections, might have a pivotal role during BKPyVAN infection in the grafted kidney.Yapici, ÜnsalKers, JesperSlavujevic-Letic, IvanaStokman, GeurtRoelofs, Joris J.T.H.van Aalderen, Michiel C.Groothoff, Jaap W.de Boer, Onno J.van der Pant, Karlijn A.M.I.Claessen, NikeHilbrands, Luuk B.Bemelman, Frederike J.ten Berge, Ineke J.M.Florquin, Sandrine2015-12-23T06:57:22-08:00doi:10.1681/ASN.2015040442hwp:resource-id:jnephrol;27/8/2502American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, renal biopsy, transplant pathology, virology, immunology and pathology, immunohistochemistryClinical ResearchClinical Researchresearch-article20162016-08-01August 201610.1681/ASN.20150404421046-66731533-34502015-12-23T06:57:22-08:002016-08Journal of the American Society of NephrologyClinical Research27825022510
- Do You Want to Ditch Sodium? Meet Nitric Oxide Synthase 1β at the Macula Densa10.1681/ASN.2015121378Mon, 22 Feb 2016 05:49:58 GMT-08:00Do You Want to Ditch Sodium? Meet Nitric Oxide Synthase 1β at the Macula DensaJose, Pedro A.Welch, William2016-02-22T05:49:58-08:00doi:10.1681/ASN.2015121378hwp:resource-id:jnephrol;27/8/2217American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytubuloglomerular feedback, macula densa, NOS1β, salt-sensitive, hypertensionUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-08-01August 201610.1681/ASN.20151213781046-66731533-34502016-02-22T05:49:58-08:002016-08Journal of the American Society of NephrologyUp Front Matters27882217234622182356
- Modified Hydrogels to Enhance Cellular Therapy for AKI: A Translational Challenge10.1681/ASN.2015121379Thu, 11 Feb 2016 05:52:02 GMT-08:00Modified Hydrogels to Enhance Cellular Therapy for AKI: A Translational ChallengeGooch, AnnaWestenfelder, Christof2016-02-11T05:52:02-08:00doi:10.1681/ASN.2015121379hwp:resource-id:jnephrol;27/8/2219American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyARF, IGF-1, stem cellUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-08-01August 201610.1681/ASN.20151213791046-66731533-34502016-02-11T05:52:02-08:002016-08Journal of the American Society of NephrologyUp Front Matters27882219235722212369
- Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic NephropathyInflammation has a critical role in the pathogenesis of diabetic complications, including diabetic nephropathy (DN). MicroRNAs have recently emerged as important regulators of DN. However, the role of microRNAs in the regulation of inflammation during DN is poorly understood. Here, we examined the in vivo role of microRNA-146a (miR-146a), a known anti-inflammatory microRNA, in the pathogenesis of DN. In a model of streptozotocin-induced diabetes, miR-146a−/− mice showed significantly exacerbated proteinuria, renal macrophage infiltration, glomerular hypertrophy, and fibrosis relative to the respective levels in control wild-type mice. Diabetes-induced upregulation of proinflammatory and profibrotic genes was significantly greater in the kidneys of miR-146a−/− than in the kidneys of wild-type mice. Notably, miR-146a expression increased in both peritoneal and intrarenal macrophages in diabetic wild-type mice. Mechanistically, miR-146a deficiency during diabetes led to increased expression of M1 activation markers and suppression of M2 markers in macrophages. Concomitant with increased expression of proinflammatory cytokines, such as IL-1β and IL-18, markers of inflammasome activation also increased in the macrophages of diabetic miR-146a−/− mice. These studies suggest that in early DN, miR-146a upregulation exerts a protective effect by downregulating target inflammation-related genes, resulting in suppression of proinflammatory and inflammasome gene activation. Loss of this protective mechanism in miR-146a−/− mice leads to accelerated DN. Taken together, these results identify miR-146a as a novel anti-inflammatory noncoding RNA modulator of DN.10.1681/ASN.2015010111Tue, 08 Dec 2015 01:27:43 GMT-08:00Anti-Inflammatory Role of MicroRNA-146a in the Pathogenesis of Diabetic NephropathyInflammation has a critical role in the pathogenesis of diabetic complications, including diabetic nephropathy (DN). MicroRNAs have recently emerged as important regulators of DN. However, the role of microRNAs in the regulation of inflammation during DN is poorly understood. Here, we examined the in vivo role of microRNA-146a (miR-146a), a known anti-inflammatory microRNA, in the pathogenesis of DN. In a model of streptozotocin-induced diabetes, miR-146a−/− mice showed significantly exacerbated proteinuria, renal macrophage infiltration, glomerular hypertrophy, and fibrosis relative to the respective levels in control wild-type mice. Diabetes-induced upregulation of proinflammatory and profibrotic genes was significantly greater in the kidneys of miR-146a−/− than in the kidneys of wild-type mice. Notably, miR-146a expression increased in both peritoneal and intrarenal macrophages in diabetic wild-type mice. Mechanistically, miR-146a deficiency during diabetes led to increased expression of M1 activation markers and suppression of M2 markers in macrophages. Concomitant with increased expression of proinflammatory cytokines, such as IL-1β and IL-18, markers of inflammasome activation also increased in the macrophages of diabetic miR-146a−/− mice. These studies suggest that in early DN, miR-146a upregulation exerts a protective effect by downregulating target inflammation-related genes, resulting in suppression of proinflammatory and inflammasome gene activation. Loss of this protective mechanism in miR-146a−/− mice leads to accelerated DN. Taken together, these results identify miR-146a as a novel anti-inflammatory noncoding RNA modulator of DN.Bhatt, KirtiLanting, Linda L.Jia, YeYadav, SaileeReddy, Marpadga A.Magilnick, NathanielBoldin, MarkNatarajan, Rama2015-12-08T13:27:43-08:00doi:10.1681/ASN.2015010111hwp:resource-id:jnephrol;27/8/2277American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, inflammation, microRNA, macrophages, renal fibrosisBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150101111046-66731533-34502015-12-08T13:27:43-08:002016-08Journal of the American Society of NephrologyBasic Research27822772288
- Severe Salt–Losing Syndrome and Hyperkalemia Induced by Adult Nephron–Specific Knockout of the Epithelial Sodium Channel α-SubunitSystemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt–losing syndrome caused by loss-of-function mutations of the amiloride–sensitive epithelial sodium channel (ENaC) and characterized by neonatal life–threatening hypovolemia and hyperkalemia. The very high plasma aldosterone levels detected under hypovolemic or hyperkalemic challenge can lead to increased or decreased sodium reabsorption, respectively, through the Na+/Cl− cotransporter (NCC). However, the role of ENaC deficiency remains incompletely defined, because constitutive inactivation of individual ENaC subunits is neonatally lethal in mice. We generated adult inducible nephron–specific αENaC-knockout mice (Scnn1aPax8/LC1) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1. Compared with control mice fed a regular-salt diet, knockout mice fed a regular-salt diet exhibited downregulated expression and phosphorylation of NCC protein, despite high plasma aldosterone levels. In knockout mice fed a high-sodium and reduced-potassium diet (rescue diet), although plasma aldosterone levels remained significantly increased, NCC expression returned to control levels, and body weight, plasma and urinary electrolyte concentrations, and excretion normalized. Finally, shift to a regular diet after the rescue diet reinstated the symptoms of severe PHA-1 syndrome and significantly reduced NCC phosphorylation. In conclusion, lack of ENaC–mediated sodium transport along the nephron cannot be compensated for by other sodium channels and/or transporters, only by a high-sodium and reduced-potassium diet. We further conclude that hyperkalemia becomes the determining factor in regulating NCC activity, regardless of sodium loss, in the ENaC–mediated salt–losing PHA-1 phenotype.10.1681/ASN.2015020154Wed, 23 Dec 2015 06:57:27 GMT-08:00Severe Salt–Losing Syndrome and Hyperkalemia Induced by Adult Nephron–Specific Knockout of the Epithelial Sodium Channel α-SubunitSystemic pseudohypoaldosteronism type 1 (PHA-1) is a severe salt–losing syndrome caused by loss-of-function mutations of the amiloride–sensitive epithelial sodium channel (ENaC) and characterized by neonatal life–threatening hypovolemia and hyperkalemia. The very high plasma aldosterone levels detected under hypovolemic or hyperkalemic challenge can lead to increased or decreased sodium reabsorption, respectively, through the Na+/Cl− cotransporter (NCC). However, the role of ENaC deficiency remains incompletely defined, because constitutive inactivation of individual ENaC subunits is neonatally lethal in mice. We generated adult inducible nephron–specific αENaC-knockout mice (Scnn1aPax8/LC1) that exhibit hyperkalemia and body weight loss when kept on a regular-salt diet, thus mimicking PHA-1. Compared with control mice fed a regular-salt diet, knockout mice fed a regular-salt diet exhibited downregulated expression and phosphorylation of NCC protein, despite high plasma aldosterone levels. In knockout mice fed a high-sodium and reduced-potassium diet (rescue diet), although plasma aldosterone levels remained significantly increased, NCC expression returned to control levels, and body weight, plasma and urinary electrolyte concentrations, and excretion normalized. Finally, shift to a regular diet after the rescue diet reinstated the symptoms of severe PHA-1 syndrome and significantly reduced NCC phosphorylation. In conclusion, lack of ENaC–mediated sodium transport along the nephron cannot be compensated for by other sodium channels and/or transporters, only by a high-sodium and reduced-potassium diet. We further conclude that hyperkalemia becomes the determining factor in regulating NCC activity, regardless of sodium loss, in the ENaC–mediated salt–losing PHA-1 phenotype.Perrier, RomainBoscardin, EmilieMalsure, SumedhaSergi, ChloéMaillard, Marc P.Loffing, JohannesLoffing-Cueni, DominiqueSørensen, Mads VaarbyKoesters, RobertRossier, Bernard C.Frateschi, SimonaHummler, Edith2015-12-23T06:57:27-08:00doi:10.1681/ASN.2015020154hwp:resource-id:jnephrol;27/8/2309American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyaldosterone, ENaC, transgenic mouseBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150201541046-66731533-34502015-12-23T06:57:27-08:002016-08Journal of the American Society of NephrologyBasic Research27823092318
- Macula Densa Nitric Oxide Synthase 1β Protects against Salt-Sensitive HypertensionNitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses α-, β-, and γ-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1β expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1β expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1β mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1α in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1α-knockout (NOS1αKO) mice. Compared with control mice, mice with macula densa–specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P<0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P<0.01) fed a high-salt diet. These results indicate that NOS1β is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP.10.1681/ASN.2015050515Tue, 08 Dec 2015 01:27:47 GMT-08:00Macula Densa Nitric Oxide Synthase 1β Protects against Salt-Sensitive HypertensionNitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses α-, β-, and γ-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1β expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1β expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1β mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1α in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1α-knockout (NOS1αKO) mice. Compared with control mice, mice with macula densa–specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P<0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P<0.01) fed a high-salt diet. These results indicate that NOS1β is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP.Lu, YanWei, JinStec, David E.Roman, Richard J.Ge, YingCheng, LiangLiu, Eddie Y.Zhang, JieHansen, Pernille B. LaerkegaardFan, FanJuncos, Luis A.Wang, LeiPollock, JenniferHuang, Paul L.Fu, YilingWang, ShaohuiLiu, Ruisheng2015-12-08T13:27:47-08:00doi:10.1681/ASN.2015050515hwp:resource-id:jnephrol;27/8/2346American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyNOS1, macula densa, tubuloglomerular feedback, salt-sensitive, hypertensionBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150505151046-66731533-34502015-12-08T13:27:47-08:002016-08Journal of the American Society of NephrologyBasic Research27882346221723562218
- A Novel Three–Dimensional Human Peritubular Microvascular SystemHuman kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system. By combining epithelial cell depletion and cell culture in media with high concentrations of vascular endothelial growth factor, we obtained HKMECs of high purity in large quantity. Unlike other endothelial cells, isolated HKMECs depended on high vascular endothelial growth factor concentration for survival and growth and exhibited high tubulogenic but low angiogenic potential. Furthermore, HKMECs had a different transcriptional profile. Under flow, HKMECs formed a thin fenestrated endothelium with a functional permeability barrier. In conclusion, this three-dimensional HKMEC-specific microphysiologic system recapitulates human kidney microvascular structure and function and shows phenotypic characteristics different from those of other microvascular endothelial cells.10.1681/ASN.2015070747Fri, 11 Dec 2015 08:21:00 GMT-08:00A Novel Three–Dimensional Human Peritubular Microvascular SystemHuman kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system. By combining epithelial cell depletion and cell culture in media with high concentrations of vascular endothelial growth factor, we obtained HKMECs of high purity in large quantity. Unlike other endothelial cells, isolated HKMECs depended on high vascular endothelial growth factor concentration for survival and growth and exhibited high tubulogenic but low angiogenic potential. Furthermore, HKMECs had a different transcriptional profile. Under flow, HKMECs formed a thin fenestrated endothelium with a functional permeability barrier. In conclusion, this three-dimensional HKMEC-specific microphysiologic system recapitulates human kidney microvascular structure and function and shows phenotypic characteristics different from those of other microvascular endothelial cells.Ligresti, GiovanniNagao, Ryan J.Xue, JunChoi, Yoon JungXu, JinRen, ShuyuAburatani, TakahideAnderson, Susan K.MacDonald, James W.Bammler, Theo K.Schwartz, Stephen M.Muczynski, Kimberly A.Duffield, Jeremy S.Himmelfarb, JonathanZheng, Ying2015-12-11T08:21:00-08:00doi:10.1681/ASN.2015070747hwp:resource-id:jnephrol;27/8/2370American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney, microphysiological system, peritubular microvessels, endothelial cells, fenestrae, angiogenesisBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150707471046-66731533-34502015-12-11T08:21:00-08:002016-08Journal of the American Society of NephrologyBasic Research27823702381
- Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging TechniqueRenal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier–transform infrared (FTIR) imaging–based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label–free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.10.1681/ASN.2015050601Fri, 18 Dec 2015 08:08:52 GMT-08:00Renal Graft Fibrosis and Inflammation Quantification by an Automated Fourier–Transform Infrared Imaging TechniqueRenal interstitial fibrosis and interstitial active inflammation are the main histologic features of renal allograft biopsy specimens. Fibrosis is currently assessed by semiquantitative subjective analysis, and color image analysis has been developed to improve the reliability and repeatability of this evaluation. However, these techniques fail to distinguish fibrosis from constitutive collagen or active inflammation. We developed an automatic, reproducible Fourier–transform infrared (FTIR) imaging–based technique for simultaneous quantification of fibrosis and inflammation in renal allograft biopsy specimens. We generated and validated a classification model using 49 renal biopsy specimens and subsequently tested the robustness of this classification algorithm on 166 renal grafts. Finally, we explored the clinical relevance of fibrosis quantification using FTIR imaging by comparing results with renal function at 3 months after transplantation (M3) and the variation of renal function between M3 and M12. We showed excellent robustness for fibrosis and inflammation classification, with >90% of renal biopsy specimens adequately classified by FTIR imaging. Finally, fibrosis quantification by FTIR imaging correlated with renal function at M3, and the variation in fibrosis between M3 and M12 correlated well with the variation in renal function over the same period. This study shows that FTIR-based analysis of renal graft biopsy specimens is a reproducible and reliable label–free technique for quantifying fibrosis and active inflammation. This technique seems to be more relevant than digital image analysis and promising for both research studies and routine clinical practice.Vuiblet, VincentFere, MichaelGobinet, CyrilBirembaut, PhilippePiot, OlivierRieu, Philippe2015-12-18T08:08:52-08:00doi:10.1681/ASN.2015050601hwp:resource-id:jnephrol;27/8/2382American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhistopathology, interstitial fibrosis, acute rejection, chronic allograft nephropathy, renal transplantation, renal pathologyBasic ResearchBasic Researchresearch-article20162016-08-01August 201610.1681/ASN.20150506011046-66731533-34502015-12-18T08:08:52-08:002016-08Journal of the American Society of NephrologyBasic Research27823822391
- Metabolism, Protein Binding, and Renal Clearance of Microbiota–Derived p-Cresol in Patients with CKD10.2215/CJN.00160116Fri, 15 Apr 2016 09:07:55 GMT-07:00Metabolism, Protein Binding, and Renal Clearance of Microbiota–Derived p-Cresol in Patients with CKDPoesen, RubenEvenepoel, Pieterde Loor, HenrietteKuypers, DirkAugustijns, PatrickMeijers, Björn2016-04-15T09:07:55-07:00doi:10.2215/CJN.00160116hwp:resource-id:clinjasn;11/7/1136American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, intestine, Cresols, Follow-Up Studies, Humans, Microbiota, Protein Binding, Renal Insufficiency, Chronic, risk factors, SulfotransferasesOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-07-07July 07, 201610.2215/CJN.001601161555-90411555-905X2016-04-15T09:07:55-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11711361144
- Predictors and Outcomes of Health–Related Quality of Life in Adults with CKD10.2215/CJN.09990915Tue, 31 May 2016 06:42:03 GMT-07:00Predictors and Outcomes of Health–Related Quality of Life in Adults with CKDPorter, Anna C.Lash, James P.Xie, DaweiPan, QiangDeLuca, JenniferKanthety, RadhikaKusek, John W.Lora, Claudia M.Nessel, LisaRicardo, Ana C.Wright Nunes, JulieFischer, Michael J.,2016-05-31T06:42:03-07:00doi:10.2215/CJN.09990915hwp:resource-id:clinjasn;11/7/1154American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, mortality risk, Cohort Studies, Disease Progression, Humans, Kidney Failure, Chronic, obesity, Prospective Studies, quality of lifeOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-07-07July 07, 201610.2215/CJN.099909151555-90411555-905X2016-05-31T06:42:03-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11771154112311621124
- Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD10.2215/CJN.10441015Wed, 08 Jun 2016 06:36:34 GMT-07:00Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKDSun, JiaAxelsson, JonasMachowska, AnnaHeimbürger, OlofBárány, PeterLindholm, BengtLindström, KarinStenvinkel, PeterQureshi, Abdul Rashid2016-06-08T06:36:34-07:00doi:10.2215/CJN.10441015hwp:resource-id:clinjasn;11/7/1163American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyInflammation, chronic kidney disease, cardiovascular disease, Interleukin-6, mortality, Biomarkers, C-Reactive Protein, Follow-Up Studies, Humans, Renal Insufficiency, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-07-07July 07, 201610.2215/CJN.104410151555-90411555-905X2016-06-08T06:36:34-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11711631172
- Bone Disease after Kidney TransplantationBone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients.10.2215/CJN.11371015Mon, 15 Feb 2016 06:59:31 GMT-08:00Bone Disease after Kidney TransplantationBone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients.Bouquegneau, AntoineSalam, SyrazahDelanaye, PierreEastell, RichardKhwaja, Arif2016-02-15T06:59:31-08:00doi:10.2215/CJN.11371015hwp:resource-id:clinjasn;11/7/1282American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, mineral metabolism, renal osteodystrophy, fracture, glucocorticoids, Bone Diseases, Metabolic, Osteoporosis, parathyroid hormone, Vitamin D, fibroblast growth factor 23Mini-ReviewMini-Reviewresearch-article20162016-07-07July 07, 201610.2215/CJN.113710151555-90411555-905X2016-02-15T06:59:31-08:002016-07-07Clinical Journal of the American Society of NephrologyMini-Review11712821296
- Atrial Fibrillation and Risk of ESRD in Adults with CKD10.2215/CJN.10921015Tue, 12 Apr 2016 08:25:44 GMT-07:00Atrial Fibrillation and Risk of ESRD in Adults with CKDBansal, NishaXie, DaweiTao, KelvinChen, JingDeo, RajatHorwitz, EdwardHsu, Chi-yuanKallem, Radha KrishnaKeane, Martin G.Lora, Claudia M.Raj, DominicSoliman, Elsayed Z.Strauss, LouiseWolf, MylesGo, Alan S.2016-04-12T08:25:44-07:00doi:10.2215/CJN.10921015hwp:resource-id:clinjasn;11/7/1189American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, renal progression, Atrial Fibrillation, diabetes mellitus, Electrocardiography, Humans, Kidney Failure, Chronic, Prospective Studies, RiskOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-07-07July 07, 201610.2215/CJN.109210151555-90411555-905X2016-04-12T08:25:44-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11711891196
- Carotid Intima-Media Thickness and Incident ESRD: The Atherosclerosis Risk in Communities (ARIC) Study10.2215/CJN.11951115Tue, 12 Apr 2016 08:25:45 GMT-07:00Carotid Intima-Media Thickness and Incident ESRD: The Atherosclerosis Risk in Communities (ARIC) StudyPang, YuanjieSang, YingyingBallew, Shoshana H.Grams, Morgan E.Heiss, GerardoCoresh, JosefMatsushita, Kunihiro2016-04-12T08:25:45-07:00doi:10.2215/CJN.11951115hwp:resource-id:clinjasn;11/7/1197American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriosclerosis, end-stage renal disease, Epidemiology and outcomes, Atherosclerosis, Carotid Intima-Media Thickness, coronary artery disease, heart failure, Humans, Kidney Failure, Chronic, StrokeOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-07-07July 07, 201610.2215/CJN.119511151555-90411555-905X2016-04-12T08:25:45-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11711971205
- Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKD10.2215/CJN.10210915Thu, 16 Jun 2016 06:46:44 GMT-07:00Genetic, Environmental, and Disease-Associated Correlates of Vitamin D Status in Children with CKDDoyon, AnkeSchmiedchen, BettinaSander, AnjaBayazit, AysunDuzova, AliCanpolat, NurThurn, DanielaAzukaitis, KarolisAnarat, AliBacchetta, JustineMir, SevgiShroff, RukshanaYilmaz, EbruCandan, CengizKemper, MarkusFischbach, MichelCortina, GerardKlaus, GünterWuttke, MatthiasKöttgen, AnnaMelk, AnetteQuerfeld, UweSchaefer, Franz2016-06-16T06:46:44-07:00doi:10.2215/CJN.10210915hwp:resource-id:clinjasn;11/7/1145American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyVitamin D, chronic kidney disease, vitamin D deficiency, vitamin d supplementation, albuminuria, Child, Humans, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, 25-hydroxyvitamin DOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-07-07July 07, 201610.2215/CJN.102109151555-90411555-905X2016-06-16T06:46:44-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11711451153
- American Society of Nephrology Quiz and Questionnaire 2015: ESRD/RRTThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. During the 2015 meeting, the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid-base disorders, glomerular disease, ESRD and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cellphone application containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then, the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.10.2215/CJN.01280216Tue, 19 Apr 2016 07:00:29 GMT-07:00American Society of Nephrology Quiz and Questionnaire 2015: ESRD/RRTThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. During the 2015 meeting, the conference hall was once again overflowing with eager quiz participants. Topics covered by the experts included electrolyte and acid-base disorders, glomerular disease, ESRD and dialysis, and kidney transplantation. Complex cases representing each of these categories together with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of nephrology fellowship programs and nephrology fellows in the United States answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on the same series of case-oriented questions in a quiz. The audience compared their answers in real time using a cellphone application containing the answers of the nephrology fellows and training program directors. The results of the online questionnaire were displayed, and then, the quiz answers were discussed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces selected content of educational value for the readers of the Clinical Journal of the American Society of Nephrology. Enjoy the clinical cases and expert discussions.Lok, Charmaine E.Perazella, Mark A.Choi, Michael J.2016-04-19T07:00:29-07:00doi:10.2215/CJN.01280216hwp:resource-id:clinjasn;11/7/1313American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hemodialysis access, hemodialysis adequacy, innovation, Ethnic Groups, Humans, Kidney Failure, Chronic, nephrologySpecial FeaturesSpecial Featuresresearch-article20162016-07-07July 07, 201610.2215/CJN.012802161555-90411555-905X2016-04-19T07:00:29-07:002016-07-07Clinical Journal of the American Society of NephrologySpecial Features11713131320
- Tuning into Qualitative Research—A Channel for the Patient Voice10.2215/CJN.05110516Tue, 31 May 2016 06:42:02 GMT-07:00Tuning into Qualitative Research—A Channel for the Patient VoiceTong, AllisonCraig, Jonathan C.2016-05-31T06:42:02-07:00doi:10.2215/CJN.05110516hwp:resource-id:clinjasn;11/7/1128American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyqualitative, patient-centered, patient experience, patient, hemodialysis, interviews, focus groups, Humans, Qualitative Research, VoiceEditorialsEditorialseditorial20162016-07-07July 07, 201610.2215/CJN.051105161555-90411555-905X2016-05-31T06:42:02-07:002016-07-07Clinical Journal of the American Society of NephrologyEditorials11771128120611301218
- A Thematic Synthesis of the Experiences of Adults Living with Hemodialysis10.2215/CJN.10561015Tue, 31 May 2016 06:42:03 GMT-07:00A Thematic Synthesis of the Experiences of Adults Living with HemodialysisReid, ClaireSeymour, JulieJones, Colin2016-05-31T06:42:03-07:00doi:10.2215/CJN.10561015hwp:resource-id:clinjasn;11/7/1206American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hemodialysis, quality of life, patient satisfaction, patient experience, qualitative research, thematic synthesis, patient centered careOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-07-07July 07, 201610.2215/CJN.105610151555-90411555-905X2016-05-31T06:42:03-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11771206112812181130
- High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients10.2215/CJN.04150415Wed, 08 Jun 2016 06:36:35 GMT-07:00High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis PatientsDeger, Serpil MugeHung, Adriana M.Ellis, Charles D.Booker, CindyBian, AihuaChen, GuanhuaAbumrad, Naji N.Ikizler, T. Alp2016-06-08T06:36:35-07:00doi:10.2215/CJN.04150415hwp:resource-id:clinjasn;11/7/1227American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, protein energy wasting, muscle protein turnover, omega-3 fatty acids, diabetes mellitus, Forearm, Homeostasis, Humans, Inflammation, Muscle ProteinsOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-07-07July 07, 201610.2215/CJN.041504151555-90411555-905X2016-06-08T06:36:35-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11771227113112351132
- Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older Adults10.2215/CJN.11111015Mon, 18 Apr 2016 06:49:46 GMT-07:00Association of Reduced eGFR and Albuminuria with Serious Fall Injuries among Older AdultsBowling, C. BarrettBromfield, Samantha G.Colantonio, Lisandro D.Gutiérrez, Orlando M.Shimbo, DaichiReynolds, KristiWright, Nicole C.Curtis, Jeffrey R.Judd, Suzanne E.Franch, HaroldWarnock, David G.McClellan, WilliamMuntner, Paul2016-04-18T06:49:46-07:00doi:10.2215/CJN.11111015hwp:resource-id:clinjasn;11/7/1236American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, falls, geriatric nephrology, Adult, albuminuria, Brain Injuries, Follow-Up Studies, Fractures, Bone, Humans, Renal Insufficiency, ChronicOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20162016-07-07July 07, 201610.2215/CJN.111110151555-90411555-905X2016-04-18T06:49:46-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11712361243
- Long–Term Renal Outcomes after Cisplatin Treatment10.2215/CJN.08070715Tue, 12 Apr 2016 08:25:46 GMT-07:00Long–Term Renal Outcomes after Cisplatin TreatmentLatcha, SheronJaimes, Edgar A.Patil, SujataGlezerman, Ilya G.Mehta, SwatiFlombaum, Carlos D.2016-04-12T08:25:46-07:00doi:10.2215/CJN.08070715hwp:resource-id:clinjasn;11/7/1173American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotoxicity, chronic kidney failure, cisplatin nephrotoxicity, cisplatin, glomerular filtration rate, Acute Kidney Injury, creatinine, Follow-Up Studies, Humans, renal dialysisOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-07-07July 07, 201610.2215/CJN.080707151555-90411555-905X2016-04-12T08:25:46-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11711731179
- Iron Therapy Challenges for the Treatment of Nondialysis CKD PatientsThe clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron–based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron–based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients.10.2215/CJN.00080116Mon, 16 May 2016 08:36:55 GMT-07:00Iron Therapy Challenges for the Treatment of Nondialysis CKD PatientsThe clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron–based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron–based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients.Locatelli, FrancescoMazzaferro, SandroYee, Jerry2016-05-16T08:36:55-07:00doi:10.2215/CJN.00080116hwp:resource-id:clinjasn;11/7/1269American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, anemia, intravenous, anemia, Erythropoiesis, Ferric Compounds, Humans, Iron, Patient Compliance, Prospective Studies, Renal Insufficiency, ChronicIn-Depth ReviewIn-Depth Reviewresearch-article20162016-07-07July 07, 201610.2215/CJN.000801161555-90411555-905X2016-05-16T08:36:55-07:002016-07-07Clinical Journal of the American Society of NephrologyIn-Depth Review11712691280
- Studying Muscle Protein Turnover in CKD10.2215/CJN.04790516Wed, 08 Jun 2016 06:36:33 GMT-07:00Studying Muscle Protein Turnover in CKDGaribotto, GiacomoVerzola, Daniela2016-06-08T06:36:33-07:00doi:10.2215/CJN.04790516hwp:resource-id:clinjasn;11/7/1131American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChronic inflammation, chronic kidney disease, nutrition, omega-3 fatty acids, Muscle Proteins, Muscles, ProteolysisEditorialsEditorialseditorial20162016-07-07July 07, 201610.2215/CJN.047905161555-90411555-905X2016-06-08T06:36:33-07:002016-07-07Clinical Journal of the American Society of NephrologyEditorials11771131122711321235
- Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care InitiativeThe past decade has witnessed a marked reduction in mortality rates among patients receiving maintenance dialysis. However, the reasons for this welcome development are uncertain, and greater understanding is needed to translate advances in care into additional survival gains. To fill important knowledge gaps and to enable dialysis provider organizations to learn from one another, with the aim of advancing patient care, the Peer Kidney Care Initiative (Peer) was created in 2014 by the chief medical officers of 14 United States dialysis provider organizations and the Chronic Disease Research Group. Areas of particular clinical importance were targeted to help shape the public health agenda in CKD and ESRD. Peer focuses on the effect of geographic variation on outcomes, the implications of seasonality for morbidity and mortality, the clinical significance of understudied disorders affecting dialysis patients, and the debate about how best to monitor and evaluate progress in care. In the realm of geovariation, Peer has provided key observations on regional variation in the rates of ESRD incidence, hospitalization, and pre-ESRD care. Regarding seasonality, Peer has reported on variation in both infection-related and non–infection-related hospitalizations, suggesting that ambient environmental conditions may affect a range of health outcomes in dialysis patients. Specific medical conditions that Peer highlights include Clostridium difficile infection, which has become strikingly more common in patients in the year after dialysis initiation, and chronic obstructive pulmonary disease, the treatments for which have the potential to contribute to sudden cardiac death. Finally, Peer challenges the nephrology community to consider alternatives to standardized mortality ratios in assessing progress in care, positing that close scrutiny of trends over time may be the most effective way to drive improvements in patient care.10.2215/CJN.12981215Tue, 22 Mar 2016 06:45:46 GMT-07:00Improving Outcomes in Patients Receiving Dialysis: The Peer Kidney Care InitiativeThe past decade has witnessed a marked reduction in mortality rates among patients receiving maintenance dialysis. However, the reasons for this welcome development are uncertain, and greater understanding is needed to translate advances in care into additional survival gains. To fill important knowledge gaps and to enable dialysis provider organizations to learn from one another, with the aim of advancing patient care, the Peer Kidney Care Initiative (Peer) was created in 2014 by the chief medical officers of 14 United States dialysis provider organizations and the Chronic Disease Research Group. Areas of particular clinical importance were targeted to help shape the public health agenda in CKD and ESRD. Peer focuses on the effect of geographic variation on outcomes, the implications of seasonality for morbidity and mortality, the clinical significance of understudied disorders affecting dialysis patients, and the debate about how best to monitor and evaluate progress in care. In the realm of geovariation, Peer has provided key observations on regional variation in the rates of ESRD incidence, hospitalization, and pre-ESRD care. Regarding seasonality, Peer has reported on variation in both infection-related and non–infection-related hospitalizations, suggesting that ambient environmental conditions may affect a range of health outcomes in dialysis patients. Specific medical conditions that Peer highlights include Clostridium difficile infection, which has become strikingly more common in patients in the year after dialysis initiation, and chronic obstructive pulmonary disease, the treatments for which have the potential to contribute to sudden cardiac death. Finally, Peer challenges the nephrology community to consider alternatives to standardized mortality ratios in assessing progress in care, positing that close scrutiny of trends over time may be the most effective way to drive improvements in patient care.Wetmore, James B.Gilbertson, David T.Liu, JiannongCollins, Allan J.2016-03-22T06:45:46-07:00doi:10.2215/CJN.12981215hwp:resource-id:clinjasn;11/7/1297American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end-stage renal disease, outcomes, death, sudden, cardiac, hospitalization, humans, incidence, morbidity, patient care, renal dialysis, renal insufficiency, chronicPublic Policy SeriesPublic Policy Seriesresearch-article20162016-07-07July 07, 201610.2215/CJN.129812151555-90411555-905X2016-03-22T06:45:46-07:002016-07-07Clinical Journal of the American Society of NephrologyPublic Policy Series11712971304
- Health–Related Quality of Life in CKD—Advancing Patient-Centered Research to Transform Patient Care10.2215/CJN.04730416Tue, 31 May 2016 06:42:03 GMT-07:00Health–Related Quality of Life in CKD—Advancing Patient-Centered Research to Transform Patient CarePowe, Neil R.2016-05-31T06:42:03-07:00doi:10.2215/CJN.04730416hwp:resource-id:clinjasn;11/7/1123American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyquality of life, chronic kidney disease, outcomes, Humans, Patient Care, Renal Insufficiency, Chronic, ResearchEditorialsEditorialseditorial20162016-07-07July 07, 201610.2215/CJN.047304161555-90411555-905X2016-05-31T06:42:03-07:002016-07-07Clinical Journal of the American Society of NephrologyEditorials11771123115411241162
- The Relevance of Geriatric Impairments in Patients Starting Dialysis: A Systematic Review10.2215/CJN.06660615Tue, 26 Apr 2016 07:08:56 GMT-07:00The Relevance of Geriatric Impairments in Patients Starting Dialysis: A Systematic Reviewvan Loon, Ismay N.Wouters, Tom R.Boereboom, Franciscus T.J.Bots, Michiel L.Verhaar, Marianne C.Hamaker, Marije E.2016-04-26T07:08:56-07:00doi:10.2215/CJN.06660615hwp:resource-id:clinjasn;11/7/1245American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, decision-making, geriatric assessment, elderly, frailty, Activities of Daily Living, Cognition, hospitalization, Humans, Kidney Failure, Chronic, Nutritional StatusOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20162016-07-07July 07, 201610.2215/CJN.066606151555-90411555-905X2016-04-26T07:08:56-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11712451259
- Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States10.2215/CJN.10370915Mon, 06 Jun 2016 07:11:51 GMT-07:00Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United StatesKim, Sun MoonLong, JinMontez-Rath, Maria E.Leonard, Mary B.Norton, Jeffrey A.Chertow, Glenn M.2016-06-06T07:11:51-07:00doi:10.2215/CJN.10370915hwp:resource-id:clinjasn;11/7/1260American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperparathyroidism, parathyroidectomy, health services research, Nationwide Inpatient Sample, Hospital Mortality, hospitalization, Humans, Hyperparathyroidism, Secondary, Kidney Failure, Chronic, Length of StayOriginal ArticlesMineral metabolism/Bone diseaseOriginal ArticlesMineral metabolism/Bone diseaseresearch-article20162016-07-07July 07, 201610.2215/CJN.103709151555-90411555-905X2016-06-06T07:11:51-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11771260113312671135
- Effects of Stenting for Atherosclerotic Renal Artery Stenosis on eGFR and Predictors of Clinical Events in the CORAL Trial10.2215/CJN.10491015Wed, 25 May 2016 06:12:32 GMT-07:00Effects of Stenting for Atherosclerotic Renal Artery Stenosis on eGFR and Predictors of Clinical Events in the CORAL TrialTuttle, Katherine R.Dworkin, Lance D.Henrich, WilliamGreco, Barbara A.Steffes, MichaelTobe, SheldonShapiro, Joseph I.Jamerson, KennethLyass, AsyaPencina, KarolMassaro, Joseph M.D’Agostino, Ralph B.Cutlip, Donald E.Murphy, Timothy P.Cooper, Christopher J.2016-05-25T06:12:32-07:00doi:10.2215/CJN.10491015hwp:resource-id:clinjasn;11/7/1180American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, glomerular filtration rate, renin angiotensin system, albuminuria, blood pressure, hypertension, Renal Artery Obstruction, StentsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-07-07July 07, 201610.2215/CJN.104910151555-90411555-905X2016-05-25T06:12:32-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11771180112511881127
- Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population HealthExpanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost–conscious care environment.10.2215/CJN.13251215Thu, 10 Mar 2016 06:57:18 GMT-08:00Urinary Stone Disease: Advancing Knowledge, Patient Care, and Population HealthExpanding epidemiologic and physiologic data suggest that urinary stone disease is best conceptualized as a chronic metabolic condition punctuated by symptomatic, preventable stone events. These acute events herald substantial future chronic morbidity, including decreased bone mineral density, cardiovascular disease, and CKD. Urinary stone disease imposes a large and growing public health burden. In the United States, 1 in 11 individuals will experience a urinary stone in their lifetime. Given this high incidence and prevalence, urinary stone disease is one of the most expensive urologic conditions, with health care charges exceeding $10 billion annually. Patient care focuses on management of symptomatic stones rather than prevention; after three decades of innovation, procedural interventions are almost exclusively minimally invasive or noninvasive, and mortality is rare. Despite these advances, the prevalence of stone disease has nearly doubled over the past 15 years, likely secondary to dietary and health trends. The NIDDK recently convened a symposium to assess knowledge and treatment gaps to inform future urinary stone disease research. Reducing the public health burden of urinary stone disease will require key advances in understanding environmental, genetic, and other individual disease determinants; improving secondary prevention; and optimal population health strategies in an increasingly cost–conscious care environment.Scales, Charles D.Tasian, Gregory E.Schwaderer, Andrew L.Goldfarb, David S.Star, Robert A.Kirkali, Ziya2016-03-10T06:57:18-08:00doi:10.2215/CJN.13251215hwp:resource-id:clinjasn;11/7/1305American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, Cardiovascular Diseases, Disease Management, Health Expenditures, Humans, Morbidity, National Institute of Diabetes and Digestive and Kidney Diseases (U.S.), Patient Care, Public Health, Secondary PreventionSpecial FeaturesSpecial Featuresresearch-article20162016-07-07July 07, 201610.2215/CJN.132512151555-90411555-905X2016-03-10T06:57:18-08:002016-07-07Clinical Journal of the American Society of NephrologySpecial Features11713051312
- Parathyroidectomy: Complex Decisions about a Complex Procedure10.2215/CJN.04950516Mon, 06 Jun 2016 07:11:51 GMT-07:00Parathyroidectomy: Complex Decisions about a Complex ProcedureWetmore, James B.2016-06-06T07:11:51-07:00doi:10.2215/CJN.04950516hwp:resource-id:clinjasn;11/7/1133American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyParathyroidectomy, parathyroid hormone, secondary hyperparathyroidism, Treatment OutcomeEditorialsEditorialseditorial20162016-07-07July 07, 201610.2215/CJN.049505161555-90411555-905X2016-06-06T07:11:51-07:002016-07-07Clinical Journal of the American Society of NephrologyEditorials11771133126011351267
- Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences10.2215/CJN.00830116Mon, 06 Jun 2016 07:11:52 GMT-07:00Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term ConsequencesMa, Terry King-WingChow, Kai MingKwan, Bonnie Ching-HaPang, Wing FaiLeung, Chi BonLi, Philip Kam-TaoSzeto, Cheuk Chun2016-06-06T07:11:52-07:00doi:10.2215/CJN.00830116hwp:resource-id:clinjasn;11/7/1219American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, peritonitis, survival, Anti-Bacterial Agents, Humans, Logistic Models, renal dialysis, Retrospective Studies, risk factors, Serum AlbuminOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-07-07July 07, 201610.2215/CJN.008301161555-90411555-905X2016-06-06T07:11:52-07:002016-07-07Clinical Journal of the American Society of NephrologyOriginal Articles11712191226
- Does Renal Artery Stenting Prevent Clinical Events?10.2215/CJN.04640416Wed, 25 May 2016 06:12:33 GMT-07:00Does Renal Artery Stenting Prevent Clinical Events?Textor, Stephen C.Misra, Sanjay2016-05-25T06:12:33-07:00doi:10.2215/CJN.04640416hwp:resource-id:clinjasn;11/7/1125American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal artery stenosis, renovascular hypertension, stent, hypertension, ischemic nephropathy, kidney, Cardiovascular System, Renal ArteryEditorialsEditorialseditorial20162016-07-07July 07, 201610.2215/CJN.046404161555-90411555-905X2016-05-25T06:12:33-07:002016-07-07Clinical Journal of the American Society of NephrologyEditorials11771125118011271188
- Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes InsipidusTo reduce lithium–induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA–specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.10.1681/ASN.2015070796Mon, 16 Nov 2015 02:09:39 GMT-08:00Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes InsipidusTo reduce lithium–induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA–specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects.de Groot, TheunSinke, Anne P.Kortenoeven, Marleen L.A.Alsady, MohammadBaumgarten, RubenDevuyst, OlivierLoffing, JohannesWetzels, Jack F.Deen, Peter M.T.2015-11-16T14:09:39-08:00doi:10.1681/ASN.2015070796hwp:resource-id:jnephrol;27/7/2082American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell and transport physiology, diabetes insipidus, diuretics, osmolality, pathophysiology of renal disease and progression, water transportBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150707961046-66731533-34502015-11-16T14:09:39-08:002016-07Journal of the American Society of NephrologyBasic Research27772082187220911874
- Unlocking the Value of Variation in CKD Prevalence10.1681/ASN.2015111280Tue, 29 Dec 2015 05:40:10 GMT-08:00Unlocking the Value of Variation in CKD PrevalenceBlack, Corrivan der Veer, Sabine N.2015-12-29T05:40:10-08:00doi:10.1681/ASN.2015111280hwp:resource-id:jnephrol;27/7/1874American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, natural experiment, prevalenceUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-07-01July 201610.1681/ASN.20151112801046-66731533-34502015-12-29T05:40:10-08:002016-07Journal of the American Society of NephrologyUp Front Matters27771874213518772147
- Utility of Prostate Cancer Screening in Kidney Transplant CandidatesScreening recommendations for prostate cancer remain controversial, and no specific guidelines exist for screening in renal transplant candidates. To examine whether the use of prostate-specific antigen (PSA)–based screening in patients with ESRD affects time to transplantation and transplant outcomes, we retrospectively analyzed 3782 male patients ≥18 years of age undergoing primary renal transplant evaluation during a 10-year period. Patients were grouped by age per American Urological Association screening guidelines: group 1, patients <55 years; group 2, patients 55–69 years; and group 3, patients >69 years. A positive screening test result was defined as a PSA level >4 ng/ml. We used univariate analysis and Cox proportional hazards models to identify the independent effect of screening on transplant waiting times, patient survival, and graft survival. Screening was performed in 63.6% of candidates, and 1198 candidates (31.7%) received kidney transplants. PSA screening was not associated with improved patient survival after transplantation (P=0.24). However, it did increase the time to listing and transplantation for candidates in groups 1 and 2 who had a positive screening result (P<0.05). Furthermore, compared with candidates who were not screened, PSA-screened candidates had a reduced likelihood of receiving a transplant regardless of the screening outcome (P<0.001). These data strongly suggest that PSA screening for prostate cancer may be more harmful than protective in renal transplant candidates because it does not appear to confer a survival benefit to these candidates and may delay listing and decrease transplantation rates.10.1681/ASN.2014121182Wed, 23 Dec 2015 06:57:24 GMT-08:00Utility of Prostate Cancer Screening in Kidney Transplant CandidatesScreening recommendations for prostate cancer remain controversial, and no specific guidelines exist for screening in renal transplant candidates. To examine whether the use of prostate-specific antigen (PSA)–based screening in patients with ESRD affects time to transplantation and transplant outcomes, we retrospectively analyzed 3782 male patients ≥18 years of age undergoing primary renal transplant evaluation during a 10-year period. Patients were grouped by age per American Urological Association screening guidelines: group 1, patients <55 years; group 2, patients 55–69 years; and group 3, patients >69 years. A positive screening test result was defined as a PSA level >4 ng/ml. We used univariate analysis and Cox proportional hazards models to identify the independent effect of screening on transplant waiting times, patient survival, and graft survival. Screening was performed in 63.6% of candidates, and 1198 candidates (31.7%) received kidney transplants. PSA screening was not associated with improved patient survival after transplantation (P=0.24). However, it did increase the time to listing and transplantation for candidates in groups 1 and 2 who had a positive screening result (P<0.05). Furthermore, compared with candidates who were not screened, PSA-screened candidates had a reduced likelihood of receiving a transplant regardless of the screening outcome (P<0.001). These data strongly suggest that PSA screening for prostate cancer may be more harmful than protective in renal transplant candidates because it does not appear to confer a survival benefit to these candidates and may delay listing and decrease transplantation rates.Vitiello, Gerardo A.Sayed, Blayne A.Wardenburg, MarlaPerez, Sebastian D.Keith, Christopher G.Canter, Daniel J.Ogan, KennethPearson, Thomas C.Turgeon, Nicole2015-12-23T06:57:24-08:00doi:10.1681/ASN.2014121182hwp:resource-id:jnephrol;27/7/2157American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplant, prostate cancer, PSA screeningClinical ResearchClinical Researchresearch-article20162016-07-01July 201610.1681/ASN.20141211821046-66731533-34502015-12-23T06:57:24-08:002016-07Journal of the American Society of NephrologyClinical Research27721572163
- Racial and Ethnic Disparities in Use of and Outcomes with Home Dialysis in the United StatesHome dialysis, which comprises peritoneal dialysis (PD) or home hemodialysis (home HD), offers patients with ESRD greater flexibility and independence. Although ESRD disproportionately affects racial/ethnic minorities, data on disparities in use and outcomes with home dialysis are sparse. We analyzed data of patients who initiated maintenance dialysis between 2007 and 2011 and were admitted to any of 2217 dialysis facilities in 43 states operated by a single large dialysis organization, with follow-up through December 31, 2011 (n=162,050, of which 17,791 underwent PD and 2536 underwent home HD for ≥91 days). Every racial/ethnic minority group was significantly less likely to be treated with home dialysis than whites. Among individuals treated with in-center HD or PD, racial/ethnic minorities had a lower risk for death than whites; among individuals undergoing home HD, only blacks had a significantly lower death risk than whites. Blacks undergoing PD or home HD had a higher risk for transfer to in-center HD than their white counterparts, whereas Asians or others undergoing PD had a lower risk than whites undergoing PD. Blacks irrespective of dialysis modality, Hispanics undergoing PD or in-center HD, and Asians and other racial groups undergoing in-center HD were significantly less likely than white counterparts to receive a kidney transplant. In conclusion, there are racial/ethnic disparities in use of and outcomes with home dialysis in the United States. Disparities in kidney transplantation evident for blacks and Hispanics undergoing home dialysis are similar to those with in-center HD. Future studies should identify modifiable causes for these disparities.10.1681/ASN.2015050472Thu, 10 Dec 2015 12:36:22 GMT-08:00Racial and Ethnic Disparities in Use of and Outcomes with Home Dialysis in the United StatesHome dialysis, which comprises peritoneal dialysis (PD) or home hemodialysis (home HD), offers patients with ESRD greater flexibility and independence. Although ESRD disproportionately affects racial/ethnic minorities, data on disparities in use and outcomes with home dialysis are sparse. We analyzed data of patients who initiated maintenance dialysis between 2007 and 2011 and were admitted to any of 2217 dialysis facilities in 43 states operated by a single large dialysis organization, with follow-up through December 31, 2011 (n=162,050, of which 17,791 underwent PD and 2536 underwent home HD for ≥91 days). Every racial/ethnic minority group was significantly less likely to be treated with home dialysis than whites. Among individuals treated with in-center HD or PD, racial/ethnic minorities had a lower risk for death than whites; among individuals undergoing home HD, only blacks had a significantly lower death risk than whites. Blacks undergoing PD or home HD had a higher risk for transfer to in-center HD than their white counterparts, whereas Asians or others undergoing PD had a lower risk than whites undergoing PD. Blacks irrespective of dialysis modality, Hispanics undergoing PD or in-center HD, and Asians and other racial groups undergoing in-center HD were significantly less likely than white counterparts to receive a kidney transplant. In conclusion, there are racial/ethnic disparities in use of and outcomes with home dialysis in the United States. Disparities in kidney transplantation evident for blacks and Hispanics undergoing home dialysis are similar to those with in-center HD. Future studies should identify modifiable causes for these disparities.Mehrotra, RajnishSoohoo, MelissaRivara, Matthew B.Himmelfarb, JonathanCheung, Alfred K.Arah, Onyebuchi A.Nissenson, Allen R.Ravel, VanessaStreja, ElaniKuttykrishnan, SoorajKatz, RonitMolnar, Miklos Z.Kalantar-Zadeh, Kamyar2015-12-10T12:36:22-08:00doi:10.1681/ASN.2015050472hwp:resource-id:jnephrol;27/7/2123American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, hemodialysis, peritoneal dialysisClinical EpidemiologyClinical Epidemiologyresearch-article20162016-07-01July 201610.1681/ASN.20150504721046-66731533-34502015-12-10T12:36:22-08:002016-07Journal of the American Society of NephrologyClinical Epidemiology27721232134
- Tubuloreticular Inclusions in Renal Allografts Associate with Viral Infections and Donor-Specific AntibodiesThe presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy–free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor–specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.10.1681/ASN.2015050478Fri, 27 Nov 2015 06:38:39 GMT-08:00Tubuloreticular Inclusions in Renal Allografts Associate with Viral Infections and Donor-Specific AntibodiesThe presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy–free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor–specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.Willicombe, MichelleMoss, JillMoran, LindaBrookes, PaulSantos-Nunez, EvaMcLean, Adam G.Cairns, ThomasTaube, DavidCook, Terence H.Roufosse, Candice2015-11-27T06:38:39-08:00doi:10.1681/ASN.2015050478hwp:resource-id:jnephrol;27/7/2188American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, transplant pathology, transplant outcomes, rejection, immunology and pathologyClinical ResearchClinical Researchresearch-article20162016-07-01July 201610.1681/ASN.20150504781046-66731533-34502015-11-27T06:38:39-08:002016-07Journal of the American Society of NephrologyClinical Research27721882195
- Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation TrialRecipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver–type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.10.1681/ASN.2015030292Wed, 04 Nov 2015 10:27:52 GMT-08:00Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation TrialRecipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver–type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes.Bansal, NishaCarpenter, Myra A.Weiner, Daniel E.Levey, Andrew S.Pfeffer, MarcKusek, John W.Cai, JianwenHunsicker, Lawrence G.Park, MeyeonBennett, MichaelLiu, Kathleen D.Hsu, Chi-yuan2015-11-04T10:27:52-08:00doi:10.1681/ASN.2015030292hwp:resource-id:jnephrol;27/7/2109American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, kidney transplantation, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20162016-07-01July 201610.1681/ASN.20150302921046-66731533-34502015-11-04T10:27:52-08:002016-07Journal of the American Society of NephrologyClinical Epidemiology27721092121
- Suitability of Patients with Autosomal Dominant Polycystic Kidney Disease for Renal Transcatheter Arterial EmbolizationIn patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.0±9.1 years old). One year after renal TAE, the RVRR ranged from 3.9% to 84.8%, and the least squares mean RVRR calculated using a linear mixed model was 45.5% (95% confidence interval [95% CI], 44.2% to 46.8%). Multivariate analysis using the linear mixed model revealed that RVRR was affected by the presence of large cysts with wall thickening (regression coefficient [RC], −6.10; 95% CI, −9.04 to −3.16; P<0.001), age (RC, −0.82; 95% CI, −1.03 to −0.60; P<0.001), dialysis duration (RC, −0.10; 95% CI, −0.18 to −0.03; P<0.01), systolic BP (RC, 0.39; 95% CI, 0.19 to 0.59; P<0.001), and the number of microcoils used for renal TAE (RC, 1.35; 95% CI, 0.83 to 1.86; P<0.001). Significantly more microcoils were needed to achieve renal TAE in patients with younger age and shorter dialysis duration. In conclusion, cyst wall thickening had an important effect on cyst volume reduction. Renal TAE was more effective in patients who were younger, had shorter dialysis duration, or had hypertension, parameters that might associate with cyst wall stiffness and renal artery blood flow.10.1681/ASN.2015010067Mon, 30 Nov 2015 03:23:17 GMT-08:00Suitability of Patients with Autosomal Dominant Polycystic Kidney Disease for Renal Transcatheter Arterial EmbolizationIn patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.0±9.1 years old). One year after renal TAE, the RVRR ranged from 3.9% to 84.8%, and the least squares mean RVRR calculated using a linear mixed model was 45.5% (95% confidence interval [95% CI], 44.2% to 46.8%). Multivariate analysis using the linear mixed model revealed that RVRR was affected by the presence of large cysts with wall thickening (regression coefficient [RC], −6.10; 95% CI, −9.04 to −3.16; P<0.001), age (RC, −0.82; 95% CI, −1.03 to −0.60; P<0.001), dialysis duration (RC, −0.10; 95% CI, −0.18 to −0.03; P<0.01), systolic BP (RC, 0.39; 95% CI, 0.19 to 0.59; P<0.001), and the number of microcoils used for renal TAE (RC, 1.35; 95% CI, 0.83 to 1.86; P<0.001). Significantly more microcoils were needed to achieve renal TAE in patients with younger age and shorter dialysis duration. In conclusion, cyst wall thickening had an important effect on cyst volume reduction. Renal TAE was more effective in patients who were younger, had shorter dialysis duration, or had hypertension, parameters that might associate with cyst wall stiffness and renal artery blood flow.Suwabe, TatsuyaUbara, YoshifumiMise, KokiUeno, ToshiharuSumida, KeiichiYamanouchi, MasayukiHayami, NorikoHoshino, JunichiKawada, MasahiroImafuku, AyaHiramatsu, RikakoHasegawa, EikoSawa, NaokiTakaichi, Kenmei2015-11-30T03:23:17-08:00doi:10.1681/ASN.2015010067hwp:resource-id:jnephrol;27/7/2177American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, dialysis, polycystic kidney disease, cystic fibrosis, cystic kidney, chronic kidney diseaseClinical ResearchClinical Researchresearch-article20162016-07-01July 201610.1681/ASN.20150100671046-66731533-34502015-11-30T03:23:17-08:002016-07Journal of the American Society of NephrologyClinical Research27721772187
- This Month's Highlights10.1681/ASN.2016040472Thu, 30 Jun 2016 10:00:56 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-06-30T10:00:56-07:00doi:10.1681/ASN.2016040472hwp:resource-id:jnephrol;27/7/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-07-01July 201610.1681/ASN.20160404721046-66731533-34502016-06-30T10:00:56-07:002016-07Journal of the American Society of NephrologyThis Month's Highlights277ii
- Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes InsipidusStore-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca2+) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca2+ levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca2+ mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca2+ levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.10.1681/ASN.2014121200Mon, 16 Nov 2015 02:09:37 GMT-08:00Defective Store-Operated Calcium Entry Causes Partial Nephrogenic Diabetes InsipidusStore-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca2+) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca2+ levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca2+ mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca2+ levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.Mamenko, MykolaDhande, IshaTomilin, ViktorZaika, OlegBoukelmoune, NabilaZhu, YamingGonzalez-Garay, Manuel L.Pochynyuk, OlehDoris, Peter A.2015-11-16T14:09:37-08:00doi:10.1681/ASN.2014121200hwp:resource-id:jnephrol;27/7/2035American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, water transport, diabetes insipidus, vasopressin, collecting ductsBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20141212001046-66731533-34502015-11-16T14:09:37-08:002016-07Journal of the American Society of NephrologyBasic Research27772035187220481874
- Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-ReperfusionA positional isomer of 3′,5′-cAMP, 2′,3′-cAMP, is produced by kidneys in response to energy depletion, and renal 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) metabolizes 2′,3′-cAMP to 2′-AMP; 2′,3′-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) –induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase−/−) versus wild-type (WT) mice using a unique two–kidney, hanging–weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion). Analysis of urinary purines showed attenuated metabolism of 2′,3′-cAMP to 2′-AMP in CNPase−/− mice. Neither genotype nor IR affected BP, heart rate, urine volume, or albumin excretion. In WT mice, renal IR reduced 14C-inulin clearance (index of GFR) and increased renal vascular resistance (measured by transit time nanoprobes) and urinary excretion of kidney injury molecule-1 and neutrophil gelatinase–associated lipocalin. IR did not affect these parameters in CNPase−/− mice. Histologic analysis revealed that IR induced severe damage in kidneys from WT mice, whereas histologic changes were minimal after IR in CNPase−/− mice. Measurements of renal cardiolipin levels, citrate synthase activity, rotenone–sensitive NADH oxidase activity, and proximal tubular mitochondrial and autophagosome area and number (by transmission electron microscopy) indicted accelerated autophagy/mitophagy in injured CNPase−/− mice. We conclude that CNPase deletion attenuates IR-induced AKI, in part by accelerating autophagy with targeted removal of damaged mitochondria.10.1681/ASN.2015040397Mon, 16 Nov 2015 02:09:40 GMT-08:00Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-ReperfusionA positional isomer of 3′,5′-cAMP, 2′,3′-cAMP, is produced by kidneys in response to energy depletion, and renal 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) metabolizes 2′,3′-cAMP to 2′-AMP; 2′,3′-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) –induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase−/−) versus wild-type (WT) mice using a unique two–kidney, hanging–weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion). Analysis of urinary purines showed attenuated metabolism of 2′,3′-cAMP to 2′-AMP in CNPase−/− mice. Neither genotype nor IR affected BP, heart rate, urine volume, or albumin excretion. In WT mice, renal IR reduced 14C-inulin clearance (index of GFR) and increased renal vascular resistance (measured by transit time nanoprobes) and urinary excretion of kidney injury molecule-1 and neutrophil gelatinase–associated lipocalin. IR did not affect these parameters in CNPase−/− mice. Histologic analysis revealed that IR induced severe damage in kidneys from WT mice, whereas histologic changes were minimal after IR in CNPase−/− mice. Measurements of renal cardiolipin levels, citrate synthase activity, rotenone–sensitive NADH oxidase activity, and proximal tubular mitochondrial and autophagosome area and number (by transmission electron microscopy) indicted accelerated autophagy/mitophagy in injured CNPase−/− mice. We conclude that CNPase deletion attenuates IR-induced AKI, in part by accelerating autophagy with targeted removal of damaged mitochondria.Jackson, Edwin K.Menshikova, Elizabeth V.Mi, ZaichuanVerrier, Jonathan D.Bansal, RashmiJanesko-Feldman, KeriJackson, Travis C.Kochanek, Patrick M.2015-11-16T14:09:40-08:00doi:10.1681/ASN.2015040397hwp:resource-id:jnephrol;27/7/2069American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cyclic AMP, ischemia-reperfusion, renal ischemia, electron microscopy, mitochondriaBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150403971046-66731533-34502015-11-16T14:09:40-08:002016-07Journal of the American Society of NephrologyBasic Research27720692081
- Enhancer of Zeste Homolog 2 Inhibition Attenuates Renal Fibrosis by Maintaining Smad7 and Phosphatase and Tensin Homolog ExpressionEnhancer of zeste homolog 2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. However, the role of EZH2 in renal fibrogenesis remains unexplored. In this study, we found high expression of EZH2 and H3K27me3 in cultured renal fibroblasts and fibrotic kidneys from mice with unilateral ureteral obstruction and humans with CKD. Pharmacologic inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) or GSK126 or siRNA-mediated silencing of EZH2 inhibited serum- and TGFβ1-induced activation of renal interstitial fibroblasts in vitro, and 3-DZNeP administration abrogated deposition of extracellular matrix proteins and expression of α-smooth muscle actin in the obstructed kidney. Injury to the kidney enhanced Smad7 degradation, Smad3 phosphorylation, and TGFβ receptor 1 expression, and 3-DZNeP administration prevented these effects. 3-DZNeP also suppressed phosphorylation of the renal EGF and PDGFβ receptors and downstream signaling molecules signal transducer and activator of transcription 3 and extracellular signal–regulated kinase 1/2 after injury. Moreover, EZH2 inhibition increased the expression of phosphatase and tensin homolog (PTEN), a protein previously associated with dephosphorylation of tyrosine kinase receptors in the injured kidney and serum–stimulated renal interstitial fibroblasts. Finally, blocking PTEN with SF1670 largely diminished the inhibitory effect of 3-DZNeP on renal myofibroblast activation. These results uncovered the important role of EZH2 in mediating the development of renal fibrosis by downregulating expression of Smad7 and PTEN, thus activating profibrotic signaling pathways. Targeted inhibition of EZH2, therefore, could be a novel therapy for treating CKD.10.1681/ASN.2015040457Wed, 23 Dec 2015 06:57:26 GMT-08:00Enhancer of Zeste Homolog 2 Inhibition Attenuates Renal Fibrosis by Maintaining Smad7 and Phosphatase and Tensin Homolog ExpressionEnhancer of zeste homolog 2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. However, the role of EZH2 in renal fibrogenesis remains unexplored. In this study, we found high expression of EZH2 and H3K27me3 in cultured renal fibroblasts and fibrotic kidneys from mice with unilateral ureteral obstruction and humans with CKD. Pharmacologic inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) or GSK126 or siRNA-mediated silencing of EZH2 inhibited serum- and TGFβ1-induced activation of renal interstitial fibroblasts in vitro, and 3-DZNeP administration abrogated deposition of extracellular matrix proteins and expression of α-smooth muscle actin in the obstructed kidney. Injury to the kidney enhanced Smad7 degradation, Smad3 phosphorylation, and TGFβ receptor 1 expression, and 3-DZNeP administration prevented these effects. 3-DZNeP also suppressed phosphorylation of the renal EGF and PDGFβ receptors and downstream signaling molecules signal transducer and activator of transcription 3 and extracellular signal–regulated kinase 1/2 after injury. Moreover, EZH2 inhibition increased the expression of phosphatase and tensin homolog (PTEN), a protein previously associated with dephosphorylation of tyrosine kinase receptors in the injured kidney and serum–stimulated renal interstitial fibroblasts. Finally, blocking PTEN with SF1670 largely diminished the inhibitory effect of 3-DZNeP on renal myofibroblast activation. These results uncovered the important role of EZH2 in mediating the development of renal fibrosis by downregulating expression of Smad7 and PTEN, thus activating profibrotic signaling pathways. Targeted inhibition of EZH2, therefore, could be a novel therapy for treating CKD.Zhou, XiaoxuZang, XiujuanPonnusamy, MurugavelMasucci, Monica V.Tolbert, EvelynGong, RujunZhao, Ting C.Liu, NaBayliss, GeorgeDworkin, Lance D.Zhuang, Shougang2015-12-23T06:57:26-08:00doi:10.1681/ASN.2015040457hwp:resource-id:jnephrol;27/7/2092American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, fibrosis, obstructive nephropathy, fibroblast, signalingBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150404571046-66731533-34502015-12-23T06:57:26-08:002016-07Journal of the American Society of NephrologyBasic Research2728772092225221082252
- Idiopathic Retroperitoneal FibrosisIdiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro-inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the B cell–depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases.10.1681/ASN.2015101110Tue, 09 Feb 2016 06:25:19 GMT-08:00Idiopathic Retroperitoneal FibrosisIdiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro-inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the B cell–depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases.Vaglio, AugustoMaritati, Federica2016-02-09T06:25:19-08:00doi:10.1681/ASN.2015101110hwp:resource-id:jnephrol;27/7/1880American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyretroperitoneal fibrosis, IgG4, hydronephrosis, vasculitis, fibrosisUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-07-01July 201610.1681/ASN.20151011101046-66731533-34502016-02-09T06:25:19-08:002016-07Journal of the American Society of NephrologyUp Front Matters27718801889
- Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney TransplantThe negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor–specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor–specific antibody generation at the individual level.10.1681/ASN.2015070781Fri, 12 Feb 2016 08:26:54 GMT-08:00Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney TransplantThe negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor–specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor–specific antibody generation at the individual level.Thaunat, OlivierKoenig, AliceLeibler, ClaireGrimbert, Philippe2016-02-12T08:26:54-08:00doi:10.1681/ASN.2015070781hwp:resource-id:jnephrol;27/7/1890American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, immunosuppression, immunologyUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-07-01July 201610.1681/ASN.20150707811046-66731533-34502016-02-12T08:26:54-08:002016-07Journal of the American Society of NephrologyUp Front Matters27718901900
- Overcoming Barriers in Kidney Health—Forging a Platform for InnovationInnovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.10.1681/ASN.2015090976Thu, 28 Apr 2016 06:19:54 GMT-07:00Overcoming Barriers in Kidney Health—Forging a Platform for InnovationInnovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology. Citing such inequities, however, is not enough. Changing the status quo will require a coordinated effort to identify and redress the existing deficits. Specifically, these deficits relate to the need to further develop and improve the following: understanding of the disease mechanisms and pathophysiology, patient engagement and activism, clinical trial infrastructure, and investigational clinical trial designs as well as coordinated efforts among critical stakeholders. This paper identifies potential solutions to these barriers, some of which are already underway through the Kidney Health Initiative. The Kidney Health Initiative is unique and will serve as a current and future platform from which to overcome these barriers to innovation in nephrology.Linde, Peter G.Archdeacon, PatrickBreyer, Matthew D.Ibrahim, TodInrig, Jula K.Kewalramani, ReshmaLee, Celeste CastilloNeuland, Carolyn Y.Roy-Chaudhury, PrabirSloand, James A.Meyer, RachelSmith, Kimberly A.Snook, JenniferWest, MelissaFalk, Ronald J.2016-04-28T06:19:54-07:00doi:10.1681/ASN.2015090976hwp:resource-id:jnephrol;27/7/1902American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney disease, clinical trial, end stage kidney disease, Pathophysiology of Renal Disease and Progression, Patient satisfactionUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-07-01July 201610.1681/ASN.20150909761046-66731533-34502016-04-28T06:19:54-07:002016-07Journal of the American Society of NephrologyUp Front Matters27719021910
- Inhibitor of NFκB Kinase Subunit 2 Blockade Hinders the Initiation but Aggravates the Progression of Crescentic GNThe NFκB transcription factor family facilitates the activation of dendritic cells (DCs) and CD4+ T helper (Th) cells, which are important for protective adaptive immunity. Inappropriate activation of these immune cells may cause inflammatory disease, and NFκB inhibitors are promising anti–inflammatory drug candidates. Here, we investigated whether inhibiting the NFκB–inducing kinase IKK2 can attenuate crescentic GN, a severe DC– and Th cell–dependent kidney inflammatory disease. Prophylactic pharmacologic IKK2 inhibition reduced DC and Th cell activation and ameliorated nephrotoxic serum–induced GN in mice. However, therapeutic IKK2 inhibition during ongoing disease aggravated the nephritogenic immune response and disease symptoms. This effect resulted from the renal loss of regulatory T cells, which have been shown to protect against crescentic GN and which require IKK2. In conclusion, although IKK2 inhibition can suppress the induction of nephritogenic immune responses in vivo, it may aggravate such responses in clinically relevant situations, because it also impairs regulatory T cells and thereby, unleashes preexisting nephritogenic responses. Our findings argue against using IKK2 inhibitors in chronic GN and perhaps, other immune–mediated diseases.10.1681/ASN.2015060699Mon, 16 Nov 2015 02:09:38 GMT-08:00Inhibitor of NFκB Kinase Subunit 2 Blockade Hinders the Initiation but Aggravates the Progression of Crescentic GNThe NFκB transcription factor family facilitates the activation of dendritic cells (DCs) and CD4+ T helper (Th) cells, which are important for protective adaptive immunity. Inappropriate activation of these immune cells may cause inflammatory disease, and NFκB inhibitors are promising anti–inflammatory drug candidates. Here, we investigated whether inhibiting the NFκB–inducing kinase IKK2 can attenuate crescentic GN, a severe DC– and Th cell–dependent kidney inflammatory disease. Prophylactic pharmacologic IKK2 inhibition reduced DC and Th cell activation and ameliorated nephrotoxic serum–induced GN in mice. However, therapeutic IKK2 inhibition during ongoing disease aggravated the nephritogenic immune response and disease symptoms. This effect resulted from the renal loss of regulatory T cells, which have been shown to protect against crescentic GN and which require IKK2. In conclusion, although IKK2 inhibition can suppress the induction of nephritogenic immune responses in vivo, it may aggravate such responses in clinically relevant situations, because it also impairs regulatory T cells and thereby, unleashes preexisting nephritogenic responses. Our findings argue against using IKK2 inhibitors in chronic GN and perhaps, other immune–mediated diseases.Gotot, JaninePiotrowski, EvelineOtte, Martin S.Tittel, André P.Linlin, GuoYao, ChenZiegelbauer, KarlPanzer, UlfGarbi, NatalioKurts, ChristianThaiss, Friedrich2015-11-16T14:09:38-08:00doi:10.1681/ASN.2015060699hwp:resource-id:jnephrol;27/7/1917American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, chronic kidney disease, immunology, immunosuppression, lymphocytes, progression of chronic renal failureBrief CommunicationsBrief Communicationsbrief-report20162016-07-01July 201610.1681/ASN.20150606991046-66731533-34502015-11-16T14:09:38-08:002016-07Journal of the American Society of NephrologyBrief Communications27719171924
- Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte DamageMitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid–resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin–induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I–IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.10.1681/ASN.2015060623Wed, 25 Nov 2015 04:42:11 GMT-08:00Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte DamageMitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid–resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin–induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I–IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction.Suzuki, TakehiroYamaguchi, HiroakiKikusato, MotoiHashizume, OsamuNagatoishi, SatoruMatsuo, AkihiroSato, TakeyaKudo, TaiMatsuhashi, TetsuroMurayama, KazutakaOhba, YukiWatanabe, ShunKanno, Shin-ichiroMinaki, DaichiSaigusa, DaisukeShinbo, HirokoMori, NobuyoshiYuri, AkinoriYokoro, MiyukiMishima, EikanShima, HisatoAkiyama, YasutoshiTakeuchi, YoichiKikuchi, KoichiToyohara, TakafumiSuzuki, ChitoseIchimura, TakaharuAnzai, Jun-ichiKohzuki, MasahiroMano, NariyasuKure, ShigeoYanagisawa, TeruyukiTomioka, YoshihisaToyomizu, MasaakiTsumoto, KoheiNakada, KazutoBonventre, Joseph V.Ito, SadayoshiOsaka, HitoshiHayashi, Ken-ichiAbe, Takaaki2015-11-25T04:42:11-08:00doi:10.1681/ASN.2015060623hwp:resource-id:jnephrol;27/7/1925American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymitochondria, acute renal failure, chronic kidney disease, ischemia-reperfusion, nephrotic syndrome, cardiovascular diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-07-01July 201610.1681/ASN.20150606231046-66731533-34502015-11-25T04:42:11-08:002016-07Journal of the American Society of NephrologyBrief Communications27771925186919321872
- The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in DiabetesEpigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions. Conversely, EZH2 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated TxnIP and attenuated oxidative stress. In diabetic rats, depletion of EZH2 decreased histone 3 lysine 27 trimethylation (H3K27me3), increased glomerular TxnIP expression, induced podocyte injury, and augmented oxidative stress and proteinuria. Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor Pax6, which was upregulated on EZH2 depletion and bound to the TxnIP promoter, controlling expression of its gene product. In high glucose–exposed podocytes and the kidneys of diabetic rats, the lower EZH2 expression detected coincided with upregulation of Pax6 and TxnIP. Finally, in a gene expression array, TxnIP was among seven of 30,854 genes upregulated by high glucose, EZH2 depletion, and the combination thereof. Thus, EZH2 represses the transcription factor Pax6, which controls expression of the antioxidant inhibitor TxnIP, and in diabetes, downregulation of EZH2 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the diabetic kidney to include antioxidant repair.10.1681/ASN.2014090898Tue, 03 Nov 2015 10:26:38 GMT-08:00The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in DiabetesEpigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions. Conversely, EZH2 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated TxnIP and attenuated oxidative stress. In diabetic rats, depletion of EZH2 decreased histone 3 lysine 27 trimethylation (H3K27me3), increased glomerular TxnIP expression, induced podocyte injury, and augmented oxidative stress and proteinuria. Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor Pax6, which was upregulated on EZH2 depletion and bound to the TxnIP promoter, controlling expression of its gene product. In high glucose–exposed podocytes and the kidneys of diabetic rats, the lower EZH2 expression detected coincided with upregulation of Pax6 and TxnIP. Finally, in a gene expression array, TxnIP was among seven of 30,854 genes upregulated by high glucose, EZH2 depletion, and the combination thereof. Thus, EZH2 represses the transcription factor Pax6, which controls expression of the antioxidant inhibitor TxnIP, and in diabetes, downregulation of EZH2 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the diabetic kidney to include antioxidant repair.Siddiqi, Ferhan S.Majumder, SyamantakThai, KerriAbdalla, MoustafaHu, PingzhaoAdvani, Suzanne L.White, Kathryn E.Bowskill, Bridgit B.Guarna, Giulianados Santos, Claudia C.Connelly, Kim A.Advani, Andrew2015-11-03T10:26:38-08:00doi:10.1681/ASN.2014090898hwp:resource-id:jnephrol;27/7/2021American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, podocyte, oxidative stressBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20140908981046-66731533-34502015-11-03T10:26:38-08:002016-07Journal of the American Society of NephrologyBasic Research27720212034
- Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case CohortTo maximize clinical benefits of genetic screening of patients with nephrotic syndrome (NS) to diagnose monogenic causes, reliably distinguishing NS-causing variants from the background of rare, noncausal variants prevalent in all genomes is vital. To determine the prevalence of monogenic NS in a North American case cohort while accounting for background prevalence of genetic variation, we sequenced 21 implicated monogenic NS genes in 312 participants from the Nephrotic Syndrome Study Network and 61 putative controls from the 1000 Genomes Project (1000G). These analyses were extended to available sequence data from approximately 2500 subjects from the 1000G. A typical pathogenicity filter identified causal variants for NS in 4.2% of patients and 5.8% of subjects from the 1000G. We devised a more stringent pathogenicity filtering strategy, reducing background prevalence of causal variants to 1.5%. When applying this stringent filter to patients, prevalence of monogenic NS was 2.9%; of these patients, 67% were pediatric, and 44% had FSGS on biopsy. The rate of complete remission did not associate with monogenic classification. Thus, we identified factors contributing to inaccurate monogenic classification of NS and developed a more accurate variant filtering strategy. The prevalence and clinical correlates of monogenic NS in this sporadically affected cohort differ substantially from those reported for patients referred for genetic analysis. Particularly in unselected, population–based cases, considering putative causal variants in known NS genes from a probabilistic rather than a deterministic perspective may be more precise. We also introduce GeneVetter, a web tool for monogenic assessment of rare disease.10.1681/ASN.2015050504Tue, 03 Nov 2015 10:26:38 GMT-08:00Using Population Genetics to Interrogate the Monogenic Nephrotic Syndrome Diagnosis in a Case CohortTo maximize clinical benefits of genetic screening of patients with nephrotic syndrome (NS) to diagnose monogenic causes, reliably distinguishing NS-causing variants from the background of rare, noncausal variants prevalent in all genomes is vital. To determine the prevalence of monogenic NS in a North American case cohort while accounting for background prevalence of genetic variation, we sequenced 21 implicated monogenic NS genes in 312 participants from the Nephrotic Syndrome Study Network and 61 putative controls from the 1000 Genomes Project (1000G). These analyses were extended to available sequence data from approximately 2500 subjects from the 1000G. A typical pathogenicity filter identified causal variants for NS in 4.2% of patients and 5.8% of subjects from the 1000G. We devised a more stringent pathogenicity filtering strategy, reducing background prevalence of causal variants to 1.5%. When applying this stringent filter to patients, prevalence of monogenic NS was 2.9%; of these patients, 67% were pediatric, and 44% had FSGS on biopsy. The rate of complete remission did not associate with monogenic classification. Thus, we identified factors contributing to inaccurate monogenic classification of NS and developed a more accurate variant filtering strategy. The prevalence and clinical correlates of monogenic NS in this sporadically affected cohort differ substantially from those reported for patients referred for genetic analysis. Particularly in unselected, population–based cases, considering putative causal variants in known NS genes from a probabilistic rather than a deterministic perspective may be more precise. We also introduce GeneVetter, a web tool for monogenic assessment of rare disease.Sampson, Matthew G.Gillies, Christopher E.Robertson, Catherine C.Crawford, BrendanVega-Warner, VirginiaOtto, Edgar A.Kretzler, MatthiasKang, Hyun Min2015-11-03T10:26:38-08:00doi:10.1681/ASN.2015050504hwp:resource-id:jnephrol;27/7/1970American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, steroid resistant nephrotic syndrome, 1000 Genomes, genetic renal disease, penetrance, expressivityBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150505041046-66731533-34502015-11-03T10:26:38-08:002016-07Journal of the American Society of NephrologyBasic Research27719701983
- Change in Measured GFR Versus eGFR and CKD OutcomesMeasured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR in explaining CKD-related comorbidities. The associations between longitudinal changes in mGFR versus eGFR and adverse outcomes have not been examined. We analyzed a subset of 942 participants with CKD in the Chronic Renal Insufficiency Cohort Study who had at least two mGFRs and two eGFRs determined concurrently by iothalamate and creatinine (eGFRcr) or cystatin C, respectively. We compared the associations between longitudinal changes in each measure of kidney function over 2 years and risks of ESRD, nonfatal cardiovascular events, and all-cause mortality using univariate Cox proportional hazards models. The associations for all outcomes except all-cause mortality associated most strongly with longitudinal decline in eGFRcr. Every 5-ml/min per 1.73 m2 decline in eGFRcr over 2 years associated with 1.54 (95% confidence interval, 1.44 to 1.66; P<0.001) times higher risk of ESRD and 1.23 (95% confidence interval, 1.12 to 1.34; P<0.001) times higher risk for cardiovascular events. All-cause mortality did not associate with longitudinal decline in mGFR or eGFR. When analyzed by tertiles of renal function decline, mGFR did not outperform eGFRcr in the association with any outcome. In conclusion, compared with declines in eGFR, declines in mGFR over a 2-year period, analyzed either as a continuous variable or in tertiles, did not consistently show enhanced association with risk of ESRD, cardiovascular events, or death.10.1681/ASN.2015040341Tue, 24 Nov 2015 06:38:53 GMT-08:00Change in Measured GFR Versus eGFR and CKD OutcomesMeasured GFR (mGFR) has long been considered the gold standard measure of kidney function, but recent studies have shown that mGFR is not consistently superior to eGFR in explaining CKD-related comorbidities. The associations between longitudinal changes in mGFR versus eGFR and adverse outcomes have not been examined. We analyzed a subset of 942 participants with CKD in the Chronic Renal Insufficiency Cohort Study who had at least two mGFRs and two eGFRs determined concurrently by iothalamate and creatinine (eGFRcr) or cystatin C, respectively. We compared the associations between longitudinal changes in each measure of kidney function over 2 years and risks of ESRD, nonfatal cardiovascular events, and all-cause mortality using univariate Cox proportional hazards models. The associations for all outcomes except all-cause mortality associated most strongly with longitudinal decline in eGFRcr. Every 5-ml/min per 1.73 m2 decline in eGFRcr over 2 years associated with 1.54 (95% confidence interval, 1.44 to 1.66; P<0.001) times higher risk of ESRD and 1.23 (95% confidence interval, 1.12 to 1.34; P<0.001) times higher risk for cardiovascular events. All-cause mortality did not associate with longitudinal decline in mGFR or eGFR. When analyzed by tertiles of renal function decline, mGFR did not outperform eGFRcr in the association with any outcome. In conclusion, compared with declines in eGFR, declines in mGFR over a 2-year period, analyzed either as a continuous variable or in tertiles, did not consistently show enhanced association with risk of ESRD, cardiovascular events, or death.Ku, ElaineXie, DaweiShlipak, MichaelHyre Anderson, AmandaChen, JingGo, Alan S.He, JiangHorwitz, Edward J.Rahman, MahboobRicardo, Ana C.Sondheimer, James H.Townsend, Raymond R.Hsu, Chi-yuan,2015-11-24T06:38:53-08:00doi:10.1681/ASN.2015040341hwp:resource-id:jnephrol;27/7/2196American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, creatinine clearance, glomerular filtration rateClinical ResearchClinical Researchresearch-article20162016-07-01July 201610.1681/ASN.20150403411046-66731533-34502015-11-24T06:38:53-08:002016-07Journal of the American Society of NephrologyClinical Research27721962204
- Ketoanalogue-Supplemented Vegetarian Very Low–Protein Diet and CKD ProgressionDietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue–supplemented vegetarian very low–protein diet (KD) compared with conventional low–protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m2, proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m2. Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m2 but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m2 in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD.10.1681/ASN.2015040369Thu, 28 Jan 2016 09:48:38 GMT-08:00Ketoanalogue-Supplemented Vegetarian Very Low–Protein Diet and CKD ProgressionDietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue–supplemented vegetarian very low–protein diet (KD) compared with conventional low–protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m2, proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m2. Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m2 but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m2 in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD.Garneata, LilianaStancu, AlexandraDragomir, DianaStefan, GabrielMircescu, Gabriel2016-01-28T09:48:38-08:00doi:10.1681/ASN.2015040369hwp:resource-id:jnephrol;27/7/2164American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynutrition, progression of chronic renal failure, phosphate binders, renal function declineClinical ResearchClinical Researchresearch-article20162016-07-01July 201610.1681/ASN.20150403691046-66731533-34502016-01-28T09:48:38-08:002016-07Journal of the American Society of NephrologyClinical Research27772164187721761879
- International Comparisons to Assess Effects of Payment and Regulatory Changes in the United States on Anemia Practice in Patients on Hemodialysis: The Dialysis Outcomes and Practice Patterns StudyFor years, erythropoiesis-stimulating agent (ESA) use among patients on dialysis was much higher in the United States than in Europe or Japan. Sweeping changes to dialysis reimbursement and regulatory policies for ESA in the United States in 2011 were expected to reduce ESA use and hemoglobin levels. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS) data from 7129 patients in 223 in–center hemodialysis facilities (average per month) to estimate and compare time trends in ESA dose and hemoglobin levels among patients on hemodialysis in the United States, Germany, Italy, Spain, the United Kingdom, and Japan. From 2010 to 2013, substantial declines in ESA use and hemoglobin levels occurred in the United States but not in other DOPPS countries. Between August of 2010 and April of 2013, mean weekly ESA dose in the United States decreased 40.4% for black patients and 38.0% for nonblack patients; mean hemoglobin decreased from 11.5 g/dl in black patients and 11.4 g/dl in nonblack patients to 10.6 g/dl in both groups. In 2010 and 2013, adjusted weekly ESA doses per kilogram were 41% and 11% lower, respectively, in patients in Europe and 60% and 18% lower, respectively, in patients in Japan than in nonblack patients in the United States. Adjusted hemoglobin levels in 2010 and 2013 were 0.07 g/dl lower and 0.56 g/dl higher, respectively, in patients in Europe and 0.93 and 0.01 g/dl lower, respectively, in patients in Japan than in nonblack patients in the United States. In conclusion, ESA dosing reductions in the United States likely reflect efforts in response to changes in reimbursement policy and regulatory guidance.10.1681/ASN.2015060673Wed, 18 Nov 2015 04:57:59 GMT-08:00International Comparisons to Assess Effects of Payment and Regulatory Changes in the United States on Anemia Practice in Patients on Hemodialysis: The Dialysis Outcomes and Practice Patterns StudyFor years, erythropoiesis-stimulating agent (ESA) use among patients on dialysis was much higher in the United States than in Europe or Japan. Sweeping changes to dialysis reimbursement and regulatory policies for ESA in the United States in 2011 were expected to reduce ESA use and hemoglobin levels. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS) data from 7129 patients in 223 in–center hemodialysis facilities (average per month) to estimate and compare time trends in ESA dose and hemoglobin levels among patients on hemodialysis in the United States, Germany, Italy, Spain, the United Kingdom, and Japan. From 2010 to 2013, substantial declines in ESA use and hemoglobin levels occurred in the United States but not in other DOPPS countries. Between August of 2010 and April of 2013, mean weekly ESA dose in the United States decreased 40.4% for black patients and 38.0% for nonblack patients; mean hemoglobin decreased from 11.5 g/dl in black patients and 11.4 g/dl in nonblack patients to 10.6 g/dl in both groups. In 2010 and 2013, adjusted weekly ESA doses per kilogram were 41% and 11% lower, respectively, in patients in Europe and 60% and 18% lower, respectively, in patients in Japan than in nonblack patients in the United States. Adjusted hemoglobin levels in 2010 and 2013 were 0.07 g/dl lower and 0.56 g/dl higher, respectively, in patients in Europe and 0.93 and 0.01 g/dl lower, respectively, in patients in Japan than in nonblack patients in the United States. In conclusion, ESA dosing reductions in the United States likely reflect efforts in response to changes in reimbursement policy and regulatory guidance.Fuller, Douglas S.Bieber, Brian A.Pisoni, Ronald L.Li, YunMorgenstern, HalAkizawa, TadaoJacobson, Stefan H.Locatelli, FrancescoPort, Friedrich K.Robinson, Bruce M.2015-11-18T04:57:59-08:00doi:10.1681/ASN.2015060673hwp:resource-id:jnephrol;27/7/2205American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyerythropoietin, ESRD, epoetin, anemia, hemodialysisClinical ResearchClinical Researchresearch-article20162016-07-01July 201610.1681/ASN.20150606731046-66731533-34502015-11-18T04:57:59-08:002016-07Journal of the American Society of NephrologyClinical Research27722052215
- Erratum10.1681/ASN.2016030381Thu, 30 Jun 2016 10:00:57 GMT-07:00ErratumAmerican Society of Nephrology2016-06-30T10:00:57-07:00doi:10.1681/ASN.2016030381hwp:resource-id:jnephrol;27/7/2216American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyErratumErratumcorrection20162016-07-01July 201610.1681/ASN.20160303811046-66731533-34502016-06-30T10:00:57-07:002016-07Journal of the American Society of NephrologyErratum27207112216230522162313
- Tubular Secretion in CKDRenal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.10.1681/ASN.2014121193Fri, 27 Nov 2015 06:38:32 GMT-08:00Tubular Secretion in CKDRenal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.Suchy-Dicey, Astrid M.Laha, ThomasHoofnagle, AndrewNewitt, RickSirich, Tammy L.Meyer, Timothy W.Thummel, Ken E.Yanez, N. DavidHimmelfarb, JonathanWeiss, Noel S.Kestenbaum, Bryan R.2015-11-27T06:38:32-08:00doi:10.1681/ASN.2014121193hwp:resource-id:jnephrol;27/7/2148American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, epidemiology and outcomes, proximal tubuleClinical EpidemiologyClinical Epidemiologyresearch-article20162016-07-01July 201610.1681/ASN.20141211931046-66731533-34502015-11-27T06:38:32-08:002016-07Journal of the American Society of NephrologyClinical Epidemiology27721482155
- Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during HemodialysisOf the 600–700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous (31P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. 31P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (−30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, βATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation.10.1681/ASN.2015050546Wed, 11 Nov 2015 05:22:25 GMT-08:00Intracellular Phosphate Dynamics in Muscle Measured by Magnetic Resonance Spectroscopy during HemodialysisOf the 600–700 mg inorganic phosphate (Pi) removed during a 4-hour hemodialysis session, a maximum of 10% may be extracted from the extracellular space. The origin of the other 90% of removed phosphate is unknown. This study tested the hypothesis that the main source of phosphate removed during hemodialysis is the intracellular compartment. Six binephrectomized pigs each underwent one 3-hour hemodialysis session, during which the extracorporeal circulation blood flow was maintained between 100 and 150 ml/min. To determine in vivo phosphate metabolism, we performed phosphorous (31P) magnetic resonance spectroscopy using a 1.5-Tesla system and a surface coil placed over the gluteal muscle region. 31P magnetic resonance spectra (repetition time =10 s; echo time =0.35 ms) were acquired every 160 seconds before, during, and after dialysis. During the dialysis sessions, plasma phosphate concentrations decreased rapidly (−30.4 %; P=0.003) and then, plateaued before increasing approximately 30 minutes before the end of the sessions; 16 mmol phosphate was removed in each session. When extracellular phosphate levels plateaued, intracellular Pi content increased significantly (11%; P<0.001). Moreover, βATP decreased significantly (P<0.001); however, calcium levels remained balanced. Results of this study show that intracellular Pi is the source of Pi removed during dialysis. The intracellular Pi increase may reflect cellular stress induced by hemodialysis and/or strong intracellular phosphate regulation.Lemoine, SandrineFournier, ThomasKocevar, GabrielBelloi, AmélieNormand, GabrielleIbarrola, DanielleSappey-Marinier, DominiqueJuillard, Laurent2015-11-11T05:22:25-08:00doi:10.1681/ASN.2015050546hwp:resource-id:jnephrol;27/7/2062American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, phosphate uptake, intracellular signal, hyperphosphatemia, intracellular pH, ion transportBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150505461046-66731533-34502015-11-11T05:22:25-08:002016-07Journal of the American Society of NephrologyBasic Research27720622068
- CKD Prevalence Varies across the European General PopulationCKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1–5 was defined as eGFR<60 ml/min per 1.73 m2, as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3–5 was defined as eGFR<60 ml/min per 1.73 m2. CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1–5 and CKD stages 3–5 prevalence across European study populations. The adjusted CKD stages 1–5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3–5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.10.1681/ASN.2015050542Wed, 23 Dec 2015 06:57:23 GMT-08:00CKD Prevalence Varies across the European General PopulationCKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1–5 was defined as eGFR<60 ml/min per 1.73 m2, as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3–5 was defined as eGFR<60 ml/min per 1.73 m2. CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1–5 and CKD stages 3–5 prevalence across European study populations. The adjusted CKD stages 1–5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3–5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.Brück, KatharinaStel, Vianda S.Gambaro, GiovanniHallan, SteinVölzke, HenryÄrnlöv, JohanKastarinen, MikaGuessous, IdrisVinhas, JoséStengel, BénédicteBrenner, HermannChudek, JerzyRomundstad, SolfridTomson, CharlesGonzalez, Alfonso OteroBello, Aminu K.Ferrieres, JeanPalmieri, LuigiBrowne, GemmaCapuano, VincenzoVan Biesen, WimZoccali, CarmineGansevoort, RonNavis, GerjanRothenbacher, DietrichFerraro, Pietro ManuelNitsch, DorotheaWanner, ChristophJager, Kitty J.Jousilahti, PekkaHelmer, CatherineMetzger, MarieRuidavets, Jean BernardBongard, VaninaKoenig, WolfgangDenkinger, Michael D.Schöttker, BenSaum, Kai-UweNauck, MatthiasStracke, SylviaPerry, Ivan J.Eustace, JosephLupo, AntonioDonfrancesco, ChiaraPalleschi, SimonettaLamaida, NormanCapuano, ErnestoSinkeler, SteefWolffenbuttel, B.H.R.Bakker, Stephan J.L.Joosten, MichelAasarød, KnutHolmen, JosteinMossakowska, MalgorzataWiecek, AndrzejGardete-Correia, LuisRaposo, João F.Martin de Francisco, A.L.Diz, P. GayosoNerpin, ElisabetLind, LarsBochud, MurielleGaspoz, Jean-MichelFletcher, AstridRoderick, PaulVan Pottelbergh, GijsVan Der Tol, ArjanHadjadj, SamyStojceva-Taneva, Olivera2015-12-23T06:57:23-08:00doi:10.1681/ASN.2015050542hwp:resource-id:jnephrol;27/7/2135American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, clinical epidemiology, creatinineClinical EpidemiologyClinical Epidemiologyresearch-article20162016-07-01July 201610.1681/ASN.20150505421046-66731533-34502015-12-23T06:57:23-08:002016-07Journal of the American Society of NephrologyClinical Epidemiology27772135187421471877
- Mitochondria in Kidney Injury: When the Power Plant Fails10.1681/ASN.2015111277Thu, 07 Jan 2016 06:07:28 GMT-08:00Mitochondria in Kidney Injury: When the Power Plant FailsTang, ChengyuanDong, Zheng2016-01-07T06:07:28-08:00doi:10.1681/ASN.2015111277hwp:resource-id:jnephrol;27/7/1869American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, acute renal failure, mitochondria, nephrotoxicityUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-07-01July 201610.1681/ASN.20151112771046-66731533-34502016-01-07T06:07:28-08:002016-07Journal of the American Society of NephrologyUp Front Matters27777186919252009187219322020
- Water, Water Everywhere: A New Cause and a New Treatment for Nephrogenic Diabetes Insipidus10.1681/ASN.2015111223Mon, 28 Dec 2015 06:30:35 GMT-08:00Water, Water Everywhere: A New Cause and a New Treatment for Nephrogenic Diabetes InsipidusSands, Jeff M.2015-12-28T06:30:35-08:00doi:10.1681/ASN.2015111223hwp:resource-id:jnephrol;27/7/1872American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvasopressin, nephrogenic diabetes insipidus, aquaporinUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-07-01July 201610.1681/ASN.20151112231046-66731533-34502015-12-28T06:30:35-08:002016-07Journal of the American Society of NephrologyUp Front Matters27777187220352082187420482091
- Dietary Protein as Kidney Protection: Quality or Quantity?10.1681/ASN.2015111286Thu, 28 Jan 2016 09:48:42 GMT-08:00Dietary Protein as Kidney Protection: Quality or Quantity?Goraya, NimritWesson, Donald E.2016-01-28T09:48:42-08:00doi:10.1681/ASN.2015111286hwp:resource-id:jnephrol;27/7/1877American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyAlkali, aging, dietUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-07-01July 201610.1681/ASN.20151112861046-66731533-34502016-01-28T09:48:42-08:002016-07Journal of the American Society of NephrologyUp Front Matters27771877216418792176
- 2-Deoxy-d-Glucose Ameliorates PKD ProgressionAutosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature of ADPKD, and inhibition of glycolysis using glucose analogs ameliorates aggressive PKD in preclinical models. Here, we investigated the effects of chronic treatment with low doses of the glucose analog 2-deoxy-d-glucose (2DG) on ADPKD progression in orthologous and slowly progressive murine models created by inducible inactivation of the Pkd1 gene postnatally. As previously reported, early inactivation (postnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (postnatal days 25–28) resulted in PKD developing in months. Irrespective of the timing of Pkd1 gene inactivation, cystic kidneys showed enhanced uptake of 13C-glucose and conversion to 13C-lactate. Administration of 2DG restored normal renal levels of the phosphorylated forms of AMP–activated protein kinase and its target acetyl-CoA carboxylase. Furthermore, 2DG greatly retarded disease progression in both model systems, reducing the increase in total kidney volume and cystic index and markedly reducing CD45–positive cell infiltration. Notably, chronic administration of low doses (100 mg/kg 5 days per week) of 2DG did not result in any obvious sign of toxicity as assessed by analysis of brain and heart histology as well as behavioral tests. Our data provide proof of principle support for the use of 2DG as a therapeutic strategy in ADPKD.10.1681/ASN.2015030231Tue, 03 Nov 2015 10:26:40 GMT-08:002-Deoxy-d-Glucose Ameliorates PKD ProgressionAutosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature of ADPKD, and inhibition of glycolysis using glucose analogs ameliorates aggressive PKD in preclinical models. Here, we investigated the effects of chronic treatment with low doses of the glucose analog 2-deoxy-d-glucose (2DG) on ADPKD progression in orthologous and slowly progressive murine models created by inducible inactivation of the Pkd1 gene postnatally. As previously reported, early inactivation (postnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (postnatal days 25–28) resulted in PKD developing in months. Irrespective of the timing of Pkd1 gene inactivation, cystic kidneys showed enhanced uptake of 13C-glucose and conversion to 13C-lactate. Administration of 2DG restored normal renal levels of the phosphorylated forms of AMP–activated protein kinase and its target acetyl-CoA carboxylase. Furthermore, 2DG greatly retarded disease progression in both model systems, reducing the increase in total kidney volume and cystic index and markedly reducing CD45–positive cell infiltration. Notably, chronic administration of low doses (100 mg/kg 5 days per week) of 2DG did not result in any obvious sign of toxicity as assessed by analysis of brain and heart histology as well as behavioral tests. Our data provide proof of principle support for the use of 2DG as a therapeutic strategy in ADPKD.Chiaravalli, MarcoRowe, IsalineMannella, ValeriaQuilici, GiacomoCanu, TamaraBianchi, VeronicaGurgone, AntoniaAntunes, SofiaD’Adamo, PatriziaEsposito, AntonioMusco, GiovannaBoletta, Alessandra2015-11-03T10:26:40-08:00doi:10.1681/ASN.2015030231hwp:resource-id:jnephrol;27/7/1958American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, ADPKD, metabolismBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150302311046-66731533-34502015-11-03T10:26:40-08:002016-07Journal of the American Society of NephrologyBasic Research27719581969
- Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet–Induced Kidney DiseaseObesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)–induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid–rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid–depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.10.1681/ASN.2015020190Tue, 03 Nov 2015 10:26:40 GMT-08:00Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet–Induced Kidney DiseaseObesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)–induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid–rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid–depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification.Kuwahara, ShojiHosojima, MichihiroKaneko, ReikaAoki, HiroyukiNakano, DaisukeSasagawa, TaijiKabasawa, HideyukiKaseda, RyoheiYasukawa, RyotaIshikawa, TomomiSuzuki, AkiyoSato, HiroyoshiKageyama, ShunTanaka, TakahiroKitamura, NobutakaNarita, IchieiKomatsu, MasaakiNishiyama, AkiraSaito, Akihiko2015-11-03T10:26:40-08:00doi:10.1681/ASN.2015020190hwp:resource-id:jnephrol;27/7/1996American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyendocytosis, obesity, proximal tubule, fibrosis, lipids, Pathophysiology of Renal Disease and ProgressionBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150201901046-66731533-34502015-11-03T10:26:40-08:002016-07Journal of the American Society of NephrologyBasic Research27719962008
- Filgrastim–Induced Crescentic Transformation of Recurrent IgG2λ GNProliferative GN with monoclonal IgG deposits is an increasingly recognized form of GN, but its relation to hematologic malignancy remains poorly understood. Filgrastim, an analog for granulocyte colony–stimulating factor produced by recombinant DNA technology, is frequently used to stimulate bone marrow release of hematopoietic progenitor cells in preparation for stem cell transplant. We report an exceptional case of proliferative GN with monoclonal IgG2λ deposits in a young man whose disease progressed slowly to CKD, which was followed by a preemptive kidney transplant. The patient developed recurrent GN in the allograft and clinically detectable plasma cell neoplasm 9 years after the first renal manifestations. Contemporaneous with filgrastim administration for stem cell mobilization, the patient’s slowly progressive GN underwent severe crescentic transformation, leading to rapidly progressive and irreversible allograft failure. This report explores the spectrum of GN with monoclonal IgG deposits and the pathophysiologic role of granulocyte colony–stimulating factor in exacerbation of preexisting GN.10.1681/ASN.2016010061Wed, 04 May 2016 05:44:32 GMT-07:00Filgrastim–Induced Crescentic Transformation of Recurrent IgG2λ GNProliferative GN with monoclonal IgG deposits is an increasingly recognized form of GN, but its relation to hematologic malignancy remains poorly understood. Filgrastim, an analog for granulocyte colony–stimulating factor produced by recombinant DNA technology, is frequently used to stimulate bone marrow release of hematopoietic progenitor cells in preparation for stem cell transplant. We report an exceptional case of proliferative GN with monoclonal IgG2λ deposits in a young man whose disease progressed slowly to CKD, which was followed by a preemptive kidney transplant. The patient developed recurrent GN in the allograft and clinically detectable plasma cell neoplasm 9 years after the first renal manifestations. Contemporaneous with filgrastim administration for stem cell mobilization, the patient’s slowly progressive GN underwent severe crescentic transformation, leading to rapidly progressive and irreversible allograft failure. This report explores the spectrum of GN with monoclonal IgG deposits and the pathophysiologic role of granulocyte colony–stimulating factor in exacerbation of preexisting GN.Batal, IbrahimMarkowitz, Glen S.Wong, WaichiAvasare, RupaliMapara, Markus Y.Appel, Gerald B.D'Agati, Vivette D.2016-05-04T05:44:32-07:00doi:10.1681/ASN.2016010061hwp:resource-id:jnephrol;27/7/1911American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, kidney biopsy, paraproteinUp Front MattersRenal Biopsy with New InsightsUp Front MattersRenal Biopsy with New Insightsresearch-article20162016-07-01July 201610.1681/ASN.20160100611046-66731533-34502016-05-04T05:44:32-07:002016-07Journal of the American Society of NephrologyUp Front Matters27719111915
- CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GNChemokines and chemokine receptors are implicated in regulatory T cell (Treg) trafficking to sites of inflammation and suppression of excessive immune responses in inflammatory and autoimmune diseases; however, the specific requirements for Treg migration into the inflamed organs and the positioning of these cells within the tissue are incompletely understood. Here, we report that Tregs expressing the TH1–associated chemokine receptor CXCR3 are enriched in the kidneys of patients with ANCA–associated crescentic GN and colocalize with CXCR3+ effector T cells. To investigate the functional role of CXCR3+ Tregs, we generated mice that lack CXCR3 in Tregs specifically (Foxp3eGFP-Cre × Cxcr3fl/fl) and induced experimental crescentic GN. Treg-specific deletion of CXCR3 resulted in reduced Treg recruitment to the kidney and an overwhelming TH1 immune response, with an aggravated course of the nephritis that was reversible on anti-IFNγ treatment. Together, these findings show that a subset of Tregs expresses CXCR3 and thereby, acquires trafficking properties of pathogenic CXCR3+ TH1 cells, allowing Treg localization and control of excessive TH1 responses at sites of inflammation.10.1681/ASN.2015020203Tue, 03 Nov 2015 10:26:36 GMT-08:00CXCR3+ Regulatory T Cells Control TH1 Responses in Crescentic GNChemokines and chemokine receptors are implicated in regulatory T cell (Treg) trafficking to sites of inflammation and suppression of excessive immune responses in inflammatory and autoimmune diseases; however, the specific requirements for Treg migration into the inflamed organs and the positioning of these cells within the tissue are incompletely understood. Here, we report that Tregs expressing the TH1–associated chemokine receptor CXCR3 are enriched in the kidneys of patients with ANCA–associated crescentic GN and colocalize with CXCR3+ effector T cells. To investigate the functional role of CXCR3+ Tregs, we generated mice that lack CXCR3 in Tregs specifically (Foxp3eGFP-Cre × Cxcr3fl/fl) and induced experimental crescentic GN. Treg-specific deletion of CXCR3 resulted in reduced Treg recruitment to the kidney and an overwhelming TH1 immune response, with an aggravated course of the nephritis that was reversible on anti-IFNγ treatment. Together, these findings show that a subset of Tregs expresses CXCR3 and thereby, acquires trafficking properties of pathogenic CXCR3+ TH1 cells, allowing Treg localization and control of excessive TH1 responses at sites of inflammation.Paust, Hans-JoachimRiedel, Jan-HendrikKrebs, Christian F.Turner, Jan-EricBrix, Silke R.Krohn, SonjaVelden, JoachimWiech, ThorstenKaffke, AnnaPeters, AnettBennstein, Sabrina B.Kapffer, SonjaMeyer-Schwesinger, CatherineWegscheid, ClaudiaTiegs, GisaThaiss, FriedrichMittrücker, Hans-WilliSteinmetz, Oliver M.Stahl, Rolf A.K.Panzer, Ulf2015-11-03T10:26:36-08:00doi:10.1681/ASN.2015020203hwp:resource-id:jnephrol;27/7/1933American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyGN, Tregs, CXCR3, traffickingBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150202031046-66731533-34502015-11-03T10:26:36-08:002016-07Journal of the American Society of NephrologyBasic Research27719331942
- Mammalian Target of Rapamycin Mediates Kidney Injury Molecule 1-Dependent Tubule Injury in a Surrogate ModelKidney injury molecule 1 (KIM-1), an epithelial phagocytic receptor, is markedly upregulated in the proximal tubule in various forms of acute and chronic kidney injury in humans and many other species. Whereas acute expression of KIM-1 has adaptive anti-inflammatory effects, chronic expression may be maladaptive in mice. Here, we characterized the zebrafish Kim family, consisting of Kim-1, Kim-3, and Kim-4. Kim-1 was markedly upregulated in kidney after gentamicin-induced injury and had conserved phagocytic activity in zebrafish. Both constitutive and tamoxifen-induced expression of Kim-1 in zebrafish kidney tubules resulted in loss of the tubule brush border, reduced GFR, pericardial edema, and increased mortality. Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. mTOR pathway inhibition in KIM-1-overexpressing transgenic mice also significantly ameliorated serum creatinine level, proteinuria, tubular injury, and kidney inflammation. In conclusion, persistent Kim-1 expression results in chronic kidney damage in zebrafish through a mechanism involving mTOR. This observation predicted the role of the mTOR pathway and the therapeutic efficacy of mTOR-targeted agents in KIM-1-mediated kidney injury and fibrosis in mice, demonstrating the utility of the Kim-1 renal tubule zebrafish models.10.1681/ASN.2015050500Wed, 04 Nov 2015 10:27:54 GMT-08:00Mammalian Target of Rapamycin Mediates Kidney Injury Molecule 1-Dependent Tubule Injury in a Surrogate ModelKidney injury molecule 1 (KIM-1), an epithelial phagocytic receptor, is markedly upregulated in the proximal tubule in various forms of acute and chronic kidney injury in humans and many other species. Whereas acute expression of KIM-1 has adaptive anti-inflammatory effects, chronic expression may be maladaptive in mice. Here, we characterized the zebrafish Kim family, consisting of Kim-1, Kim-3, and Kim-4. Kim-1 was markedly upregulated in kidney after gentamicin-induced injury and had conserved phagocytic activity in zebrafish. Both constitutive and tamoxifen-induced expression of Kim-1 in zebrafish kidney tubules resulted in loss of the tubule brush border, reduced GFR, pericardial edema, and increased mortality. Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. mTOR pathway inhibition in KIM-1-overexpressing transgenic mice also significantly ameliorated serum creatinine level, proteinuria, tubular injury, and kidney inflammation. In conclusion, persistent Kim-1 expression results in chronic kidney damage in zebrafish through a mechanism involving mTOR. This observation predicted the role of the mTOR pathway and the therapeutic efficacy of mTOR-targeted agents in KIM-1-mediated kidney injury and fibrosis in mice, demonstrating the utility of the Kim-1 renal tubule zebrafish models.Yin, WenqingNaini, Said MovahediChen, GuochunHentschel, Dirk M.Humphreys, Benjamin D.Bonventre, Joseph V.2015-11-04T10:27:54-08:00doi:10.1681/ASN.2015050500hwp:resource-id:jnephrol;27/7/1943American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, chronic kidney disease, nephrotoxicityBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150505001046-66731533-34502015-11-04T10:27:54-08:002016-07Journal of the American Society of NephrologyBasic Research27719431957
- Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular DevelopmentThe close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1+ progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein–coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1+ progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development.10.1681/ASN.2015060610Tue, 03 Nov 2015 10:26:41 GMT-08:00Hemovascular Progenitors in the Kidney Require Sphingosine-1-Phosphate Receptor 1 for Vascular DevelopmentThe close relationship between endothelial and hematopoietic precursors during early development of the vascular system suggested the possibility of a common yet elusive precursor for both cell types. Whether similar or related progenitors for endothelial and hematopoietic cells are present during organogenesis is unclear. Using inducible transgenic mice that specifically label endothelial and hematopoietic precursors, we performed fate-tracing studies combined with colony-forming assays and crosstransplantation studies. We identified a progenitor, marked by the expression of helix-loop-helix transcription factor stem cell leukemia (SCL/Tal1). During organogenesis of the kidney, SCL/Tal1+ progenitors gave rise to endothelium and blood precursors with multipotential colony-forming capacity. Furthermore, appropriate morphogenesis of the kidney vasculature, including glomerular capillary development, arterial mural cell coating, and lymphatic vessel development, required sphingosine 1-phosphate (S1P) signaling via the G protein–coupled S1P receptor 1 in these progenitors. Overall, these results show that SCL/Tal1+ progenitors with hemogenic capacity originate and differentiate within the early embryonic kidney by hemovasculogenesis (the concomitant formation of blood and vessels) and underscore the importance of the S1P pathway in vascular development.Hu, YanLi, MinghongGöthert, Joachim R.Gomez, R. ArielSequeira-Lopez, Maria Luisa S.2015-11-03T10:26:41-08:00doi:10.1681/ASN.2015060610hwp:resource-id:jnephrol;27/7/1984American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvascular, renal development, renal vascular precursorsBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150606101046-66731533-34502015-11-03T10:26:41-08:002016-07Journal of the American Society of NephrologyBasic Research27719841995
- Role of Mitochondrial DNA in Septic AKI via Toll-Like Receptor 9Toll-like receptor 9 (TLR9) contributes to the development of polymicrobial septic AKI. However, the mechanisms that activate the TLR9 pathway and cause kidney injury during sepsis remain unknown. To determine the role of mitochondrial DNA (mtDNA) in TLR9-associated septic AKI, we established a cecal ligation and puncture (CLP) model of sepsis in wild-type (WT) and Tlr9-knockout (Tlr9KO) mice. We evaluated systemic circulation and peritoneal cavity dynamics and immune response and tubular mitochondrial dysfunction to determine upstream and downstream effects on the TLR9 pathway, respectively. CLP increased mtDNA levels in the plasma and peritoneal cavity of WT and Tlr9KO mice in the early phase, but the increase in the peritoneal cavity was significantly higher in Tlr9KO mice than in WT mice. Concomitantly, leukocyte migration to the peritoneal cavity increased, and plasma cytokine production and splenic apoptosis decreased in Tlr9KO mice compared with WT mice. Furthermore, CLP-generated renal mitochondrial oxidative stress and mitochondrial vacuolization in the proximal tubules in the early phase were reversed in Tlr9KO mice. To elucidate the effects of mtDNA on immune response and kidney injury, we intravenously injected mice with mitochondrial debris (MTD), including substantial amounts of mtDNA. MTD caused an immune response similar to that induced by CLP, including upregulated levels of plasma IL-12, splenic apoptosis, and mitochondrial injury, but this effect was attenuated by Tlr9KO. Moreover, MTD-induced renal mitochondrial injury was abolished by DNase pretreatment. These findings suggest that mtDNA activates TLR9 and contributes to cytokine production, splenic apoptosis, and kidney injury during polymicrobial sepsis.10.1681/ASN.2015040376Mon, 16 Nov 2015 02:09:36 GMT-08:00Role of Mitochondrial DNA in Septic AKI via Toll-Like Receptor 9Toll-like receptor 9 (TLR9) contributes to the development of polymicrobial septic AKI. However, the mechanisms that activate the TLR9 pathway and cause kidney injury during sepsis remain unknown. To determine the role of mitochondrial DNA (mtDNA) in TLR9-associated septic AKI, we established a cecal ligation and puncture (CLP) model of sepsis in wild-type (WT) and Tlr9-knockout (Tlr9KO) mice. We evaluated systemic circulation and peritoneal cavity dynamics and immune response and tubular mitochondrial dysfunction to determine upstream and downstream effects on the TLR9 pathway, respectively. CLP increased mtDNA levels in the plasma and peritoneal cavity of WT and Tlr9KO mice in the early phase, but the increase in the peritoneal cavity was significantly higher in Tlr9KO mice than in WT mice. Concomitantly, leukocyte migration to the peritoneal cavity increased, and plasma cytokine production and splenic apoptosis decreased in Tlr9KO mice compared with WT mice. Furthermore, CLP-generated renal mitochondrial oxidative stress and mitochondrial vacuolization in the proximal tubules in the early phase were reversed in Tlr9KO mice. To elucidate the effects of mtDNA on immune response and kidney injury, we intravenously injected mice with mitochondrial debris (MTD), including substantial amounts of mtDNA. MTD caused an immune response similar to that induced by CLP, including upregulated levels of plasma IL-12, splenic apoptosis, and mitochondrial injury, but this effect was attenuated by Tlr9KO. Moreover, MTD-induced renal mitochondrial injury was abolished by DNase pretreatment. These findings suggest that mtDNA activates TLR9 and contributes to cytokine production, splenic apoptosis, and kidney injury during polymicrobial sepsis.Tsuji, NaokoTsuji, TakayukiOhashi, NaroKato, AkihikoFujigaki, YoshihideYasuda, Hideo2015-11-16T14:09:36-08:00doi:10.1681/ASN.2015040376hwp:resource-id:jnephrol;27/7/2009American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, Immunology and pathology, renal injury, mitochondriaBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150403761046-66731533-34502015-11-16T14:09:36-08:002016-07Journal of the American Society of NephrologyBasic Research27772009186920201872
- Impaired Lysosomal Function Underlies Monoclonal Light Chain–Associated Renal Fanconi SyndromeMonoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Before the onset of renal failure, mice overexpressing RFS-κLCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κLCs. Exposure of PT cells to RFS-κLCs resulted in κLC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS-κLC variable (V) sequence, because they did not occur with control LCs or the same RFS-κLC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS-κLCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κLCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS.10.1681/ASN.2015050581Fri, 27 Nov 2015 06:38:33 GMT-08:00Impaired Lysosomal Function Underlies Monoclonal Light Chain–Associated Renal Fanconi SyndromeMonoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Before the onset of renal failure, mice overexpressing RFS-κLCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κLCs. Exposure of PT cells to RFS-κLCs resulted in κLC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS-κLC variable (V) sequence, because they did not occur with control LCs or the same RFS-κLC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS-κLCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κLCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS.Luciani, AlessandroSirac, ChristopheTerryn, SaraJavaugue, VincentPrange, Jenny AnnBender, SébastienBonaud, AmélieCogné, MichelAucouturier, PierreRonco, PierreBridoux, FrankDevuyst, Olivier2015-11-27T06:38:33-08:00doi:10.1681/ASN.2015050581hwp:resource-id:jnephrol;27/7/2049American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproximal tubule, multiple myeloma, endocytosis, renal proximal tubule cell, cell & transport physiologyBasic ResearchBasic Researchresearch-article20162016-07-01July 201610.1681/ASN.20150505811046-66731533-34502015-11-27T06:38:33-08:002016-07Journal of the American Society of NephrologyBasic Research27720492061
- Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA Nephropathy10.2215/CJN.10150915Tue, 29 Mar 2016 09:49:16 GMT-07:00Measures of Urinary Protein and Albumin in the Prediction of Progression of IgA NephropathyZhao, Yan-fengZhu, LiLiu, Li-junShi, Su-fangLv, Ji-chengZhang, Hong2016-03-29T09:49:16-07:00doi:10.2215/CJN.10150915hwp:resource-id:clinjasn;11/6/947American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, albuminuria, proteinuria, creatinine, Follow-Up Studies, Glomerulonephritis, IGA, Humans, Kidney Failure, Chronic, Prognosis, UrinalysisOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-06-06June 06, 201610.2215/CJN.101509151555-90411555-905X2016-03-29T09:49:16-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles116947955
- Risk of Hospital-Acquired Complications in Patients with Chronic Kidney Disease10.2215/CJN.09450915Thu, 12 May 2016 11:21:22 GMT-07:00Risk of Hospital-Acquired Complications in Patients with Chronic Kidney DiseaseBohlouli, BabakTonelli, MarcelloJackson, TerriHemmelgam, BrendaKlarenbach, Scott2016-05-12T11:21:22-07:00doi:10.2215/CJN.09450915hwp:resource-id:clinjasn;11/6/956American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hospitalization, hospital acquired complication, preventable hospital complications, renal insufficiency, chronic, patient safety, cohort studies, medical errors, health care costs, humansOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-06-06June 06, 201610.2215/CJN.094509151555-90411555-905X2016-05-12T11:21:22-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles116956963
- The See Kidney Disease Targeted Screening Program for CKD10.2215/CJN.11961115Thu, 19 May 2016 06:54:25 GMT-07:00The See Kidney Disease Targeted Screening Program for CKDGalbraith, Lauren E.Ronksley, Paul E.Barnieh, Lianne J.Kappel, JoanneManns, Braden J.Samuel, Susan M.Jun, MinWeaver, RobValk, NadineHemmelgarn, Brenda R.2016-05-19T06:54:25-07:00doi:10.2215/CJN.11961115hwp:resource-id:clinjasn;11/6/964American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, targeted screening, Canada, creatinine, glomerular filtration rate, Humans, hypertension, kidney, Prevalence, Renal Insufficiency, ChronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-06-06June 06, 201610.2215/CJN.119611151555-90411555-905X2016-05-19T06:54:25-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles1166964925972927
- Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up Study10.2215/CJN.09770915Wed, 13 Apr 2016 08:04:02 GMT-07:00Progression of Kidney Disease in Indigenous Australians: The eGFR Follow-up StudyMaple-Brown, Louise J.Hughes, Jaquelyne T.Ritte, RebeccaBarzi, FedericaHoy, Wendy E.Lawton, Paul D.Jones, Graham R.D.Death, ElizabethSimmonds, AlisonSinha, Ashim K.Cherian, SajivThomas, Mark A.B.McDermott, RobynBrown, Alex D.H.O’Dea, KerinJerums, GeorgeCass, AlanMacIsaac, Richard J.2016-04-13T08:04:02-07:00doi:10.2215/CJN.09770915hwp:resource-id:clinjasn;11/6/993American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, albuminuria, indigenous Australian, end stage kidney disease, eGFR, Australia, humans, kidney failure, chronic, kidney function tests, longitudinal studiesOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-06-06June 06, 201610.2215/CJN.097709151555-90411555-905X2016-04-13T08:04:02-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles1169931004
- Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency Department10.2215/CJN.10551015Tue, 29 Mar 2016 09:49:17 GMT-07:00Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency DepartmentKimmel, MartinShi, JingLatus, JoergWasser, ChristophKitterer, DanielBraun, NikoAlscher, Mark Dominik2016-03-29T09:49:17-07:00doi:10.2215/CJN.10551015hwp:resource-id:clinjasn;11/6/938American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, biomarkers, emergency departments, tissue inhibitor of metalloproteinase-2, insulin like-growth factor binding protein-7, emergency service, hospital, humans, kidney risk factors, tissue inhibitor of metalloproteinase-2Original ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-06-06June 06, 201610.2215/CJN.105510151555-90411555-905X2016-03-29T09:49:17-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles116938946
- A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the UrineMonoclonal gammopathy is increasingly recognized as a cause of kidney injury. These renal conditions behave differently than ones without monoclonal gammopathy and require specific treatment. To avoid misdiagnosis, testing for paraprotein should be performed in addition to vasculitis and autoimmune diseases serologies in adults with unexplained AKI or proteinuria. Because the prevalence of monoclonal gammopathy is much more common than glomerular diseases, the nephrotoxicity of the monoclonal protein must be confirmed before cytotoxic therapy is initiated. This can only be done by a kidney biopsy. After a monoclonal gammopathy of renal significant is verified, the evaluation should then focus on the identification of the pathologic clone, because therapy is clone specific. We present this patient to illustrate the clinical presentation of a patient with renal dysfunction and a monoclonal gammopathy. This patient is also used to discuss the diagnostic process in detail when monoclonal gammopathy–associated renal disease is suspected.10.2215/CJN.10641015Fri, 18 Mar 2016 06:47:04 GMT-07:00A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the UrineMonoclonal gammopathy is increasingly recognized as a cause of kidney injury. These renal conditions behave differently than ones without monoclonal gammopathy and require specific treatment. To avoid misdiagnosis, testing for paraprotein should be performed in addition to vasculitis and autoimmune diseases serologies in adults with unexplained AKI or proteinuria. Because the prevalence of monoclonal gammopathy is much more common than glomerular diseases, the nephrotoxicity of the monoclonal protein must be confirmed before cytotoxic therapy is initiated. This can only be done by a kidney biopsy. After a monoclonal gammopathy of renal significant is verified, the evaluation should then focus on the identification of the pathologic clone, because therapy is clone specific. We present this patient to illustrate the clinical presentation of a patient with renal dysfunction and a monoclonal gammopathy. This patient is also used to discuss the diagnostic process in detail when monoclonal gammopathy–associated renal disease is suspected.Leung, NelsonNasr, Samih H.2016-03-18T06:47:04-07:00doi:10.2215/CJN.10641015hwp:resource-id:clinjasn;11/6/1073American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymultiple myeloma, glomerular disease, kidney biopsy, renal failure, MGRS, Acute Kidney Injury, Adult, Humans, Paraproteins, proteinuriaAttending RoundsAttending Roundsresearch-article20162016-06-06June 06, 201610.2215/CJN.106410151555-90411555-905X2016-03-18T06:47:04-07:002016-06-06Clinical Journal of the American Society of NephrologyAttending Rounds11610731082
- Screening Strategies for Unrecognized CKD10.2215/CJN.04190416Thu, 19 May 2016 06:54:26 GMT-07:00Screening Strategies for Unrecognized CKDKomenda, PaulRigatto, ClaudioTangri, Navdeep2016-05-19T06:54:26-07:00doi:10.2215/CJN.04190416hwp:resource-id:clinjasn;11/6/925American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, screening, risk factors, chronic kidney disease, Mass ScreeningEditorialsEditorialseditorial20162016-06-06June 06, 201610.2215/CJN.041904161555-90411555-905X2016-05-19T06:54:26-07:002016-06-06Clinical Journal of the American Society of NephrologyEditorials1166925964927972
- Beyond APOL1: Genetic Inroads into Understanding Population Disparities in Diabetic Kidney Disease10.2215/CJN.04680416Thu, 19 May 2016 06:54:29 GMT-07:00Beyond APOL1: Genetic Inroads into Understanding Population Disparities in Diabetic Kidney DiseaseSkorecki, KarlWasser, Walter G.2016-05-19T06:54:29-07:00doi:10.2215/CJN.04680416hwp:resource-id:clinjasn;11/6/928American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetics, kidney disease, APOL1, African Americans, African Continental Ancestry Group, Chromosome Mapping, Humans, Kidney Failure, ChronicEditorialsEditorialseditorial20162016-06-06June 06, 201610.2215/CJN.046804161555-90411555-905X2016-05-19T06:54:29-07:002016-06-06Clinical Journal of the American Society of NephrologyEditorials116692810349311043
- Integrating a Smartphone–Based Self–Management System into Usual Care of Advanced CKD10.2215/CJN.10681015Thu, 12 May 2016 11:21:22 GMT-07:00Integrating a Smartphone–Based Self–Management System into Usual Care of Advanced CKDOng, Stephanie W.Jassal, Sarbjit V.Miller, Judith A.Porter, Eveline C.Cafazzo, Joseph A.Seto, EmilyThorpe, Kevin E.Logan, Alexander G.2016-05-12T11:21:22-07:00doi:10.2215/CJN.10681015hwp:resource-id:clinjasn;11/6/1054American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, hypertension, self-management, smartphone, telemedicine, ambulatory care, blood pressure, Humans, Renal Insufficiency, Chronic, Self CareOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20162016-06-06June 06, 201610.2215/CJN.106810151555-90411555-905X2016-05-12T11:21:22-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles1166510549357471062937749
- Preeclampsia: Updates in Pathogenesis, Definitions, and GuidelinesPreeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.10.2215/CJN.12081115Tue, 19 Apr 2016 07:00:30 GMT-07:00Preeclampsia: Updates in Pathogenesis, Definitions, and GuidelinesPreeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.Phipps, ElizabethPrasanna, DevikaBrima, WunnieJim, Belinda2016-04-19T07:00:30-07:00doi:10.2215/CJN.12081115hwp:resource-id:clinjasn;11/6/1102American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyproteinuria, VEGF, blood pressure, clinical hypertension, Cardiovascular Diseases, Humans, obesity, Pre-Eclampsia, Prevalence, risk factorsMini-ReviewMini-Reviewreview-article20162016-06-06June 06, 201610.2215/CJN.120811151555-90411555-905X2016-04-19T07:00:30-07:002016-06-06Clinical Journal of the American Society of NephrologyMini-Review11611021113
- American Society of Nephrology Quiz and Questionnaire 2015: TransplantationThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of US nephrology fellowship programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special application with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces its educational value for the Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.10.2215/CJN.13451215Thu, 25 Feb 2016 07:14:55 GMT-08:00American Society of Nephrology Quiz and Questionnaire 2015: TransplantationThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, training program directors of US nephrology fellowship programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special application with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this highly educational session. This article recapitulates the session and reproduces its educational value for the Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.Josephson, Michelle A.Perazella, Mark A.Choi, Michael J.2016-02-25T07:14:55-08:00doi:10.2215/CJN.13451215hwp:resource-id:clinjasn;11/6/1114American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, Fungal pneumonia, heart failure, Judgment, kidney, Kidney Diseases, Kidney Failure, Chronic, nephrology, renal dialysis, Surveys and QuestionnairesSpecial FeatureSpecial Featureresearch-article20162016-06-06June 06, 201610.2215/CJN.134512151555-90411555-905X2016-02-25T07:14:55-08:002016-06-06Clinical Journal of the American Society of NephrologySpecial Feature11611141122
- Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy10.2215/CJN.02300215Fri, 29 Apr 2016 06:47:59 GMT-07:00Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA NephropathySarcina, CristinaTinelli, CarmineFerrario, FrancescaPani, AntonelloDe Silvestri, AnnalisaScaini, PatriziaDel Vecchio, LuciaAlberghini, ElenaBuzzi, LauraBaragetti, IvanoPozzi, Claudio2016-04-29T06:47:59-07:00doi:10.2215/CJN.02300215hwp:resource-id:clinjasn;11/6/973American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIgA nephropathy, proteinuria, histopathology, chronic kidney disease, azathioprine, follow-up studies, humans, kidney, prospective studies, renal insufficiencyOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-06-06June 06, 201610.2215/CJN.023002151555-90411555-905X2016-04-29T06:47:59-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles11116999731721172198117211721
- Predictors of 30-Day Hospital Readmission among Maintenance Hemodialysis Patients: A Hospital’s Perspective10.2215/CJN.11611115Thu, 05 May 2016 06:45:49 GMT-07:00Predictors of 30-Day Hospital Readmission among Maintenance Hemodialysis Patients: A Hospital’s PerspectiveFlythe, Jennifer E.Katsanos, Suzanne L.Hu, YichunKshirsagar, Abhijit V.Falk, Ronald J.Moore, Carlton R.2016-05-05T06:45:49-07:00doi:10.2215/CJN.11611115hwp:resource-id:clinjasn;11/6/1005American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhospitalization, hemodialysis, ESRD, Humans, Patient Discharge, Patient Readmission, renal dialysis, risk factors, Serum AlbuminOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-06-06June 06, 201610.2215/CJN.116111151555-90411555-905X2016-05-05T06:45:49-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles11610051014
- Smartphone Apps: A Patient’s New Best Friend?10.2215/CJN.03650316Thu, 12 May 2016 11:21:23 GMT-07:00Smartphone Apps: A Patient’s New Best Friend?Desai, TejasYee, JerrySoman, Sandeep2016-05-12T11:21:23-07:00doi:10.2215/CJN.03650316hwp:resource-id:clinjasn;11/6/935American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytechnology, apps, smartphone, Humans, Renal Insufficiency, Chronic, Self Care, outpatientEditorialsEditorialseditorial20162016-06-06June 06, 201610.2215/CJN.036503161555-90411555-905X2016-05-12T11:21:23-07:002016-06-06Clinical Journal of the American Society of NephrologyEditorials116693510549371062
- Bone Parameters and Risk of Hip and Femur Fractures in Patients on Hemodialysis10.2215/CJN.09280915Tue, 29 Mar 2016 09:49:18 GMT-07:00Bone Parameters and Risk of Hip and Femur Fractures in Patients on HemodialysisFishbane, StevenHazzan, Azzour D.Jhaveri, Kenar D.Ma, LinLacson, Eduardo2016-03-29T09:49:18-07:00doi:10.2215/CJN.09280915hwp:resource-id:clinjasn;11/6/1063American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyparathyroid hormone, hemodialysis, calcium, Bone and Bones, Follow-Up Studies, Hip Fractures, Humans, hyperparathyroidism, Incidence, Kidney Failure, ChronicOriginal ArticlesMineral metabolism/Bone diseaseOriginal ArticlesMineral metabolism/Bone diseaseresearch-article20162016-06-06June 06, 201610.2215/CJN.092809151555-90411555-905X2016-03-29T09:49:18-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles11610631072
- Phosphate Toxicity in CKD: The Killer among UsMaintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last half-century of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.10.2215/CJN.11901115Wed, 10 Feb 2016 06:45:28 GMT-08:00Phosphate Toxicity in CKD: The Killer among UsMaintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last half-century of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.Ritter, Cynthia S.Slatopolsky, Eduardo2016-02-10T06:45:28-08:00doi:10.2215/CJN.11901115hwp:resource-id:clinjasn;11/6/1088American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyphosphate, klotho, parathyroid hormone, chronic kidney disease, calcitriol, cardiovascular diseases, humans, hyperparathyroidism, secondary, hyperphosphatemia, fibroblast growth factor 23In-Depth ReviewIn-Depth Reviewreview-article20162016-06-06June 06, 201610.2215/CJN.119011151555-90411555-905X2016-02-10T06:45:28-08:002016-06-06Clinical Journal of the American Society of NephrologyIn-Depth Review11610881100
- Survival by Dialysis Modality—Who Cares?In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups. In clinical practice, modality choice should be individualized with the aim of maximizing quality of life, patient-reported outcomes, and achieving patient-centered goals. Expected survival is often irrelevant to modality choice. Even for the younger and fitter home hemodialysis population, quality of life, not just duration of survival, is a major priority. On the other hand, increasing evidence suggests that patients with ESRD continue to experience poor quality of life because of high symptom burden, unsolved clinical problems, and unmet needs. Patients care more about how they will live instead of how long. It is our responsibility to align our research with their needs. Only by doing so can we meet the challenges of ESRD patient care in the coming decades.10.2215/CJN.13261215Thu, 11 Feb 2016 06:38:11 GMT-08:00Survival by Dialysis Modality—Who Cares?In light of the recent emphasis on patient-centered outcomes and quality of life for patients with kidney disease, we contend that the nephrology community should no longer fund, perform, or publish studies that compare survival by dialysis modality. These studies have become redundant; they are methodologically limited, unhelpful in practice, and therefore a waste of resources. More than two decades of these publications show similar survival between patients undergoing peritoneal dialysis and those receiving thrice-weekly conventional hemodialysis, with differences only for specific subgroups. In clinical practice, modality choice should be individualized with the aim of maximizing quality of life, patient-reported outcomes, and achieving patient-centered goals. Expected survival is often irrelevant to modality choice. Even for the younger and fitter home hemodialysis population, quality of life, not just duration of survival, is a major priority. On the other hand, increasing evidence suggests that patients with ESRD continue to experience poor quality of life because of high symptom burden, unsolved clinical problems, and unmet needs. Patients care more about how they will live instead of how long. It is our responsibility to align our research with their needs. Only by doing so can we meet the challenges of ESRD patient care in the coming decades.Lee, Martin B.Bargman, Joanne M.2016-02-11T06:38:11-08:00doi:10.2215/CJN.13261215hwp:resource-id:clinjasn;11/6/1083American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, outcomes, quality of life, humans, kidney diseases, kidney failure, chronic, nephrology, patient care, patient outcome assessment, renal dialysisCommentaryCommentaryarticle-commentary20162016-06-06June 06, 201610.2215/CJN.132612151555-90411555-905X2016-02-11T06:38:11-08:002016-06-06Clinical Journal of the American Society of NephrologyCommentary11610831087
- A Qualitative Study to Explore Patient and Staff Perceptions of Intradialytic Exercise10.2215/CJN.11981115Tue, 29 Mar 2016 09:49:15 GMT-07:00A Qualitative Study to Explore Patient and Staff Perceptions of Intradialytic ExerciseThompson, StephanieTonelli, MarcelloKlarenbach, ScottMolzahn, Anita2016-03-29T09:49:15-07:00doi:10.2215/CJN.11981115hwp:resource-id:clinjasn;11/6/1024American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end-stage renal disease, hemodialysis, quality of life, exercise, qualitative research, Humans, Perception, Randomized Controlled Trials as Topic, SensationOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-06-06June 06, 201610.2215/CJN.119811151555-90411555-905X2016-03-29T09:49:15-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles11610241033
- Strategies for BP Control in Developing Countries and Effects on Kidney Function10.2215/CJN.03690316Thu, 19 May 2016 06:54:27 GMT-07:00Strategies for BP Control in Developing Countries and Effects on Kidney FunctionJun, MinHemmelgarn, Brenda R.2016-05-19T06:54:27-07:00doi:10.2215/CJN.03690316hwp:resource-id:clinjasn;11/6/932American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney function, developing countries, blood pressure, Blood Pressure Determination, Urinary Tract Physiological PhenomenaEditorialsEditorialseditorial20162016-06-06June 06, 201610.2215/CJN.036903161555-90411555-905X2016-05-19T06:54:27-07:002016-06-06Clinical Journal of the American Society of NephrologyEditorials116693210449341053
- Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD10.2215/CJN.06890615Tue, 19 Apr 2016 07:00:31 GMT-07:00Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKDProvenzano, RobertBesarab, AnatoleSun, Chao H.Diamond, Susan A.Durham, John H.Cangiano, Jose L.Aiello, Joseph R.Novak, James E.Lee, TysonLeong, RobertRoberts, Brian K.Saikali, Khalil G.Hemmerich, StefanSzczech, Lynda A.Yu, Kin-Hung PeonyNeff, Thomas B.2016-04-19T07:00:31-07:00doi:10.2215/CJN.06890615hwp:resource-id:clinjasn;11/6/982American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical trial, anemia, C-Reactive Protein, Erythropoiesis, Hemoglobins, Hepcidins, Humans, Iron, Renal Insufficiency, ChronicOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-06-06June 06, 201610.2215/CJN.068906151555-90411555-905X2016-04-19T07:00:31-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles116982991
- Longitudinal Study of Serum Uric Acid, Nutritional Status, and Mortality in Maintenance Hemodialysis Patients10.2215/CJN.10400915Tue, 29 Mar 2016 09:49:17 GMT-07:00Longitudinal Study of Serum Uric Acid, Nutritional Status, and Mortality in Maintenance Hemodialysis PatientsBeberashvili, IliaErlich, AnatoliAzar, AdaSinuani, InnaFeldman, LeonidGorelik, OlegStav, KobiEfrati, Shai2016-03-29T09:49:17-07:00doi:10.2215/CJN.10400915hwp:resource-id:clinjasn;11/6/1015American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuric acid, hemodialysis, inflammation, nutrition, geriatric nutritional risk index, mortality, Cohort Studies, Humans, Longitudinal Studies, Nutritional StatusOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-06-06June 06, 201610.2215/CJN.104009151555-90411555-905X2016-03-29T09:49:17-07:002016-06-06Clinical Journal of the American Society of NephrologyOriginal Articles11610151023
- Cystinosin is a Component of the Vacuolar H+-ATPase-Ragulator-Rag Complex Controlling Mammalian Target of Rapamycin Complex 1 SignalingCystinosis is a rare autosomal recessive storage disorder characterized by defective lysosomal efflux of cystine due to mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin. Lysosomal cystine accumulation leads to crystal formation and functional impairment of multiple organs. Moreover, cystinosis is the most common inherited cause of renal Fanconi syndrome in children. Oral cysteamine therapy delays disease progression by reducing intracellular cystine levels. However, because cysteamine does not correct all complications of cystinosis, including Fanconi syndrome, we hypothesized that cystinosin could have novel roles in addition to transporting cystine out of the lysosome. By coimmunoprecipitation experiments and mass spectrometry, we found cystinosin interacts with almost all components of vacuolar H+-ATPase and the Ragulator complex and with the small GTPases Ras-related GTP-binding protein A (RagA) and RagC. Furthermore, the mammalian target of rapamycin complex 1 (mTORC1) pathway was downregulated in proximal tubular cell lines derived from Ctns−/− mice. Decrease of lysosomal cystine levels by cysteamine did not rescue mTORC1 activation in these cells, suggesting that the downregulation of mTORC1 is due to the absence of cystinosin rather than to the accumulation of cystine. Our results show a dual role for cystinosin as a cystine transporter and as a component of the mTORC1 pathway, and provide an explanation for the appearance of Fanconi syndrome in cystinosis. Furthermore, this study highlights the need to develop new treatments not dependent on lysosomal cystine depletion alone for this devastating disease.10.1681/ASN.2014090937Thu, 08 Oct 2015 10:32:19 GMT-07:00Cystinosin is a Component of the Vacuolar H+-ATPase-Ragulator-Rag Complex Controlling Mammalian Target of Rapamycin Complex 1 SignalingCystinosis is a rare autosomal recessive storage disorder characterized by defective lysosomal efflux of cystine due to mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin. Lysosomal cystine accumulation leads to crystal formation and functional impairment of multiple organs. Moreover, cystinosis is the most common inherited cause of renal Fanconi syndrome in children. Oral cysteamine therapy delays disease progression by reducing intracellular cystine levels. However, because cysteamine does not correct all complications of cystinosis, including Fanconi syndrome, we hypothesized that cystinosin could have novel roles in addition to transporting cystine out of the lysosome. By coimmunoprecipitation experiments and mass spectrometry, we found cystinosin interacts with almost all components of vacuolar H+-ATPase and the Ragulator complex and with the small GTPases Ras-related GTP-binding protein A (RagA) and RagC. Furthermore, the mammalian target of rapamycin complex 1 (mTORC1) pathway was downregulated in proximal tubular cell lines derived from Ctns−/− mice. Decrease of lysosomal cystine levels by cysteamine did not rescue mTORC1 activation in these cells, suggesting that the downregulation of mTORC1 is due to the absence of cystinosin rather than to the accumulation of cystine. Our results show a dual role for cystinosin as a cystine transporter and as a component of the mTORC1 pathway, and provide an explanation for the appearance of Fanconi syndrome in cystinosis. Furthermore, this study highlights the need to develop new treatments not dependent on lysosomal cystine depletion alone for this devastating disease.Andrzejewska, ZuzannaNevo, NathalieThomas, LucieChhuon, CerinaBailleux, AnneChauvet, VéroniqueCourtoy, Pierre J.Chol, MarieGuerrera, Ida ChiaraAntignac, Corinne2015-10-08T10:32:19-07:00doi:10.1681/ASN.2014090937hwp:resource-id:jnephrol;27/6/1678American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologymTORC1, cystinosis, Fanconi syndrome, cystinosinBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20140909371046-66731533-34502015-10-08T10:32:19-07:002016-06Journal of the American Society of NephrologyBasic Research27616781688
- Enhancing Nephrology Career Interest through the ASN Kidney TREKS ProgramThe Kidney Tutored Research and Education for Kidney Students (TREKS) Program is a product of the American Society of Nephrology (ASN) Workforce Committee that seeks to connect medical and graduate students to nephrology. This program starts with a weeklong camp–like course introducing participants to renal physiology through classic and modern experiments. Next, each student is matched with a nephrology mentor at his or her home institution to foster a better understanding of a nephrology career. Lastly, the students are encouraged to participate in scholarly activities and attend the ASN Kidney Week. Now in its third year, with a total of 84 participants, survey data suggest early success of the program, with a self–reported 40% increased interest in nephrology fellowship and/or research careers. In addition, students give high ratings to the course components and mentorship pairings. Continued student tracking will be necessary to determine the long–term program effect.10.1681/ASN.2015101086Tue, 29 Mar 2016 07:00:01 GMT-07:00Enhancing Nephrology Career Interest through the ASN Kidney TREKS ProgramThe Kidney Tutored Research and Education for Kidney Students (TREKS) Program is a product of the American Society of Nephrology (ASN) Workforce Committee that seeks to connect medical and graduate students to nephrology. This program starts with a weeklong camp–like course introducing participants to renal physiology through classic and modern experiments. Next, each student is matched with a nephrology mentor at his or her home institution to foster a better understanding of a nephrology career. Lastly, the students are encouraged to participate in scholarly activities and attend the ASN Kidney Week. Now in its third year, with a total of 84 participants, survey data suggest early success of the program, with a self–reported 40% increased interest in nephrology fellowship and/or research careers. In addition, students give high ratings to the course components and mentorship pairings. Continued student tracking will be necessary to determine the long–term program effect.Maursetter, Laura J.Stern, Lauren D.Sozio, Stephen M.Patel, Ankit B.Rao, ReenaShah, Hitesh H.Leight, KatlynOkusa, Mark D.Zeidel, Mark L.Parker, Mark G.2016-03-29T07:00:01-07:00doi:10.1681/ASN.2015101086hwp:resource-id:jnephrol;27/6/1604American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyeducation, nephrology, Mentor, Career choice, Physiology courseUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-06-01June 201610.1681/ASN.20151010861046-66731533-34502016-03-29T07:00:01-07:002016-06Journal of the American Society of NephrologyUp Front Matters27616041607
- Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney TransplantationSeveral studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.10.1681/ASN.2015040391Thu, 08 Oct 2015 10:32:22 GMT-07:00Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney TransplantationSeveral studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.Huang, Johnny W.Famure, OlusegunLi, YanhongKim, S. Joseph2015-10-08T10:32:22-07:00doi:10.1681/ASN.2015040391hwp:resource-id:jnephrol;27/6/1793American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, diabetes mellitus, hypomagnesemiaClinical EpidemiologyClinical Epidemiologyresearch-article20162016-06-01June 201610.1681/ASN.20150403911046-66731533-34502015-10-08T10:32:22-07:002016-06Journal of the American Society of NephrologyClinical Epidemiology27617931800
- Mushroom Clouds for Vitamin D?10.1681/ASN.2015111279Thu, 14 Jan 2016 07:16:18 GMT-08:00Mushroom Clouds for Vitamin D?Elder, Grahame J.2016-01-14T07:16:18-08:00doi:10.1681/ASN.2015111279hwp:resource-id:jnephrol;27/6/1581American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyVitamin D, CKD, supplementationUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-06-01June 201610.1681/ASN.20151112791046-66731533-34502016-01-14T07:16:18-08:002016-06Journal of the American Society of NephrologyUp Front Matters27661581180115841810
- Busy Bs10.1681/ASN.2015101171Mon, 30 Nov 2015 03:23:15 GMT-08:00Busy BsTrachtman, Howard2015-11-30T03:23:15-08:00doi:10.1681/ASN.2015101171hwp:resource-id:jnephrol;27/6/1584American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynephrotic syndrome, rituximab, switched memory B cells, minimal change diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-06-01June 201610.1681/ASN.20151011711046-66731533-34502015-11-30T03:23:15-08:002016-06Journal of the American Society of NephrologyUp Front Matters27661584181115861822
- Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN.10.1681/ASN.2015020149Fri, 09 Oct 2015 12:18:31 GMT-07:00Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN.Djudjaj, SonjaLue, HongqiRong, SongPapasotiriou, MariosKlinkhammer, Barbara M.Zok, StephanieKlaener, OleBraun, Gerald S.Lindenmeyer, Maja T.Cohen, Clemens D.Bucala, RichardTittel, Andre P.Kurts, ChristianMoeller, Marcus J.Floege, JuergenOstendorf, TammoBernhagen, JürgenBoor, Peter2015-10-09T12:18:31-07:00doi:10.1681/ASN.2015020149hwp:resource-id:jnephrol;27/6/1650American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycrescentic GN, parietal epithelial cells, mesangial cells, proliferation, migration inhibitory factor, CD44Basic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150201491046-66731533-34502015-10-09T12:18:31-07:002016-06Journal of the American Society of NephrologyBasic Research27616501664
- RNA Sequencing Identifies Novel Translational Biomarkers of Kidney FibrosisCKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten- to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two- to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P<0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD.10.1681/ASN.2015020225Thu, 08 Oct 2015 10:32:20 GMT-07:00RNA Sequencing Identifies Novel Translational Biomarkers of Kidney FibrosisCKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten- to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two- to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P<0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD.Craciun, Florin L.Bijol, VanesaAjay, Amrendra K.Rao, PoornimaKumar, Ramya K.Hutchinson, JohnHofmann, OliverJoshi, NikitaLuyendyk, James P.Kusebauch, UlrikeMoss, Christopher L.Srivastava, AnandHimmelfarb, JonathanWaikar, Sushrut S.Moritz, Robert L.Vaidya, Vishal S.2015-10-08T10:32:20-07:00doi:10.1681/ASN.2015020225hwp:resource-id:jnephrol;27/6/1702American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, fibrosis, transcriptional profilingBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150202251046-66731533-34502015-10-08T10:32:20-07:002016-06Journal of the American Society of NephrologyBasic Research27617021713
- Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor ConstructRenovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD. We measured single-kidney blood flow (RBF) and GFR and established the degree of renal damage after 6 weeks of RVD. Pigs then received a single stenotic kidney infusion of ELP-VEGF (100 μg/kg), a matching concentration of unconjugated VEGF (18.65 μg/kg), ELP alone (100 μg/kg), or placebo. Analysis of organ distribution showed high renal binding of ELP-VEGF 4 hours after stenotic kidney infusion. Therapeutic efficacy was determined 4 weeks after infusion. ELP-VEGF therapy improved renal protein expression attenuated in RVD, restoring expression levels of VEGF, VEGF receptor Flk-1, and downstream angiogenic mediators, including phosphorylated Akt and angiopoietin-1 and -2. This effect was accompanied by restored MV density, attenuated fibrogenic activity, and improvements in RBF and GFR greater than those observed with placebo, ELP alone, or unconjugated VEGF. In summary, we demonstrated the feasibility of a novel therapy to curtail renal injury. Recovery of the stenotic kidney in RVD after ELP-VEGF therapy may be driven by restoration of renal angiogenic signaling and attenuated fibrogenic activity, which ameliorates MV rarefaction and improves renal function.10.1681/ASN.2015040346Thu, 05 Nov 2015 04:37:26 GMT-08:00Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor ConstructRenovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD. We measured single-kidney blood flow (RBF) and GFR and established the degree of renal damage after 6 weeks of RVD. Pigs then received a single stenotic kidney infusion of ELP-VEGF (100 μg/kg), a matching concentration of unconjugated VEGF (18.65 μg/kg), ELP alone (100 μg/kg), or placebo. Analysis of organ distribution showed high renal binding of ELP-VEGF 4 hours after stenotic kidney infusion. Therapeutic efficacy was determined 4 weeks after infusion. ELP-VEGF therapy improved renal protein expression attenuated in RVD, restoring expression levels of VEGF, VEGF receptor Flk-1, and downstream angiogenic mediators, including phosphorylated Akt and angiopoietin-1 and -2. This effect was accompanied by restored MV density, attenuated fibrogenic activity, and improvements in RBF and GFR greater than those observed with placebo, ELP alone, or unconjugated VEGF. In summary, we demonstrated the feasibility of a novel therapy to curtail renal injury. Recovery of the stenotic kidney in RVD after ELP-VEGF therapy may be driven by restoration of renal angiogenic signaling and attenuated fibrogenic activity, which ameliorates MV rarefaction and improves renal function.Chade, Alejandro R.Tullos, Nathan A.Harvey, Taylor W.Mahdi, FakhriBidwell, Gene L.2015-11-05T04:37:26-08:00doi:10.1681/ASN.2015040346hwp:resource-id:jnephrol;27/6/1741American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal artery stenosis, renal protection, VEGF, angiogenesis, drug, transporter, microcirculationBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150403461046-66731533-34502015-11-05T04:37:26-08:002016-06Journal of the American Society of NephrologyBasic Research27617411752
- Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental TransplantationGlomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro. These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm–like structures. Microarray analysis of sorted iPS cell–derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo. Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell–derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell–derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases.10.1681/ASN.2015010096Thu, 19 Nov 2015 07:06:52 GMT-08:00Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental TransplantationGlomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro. These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm–like structures. Microarray analysis of sorted iPS cell–derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo. Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell–derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell–derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases.Sharmin, SaziaTaguchi, AtsuhiroKaku, YusukeYoshimura, YasuhiroOhmori, TomokoSakuma, TetsushiMukoyama, MasashiYamamoto, TakashiKurihara, HidetakeNishinakamura, Ryuichi2015-11-19T07:06:52-08:00doi:10.1681/ASN.2015010096hwp:resource-id:jnephrol;27/6/1778American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, stem cell, kidney developmentBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150100961046-66731533-34502015-11-19T07:06:52-08:002016-06Journal of the American Society of NephrologyBasic Research27661778157917911581
- B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic SyndromeThe pathogenesis of nephrotic syndrome is unclear. However, the efficacy of rituximab, a B cell–depleting antibody, in nephrotic syndrome suggests a pathogenic role of B cells. In this retrospective study, we determined by flow cytometry levels of B and T cell subpopulations before and after rituximab infusion in 28 pediatric patients with frequently relapsing or steroid–dependent nephrotic syndrome. At baseline, patients had lower median percentages of transitional and mature B cells than age–matched healthy controls (P<0.001). Rituximab induced full depletion of B cells (<1% of lymphocytes). At 1 year, most patients exhibited complete total and mature B cell recovery, whereas memory B cell subsets remained significantly depleted. Total T cell concentration did not change with rituximab, whereas the CD4+/CD8+ T cell ratio tended to increase. Fourteen patients relapsed within 24 months, with a median follow-up of 11.2 months (interquartile range, 8–17.7 months). We observed no difference at baseline between nonrelapsing and relapsing patients in several clinical parameters and cell subset concentrations. Reconstitution of all memory B cell subpopulations, number of immunosuppressive drugs, and dose of tacrolimus during the last 4 months of follow-up were predictive of relapse in univariate Cox regression analysis. However, only delayed reconstitution of switched memory B cells, independent of immunosuppressive treatment, was protective against relapse in multivariate (P<0.01) and receiver operator characteristic (P<0.01 for percentage of lymphocytes; P=0.02 for absolute count) analyses. Evaluation of switched memory B cell recovery after rituximab may be useful for predicting relapse in patients with nephrotic syndrome.10.1681/ASN.2015050523Fri, 13 Nov 2015 09:34:22 GMT-08:00B Cell Reconstitution after Rituximab Treatment in Idiopathic Nephrotic SyndromeThe pathogenesis of nephrotic syndrome is unclear. However, the efficacy of rituximab, a B cell–depleting antibody, in nephrotic syndrome suggests a pathogenic role of B cells. In this retrospective study, we determined by flow cytometry levels of B and T cell subpopulations before and after rituximab infusion in 28 pediatric patients with frequently relapsing or steroid–dependent nephrotic syndrome. At baseline, patients had lower median percentages of transitional and mature B cells than age–matched healthy controls (P<0.001). Rituximab induced full depletion of B cells (<1% of lymphocytes). At 1 year, most patients exhibited complete total and mature B cell recovery, whereas memory B cell subsets remained significantly depleted. Total T cell concentration did not change with rituximab, whereas the CD4+/CD8+ T cell ratio tended to increase. Fourteen patients relapsed within 24 months, with a median follow-up of 11.2 months (interquartile range, 8–17.7 months). We observed no difference at baseline between nonrelapsing and relapsing patients in several clinical parameters and cell subset concentrations. Reconstitution of all memory B cell subpopulations, number of immunosuppressive drugs, and dose of tacrolimus during the last 4 months of follow-up were predictive of relapse in univariate Cox regression analysis. However, only delayed reconstitution of switched memory B cells, independent of immunosuppressive treatment, was protective against relapse in multivariate (P<0.01) and receiver operator characteristic (P<0.01 for percentage of lymphocytes; P=0.02 for absolute count) analyses. Evaluation of switched memory B cell recovery after rituximab may be useful for predicting relapse in patients with nephrotic syndrome.Colucci, ManuelaCarsetti, RitaCascioli, SimonaCasiraghi, FedericaPerna, AnnalisaRavà, LucillaRuggiero, BarbaraEmma, FrancescoVivarelli, Marina2015-11-13T09:34:22-08:00doi:10.1681/ASN.2015050523hwp:resource-id:jnephrol;27/6/1811American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyidiopathic nephrotic syndrome, immunosuppression, lymphocytes, clinical immunology, glomerular diseaseClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150505231046-66731533-34502015-11-13T09:34:22-08:002016-06Journal of the American Society of NephrologyClinical Research27661811158418221586
- Lithium in the Kidney: Friend and Foe?Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long–term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium–induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.10.1681/ASN.2015080907Tue, 17 Nov 2015 06:52:54 GMT-08:00Lithium in the Kidney: Friend and Foe?Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long–term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium–induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.Alsady, MohammadBaumgarten, RubenDeen, Peter M.T.de Groot, Theun2015-11-17T06:52:54-08:00doi:10.1681/ASN.2015080907hwp:resource-id:jnephrol;27/6/1587American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cell and transport physiology, cell signaling, end-stage renal disease, diabetes insipidus, drug nephrotoxicityUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-06-01June 201610.1681/ASN.20150809071046-66731533-34502015-11-17T06:52:54-08:002016-06Journal of the American Society of NephrologyUp Front Matters27615871595
- Alternative Splicing in CKDAlternative splicing (AS) has emerged in the postgenomic era as one of the main drivers of proteome diversity, with ≥94% of multiexon genes alternatively spliced in humans. AS is therefore one of the main control mechanisms for cell phenotype, and is a process deregulated in disease. Numerous reports describe pathogenic mutations in splice factors, splice sites, or regulatory sequences. Additionally, compared with the physiologic state, disease often associates with an abnormal proportion of splice isoforms (or novel isoforms), without an apparent driver mutation. It is therefore essential to study how AS is regulated in physiology, how it contributes to pathogenesis, and whether we can manipulate faulty splicing for therapeutic advantage. Although the disease most commonly linked to deregulation of AS in several genes is cancer, many reports detail pathogenic splice variants in diseases ranging from neuromuscular disorders to diabetes or cardiomyopathies. A plethora of splice variants have been implicated in CKDs as well. In this review, we describe examples of these CKD-associated splice variants and ideas on how to manipulate them for therapeutic benefit.10.1681/ASN.2015080908Wed, 13 Jan 2016 08:23:55 GMT-08:00Alternative Splicing in CKDAlternative splicing (AS) has emerged in the postgenomic era as one of the main drivers of proteome diversity, with ≥94% of multiexon genes alternatively spliced in humans. AS is therefore one of the main control mechanisms for cell phenotype, and is a process deregulated in disease. Numerous reports describe pathogenic mutations in splice factors, splice sites, or regulatory sequences. Additionally, compared with the physiologic state, disease often associates with an abnormal proportion of splice isoforms (or novel isoforms), without an apparent driver mutation. It is therefore essential to study how AS is regulated in physiology, how it contributes to pathogenesis, and whether we can manipulate faulty splicing for therapeutic advantage. Although the disease most commonly linked to deregulation of AS in several genes is cancer, many reports detail pathogenic splice variants in diseases ranging from neuromuscular disorders to diabetes or cardiomyopathies. A plethora of splice variants have been implicated in CKDs as well. In this review, we describe examples of these CKD-associated splice variants and ideas on how to manipulate them for therapeutic benefit.Stevens, MeganOltean, Sebastian2016-01-13T08:23:55-08:00doi:10.1681/ASN.2015080908hwp:resource-id:jnephrol;27/6/1596American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, gene expression, mRNAUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-06-01June 201610.1681/ASN.20150809081046-66731533-34502016-01-13T08:23:55-08:002016-06Journal of the American Society of NephrologyUp Front Matters27615961603
- Autophagy Induces Prosenescent Changes in Proximal Tubular S3 SegmentsEvidence suggests that autophagy promotes the development of cellular senescence. Because cellular senescence contributes to renal aging and promotes the progression from AKI to CKD, we investigated the potential effect of tubular autophagy on senescence induction. Compared with kidneys from control mice, kidneys from mice with conditional deletion of autophagy-related 5 (Atg5) for selective ablation of autophagy in proximal tubular S3 segments (Atg5Δflox/Δflox) presented with significantly less tubular senescence, reduced interstitial fibrosis, and superior renal function 30 days after ischemia/reperfusion injury. To correlate this long-term outcome with differences in the early injury process, kidneys were analyzed 2 hours and 3 days after reperfusion. Notably, compared with kidneys of control mice, Atg5Δflox/Δflox kidneys showed more cell death in outer medullary S3 segments at 2 hours but less tubular damage and inflammation at day 3. These data suggest that the lack of autophagy prevents early survival mechanisms in severely damaged tubular cells. However, if such compromised cells persist, then they may lead to maladaptive repair and proinflammatory changes, thereby facilitating the development of a senescent phenotype and CKD.10.1681/ASN.2014111059Tue, 20 Oct 2015 08:37:49 GMT-07:00Autophagy Induces Prosenescent Changes in Proximal Tubular S3 SegmentsEvidence suggests that autophagy promotes the development of cellular senescence. Because cellular senescence contributes to renal aging and promotes the progression from AKI to CKD, we investigated the potential effect of tubular autophagy on senescence induction. Compared with kidneys from control mice, kidneys from mice with conditional deletion of autophagy-related 5 (Atg5) for selective ablation of autophagy in proximal tubular S3 segments (Atg5Δflox/Δflox) presented with significantly less tubular senescence, reduced interstitial fibrosis, and superior renal function 30 days after ischemia/reperfusion injury. To correlate this long-term outcome with differences in the early injury process, kidneys were analyzed 2 hours and 3 days after reperfusion. Notably, compared with kidneys of control mice, Atg5Δflox/Δflox kidneys showed more cell death in outer medullary S3 segments at 2 hours but less tubular damage and inflammation at day 3. These data suggest that the lack of autophagy prevents early survival mechanisms in severely damaged tubular cells. However, if such compromised cells persist, then they may lead to maladaptive repair and proinflammatory changes, thereby facilitating the development of a senescent phenotype and CKD.Baisantry, ArpitaBhayana, SagarRong, SongErmeling, EstherWrede, ChristophHegermann, JanPennekamp, PetraSörensen-Zender, IngaHaller, HermannMelk, AnetteSchmitt, Roland2015-10-20T08:37:49-07:00doi:10.1681/ASN.2014111059hwp:resource-id:jnephrol;27/6/1609American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, ischemia/reperfusion, proximal tubule, fibrosis, pathophysiology of renal disease and progression, progression of renal failureBrief CommunicationsBrief Communicationsbrief-report20162016-06-01June 201610.1681/ASN.20141110591046-66731533-34502015-10-20T08:37:49-07:002016-06Journal of the American Society of NephrologyBrief Communications27616091616
- A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic SyndromeThe regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H–related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology–mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.10.1681/ASN.2015010100Wed, 21 Oct 2015 08:11:00 GMT-07:00A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H–Related 3 Gene in Atypical Hemolytic Uremic SyndromeThe regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H–related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology–mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic disorders may arise.Challis, Rachel C.Araujo, Geisilaine S.R.Wong, Edwin K.S.Anderson, Holly E.Awan, AtifDorman, Anthony M.Waldron, MaryWilson, ValerieBrocklebank, VickyStrain, LisaMorgan, B. PaulHarris, Claire L.Marchbank, Kevin J.Goodship, Timothy H.J.Kavanagh, David2015-10-21T08:11:00-07:00doi:10.1681/ASN.2015010100hwp:resource-id:jnephrol;27/6/1617American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, hemolytic uremic syndrome, genetic renal diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-06-01June 201610.1681/ASN.20150101001046-66731533-34502015-10-21T08:11:00-07:002016-06Journal of the American Society of NephrologyBrief Communications27616171624
- Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes ComplicationsEndothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia–induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68+ intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage–derived circulating PAR2 agonist and mediator of endothelial dysfunction–related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.10.1681/ASN.2015020208Fri, 13 Nov 2015 09:34:21 GMT-08:00Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes ComplicationsEndothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia–induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68+ intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage–derived circulating PAR2 agonist and mediator of endothelial dysfunction–related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.Kumar VR, SanthoshDarisipudi, Murthy N.Steiger, StefanieDevarapu, Satish KumarTato, MaiaKukarni, Onkar P.Mulay, Shrikant R.Thomasova, DanaPopper, BastianDemleitner, JanaZuchtriegel, GabrieleReichel, ChristophCohen, Clemens D.Lindenmeyer, Maja T.Liapis, HelenMoll, SolangeReid, EmmaStitt, Alan W.Schott, BrigitteGruner, SabineHaap, WolfgangEbeling, MartinHartmann, GuidoAnders, Hans-Joachim2015-11-13T09:34:21-08:00doi:10.1681/ASN.2015020208hwp:resource-id:jnephrol;27/6/1635American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, endothelial cells, albuminuria, macrophagesBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150202081046-66731533-34502015-11-13T09:34:21-08:002016-06Journal of the American Society of NephrologyBasic Research27661635157716491579
- A Familial C3GN Secondary to Defective C3 Regulation by Complement Receptor 1 and Complement Factor HC3 glomerulopathy is a recently described form of CKD. C3GN is a subtype of C3 glomerulopathy characterized by predominant C3 deposits in the glomeruli and is commonly the result of acquired or genetic abnormalities in the alternative pathway (AP) of the complement system. We identified and characterized the first mutation of the C3 gene (p. I734T) in two related individuals diagnosed with C3GN. Immunofluorescence and electron microscopy studies showed C3 deposits in the subendothelial space, associated with unusual deposits located near the complement receptor 1 (CR1)-expressing podocytes. In vitro, this C3 mutation exhibited decreased binding to CR1, resulting in less CR1-dependent cleavage of C3b by factor 1. Both patients had normal plasma C3 levels, and the mutant C3 interacted with factor B comparably to wild-type (WT) C3 to form a C3 convertase. Binding of mutant C3 to factor H was normal, but mutant C3 was less efficiently cleaved by factor I in the presence of factor H, leading to enhanced C3 fragment deposition on glomerular cells. In conclusion, our results reveal that a CR1 functional deficiency is a mechanism of intraglomerular AP dysregulation and could influence the localization of the glomerular C3 deposits.10.1681/ASN.2015040348Thu, 15 Oct 2015 05:08:05 GMT-07:00A Familial C3GN Secondary to Defective C3 Regulation by Complement Receptor 1 and Complement Factor HC3 glomerulopathy is a recently described form of CKD. C3GN is a subtype of C3 glomerulopathy characterized by predominant C3 deposits in the glomeruli and is commonly the result of acquired or genetic abnormalities in the alternative pathway (AP) of the complement system. We identified and characterized the first mutation of the C3 gene (p. I734T) in two related individuals diagnosed with C3GN. Immunofluorescence and electron microscopy studies showed C3 deposits in the subendothelial space, associated with unusual deposits located near the complement receptor 1 (CR1)-expressing podocytes. In vitro, this C3 mutation exhibited decreased binding to CR1, resulting in less CR1-dependent cleavage of C3b by factor 1. Both patients had normal plasma C3 levels, and the mutant C3 interacted with factor B comparably to wild-type (WT) C3 to form a C3 convertase. Binding of mutant C3 to factor H was normal, but mutant C3 was less efficiently cleaved by factor I in the presence of factor H, leading to enhanced C3 fragment deposition on glomerular cells. In conclusion, our results reveal that a CR1 functional deficiency is a mechanism of intraglomerular AP dysregulation and could influence the localization of the glomerular C3 deposits.Chauvet, SophieRoumenina, Lubka T.Bruneau, SarahMarinozzi, Maria ChiaraRybkine, TaniaSchramm, Elizabeth C.Java, AnujaAtkinson, John P.Aldigier, Jean ClaudeBridoux, FrankTouchard, GuyFremeaux-Bacchi, Veronique2015-10-15T05:08:05-07:00doi:10.1681/ASN.2015040348hwp:resource-id:jnephrol;27/6/1665American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology and pathology, C, glomerular diseaseBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150403481046-66731533-34502015-10-15T05:08:05-07:002016-06Journal of the American Society of NephrologyBasic Research27616651677
- Extrarenal Progenitor Cells Do Not Contribute to Renal Endothelial RepairEndothelial progenitor cells (EPCs) may be relevant contributors to endothelial cell (EC) repair in various organ systems. In this study, we investigated the potential role of EPCs in renal EC repair. We analyzed the major EPC subtypes in murine kidneys, blood, and spleens after induction of selective EC injury using the concanavalin A/anti-concanavalin A model and after ischemia/reperfusion (I/R) injury as well as the potential of extrarenal cells to substitute for injured local EC. Bone marrow transplantation (BMTx), kidney transplantation, or a combination of both were performed before EC injury to allow distinction of extrarenal or BM-derived cells from intrinsic renal cells. During endothelial regeneration, cells expressing markers of endothelial colony-forming cells (ECFCs) were the most abundant EPC subtype in kidneys, but were not detected in blood or spleen. Few cells expressing markers of EC colony-forming units (EC-CFUs) were detected. In BM chimeric mice (C57BL/6 with tandem dimer Tomato-positive [tdT+] BM cells), circulating and splenic EC-CFUs were BM-derived (tdT+), whereas cells positive for ECFC markers in kidneys were not. Indeed, most BM-derived tdT+ cells in injured kidneys were inflammatory cells. Kidneys from C57BL/6 donors transplanted into tdT+ recipients with or without prior BMTx from C57BL/6 mice were negative for BM-derived or extrarenal ECFCs. Overall, extrarenal cells did not substitute for any intrinsic ECs. These results demonstrate that endothelial repair in mouse kidneys with acute endothelial lesions depends exclusively on local mechanisms.10.1681/ASN.2015030321Fri, 09 Oct 2015 12:18:25 GMT-07:00Extrarenal Progenitor Cells Do Not Contribute to Renal Endothelial RepairEndothelial progenitor cells (EPCs) may be relevant contributors to endothelial cell (EC) repair in various organ systems. In this study, we investigated the potential role of EPCs in renal EC repair. We analyzed the major EPC subtypes in murine kidneys, blood, and spleens after induction of selective EC injury using the concanavalin A/anti-concanavalin A model and after ischemia/reperfusion (I/R) injury as well as the potential of extrarenal cells to substitute for injured local EC. Bone marrow transplantation (BMTx), kidney transplantation, or a combination of both were performed before EC injury to allow distinction of extrarenal or BM-derived cells from intrinsic renal cells. During endothelial regeneration, cells expressing markers of endothelial colony-forming cells (ECFCs) were the most abundant EPC subtype in kidneys, but were not detected in blood or spleen. Few cells expressing markers of EC colony-forming units (EC-CFUs) were detected. In BM chimeric mice (C57BL/6 with tandem dimer Tomato-positive [tdT+] BM cells), circulating and splenic EC-CFUs were BM-derived (tdT+), whereas cells positive for ECFC markers in kidneys were not. Indeed, most BM-derived tdT+ cells in injured kidneys were inflammatory cells. Kidneys from C57BL/6 donors transplanted into tdT+ recipients with or without prior BMTx from C57BL/6 mice were negative for BM-derived or extrarenal ECFCs. Overall, extrarenal cells did not substitute for any intrinsic ECs. These results demonstrate that endothelial repair in mouse kidneys with acute endothelial lesions depends exclusively on local mechanisms.Sradnick, JanRong, SongLuedemann, AnikaParmentier, Simon P.Bartaun, ChristophTodorov, Vladimir T.Gueler, FaikahHugo, Christian P.Hohenstein, Bernd2015-10-09T12:18:25-07:00doi:10.1681/ASN.2015030321hwp:resource-id:jnephrol;27/6/1714American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyendothelial injury, endothelial progenitor cell, endothelial repair, thrombotic, glomerulonephritisBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150303211046-66731533-34502015-10-09T12:18:25-07:002016-06Journal of the American Society of NephrologyBasic Research27617141726
- This Month's Highlights10.1681/ASN.2016030364Tue, 31 May 2016 10:00:54 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-05-31T10:00:54-07:00doi:10.1681/ASN.2016030364hwp:resource-id:jnephrol;27/6/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month’s HighlightsThis Month’s Highlightsin-brief20162016-06-01June 201610.1681/ASN.20160303641046-66731533-34502016-05-31T10:00:54-07:002016-06Journal of the American Society of NephrologyThis Month’s Highlights276ii
- Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney DiseaseRenal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height–adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in–frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in–frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.10.1681/ASN.2015060648Fri, 09 Oct 2015 12:18:27 GMT-07:00Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney DiseaseRenal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine ≤1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height–adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in–frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in–frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of PKD1 and PKD2 may provide useful clinical prognostication for ADPKD.Hwang, Young-HwanConklin, JohnChan, WinnieRoslin, Nicole M.Liu, JannelHe, NingWang, KairongSundsbak, Jamie L.Heyer, Christina M.Haider, MasoomPaterson, Andrew D.Harris, Peter C.Pei, York2015-10-09T12:18:27-07:00doi:10.1681/ASN.2015060648hwp:resource-id:jnephrol;27/6/1861American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, genetic renal disease, genetics and developmentClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150606481046-66731533-34502015-10-09T12:18:27-07:002016-06Journal of the American Society of NephrologyClinical Research27618611868
- Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell DiseaseThe earliest symptom of glomerular injury in patients with sickle cell disease (SCD) is microalbuminuria. The effect of hydroxyurea (HU) on urine albumin-to-creatinine ratio (ACR) is unclear and should be determined, because increasing numbers of patients with SCD take this drug to improve red blood cell function. In this cohort study of 58 SS-homozygous adults with SCD who initiated HU therapy, we evaluated ACR changes and relationships of these changes with demographic, clinical, and biologic parameters at HU initiation (baseline) and 6 months later (follow-up). Between baseline and follow-up, ACR declined significantly for the entire population (3.0–1.7 mg/mmol; P<0.01), but this was primarily driven by the ACR reduction in the microalbuminuria subgroup (8.1–2.3 mg/mmol; P=0.03; n=23). According to bivariate analyses on 39 patients who did not receive a blood transfusion during the study period, the baseline to follow-up ACR decline was strongly associated with decreases in levels of hemolysis markers, percentage of dense red blood cells, and systolic BP. Bivariate analysis also revealed a close association between the ACR decrease and high baseline levels of hemolysis markers and percentage of dense red blood cells. These results show that urine ACR decreased significantly after 6 months of HU and confirm a close relationship between ACR and hemolysis evolution in patients with SCD.10.1681/ASN.2014111126Thu, 19 Nov 2015 07:06:54 GMT-08:00Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell DiseaseThe earliest symptom of glomerular injury in patients with sickle cell disease (SCD) is microalbuminuria. The effect of hydroxyurea (HU) on urine albumin-to-creatinine ratio (ACR) is unclear and should be determined, because increasing numbers of patients with SCD take this drug to improve red blood cell function. In this cohort study of 58 SS-homozygous adults with SCD who initiated HU therapy, we evaluated ACR changes and relationships of these changes with demographic, clinical, and biologic parameters at HU initiation (baseline) and 6 months later (follow-up). Between baseline and follow-up, ACR declined significantly for the entire population (3.0–1.7 mg/mmol; P<0.01), but this was primarily driven by the ACR reduction in the microalbuminuria subgroup (8.1–2.3 mg/mmol; P=0.03; n=23). According to bivariate analyses on 39 patients who did not receive a blood transfusion during the study period, the baseline to follow-up ACR decline was strongly associated with decreases in levels of hemolysis markers, percentage of dense red blood cells, and systolic BP. Bivariate analysis also revealed a close association between the ACR decrease and high baseline levels of hemolysis markers and percentage of dense red blood cells. These results show that urine ACR decreased significantly after 6 months of HU and confirm a close relationship between ACR and hemolysis evolution in patients with SCD.Bartolucci, PabloHabibi, AnooshaStehlé, ThomasDi Liberto, GaetanaRakotoson, Marie GeorgineGellen-Dautremer, JustineLoric, SylvainMoutereau, StéphaneSahali, DilWagner-Ballon, OrianneRemy, PhilippeLang, PhilippeGrimbert, PhilippeAudureau, EtienneGodeau, BertrandGalacteros, FrédéricAudard, Vincent2015-11-19T07:06:54-08:00doi:10.1681/ASN.2014111126hwp:resource-id:jnephrol;27/6/1847American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, sickle cell disease, hydroxyureaClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20141111261046-66731533-34502015-11-19T07:06:54-08:002016-06Journal of the American Society of NephrologyClinical Research27618471853
- Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical TrialLocally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D <30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean±SD serum 25(OH)D increased from 16.0±5.9 ng/ml at baseline to 39.2±14.9 ng/ml in the ergocalciferol arm and did not change (16.9±6.4 ng/ml and 17.5±7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes.10.1681/ASN.2015040468Thu, 17 Dec 2015 07:44:12 GMT-08:00Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical TrialLocally produced 1,25-dihydroxyvitamin D3 may have pleiotropic effects outside of bone. Experimental and observational studies suggest that nutritional vitamin D may enhance erythropoiesis in settings of 25-hydroxy vitamin D (25(OH)D) deficiency. We conducted a double-blind, placebo-controlled, randomized clinical trial to assess the effects of supplementation with ergocalciferol on epoetin utilization and other secondary outcomes in patients on hemodialysis with serum 25(OH)D <30 ng/ml. In all, 276 patients were randomized to 6 months of ergocalciferol or placebo. Mean±SD serum 25(OH)D increased from 16.0±5.9 ng/ml at baseline to 39.2±14.9 ng/ml in the ergocalciferol arm and did not change (16.9±6.4 ng/ml and 17.5±7.4 ng/ml, respectively) in the placebo arm. There was no significant change in epoetin dose over 6 months in the ergocalciferol or placebo arms (geometric mean rate 0.98 [95% confidence interval (95% CI), 0.94 to 1.02] versus 0.99 [95% CI, 0.95 to 1.03], respectively) and no difference across arms (P=0.78). No change occurred in serum calcium, phosphorus, intact parathyroid hormone, or C-reactive protein levels, cinacalcet use, or phosphate binder or calcitriol dose in either study arm. Rates of all-cause, cardiovascular, and infection-related hospitalizations did not differ by study arm, although statistical power was limited for these outcomes. In conclusion, 6 months of supplementation with ergocalciferol increased serum 25(OH)D levels in patients on hemodialysis with vitamin D insufficiency or deficiency, but had no effect on epoetin utilization or secondary biochemical and clinical outcomes.Miskulin, Dana C.Majchrzak, KarenTighiouart, HocineMuther, Richard S.Kapoian, TorosJohnson, Doug S.Weiner, Daniel E.2015-12-17T07:44:12-08:00doi:10.1681/ASN.2015040468hwp:resource-id:jnephrol;27/6/1801American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, randomized controlled trials, vitamin D, hyperparathyroidismClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150404681046-66731533-34502015-12-17T07:44:12-08:002016-06Journal of the American Society of NephrologyClinical Research27661801158118101584
- Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRDCapillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all–cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2–1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log–transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all–cause and cardiovascular mortality in patients with dd-ESRD.10.1681/ASN.2015030301Mon, 12 Oct 2015 12:31:23 GMT-07:00Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRDCapillary rarefaction of the coronary microcirculation is a consistent phenotype in patients with dialysis-dependent ESRD (dd-ESRD) and may help explain their excess mortality. Global coronary flow reserve (CFR) assessed by positron emission tomography (PET) is a noninvasive, quantitative marker of myocardial perfusion and ischemia that integrates the hemodynamic effects of epicardial stenosis, diffuse atherosclerosis, and microvascular dysfunction. We tested whether global CFR provides risk stratification in patients with dd-ESRD. Consecutive patients with dd-ESRD clinically referred for myocardial perfusion PET imaging were retrospectively included, excluding patients with prior renal transplantation. Per-patient CFR was calculated as the ratio of stress to rest absolute myocardial blood flow. Multivariable Cox proportional hazards models, including age, overt cardiovascular disease, and myocardial scar/ischemia burden, were used to assess the independent association of global CFR with all–cause and cardiovascular mortality. The incremental value of global CFR was assessed with relative integrated discrimination index and net reclassification improvement. In 168 patients included, median global CFR was 1.4 (interquartile range, 1.2–1.8). During follow-up (median of 3 years), 36 patients died, including 21 cardiovascular deaths. Log–transformed global CFR independently associated with all-cause mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.14; P<0.001) and cardiovascular mortality (hazard ratio, 0.01 per 0.5-unit increase; 95% confidence interval, <0.01 to 0.15; P=0.002). For all-cause mortality, addition of global CFR resulted in risk reclassification in 27% of patients. Thus, global CFR may provide independent and incremental risk stratification for all–cause and cardiovascular mortality in patients with dd-ESRD.Shah, Nishant R.Charytan, David M.Murthy, Venkatesh L.Skali Lami, HichamVeeranna, VikasCheezum, Michael K.Taqueti, Viviany R.Kato, TakashiFoster, Courtney R.Hainer, JonGaber, MariyaKlein, JoshDorbala, SharmilaBlankstein, RonDi Carli, Marcelo F.2015-10-12T12:31:23-07:00doi:10.1681/ASN.2015030301hwp:resource-id:jnephrol;27/6/1823American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologysurvival, mortality risk, outcomes, cardiovascular diseaseClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150303011046-66731533-34502015-10-12T12:31:23-07:002016-06Journal of the American Society of NephrologyClinical Research27618231829
- Aortic Aging in ESRD: Structural, Hemodynamic, and Mortality ImplicationsAging incurs aortic stiffening and dilation, but these changes are less pronounced in peripheral arteries, resulting in stiffness and geometry gradients influencing progression of the forward and reflected pressure waves. Because premature arterial aging is observed in ESRD, we determined the respective roles of stiffness and aortic geometry gradients in 73 controls and 156 patients on hemodialysis. We measured aortic pulse wave velocity (PWV) and brachial PWV to evaluate the stiffness gradient [(brachial PWV/aortic PWV)0.5] and ascending aortic and aortic bifurcation diameters to assess aortic taper (ascending aortic diameter/aortic bifurcation diameter). The global reflection coefficient was estimated from characteristic impedance and vascular resistance. Cox proportional hazard models were used to determine mortality risk. The age-associated increase in aortic PWV was higher in patients (P<0.001). In controls, aortic ascending and bifurcation diameters increased with age, with an unchanged aortic taper. In patients on hemodialysis, age did not associate with increased ascending aortic diameter but did associate with increased aortic bifurcation diameter and decreased aortic taper, both of which also associated with abdominal aortic calcifications and smaller global reflection coefficient (P<0.001). In patients, multivariate models revealed all-cause and cardiovascular mortality associated with age, aortic PWV, and aortic bifurcation diameter with high specificity and sensitivity. Using stiffness gradient, aortic taper, or global reflection coefficient in the model produced similar results. Thus, whereas aortic stiffness is a known independent predictor of mortality, these results indicate the importance of also evaluating the aortic geometry in patients on hemodialysis.10.1681/ASN.2015060617Fri, 16 Oct 2015 06:50:09 GMT-07:00Aortic Aging in ESRD: Structural, Hemodynamic, and Mortality ImplicationsAging incurs aortic stiffening and dilation, but these changes are less pronounced in peripheral arteries, resulting in stiffness and geometry gradients influencing progression of the forward and reflected pressure waves. Because premature arterial aging is observed in ESRD, we determined the respective roles of stiffness and aortic geometry gradients in 73 controls and 156 patients on hemodialysis. We measured aortic pulse wave velocity (PWV) and brachial PWV to evaluate the stiffness gradient [(brachial PWV/aortic PWV)0.5] and ascending aortic and aortic bifurcation diameters to assess aortic taper (ascending aortic diameter/aortic bifurcation diameter). The global reflection coefficient was estimated from characteristic impedance and vascular resistance. Cox proportional hazard models were used to determine mortality risk. The age-associated increase in aortic PWV was higher in patients (P<0.001). In controls, aortic ascending and bifurcation diameters increased with age, with an unchanged aortic taper. In patients on hemodialysis, age did not associate with increased ascending aortic diameter but did associate with increased aortic bifurcation diameter and decreased aortic taper, both of which also associated with abdominal aortic calcifications and smaller global reflection coefficient (P<0.001). In patients, multivariate models revealed all-cause and cardiovascular mortality associated with age, aortic PWV, and aortic bifurcation diameter with high specificity and sensitivity. Using stiffness gradient, aortic taper, or global reflection coefficient in the model produced similar results. Thus, whereas aortic stiffness is a known independent predictor of mortality, these results indicate the importance of also evaluating the aortic geometry in patients on hemodialysis.London, Gérard M.Safar, Michel E.Pannier, Bruno2015-10-16T06:50:09-07:00doi:10.1681/ASN.2015060617hwp:resource-id:jnephrol;27/6/1837American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyarteries, pulse wave velocity, cardiovascular disease, vascular calcification, chronic kidney failure, mortalityClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150606171046-66731533-34502015-10-16T06:50:09-07:002016-06Journal of the American Society of NephrologyClinical Research27618371846
- Androgens Enhance Male Urinary Tract Infection Severity in a New ModelUrinary tract infections (UTIs) occur predominantly in females but also affect substantial male patient populations; indeed, morbidity in complicated UTI is higher in males. Because of technical obstacles, preclinical modeling of UTI in male mice has been limited. We devised a minimally invasive surgical bladder inoculation technique that yields reproducible upper and lower UTI in both male and female mice, enabling studies of sex differences in these infections. Acute uropathogenic Escherichia coli (UPEC) cystitis in C57BL/6 and C3H/HeN males recapitulated the intracellular bacterial community pathway previously shown in females. However, surgically infected females of these strains exhibited more robust bladder cytokine responses and more efficient UPEC control than males. Compared with females, C3H/HeN males displayed a striking predilection for chronic cystitis, manifesting as persistent bacteriuria, high-titer bladder bacterial burdens, and chronic inflammation. Furthermore, males developed more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in female mice). These phenotypes were sharply abrogated after castration but restored with exogenous testosterone, suggesting that male susceptibility to UTI is strongly influenced by androgen exposure. These data substantiate the long-standing presumption that anatomic differences in urogenital anatomy confer protection from UTI in males; however, as clinically observed, male sex associated with more severe UTI once these traditional anatomic barriers were bypassed. This study introduces a highly tractable preclinical model for interrogating sex differences in UTI susceptibility and pathogenesis, and illuminates an interplay between host sex and UTI that is more complex than previously appreciated.10.1681/ASN.2015030327Thu, 08 Oct 2015 10:32:17 GMT-07:00Androgens Enhance Male Urinary Tract Infection Severity in a New ModelUrinary tract infections (UTIs) occur predominantly in females but also affect substantial male patient populations; indeed, morbidity in complicated UTI is higher in males. Because of technical obstacles, preclinical modeling of UTI in male mice has been limited. We devised a minimally invasive surgical bladder inoculation technique that yields reproducible upper and lower UTI in both male and female mice, enabling studies of sex differences in these infections. Acute uropathogenic Escherichia coli (UPEC) cystitis in C57BL/6 and C3H/HeN males recapitulated the intracellular bacterial community pathway previously shown in females. However, surgically infected females of these strains exhibited more robust bladder cytokine responses and more efficient UPEC control than males. Compared with females, C3H/HeN males displayed a striking predilection for chronic cystitis, manifesting as persistent bacteriuria, high-titer bladder bacterial burdens, and chronic inflammation. Furthermore, males developed more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in female mice). These phenotypes were sharply abrogated after castration but restored with exogenous testosterone, suggesting that male susceptibility to UTI is strongly influenced by androgen exposure. These data substantiate the long-standing presumption that anatomic differences in urogenital anatomy confer protection from UTI in males; however, as clinically observed, male sex associated with more severe UTI once these traditional anatomic barriers were bypassed. This study introduces a highly tractable preclinical model for interrogating sex differences in UTI susceptibility and pathogenesis, and illuminates an interplay between host sex and UTI that is more complex than previously appreciated.Olson, Patrick D.Hruska, Keith A.Hunstad, David A.2015-10-08T10:32:17-07:00doi:10.1681/ASN.2015030327hwp:resource-id:jnephrol;27/6/1625American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypyelonephritis, sex differences, urinary tract infection, testosteroneBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150303271046-66731533-34502015-10-08T10:32:17-07:002016-06Journal of the American Society of NephrologyBasic Research27616251634
- Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic KidneyActivation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein expression and phosphorylation were upregulated in diabetic mouse renal proximal tubule epithelial cells, which were inhibited in diabetic proximal tubule EGFR-knockout mice (EGFRptKO) or administration of an EGFR tyrosine kinase inhibitor erlotinib. Furthermore, activation of an EGFR-PI3K-Akt-CREB signaling pathway mediated YAP gene expression and YAP nuclear translocation and interaction with the TEA domain (TEAD) transcription factor complex, which led to upregulated expression of two TEAD-dependent genes, the connective tissue growth factor and amphiregulin genes. In a renal proximal tubule cell line, either pharmacologic or genetic inhibition of EGFR, Akt, or CREB blunted YAP expression in response to high-glucose treatment. Additionally, knocking down YAP expression by specific siRNA inhibited cell proliferation in response to high glucose or exogenous EGF. Therefore, these results link the Hippo pathway to EGFR-mediated renal epithelial injury in diabetes.10.1681/ASN.2015040415Fri, 09 Oct 2015 12:18:28 GMT-07:00Interaction of the EGF Receptor and the Hippo Pathway in the Diabetic KidneyActivation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein expression and phosphorylation were upregulated in diabetic mouse renal proximal tubule epithelial cells, which were inhibited in diabetic proximal tubule EGFR-knockout mice (EGFRptKO) or administration of an EGFR tyrosine kinase inhibitor erlotinib. Furthermore, activation of an EGFR-PI3K-Akt-CREB signaling pathway mediated YAP gene expression and YAP nuclear translocation and interaction with the TEA domain (TEAD) transcription factor complex, which led to upregulated expression of two TEAD-dependent genes, the connective tissue growth factor and amphiregulin genes. In a renal proximal tubule cell line, either pharmacologic or genetic inhibition of EGFR, Akt, or CREB blunted YAP expression in response to high-glucose treatment. Additionally, knocking down YAP expression by specific siRNA inhibited cell proliferation in response to high glucose or exogenous EGF. Therefore, these results link the Hippo pathway to EGFR-mediated renal epithelial injury in diabetes.Chen, JianchunHarris, Raymond C.2015-10-09T12:18:28-07:00doi:10.1681/ASN.2015040415hwp:resource-id:jnephrol;27/6/1689American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, cell signaling, epidermal growth factorBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150404151046-66731533-34502015-10-09T12:18:28-07:002016-06Journal of the American Society of NephrologyBasic Research27616891700
- Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD ProgressionAKI is increasingly recognized as a major risk factor for progression to CKD. However, the factors governing AKI to CKD progression are poorly understood. In this study, we investigated this issue using moderate (20 minutes) and severe (30 minutes) ischemia/reperfusion injury (IRI) in mice. Moderate IRI led to acute kidney failure and transient Wnt/β-catenin activation, which was followed by the restoration of kidney morphology and function. However, severe IRI resulted in sustained and exaggerated Wnt/β-catenin activation, which was accompanied by development of renal fibrotic lesions characterized by interstitial myofibroblast activation and excessive extracellular matrix deposition. To assess the role of sustained Wnt/β-catenin signaling in mediating AKI to CKD progression, we manipulated this signaling by overexpression of Wnt ligand or pharmacologic inhibition of β-catenin. In vivo, overexpression of Wnt1 at 5 days after IRI induced β-catenin activation and accelerated AKI to CKD progression. Conversely, blockade of Wnt/β-catenin by small molecule inhibitor ICG-001 at this point hindered AKI to CKD progression. In vitro, Wnt ligands induced renal interstitial fibroblast activation and promoted fibronectin expression. However, activated fibroblasts readily reverted to a quiescent phenotype after Wnt ligands were removed, suggesting that fibroblast activation requires persistent Wnt signaling. These results indicate that sustained, but not transient, activation of Wnt/β-catenin signaling has a decisive role in driving AKI to CKD progression.10.1681/ASN.2015040449Fri, 09 Oct 2015 12:18:29 GMT-07:00Sustained Activation of Wnt/β-Catenin Signaling Drives AKI to CKD ProgressionAKI is increasingly recognized as a major risk factor for progression to CKD. However, the factors governing AKI to CKD progression are poorly understood. In this study, we investigated this issue using moderate (20 minutes) and severe (30 minutes) ischemia/reperfusion injury (IRI) in mice. Moderate IRI led to acute kidney failure and transient Wnt/β-catenin activation, which was followed by the restoration of kidney morphology and function. However, severe IRI resulted in sustained and exaggerated Wnt/β-catenin activation, which was accompanied by development of renal fibrotic lesions characterized by interstitial myofibroblast activation and excessive extracellular matrix deposition. To assess the role of sustained Wnt/β-catenin signaling in mediating AKI to CKD progression, we manipulated this signaling by overexpression of Wnt ligand or pharmacologic inhibition of β-catenin. In vivo, overexpression of Wnt1 at 5 days after IRI induced β-catenin activation and accelerated AKI to CKD progression. Conversely, blockade of Wnt/β-catenin by small molecule inhibitor ICG-001 at this point hindered AKI to CKD progression. In vitro, Wnt ligands induced renal interstitial fibroblast activation and promoted fibronectin expression. However, activated fibroblasts readily reverted to a quiescent phenotype after Wnt ligands were removed, suggesting that fibroblast activation requires persistent Wnt signaling. These results indicate that sustained, but not transient, activation of Wnt/β-catenin signaling has a decisive role in driving AKI to CKD progression.Xiao, LiangxiangZhou, DongTan, Roderick J.Fu, HaiyanZhou, LiliHou, Fan FanLiu, Youhua2015-10-09T12:18:29-07:00doi:10.1681/ASN.2015040449hwp:resource-id:jnephrol;27/6/1727American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, CKD, ischemia-reperfusion, renal ischemia, fibroblastBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150404491046-66731533-34502015-10-09T12:18:29-07:002016-06Journal of the American Society of NephrologyBasic Research27617271740
- T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal ImpairmentReduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment.10.1681/ASN.2015050540Thu, 08 Oct 2015 10:32:18 GMT-07:00T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal ImpairmentReduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment.Dong, LeiNordlohne, JohannesGe, ShuwangHertel, BarbaraMelk, AnetteRong, SongHaller, Hermannvon Vietinghoff, Sibylle2015-10-08T10:32:18-07:00doi:10.1681/ASN.2015050540hwp:resource-id:jnephrol;27/6/1753American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriosclerosis, chemokine receptor, lymphocytesBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150505401046-66731533-34502015-10-08T10:32:18-07:002016-06Journal of the American Society of NephrologyBasic Research27617531764
- Long-Term Effects of Frequent In–Center HemodialysisThe Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in–center hemodialysis sessions per week for 12 months. As reported previously, frequent in–center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self–reported physical health. Here, we determined the long-term effects of the 12-month frequent in–center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%–90% range, 1.5–5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self–reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post–trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in–center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.10.1681/ASN.2015040426Wed, 14 Oct 2015 06:50:59 GMT-07:00Long-Term Effects of Frequent In–Center HemodialysisThe Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in–center hemodialysis sessions per week for 12 months. As reported previously, frequent in–center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self–reported physical health. Here, we determined the long-term effects of the 12-month frequent in–center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%–90% range, 1.5–5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self–reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post–trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in–center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.Chertow, Glenn M.Levin, Nathan W.Beck, Gerald J.Daugirdas, John T.Eggers, Paul W.Kliger, Alan S.Larive, BrettRocco, Michael V.Greene, Tom2015-10-14T06:50:59-07:00doi:10.1681/ASN.2015040426hwp:resource-id:jnephrol;27/6/1830American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, hemodialysis, clinical trialClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150404261046-66731533-34502015-10-14T06:50:59-07:002016-06Journal of the American Society of NephrologyClinical Research27618301836
- AKI after Transcatheter or Surgical Aortic Valve ReplacementTranscatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.10.1681/ASN.2015050577Tue, 20 Oct 2015 08:37:50 GMT-07:00AKI after Transcatheter or Surgical Aortic Valve ReplacementTranscatheter aortic valve replacement (TAVR) is an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis who are at high risk of perioperative mortality. Previous studies showed increased risk of postoperative AKI with TAVR, but it is unclear whether differences in patient risk profiles confounded the results. To conduct a propensity-matched study, we identified all adult patients undergoing isolated aortic valve replacement for aortic stenosis at Mayo Clinic Hospital in Rochester, Minnesota from January 1, 2008 to June 30, 2014. Using propensity score matching on the basis of clinical characteristics and preoperative variables, we compared the postoperative incidence of AKI, defined by Kidney Disease Improving Global Outcomes guidelines, and major adverse kidney events in patients treated with TAVR with that in patients treated with SAVR. Major adverse kidney events were the composite of in-hospital mortality, use of RRT, and persistent elevated serum creatinine ≥200% from baseline at hospital discharge. Of 1563 eligible patients, 195 matched pairs (390 patients) were created. In the matched cohort, baseline characteristics, including Society of Thoracic Surgeons risk score and eGFR, were comparable between the two groups. Furthermore, no significant differences existed between the TAVR and SAVR groups in postoperative AKI (24.1% versus 29.7%; P=0.21), major adverse kidney events (2.1% versus 1.5%; P=0.70), or mortality >6 months after surgery (6.0% versus 8.3%; P=0.51). Thus, TAVR did not affect postoperative AKI risk. Because it is less invasive than SAVR, TAVR may be preferred in high-risk individuals.Thongprayoon, CharatCheungpasitporn, WisitSrivali, NaratHarrison, Andrew M.Gunderson, Tina M.Kittanamongkolchai, WonngarmGreason, Kevin L.Kashani, Kianoush B.2015-10-20T08:37:50-07:00doi:10.1681/ASN.2015050577hwp:resource-id:jnephrol;27/6/1854American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, outcomes, cardiovascular diseaseClinical ResearchClinical Researchresearch-article20162016-06-01June 201610.1681/ASN.20150505771046-66731533-34502015-10-20T08:37:50-07:002016-06Journal of the American Society of NephrologyClinical Research27618541860
- Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone SynthesisDeficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate–limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/−) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency–induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/−) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency–induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis.10.1681/ASN.2015010093Thu, 15 Oct 2015 05:08:06 GMT-07:00Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone SynthesisDeficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate–limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/−) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency–induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/−) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency–induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis.Zhou, XiaoliChen, KaiWang, YongjunSchuman, MarianoLei, HanSun, Zhongjie2015-10-15T05:08:06-07:00doi:10.1681/ASN.2015010093hwp:resource-id:jnephrol;27/6/1765American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyBP, aldosterone, hypertension, immune complexes, kidney dysfunction, macrophagesBasic ResearchBasic Researchresearch-article20162016-06-01June 201610.1681/ASN.20150100931046-66731533-34502015-10-15T05:08:06-07:002016-06Journal of the American Society of NephrologyBasic Research27617651776
- Celebrating the ASN at 5010.1681/ASN.2016040445Tue, 03 May 2016 05:48:10 GMT-07:00Celebrating the ASN at 50Harris, Raymond C.Ibrahim, TodNath, Karl A.2016-05-03T05:48:10-07:00doi:10.1681/ASN.2016040445hwp:resource-id:jnephrol;27/6/1575American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyASN, History, 50Up Front MattersEditorialsUp Front MattersEditorialseditorial20162016-06-01June 201610.1681/ASN.20160404451046-66731533-34502016-05-03T05:48:10-07:002016-06Journal of the American Society of NephrologyUp Front Matters27615751576
- Cathepsin S–Dependent Protease–Activated Receptor-2 Activation: A New Mechanism of Endothelial Dysfunction10.1681/ASN.2015101162Fri, 20 Nov 2015 05:59:48 GMT-08:00Cathepsin S–Dependent Protease–Activated Receptor-2 Activation: A New Mechanism of Endothelial DysfunctionNikolic-Paterson, David J.2015-11-20T05:59:48-08:00doi:10.1681/ASN.2015101162hwp:resource-id:jnephrol;27/6/1577American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymacrophage, diabetic nephropathy, cathepsin S, PAR-2, therapyUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-06-01June 201610.1681/ASN.20151011621046-66731533-34502015-11-20T05:59:48-08:002016-06Journal of the American Society of NephrologyUp Front Matters27661577163515791649
- The Ever–Expanding Kidney Repair Shop10.1681/ASN.2015111207Mon, 07 Dec 2015 06:42:15 GMT-08:00The Ever–Expanding Kidney Repair ShopDekel, Benjamin2015-12-07T06:42:15-08:00doi:10.1681/ASN.2015111207hwp:resource-id:jnephrol;27/6/1579American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologystem cell, renal development, renal progenitor, pluripotent stem cells, cell therapy, metanephrosUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-06-01June 201610.1681/ASN.20151112071046-66731533-34502015-12-07T06:42:15-08:002016-06Journal of the American Society of NephrologyUp Front Matters27661579177815811791
- HLA-DQ Mismatches and Rejection in Kidney Transplant Recipients10.2215/CJN.11641115Thu, 31 Mar 2016 06:46:06 GMT-07:00HLA-DQ Mismatches and Rejection in Kidney Transplant RecipientsLim, Wai H.Chapman, Jeremy R.Coates, Patrick T.Lewis, Joshua R.Russ, Graeme R.Watson, NarelleHoldsworth, RhondaWong, Germaine2016-03-31T06:46:06-07:00doi:10.2215/CJN.11641115hwp:resource-id:clinjasn;11/5/875American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and outcomes, HLA-matching, registry, acute allograft rejection, kidney transplantation, Allografts, HLA Antigens, Humans, immunosuppression, renal dialysisOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-05-06May 06, 201610.2215/CJN.116411151555-90411555-905X2016-03-31T06:46:06-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles1155875759883760
- HLA-DQ Mismatching: Mounting Evidence for a Role in Kidney Transplant Rejection10.2215/CJN.02970316Thu, 31 Mar 2016 06:46:07 GMT-07:00HLA-DQ Mismatching: Mounting Evidence for a Role in Kidney Transplant RejectionSarabu, NagarajuHricik, Donald E.2016-03-31T06:46:07-07:00doi:10.2215/CJN.02970316hwp:resource-id:clinjasn;11/5/759American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute allograft rejection, kidney transplantation, human genetics, humans, Graft Rejection, HLA-DQ Antigens, Kidney DiseasesEditorialsEditorialseditorial20162016-05-06May 06, 201610.2215/CJN.029703161555-90411555-905X2016-03-31T06:46:07-07:002016-05-06Clinical Journal of the American Society of NephrologyEditorials1155759875760883
- Apoprotein B/Apoprotein A-1 Ratio and Mortality among Prevalent Dialysis Patients10.2215/CJN.09830915Mon, 15 Feb 2016 06:59:30 GMT-08:00Apoprotein B/Apoprotein A-1 Ratio and Mortality among Prevalent Dialysis PatientsSato, YujiFujimoto, ShouichiToida, TatsunoriNakagawa, HidetoYamashita, YasuhiroIwakiri, TakashiFukuda, AkihiroIwatsubo, Shuji2016-02-15T06:59:30-08:00doi:10.2215/CJN.09830915hwp:resource-id:clinjasn;11/5/840American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyApoprotein, hemodialysis, cardiovascular disease, mortality, blood pressure, C-Reactive Protein, Humans, Kidney Diseases, Prospective Studies, Regression AnalysisOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-05-06May 06, 201610.2215/CJN.098309151555-90411555-905X2016-02-15T06:59:30-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115840846
- Association of Plasminuria with Overhydration in Patients with CKD10.2215/CJN.12261115Tue, 01 Mar 2016 06:43:37 GMT-08:00Association of Plasminuria with Overhydration in Patients with CKDSchork, AnjaWoern, MatthiasKalbacher, HubertVoelter, WolfgangNacken, ReginaBertog, MarkoHaerteis, SilkeKorbmacher, ChristophHeyne, NilsPeter, AndreasHäring, Hans-UlrichArtunc, Ferruh2016-03-01T06:43:37-08:00doi:10.2215/CJN.12261115hwp:resource-id:clinjasn;11/5/761American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, proteinuria, Plasminuria, Overhydration, body composition monitor, epithelial sodium channel, plasmin, Edema, Humans, PlasminogenOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-05-06May 06, 201610.2215/CJN.122611151555-90411555-905X2016-03-01T06:43:37-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115761769
- Early Requirement for RRT in Children at Presentation in the United Kingdom: Association with Transplantation and Survival10.2215/CJN.08190815Mon, 15 Feb 2016 06:59:31 GMT-08:00Early Requirement for RRT in Children at Presentation in the United Kingdom: Association with Transplantation and SurvivalPruthi, RishiCasula, AnnaInward, CarolRoderick, PaulSinha, Manish D.2016-02-15T06:59:31-08:00doi:10.2215/CJN.08190815hwp:resource-id:clinjasn;11/5/795American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, child, late referral, follow-up studies, humans, kidney transplantation, living donors, renal dialysis, renal replacement therapyOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.081908151555-90411555-905X2016-02-15T06:59:31-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115795802
- Age and Outcomes Associated with BP in Patients with Incident CKD10.2215/CJN.08660815Thu, 21 Apr 2016 06:58:07 GMT-07:00Age and Outcomes Associated with BP in Patients with Incident CKDKovesdy, Csaba P.Alrifai, AhmedGosmanova, Elvira O.Lu, Jun LingCanada, Robert B.Wall, Barry M.Hung, Adriana M.Molnar, Miklos Z.Kalantar-Zadeh, Kamyar2016-04-21T06:58:07-07:00doi:10.2215/CJN.08660815hwp:resource-id:clinjasn;11/5/821American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical epidemiology, chronic kidney disease, blood pressure, follow-up studies, humans, hypertension, incidence, kidney failure, chronic, renal insufficiency, chronic, risk factorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-05-06May 06, 201610.2215/CJN.086608151555-90411555-905X2016-04-21T06:58:07-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles1155821753831755
- Height at First RRT and Mortality in Children10.2215/CJN.08250815Tue, 01 Mar 2016 06:43:38 GMT-08:00Height at First RRT and Mortality in ChildrenKu, ElaineFine, Richard N.Hsu, Chi-yuanMcCulloch, CharlesGlidden, David V.Grimes, BarbaraJohansen, Kirsten L.2016-03-01T06:43:38-08:00doi:10.2215/CJN.08250815hwp:resource-id:clinjasn;11/5/832American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyheight, growth failure, pediatric ESRD, body height, body mass index, child, follow-up studies, humans, renal dialysis, renal replacement therapyOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-05-06May 06, 201610.2215/CJN.082508151555-90411555-905X2016-03-01T06:43:38-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115832839
- American Society of Nephrology Quiz and Questionnaire 2015: Glomerular DiseasesThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories, along with single-best-answer questions, were prepared and submitted by the panel of experts. Before the meeting, training program directors of United States nephrology fellowship programs and nephrology fellows answered the questions through an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special app with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.10.2215/CJN.12871215Thu, 04 Feb 2016 06:46:00 GMT-08:00American Society of Nephrology Quiz and Questionnaire 2015: Glomerular DiseasesThe Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories, along with single-best-answer questions, were prepared and submitted by the panel of experts. Before the meeting, training program directors of United States nephrology fellowship programs and nephrology fellows answered the questions through an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special app with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions.Bomback, Andrew S.Perazella, Mark A.Choi, Michael J.2016-02-04T06:46:00-08:00doi:10.2215/CJN.12871215hwp:resource-id:clinjasn;11/5/884American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney diseases, kidney failure, chronic, kidney transplantation, renal dialysis, renal insufficiency, chronic, surveys and questionnaires, glomerular disease, focal segmental glomerulosclerosis, Henoch-Schonlein purpura, kidneySpecial FeatureSpecial Featureresearch-article20162016-05-06May 06, 201610.2215/CJN.128712151555-90411555-905X2016-02-04T06:46:00-08:002016-05-06Clinical Journal of the American Society of NephrologySpecial Feature11115888415138901513
- How to Begin a Quality Improvement ProjectQuality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.10.2215/CJN.11491015Fri, 25 Mar 2016 06:43:18 GMT-07:00How to Begin a Quality Improvement ProjectQuality improvement involves a combined effort among health care staff and stakeholders to diagnose and treat problems in the health care system. However, health care professionals often lack training in quality improvement methods, which makes it challenging to participate in improvement efforts. This article familiarizes health care professionals with how to begin a quality improvement project. The initial steps involve forming an improvement team that possesses expertise in the quality of care problem, leadership, and change management. Stakeholder mapping and analysis are useful tools at this stage, and these are reviewed to help identify individuals who might have a vested interest in the project. Physician engagement is a particularly important component of project success, and the knowledge that patients/caregivers can offer as members of a quality improvement team should not be overlooked. After a team is formed, an improvement framework helps to organize the scientific process of system change. Common quality improvement frameworks include Six Sigma, Lean, and the Model for Improvement. These models are contrasted, with a focus on the Model for Improvement, because it is widely used and applicable to a variety of quality of care problems without advanced training. It involves three steps: setting aims to focus improvement, choosing a balanced set of measures to determine if improvement occurs, and testing new ideas to change the current process. These new ideas are evaluated using Plan-Do-Study-Act cycles, where knowledge is gained by testing changes and reflecting on their effect. To show the real world utility of the quality improvement methods discussed, they are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis). This provides an example that kidney health care professionals can use to begin their own quality improvement projects.Silver, Samuel A.Harel, ZivMcQuillan, RoryWeizman, Adam V.Thomas, AlisonChertow, Glenn M.Nesrallah, GihadBell, Chaim M.Chan, Christopher T.2016-03-25T06:43:18-07:00doi:10.2215/CJN.11491015hwp:resource-id:clinjasn;11/5/893American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical nephrology, end stage kidney disease, Delivery of Health Care, Hemodialysis, Home, Humans, Leadership, Quality Improvement, renal dialysis, Total Quality ManagementMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.114910151555-90411555-905X2016-03-25T06:43:18-07:002016-05-06Clinical Journal of the American Society of NephrologyMoving Points in Nephrology115893900
- How to Measure and Interpret Quality Improvement DataThis article will demonstrate how to conduct a quality improvement project using the change idea generated in “How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem” by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan–Do–Study–Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.10.2215/CJN.11511015Fri, 25 Mar 2016 06:43:18 GMT-07:00How to Measure and Interpret Quality Improvement DataThis article will demonstrate how to conduct a quality improvement project using the change idea generated in “How To Use Quality Improvement Tools in Clinical Practice: How To Diagnose Solutions to a Quality of Care Problem” by Dr. Ziv Harel and colleagues in this Moving Points feature. This change idea involves the introduction of a nurse educator into a CKD clinic with a goal of increasing rates of patients performing dialysis independently at home (home hemodialysis or peritoneal dialysis). Using this example, we will illustrate a Plan–Do–Study–Act (PDSA) cycle in action and highlight the principles of rapid cycle change methodology. We will then discuss the selection of outcome, process, and balancing measures, and the practicalities of collecting these data in the clinic environment. We will also introduce the PDSA worksheet as a practical way to oversee the progress of a quality improvement project. Finally, we will demonstrate how run charts are used to visually illustrate improvement in real time, and how this information can be used to validate achievement, respond appropriately to challenges the project may encounter, and prove the significance of results. This article aims to provide readers with a clear and practical framework upon which to trial their own ideas for quality improvement in the clinical setting.McQuillan, Rory FrancisSilver, Samuel AdamHarel, ZivWeizman, AdamThomas, AlisonBell, ChaimChertow, Glenn M.Chan, Christopher T.Nesrallah, Gihad2016-03-25T06:43:18-07:00doi:10.2215/CJN.11511015hwp:resource-id:clinjasn;11/5/908American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHome Dialysis, Model for Improvement, Quality Improvement, Run chart, Ambulatory Care Facilities, Goals, Humans, peritoneal dialysis, renal dialysis, Renal Insufficiency, ChronicMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.115110151555-90411555-905X2016-03-25T06:43:18-07:002016-05-06Clinical Journal of the American Society of NephrologyMoving Points in Nephrology115908914
- The Continued Quest for Optimal BP Targets in Older Adults with Kidney Disease10.2215/CJN.03100316Thu, 21 Apr 2016 06:58:07 GMT-07:00The Continued Quest for Optimal BP Targets in Older Adults with Kidney DiseaseWeiss, Jessica W.2016-04-21T06:58:07-07:00doi:10.2215/CJN.03100316hwp:resource-id:clinjasn;11/5/753American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal disease, blood pressure, elderly, Adult, Blood Pressure Determination, Humans, Kidney DiseasesEditorialsEditorialseditorial20162016-05-06May 06, 201610.2215/CJN.031003161555-90411555-905X2016-04-21T06:58:07-07:002016-05-06Clinical Journal of the American Society of NephrologyEditorials1155753821755831
- Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-410.2215/CJN.09900915Mon, 22 Feb 2016 06:48:48 GMT-08:00Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4Ruggenenti, PieroGentile, GiorgioPerico, NorbertoPerna, AnnalisaBarcella, LucaTrillini, MatiasCortinovis, MonicaFerrer Siles, Claudia PatriciaReyes Loaeza, Jorge ArturoAparicio, Maria CarolinaFasolini, GiorgioGaspari, FlavioMartinetti, DavideCarrara, FabiolaRubis, NadiaPrandini, SilviaCaroli, AnnaSharma, KanishkaAntiga, LucaRemuzzi, AndreaRemuzzi, Giuseppe2016-02-22T06:48:48-08:00doi:10.2215/CJN.09900915hwp:resource-id:clinjasn;11/5/785American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrandomized controlled trials, sirolimus, kidney failure, chronic, adverse effects, proteinuria, Adult, Humans, Polycystic Kidney, Autosomal Dominant, Prospective Studies, Renal InsufficiencyOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.099009151555-90411555-905X2016-02-22T06:48:48-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115785794
- In–Center Nutrition Practices of Clinics within a Large Hemodialysis Provider in the United States10.2215/CJN.09270915Fri, 15 Apr 2016 09:07:57 GMT-07:00In–Center Nutrition Practices of Clinics within a Large Hemodialysis Provider in the United StatesBenner, DebbieBurgess, MaryStasios, MariaBrosch, BeckyWilund, KenShen, SaKistler, Brandon2016-04-15T09:07:57-07:00doi:10.2215/CJN.09270915hwp:resource-id:clinjasn;11/5/770American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, blood pressure, hemodialysis, hypotension, follow-up studies, humans, logistic models, nutritional status, renal dialysis, United StatesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.092709151555-90411555-905X2016-04-15T09:07:57-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles1155770747775749
- How to Diagnose Solutions to a Quality of Care ProblemTo change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.10.2215/CJN.11481015Fri, 25 Mar 2016 06:43:16 GMT-07:00How to Diagnose Solutions to a Quality of Care ProblemTo change a particular quality of care outcome within a system, quality improvement initiatives must first understand the causes contributing to the outcome. After the causes of a particular outcome are known, changes can be made to address these causes and change the outcome. Using the example of home dialysis (home hemodialysis and peritoneal dialysis), this article within this Moving Points feature on quality improvement will provide health care professionals with the tools necessary to analyze the steps contributing to certain outcomes in health care quality and develop ideas that will ultimately lead to their resolution. The tools used to identify the main contributors to a quality of care outcome will be described, including cause and effect diagrams, Pareto analysis, and process mapping. We will also review common change concepts and brainstorming activities to identify effective change ideas. These methods will be applied to our home dialysis quality improvement project, providing a practical example that other kidney health care professionals can replicate at their local centers.Harel, ZivSilver, Samuel A.McQuillan, Rory F.Weizman, Adam V.Thomas, AlisonChertow, Glenn M.Nesrallah, GihadChan, Christopher T.Bell, Chaim M.2016-03-25T06:43:16-07:00doi:10.2215/CJN.11481015hwp:resource-id:clinjasn;11/5/901American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChange ideas, Root cause analysis, Home dialysis, Quality improvement, Health Personnel, Humans, kidney, peritoneal dialysis, Quality of Health Care, renal dialysisMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.114810151555-90411555-905X2016-03-25T06:43:16-07:002016-05-06Clinical Journal of the American Society of NephrologyMoving Points in Nephrology115901907
- Optimal Approach for the Diagnosis of Hemodialysis Catheter–Related Bacteremia10.2215/CJN.02910316Fri, 01 Apr 2016 06:30:13 GMT-07:00Optimal Approach for the Diagnosis of Hemodialysis Catheter–Related BacteremiaJohns, Tanya S.Mokrzycki, Michele H.2016-04-01T06:30:13-07:00doi:10.2215/CJN.02910316hwp:resource-id:clinjasn;11/5/756American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycatheter, bacteremia, hemodialysis access, sepsis, infection, diagnosis, blood cultures, dialysis access, hemocatheter, Catheterization, renal dialysisEditorialsEditorialseditorial20162016-05-06May 06, 201610.2215/CJN.029103161555-90411555-905X2016-04-01T06:30:13-07:002016-05-06Clinical Journal of the American Society of NephrologyEditorials1155756847758854
- Peanuts or Pretzels? Changing Attitudes about Eating on Hemodialysis10.2215/CJN.03050316Fri, 15 Apr 2016 09:07:56 GMT-07:00Peanuts or Pretzels? Changing Attitudes about Eating on HemodialysisFranch, Harold2016-04-15T09:07:56-07:00doi:10.2215/CJN.03050316hwp:resource-id:clinjasn;11/5/747American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, Protein energy wasting, hemodialysis, hypotension, dietitian, Attitude, Eating, Food, renal dialysisEditorialsEditorialseditorial20162016-05-06May 06, 201610.2215/CJN.030503161555-90411555-905X2016-04-15T09:07:56-07:002016-05-06Clinical Journal of the American Society of NephrologyEditorials1155674777010547497751062
- How to Use Quality Improvement Tools in Clinical Practice: A Primer for Nephrologists10.2215/CJN.11521015Fri, 25 Mar 2016 06:43:17 GMT-07:00How to Use Quality Improvement Tools in Clinical Practice: A Primer for NephrologistsChan, Christopher T.Chertow, Glenn M.Nesrallah, GihadBell, Chaim M.2016-03-25T06:43:17-07:00doi:10.2215/CJN.11521015hwp:resource-id:clinjasn;11/5/891American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytools, primer, primary health care, quality assurance, health care, quality improvementMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.115210151555-90411555-905X2016-03-25T06:43:17-07:002016-05-06Clinical Journal of the American Society of NephrologyMoving Points in Nephrology115891892
- Provider Perspectives on Advance Care Planning for Patients with Kidney Disease: Whose Job Is It Anyway?10.2215/CJN.11351015Fri, 15 Apr 2016 09:07:56 GMT-07:00Provider Perspectives on Advance Care Planning for Patients with Kidney Disease: Whose Job Is It Anyway?O’Hare, Ann M.Szarka, JackieMcFarland, Lynne V.Taylor, Janelle S.Sudore, Rebecca L.Trivedi, RanakReinke, Lynn F.Vig, Elizabeth K.2016-04-15T09:07:56-07:00doi:10.2215/CJN.11351015hwp:resource-id:clinjasn;11/5/855American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, advance care planning, care complexity, multidisciplinary, end-of-life, communication, cooperative behavior, decision making, grounded theory, humans, renal dialysisOriginal ArticlesHealth Services ResearchOriginal ArticlesHealth Services Researchresearch-article20162016-05-06May 06, 201610.2215/CJN.113510151555-90411555-905X2016-04-15T09:07:56-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles1155855750866752
- Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKD10.2215/CJN.09690915Thu, 07 Apr 2016 07:28:43 GMT-07:00Immunogenicity of Human Papillomavirus Recombinant Vaccine in Children with CKDNelson, Delphine R.Neu, Alicia M.Abraham, AlisonAmaral, SandraBatisky, DonaldFadrowski, Jeffrey J.2016-04-07T07:28:43-07:00doi:10.2215/CJN.09690915hwp:resource-id:clinjasn;11/5/776American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, clinical immunology, kidney transplantation, renal dialysis, immunosuppression, Antibody Formation, Child, Humans, Papillomavirus Infections, Papillomavirus VaccinesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.096909151555-90411555-905X2016-04-07T07:28:43-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115776784
- Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial10.2215/CJN.06300615Tue, 23 Feb 2016 07:34:40 GMT-08:00Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 TrialTorres, Vicente E.Higashihara, EijiDevuyst, OlivierChapman, Arlene B.Gansevoort, Ronald T.Grantham, Jared J.Perrone, Ronald D.Ouyang, JohnBlais, Jaime D.Czerwiec, Frank S.2016-02-23T07:34:40-08:00doi:10.2215/CJN.06300615hwp:resource-id:clinjasn;11/5/803American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, chronic kidney disease, albuminuria, glomerular filtration rate, humans, pain, polycystic kidney, autosomal dominant, receptors, vasopressin, renal insufficiency, chronic, tolvaptanOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.063006151555-90411555-905X2016-02-23T07:34:40-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115803811
- Nighttime BP in Elderly Individuals with Prediabetes/Diabetes with and without CKD: The HEIJO-KYO Study10.2215/CJN.07700715Thu, 25 Feb 2016 07:14:56 GMT-08:00Nighttime BP in Elderly Individuals with Prediabetes/Diabetes with and without CKD: The HEIJO-KYO StudyObayashi, KenjiSaeki, KeigoKurumatani, Norio2016-02-25T07:14:56-08:00doi:10.2215/CJN.07700715hwp:resource-id:clinjasn;11/5/867American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, diabetes, Epidemiology and outcomes, hypertension, Cross-Sectional Studies, diabetes mellitus, Humans, Prediabetic State, Renal Insufficiency, Chronic, SmokingOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20162016-05-06May 06, 201610.2215/CJN.077007151555-90411555-905X2016-02-25T07:14:56-08:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles115867874
- Evaluating Approaches for the Diagnosis of Hemodialysis Catheter–Related Bloodstream Infections10.2215/CJN.09110815Fri, 01 Apr 2016 06:30:12 GMT-07:00Evaluating Approaches for the Diagnosis of Hemodialysis Catheter–Related Bloodstream InfectionsQuittnat Pelletier, FriederikeJoarder, MohammadPoutanen, Susan M.Lok, Charmaine E.2016-04-01T06:30:12-07:00doi:10.2215/CJN.09110815hwp:resource-id:clinjasn;11/5/847American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybacteremia, indwelling catheters, sensitivity and specificity, catheter-related infections, catheterization, catheters, indwelling, humans, phlebotomy, renal dialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-05-06May 06, 201610.2215/CJN.091108151555-90411555-905X2016-04-01T06:30:12-07:002016-05-06Clinical Journal of the American Society of NephrologyOriginal Articles1155847756854758
- How to Sustain Change and Support Continuous Quality ImprovementTo achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).10.2215/CJN.11501015Fri, 25 Mar 2016 06:43:17 GMT-07:00How to Sustain Change and Support Continuous Quality ImprovementTo achieve sustainable change, quality improvement initiatives must become the new way of working rather than something added on to routine clinical care. However, most organizational change is not maintained. In this next article in this Moving Points in Nephrology feature on quality improvement, we provide health care professionals with strategies to sustain and support quality improvement. Threats to sustainability may be identified both at the beginning of a project and when it is ready for implementation. The National Health Service Sustainability Model is reviewed as one example to help identify issues that affect long-term success of quality improvement projects. Tools to help sustain improvement include process control boards, performance boards, standard work, and improvement huddles. Process control and performance boards are methods to communicate improvement results to staff and leadership. Standard work is a written or visual outline of current best practices for a task and provides a framework to ensure that changes that have improved patient care are consistently and reliably applied to every patient encounter. Improvement huddles are short, regular meetings among staff to anticipate problems, review performance, and support a culture of improvement. Many of these tools rely on principles of visual management, which are systems transparent and simple so that every staff member can rapidly distinguish normal from abnormal working conditions. Even when quality improvement methods are properly applied, the success of a project still depends on contextual factors. Context refers to aspects of the local setting in which the project operates. Context affects resources, leadership support, data infrastructure, team motivation, and team performance. For these reasons, the same project may thrive in a supportive context and fail in a different context. To demonstrate the practical applications of these quality improvement principles, these principles are applied to a hypothetical quality improvement initiative that aims to promote home dialysis (home hemodialysis and peritoneal dialysis).Silver, Samuel A.McQuillan, RoryHarel, ZivWeizman, Adam V.Thomas, AlisonNesrallah, GihadBell, Chaim M.Chan, Christopher T.Chertow, Glenn M.2016-03-25T06:43:17-07:00doi:10.2215/CJN.11501015hwp:resource-id:clinjasn;11/5/916American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend stage kidney disease, chronic kidney disease, clinical nephrology, health resources, hemodialysis, home, humans, organizational innovation, peritoneal dialysis, quality improvement, renal dialysisMoving Points in NephrologyMoving Points in Nephrologyresearch-article20162016-05-06May 06, 201610.2215/CJN.115010151555-90411555-905X2016-03-25T06:43:17-07:002016-05-06Clinical Journal of the American Society of NephrologyMoving Points in Nephrology115916924
- The Provider’s Role in Conservative Care and Advance Care Planning for Patients with ESRD10.2215/CJN.03150316Fri, 15 Apr 2016 09:07:54 GMT-07:00The Provider’s Role in Conservative Care and Advance Care Planning for Patients with ESRDObrador, Gregorio T.2016-04-15T09:07:54-07:00doi:10.2215/CJN.03150316hwp:resource-id:clinjasn;11/5/750American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyadvance care planning, conservative care, Humans, Kidney Failure, Chronic, renal dialysisEditorialsEditorialseditorial20162016-05-06May 06, 201610.2215/CJN.031503161555-90411555-905X2016-04-15T09:07:54-07:002016-05-06Clinical Journal of the American Society of NephrologyEditorials11555750812855752820866
- The Obesity Paradox and the Role of Inflammation10.1681/ASN.2015101116Mon, 23 Nov 2015 05:54:36 GMT-08:00The Obesity Paradox and the Role of InflammationDrechsler, ChristianeWanner, Christoph2015-11-23T05:54:36-08:00doi:10.1681/ASN.2015101116hwp:resource-id:jnephrol;27/5/1270American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyobesity, chronic dialysis, chronic inflammationUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-05-01May 201610.1681/ASN.20151011161046-66731533-34502015-11-23T05:54:36-08:002016-05Journal of the American Society of NephrologyUp Front Matters27551270147912721486
- Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase GlomerulonephritisObservations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4+ effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV.10.1681/ASN.2014090906Tue, 15 Sep 2015 04:07:45 GMT-07:00Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase GlomerulonephritisObservations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4+ effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV.Gan, Poh-YiO’Sullivan, Kim M.Ooi, Joshua D.Alikhan, Maliha A.Odobasic, DraganaSummers, Shaun A.Kitching, A. RichardHoldsworth, Stephen R.2015-09-15T16:07:45-07:00doi:10.1681/ASN.2014090906hwp:resource-id:jnephrol;27/5/1321American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20140909061046-66731533-34502015-09-15T16:07:45-07:002016-05Journal of the American Society of NephrologyBasic Research27513211333
- Partial Complement Factor H Deficiency Associates with C3 Glomerulopathy and Thrombotic MicroangiopathyThe complement–mediated renal diseases C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) strongly associate with inherited and acquired abnormalities in the regulation of the complement alternative pathway (AP). The major negative regulator of the AP is the plasma protein complement factor H (FH). Abnormalities in FH result in uncontrolled activation of C3 through the AP and associate with susceptibility to both C3G and aHUS. Although previously developed FH–deficient animal models have provided important insights into the mechanisms underlying susceptibility to these unique phenotypes, these models do not entirely reproduce the clinical observations. FH is predominantly synthesized in the liver. We generated mice with hepatocyte–specific FH deficiency and showed that these animals have reduced plasma FH levels with secondary reduction in plasma C3. Unlike mice with complete FH deficiency, hepatocyte–specific FH–deficient animals developed neither plasma C5 depletion nor accumulation of C3 along the glomerular basement membrane. In contrast, subtotal FH deficiency associated with mesangial C3 accumulation consistent with C3G. Although there was no evidence of spontaneous thrombotic microangiopathy, the hepatocyte–specific FH–deficient animals developed severe C5–dependent thrombotic microangiopathy after induction of complement activation within the kidney by accelerated serum nephrotoxic nephritis. Taken together, our data indicate that subtotal FH deficiency can give rise to either spontaneous C3G or aHUS after a complement-activating trigger within the kidney and that the latter is C5 dependent.10.1681/ASN.2015030295Tue, 15 Sep 2015 04:07:46 GMT-07:00Partial Complement Factor H Deficiency Associates with C3 Glomerulopathy and Thrombotic MicroangiopathyThe complement–mediated renal diseases C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) strongly associate with inherited and acquired abnormalities in the regulation of the complement alternative pathway (AP). The major negative regulator of the AP is the plasma protein complement factor H (FH). Abnormalities in FH result in uncontrolled activation of C3 through the AP and associate with susceptibility to both C3G and aHUS. Although previously developed FH–deficient animal models have provided important insights into the mechanisms underlying susceptibility to these unique phenotypes, these models do not entirely reproduce the clinical observations. FH is predominantly synthesized in the liver. We generated mice with hepatocyte–specific FH deficiency and showed that these animals have reduced plasma FH levels with secondary reduction in plasma C3. Unlike mice with complete FH deficiency, hepatocyte–specific FH–deficient animals developed neither plasma C5 depletion nor accumulation of C3 along the glomerular basement membrane. In contrast, subtotal FH deficiency associated with mesangial C3 accumulation consistent with C3G. Although there was no evidence of spontaneous thrombotic microangiopathy, the hepatocyte–specific FH–deficient animals developed severe C5–dependent thrombotic microangiopathy after induction of complement activation within the kidney by accelerated serum nephrotoxic nephritis. Taken together, our data indicate that subtotal FH deficiency can give rise to either spontaneous C3G or aHUS after a complement-activating trigger within the kidney and that the latter is C5 dependent.Vernon, Katherine A.Ruseva, Marieta M.Cook, H. TerenceBotto, MarinaMalik, Talat H.Pickering, Matthew C.2015-09-15T16:07:46-07:00doi:10.1681/ASN.2015030295hwp:resource-id:jnephrol;27/5/1334American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, GN, immunology, thrombosis, transgenic mouseBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150302951046-66731533-34502015-09-15T16:07:46-07:002016-05Journal of the American Society of NephrologyBasic Research27513341342
- Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant OutcomesAssessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m2. In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.10.1681/ASN.2015040345Tue, 15 Sep 2015 04:07:47 GMT-07:00Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant OutcomesAssessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m2. In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.Reese, Peter P.Hall, Isaac E.Weng, Francis L.Schröppel, BerndDoshi, Mona D.Hasz, Rick D.Thiessen-Philbrook, HeatherFicek, JosephRao, VeenaMurray, PatrickLin, HaiqunParikh, Chirag R.2015-09-15T16:07:47-07:00doi:10.1681/ASN.2015040345hwp:resource-id:jnephrol;27/5/1534American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cadaver organ transplantation, delayed graft functionClinical ResearchClinical Researchresearch-article20162016-05-01May 201610.1681/ASN.20150403451046-66731533-34502015-09-15T16:07:47-07:002016-05Journal of the American Society of NephrologyClinical Research27515341543
- Amniotic Fluid Stem Cells within Chimeric Kidney Rudiments Differentiate to Functional Podocytes after Transplantation into Mature Rat Kidneys10.1681/ASN.2015101115Thu, 29 Oct 2015 06:08:30 GMT-07:00Amniotic Fluid Stem Cells within Chimeric Kidney Rudiments Differentiate to Functional Podocytes after Transplantation into Mature Rat KidneysWilm, BettinaMurray, Patricia2015-10-29T06:08:30-07:00doi:10.1681/ASN.2015101115hwp:resource-id:jnephrol;27/5/1266American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychimeric kidney rudiments, podocytes, AFSCsUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-05-01May 201610.1681/ASN.20151011151046-66731533-34502015-10-29T06:08:30-07:002016-05Journal of the American Society of NephrologyUp Front Matters27551266140012681411
- CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk PatientsMost morbidity associated with malignancy in long-term renal transplant recipients is due to cutaneous squamous cell carcinoma (SCC). Previously identified measures to stratify SCC risk have limited use, however. We hypothesized that an increased proportion of senescent, terminally differentiated CD8+ T cells would identify renal transplant recipients at elevated SCC risk. Peripheral blood lymphocytes were isolated from 117 stable transplant recipients at high risk of SCC and analyzed phenotypically by flow cytometry. Participants were followed up prospectively for SCC development. The predictive value of variables was assessed using Cox regression. Age at transplant and enrollment, dialysis duration, and previous disease were predictive of SCC development during follow-up. Previously published clinical phenotype-based risk scores lost predictive value with the removal of age as a covariate. The percentage of CD57-expressing CD8+ T cells was the strongest immunologic predictor of future SCC and correlated with increasing CD8+ T cell differentiation. We dichotomized participants into those with a majority (CD57hi) and a minority (CD57lo) of CD8+ T cells expressing CD57; CD57hi participants were more likely to develop SCC during follow-up (hazard ratio, 2.9; 95% confidence interval, 1.0 to 8.0), independent of potential confounders, and tended to develop earlier recurrence. The CD57hi phenotype was stable with time and associated with increasing age and cytomegalovirus seropositivity. Our results show that the CD57hi phenotype is a strong predictor of SCC development and recurrence in this cohort of long-term, high-risk renal transplant recipients. This information may allow identification of recipients who may benefit from intensive dermatologic screening and immunosuppression reduction.10.1681/ASN.2015030250Thu, 12 Nov 2015 07:53:34 GMT-08:00CD8+ Immunosenescence Predicts Post-Transplant Cutaneous Squamous Cell Carcinoma in High-Risk PatientsMost morbidity associated with malignancy in long-term renal transplant recipients is due to cutaneous squamous cell carcinoma (SCC). Previously identified measures to stratify SCC risk have limited use, however. We hypothesized that an increased proportion of senescent, terminally differentiated CD8+ T cells would identify renal transplant recipients at elevated SCC risk. Peripheral blood lymphocytes were isolated from 117 stable transplant recipients at high risk of SCC and analyzed phenotypically by flow cytometry. Participants were followed up prospectively for SCC development. The predictive value of variables was assessed using Cox regression. Age at transplant and enrollment, dialysis duration, and previous disease were predictive of SCC development during follow-up. Previously published clinical phenotype-based risk scores lost predictive value with the removal of age as a covariate. The percentage of CD57-expressing CD8+ T cells was the strongest immunologic predictor of future SCC and correlated with increasing CD8+ T cell differentiation. We dichotomized participants into those with a majority (CD57hi) and a minority (CD57lo) of CD8+ T cells expressing CD57; CD57hi participants were more likely to develop SCC during follow-up (hazard ratio, 2.9; 95% confidence interval, 1.0 to 8.0), independent of potential confounders, and tended to develop earlier recurrence. The CD57hi phenotype was stable with time and associated with increasing age and cytomegalovirus seropositivity. Our results show that the CD57hi phenotype is a strong predictor of SCC development and recurrence in this cohort of long-term, high-risk renal transplant recipients. This information may allow identification of recipients who may benefit from intensive dermatologic screening and immunosuppression reduction.Bottomley, Matthew J.Harden, Paul N.Wood, Kathryn J.2015-11-12T07:53:34-08:00doi:10.1681/ASN.2015030250hwp:resource-id:jnephrol;27/5/1505American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycancer, risk factors, renal transplantation, immunology, cytomegalovirusClinical ResearchClinical Researchresearch-article20162016-05-01May 201610.1681/ASN.20150302501046-66731533-34502015-11-12T07:53:34-08:002016-05Journal of the American Society of NephrologyClinical Research27551505127215151275
- A Systematic Method for Categorizing GN10.1681/ASN.2015101160Tue, 24 Nov 2015 06:38:52 GMT-08:00A Systematic Method for Categorizing GNJohnson, Richard J.Shankland, Stuart J.Lucia, M. Scott2015-11-24T06:38:52-08:00doi:10.1681/ASN.2015101160hwp:resource-id:jnephrol;27/5/1265American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, nephritis, kidney diseaseUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-05-01May 201610.1681/ASN.20151011601046-66731533-34502015-11-24T06:38:52-08:002016-05Journal of the American Society of NephrologyUp Front Matters27551265127812661287
- G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and DiabetesObesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined the regulation and role of the G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN). Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68 macrophage infiltration in the kidney. INT-777 also induced renal expression of master regulators of mitochondrial biogenesis, inhibitors of oxidative stress, and inducers of fatty acid β-oxidation, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of the increased acetylation of mitochondrial superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly, INT-777 decreased mitochondrial H2O2 generation and increased the activity of SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric acid reactive substances. Furthermore, INT-777 decreased renal lipid accumulation. INT-777 also prevented kidney disease in mice with diet-induced obesity. In human podocytes cultured with high glucose, INT-777 induced mitochondrial biogenesis, decreased oxidative stress, and increased fatty acid β-oxidation. Compared with normal kidney biopsy specimens, kidney specimens from patients with established ORG or DN expressed significantly less TGR5 mRNA, and levels inversely correlated with disease progression. Our results indicate that TGR5 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes.10.1681/ASN.2014121271Wed, 30 Sep 2015 05:41:37 GMT-07:00G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and DiabetesObesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined the regulation and role of the G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN). Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68 macrophage infiltration in the kidney. INT-777 also induced renal expression of master regulators of mitochondrial biogenesis, inhibitors of oxidative stress, and inducers of fatty acid β-oxidation, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of the increased acetylation of mitochondrial superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly, INT-777 decreased mitochondrial H2O2 generation and increased the activity of SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric acid reactive substances. Furthermore, INT-777 decreased renal lipid accumulation. INT-777 also prevented kidney disease in mice with diet-induced obesity. In human podocytes cultured with high glucose, INT-777 induced mitochondrial biogenesis, decreased oxidative stress, and increased fatty acid β-oxidation. Compared with normal kidney biopsy specimens, kidney specimens from patients with established ORG or DN expressed significantly less TGR5 mRNA, and levels inversely correlated with disease progression. Our results indicate that TGR5 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes.Wang, Xiaoxin X.Edelstein, Michal HermanGafter, UziQiu, LiruLuo, YuhuanDobrinskikh, EvgeniaLucia, ScottAdorini, LucianoD’Agati, Vivette D.Levi, JonathanRosenberg, AviKopp, Jeffrey B.Gius, David R.Saleem, Moin A.Levi, Moshe2015-09-30T05:41:37-07:00doi:10.1681/ASN.2014121271hwp:resource-id:jnephrol;27/5/1362American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, obesity, metabolism, mitochondria, oxidative stressBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20141212711046-66731533-34502015-09-30T05:41:37-07:002016-05Journal of the American Society of NephrologyBasic Research27513621378
- Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment EraLight chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.10.1681/ASN.2015020185Tue, 15 Sep 2015 04:07:46 GMT-07:00Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment EraLight chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.Stokes, Michael B.Valeri, Anthony M.Herlitz, LealKhan, Abdullah M.Siegel, David S.Markowitz, Glen S.D’Agati, Vivette D.2015-09-15T16:07:46-07:00doi:10.1681/ASN.2015020185hwp:resource-id:jnephrol;27/5/1555American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyRenal pathology, renal proximal tubule cell, multiple myelomaClinical ResearchClinical Researchresearch-article20162016-05-01May 201610.1681/ASN.20150201851046-66731533-34502015-09-15T16:07:46-07:002016-05Journal of the American Society of NephrologyClinical Research27515551565
- Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem CellsGenerating kidney organoids using human stem cells could offer promising prospects for research and therapeutic purposes. However, no cell-based strategy has generated nephrons displaying an intact three-dimensional epithelial filtering barrier. Here, we generated organoids using murine embryonic kidney cells, and documented that these tissues recapitulated the complex three-dimensional filtering structure of glomerular slits in vivo and accomplished selective glomerular filtration and tubular reabsorption. Exploiting this technology, we mixed human amniotic fluid stem cells with mouse embryonic kidney cells to establish three-dimensional chimeric organoids that engrafted in vivo and grew to form vascularized glomeruli and tubular structures. Human cells contributed to the formation of glomerular structures, differentiated into podocytes with slit diaphragms, and internalized exogenously infused BSA, thus attaining in vivo degrees of specialization and function unprecedented for donor stem cells. In conclusion, human amniotic fluid stem cell chimeric organoids may offer new paths for studying renal development and human podocyte disease, and for facilitating drug discovery and translational research.10.1681/ASN.2015030316Thu, 29 Oct 2015 06:08:31 GMT-07:00Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem CellsGenerating kidney organoids using human stem cells could offer promising prospects for research and therapeutic purposes. However, no cell-based strategy has generated nephrons displaying an intact three-dimensional epithelial filtering barrier. Here, we generated organoids using murine embryonic kidney cells, and documented that these tissues recapitulated the complex three-dimensional filtering structure of glomerular slits in vivo and accomplished selective glomerular filtration and tubular reabsorption. Exploiting this technology, we mixed human amniotic fluid stem cells with mouse embryonic kidney cells to establish three-dimensional chimeric organoids that engrafted in vivo and grew to form vascularized glomeruli and tubular structures. Human cells contributed to the formation of glomerular structures, differentiated into podocytes with slit diaphragms, and internalized exogenously infused BSA, thus attaining in vivo degrees of specialization and function unprecedented for donor stem cells. In conclusion, human amniotic fluid stem cell chimeric organoids may offer new paths for studying renal development and human podocyte disease, and for facilitating drug discovery and translational research.Xinaris, ChristodoulosBenedetti, ValentinaNovelli, RubinaAbbate, MauroRizzo, PaolaConti, SaraTomasoni, SusannaCorna, DanielaPozzobon, MichelaCavallotti, DanielaYokoo, TakashiMorigi, MarinaBenigni, ArielaRemuzzi, Giuseppe2015-10-29T06:08:31-07:00doi:10.1681/ASN.2015030316hwp:resource-id:jnephrol;27/5/1400American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney regeneration, podocyte, human amniotic fluid stem cells, kidney organoids, glomerulogenesis, filtration slitsBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150303161046-66731533-34502015-10-29T06:08:31-07:002016-05Journal of the American Society of NephrologyBasic Research27551400126614111268
- This Month's Highlights10.1681/ASN.2016020174Fri, 29 Apr 2016 10:00:59 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-04-29T10:00:59-07:00doi:10.1681/ASN.2016020174hwp:resource-id:jnephrol;27/5/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-05-01May 201610.1681/ASN.20160201741046-66731533-34502016-04-29T10:00:59-07:002016-05Journal of the American Society of NephrologyThis Month's Highlights275ii
- Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GNRenal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.10.1681/ASN.2015060612Fri, 13 Nov 2015 09:34:21 GMT-08:00Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GNRenal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.Sethi, SanjeevHaas, MarkMarkowitz, Glen S.D’Agati, Vivette D.Rennke, Helmut G.Jennette, J. CharlesBajema, Ingeborg M.Alpers, Charles E.Chang, AnthonyCornell, Lynn D.Cosio, Fernando G.Fogo, Agnes B.Glassock, Richard J.Hariharan, SundaramKambham, NeerajaLager, Donna J.Leung, NelsonMengel, MichaelNath, Karl A.Roberts, Ian S.Rovin, Brad H.Seshan, Surya V.Smith, Richard J.H.Walker, Patrick D.Winearls, Christopher G.Appel, Gerald B.Alexander, Mariam P.Cattran, Daniel C.Casado, Carmen AvilaCook, H. TerenceDe Vriese, An S.Radhakrishnan, JaiRacusen, Lorraine C.Ronco, PierreFervenza, Fernando C.2015-11-13T09:34:21-08:00doi:10.1681/ASN.2015060612hwp:resource-id:jnephrol;27/5/1278American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, renal biopsy, kidney biopsyUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20162016-05-01May 201610.1681/ASN.20150606121046-66731533-34502015-11-13T09:34:21-08:002016-05Journal of the American Society of NephrologyUp Front Matters27551278126512871266
- Cellular and Molecular Mechanisms of AKIIn this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed. Comorbidities that could alter patient susceptibility to AKI, such as underlying diabetes, aging, obesity, cancer, and CKD, should also be considered in developing these models. Finally, harmonization between academia and industry for more clinically relevant preclinical testing of potential therapeutic targets and better translational clinical trial design is also needed to achieve the goal of developing effective interventions for AKI.10.1681/ASN.2015070740Tue, 09 Feb 2016 06:25:17 GMT-08:00Cellular and Molecular Mechanisms of AKIIn this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed. Comorbidities that could alter patient susceptibility to AKI, such as underlying diabetes, aging, obesity, cancer, and CKD, should also be considered in developing these models. Finally, harmonization between academia and industry for more clinically relevant preclinical testing of potential therapeutic targets and better translational clinical trial design is also needed to achieve the goal of developing effective interventions for AKI.Agarwal, AnupamDong, ZhengHarris, RaymondMurray, PatrickParikh, Samir M.Rosner, Mitchell H.Kellum, John A.Ronco, Claudio2016-02-09T06:25:17-08:00doi:10.1681/ASN.2015070740hwp:resource-id:jnephrol;27/5/1288American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, kidney, pathophysiology of renal disease and progressionUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20162016-05-01May 201610.1681/ASN.20150707401046-66731533-34502016-02-09T06:25:17-08:002016-05Journal of the American Society of NephrologyUp Front Matters27512881299
- Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 SubfamiliesAberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2−/WS25 background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) –driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2−/WS25 mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A–phosphorylated (Ser133) cAMP–responsive binding protein (P-CREB), activating transcription factor-1, and CREB–induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2−/WS25;Pde1a−/−, Pkd2−/WS25;Pde1c−/−, and Pkd2−/WS25;Pde3a−/− kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2−/WS25;Pde3a−/− mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR–driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.10.1681/ASN.2015010057Tue, 15 Sep 2015 04:07:48 GMT-07:00Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 SubfamiliesAberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2−/WS25 background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) –driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2−/WS25 mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A–phosphorylated (Ser133) cAMP–responsive binding protein (P-CREB), activating transcription factor-1, and CREB–induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2−/WS25;Pde1a−/−, Pkd2−/WS25;Pde1c−/−, and Pkd2−/WS25;Pde3a−/− kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2−/WS25;Pde3a−/− mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR–driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.Ye, HongWang, XiaofangSussman, Caroline R.Hopp, KatharinaIrazabal, Maria V.Bakeberg, Jason L.LaRiviere, Wells B.Manganiello, Vincent C.Vorhees, Charles V.Zhao, HaiqingHarris, Peter C.van Deursen, JanWard, Christopher J.Torres, Vicente E.2015-09-15T16:07:48-07:00doi:10.1681/ASN.2015010057hwp:resource-id:jnephrol;27/5/1312American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypolycystic kidney disease, cystic kidney, cAMPBrief CommunicationsBrief Communicationsbrief-report20162016-05-01May 201610.1681/ASN.20150100571046-66731533-34502015-09-15T16:07:48-07:002016-05Journal of the American Society of NephrologyBrief Communications27513121320
- CD103+ Dendritic Cells Elicit CD8+ T Cell Responses to Accelerate Kidney Injury in Adriamycin NephropathyCD103+ dendritic cells (DCs) in nonlymphoid organs exhibit two main functions: maintaining tolerance by induction of regulatory T cells and protecting against tissue infection through cross-presentation of foreign antigens to CD8+ T cells. However, the role of CD103+ DCs in kidney disease is unknown. In this study, we show that CD103+ DCs are one of four subpopulations of renal mononuclear phagocytes in normal kidneys. CD103+ DCs expressed DC-specific surface markers, transcription factors, and growth factor receptors and were found in the kidney cortex but not in the medulla. The number of kidney CD103+ DCs was significantly higher in mice with adriamycin nephropathy (AN) than in normal mice, and depletion of CD103+ DCs attenuated kidney injury in AN mice. In vitro, kidney CD103+ DCs preferentially primed CD8+ T cells and did not directly induce tubular epithelial cell apoptosis. Adoptive transfer of CD8+ T cells significantly exacerbated kidney injury in AN SCID mice, whereas depletion of CD103+ DCs in these mice impaired activation and proliferation of transfused CD8+ T cells and prevented the exacerbation of kidney injury associated with this transfusion. In conclusion, kidney CD103+ DCs display a pathogenic role in murine CKD via activation of CD8+ T cells.10.1681/ASN.2015030229Wed, 16 Sep 2015 09:16:47 GMT-07:00CD103+ Dendritic Cells Elicit CD8+ T Cell Responses to Accelerate Kidney Injury in Adriamycin NephropathyCD103+ dendritic cells (DCs) in nonlymphoid organs exhibit two main functions: maintaining tolerance by induction of regulatory T cells and protecting against tissue infection through cross-presentation of foreign antigens to CD8+ T cells. However, the role of CD103+ DCs in kidney disease is unknown. In this study, we show that CD103+ DCs are one of four subpopulations of renal mononuclear phagocytes in normal kidneys. CD103+ DCs expressed DC-specific surface markers, transcription factors, and growth factor receptors and were found in the kidney cortex but not in the medulla. The number of kidney CD103+ DCs was significantly higher in mice with adriamycin nephropathy (AN) than in normal mice, and depletion of CD103+ DCs attenuated kidney injury in AN mice. In vitro, kidney CD103+ DCs preferentially primed CD8+ T cells and did not directly induce tubular epithelial cell apoptosis. Adoptive transfer of CD8+ T cells significantly exacerbated kidney injury in AN SCID mice, whereas depletion of CD103+ DCs in these mice impaired activation and proliferation of transfused CD8+ T cells and prevented the exacerbation of kidney injury associated with this transfusion. In conclusion, kidney CD103+ DCs display a pathogenic role in murine CKD via activation of CD8+ T cells.Cao, QiLu, JunyuLi, QingWang, ChangqiWang, Xin MaggieLee, Vincent W.S.Wang, ChengshiNguyen, HanhZheng, GuopingZhao, YeAlexander, Stephen I.Wang, YipingHarris, David C.H.2015-09-16T09:16:47-07:00doi:10.1681/ASN.2015030229hwp:resource-id:jnephrol;27/5/1344American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal mononuclear phagocyte, CD103+ dendritic cell, CD8 T cell, adriamycin nephropathyBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150302291046-66731533-34502015-09-16T09:16:47-07:002016-05Journal of the American Society of NephrologyBasic Research27513441360
- Molecular Basis of Factor H R1210C Association with Ocular and Renal DiseasesThe complement factor H (FH) mutation R1210C, which was described in association with atypical hemolytic uremic syndrome (aHUS), also confers high risk of age-related macular degeneration (AMD) and associates with C3 glomerulopathy (C3G). To reveal the molecular basis of these associations and to provide insight into what determines the disease phenotype in FH-R1210C carriers, we identified FH-R1210C carriers in our aHUS, C3G, and AMD cohorts. Disease status, determined in patients and relatives, revealed an absence of AMD phenotypes in the aHUS cohort and, vice versa, a lack of renal disease in the AMD cohort. These findings were consistent with differences in the R1210C-independent overall risk for aHUS and AMD between mutation carriers developing one pathology or the other. R1210C is an unusual mutation that generates covalent complexes between FH and HSA. Using purified FH proteins and surface plasmon resonance analyses, we demonstrated that formation of these FH-HSA complexes impairs accessibility to all FH functional domains. These data suggest that R1210C is a unique C-terminal FH mutation that behaves as a partial FH deficiency, predisposing individuals to diverse pathologies with distinct underlying pathogenic mechanisms; the final disease outcome is then determined by R1210C-independent genetic risk factors.10.1681/ASN.2015050580Wed, 16 Sep 2015 09:16:47 GMT-07:00Molecular Basis of Factor H R1210C Association with Ocular and Renal DiseasesThe complement factor H (FH) mutation R1210C, which was described in association with atypical hemolytic uremic syndrome (aHUS), also confers high risk of age-related macular degeneration (AMD) and associates with C3 glomerulopathy (C3G). To reveal the molecular basis of these associations and to provide insight into what determines the disease phenotype in FH-R1210C carriers, we identified FH-R1210C carriers in our aHUS, C3G, and AMD cohorts. Disease status, determined in patients and relatives, revealed an absence of AMD phenotypes in the aHUS cohort and, vice versa, a lack of renal disease in the AMD cohort. These findings were consistent with differences in the R1210C-independent overall risk for aHUS and AMD between mutation carriers developing one pathology or the other. R1210C is an unusual mutation that generates covalent complexes between FH and HSA. Using purified FH proteins and surface plasmon resonance analyses, we demonstrated that formation of these FH-HSA complexes impairs accessibility to all FH functional domains. These data suggest that R1210C is a unique C-terminal FH mutation that behaves as a partial FH deficiency, predisposing individuals to diverse pathologies with distinct underlying pathogenic mechanisms; the final disease outcome is then determined by R1210C-independent genetic risk factors.Recalde, SergioTortajada, AgustinSubias, MartaAnter, JaouadBlasco, MiquelMaranta, RamonaCoco, RosaPinto, SheilaNoris, MarinaGarcía-Layana, AlfredoRodríguez de Córdoba, Santiago2015-09-16T09:16:47-07:00doi:10.1681/ASN.2015050580hwp:resource-id:jnephrol;27/5/1305American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, hemolytic uremic syndrome, glomerular diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-05-01May 201610.1681/ASN.20150505801046-66731533-34502015-09-16T09:16:47-07:002016-05Journal of the American Society of NephrologyBrief Communications27513051311
- Immune Response against Autoantigen PLA2R Is not Gambling: Implications for Pathophysiology, Prognosis, and Therapy10.1681/ASN.2015101170Fri, 11 Dec 2015 08:20:58 GMT-08:00Immune Response against Autoantigen PLA2R Is not Gambling: Implications for Pathophysiology, Prognosis, and TherapyDebiec, HannaRonco, Pierre2015-12-11T08:20:58-08:00doi:10.1681/ASN.2015101170hwp:resource-id:jnephrol;27/5/1275American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, immunology and pathology, membranous nephropathyUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-05-01May 201610.1681/ASN.20151011701046-66731533-34502015-12-11T08:20:58-08:002016-05Journal of the American Society of NephrologyUp Front Matters27551275151712771533
- Complement Factor H-Related 5-Hybrid Proteins Anchor Properdin and Activate Complement at Self-SurfacesC3 glomerulopathy (C3G) is a severe kidney disease for which no specific therapy exists. The causes of C3G are heterogeneous, and defective complement regulation is often linked to C3G pathogenesis. Copy number variations in the complement factor H-related (CFHR) gene cluster on chromosome 1q32 and CFHR5 mutant proteins associate with this disease. Here, we identified CFHR5 as a pattern recognition protein that binds to damaged human endothelial cell surfaces and to properdin, the human complement activator. We found the two N-terminal short consensus repeat domains of CFHR5 contact properdin and mediate dimer formation. These properdin-binding segments are duplicated in two mutant CFHR5 proteins, CFHR2-CFHR5Hyb from German patients with C3G and CFHR5Dup from Cypriot patients with C3G. Each of these mutated proteins assembled into large multimeric complexes and, compared to CFHR5, bound damaged human cell surfaces and properdin with greater intensity and exacerbated local complement activation. This enhanced surface binding and properdin recruitment was further evidenced in the mesangia of a transplanted and explanted kidney from a German patient with a CFHR2-CFHR5Hyb protein. Enhanced properdin staining correlated with local complement activation with C3b and C5b-9 deposition on the mesangial cell surface in vitro. This gain of function in complement activation for two disease-associated CFHR5 mutants describes a new disease mechanism of C3G, which is relevant for defining appropriate treatment options for this disorder.10.1681/ASN.2015020212Fri, 02 Oct 2015 06:42:15 GMT-07:00Complement Factor H-Related 5-Hybrid Proteins Anchor Properdin and Activate Complement at Self-SurfacesC3 glomerulopathy (C3G) is a severe kidney disease for which no specific therapy exists. The causes of C3G are heterogeneous, and defective complement regulation is often linked to C3G pathogenesis. Copy number variations in the complement factor H-related (CFHR) gene cluster on chromosome 1q32 and CFHR5 mutant proteins associate with this disease. Here, we identified CFHR5 as a pattern recognition protein that binds to damaged human endothelial cell surfaces and to properdin, the human complement activator. We found the two N-terminal short consensus repeat domains of CFHR5 contact properdin and mediate dimer formation. These properdin-binding segments are duplicated in two mutant CFHR5 proteins, CFHR2-CFHR5Hyb from German patients with C3G and CFHR5Dup from Cypriot patients with C3G. Each of these mutated proteins assembled into large multimeric complexes and, compared to CFHR5, bound damaged human cell surfaces and properdin with greater intensity and exacerbated local complement activation. This enhanced surface binding and properdin recruitment was further evidenced in the mesangia of a transplanted and explanted kidney from a German patient with a CFHR2-CFHR5Hyb protein. Enhanced properdin staining correlated with local complement activation with C3b and C5b-9 deposition on the mesangial cell surface in vitro. This gain of function in complement activation for two disease-associated CFHR5 mutants describes a new disease mechanism of C3G, which is relevant for defining appropriate treatment options for this disorder.Chen, QianManzke, MelanieHartmann, AndreaBüttner, MaikeAmann, KerstinPauly, DianaWiesener, MichaelSkerka, ChristineZipfel, Peter F.2015-10-02T06:42:15-07:00doi:10.1681/ASN.2015020212hwp:resource-id:jnephrol;27/5/1413American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, ESRD, glomerulopathy, immune deficiency, pathology, pediatric nephrologyBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150202121046-66731533-34502015-10-02T06:42:15-07:002016-05Journal of the American Society of NephrologyBasic Research27514131425
- Food Restriction Ameliorates the Development of Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%–40%) FR reduced cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD.10.1681/ASN.2015020132Wed, 04 Nov 2015 10:27:55 GMT-08:00Food Restriction Ameliorates the Development of Polycystic Kidney DiseaseAutosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%–40%) FR reduced cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD.Warner, GinaHein, Kyaw ZawNin, VeronicaEdwards, MarikaChini, Claudia C.S.Hopp, KatharinaHarris, Peter C.Torres, Vicente E.Chini, Eduardo N.2015-11-04T10:27:55-08:00doi:10.1681/ASN.2015020132hwp:resource-id:jnephrol;27/5/1437American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, nutrition, mTOR, metabolism, AMPK, polycystic kidney diseaseBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150201321046-66731533-34502015-11-04T10:27:55-08:002016-05Journal of the American Society of NephrologyBasic Research27551437126814471270
- Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1+/+/UT-A3−/−). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1+/+/UT-A3−/− and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1+/+/UT-A3−/− and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1+/+/UT-A3−/− mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1+/+/UT-A3−/− mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1+/+/UT-A3−/− mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1+/+/UT-A3−/− mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability.10.1681/ASN.2014121267Fri, 25 Sep 2015 01:24:18 GMT-07:00Transgenic Restoration of Urea Transporter A1 Confers Maximal Urinary Concentration in the Absence of Urea Transporter A3Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1+/+/UT-A3−/−). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1+/+/UT-A3−/− and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1+/+/UT-A3−/− and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1+/+/UT-A3−/− mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1+/+/UT-A3−/− mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1+/+/UT-A3−/− mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1+/+/UT-A3−/− mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability.Klein, Janet D.Wang, YanhuaMistry, AbinashLaRocque, Lauren M.Molina, Patrick A.Rogers, Richard T.Blount, Mitsi A.Sands, Jeff M.2015-09-25T13:24:18-07:00doi:10.1681/ASN.2014121267hwp:resource-id:jnephrol;27/5/1448American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvasopressin, urea transporter, IMCD, transgenic mice, aquaporin, urine, concentrating mechanismBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20141212671046-66731533-34502015-09-25T13:24:18-07:002016-05Journal of the American Society of NephrologyBasic Research27514481455
- Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced HypertensionTacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disruption alone did not cause phenotypic effects. When treated with tacrolimus, however, BP and the renal abundance of phosphorylated NCC were lower in mice lacking FKBP12 along the nephron than in control mice. Mice lacking FKBP12 along the nephron also maintained a normal relationship between plasma potassium levels and the abundance of phosphorylated NCC with tacrolimus treatment. In cultured cells, tacrolimus inhibited dephosphorylation of NCC. Together, these results suggest that tacrolimus causes hypertension predominantly by inhibiting calcineurin directly in cells expressing NCC, indicating thiazide diuretics may be particularly effective for lowering BP in tacrolimus-treated patients with hypertension.10.1681/ASN.2015040466Fri, 02 Oct 2015 06:42:16 GMT-07:00Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced HypertensionTacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disruption alone did not cause phenotypic effects. When treated with tacrolimus, however, BP and the renal abundance of phosphorylated NCC were lower in mice lacking FKBP12 along the nephron than in control mice. Mice lacking FKBP12 along the nephron also maintained a normal relationship between plasma potassium levels and the abundance of phosphorylated NCC with tacrolimus treatment. In cultured cells, tacrolimus inhibited dephosphorylation of NCC. Together, these results suggest that tacrolimus causes hypertension predominantly by inhibiting calcineurin directly in cells expressing NCC, indicating thiazide diuretics may be particularly effective for lowering BP in tacrolimus-treated patients with hypertension.Lazelle, Rebecca A.McCully, Belinda H.Terker, Andrew S.Himmerkus, NinaBlankenstein, Katharina I.Mutig, KerimBleich, MarkusBachmann, SebastianYang, Chao-LingEllison, David H.2015-10-02T06:42:16-07:00doi:10.1681/ASN.2015040466hwp:resource-id:jnephrol;27/5/1456American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, immunosuppression, ion transport, K channels, kidney tubule, tacrolimusBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150404661046-66731533-34502015-10-02T06:42:16-07:002016-05Journal of the American Society of NephrologyBasic Research27514561464
- Integrin-linked Kinase Controls Renal Branching Morphogenesis via Dual Specificity Phosphatase 8Integrin-linked kinase (ILK) is an intracellular scaffold protein with critical cell-specific functions in the embryonic and mature mammalian kidney. Previously, we demonstrated a requirement for Ilk during ureteric branching and cell cycle regulation in collecting duct cells in vivo. Although in vitro data indicate that ILK controls p38 mitogen-activated protein kinase (p38MAPK) activity, the contribution of ILK-p38MAPK signaling to branching morphogenesis in vivo is not defined. Here, we identified genes that are regulated by Ilk in ureteric cells using a whole-genome expression analysis of whole-kidney mRNA in mice with Ilk deficiency in the ureteric cell lineage. Six genes with expression in ureteric tip cells, including Wnt11, were downregulated, whereas the expression of dual-specificity phosphatase 8 (DUSP8) was upregulated. Phosphorylation of p38MAPK was decreased in kidney tissue with Ilk deficiency, but no significant decrease in the phosphorylation of other intracellular effectors previously shown to control renal morphogenesis was observed. Pharmacologic inhibition of p38MAPK activity in murine inner medullary collecting duct 3 (mIMCD3) cells decreased expression of Wnt11, Krt23, and Slo4c1. DUSP8 overexpression in mIMCD3 cells significantly inhibited p38MAPK activation and the expression of Wnt11 and Slo4c1. Adenovirus-mediated overexpression of DUSP8 in cultured embryonic murine kidneys decreased ureteric branching and p38MAPK activation. Together, these data demonstrate that Ilk controls branching morphogenesis by regulating the expression of DUSP8, which inhibits p38MAPK activity and decreases branching morphogenesis.10.1681/ASN.2015020139Fri, 25 Sep 2015 01:24:18 GMT-07:00Integrin-linked Kinase Controls Renal Branching Morphogenesis via Dual Specificity Phosphatase 8Integrin-linked kinase (ILK) is an intracellular scaffold protein with critical cell-specific functions in the embryonic and mature mammalian kidney. Previously, we demonstrated a requirement for Ilk during ureteric branching and cell cycle regulation in collecting duct cells in vivo. Although in vitro data indicate that ILK controls p38 mitogen-activated protein kinase (p38MAPK) activity, the contribution of ILK-p38MAPK signaling to branching morphogenesis in vivo is not defined. Here, we identified genes that are regulated by Ilk in ureteric cells using a whole-genome expression analysis of whole-kidney mRNA in mice with Ilk deficiency in the ureteric cell lineage. Six genes with expression in ureteric tip cells, including Wnt11, were downregulated, whereas the expression of dual-specificity phosphatase 8 (DUSP8) was upregulated. Phosphorylation of p38MAPK was decreased in kidney tissue with Ilk deficiency, but no significant decrease in the phosphorylation of other intracellular effectors previously shown to control renal morphogenesis was observed. Pharmacologic inhibition of p38MAPK activity in murine inner medullary collecting duct 3 (mIMCD3) cells decreased expression of Wnt11, Krt23, and Slo4c1. DUSP8 overexpression in mIMCD3 cells significantly inhibited p38MAPK activation and the expression of Wnt11 and Slo4c1. Adenovirus-mediated overexpression of DUSP8 in cultured embryonic murine kidneys decreased ureteric branching and p38MAPK activation. Together, these data demonstrate that Ilk controls branching morphogenesis by regulating the expression of DUSP8, which inhibits p38MAPK activity and decreases branching morphogenesis.Smeeton, JoannaDhir, PriyaHu, DiFeeney, Meghan M.Chen, LinRosenblum, Norman D.2015-09-25T13:24:18-07:00doi:10.1681/ASN.2015020139hwp:resource-id:jnephrol;27/5/1465American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell signaling, gene expression, genetics and development, kidney development, p38 mitogen-activated protein kinaseBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150201391046-66731533-34502015-09-25T13:24:18-07:002016-05Journal of the American Society of NephrologyBasic Research27514651477
- Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction IntervalsAmong patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin’s lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin’s lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin’s lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.10.1681/ASN.2015040373Thu, 12 Nov 2015 07:53:33 GMT-08:00Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction IntervalsAmong patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin’s lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin’s lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin’s lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.Yanik, Elizabeth L.Clarke, Christina A.Snyder, Jon J.Pfeiffer, Ruth M.Engels, Eric A.2015-11-12T07:53:33-08:00doi:10.1681/ASN.2015040373hwp:resource-id:jnephrol;27/5/1495American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycancer, epidemiology and outcomes, kidney transplantation, dialysisClinical EpidemiologyClinical Epidemiologyresearch-article20162016-05-01May 201610.1681/ASN.20150403731046-66731533-34502015-11-12T07:53:33-08:002016-05Journal of the American Society of NephrologyClinical Epidemiology27551495127215041275
- Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous NephropathyThe phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR–restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m2 at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis.10.1681/ASN.2014111061Fri, 13 Nov 2015 09:34:24 GMT-08:00Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous NephropathyThe phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR–restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m2 at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis.Seitz-Polski, BarbaraDolla, GuillaumePayré, ChristineGirard, Christophe A.Polidori, JoelZorzi, KevinBirgy-Barelli, EléonoreJullien, PerrineCourivaud, CécileKrummel, ThierryBenzaken, SylviaBernard, GhislaineBurtey, StéphaneMariat, ChristopheEsnault, Vincent L.M.Lambeau, Gérard2015-11-13T09:34:24-08:00doi:10.1681/ASN.2014111061hwp:resource-id:jnephrol;27/5/1517American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, epidemiology and outcomes, chronic kidney diseaseClinical ResearchClinical Researchresearch-article20162016-05-01May 201610.1681/ASN.20141110611046-66731533-34502015-11-13T09:34:24-08:002016-05Journal of the American Society of NephrologyClinical Research27551517127515331277
- The Vacuolar H+-ATPase B1 Subunit Polymorphism p.E161K Associates with Impaired Urinary Acidification in Recurrent Stone FormersMutations in the vacuolar–type H+-ATPase B1 subunit gene ATP6V1B1 cause autosomal–recessive distal renal tubular acidosis (dRTA). We previously identified a single-nucleotide polymorphism (SNP) in the human B1 subunit (c.481G>A; p.E161K) that causes greatly diminished pump function in vitro. To investigate the effect of this SNP on urinary acidification, we conducted a genotype-phenotype analysis of recurrent stone formers in the Dallas and Bern kidney stone registries. Of 555 patients examined, 32 (5.8%) were heterozygous for the p.E161K SNP, and the remaining 523 (94.2%) carried two wild–type alleles. After adjustment for sex, age, body mass index, and dietary acid and alkali intake, p.E161K SNP carriers had a nonsignificant tendency to higher urinary pH on a random diet (6.31 versus 6.09; P=0.09). Under an instructed low–Ca and low–Na diet, urinary pH was higher in p.E161K SNP carriers (6.56 versus 6.01; P<0.01). Kidney stones of p.E161K carriers were more likely to contain calcium phosphate than stones of wild-type patients. In acute NH4Cl loading, p.E161K carriers displayed a higher trough urinary pH (5.34 versus 4.89; P=0.01) than wild-type patients. Overall, 14.6% of wild-type patients and 52.4% of p.E161K carriers were unable to acidify their urine below pH 5.3 and thus, can be considered to have incomplete dRTA. In summary, our data indicate that recurrent stone formers with the vacuolar H+-ATPase B1 subunit p.E161K SNP exhibit a urinary acidification deficit with an increased prevalence of calcium phosphate–containing kidney stones. The burden of E161K heterozygosity may be a forme fruste of dRTA.10.1681/ASN.2015040367Fri, 09 Oct 2015 12:18:30 GMT-07:00The Vacuolar H+-ATPase B1 Subunit Polymorphism p.E161K Associates with Impaired Urinary Acidification in Recurrent Stone FormersMutations in the vacuolar–type H+-ATPase B1 subunit gene ATP6V1B1 cause autosomal–recessive distal renal tubular acidosis (dRTA). We previously identified a single-nucleotide polymorphism (SNP) in the human B1 subunit (c.481G>A; p.E161K) that causes greatly diminished pump function in vitro. To investigate the effect of this SNP on urinary acidification, we conducted a genotype-phenotype analysis of recurrent stone formers in the Dallas and Bern kidney stone registries. Of 555 patients examined, 32 (5.8%) were heterozygous for the p.E161K SNP, and the remaining 523 (94.2%) carried two wild–type alleles. After adjustment for sex, age, body mass index, and dietary acid and alkali intake, p.E161K SNP carriers had a nonsignificant tendency to higher urinary pH on a random diet (6.31 versus 6.09; P=0.09). Under an instructed low–Ca and low–Na diet, urinary pH was higher in p.E161K SNP carriers (6.56 versus 6.01; P<0.01). Kidney stones of p.E161K carriers were more likely to contain calcium phosphate than stones of wild-type patients. In acute NH4Cl loading, p.E161K carriers displayed a higher trough urinary pH (5.34 versus 4.89; P=0.01) than wild-type patients. Overall, 14.6% of wild-type patients and 52.4% of p.E161K carriers were unable to acidify their urine below pH 5.3 and thus, can be considered to have incomplete dRTA. In summary, our data indicate that recurrent stone formers with the vacuolar H+-ATPase B1 subunit p.E161K SNP exhibit a urinary acidification deficit with an increased prevalence of calcium phosphate–containing kidney stones. The burden of E161K heterozygosity may be a forme fruste of dRTA.Dhayat, Nasser A.Schaller, AndreAlbano, GiuseppePoindexter, JohnGriffith, CarolynPasch, AndreasGallati, SabinaVogt, BrunoMoe, Orson W.Fuster, Daniel G.2015-10-09T12:18:30-07:00doi:10.1681/ASN.2015040367hwp:resource-id:jnephrol;27/5/1544American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal tubular acidosis, human genetics, kidney stonesClinical ResearchClinical Researchresearch-article20162016-05-01May 201610.1681/ASN.20150403671046-66731533-34502015-10-09T12:18:30-07:002016-05Journal of the American Society of NephrologyClinical Research27515441554
- The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in BloodBisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/106 cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/106 cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.10.1681/ASN.2015030312Fri, 02 Oct 2015 06:42:14 GMT-07:00The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in BloodBisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD. Observational studies have linked BPA exposure to kidney and cardiovascular injury in humans, and animal studies have described a causative link. Normal kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients with CKD to adverse the effects of BPA. Using a crossover design, we studied the effect of dialysis with BPA-containing polysulfone or BPA-free polynephron dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients started on polysulfone dialyzers and were switched to polynephron dialyzers; 41 patients started on polynephron dialyzers and were switched to polysulfone dialyzers. Results were grouped for analysis. Mean BPA levels increased after one hemodialysis session with polysulfone dialyzers but not with polynephron dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly increase predialysis serum BPA levels, although a trend toward increase was detected (from 48.8±6.8 to 69.1±10.1 ng/ml). Chronic use of polynephron dialyzers reduced predialysis serum BPA (from 70.6±8.4 to 47.1±7.5 ng/ml, P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with polysulfone dialyzers (from 0.039±0.002 to 0.043±0.001 ng/106 cells, P<0.01), but decreased with polynephron dialyzers (from 0.045±0.001 to 0.036±0.001 ng/106 cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone dialyzers increased oxidative stress in PBMCs and inflammatory marker concentrations in circulation. In vitro, polysulfone membranes released significantly more BPA into the culture medium and induced more cytokine production in cultured PBMCs than did polynephron membranes. In conclusion, dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.Bosch-Panadero, EnriqueMas, SebastianSanchez-Ospina, DidierCamarero, VanesaPérez-Gómez, Maria V.Saez-Calero, IsabelAbaigar, PedroOrtiz, AlbertoEgido, JesusGonzález-Parra, Emilio2015-10-02T06:42:14-07:00doi:10.1681/ASN.2015030312hwp:resource-id:jnephrol;27/5/1566American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, oxidative stress, ESRDClinical ResearchClinical Researchresearch-article20162016-05-01May 201610.1681/ASN.20150303121046-66731533-34502015-10-02T06:42:14-07:002016-05Journal of the American Society of NephrologyClinical Research27515661574
- Inflammation Modifies the Paradoxical Association between Body Mass Index and Mortality in Hemodialysis PatientsHigh body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007–2009 (312 facilities; 15 European countries) with ≥3 months of follow-up. Patients were classified by presence (n=3231) or absence (n=2673) of inflammation (C-reactive protein ≥10 mg/l and/or albumin ≤35 g/l). Patients were divided into quintiles by BMI (Q1–Q5: <21.5, 21.5–24.0, >24.0–26.4, >26.4–29.8, and >29.8 kg/m2, respectively). Noninflamed patients in BMI Q5 formed the reference group. During a median follow-up period of 36.7 months, 1929 deaths occurred (822 cardiovascular), with 655 patients censored for renal transplantation and 1183 for loss to follow-up. Greater mortality was observed in inflamed patients (P<0.001). In fully adjusted time-dependent analyses, the all-cause mortality risk in noninflamed patients was higher only in the lowest BMI quintile (hazard ratio [HR, 1.80; 95% confidence interval [95% CI], 1.26 to 2.56). No protective effect was associated with higher BMI quintiles in noninflamed patients. Conversely, higher BMI associated with lower all-cause mortality risk in inflamed patients (HR [95% CI] for Q1: 5.63 [4.25 to 7.46]; Q2: 3.88 [2.91 to 5.17]; Q3: 2.89 [2.16 to 3.89]; Q4: 2.14 [1.59 to 2.90]; and Q5: 1.77 [1.30 to 2.40]). Thus, whereas a protective effect of high BMI was observed in inflamed patients, this effect was mitigated in noninflamed patients.10.1681/ASN.2015030252Fri, 13 Nov 2015 09:34:23 GMT-08:00Inflammation Modifies the Paradoxical Association between Body Mass Index and Mortality in Hemodialysis PatientsHigh body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007–2009 (312 facilities; 15 European countries) with ≥3 months of follow-up. Patients were classified by presence (n=3231) or absence (n=2673) of inflammation (C-reactive protein ≥10 mg/l and/or albumin ≤35 g/l). Patients were divided into quintiles by BMI (Q1–Q5: <21.5, 21.5–24.0, >24.0–26.4, >26.4–29.8, and >29.8 kg/m2, respectively). Noninflamed patients in BMI Q5 formed the reference group. During a median follow-up period of 36.7 months, 1929 deaths occurred (822 cardiovascular), with 655 patients censored for renal transplantation and 1183 for loss to follow-up. Greater mortality was observed in inflamed patients (P<0.001). In fully adjusted time-dependent analyses, the all-cause mortality risk in noninflamed patients was higher only in the lowest BMI quintile (hazard ratio [HR, 1.80; 95% confidence interval [95% CI], 1.26 to 2.56). No protective effect was associated with higher BMI quintiles in noninflamed patients. Conversely, higher BMI associated with lower all-cause mortality risk in inflamed patients (HR [95% CI] for Q1: 5.63 [4.25 to 7.46]; Q2: 3.88 [2.91 to 5.17]; Q3: 2.89 [2.16 to 3.89]; Q4: 2.14 [1.59 to 2.90]; and Q5: 1.77 [1.30 to 2.40]). Thus, whereas a protective effect of high BMI was observed in inflamed patients, this effect was mitigated in noninflamed patients.Stenvinkel, PeterGillespie, Iain A.Tunks, JamieAddison, JanetKronenberg, FlorianDrueke, Tilman B.Marcelli, DanieleSchernthaner, GuntramEckardt, Kai-UweFloege, JürgenFroissart, MarcAnker, Stefan D2015-11-13T09:34:23-08:00doi:10.1681/ASN.2015030252hwp:resource-id:jnephrol;27/5/1479American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, chronic inflammation, obesityClinical EpidemiologyClinical Epidemiologyresearch-article20162016-05-01May 201610.1681/ASN.20150302521046-66731533-34502015-11-13T09:34:23-08:002016-05Journal of the American Society of NephrologyClinical Epidemiology27551479127014861272
- ESRD due to Multiple Myeloma in the United States, 2001–2010Although management of multiple myeloma has changed substantially in the last decade, it is unknown whether the burden of ESRD due to multiple myeloma has changed, or whether survival of patients with multiple myeloma on RRT has improved. Regarding ESRD due to multiple myeloma necessitating RRT in the United States, we evaluated temporal trends between 2001 and 2010 for demography-adjusted incidence ratios, relative to rates in 2001–2002, and mortality hazards from RRT initiation, relative to hazards in 2001–2002. In this retrospective cohort study, we used the US Renal Data System database (n=1,069,343), 2001–2010, to identify patients with ESRD due to multiple myeloma treated with RRT (n=12,703). Demography-adjusted incidence ratios of ESRD from multiple myeloma decreased between 2001–2002 and 2009–2010 in the overall population (demography-adjusted incidence ratio 0.82; 95% confidence interval, 0.79 to 0.86) and in most demographic subgroups examined. Mortality rates were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, respectively, compared with 32.3, 20.6, and 21.3 in matched controls without multiple myeloma. Unadjusted mortality hazards ratios declined monotonically after 2004 to a value of 0.72; 95% confidence interval, 0.67 to 0.77 in 2009–2010, and declines between 2001–2002 and 2008–2009 were observed (P<0.05) in most demographic subgroups examined. Findings were similar when adjustment was made for demographic characteristics, comorbidity markers, and laboratory test values. These data suggest the incidence of RRT from multiple myeloma in the United States has decreased in the last decade, and clinically meaningful increases in survival have occurred for these patients.10.1681/ASN.2014090876Thu, 29 Oct 2015 06:08:32 GMT-07:00ESRD due to Multiple Myeloma in the United States, 2001–2010Although management of multiple myeloma has changed substantially in the last decade, it is unknown whether the burden of ESRD due to multiple myeloma has changed, or whether survival of patients with multiple myeloma on RRT has improved. Regarding ESRD due to multiple myeloma necessitating RRT in the United States, we evaluated temporal trends between 2001 and 2010 for demography-adjusted incidence ratios, relative to rates in 2001–2002, and mortality hazards from RRT initiation, relative to hazards in 2001–2002. In this retrospective cohort study, we used the US Renal Data System database (n=1,069,343), 2001–2010, to identify patients with ESRD due to multiple myeloma treated with RRT (n=12,703). Demography-adjusted incidence ratios of ESRD from multiple myeloma decreased between 2001–2002 and 2009–2010 in the overall population (demography-adjusted incidence ratio 0.82; 95% confidence interval, 0.79 to 0.86) and in most demographic subgroups examined. Mortality rates were 86.7, 41.4, and 34.4 per 100 person-years in the first 3 years of RRT, respectively, compared with 32.3, 20.6, and 21.3 in matched controls without multiple myeloma. Unadjusted mortality hazards ratios declined monotonically after 2004 to a value of 0.72; 95% confidence interval, 0.67 to 0.77 in 2009–2010, and declines between 2001–2002 and 2008–2009 were observed (P<0.05) in most demographic subgroups examined. Findings were similar when adjustment was made for demographic characteristics, comorbidity markers, and laboratory test values. These data suggest the incidence of RRT from multiple myeloma in the United States has decreased in the last decade, and clinically meaningful increases in survival have occurred for these patients.Reule, ScottSexton, Donal J.Solid, Craig A.Chen, Shu-ChengFoley, Robert N.2015-10-29T06:08:32-07:00doi:10.1681/ASN.2014090876hwp:resource-id:jnephrol;27/5/1487American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyPI3K, vesicular trafficking, cystic kidney, polycystins, primary cilium, proliferationClinical EpidemiologyClinical Epidemiologyresearch-article20162016-05-01May 201610.1681/ASN.20140908761046-66731533-34502015-10-29T06:08:32-07:002016-05Journal of the American Society of NephrologyClinical Epidemiology27514871494
- Endothelial Krüppel-Like Factor 4 Mediates the Protective Effect of Statins against Ischemic AKIEndothelial cells participate in the pathophysiology of ischemic AKI by increasing the expression of cell adhesion molecules and by recruiting inflammatory cells. We previously showed that endothelial Krüppel-like factor 4 (Klf4) regulates vascular cell adhesion molecule 1 (Vcam1) expression and neointimal formation after carotid injury. In this study, we determined whether endothelial Klf4 is involved in ischemic AKI using endothelial Klf4 conditional knockout (Klf4 cKO) mice generated by breeding Tek-Cre mice and Klf4 floxed mice. Klf4 cKO mice were phenotypically normal before surgery. However, after renal ischemia-reperfusion injury, Klf4 cKO mice exhibited elevated serum levels of urea nitrogen and creatinine and aggravated renal histology compared with those of Klf4 floxed controls. Moreover, Klf4 cKO mice exhibited enhanced accumulation of neutrophils and lymphocytes and elevated expression of cell adhesion molecules, including Vcam1 and Icam1, in injured kidneys. Notably, statins ameliorated renal ischemia-reperfusion injury in control mice but not in Klf4 cKO mice. Mechanistic analyses in cultured endothelial cells revealed that statins increased KLF4 expression and that KLF4 mediated the suppressive effect of statins on TNF-α–induced VCAM1 expression by reducing NF-κB binding to the VCAM1 promoter. These results provide evidence that endothelial Klf4 is renoprotective and mediates statin-induced protection against ischemic AKI by regulating the expression of cell adhesion molecules and concomitant recruitment of inflammatory cells.10.1681/ASN.2015040460Thu, 15 Oct 2015 05:08:07 GMT-07:00Endothelial Krüppel-Like Factor 4 Mediates the Protective Effect of Statins against Ischemic AKIEndothelial cells participate in the pathophysiology of ischemic AKI by increasing the expression of cell adhesion molecules and by recruiting inflammatory cells. We previously showed that endothelial Krüppel-like factor 4 (Klf4) regulates vascular cell adhesion molecule 1 (Vcam1) expression and neointimal formation after carotid injury. In this study, we determined whether endothelial Klf4 is involved in ischemic AKI using endothelial Klf4 conditional knockout (Klf4 cKO) mice generated by breeding Tek-Cre mice and Klf4 floxed mice. Klf4 cKO mice were phenotypically normal before surgery. However, after renal ischemia-reperfusion injury, Klf4 cKO mice exhibited elevated serum levels of urea nitrogen and creatinine and aggravated renal histology compared with those of Klf4 floxed controls. Moreover, Klf4 cKO mice exhibited enhanced accumulation of neutrophils and lymphocytes and elevated expression of cell adhesion molecules, including Vcam1 and Icam1, in injured kidneys. Notably, statins ameliorated renal ischemia-reperfusion injury in control mice but not in Klf4 cKO mice. Mechanistic analyses in cultured endothelial cells revealed that statins increased KLF4 expression and that KLF4 mediated the suppressive effect of statins on TNF-α–induced VCAM1 expression by reducing NF-κB binding to the VCAM1 promoter. These results provide evidence that endothelial Klf4 is renoprotective and mediates statin-induced protection against ischemic AKI by regulating the expression of cell adhesion molecules and concomitant recruitment of inflammatory cells.Yoshida, TadashiYamashita, MahoIwai, MiekoHayashi, Matsuhiko2015-10-15T05:08:07-07:00doi:10.1681/ASN.2015040460hwp:resource-id:jnephrol;27/5/1379American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, endothelial cells, transcription factors, acute renal failure, adhesion moleculeBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150404601046-66731533-34502015-10-15T05:08:07-07:002016-05Journal of the American Society of NephrologyBasic Research27513791388
- The Influence of CKD on Colonic Microbial MetabolismThere is increasing interest in the colonic microbiota as a relevant source of uremic retention solutes accumulating in CKD. Renal disease can also profoundly affect the colonic microenvironment and has been associated with a distinct colonic microbial composition. However, the influence of CKD on the colonic microbial metabolism is largely unknown. Therefore, we studied fecal metabolite profiles of hemodialysis patients and healthy controls using a gas chromatography-mass spectrometry method. We observed a clear discrimination between both groups, with 81 fecal volatile organic compounds detected at significantly different levels in hemodialysis patients and healthy controls. To further explore the differential impact of renal function loss per se versus the effect of dietary and other CKD-related factors, we also compared fecal metabolite profiles between patients on hemodialysis and household contacts on the same diet, which revealed a close resemblance. In contrast, significant differences were noted between the fecal samples of rats 6 weeks after 5/6th nephrectomy and those of sham-operated rats, still suggesting an independent influence of renal function loss. Thus, CKD associates with a distinct colonic microbial metabolism, although the effect of renal function loss per se in humans may be inferior to the effects of dietary and other CKD-related factors. The potential beneficial effect of therapeutics targeting colonic microbiota in patients with CKD remains to be examined.10.1681/ASN.2015030279Wed, 23 Sep 2015 12:03:13 GMT-07:00The Influence of CKD on Colonic Microbial MetabolismThere is increasing interest in the colonic microbiota as a relevant source of uremic retention solutes accumulating in CKD. Renal disease can also profoundly affect the colonic microenvironment and has been associated with a distinct colonic microbial composition. However, the influence of CKD on the colonic microbial metabolism is largely unknown. Therefore, we studied fecal metabolite profiles of hemodialysis patients and healthy controls using a gas chromatography-mass spectrometry method. We observed a clear discrimination between both groups, with 81 fecal volatile organic compounds detected at significantly different levels in hemodialysis patients and healthy controls. To further explore the differential impact of renal function loss per se versus the effect of dietary and other CKD-related factors, we also compared fecal metabolite profiles between patients on hemodialysis and household contacts on the same diet, which revealed a close resemblance. In contrast, significant differences were noted between the fecal samples of rats 6 weeks after 5/6th nephrectomy and those of sham-operated rats, still suggesting an independent influence of renal function loss. Thus, CKD associates with a distinct colonic microbial metabolism, although the effect of renal function loss per se in humans may be inferior to the effects of dietary and other CKD-related factors. The potential beneficial effect of therapeutics targeting colonic microbiota in patients with CKD remains to be examined.Poesen, RubenWindey, KarenNeven, EllenKuypers, DirkDe Preter, VickyAugustijns, PatrickD’Haese, PatrickEvenepoel, PieterVerbeke, KristinMeijers, Björn2015-09-23T12:03:13-07:00doi:10.1681/ASN.2015030279hwp:resource-id:jnephrol;27/5/1389American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, intestine, nutritionBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150302791046-66731533-34502015-09-23T12:03:13-07:002016-05Journal of the American Society of NephrologyBasic Research27513891399
- Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause GlucosuriaA heterozygous mutation (c.643C>A; p.Q215X) in the monocarboxylate transporter 12-encoding gene MCT12 (also known as SLC16A12) that mediates creatine transport was recently identified as the cause of a syndrome with juvenile cataracts, microcornea, and glucosuria in a single family. Whereas the MCT12 mutation cosegregated with the eye phenotype, poor correlation with the glucosuria phenotype did not support a pathogenic role of the mutation in the kidney. Here, we examined MCT12 in the kidney and found that it resides on basolateral membranes of proximal tubules. Patients with MCT12 mutation exhibited reduced plasma levels and increased fractional excretion of guanidinoacetate, but normal creatine levels, suggesting that MCT12 may function as a guanidinoacetate transporter in vivo. However, functional studies in Xenopus oocytes revealed that MCT12 transports creatine but not its precursor, guanidinoacetate. Genetic analysis revealed a separate, undescribed heterozygous mutation (c.265G>A; p.A89T) in the sodium/glucose cotransporter 2-encoding gene SGLT2 (also known as SLC5A2) in the family that segregated with the renal glucosuria phenotype. When overexpressed in HEK293 cells, the mutant SGLT2 transporter did not efficiently translocate to the plasma membrane, and displayed greatly reduced transport activity. In summary, our data indicate that MCT12 functions as a basolateral exit pathway for creatine in the proximal tubule. Heterozygous mutation of MCT12 affects systemic levels and renal handling of guanidinoacetate, possibly through an indirect mechanism. Furthermore, our data reveal a digenic syndrome in the index family, with simultaneous MCT12 and SGLT2 mutation. Thus, glucosuria is not part of the MCT12 mutation syndrome.10.1681/ASN.2015040411Wed, 16 Sep 2015 09:16:45 GMT-07:00Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause GlucosuriaA heterozygous mutation (c.643C>A; p.Q215X) in the monocarboxylate transporter 12-encoding gene MCT12 (also known as SLC16A12) that mediates creatine transport was recently identified as the cause of a syndrome with juvenile cataracts, microcornea, and glucosuria in a single family. Whereas the MCT12 mutation cosegregated with the eye phenotype, poor correlation with the glucosuria phenotype did not support a pathogenic role of the mutation in the kidney. Here, we examined MCT12 in the kidney and found that it resides on basolateral membranes of proximal tubules. Patients with MCT12 mutation exhibited reduced plasma levels and increased fractional excretion of guanidinoacetate, but normal creatine levels, suggesting that MCT12 may function as a guanidinoacetate transporter in vivo. However, functional studies in Xenopus oocytes revealed that MCT12 transports creatine but not its precursor, guanidinoacetate. Genetic analysis revealed a separate, undescribed heterozygous mutation (c.265G>A; p.A89T) in the sodium/glucose cotransporter 2-encoding gene SGLT2 (also known as SLC5A2) in the family that segregated with the renal glucosuria phenotype. When overexpressed in HEK293 cells, the mutant SGLT2 transporter did not efficiently translocate to the plasma membrane, and displayed greatly reduced transport activity. In summary, our data indicate that MCT12 functions as a basolateral exit pathway for creatine in the proximal tubule. Heterozygous mutation of MCT12 affects systemic levels and renal handling of guanidinoacetate, possibly through an indirect mechanism. Furthermore, our data reveal a digenic syndrome in the index family, with simultaneous MCT12 and SGLT2 mutation. Thus, glucosuria is not part of the MCT12 mutation syndrome.Dhayat, NasserSimonin, AlexandreAnderegg, ManuelPathare, GaneshLüscher, Benjamin PDeisl, ChristineAlbano, GiuseppeMordasini, DavidHediger, Matthias A.Surbek, Daniel V.Vogt, BrunoSass, Jörn OliverKloeckener-Gruissem, BarbaraFuster, Daniel G.2015-09-16T09:16:45-07:00doi:10.1681/ASN.2015040411hwp:resource-id:jnephrol;27/5/1426American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell and transport physiology, familial nephropathy, genetic renal diseaseBasic ResearchBasic Researchresearch-article20162016-05-01May 201610.1681/ASN.20150404111046-66731533-34502015-09-16T09:16:45-07:002016-05Journal of the American Society of NephrologyBasic Research27514261436
- Slowing Polycystic Kidney Disease by Fasting10.1681/ASN.2015101113Wed, 04 Nov 2015 10:27:51 GMT-08:00Slowing Polycystic Kidney Disease by FastingBoletta, Alessandra2015-11-04T10:27:51-08:00doi:10.1681/ASN.2015101113hwp:resource-id:jnephrol;27/5/1268American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyADPKD, polycystic kidney disease, metabolism, calorie restriction, food, restrictionUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-05-01May 201610.1681/ASN.20151011131046-66731533-34502015-11-04T10:27:51-08:002016-05Journal of the American Society of NephrologyUp Front Matters27551268143712701447
- Medullary Microvascular Thrombosis and Injury in Sickle Hemoglobin C DiseaseSickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/β0-thalassemia, and hemoglobin S/β+-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.10.1681/ASN.2015040399Fri, 06 Nov 2015 05:24:12 GMT-08:00Medullary Microvascular Thrombosis and Injury in Sickle Hemoglobin C DiseaseSickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/β0-thalassemia, and hemoglobin S/β+-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.Bissonnette, Mei Lin Z.Henriksen, Kammi J.Delaney, KristieStankus, NicoleChang, Anthony2015-11-06T05:24:12-08:00doi:10.1681/ASN.2015040399hwp:resource-id:jnephrol;27/5/1300American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyendothelial cells, renal pathology, thrombosis, peritubular capillaryUp Front MattersPathophysiology of the Renal BiopsyUp Front MattersPathophysiology of the Renal Biopsyresearch-article20162016-05-01May 201610.1681/ASN.20150403991046-66731533-34502015-11-06T05:24:12-08:002016-05Journal of the American Society of NephrologyUp Front Matters27513001304
- Cancer in ESRD: Clear on the Epidemiology, Hazy on the Mechanisms10.1681/ASN.2015091021Thu, 12 Nov 2015 07:53:33 GMT-08:00Cancer in ESRD: Clear on the Epidemiology, Hazy on the MechanismsLim, Wai HChadban, Steven J2015-11-12T07:53:33-08:00doi:10.1681/ASN.2015091021hwp:resource-id:jnephrol;27/5/1272American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycancer, kidney disease, immunology, transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-05-01May 201610.1681/ASN.20150910211046-66731533-34502015-11-12T07:53:33-08:002016-05Journal of the American Society of NephrologyUp Front Matters27555127214951505127515041515
- Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-d-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic Nephropathy10.2215/CJN.04980515Fri, 22 Jan 2016 07:37:11 GMT-08:00Prognostic Value of Tubulointerstitial Lesions, Urinary N-Acetyl-β-d-Glucosaminidase, and Urinary β2-Microglobulin in Patients with Type 2 Diabetes and Biopsy–Proven Diabetic NephropathyMise, KokiHoshino, JunichiUeno, ToshiharuHazue, RyoHasegawa, JumpeiSekine, AkinariSumida, KeiichiHiramatsu, RikakoHasegawa, EikoYamanouchi, MasayukiHayami, NorikoSuwabe, TatsuyaSawa, NaokiFujii, TakeshiHara, ShigekoOhashi, KenichiTakaichi, KenmeiUbara, Yoshifumi2016-01-22T07:37:11-08:00doi:10.2215/CJN.04980515hwp:resource-id:clinjasn;11/4/593American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, renal pathology, renal prognosis, tubulointerstitial lesion, urinary biomarker, diabetes mellitus, type 2, disease progression, follow-up studies, humans, kidney failure, chronicOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20162016-04-07April 07, 201610.2215/CJN.049805151555-90411555-905X2016-01-22T07:37:11-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114593601
- Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti–Glomerular Basement Membrane Disease10.2215/CJN.05270515Tue, 26 Jan 2016 06:47:26 GMT-08:00Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti–Glomerular Basement Membrane DiseaseLi, Jian-nanCui, ZhaoWang, JiaHu, Shui-yiJia, Xiao-yuGuan, ZheChen, MinXie, CanZhao, Ming-hui2016-01-26T06:47:26-08:00doi:10.2215/CJN.05270515hwp:resource-id:clinjasn;11/4/568American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyANCA, Goodpasture-s syndrome, anti-glomerular basement membrane disease, autoantibodies, follow-up studies, glomerular basement membrane, humans, kidney failure, chronic, survival analysis, antibodyOriginal ArticlesClinical Immunology and PathologyOriginal ArticlesClinical Immunology and Pathologyresearch-article20162016-04-07April 07, 201610.2215/CJN.052705151555-90411555-905X2016-01-26T06:47:26-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114568575
- Comparative Survival among Older Adults with Advanced Kidney Disease Managed Conservatively Versus with Dialysis10.2215/CJN.07510715Thu, 17 Mar 2016 12:54:55 GMT-07:00Comparative Survival among Older Adults with Advanced Kidney Disease Managed Conservatively Versus with DialysisVerberne, Wouter R.Geers, A.B.M. TomJellema, Wilbert T.Vincent, Hieronymus H.van Delden, Johannes J.M.Bos, Willem Jan W.2016-03-17T12:54:55-07:00doi:10.2215/CJN.07510715hwp:resource-id:clinjasn;11/4/633American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyconservative management, renal dialysis, aged, chronic kidney failure, survival analysis, comorbidity, Humans, Kidney Diseases, Renal Replacement Therapy, Retrospective StudiesOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-04-07April 07, 201610.2215/CJN.075107151555-90411555-905X2016-03-17T12:54:55-07:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1144633552640554
- Dying to Feel Better: The Central Role of Dialysis–Induced Tissue Hypoxia10.2215/CJN.01380216Wed, 02 Mar 2016 06:43:28 GMT-08:00Dying to Feel Better: The Central Role of Dialysis–Induced Tissue HypoxiaMcIntyre, ChristopherCrowley, Lisa2016-03-02T06:43:28-08:00doi:10.2215/CJN.01380216hwp:resource-id:clinjasn;11/4/549American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymortality, symptoms, cardiac stunning, cognitive impairment, hemodialysis, Anoxia, Emotions, Fluid Therapy, renal dialysisEditorialsEditorialseditorial20162016-04-07April 07, 201610.2215/CJN.013802161555-90411555-905X2016-03-02T06:43:28-08:002016-04-07Clinical Journal of the American Society of NephrologyEditorials1144549616551625
- Arrhythmia and Sudden Death in Hemodialysis Patients: Protocol and Baseline Characteristics of the Monitoring in Dialysis Study10.2215/CJN.09350915Wed, 13 Jan 2016 07:12:56 GMT-08:00Arrhythmia and Sudden Death in Hemodialysis Patients: Protocol and Baseline Characteristics of the Monitoring in Dialysis StudyCharytan, David M.Foley, RobertMcCullough, Peter A.Rogers, John D.Zimetbaum, PeterHerzog, Charles A.Tumlin, James A.2016-01-13T07:12:56-08:00doi:10.2215/CJN.09350915hwp:resource-id:clinjasn;11/4/721American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, cardiovascular disease, hemodialysis, arrhythmias, cardiac, cohort studies, death, sudden, heart conduction system, humans, kidney failure, chronic, renal dialysisSpecial FeatureSpecial Featureresearch-article20162016-04-07April 07, 201610.2215/CJN.093509151555-90411555-905X2016-01-13T07:12:56-08:002016-04-07Clinical Journal of the American Society of NephrologySpecial Feature114721734
- Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis10.2215/CJN.07540715Tue, 19 Jan 2016 06:59:05 GMT-08:00Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or NephrocalcinosisBraun, Daniela AnneLawson, Jennifer AshleyGee, Heon YungHalbritter, JanShril, ShirleeTan, WeizhenStein, DeborahWassner, Ari J.Ferguson, Michael A.Gucev, ZoranFisher, BrittanySpaneas, LeslieVarner, JenniferSayer, John A.Milosevic, DankoBaum, MichelleTasic, VeliborHildebrandt, Friedhelm2016-01-19T06:59:05-08:00doi:10.2215/CJN.07540715hwp:resource-id:clinjasn;11/4/664American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, kidney stones, hypercalciuria, nephrocalcinosis, mutation, child, Europe, exons, genes, dominant, humansOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20162016-04-07April 07, 201610.2215/CJN.075407151555-90411555-905X2016-01-19T06:59:05-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114664672
- The Evolving Ethics of Dialysis in the United States: A Principlist Bioethics ApproachThroughout the history of dialysis, four bioethical principles — beneficence, nonmaleficence, autonomy and justice — have been weighted differently based upon changing forces of technologic innovation, resource limitation, and societal values. In the 1960s, a committee of lay people in Seattle attempted to fairly distribute a limited number of maintenance hemodialysis stations guided by considerations of justice. As technology advanced and dialysis was funded under an amendment to the Social Security Act in 1972, focus shifted to providing dialysis for all in need while balancing the burdens of treatment and quality of life, supported by the concepts of beneficence and nonmaleficence. At the end of the last century, the importance of patient preferences and personal values became paramount in medical decisions, reflecting a focus on the principle of autonomy. More recently, greater recognition that health care financial resources are limited makes fair allocation more pressing, again highlighting the importance of distributive justice. The varying application and prioritization of these four principles to both policy and clinical decisions in the United States over the last 50 years makes the history of hemodialysis an instructive platform for understanding principlist bioethics. As medical technology evolves in a landscape of changing personal and societal values, a comprehensive understanding of an ethical framework for evaluating appropriate use of medical interventions enables the clinician to systematically negotiate and optimize difficult ethical situations.10.2215/CJN.04780515Thu, 11 Feb 2016 06:38:11 GMT-08:00The Evolving Ethics of Dialysis in the United States: A Principlist Bioethics ApproachThroughout the history of dialysis, four bioethical principles — beneficence, nonmaleficence, autonomy and justice — have been weighted differently based upon changing forces of technologic innovation, resource limitation, and societal values. In the 1960s, a committee of lay people in Seattle attempted to fairly distribute a limited number of maintenance hemodialysis stations guided by considerations of justice. As technology advanced and dialysis was funded under an amendment to the Social Security Act in 1972, focus shifted to providing dialysis for all in need while balancing the burdens of treatment and quality of life, supported by the concepts of beneficence and nonmaleficence. At the end of the last century, the importance of patient preferences and personal values became paramount in medical decisions, reflecting a focus on the principle of autonomy. More recently, greater recognition that health care financial resources are limited makes fair allocation more pressing, again highlighting the importance of distributive justice. The varying application and prioritization of these four principles to both policy and clinical decisions in the United States over the last 50 years makes the history of hemodialysis an instructive platform for understanding principlist bioethics. As medical technology evolves in a landscape of changing personal and societal values, a comprehensive understanding of an ethical framework for evaluating appropriate use of medical interventions enables the clinician to systematically negotiate and optimize difficult ethical situations.Butler, Catherine R.Mehrotra, RajnishTonelli, Mark R.Lam, Daniel Y.2016-02-11T06:38:11-08:00doi:10.2215/CJN.04780515hwp:resource-id:clinjasn;11/4/704American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, ESRD, Beneficence, Bioethics, Humans, Patient Preference, quality of life, Social Justice, United StatesEthics SeriesEthics Seriesresearch-article20162016-04-07April 07, 201610.2215/CJN.047805151555-90411555-905X2016-02-11T06:38:11-08:002016-04-07Clinical Journal of the American Society of NephrologyEthics Series114704709
- Educating Patients about CKD: The Path to Self-Management and Patient-Centered CarePatient education is associated with better patient outcomes and supported by international guidelines and organizations, but a range of barriers prevent widespread implementation of comprehensive education for people with progressive kidney disease, especially in the United States. Among United States patients, obstacles to education include the complex nature of kidney disease information, low baseline awareness, limited health literacy and numeracy, limited availability of CKD information, and lack of readiness to learn. For providers, lack of time and clinical confidence combine with competing education priorities and confusion about diagnosing CKD to limit educational efforts. At the system level, lack of provider incentives, limited availability of practical decision support tools, and lack of established interdisciplinary care models inhibit patient education. Despite these barriers, innovative education approaches for people with CKD exist, including self-management support, shared decision making, use of digital media, and engaging families and communities. Education efficiency may be increased by focusing on people with progressive disease, establishing interdisciplinary care management including community health workers, and providing education in group settings. New educational approaches are being developed through research and quality improvement efforts, but challenges to evaluating public awareness and patient education programs inhibit identification of successful strategies for broader implementation. However, growing interest in improving patient-centered outcomes may provide new approaches to effective education of people with CKD.10.2215/CJN.07680715Wed, 04 Nov 2015 10:15:13 GMT-08:00Educating Patients about CKD: The Path to Self-Management and Patient-Centered CarePatient education is associated with better patient outcomes and supported by international guidelines and organizations, but a range of barriers prevent widespread implementation of comprehensive education for people with progressive kidney disease, especially in the United States. Among United States patients, obstacles to education include the complex nature of kidney disease information, low baseline awareness, limited health literacy and numeracy, limited availability of CKD information, and lack of readiness to learn. For providers, lack of time and clinical confidence combine with competing education priorities and confusion about diagnosing CKD to limit educational efforts. At the system level, lack of provider incentives, limited availability of practical decision support tools, and lack of established interdisciplinary care models inhibit patient education. Despite these barriers, innovative education approaches for people with CKD exist, including self-management support, shared decision making, use of digital media, and engaging families and communities. Education efficiency may be increased by focusing on people with progressive disease, establishing interdisciplinary care management including community health workers, and providing education in group settings. New educational approaches are being developed through research and quality improvement efforts, but challenges to evaluating public awareness and patient education programs inhibit identification of successful strategies for broader implementation. However, growing interest in improving patient-centered outcomes may provide new approaches to effective education of people with CKD.Narva, Andrew S.Norton, Jenna M.Boulware, L. Ebony2015-11-04T10:15:13-08:00doi:10.2215/CJN.07680715hwp:resource-id:clinjasn;11/4/694American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologypatient education, self-management, shared decision making, chronic kidney disease, patient centered care, decision making, health literacy, humans, kidney diseases, learningEducation SeriesEducation Seriesresearch-article20162016-04-07April 07, 201610.2215/CJN.076807151555-90411555-905X2015-11-04T10:15:13-08:002016-04-07Clinical Journal of the American Society of NephrologyEducation Series114694703
- Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney Disease10.2215/CJN.08300815Thu, 21 Jan 2016 08:03:58 GMT-08:00Automated Segmentation of Kidneys from MR Images in Patients with Autosomal Dominant Polycystic Kidney DiseaseKim, YoungwooGe, YinghuiTao, ChengZhu, JianbingChapman, Arlene B.Torres, Vicente E.Yu, Alan S.L.Mrug, MichalBennett, William M.Flessner, Michael F.Landsittel, Doug P.Bae, Kyongtae T.,2016-01-21T08:03:58-08:00doi:10.2215/CJN.08300815hwp:resource-id:clinjasn;11/4/576American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney, kidney disease, ADPKD, genetic renal disease, kidney volume, glomerular filtration rate, Humans, Magnetic Resonance Imaging, Polycystic Kidney, Autosomal DominantOriginal ArticlesClinical nephrologyOriginal ArticlesClinical nephrologyresearch-article20162016-04-07April 07, 201610.2215/CJN.083008151555-90411555-905X2016-01-21T08:03:58-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114576584
- Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ Damage10.2215/CJN.08530815Thu, 18 Feb 2016 06:34:45 GMT-08:00Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ DamageDrawz, Paul E.Alper, Arnold B.Anderson, Amanda H.Brecklin, Carolyn S.Charleston, JeanneChen, JingDeo, RajatFischer, Michael J.He, JiangHsu, Chi-yuanHuan, YonghongKeane, Martin G.Kusek, John W.Makos, Gail K.Miller, Edgar R.Soliman, Elsayed Z.Steigerwalt, Susan P.Taliercio, Jonathan J.Townsend, Raymond R.Weir, Matthew R.Wright, Jackson T.Xie, DaweiRahman, Mahboob,2016-02-18T06:34:45-08:00doi:10.2215/CJN.08530815hwp:resource-id:clinjasn;11/4/642American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, left ventricular hypertrophy, ambulatory blood pressure monitoring, pulse wave analysis, nighttime, blood pressure, humans, hypertension, masked hypertensionOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20162016-04-07April 07, 201610.2215/CJN.085308151555-90411555-905X2016-02-18T06:34:45-08:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles114642652
- Clinical–Morphological Features and Outcomes of Lupus Podocytopathy10.2215/CJN.06720615Wed, 16 Mar 2016 10:16:14 GMT-07:00Clinical–Morphological Features and Outcomes of Lupus PodocytopathyHu, WeixinChen, YinghuaWang, ShaofanChen, HaoLiu, ZhengzhaoZeng, CaihongZhang, HaitaoLiu, Zhihong2016-03-16T10:16:14-07:00doi:10.2215/CJN.06720615hwp:resource-id:clinjasn;11/4/585American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, pathology, acute kidney injury, biopsy, follow-up studies, glomerulosclerosis, focal segmental, humans, kidney failure, chronic, nephrotic syndrome, proteinuriaOriginal ArticlesClinical nephrologyOriginal ArticlesClinical nephrologyresearch-article20162016-04-07April 07, 201610.2215/CJN.067206151555-90411555-905X2016-03-16T10:16:14-07:002016-04-07Clinical Journal of the American Society of NephrologyOriginal Articles1144585547592548
- Does the Evidence Support Conservative Management as an Alternative to Dialysis for Older Patients with Advanced Kidney Disease?10.2215/CJN.01910216Thu, 17 Mar 2016 12:54:55 GMT-07:00Does the Evidence Support Conservative Management as an Alternative to Dialysis for Older Patients with Advanced Kidney Disease?Tam-Tham, HelenThomas, Chandra M.2016-03-17T12:54:55-07:00doi:10.2215/CJN.01910216hwp:resource-id:clinjasn;11/4/552American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic dialysis, end stage kidney disease, conservative management, geriatric nephrology, Fluid Therapy, Humans, kidney, Kidney Diseases, renal dialysisEditorialsEditorialseditorial20162016-04-07April 07, 201610.2215/CJN.019102161555-90411555-905X2016-03-17T12:54:55-07:002016-04-07Clinical Journal of the American Society of NephrologyEditorials1144552633554640
- A Metabolome-Wide Association Study of Kidney Function and Disease in the General PopulationSmall molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum. The associations of these molecules with GFR estimated on the basis of creatinine (eGFRcr) and cystatin C levels were assessed in ≤1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r≥0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine. Higher C-mannosyltryptophan, pseudouridine, and O-sulfo-L-tyrosine concentrations associated with incident CKD (eGFRcr <60 ml/min per 1.73 m2) in the KORA F4 study. In contrast with serum creatinine, C-mannosyltryptophan and pseudouridine concentrations showed little dependence on sex. Furthermore, correlation with measured GFR in 200 participants in the AASK study was 0.78 for both C-mannosyltryptophan and pseudouridine concentration, and highly significant associations of both metabolites with incident ESRD disappeared upon adjustment for measured GFR. Thus, these molecules may be alternative or complementary markers of kidney function. In conclusion, our study provides a comprehensive list of kidney function–associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR.10.1681/ASN.2014111099Thu, 08 Oct 2015 10:32:21 GMT-07:00A Metabolome-Wide Association Study of Kidney Function and Disease in the General PopulationSmall molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum. The associations of these molecules with GFR estimated on the basis of creatinine (eGFRcr) and cystatin C levels were assessed in ≤1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r≥0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine. Higher C-mannosyltryptophan, pseudouridine, and O-sulfo-L-tyrosine concentrations associated with incident CKD (eGFRcr <60 ml/min per 1.73 m2) in the KORA F4 study. In contrast with serum creatinine, C-mannosyltryptophan and pseudouridine concentrations showed little dependence on sex. Furthermore, correlation with measured GFR in 200 participants in the AASK study was 0.78 for both C-mannosyltryptophan and pseudouridine concentration, and highly significant associations of both metabolites with incident ESRD disappeared upon adjustment for measured GFR. Thus, these molecules may be alternative or complementary markers of kidney function. In conclusion, our study provides a comprehensive list of kidney function–associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR.Sekula, PeggyGoek, Oemer-NecmiQuaye, LydiaBarrios, ClaraLevey, Andrew S.Römisch-Margl, WernerMenni, CristinaYet, IdilGieger, ChristianInker, Lesley A.Adamski, JerzyGronwald, WolframIllig, ThomasDettmer, KatjaKrumsiek, JanOefner, Peter J.Valdes, Ana M.Meisinger, ChristaCoresh, JosefSpector, Tim D.Mohney, Robert P.Suhre, KarstenKastenmüller, GabiKöttgen, Anna2015-10-08T10:32:21-07:00doi:10.1681/ASN.2014111099hwp:resource-id:jnephrol;27/4/1175American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, metabolism, epidemiology, outcomes, GFRClinical EpidemiologyClinical Epidemiologyresearch-article20162016-04-01April 201610.1681/ASN.20141110991046-66731533-34502015-10-08T10:32:21-07:002016-04Journal of the American Society of NephrologyClinical Epidemiology27411751188
- Nephrin Trafficking beyond the Kidney—Role in Glucose–Stimulated Insulin Secretion in β Cells10.1681/ASN.2015080960Wed, 23 Sep 2015 12:03:10 GMT-07:00Nephrin Trafficking beyond the Kidney—Role in Glucose–Stimulated Insulin Secretion in β CellsLehtonen, SannaJalanko, Hannu2015-09-23T12:03:10-07:00doi:10.1681/ASN.2015080960hwp:resource-id:jnephrol;27/4/965American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynephrin, pancreas, insulin secretion, β cellUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-04-01April 201610.1681/ASN.20150809601046-66731533-34502015-09-23T12:03:10-07:002016-04Journal of the American Society of NephrologyUp Front Matters274496510299681041
- Targeting Endogenous Repair Pathways after AKIAKI remains a highly prevalent disease associated with poor short– and long–term outcomes and high costs. Although significant advances in our understanding of repair after AKI have been made over the last 5 years, this knowledge has not yet been translated into new AKI therapies. A consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 and reviewed new evidence on successful kidney repair to identify the most promising pathways that could be translated into new treatments. In this paper, we provide a summary of current knowledge regarding successful kidney repair and offer a framework for conceptualizing the therapeutic targeting that may facilitate this process. We outline gaps in knowledge and suggest a research agenda to more efficiently bring new discoveries regarding repair after AKI to the clinic.10.1681/ASN.2015030286Wed, 18 Nov 2015 04:57:55 GMT-08:00Targeting Endogenous Repair Pathways after AKIAKI remains a highly prevalent disease associated with poor short– and long–term outcomes and high costs. Although significant advances in our understanding of repair after AKI have been made over the last 5 years, this knowledge has not yet been translated into new AKI therapies. A consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 and reviewed new evidence on successful kidney repair to identify the most promising pathways that could be translated into new treatments. In this paper, we provide a summary of current knowledge regarding successful kidney repair and offer a framework for conceptualizing the therapeutic targeting that may facilitate this process. We outline gaps in knowledge and suggest a research agenda to more efficiently bring new discoveries regarding repair after AKI to the clinic.Humphreys, Benjamin D.Cantaluppi, VincenzoPortilla, DidierSingbartl, KaiYang, LiRosner, Mitchell H.Kellum, John A.Ronco, Claudio,2015-11-18T04:57:55-08:00doi:10.1681/ASN.2015030286hwp:resource-id:jnephrol;27/4/990American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cell biology and structure, cell survival, CKD, stem cell, interstitial fibrosisUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-04-01April 201610.1681/ASN.20150302861046-66731533-34502015-11-18T04:57:55-08:002016-04Journal of the American Society of NephrologyUp Front Matters274990998
- Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1–Induced Parathyroid Cell Proliferation in Secondary HyperparathyroidismSecondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6p−/− mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid–induced AKI. Uremic rpS6p−/− mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild–type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6.10.1681/ASN.2015040339Mon, 17 Aug 2015 05:39:11 GMT-07:00Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1–Induced Parathyroid Cell Proliferation in Secondary HyperparathyroidismSecondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6p−/− mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid–induced AKI. Uremic rpS6p−/− mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild–type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6.Volovelsky, OdedCohen, GiliKenig, ArielWasserman, GiladDreazen, AvigailMeyuhas, OdedSilver, JustinNaveh-Many, Tally2015-08-17T05:39:11-07:00doi:10.1681/ASN.2015040339hwp:resource-id:jnephrol;27/4/1091American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal failure, mineral metabolism, parathyroid hormone, calcium-sensing receptorBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150403391046-66731533-34502015-08-17T05:39:11-07:002016-04Journal of the American Society of NephrologyBasic Research27410911101
- Nephrin Contributes to Insulin Secretion and Affects Mammalian Target of Rapamycin Signaling Independently of Insulin ReceptorNephrin belongs to a family of highly conserved proteins with a well characterized function as modulators of cell adhesion and guidance, and nephrin may have a role in metabolic pathways linked to podocyte and pancreatic β–cell survival. However, this role is incompletely characterized. In this study, we developed floxed nephrin mice for pancreatic β-cell–specific deletion of nephrin, which had no effect on islet size and glycemia. Nephrin deficiency, however, resulted in glucose intolerance in vivo and impaired glucose–stimulated insulin release ex vivo. Glucose intolerance was also observed in eight patients with nephrin mutations compared with three patients with other genetic forms of nephrotic syndrome or nine healthy controls. In vitro experiments were conducted to investigate if nephrin affects autocrine signaling through insulin receptor A (IRA) and B (IRB), which are both expressed in human podocytes and pancreatic islets. Coimmunoprecipitation of nephrin and IRB but not IRA was observed and required IR phosphorylation. Nephrin per se was sufficient to induce phosphorylation of p70S6K in an phosphatidylinositol 3-kinase–dependent but IR/Src-independent manner, which was not augmented by exogenous insulin. These results suggest a role for nephrin as an independent modulator of podocyte and pancreatic β–cell nutrient sensing in the fasting state and the potential of nephrin as a drug target in diabetes.10.1681/ASN.2015020210Wed, 23 Sep 2015 12:03:12 GMT-07:00Nephrin Contributes to Insulin Secretion and Affects Mammalian Target of Rapamycin Signaling Independently of Insulin ReceptorNephrin belongs to a family of highly conserved proteins with a well characterized function as modulators of cell adhesion and guidance, and nephrin may have a role in metabolic pathways linked to podocyte and pancreatic β–cell survival. However, this role is incompletely characterized. In this study, we developed floxed nephrin mice for pancreatic β-cell–specific deletion of nephrin, which had no effect on islet size and glycemia. Nephrin deficiency, however, resulted in glucose intolerance in vivo and impaired glucose–stimulated insulin release ex vivo. Glucose intolerance was also observed in eight patients with nephrin mutations compared with three patients with other genetic forms of nephrotic syndrome or nine healthy controls. In vitro experiments were conducted to investigate if nephrin affects autocrine signaling through insulin receptor A (IRA) and B (IRB), which are both expressed in human podocytes and pancreatic islets. Coimmunoprecipitation of nephrin and IRB but not IRA was observed and required IR phosphorylation. Nephrin per se was sufficient to induce phosphorylation of p70S6K in an phosphatidylinositol 3-kinase–dependent but IR/Src-independent manner, which was not augmented by exogenous insulin. These results suggest a role for nephrin as an independent modulator of podocyte and pancreatic β–cell nutrient sensing in the fasting state and the potential of nephrin as a drug target in diabetes.Villarreal, RodrigoMitrofanova, AllaMaiguel, DonyMorales, XimenaJeon, JongminGrahammer, FlorianLeibiger, Ingo B.Guzman, JohannaFachado, AlbertoYoo, Tae H.Busher Katin, AnjaGellermann, JuttaMerscher, SandraBurke, George W.Berggren, Per-OlofOh, JunHuber, Tobias B.Fornoni, Alessia2015-09-23T12:03:12-07:00doi:10.1681/ASN.2015020210hwp:resource-id:jnephrol;27/4/1029American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologynephrin, diabetes, metabolism, signalingBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150202101046-66731533-34502015-09-23T12:03:12-07:002016-04Journal of the American Society of NephrologyBasic Research274410299651041968
- HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney DiseaseHereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman’s capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44, α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman’s capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders.10.1681/ASN.2014121217Mon, 10 Aug 2015 07:04:01 GMT-07:00HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney DiseaseHereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman’s capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44, α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman’s capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders.Chen, ZhiyongMigeon, TiffanyVerpont, Marie-ChristineZaidan, MohamadSado, YoshikazuKerjaschki, DontschoRonco, PierrePlaisier, Emmanuelle2015-08-10T07:04:01-07:00doi:10.1681/ASN.2014121217hwp:resource-id:jnephrol;27/4/1042American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, glomerular epithelial cells, molecular biology, kidney developmentBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20141212171046-66731533-34502015-08-10T07:04:01-07:002016-04Journal of the American Society of NephrologyBasic Research27410421054
- Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in PodocytesPodocytes are terminally differentiated epithelial cells that reside along the glomerular filtration barrier. Evidence suggests that after podocyte injury, endoplasmic reticulum stress response is activated, but the molecular mechanisms involved are incompletely defined. In a mouse model, we confirmed that podocyte injury induces endoplasmic reticulum stress response and upregulated unfolded protein response pathways, which have been shown to mitigate damage by preventing the accumulation of misfolded proteins in the endoplasmic reticulum. Furthermore, simultaneous podocyte-specific genetic inactivation of X-box binding protein-1 (Xbp1), a transcription factor activated during endoplasmic reticulum stress and critically involved in the untranslated protein response, and Sec63, a heat shock protein-40 chaperone required for protein folding in the endoplasmic reticulum, resulted in progressive albuminuria, foot process effacement, and histology consistent with ESRD. Finally, loss of both Sec63 and Xbp1 induced apoptosis in podocytes, which associated with activation of the JNK pathway. Collectively, our results indicate that an intact Xbp1 pathway operating to mitigate stress in the endoplasmic reticulum is essential for the maintenance of a normal glomerular filtration barrier.10.1681/ASN.2015020191Mon, 24 Aug 2015 07:37:10 GMT-07:00Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in PodocytesPodocytes are terminally differentiated epithelial cells that reside along the glomerular filtration barrier. Evidence suggests that after podocyte injury, endoplasmic reticulum stress response is activated, but the molecular mechanisms involved are incompletely defined. In a mouse model, we confirmed that podocyte injury induces endoplasmic reticulum stress response and upregulated unfolded protein response pathways, which have been shown to mitigate damage by preventing the accumulation of misfolded proteins in the endoplasmic reticulum. Furthermore, simultaneous podocyte-specific genetic inactivation of X-box binding protein-1 (Xbp1), a transcription factor activated during endoplasmic reticulum stress and critically involved in the untranslated protein response, and Sec63, a heat shock protein-40 chaperone required for protein folding in the endoplasmic reticulum, resulted in progressive albuminuria, foot process effacement, and histology consistent with ESRD. Finally, loss of both Sec63 and Xbp1 induced apoptosis in podocytes, which associated with activation of the JNK pathway. Collectively, our results indicate that an intact Xbp1 pathway operating to mitigate stress in the endoplasmic reticulum is essential for the maintenance of a normal glomerular filtration barrier.Hassan, HossamTian, XuefeiInoue, KazunoriChai, NathanLiu, ChangSoda, KeitaMoeckel, GilbertTufro, AldaLee, Ann-HweeSomlo, StefanFedeles, SorinIshibe, Shuta2015-08-24T07:37:10-07:00doi:10.1681/ASN.2015020191hwp:resource-id:jnephrol;27/4/1055American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular epithelial cells, glomerulosclerosis, proteinuriaBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150201911046-66731533-34502015-08-24T07:37:10-07:002016-04Journal of the American Society of NephrologyBasic Research27410551065
- Loss of Epithelial Membrane Protein 2 Aggravates Podocyte Injury via Upregulation of Caveolin-1Nephrotic syndrome is a CKD defined by proteinuria with subsequent hypoalbuminemia, hyperlipidemia, and edema caused by impaired renal glomerular filtration barrier function. We previously identified mutations in epithelial membrane protein 2 (EMP2) as a monogenic cause of this disease. Here, we generated an emp2-knockout zebrafish model using transcription activator-like effector nuclease–based genome editing. We found that loss of emp2 in zebrafish upregulated caveolin-1 (cav1), a major component of caveolae, in embryos and adult mesonephric glomeruli and exacerbated podocyte injury. This phenotype was partially rescued by glucocorticoids. Furthermore, overexpression of cav1 in zebrafish podocytes was sufficient to induce the same phenotype observed in emp2 homozygous mutants, which was also treatable with glucocorticoids. Similarly, knockdown of EMP2 in cultured human podocytes resulted in increased CAV1 expression and decreased podocyte survival in the presence of puromycin aminonucleoside, whereas glucocorticoid treatment ameliorated this phenotype. Taken together, we have established excessive CAV1 as a mediator of the predisposition to podocyte injury because of loss of EMP2, suggesting CAV1 could be a novel therapeutic target in nephrotic syndrome and podocyte injury.10.1681/ASN.2014121197Tue, 11 Aug 2015 08:17:37 GMT-07:00Loss of Epithelial Membrane Protein 2 Aggravates Podocyte Injury via Upregulation of Caveolin-1Nephrotic syndrome is a CKD defined by proteinuria with subsequent hypoalbuminemia, hyperlipidemia, and edema caused by impaired renal glomerular filtration barrier function. We previously identified mutations in epithelial membrane protein 2 (EMP2) as a monogenic cause of this disease. Here, we generated an emp2-knockout zebrafish model using transcription activator-like effector nuclease–based genome editing. We found that loss of emp2 in zebrafish upregulated caveolin-1 (cav1), a major component of caveolae, in embryos and adult mesonephric glomeruli and exacerbated podocyte injury. This phenotype was partially rescued by glucocorticoids. Furthermore, overexpression of cav1 in zebrafish podocytes was sufficient to induce the same phenotype observed in emp2 homozygous mutants, which was also treatable with glucocorticoids. Similarly, knockdown of EMP2 in cultured human podocytes resulted in increased CAV1 expression and decreased podocyte survival in the presence of puromycin aminonucleoside, whereas glucocorticoid treatment ameliorated this phenotype. Taken together, we have established excessive CAV1 as a mediator of the predisposition to podocyte injury because of loss of EMP2, suggesting CAV1 could be a novel therapeutic target in nephrotic syndrome and podocyte injury.Wan, XiaoyangChen, ZhaohongChoi, Won-IlGee, Heon YungHildebrandt, FriedhelmZhou, Weibin2015-08-11T08:17:37-07:00doi:10.1681/ASN.2014121197hwp:resource-id:jnephrol;27/4/1066American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, nephrotic syndrome, podocyte, zebrafishBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20141211971046-66731533-34502015-08-11T08:17:37-07:002016-04Journal of the American Society of NephrologyBasic Research27410661075
- Four-Week Studies of Oral Hypoxia-Inducible Factor–Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of AnemiaHypoxia-inducible factor prolyl hydroxylase inhibitors stabilize levels of hypoxia-inducible factor that upregulate transcription of multiple genes associated with the response to hypoxia, including production of erythropoietin. We conducted two phase 2a studies to explore the relationship between the dose of the hypoxia-inducible factor–prolyl hydroxylase inhibitor GSK1278863 and hemoglobin response in patients with anemia of CKD (baseline hemoglobin 8.5–11.0 g/dl) not undergoing dialysis and not receiving recombinant human erythropoietin (nondialysis study) and in patients with anemia of CKD (baseline hemoglobin 9.5–12.0 g/dl) on hemodialysis and being treated with stable doses of recombinant human erythropoietin (hemodialysis study). Participants were randomized 1:1:1:1 to a once-daily oral dose of GSK1278863 (0.5 mg, 2 mg, or 5 mg) or control (placebo for the nondialysis study; continuing on recombinant human erythropoietin for the hemodialysis study) for 4 weeks, with a 2-week follow-up. In the nondialysis study, GSK1278863 produced dose-dependent effects on hemoglobin, with the highest dose resulting in a mean increase of 1 g/dl at week 4. In the hemodialysis study, treatment with GSK1278863 in the 5-mg arm maintained mean hemoglobin concentrations after the switch from recombinant human erythropoietin, whereas mean hemoglobin decreased in the lower-dose arms. In both studies, the effects on hemoglobin occurred with elevations in endogenous erythropoietin within the range usually observed in the respective populations and markedly lower than those in the recombinant human erythropoietin control arm in the hemodialysis study, and without clinically significant elevations in plasma vascular endothelial growth factor concentrations. GSK1278863 was generally safe and well tolerated at the doses and duration studied. GSK1278863 may prove an effective alternative for managing anemia of CKD.10.1681/ASN.2014111139Thu, 22 Oct 2015 07:49:12 GMT-07:00Four-Week Studies of Oral Hypoxia-Inducible Factor–Prolyl Hydroxylase Inhibitor GSK1278863 for Treatment of AnemiaHypoxia-inducible factor prolyl hydroxylase inhibitors stabilize levels of hypoxia-inducible factor that upregulate transcription of multiple genes associated with the response to hypoxia, including production of erythropoietin. We conducted two phase 2a studies to explore the relationship between the dose of the hypoxia-inducible factor–prolyl hydroxylase inhibitor GSK1278863 and hemoglobin response in patients with anemia of CKD (baseline hemoglobin 8.5–11.0 g/dl) not undergoing dialysis and not receiving recombinant human erythropoietin (nondialysis study) and in patients with anemia of CKD (baseline hemoglobin 9.5–12.0 g/dl) on hemodialysis and being treated with stable doses of recombinant human erythropoietin (hemodialysis study). Participants were randomized 1:1:1:1 to a once-daily oral dose of GSK1278863 (0.5 mg, 2 mg, or 5 mg) or control (placebo for the nondialysis study; continuing on recombinant human erythropoietin for the hemodialysis study) for 4 weeks, with a 2-week follow-up. In the nondialysis study, GSK1278863 produced dose-dependent effects on hemoglobin, with the highest dose resulting in a mean increase of 1 g/dl at week 4. In the hemodialysis study, treatment with GSK1278863 in the 5-mg arm maintained mean hemoglobin concentrations after the switch from recombinant human erythropoietin, whereas mean hemoglobin decreased in the lower-dose arms. In both studies, the effects on hemoglobin occurred with elevations in endogenous erythropoietin within the range usually observed in the respective populations and markedly lower than those in the recombinant human erythropoietin control arm in the hemodialysis study, and without clinically significant elevations in plasma vascular endothelial growth factor concentrations. GSK1278863 was generally safe and well tolerated at the doses and duration studied. GSK1278863 may prove an effective alternative for managing anemia of CKD.Holdstock, LouisMeadowcroft, Amy M.Maier, RaymaJohnson, Brendan M.Jones, DelythRastogi, AnjayZeig, StevenLepore, John J.Cobitz, Alexander R.2015-10-22T07:49:12-07:00doi:10.1681/ASN.2014111139hwp:resource-id:jnephrol;27/4/1234American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, anemia, erythropoietinClinical ResearchClinical Researchresearch-article20162016-04-01April 201610.1681/ASN.20141111391046-66731533-34502015-10-22T07:49:12-07:002016-04Journal of the American Society of NephrologyClinical Research274412349681244970
- This Month's Highlights10.1681/ASN.2015121334Thu, 31 Mar 2016 10:01:05 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2016-03-31T10:01:05-07:00doi:10.1681/ASN.2015121334hwp:resource-id:jnephrol;27/4/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-04-01April 201610.1681/ASN.20151213341046-66731533-34502016-03-31T10:01:05-07:002016-04Journal of the American Society of NephrologyThis Month's Highlights274ii
- Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced DiabetesEvaluating the mRNA profile of podocytes in the diabetic kidney may indicate genes involved in the pathogenesis of diabetic nephropathy. To determine if the podocyte-specific gene information contained in mRNA profiles of the whole glomerulus of the diabetic kidney accurately reflects gene expression in the isolated podocytes, we crossed Nos3−/− IRG mice with podocin-rtTA and TetON-Cre mice for enhanced green fluorescent protein labeling of podocytes before diabetic injury. Diabetes was induced by streptozotocin, and mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice were examined 10 weeks later. Expression of podocyte-specific markers in glomeruli was downregulated in diabetic mice compared with controls. However, expression of these markers was not altered in sorted podocytes from diabetic mice. When mRNA levels of glomeruli were corrected for podocyte number per glomerulus, the differences in podocyte marker expression disappeared. Analysis of the differentially expressed genes in diabetic mice also revealed distinct upregulated pathways in the glomeruli (mitochondrial function, oxidative stress) and in podocytes (actin organization). In conclusion, our data suggest reduced expression of podocyte markers in glomeruli is a secondary effect of reduced podocyte number, thus podocyte-specific gene expression detected in the whole glomerulus may not represent that in podocytes in the diabetic kidney.10.1681/ASN.2015040421Tue, 11 Aug 2015 08:17:38 GMT-07:00Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced DiabetesEvaluating the mRNA profile of podocytes in the diabetic kidney may indicate genes involved in the pathogenesis of diabetic nephropathy. To determine if the podocyte-specific gene information contained in mRNA profiles of the whole glomerulus of the diabetic kidney accurately reflects gene expression in the isolated podocytes, we crossed Nos3−/− IRG mice with podocin-rtTA and TetON-Cre mice for enhanced green fluorescent protein labeling of podocytes before diabetic injury. Diabetes was induced by streptozotocin, and mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice were examined 10 weeks later. Expression of podocyte-specific markers in glomeruli was downregulated in diabetic mice compared with controls. However, expression of these markers was not altered in sorted podocytes from diabetic mice. When mRNA levels of glomeruli were corrected for podocyte number per glomerulus, the differences in podocyte marker expression disappeared. Analysis of the differentially expressed genes in diabetic mice also revealed distinct upregulated pathways in the glomeruli (mitochondrial function, oxidative stress) and in podocytes (actin organization). In conclusion, our data suggest reduced expression of podocyte markers in glomeruli is a secondary effect of reduced podocyte number, thus podocyte-specific gene expression detected in the whole glomerulus may not represent that in podocytes in the diabetic kidney.Fu, JiaWei, ChengguoLee, KyungZhang, WeijiaHe, WuChuang, PeterLiu, ZhihongHe, John Cijiang2015-08-11T08:17:38-07:00doi:10.1681/ASN.2015040421hwp:resource-id:jnephrol;27/4/1006American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, gene transcription, glomerulus, podocyte, signalingBrief CommunicationsBrief Communicationsbrief-report20162016-04-01April 201610.1681/ASN.20150404211046-66731533-34502015-08-11T08:17:38-07:002016-04Journal of the American Society of NephrologyBrief Communications27410061014
- New Solutions to Reduce Discard of Kidneys Donated for TransplantationKidney transplantation is a cost-saving treatment that extends the lives of patients with ESRD. Unfortunately, the kidney transplant waiting list has ballooned to over 100,000 Americans. Across large areas of the United States, many kidney transplant candidates spend over 5 years waiting and often die before undergoing transplantation. However, more than 2500 kidneys (>17% of the total recovered from deceased donors) were discarded in 2013, despite evidence that many of these kidneys would provide a survival benefit to wait-listed patients. Transplant leaders have focused attention on transplant center report cards as a likely cause for this discard problem, although that focus is too narrow. In this review, we examine the risks associated with accepting various categories of donated kidneys, including discarded kidneys, compared with the risk of remaining on dialysis. With the goal of improving access to kidney transplant, we describe feasible proposals to increase acceptance of currently discarded organs.10.1681/ASN.2015010023Mon, 14 Sep 2015 04:57:21 GMT-07:00New Solutions to Reduce Discard of Kidneys Donated for TransplantationKidney transplantation is a cost-saving treatment that extends the lives of patients with ESRD. Unfortunately, the kidney transplant waiting list has ballooned to over 100,000 Americans. Across large areas of the United States, many kidney transplant candidates spend over 5 years waiting and often die before undergoing transplantation. However, more than 2500 kidneys (>17% of the total recovered from deceased donors) were discarded in 2013, despite evidence that many of these kidneys would provide a survival benefit to wait-listed patients. Transplant leaders have focused attention on transplant center report cards as a likely cause for this discard problem, although that focus is too narrow. In this review, we examine the risks associated with accepting various categories of donated kidneys, including discarded kidneys, compared with the risk of remaining on dialysis. With the goal of improving access to kidney transplant, we describe feasible proposals to increase acceptance of currently discarded organs.Reese, Peter P.Harhay, Meera N.Abt, Peter L.Levine, Matthew H.Halpern, Scott D.2015-09-14T04:57:21-07:00doi:10.1681/ASN.2015010023hwp:resource-id:jnephrol;27/4/973American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, outcomes, epidemiology and outcomesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-04-01April 201610.1681/ASN.20150100231046-66731533-34502015-09-14T04:57:21-07:002016-04Journal of the American Society of NephrologyUp Front Matters274973980
- Potassium and Its Discontents: New Insight, New TreatmentsHyperkalemia is common in patients with impaired kidney function or who take drugs that inhibit the renin-angiotensin-aldosterone axis. During the past decade, substantial advances in understanding how the body controls potassium excretion have been made, which may lead to improved standard of care for these patients. Renal potassium disposition is primarily handled by a short segment of the nephron, comprising part of the distal convoluted tubule and the connecting tubule, and regulation results from the interplay between aldosterone and plasma potassium. When dietary potassium intake and plasma potassium are low, the electroneutral sodium chloride cotransporter is activated, leading to salt retention. This effect limits sodium delivery to potassium secretory segments, limiting potassium losses. In contrast, when dietary potassium intake is high, aldosterone is stimulated. Simultaneously, potassium inhibits the sodium chloride cotransporter. Because more sodium is then delivered to potassium secretory segments, primed by aldosterone, kaliuresis results. When these processes are disrupted, hyperkalemia results. Recently, new agents capable of removing potassium from the body and treating hyperkalemia have been tested in clinical trials. This development suggests that more effective and safer approaches to the prevention and treatment of hyperkalemia may be on the horizon.10.1681/ASN.2015070751Wed, 28 Oct 2015 07:03:12 GMT-07:00Potassium and Its Discontents: New Insight, New TreatmentsHyperkalemia is common in patients with impaired kidney function or who take drugs that inhibit the renin-angiotensin-aldosterone axis. During the past decade, substantial advances in understanding how the body controls potassium excretion have been made, which may lead to improved standard of care for these patients. Renal potassium disposition is primarily handled by a short segment of the nephron, comprising part of the distal convoluted tubule and the connecting tubule, and regulation results from the interplay between aldosterone and plasma potassium. When dietary potassium intake and plasma potassium are low, the electroneutral sodium chloride cotransporter is activated, leading to salt retention. This effect limits sodium delivery to potassium secretory segments, limiting potassium losses. In contrast, when dietary potassium intake is high, aldosterone is stimulated. Simultaneously, potassium inhibits the sodium chloride cotransporter. Because more sodium is then delivered to potassium secretory segments, primed by aldosterone, kaliuresis results. When these processes are disrupted, hyperkalemia results. Recently, new agents capable of removing potassium from the body and treating hyperkalemia have been tested in clinical trials. This development suggests that more effective and safer approaches to the prevention and treatment of hyperkalemia may be on the horizon.Ellison, David H.Terker, Andrew S.Gamba, Gerardo2015-10-28T07:03:12-07:00doi:10.1681/ASN.2015070751hwp:resource-id:jnephrol;27/4/981American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyion transport, K channels, ion channelUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-04-01April 201610.1681/ASN.20150707511046-66731533-34502015-10-28T07:03:12-07:002016-04Journal of the American Society of NephrologyUp Front Matters274981989
- B7–1 Is Not Induced in Podocytes of Human and Experimental Diabetic NephropathyThe incidence of progressive kidney disease associated with diabetes continues to rise worldwide. Current standard therapy with angiotensin–converting enzyme inhibitors and/or angiotensin receptor blockers achieves only partial renoprotection, increasing the need for novel therapeutic approaches. Previous studies described B7–1 induction in podocytes of patients with proteinuria, including those with FSGS and type 2 diabetic nephropathy (DN). These findings sparked great excitement in the renal community, implying that abatacept, a costimulatory inhibitor that targets B7–1, could be a novel therapy for diabetic renal disease. Given previous concerns over the value of B7–1 immunostaining and the efficacy of abatacept in patients with recurrent FSGS after renal transplantation, we investigated B7–1 expression in human and experimental DN before embarking on clinical studies of the use of B7–1 targeting strategies to treat proteinuria in DN. Immunohistochemical analysis of kidney specimens using different antibodies revealed that B7–1 is not induced in podocytes of patients with DN, independent of disease stage, or BTBR ob/ob mice, a model of type 2 diabetes. These results do not support the use of abatacept as a therapeutic strategy for targeting podocyte B7–1 for the prevention or treatment of DN.10.1681/ASN.2015030266Fri, 28 Aug 2015 08:24:05 GMT-07:00B7–1 Is Not Induced in Podocytes of Human and Experimental Diabetic NephropathyThe incidence of progressive kidney disease associated with diabetes continues to rise worldwide. Current standard therapy with angiotensin–converting enzyme inhibitors and/or angiotensin receptor blockers achieves only partial renoprotection, increasing the need for novel therapeutic approaches. Previous studies described B7–1 induction in podocytes of patients with proteinuria, including those with FSGS and type 2 diabetic nephropathy (DN). These findings sparked great excitement in the renal community, implying that abatacept, a costimulatory inhibitor that targets B7–1, could be a novel therapy for diabetic renal disease. Given previous concerns over the value of B7–1 immunostaining and the efficacy of abatacept in patients with recurrent FSGS after renal transplantation, we investigated B7–1 expression in human and experimental DN before embarking on clinical studies of the use of B7–1 targeting strategies to treat proteinuria in DN. Immunohistochemical analysis of kidney specimens using different antibodies revealed that B7–1 is not induced in podocytes of patients with DN, independent of disease stage, or BTBR ob/ob mice, a model of type 2 diabetes. These results do not support the use of abatacept as a therapeutic strategy for targeting podocyte B7–1 for the prevention or treatment of DN.Gagliardini, ElenaNovelli, RubinaCorna, DanielaZoja, CarlamariaRuggiero, BarbaraBenigni, ArielaRemuzzi, Giuseppe2015-08-28T08:24:05-07:00doi:10.1681/ASN.2015030266hwp:resource-id:jnephrol;27/4/999American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, podocyte, B7–1Brief CommunicationsBrief Communicationsbrief-report20162016-04-01April 201610.1681/ASN.20150302661046-66731533-34502015-08-28T08:24:05-07:002016-04Journal of the American Society of NephrologyBrief Communications27449999631005965
- Sphingosine 1-Phosphate Receptor 3–Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion InjuryThe plasticity of dendritic cells (DCs) permits phenotypic modulation ex vivo by gene expression or pharmacologic agents, and these modified DCs can exert therapeutic immunosuppressive effects in vivo through direct interactions with T cells, either inducing T regulatory cells (TREGs) or causing anergy. Sphingosine 1-phosphate (S1P) is a sphingolipid and the natural ligand for five G protein–coupled receptors (S1P1, S1P2, S1P3, S1P4, and S1P5), and S1PR agonists reduce kidney ischemia-reperfusion injury (IRI) in mice. S1pr3−/− mice are protected from kidney IRI, because DCs do not mature. We tested the therapeutic advantage of S1pr3−/− bone marrow–derived dendritic cell (BMDC) transfers in kidney IRI. IRI produced a rise in plasma creatinine (PCr) levels in mice receiving no cells (NCs) and mice pretreated with wild-type (WT) BMDCs. However, S1pr3−/− BMDC–pretreated mice were protected from kidney IRI. S1pr3−/− BMDC–pretreated mice had significantly higher numbers of splenic TREGs compared with NC and WT BMDC–pretreated mice. S1pr3−/− BMDCs did not attenuate IRI in splenectomized, Rag-1−/−, or CD11c+ DC–depleted mice. Additionally, S1pr3−/− BMDC–dependent protection required CD169+ marginal zone macrophages and the macrophage–derived chemokine CCL22 to increase splenic CD4+Foxp3+ TREGs. Pretreatment with S1pr3−/− BMDCs also induced TREG-dependent protection against IRI in an allogeneic mouse model. In summary, adoptively transferred S1pr3−/− BMDCs prevent kidney IRI through interactions within the spleen and expansion of splenic CD4+Foxp3+ TREGs. We conclude that genetically induced deficiency of S1pr3 in allogenic BMDCs could serve as a therapeutic approach to prevent IRI-induced AKI.10.1681/ASN.2015010095Tue, 18 Aug 2015 06:20:02 GMT-07:00Sphingosine 1-Phosphate Receptor 3–Deficient Dendritic Cells Modulate Splenic Responses to Ischemia-Reperfusion InjuryThe plasticity of dendritic cells (DCs) permits phenotypic modulation ex vivo by gene expression or pharmacologic agents, and these modified DCs can exert therapeutic immunosuppressive effects in vivo through direct interactions with T cells, either inducing T regulatory cells (TREGs) or causing anergy. Sphingosine 1-phosphate (S1P) is a sphingolipid and the natural ligand for five G protein–coupled receptors (S1P1, S1P2, S1P3, S1P4, and S1P5), and S1PR agonists reduce kidney ischemia-reperfusion injury (IRI) in mice. S1pr3−/− mice are protected from kidney IRI, because DCs do not mature. We tested the therapeutic advantage of S1pr3−/− bone marrow–derived dendritic cell (BMDC) transfers in kidney IRI. IRI produced a rise in plasma creatinine (PCr) levels in mice receiving no cells (NCs) and mice pretreated with wild-type (WT) BMDCs. However, S1pr3−/− BMDC–pretreated mice were protected from kidney IRI. S1pr3−/− BMDC–pretreated mice had significantly higher numbers of splenic TREGs compared with NC and WT BMDC–pretreated mice. S1pr3−/− BMDCs did not attenuate IRI in splenectomized, Rag-1−/−, or CD11c+ DC–depleted mice. Additionally, S1pr3−/− BMDC–dependent protection required CD169+ marginal zone macrophages and the macrophage–derived chemokine CCL22 to increase splenic CD4+Foxp3+ TREGs. Pretreatment with S1pr3−/− BMDCs also induced TREG-dependent protection against IRI in an allogeneic mouse model. In summary, adoptively transferred S1pr3−/− BMDCs prevent kidney IRI through interactions within the spleen and expansion of splenic CD4+Foxp3+ TREGs. We conclude that genetically induced deficiency of S1pr3 in allogenic BMDCs could serve as a therapeutic approach to prevent IRI-induced AKI.Bajwa, AmandeepHuang, LipingKurmaeva, ElviraGigliotti, Joseph C.Ye, HongMiller, JacquelineRosin, Diane L.Lobo, Peter I.Okusa, Mark D.2015-08-18T06:20:02-07:00doi:10.1681/ASN.2015010095hwp:resource-id:jnephrol;27/4/1076American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, ischemia-reperfusion, immunosuppression, immunologyBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150100951046-66731533-34502015-08-18T06:20:02-07:002016-04Journal of the American Society of NephrologyBasic Research27410761090
- Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKDTraditional histologic methods are limited in their ability to detect pathologic changes of CKD, of which cisplatin therapy is an important cause. In addition, poor reproducibility of available methods has limited analysis of the role of fibrosis in CKD. Highly labor-intensive serial sectioning studies have demonstrated that three-dimensional perspective can reveal useful morphologic information on cisplatin-induced CKD. By applying the new technique of multiphoton microscopy (MPM) with clearing to a new mouse model of cisplatin-induced CKD, we obtained detailed morphologic and collagen reconstructions of millimeter-thick renal sections that provided new insights into pathophysiology. Quantitative analysis revealed that a major long-term cisplatin effect is reduction in the number of cuboidal cells of the glomerular capsule, a change we term the "uncapped glomerulus lesion." Glomerulotubular disconnection was confirmed, but connection remnants between damaged tubules and atubular glomeruli were observed. Reductions in normal glomerular capsules corresponded to reductions in GFR. Mild increases in collagen were noted, but the fibrosis was not spatially correlated with atubular glomeruli. Glomerular volume and number remained unaltered with cisplatin exposure, but cortical tubulointerstitial mass decreased. In conclusion, new observations were made possible by using clearing MPM, demonstrating the utility of this technique for studies of renal disease. This technique should prove valuable for further characterizing the evolution of CKD with cisplatin therapy and of other conditions.10.1681/ASN.2015010079Mon, 24 Aug 2015 07:37:12 GMT-07:00Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKDTraditional histologic methods are limited in their ability to detect pathologic changes of CKD, of which cisplatin therapy is an important cause. In addition, poor reproducibility of available methods has limited analysis of the role of fibrosis in CKD. Highly labor-intensive serial sectioning studies have demonstrated that three-dimensional perspective can reveal useful morphologic information on cisplatin-induced CKD. By applying the new technique of multiphoton microscopy (MPM) with clearing to a new mouse model of cisplatin-induced CKD, we obtained detailed morphologic and collagen reconstructions of millimeter-thick renal sections that provided new insights into pathophysiology. Quantitative analysis revealed that a major long-term cisplatin effect is reduction in the number of cuboidal cells of the glomerular capsule, a change we term the "uncapped glomerulus lesion." Glomerulotubular disconnection was confirmed, but connection remnants between damaged tubules and atubular glomeruli were observed. Reductions in normal glomerular capsules corresponded to reductions in GFR. Mild increases in collagen were noted, but the fibrosis was not spatially correlated with atubular glomeruli. Glomerular volume and number remained unaltered with cisplatin exposure, but cortical tubulointerstitial mass decreased. In conclusion, new observations were made possible by using clearing MPM, demonstrating the utility of this technique for studies of renal disease. This technique should prove valuable for further characterizing the evolution of CKD with cisplatin therapy and of other conditions.Torres, RichardVelazquez, HeinoChang, John J.Levene, Michael J.Moeckel, GilbertDesir, Gary V.Safirstein, Robert2015-08-24T07:37:12-07:00doi:10.1681/ASN.2015010079hwp:resource-id:jnephrol;27/4/1102American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal failure, cisplatin nephrotoxicity, histopathology, pathology, renal pathology, renal microscopyBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150100791046-66731533-34502015-08-24T07:37:12-07:002016-04Journal of the American Society of NephrologyBasic Research27411021112
- Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney DiseasecAMP stimulates cell proliferation and Cl–-dependent fluid secretion, promoting the progressive enlargement of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). Intracellular cAMP levels are determined by the balance of cAMP synthesis by adenylyl cyclases and degradation by phosphodiesterases (PDEs). Therefore, PDE isoform expression and activity strongly influence global and compartmentalized cAMP levels. We report here that PDE3 and PDE4 expression levels are lower in human ADPKD tissue and cells compared with those of normal human kidneys (NHKs), whereas PDE1 levels are not significantly different. Inhibition of PDE4 caused a greater increase in basal and vasopressin (AVP)-stimulated cAMP levels and Cl– secretion by ADPKD cells than inhibition of PDE1, and inhibition of PDE4 induced cyst-like dilations in cultured mouse Pkd1−/− embryonic kidneys. In contrast, inhibition of PDE1 caused greater stimulation of extracellular signal–regulated kinase (ERK) and proliferation of ADPKD cells than inhibition of PDE4, and inhibition of PDE1 enhanced AVP-induced ERK activation. Notably, inhibition of PDE1, the only family of Ca2+-regulated PDEs, also induced a mitogenic response to AVP in NHK cells, similar to the effect of restricting intracellular Ca2+. PDE1 coimmunoprecipitated with B-Raf and A-kinase anchoring protein 79, and AVP increased this interaction in ADPKD but not NHK cells. These data suggest that whereas PDE4 is the major PDE isoform involved in the regulation of global intracellular cAMP and Cl– secretion, PDE1 specifically affects the cAMP signal to the B-Raf/MEK/ERK pathway and regulates AVP-induced proliferation of ADPKD cells.10.1681/ASN.2015010047Wed, 19 Aug 2015 05:50:23 GMT-07:00Phosphodiesterase Isoform Regulation of Cell Proliferation and Fluid Secretion in Autosomal Dominant Polycystic Kidney DiseasecAMP stimulates cell proliferation and Cl–-dependent fluid secretion, promoting the progressive enlargement of renal cysts in autosomal dominant polycystic kidney disease (ADPKD). Intracellular cAMP levels are determined by the balance of cAMP synthesis by adenylyl cyclases and degradation by phosphodiesterases (PDEs). Therefore, PDE isoform expression and activity strongly influence global and compartmentalized cAMP levels. We report here that PDE3 and PDE4 expression levels are lower in human ADPKD tissue and cells compared with those of normal human kidneys (NHKs), whereas PDE1 levels are not significantly different. Inhibition of PDE4 caused a greater increase in basal and vasopressin (AVP)-stimulated cAMP levels and Cl– secretion by ADPKD cells than inhibition of PDE1, and inhibition of PDE4 induced cyst-like dilations in cultured mouse Pkd1−/− embryonic kidneys. In contrast, inhibition of PDE1 caused greater stimulation of extracellular signal–regulated kinase (ERK) and proliferation of ADPKD cells than inhibition of PDE4, and inhibition of PDE1 enhanced AVP-induced ERK activation. Notably, inhibition of PDE1, the only family of Ca2+-regulated PDEs, also induced a mitogenic response to AVP in NHK cells, similar to the effect of restricting intracellular Ca2+. PDE1 coimmunoprecipitated with B-Raf and A-kinase anchoring protein 79, and AVP increased this interaction in ADPKD but not NHK cells. These data suggest that whereas PDE4 is the major PDE isoform involved in the regulation of global intracellular cAMP and Cl– secretion, PDE1 specifically affects the cAMP signal to the B-Raf/MEK/ERK pathway and regulates AVP-induced proliferation of ADPKD cells.Pinto, Cibele S.Raman, ArchanaReif, Gail A.Magenheimer, Brenda S.White, CoreyCalvet, James P.Wallace, Darren P.2015-08-19T05:50:23-07:00doi:10.1681/ASN.2015010047hwp:resource-id:jnephrol;27/4/1124American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycyclic AMP, cyclic GMP, polycystic kidney disease, proliferation, renal, epithelial cell, AVPBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150100471046-66731533-34502015-08-19T05:50:23-07:002016-04Journal of the American Society of NephrologyBasic Research27411241134
- The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 TraffickingMutations in polycystin-1 (PC1) give rise to autosomal dominant polycystic kidney disease, an important and common cause of kidney failure. Despite its medical importance, the function of PC1 remains poorly understood. Here, we investigated the role of the intracellular polycystin-1, lipoxygenase, and α-toxin (PLAT) signature domain of PC1 using nuclear magnetic resonance, biochemical, cellular, and in vivo functional approaches. We found that the PLAT domain targets PC1 to the plasma membrane in polarized epithelial cells by a mechanism involving the selective binding of the PLAT domain to phosphatidylserine and l-α-phosphatidylinositol-4-phosphate (PI4P) enriched in the plasma membrane. This process is regulated by protein kinase A phosphorylation of the PLAT domain, which reduces PI4P binding and recruits β-arrestins and the clathrin adaptor AP2 to trigger PC1 internalization. Our results reveal a physiological role for the PC1-PLAT domain in renal epithelial cells and suggest that phosphorylation-dependent internalization of PC1 is closely linked to its function in renal development and homeostasis.10.1681/ASN.2014111074Wed, 26 Aug 2015 06:22:19 GMT-07:00The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 TraffickingMutations in polycystin-1 (PC1) give rise to autosomal dominant polycystic kidney disease, an important and common cause of kidney failure. Despite its medical importance, the function of PC1 remains poorly understood. Here, we investigated the role of the intracellular polycystin-1, lipoxygenase, and α-toxin (PLAT) signature domain of PC1 using nuclear magnetic resonance, biochemical, cellular, and in vivo functional approaches. We found that the PLAT domain targets PC1 to the plasma membrane in polarized epithelial cells by a mechanism involving the selective binding of the PLAT domain to phosphatidylserine and l-α-phosphatidylinositol-4-phosphate (PI4P) enriched in the plasma membrane. This process is regulated by protein kinase A phosphorylation of the PLAT domain, which reduces PI4P binding and recruits β-arrestins and the clathrin adaptor AP2 to trigger PC1 internalization. Our results reveal a physiological role for the PC1-PLAT domain in renal epithelial cells and suggest that phosphorylation-dependent internalization of PC1 is closely linked to its function in renal development and homeostasis.Xu, YaoxianStreets, Andrew J.Hounslow, Andrea M.Tran, UyenJean-Alphonse, FredericNeedham, Andrew J.Vilardaga, Jean-PierreWessely, OliverWilliamson, Michael P.Ong, Albert C.M.2015-08-26T06:22:19-07:00doi:10.1681/ASN.2014111074hwp:resource-id:jnephrol;27/4/1159American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyautosomal dominant polycystic kidney disease, polycystic kidney disease, genetics and developmentBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20141110741046-66731533-34502015-08-26T06:22:19-07:002016-04Journal of the American Society of NephrologyBasic Research27411591173
- Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion–Induced Kidney GrowthThe molecular mechanisms underlying renal growth and renal growth–induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in these Tsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast, Tsc1 single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules of Tsc1 and rpS6 double-mutant mice. Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis in Tsc1-deleted kidneys.10.1681/ASN.2014121264Fri, 21 Aug 2015 04:45:35 GMT-07:00Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion–Induced Kidney GrowthThe molecular mechanisms underlying renal growth and renal growth–induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in these Tsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast, Tsc1 single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules of Tsc1 and rpS6 double-mutant mice. Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis in Tsc1-deleted kidneys.Wu, HuijuanChen, JianchunXu, JinxianDong, ZhengMeyuhas, OdedChen, Jian-Kang2015-08-21T04:45:35-07:00doi:10.1681/ASN.2014121264hwp:resource-id:jnephrol;27/4/1145American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal proximal tubule cells, molecular signaling to cell growth and proliferation, kidney growth, nephron damage, cystic kidney, renal fibrosisBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20141212641046-66731533-34502015-08-21T04:45:35-07:002016-04Journal of the American Society of NephrologyBasic Research27411451158
- Urinary Sodium and Potassium Excretion and CKD ProgressionCKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (<116.8 mmol/24 h), hazard ratios (95% confidence intervals) for the highest quartile of urinary sodium excretion (≥194.6 mmol/24 h) were 1.54 (1.23 to 1.92) for CKD progression, 1.45 (1.08 to 1.95) for all-cause mortality, and 1.43 (1.18 to 1.73) for the composite outcome of CKD progression and all-cause mortality after adjusting for multiple covariates, including baseline eGFR. Additionally, compared with the lowest quartile of urinary potassium excretion (<39.4 mmol/24 h), hazard ratios for the highest quartile of urinary potassium excretion (≥67.1 mmol/24 h) were 1.59 (1.25 to 2.03) for CKD progression, 0.98 (0.71 to 1.35) for all-cause mortality, and 1.42 (1.15 to 1.74) for the composite outcome. These data indicate that high urinary sodium and potassium excretion are associated with increased risk of CKD progression. Clinical trials are warranted to test the effect of sodium and potassium reduction on CKD progression.10.1681/ASN.2015010022Thu, 17 Sep 2015 06:02:00 GMT-07:00Urinary Sodium and Potassium Excretion and CKD ProgressionCKD is a major risk factor for ESRD, cardiovascular disease, and premature death. Whether dietary sodium and potassium intake affect CKD progression remains unclear. We prospectively studied the association of urinary sodium and potassium excretion with CKD progression and all-cause mortality among 3939 patients with CKD in the Chronic Renal Insufficiency Cohort Study. Urinary sodium and potassium excretion were measured using three 24-hour urine specimens, and CKD progression was defined as incident ESRD or halving of eGFR. During follow-up, 939 CKD progression events and 540 deaths occurred. Compared with the lowest quartile of urinary sodium excretion (<116.8 mmol/24 h), hazard ratios (95% confidence intervals) for the highest quartile of urinary sodium excretion (≥194.6 mmol/24 h) were 1.54 (1.23 to 1.92) for CKD progression, 1.45 (1.08 to 1.95) for all-cause mortality, and 1.43 (1.18 to 1.73) for the composite outcome of CKD progression and all-cause mortality after adjusting for multiple covariates, including baseline eGFR. Additionally, compared with the lowest quartile of urinary potassium excretion (<39.4 mmol/24 h), hazard ratios for the highest quartile of urinary potassium excretion (≥67.1 mmol/24 h) were 1.59 (1.25 to 2.03) for CKD progression, 0.98 (0.71 to 1.35) for all-cause mortality, and 1.42 (1.15 to 1.74) for the composite outcome. These data indicate that high urinary sodium and potassium excretion are associated with increased risk of CKD progression. Clinical trials are warranted to test the effect of sodium and potassium reduction on CKD progression.He, JiangMills, Katherine T.Appel, Lawrence J.Yang, WeiChen, JingLee, Belinda T.Rosas, Sylvia E.Porter, AnnaMakos, GailWeir, Matthew R.Hamm, L. LeeKusek, John W.,2015-09-17T06:02:00-07:00doi:10.1681/ASN.2015010022hwp:resource-id:jnephrol;27/4/1202American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, nutrition, ESRD, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20162016-04-01April 201610.1681/ASN.20150100221046-66731533-34502015-09-17T06:02:00-07:002016-04Journal of the American Society of NephrologyClinical Epidemiology27412021212
- Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GNNoninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.10.1681/ASN.2015020114Mon, 10 Aug 2015 07:04:03 GMT-07:00Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GNNoninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.Zaidan, MohamadTerrier, BenjaminPozdzik, AgnieszkaFrouget, ThierryRioux-Leclercq, NathalieCombe, ChristianLepreux, SébastienHummel, AurélieNoël, Laure-HélèneMarie, IsabelleLegallicier, BrunoFrançois, ArnaudHuart, AntoineLaunay, DavidKaplanski, GillesBridoux, FrankVanhille, PhilippeMakdassi, RaifahAugusto, Jean-FrançoisRouvier, PhilippeKarras, AlexandreJouanneau, ChantalVerpont, Marie-ChristineCallard, PatriceCarrat, FabriceHermine, OlivierLéger, Jean-MarcMariette, XavierSenet, PatriciaSaadoun, DavidRonco, PierreBrochériou, IsabelleCacoub, PatricePlaisier, Emmanuelle,2015-08-10T07:04:03-07:00doi:10.1681/ASN.2015020114hwp:resource-id:jnephrol;27/4/1213American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologymembranoproliferative GN, histopathology,Clinical ResearchClinical Researchresearch-article20162016-04-01April 201610.1681/ASN.20150201141046-66731533-34502015-08-10T07:04:03-07:002016-04Journal of the American Society of NephrologyClinical Research27412131224
- Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis PatientsSafety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Mean±SD baseline Hb was 8.3±1.0 g/dl in enrolled patients. Roxadustat at titrated doses increased mean Hb by ≥2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean±SEM maximal change in Hb from baseline (ΔHbmax), the primary endpoint, was 3.1±0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, ΔHbmax was similar and larger than in the no-iron group. Hb response (increase in Hb of ≥1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.10.1681/ASN.2015030241Thu, 22 Oct 2015 07:49:14 GMT-07:00Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis PatientsSafety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Mean±SD baseline Hb was 8.3±1.0 g/dl in enrolled patients. Roxadustat at titrated doses increased mean Hb by ≥2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean±SEM maximal change in Hb from baseline (ΔHbmax), the primary endpoint, was 3.1±0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, ΔHbmax was similar and larger than in the no-iron group. Hb response (increase in Hb of ≥1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.Besarab, AnatoleChernyavskaya, ElenaMotylev, IgorShutov, EvgenyKumbar, Lalathaksha M.Gurevich, KonstantinChan, Daniel Tak MaoLeong, RobertPoole, LonaZhong, MingSaikali, Khalil G.Franco, MariettaHemmerich, StefanYu, Kin-Hung PeonyNeff, Thomas B.2015-10-22T07:49:14-07:00doi:10.1681/ASN.2015030241hwp:resource-id:jnephrol;27/4/1225American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, dialysis, erythropoietin, anemiaClinical ResearchClinical Researchresearch-article20162016-04-01April 201610.1681/ASN.20150302411046-66731533-34502015-10-22T07:49:14-07:002016-04Journal of the American Society of NephrologyClinical Research274412259681233970
- A Quantitative Approach to Screen for Nephrotoxic Compounds In VitroNephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals.10.1681/ASN.2015010060Mon, 10 Aug 2015 07:04:02 GMT-07:00A Quantitative Approach to Screen for Nephrotoxic Compounds In VitroNephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals.Adler, MelanieRamm, SusanneHafner, MarcMuhlich, Jeremy L.Gottwald, Esther MariaWeber, ElijahJaklic, AlenkaAjay, Amrendra KumarSvoboda, DanielAuerbach, ScottKelly, Edward J.Himmelfarb, JonathanVaidya, Vishal S.2015-08-10T07:04:02-07:00doi:10.1681/ASN.2015010060hwp:resource-id:jnephrol;27/4/1015American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, tubule cells, nephrotoxicityBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20150100601046-66731533-34502015-08-10T07:04:02-07:002016-04Journal of the American Society of NephrologyBasic Research27410151028
- High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 GlomerulopathiesThe thrombotic microangiopathies (TMAs) and C3 glomerulopathies (C3Gs) include a spectrum of rare diseases such as atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, C3GN, and dense deposit disease, which share phenotypic similarities and underlying genetic commonalities. Variants in several genes contribute to the pathogenesis of these diseases, and identification of these variants may inform the diagnosis and treatment of affected patients. We have developed and validated a comprehensive genetic panel that screens all exons of all genes implicated in TMA and C3G. The closely integrated pipeline implemented includes targeted genomic enrichment, massively parallel sequencing, bioinformatic analysis, and a multidisciplinary conference to analyze identified variants in the context of each patient’s specific phenotype. Herein, we present our 1-year experience with this panel, during which time we studied 193 patients. We identified 17 novel and 74 rare variants, which we classified as pathogenic (11), likely pathogenic (12), and of uncertain significance (68). Compared with controls, patients with C3G had a higher frequency of rare and novel variants in C3 convertase (C3 and CFB) and complement regulator (CFH, CFI, CFHR5, and CD46) genes (P<0.05). In contrast, patients with TMA had an increase in rare and novel variants only in complement regulator genes (P<0.01), a distinction consistent with differing sites of complement dysregulation in these two diseases. In summary, we were able to provide a positive genetic diagnosis in 43% and 41% of patients carrying the clinical diagnosis of C3G and TMA, respectively.10.1681/ASN.2015040385Mon, 17 Aug 2015 05:39:13 GMT-07:00High-Throughput Genetic Testing for Thrombotic Microangiopathies and C3 GlomerulopathiesThe thrombotic microangiopathies (TMAs) and C3 glomerulopathies (C3Gs) include a spectrum of rare diseases such as atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, C3GN, and dense deposit disease, which share phenotypic similarities and underlying genetic commonalities. Variants in several genes contribute to the pathogenesis of these diseases, and identification of these variants may inform the diagnosis and treatment of affected patients. We have developed and validated a comprehensive genetic panel that screens all exons of all genes implicated in TMA and C3G. The closely integrated pipeline implemented includes targeted genomic enrichment, massively parallel sequencing, bioinformatic analysis, and a multidisciplinary conference to analyze identified variants in the context of each patient’s specific phenotype. Herein, we present our 1-year experience with this panel, during which time we studied 193 patients. We identified 17 novel and 74 rare variants, which we classified as pathogenic (11), likely pathogenic (12), and of uncertain significance (68). Compared with controls, patients with C3G had a higher frequency of rare and novel variants in C3 convertase (C3 and CFB) and complement regulator (CFH, CFI, CFHR5, and CD46) genes (P<0.05). In contrast, patients with TMA had an increase in rare and novel variants only in complement regulator genes (P<0.01), a distinction consistent with differing sites of complement dysregulation in these two diseases. In summary, we were able to provide a positive genetic diagnosis in 43% and 41% of patients carrying the clinical diagnosis of C3G and TMA, respectively.Bu, FengxiaoBorsa, Nicolo GhiringhelliJones, Michael B.Takanami, ErikaNishimura, CarlaHauer, Jill J.Azaiez, HelaBlack-Ziegelbein, Elizabeth A.Meyer, Nicole C.Kolbe, Diana L.Li, YingyueFrees, KathySchnieders, Michael J.Thomas, ChristieNester, CarlaSmith, Richard J.H.2015-08-17T05:39:13-07:00doi:10.1681/ASN.2015040385hwp:resource-id:jnephrol;27/4/1245American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyGenetic testing, Thrombotic Microangiopathy, C3 GlomerulopathyClinical ResearchClinical Researchresearch-article20162016-04-01April 201610.1681/ASN.20150403851046-66731533-34502015-08-17T05:39:13-07:002016-04Journal of the American Society of NephrologyClinical Research27412451253
- Serum Indoxyl Sulfate Associates with Postangioplasty Thrombosis of Dialysis GraftsHemodialysis vascular accesses are prone to recurrent stenosis and thrombosis after endovascular interventions. In vitro data suggest that indoxyl sulfate, a protein-bound uremic toxin, may induce vascular dysfunction and thrombosis. However, there is no clinical evidence regarding the role of indoxyl sulfate in hemodialysis vascular access. From January 2010 to June 2013, we prospectively enrolled patients undergoing angioplasty for dialysis access dysfunction. Patients were stratified into tertiles by baseline serum indoxyl sulfate levels. Study participants received clinical follow-up at 6-month intervals until June 2014. Primary end points were restenosis, thrombosis, and failure of vascular access. Median follow-up duration was 32 months. Of the 306 patients enrolled, 262 (86%) had symptomatic restenosis, 153 (50%) had access thrombosis, and 25 (8%) had access failure. In patients with graft access, free indoxyl sulfate tertiles showed a negative association with thrombosis-free patency (thrombosis-free patency rates of 54%, 38%, and 26% for low, middle, and high tertiles, respectively; P=0.001). Patients with graft thrombosis had higher free and total indoxyl sulfate levels. Using multivariate Cox regression analysis, graft thrombosis was independently predicted by absolute levels of free indoxyl sulfate (hazard ratio=1.14; P=0.01) and free indoxyl sulfate tertiles (high versus low, hazard ratio=2.41; P=0.001). Results of this study provide translational evidence that serum indoxyl sulfate is a novel risk factor for dialysis graft thrombosis after endovascular interventions.10.1681/ASN.2015010068Fri, 09 Oct 2015 12:18:26 GMT-07:00Serum Indoxyl Sulfate Associates with Postangioplasty Thrombosis of Dialysis GraftsHemodialysis vascular accesses are prone to recurrent stenosis and thrombosis after endovascular interventions. In vitro data suggest that indoxyl sulfate, a protein-bound uremic toxin, may induce vascular dysfunction and thrombosis. However, there is no clinical evidence regarding the role of indoxyl sulfate in hemodialysis vascular access. From January 2010 to June 2013, we prospectively enrolled patients undergoing angioplasty for dialysis access dysfunction. Patients were stratified into tertiles by baseline serum indoxyl sulfate levels. Study participants received clinical follow-up at 6-month intervals until June 2014. Primary end points were restenosis, thrombosis, and failure of vascular access. Median follow-up duration was 32 months. Of the 306 patients enrolled, 262 (86%) had symptomatic restenosis, 153 (50%) had access thrombosis, and 25 (8%) had access failure. In patients with graft access, free indoxyl sulfate tertiles showed a negative association with thrombosis-free patency (thrombosis-free patency rates of 54%, 38%, and 26% for low, middle, and high tertiles, respectively; P=0.001). Patients with graft thrombosis had higher free and total indoxyl sulfate levels. Using multivariate Cox regression analysis, graft thrombosis was independently predicted by absolute levels of free indoxyl sulfate (hazard ratio=1.14; P=0.01) and free indoxyl sulfate tertiles (high versus low, hazard ratio=2.41; P=0.001). Results of this study provide translational evidence that serum indoxyl sulfate is a novel risk factor for dialysis graft thrombosis after endovascular interventions.Wu, Chih-ChengHsieh, Mu-YangHung, Szu-ChunKuo, Ko-LinTsai, Tung-HuLai, Chao-LunChen, Jaw-WenLin, Shing-JongHuang, Po-HsunTarng, Der-Cherng2015-10-09T12:18:26-07:00doi:10.1681/ASN.2015010068hwp:resource-id:jnephrol;27/4/1254American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis access, thrombosis, arteriovenous shuntClinical ResearchClinical Researchresearch-article20162016-04-01April 201610.1681/ASN.20150100681046-66731533-34502015-10-09T12:18:26-07:002016-04Journal of the American Society of NephrologyClinical Research274412549701264972
- Predictors of Recurrent AKIRecurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19–167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted.10.1681/ASN.2014121218Tue, 11 Aug 2015 08:17:36 GMT-07:00Predictors of Recurrent AKIRecurrent AKI is common among patients after hospitalized AKI and is associated with progressive CKD. In this study, we identified clinical risk factors for recurrent AKI present during index AKI hospitalizations that occurred between 2003 and 2010 using a regional Veterans Administration database in the United States. AKI was defined as a 0.3 mg/dl or 50% increase from a baseline creatinine measure. The primary outcome was hospitalization with recurrent AKI within 12 months of discharge from the index hospitalization. Time to recurrent AKI was examined using Cox regression analysis, and sensitivity analyses were performed using a competing risk approach. Among 11,683 qualifying AKI hospitalizations, 2954 patients (25%) were hospitalized with recurrent AKI within 12 months of discharge. Median time to recurrent AKI within 12 months was 64 (interquartile range 19–167) days. In addition to known demographic and comorbid risk factors for AKI, patients with longer AKI duration and those whose discharge diagnosis at index AKI hospitalization included congestive heart failure (primary diagnosis), decompensated advanced liver disease, cancer with or without chemotherapy, acute coronary syndrome, or volume depletion, were at highest risk for being hospitalized with recurrent AKI. Risk factors identified were similar when a competing risk model for death was applied. In conclusion, several inpatient conditions associated with AKI may increase the risk for recurrent AKI. These findings should facilitate risk stratification, guide appropriate patient referral after AKI, and help generate potential risk reduction strategies. Efforts to identify modifiable factors to prevent recurrent AKI in these patients are warranted.Siew, Edward D.Parr, Sharidan K.Abdel-Kader, KhaledEden, Svetlana K.Peterson, Josh F.Bansal, NishaHung, Adriana M.Fly, JamesSperoff, TedIkizler, T. AlpMatheny, Michael E.2015-08-11T08:17:36-07:00doi:10.1681/ASN.2014121218hwp:resource-id:jnephrol;27/4/1190American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, outcomes, clinical epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20162016-04-01April 201610.1681/ASN.20141212181046-66731533-34502015-08-11T08:17:36-07:002016-04Journal of the American Society of NephrologyClinical Epidemiology27411901200
- Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human KidneyIschemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4+ T cells, natural killer T cells, and CD4+CD25+FoxP3+ Tregs in AKI pathogenesis. We recently identified CD4−CD8− (double-negative; DN) T cells as an important subset of αβ T cell receptor–positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4+ and CD8+ T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4+ T cells. Within the first 3–24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10–dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ+ T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties.10.1681/ASN.2014121214Thu, 27 Aug 2015 12:11:09 GMT-07:00Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human KidneyIschemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4+ T cells, natural killer T cells, and CD4+CD25+FoxP3+ Tregs in AKI pathogenesis. We recently identified CD4−CD8− (double-negative; DN) T cells as an important subset of αβ T cell receptor–positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4+ and CD8+ T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4+ T cells. Within the first 3–24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10–dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ+ T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties.Martina, Maria N.Noel, SanjeevSaxena, AnkitBandapalle, SamathaMajithia, RichaJie, ChunfaArend, Lois J.Allaf, Mohamad E.Rabb, HamidRahim A. Hamad, Abdel2015-08-27T12:11:09-07:00doi:10.1681/ASN.2014121214hwp:resource-id:jnephrol;27/4/1113American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, double-negative T cells, CD4−CD8−, human kidney, acute kidney injuryBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20141212141046-66731533-34502015-08-27T12:11:09-07:002016-04Journal of the American Society of NephrologyBasic Research27411131123
- Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst FormationSignaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2α resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2α controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2α was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2α in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2α is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease.10.1681/ASN.2014100967Thu, 13 Aug 2015 08:11:27 GMT-07:00Phosphoinositide 3-Kinase-C2α Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst FormationSignaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2α (PI3K-C2α) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2α resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2α controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2α was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2α in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2α is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease.Franco, IreneMargaria, Jean PieroDe Santis, Maria ChiaraRanghino, AndreaMonteyne, DanielChiaravalli, MarcoPema, MonikaCampa, Carlo CosimoRatto, EdoardoGulluni, FedericoPerez-Morga, DavidSomlo, StefanMerlo, Giorgio R.Boletta, AlessandraHirsch, Emilio2015-08-13T08:11:27-07:00doi:10.1681/ASN.2014100967hwp:resource-id:jnephrol;27/4/1135American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyPI3K, vesicular trafficking, cystic kidney, polycystins, primary cilium, proliferationBasic ResearchBasic Researchresearch-article20162016-04-01April 201610.1681/ASN.20141009671046-66731533-34502015-08-13T08:11:27-07:002016-04Journal of the American Society of NephrologyBasic Research27411351144
- Dialysis Vascular Access Intervention and the Search for Biomarkers10.1681/ASN.2015090982Fri, 09 Oct 2015 12:18:28 GMT-07:00Dialysis Vascular Access Intervention and the Search for BiomarkersNath, Karl A.2015-10-09T12:18:28-07:00doi:10.1681/ASN.2015090982hwp:resource-id:jnephrol;27/4/970American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis access, endovascular intervention, indoxyl sulfate, thrombosis, biomarkerUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-04-01April 201610.1681/ASN.20150909821046-66731533-34502015-10-09T12:18:28-07:002016-04Journal of the American Society of NephrologyUp Front Matters274497012549721264
- Podocyte Expression of B7-1/CD80: Is it a Reliable Biomarker for the Treatment of Proteinuric Kidney Diseases with Abatacept?10.1681/ASN.2015080947Wed, 23 Sep 2015 12:03:10 GMT-07:00Podocyte Expression of B7-1/CD80: Is it a Reliable Biomarker for the Treatment of Proteinuric Kidney Diseases with Abatacept?Salant, David J.2015-09-23T12:03:10-07:00doi:10.1681/ASN.2015080947hwp:resource-id:jnephrol;27/4/963American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, focal segmental glomerulosclerosis, B7-1, CD80, CTLA4-Ig, abataceptUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-04-01April 201610.1681/ASN.20150809471046-66731533-34502015-09-23T12:03:10-07:002016-04Journal of the American Society of NephrologyUp Front Matters27449639999651005
- The Dawning of a New Day in CKD Anemia Care?10.1681/ASN.2015091009Thu, 22 Oct 2015 07:49:12 GMT-07:00The Dawning of a New Day in CKD Anemia Care?Lenihan, Colin R.Winkelmayer, Wolfgang C.2015-10-22T07:49:12-07:00doi:10.1681/ASN.2015091009hwp:resource-id:jnephrol;27/4/968American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, hypoxia, VEGFUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-04-01April 201610.1681/ASN.20150910091046-66731533-34502015-10-22T07:49:12-07:002016-04Journal of the American Society of NephrologyUp Front Matters274449681225123497012331244
- Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry10.2215/CJN.04810515Mon, 28 Dec 2015 06:48:14 GMT-08:00Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone HistomorphometryPereira, Renata C.Bischoff, David S.Yamaguchi, DeanSalusky, Isidro B.Wesseling-Perry, Katherine2015-12-28T06:48:14-08:00doi:10.2215/CJN.04810515hwp:resource-id:clinjasn;11/3/481American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal osteodystrophy, bone biopsy, micro CT, bone density, calcification, physiologic, child, humans, kidney failure, chronic, renal dialysisOriginal ArticlesMineral Metabolism/Bone DiseaseOriginal ArticlesMineral Metabolism/Bone Diseaseresearch-article20162016-03-07March 07, 201610.2215/CJN.048105151555-90411555-905X2015-12-28T06:48:14-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113481487
- Association of Dialysis Duration with Outcomes after Transplantation in a Japanese Cohort10.2215/CJN.08670815Mon, 04 Jan 2016 06:37:22 GMT-08:00Association of Dialysis Duration with Outcomes after Transplantation in a Japanese CohortGoto, NorihikoOkada, ManabuYamamoto, TakayukiTsujita, MakotoHiramitsu, TakahisaNarumi, ShunjiKatayama, AkioKobayashi, TakaakiUchida, KazuharuWatarai, Yoshihiko2016-01-04T06:37:22-08:00doi:10.2215/CJN.08670815hwp:resource-id:clinjasn;11/3/497American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyliving donor, cohort studies, humans, kidney transplantation, living donors, proportional hazards models, renal dialysis, risk factorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-03-07March 07, 201610.2215/CJN.086708151555-90411555-905X2016-01-04T06:37:22-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113497504
- Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD10.2215/CJN.07900715Mon, 04 Jan 2016 06:37:20 GMT-08:00Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKDFernández-Laso, ValvaneraSastre, CristinaValdivielso, Jose M.Betriu, AngelsFernández, ElviraEgido, JesúsMartín-Ventura, Jose L.Blanco-Colio, Luis M.2016-01-04T06:37:20-08:00doi:10.2215/CJN.07900715hwp:resource-id:clinjasn;11/3/413American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, chronic kidney disease, cytokines, outcomes, sTWEAK, ankle brachial index, carotid intima-media thickness, humans, prospective studies, renal insufficiency, chronic, tumor necrosis factorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-03-07March 07, 201610.2215/CJN.079007151555-90411555-905X2016-01-04T06:37:20-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113413422
- Quality of Life and Physical Function in Older Patients on Dialysis: A Comparison of Assisted Peritoneal Dialysis with Hemodialysis10.2215/CJN.01050115Mon, 28 Dec 2015 06:48:13 GMT-08:00Quality of Life and Physical Function in Older Patients on Dialysis: A Comparison of Assisted Peritoneal Dialysis with HemodialysisIyasere, Osasuyi U.Brown, Edwina A.Johansson, LinaHuson, LesSmee, JoannaMaxwell, Alexander P.Farrington, KenDavenport, Andrew2015-12-28T06:48:13-08:00doi:10.2215/CJN.01050115hwp:resource-id:clinjasn;11/3/423American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyquality of life, hemodialysis, peritoneal dialysis, anxiety, depression, humans, personal satisfaction, prevalence, questionnaires, renal dialysisOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-03-07March 07, 201610.2215/CJN.010501151555-90411555-905X2015-12-28T06:48:13-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113423430
- Rethinking First-Line Immunosuppression for Idiopathic FSGS10.2215/CJN.00780116Tue, 16 Feb 2016 06:40:03 GMT-08:00Rethinking First-Line Immunosuppression for Idiopathic FSGSCohen, Jordana B.Hogan, Jonathan J.2016-02-16T06:40:03-08:00doi:10.2215/CJN.00780116hwp:resource-id:clinjasn;11/3/372American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyglomerular disease, focal segmental glomerulosclerosis, immunosuppression, treatment, Immune ToleranceEditorialsEditorialseditorial20162016-03-07March 07, 201610.2215/CJN.007801161555-90411555-905X2016-02-16T06:40:03-08:002016-03-07Clinical Journal of the American Society of NephrologyEditorials1133372386373394
- Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGS10.2215/CJN.07110615Tue, 16 Feb 2016 06:40:03 GMT-08:00Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGSLaurin, Louis-PhilippeGasim, Adil M.Poulton, Caroline J.Hogan, Susan L.Jennette, J. CharlesFalk, Ronald J.Foster, Bethany J.Nachman, Patrick H.2016-02-16T06:40:03-08:00doi:10.2215/CJN.07110615hwp:resource-id:clinjasn;11/3/386American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfocal segmental glomerulosclerosis, immunosuppression, ESRD, nephrotic syndrome, glomerular disease, calcineurin inhibitors, glucocorticoids, humans, immunosuppressive agentsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-03-07March 07, 201610.2215/CJN.071106151555-90411555-905X2016-02-16T06:40:03-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1133386372394373
- Optimizing Enrollment of Patients into Nephrology Research StudiesAdvances in medical care and biomedical research depend on the participation of human subjects. Poor patient enrollment in research has limited past clinical and translational research endeavors in nephrology. Simultaneously, patients and their caregivers are seeking better diagnostic, monitoring, and therapeutic approaches to improve or restore kidney and overall health. This manuscript will discuss a framework and strategies to optimize patient enrollment within nephrology research and provide examples of success from existing nephrology research programs.10.2215/CJN.00500115Thu, 16 Jul 2015 07:22:27 GMT-07:00Optimizing Enrollment of Patients into Nephrology Research StudiesAdvances in medical care and biomedical research depend on the participation of human subjects. Poor patient enrollment in research has limited past clinical and translational research endeavors in nephrology. Simultaneously, patients and their caregivers are seeking better diagnostic, monitoring, and therapeutic approaches to improve or restore kidney and overall health. This manuscript will discuss a framework and strategies to optimize patient enrollment within nephrology research and provide examples of success from existing nephrology research programs.Selewski, David T.Herreshoff, Emily G.Gipson, Debbie S.2015-07-16T07:22:27-07:00doi:10.2215/CJN.00500115hwp:resource-id:clinjasn;11/3/512American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyclinical trial, recruitment, study participation, CKD, patient engagementCommentaryCommentaryarticle-commentary20162016-03-07March 07, 201610.2215/CJN.005001151555-90411555-905X2015-07-16T07:22:27-07:002016-03-07Clinical Journal of the American Society of NephrologyCommentary113512517
- The American Society of Nephrology at 50: A Personal Perspective10.2215/CJN.11291015Thu, 18 Feb 2016 06:34:44 GMT-08:00The American Society of Nephrology at 50: A Personal PerspectiveBennett, William M.2016-02-18T06:34:44-08:00doi:10.2215/CJN.11291015hwp:resource-id:clinjasn;11/3/369American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanniversary, nephrology, ASN, ASN meetingCommentaryCommentaryarticle-commentary20162016-03-07March 07, 201610.2215/CJN.112910151555-90411555-905X2016-02-18T06:34:44-08:002016-03-07Clinical Journal of the American Society of NephrologyCommentary113369371
- CKD of Uncertain Etiology: A Systematic Review10.2215/CJN.07500715Mon, 28 Dec 2015 06:48:14 GMT-08:00CKD of Uncertain Etiology: A Systematic ReviewLunyera, JosephMohottige, DinushikaIsenburg, Megan VonJeuland, MarcPatel, Uptal D.Stanifer, John W.2015-12-28T06:48:14-08:00doi:10.2215/CJN.07500715hwp:resource-id:clinjasn;11/3/379American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, nephrotoxicity, risk factors, global health, low- and middle-income countries, humans, occupations, public health, renal insufficiency, chronic, temperatureOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-03-07March 07, 201610.2215/CJN.075007151555-90411555-905X2015-12-28T06:48:14-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113379385
- Effect of Lowering the Dialysate Temperature in Chronic Hemodialysis: A Systematic Review and Meta-Analysis10.2215/CJN.04580415Mon, 28 Dec 2015 06:48:12 GMT-08:00Effect of Lowering the Dialysate Temperature in Chronic Hemodialysis: A Systematic Review and Meta-AnalysisMustafa, Reem A.Bdair, FadiAkl, Elie A.Garg, Amit X.Thiessen-Philbrook, HeatherSalameh, HassanKisra, SoodNesrallah, GihadAl-Jaishi, AhmadPatel, ParthPatel, PayalMustafa, Ahmad A.Schünemann, Holger J.2015-12-28T06:48:12-08:00doi:10.2215/CJN.04580415hwp:resource-id:clinjasn;11/3/442American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, hemodialysis, end stage renal disease, chronic hemodialysis, cold temperature, dialysis solutions, follow-up studies, humans, hypotension, renal dialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-03-07March 07, 201610.2215/CJN.045804151555-90411555-905X2015-12-28T06:48:12-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113442457
- Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease10.2215/CJN.03620415Tue, 19 Jan 2016 06:59:08 GMT-08:00Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular DiseaseHerrmann, Sandra M.S.Saad, AhmedEirin, AlfonsoWoollard, JohnTang, HuiMcKusick, Michael A.Misra, SanjayGlockner, James F.Lerman, Lilach O.Textor, Stephen C.2016-01-19T06:59:08-08:00doi:10.2215/CJN.03620415hwp:resource-id:clinjasn;11/3/458American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal artery stenosis, BOLD-MRI, renal tissue oxygenation, single kidney glomerular filtration rate, renin, renal biomarkers, renovascular hypertensionOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20162016-03-07March 07, 201610.2215/CJN.036204151555-90411555-905X2016-01-19T06:59:08-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113458469
- Educational Tools: Thinking Outside the BoxThe understanding, study, and use of educational tools and their application to the education of adults in professional fields are increasingly important. In this review, we have compiled a description of educational tools on the basis of the teaching and learning setting: the classroom, simulation center, hospital or clinic, and independent learning space. When available, examples of tools used in nephrology are provided. We emphasize that time should be taken to consider the goals of the educational activity and the type of learners and use the most appropriate tools needed to meet the goals. Constant reassessment of tools is important to discover innovation and reforms that improve teaching and learning.10.2215/CJN.02570315Wed, 04 Nov 2015 10:15:14 GMT-08:00Educational Tools: Thinking Outside the BoxThe understanding, study, and use of educational tools and their application to the education of adults in professional fields are increasingly important. In this review, we have compiled a description of educational tools on the basis of the teaching and learning setting: the classroom, simulation center, hospital or clinic, and independent learning space. When available, examples of tools used in nephrology are provided. We emphasize that time should be taken to consider the goals of the educational activity and the type of learners and use the most appropriate tools needed to meet the goals. Constant reassessment of tools is important to discover innovation and reforms that improve teaching and learning.Woods, MajkaRosenberg, Mark E.2015-11-04T10:15:14-08:00doi:10.2215/CJN.02570315hwp:resource-id:clinjasn;11/3/518American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyeducation, tools, active learning, adult, ambulatory care facilities, goals, hospitals, humans, learning, nephrologyEducation SeriesEducation Seriesresearch-article20162016-03-07March 07, 201610.2215/CJN.025703151555-90411555-905X2015-11-04T10:15:14-08:002016-03-07Clinical Journal of the American Society of NephrologyEducation Series113518526
- A Matter of Choice: Opportunities and Obstacles Facing People with ESRDKidney failure is an overwhelming, life–shattering event, but patients with ESRD do not see themselves as being at the end stage of their lives. On the contrary, patients opting for kidney dialysis are choosing to live. Ideally, then, public policy would support patients’ choices about how to live—specifically, the choice to continue working. Many patients with ESRD faced with the limitations of their health status and the demands of their treatment understandably choose to leave their jobs, a choice that is facilitated by the availability of public disability and health insurance. However, other patients who have the desire and opportunity to continue working may not get the guidance and support that can actually make their employment possible. Specifically, current disability and health insurance may fail to provide timely treatment and employment counseling to help patients with ESRD remain in their jobs. We, therefore, propose that the Center for Medicare and Medicaid Services support ESRD Networks to initiate more timely employment and treatment counseling in both the ESRD and the late–stage pre–ESRD setting. Although it is too late to require such counseling in the new network scope of work for 2016–2020, active experimentation in the next few years can lay the groundwork for a subsequent contract.10.2215/CJN.04470415Mon, 09 Nov 2015 06:47:22 GMT-08:00A Matter of Choice: Opportunities and Obstacles Facing People with ESRDKidney failure is an overwhelming, life–shattering event, but patients with ESRD do not see themselves as being at the end stage of their lives. On the contrary, patients opting for kidney dialysis are choosing to live. Ideally, then, public policy would support patients’ choices about how to live—specifically, the choice to continue working. Many patients with ESRD faced with the limitations of their health status and the demands of their treatment understandably choose to leave their jobs, a choice that is facilitated by the availability of public disability and health insurance. However, other patients who have the desire and opportunity to continue working may not get the guidance and support that can actually make their employment possible. Specifically, current disability and health insurance may fail to provide timely treatment and employment counseling to help patients with ESRD remain in their jobs. We, therefore, propose that the Center for Medicare and Medicaid Services support ESRD Networks to initiate more timely employment and treatment counseling in both the ESRD and the late–stage pre–ESRD setting. Although it is too late to require such counseling in the new network scope of work for 2016–2020, active experimentation in the next few years can lay the groundwork for a subsequent contract.Feder, JudithNadel, Mark V.Krishnan, Mahesh2015-11-09T06:47:22-08:00doi:10.2215/CJN.04470415hwp:resource-id:clinjasn;11/3/536American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic renal failure, patient education, employment support, health insurancePublic Policy SeriesPublic Policy Seriesresearch-article20162016-03-07March 07, 201610.2215/CJN.044704151555-90411555-905X2015-11-09T06:47:22-08:002016-03-07Clinical Journal of the American Society of NephrologyPublic Policy Series113536538
- Annual Incidence of Nephrolithiasis among Children and Adults in South Carolina from 1997 to 201210.2215/CJN.07610715Thu, 14 Jan 2016 07:03:04 GMT-08:00Annual Incidence of Nephrolithiasis among Children and Adults in South Carolina from 1997 to 2012Tasian, Gregory E.Ross, Michelle E.Song, LihaiSas, David J.Keren, RonDenburg, Michelle R.Chu, David I.Copelovitch, LawrenceSaigal, Christopher S.Furth, Susan L.2016-01-14T07:03:04-08:00doi:10.2215/CJN.07610715hwp:resource-id:clinjasn;11/3/488American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney stones, children, adults, incidence, epidemiology, temporal trends, humans, nephrolithiasis, prevalenceOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20162016-03-07March 07, 201610.2215/CJN.076107151555-90411555-905X2016-01-14T07:03:04-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113488496
- Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on DialysisThe effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD.10.2215/CJN.06370615Fri, 27 Nov 2015 06:36:50 GMT-08:00Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on DialysisThe effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD.Parfrey, Patrick S.Block, Geoffrey A.Correa-Rotter, RicardoDrüeke, Tilman B.Floege, JürgenHerzog, Charles A.London, Gerard M.Mahaffey, Kenneth W.Moe, Sharon M.Wheeler, David C.Chertow, Glenn M.2015-11-27T06:36:50-08:00doi:10.2215/CJN.06370615hwp:resource-id:clinjasn;11/3/539American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, parathyroid hormone, chronic kidney disease, cardiovascular disease, hyperparathyroidism, cardiovascular diseases, humans, randomized controlled trials as topic, cinacalcetSpecial FeatureSpecial Featureresearch-article20162016-03-07March 07, 201610.2215/CJN.063706151555-90411555-905X2015-11-27T06:36:50-08:002016-03-07Clinical Journal of the American Society of NephrologySpecial Feature113539546
- Allocating Deceased Donor Kidneys to Sensitized Candidates10.2215/CJN.13641215Tue, 02 Feb 2016 06:44:44 GMT-08:00Allocating Deceased Donor Kidneys to Sensitized CandidatesFormica, Richard N.2016-02-02T06:44:44-08:00doi:10.2215/CJN.13641215hwp:resource-id:clinjasn;11/3/377American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, transplant outcomes, cadaver organ transplantation, death, tissue donorsEditorialsEditorialseditorial20162016-03-07March 07, 201610.2215/CJN.136412151555-90411555-905X2016-02-02T06:44:44-08:002016-03-07Clinical Journal of the American Society of NephrologyEditorials1133377505378511
- Visit-to-Visit Variability of BP and CKD Outcomes: Results from the ALLHAT10.2215/CJN.04660415Thu, 18 Feb 2016 06:34:44 GMT-08:00Visit-to-Visit Variability of BP and CKD Outcomes: Results from the ALLHATWhittle, JeffLynch, Amy I.Tanner, Rikki M.Simpson, Lara M.Davis, Barry R.Rahman, MahboobWhelton, Paul K.Oparil, SuzanneMuntner, Paul2016-02-18T06:34:44-08:00doi:10.2215/CJN.04660415hwp:resource-id:clinjasn;11/3/471American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhypertension, blood pressure variability, clinical trial, antihypertensive agents, blood pressure, cardiovascular diseases, follow-up studies, glomerular filtration rate, kidney failure, chronic, random allocationOriginal ArticlesHypertensionOriginal ArticlesHypertensionresearch-article20162016-03-07March 07, 201610.2215/CJN.046604151555-90411555-905X2016-02-18T06:34:44-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1133471374480376
- eGFR and Outcomes in Patients with Acute Decompensated Heart Failure with or without Elevated BUN10.2215/CJN.08210815Thu, 14 Jan 2016 07:03:03 GMT-08:00eGFR and Outcomes in Patients with Acute Decompensated Heart Failure with or without Elevated BUNKajimoto, KatsuyaSato, NaokiTakano, Teruo2016-01-14T07:03:03-08:00doi:10.2215/CJN.08210815hwp:resource-id:clinjasn;11/3/405American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyheart failure, blood urea nitrogen, glomerular filtration rate, outcomes assessment, Comorbidity, Follow-Up Studies, hospitalization, Humans, Patient Discharge, RegistriesOriginal ArticlesCritical Care NephrologyOriginal ArticlesCritical Care Nephrologyresearch-article20162016-03-07March 07, 201610.2215/CJN.082108151555-90411555-905X2016-01-14T07:03:03-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113405412
- Finding a Signal in the Noise10.2215/CJN.00880116Thu, 18 Feb 2016 06:34:44 GMT-08:00Finding a Signal in the NoiseMcMullan, Ciaran J.Forman, John P.2016-02-18T06:34:44-08:00doi:10.2215/CJN.00880116hwp:resource-id:clinjasn;11/3/374American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, ESRD, visit to visit variability in blood pressure, Blood Pressure Determination, Outpatients, Renal Insufficiency, ChronicEditorialsEditorialseditorial20162016-03-07March 07, 201610.2215/CJN.008801161555-90411555-905X2016-02-18T06:34:44-08:002016-03-07Clinical Journal of the American Society of NephrologyEditorials1133374471376480
- Trends in Survival and Renal Recovery in Patients with Multiple Myeloma or Light-Chain Amyloidosis on Chronic Dialysis10.2215/CJN.06290615Mon, 04 Jan 2016 06:37:19 GMT-08:00Trends in Survival and Renal Recovery in Patients with Multiple Myeloma or Light-Chain Amyloidosis on Chronic DialysisDecourt, AlexandreGondouin, BertrandDelaroziere, Jean ChristopheBrunet, PhilippeSallée, MarionBurtey, StephaneDussol, BertrandIvanov, VadimCostello, RegisCouchoud, CecileJourde-Chiche, Noemie2016-01-04T06:37:19-08:00doi:10.2215/CJN.06290615hwp:resource-id:clinjasn;11/3/431American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, end stage kidney disease, light chain deposition disease, monoclonal gammopathy, kidney transplantation, amyloidosis, humans, multiple myeloma, paraproteinemias, renal dialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-03-07March 07, 201610.2215/CJN.062906151555-90411555-905X2016-01-04T06:37:19-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113431441
- Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven Model10.2215/CJN.03560315Fri, 22 Jan 2016 07:37:11 GMT-08:00Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven ModelBernardi, Martin HermannSchmidlin, DanielRistl, RobinHeitzinger, ClemensSchiferer, ArnoNeugebauer, ThomasWrba, ThomasHiesmayr, MichaelDruml, WilfredLassnigg, Andrea2016-01-22T07:37:11-08:00doi:10.2215/CJN.03560315hwp:resource-id:clinjasn;11/3/395American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologySerum creatinine, cardiac surgery, acute kidney injury, estimation methods, glomerular filtration rate, humans, kidney diseases, kidney function tests, renal insufficiency, chronicOriginal ArticlesCritical Care NephrologyOriginal ArticlesCritical Care Nephrologyresearch-article20162016-03-07March 07, 201610.2215/CJN.035603151555-90411555-905X2016-01-22T07:37:11-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles113395404
- Allocating Deceased Donor Kidneys to Candidates with High Panel–Reactive Antibodies10.2215/CJN.07720715Tue, 02 Feb 2016 06:44:44 GMT-08:00Allocating Deceased Donor Kidneys to Candidates with High Panel–Reactive AntibodiesGebel, Howard M.Kasiske, Bertram L.Gustafson, Sally K.Pyke, JoshuaShteyn, EugeneIsrani, Ajay K.Bray, Robert A.Snyder, Jon J.Friedewald, John J.Segev, Dorry L.2016-02-02T06:44:44-08:00doi:10.2215/CJN.07720715hwp:resource-id:clinjasn;11/3/505American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney transplantation, transplantation, transplant outcomes, adult, HLA antigens, humans, kidney, tissue donorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-03-07March 07, 201610.2215/CJN.077207151555-90411555-905X2016-02-02T06:44:44-08:002016-03-07Clinical Journal of the American Society of NephrologyOriginal Articles1133505377511378
- Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP SignalingThe transient receptor potential melastatin type 6 (TRPM6) epithelial Mg2+ channels participate in transcellular Mg2+ transport in the kidney and intestine. Previous reports suggested a hormonal cAMP-dependent regulation of Mg2+ reabsorption in the kidney. The molecular details of this process are, however, unknown. Adenylate cyclase 3 (Adcy3) has been shown to colocalize with the Na+/Cl− cotransporter, a marker of the distal convoluted segment of the kidney, the principal site of TRPM6 expression. Given the critical role of TRPM6 in Mg2+ reabsorption, an inducible kidney-specific Adcy3 deletion mouse model was characterized for blood and urinary electrolyte disturbances under a normal—and low—Mg2+ diet. Increased urinary Mg2+ wasting and Trpm6 mRNA levels were observed in the urine and kidney of Adcy3-deleted animals compared with wild-type controls. Serum Mg2+ concentration was significantly lower in Adcy3-deleted animals at day 7 on the low Mg2+ diet. Using patch clamp electrophysiology, cell surface biotinylation, and total internal reflection fluorescence live cell imaging of transfected HEK293 cells, we demonstrated that cAMP signaling rapidly potentiates TRPM6 activity by promoting TRPM6 accumulation at the plasma membrane and increasing its single-channel conductance. Comparison of electrophysiological data from cells expressing the phosphorylation-deficient S1252A or phosphomimetic S1252D TRPM6 mutants suggests that phosphorylation at this intracellular residue participates in the observed stimulation of channel activity. Altogether, these data support a physiologically relevant magnesiotropic role of cAMP signaling in the kidney by a direct stimulatory action of protein kinase A on the plasma membrane trafficking and function of TRPM6 ion channels.10.1681/ASN.2014121228Mon, 06 Jul 2015 07:55:58 GMT-07:00Regulation of Mg2+ Reabsorption and Transient Receptor Potential Melastatin Type 6 Activity by cAMP SignalingThe transient receptor potential melastatin type 6 (TRPM6) epithelial Mg2+ channels participate in transcellular Mg2+ transport in the kidney and intestine. Previous reports suggested a hormonal cAMP-dependent regulation of Mg2+ reabsorption in the kidney. The molecular details of this process are, however, unknown. Adenylate cyclase 3 (Adcy3) has been shown to colocalize with the Na+/Cl− cotransporter, a marker of the distal convoluted segment of the kidney, the principal site of TRPM6 expression. Given the critical role of TRPM6 in Mg2+ reabsorption, an inducible kidney-specific Adcy3 deletion mouse model was characterized for blood and urinary electrolyte disturbances under a normal—and low—Mg2+ diet. Increased urinary Mg2+ wasting and Trpm6 mRNA levels were observed in the urine and kidney of Adcy3-deleted animals compared with wild-type controls. Serum Mg2+ concentration was significantly lower in Adcy3-deleted animals at day 7 on the low Mg2+ diet. Using patch clamp electrophysiology, cell surface biotinylation, and total internal reflection fluorescence live cell imaging of transfected HEK293 cells, we demonstrated that cAMP signaling rapidly potentiates TRPM6 activity by promoting TRPM6 accumulation at the plasma membrane and increasing its single-channel conductance. Comparison of electrophysiological data from cells expressing the phosphorylation-deficient S1252A or phosphomimetic S1252D TRPM6 mutants suggests that phosphorylation at this intracellular residue participates in the observed stimulation of channel activity. Altogether, these data support a physiologically relevant magnesiotropic role of cAMP signaling in the kidney by a direct stimulatory action of protein kinase A on the plasma membrane trafficking and function of TRPM6 ion channels.Blanchard, Maxime G.Kittikulsuth, WararatNair, Anil V.de Baaij, Jeroen H.F.Latta, FemkeGenzen, Jonathan R.Kohan, Donald E.Bindels, René J.M.Hoenderop, Joost G.J.2015-07-06T07:55:58-07:00doi:10.1681/ASN.2014121228hwp:resource-id:jnephrol;27/3/804American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell and transport physiology, cell signaling, cAMP, electrophysiology, magnesium, ion channelBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141212281046-66731533-34502015-07-06T07:55:58-07:002016-03Journal of the American Society of NephrologyBasic Research273804813
- Glycosylation Profile of IgG in Moderate Kidney DysfunctionGlycans constitute the most abundant and diverse form of the post-translational modifications, and animal studies have suggested the involvement of IgG glycosylation in mechanisms of renal damage. Here, we explored the associations between IgG glycans and renal function in 3274 individuals from the TwinsUK registry. We analyzed the correlation between renal function measured as eGFR and 76 N-glycan traits using linear regressions adjusted for covariates and multiple testing in the larger population. We replicated our results in 31 monozygotic twin pairs discordant for renal function. Results from both analyses were then meta-analyzed. Fourteen glycan traits were associated with renal function in the discovery sample (P<6.5×10−4) and remained significant after validation. Those glycan traits belong to three main glycosylation features: galactosylation, sialylation, and level of bisecting N-acetylglucosamine of the IgG glycans. These results show the role of IgG glycosylation in kidney function and provide novel insight into the pathophysiology of CKD and potential diagnostic and therapeutic targets.10.1681/ASN.2015010109Thu, 16 Jul 2015 06:29:57 GMT-07:00Glycosylation Profile of IgG in Moderate Kidney DysfunctionGlycans constitute the most abundant and diverse form of the post-translational modifications, and animal studies have suggested the involvement of IgG glycosylation in mechanisms of renal damage. Here, we explored the associations between IgG glycans and renal function in 3274 individuals from the TwinsUK registry. We analyzed the correlation between renal function measured as eGFR and 76 N-glycan traits using linear regressions adjusted for covariates and multiple testing in the larger population. We replicated our results in 31 monozygotic twin pairs discordant for renal function. Results from both analyses were then meta-analyzed. Fourteen glycan traits were associated with renal function in the discovery sample (P<6.5×10−4) and remained significant after validation. Those glycan traits belong to three main glycosylation features: galactosylation, sialylation, and level of bisecting N-acetylglucosamine of the IgG glycans. These results show the role of IgG glycosylation in kidney function and provide novel insight into the pathophysiology of CKD and potential diagnostic and therapeutic targets.Barrios, ClaraZierer, JonasGudelj, IvanŠtambuk, JerkoUgrina, IvoRodríguez, EvaSoler, María JoséPavić, TamaraŠimurina, MirnaKeser, TomaPučić-Baković, MajaMangino, MassimoPascual, JulioSpector, Tim DLauc, GordanMenni, Cristina2015-07-16T06:29:57-07:00doi:10.1681/ASN.2015010109hwp:resource-id:jnephrol;27/3/933American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, glycation, renal function declineClinical ResearchClinical Researchresearch-article20162016-03-01March 201610.1681/ASN.20150101091046-66731533-34502015-07-16T06:29:57-07:002016-03Journal of the American Society of NephrologyClinical Research273933941
- Progression after AKI: Understanding Maladaptive Repair Processes to Predict and Identify Therapeutic TreatmentsRecent clinical studies indicate a strong link between AKI and progression of CKD. The increasing prevalence of AKI must compel the nephrology community to consider the long-term ramifications of this syndrome. Considerable gaps in knowledge exist regarding the connection between AKI and CKD. The 13th Acute Dialysis Quality Initiative meeting entitled “Therapeutic Targets of Human Acute Kidney Injury: Harmonizing Human and Experimental Animal Acute Kidney Injury” convened in April of 2014 and assigned a working group to focus on issues related to progression after AKI. This article provides a summary of the key conclusions and recommendations of the group, including an emphasis on terminology related to injury and repair processes for both clinical and preclinical studies, elucidation of pathophysiologic alterations of AKI, identification of potential treatment strategies, identification of patients predisposed to progression, and potential management strategies.10.1681/ASN.2015030309Fri, 30 Oct 2015 07:47:14 GMT-07:00Progression after AKI: Understanding Maladaptive Repair Processes to Predict and Identify Therapeutic TreatmentsRecent clinical studies indicate a strong link between AKI and progression of CKD. The increasing prevalence of AKI must compel the nephrology community to consider the long-term ramifications of this syndrome. Considerable gaps in knowledge exist regarding the connection between AKI and CKD. The 13th Acute Dialysis Quality Initiative meeting entitled “Therapeutic Targets of Human Acute Kidney Injury: Harmonizing Human and Experimental Animal Acute Kidney Injury” convened in April of 2014 and assigned a working group to focus on issues related to progression after AKI. This article provides a summary of the key conclusions and recommendations of the group, including an emphasis on terminology related to injury and repair processes for both clinical and preclinical studies, elucidation of pathophysiologic alterations of AKI, identification of potential treatment strategies, identification of patients predisposed to progression, and potential management strategies.Basile, David P.Bonventre, Joseph V.Mehta, RavindraNangaku, MasaomiUnwin, RobertRosner, Mitchell H.Kellum, John A.Ronco, Claudio2015-10-30T07:47:14-07:00doi:10.1681/ASN.2015030309hwp:resource-id:jnephrol;27/3/687American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, progression of renal failure, fibrosis, chronic renal, diseaseUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-03-01March 201610.1681/ASN.20150303091046-66731533-34502015-10-30T07:47:14-07:002016-03Journal of the American Society of NephrologyUp Front Matters273687697
- Intravital Imaging Reveals Angiotensin II–Induced Transcytosis of Albumin by PodocytesAlbuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P<0.001), and 239.4±34.6 µm3 (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang II–infused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function.10.1681/ASN.2014111125Fri, 26 Jun 2015 05:45:29 GMT-07:00Intravital Imaging Reveals Angiotensin II–Induced Transcytosis of Albumin by PodocytesAlbuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P<0.001), and 239.4±34.6 µm3 (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang II–infused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function.Schießl, Ina MariaHammer, AnnaKattler, VeronikaGess, BernhardTheilig, FranziskaWitzgall, RalphCastrop, Hayo2015-06-26T05:45:29-07:00doi:10.1681/ASN.2014111125hwp:resource-id:jnephrol;27/3/731American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, podocyte, angiotensinBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141111251046-66731533-34502015-06-26T05:45:29-07:002016-03Journal of the American Society of NephrologyBasic Research273731744
- Elevated BP after AKIThe connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP—defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit—during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.10.1681/ASN.2014111114Wed, 01 Jul 2015 07:17:38 GMT-07:00Elevated BP after AKIThe connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP—defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit—during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.Hsu, Chi-yuanHsu, Raymond K.Yang, JingrongOrdonez, Juan D.Zheng, SijieGo, Alan S.2015-07-01T07:17:38-07:00doi:10.1681/ASN.2014111114hwp:resource-id:jnephrol;27/3/914American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyBP, acute renal failure, hypertension, risk factorsClinical ResearchClinical Researchresearch-article20162016-03-01March 201610.1681/ASN.20141111141046-66731533-34502015-07-01T07:17:38-07:002016-03Journal of the American Society of NephrologyClinical Research273914923
- Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal DisorganizationPodocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes.10.1681/ASN.2014111144Thu, 09 Jul 2015 08:44:17 GMT-07:00Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal DisorganizationPodocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes.Forst, Anna-LenaOlteanu, Vlad SorinMollet, GéraldineWlodkowski, TanjaSchaefer, FranzDietrich, AlexanderReiser, JochenGudermann, ThomasMederos y Schnitzler, MichaelStorch, Ursula2015-07-09T08:44:17-07:00doi:10.1681/ASN.2014111144hwp:resource-id:jnephrol;27/3/848American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell signaling, cell and transport physiology, glomerulosclerosisBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141111441046-66731533-34502015-07-09T08:44:17-07:002016-03Journal of the American Society of NephrologyBasic Research273848862
- Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney InjuryEndoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang−/−) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism.10.1681/ASN.2015020196Mon, 20 Jul 2015 09:15:09 GMT-07:00Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney InjuryEndoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang−/−) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism.Mami, IadhBouvier, NicolasEl Karoui, KhalilGallazzini, MorganRabant, MarionLaurent-Puig, PierreLi, ShupingTharaux, Pierre-LouisBeaune, PhilippeThervet, EricChevet, EricHu, Guo-FuPallet, Nicolas2015-07-20T09:15:09-07:00doi:10.1681/ASN.2015020196hwp:resource-id:jnephrol;27/3/863American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyapoptosis, acute renal failure, cell biology and structure, chronic allograft nephropathy, renal cell biology, renal epithelial cellBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20150201961046-66731533-34502015-07-20T09:15:09-07:002016-03Journal of the American Society of NephrologyBasic Research273863876
- Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in PreeclampsiaPreeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20–38 years of age) with very preterm preeclampsia (23–32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%–28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2–11) and 15 days (range 11–21) in women treated once and multiple times, respectively, compared with 3 days (range 0–14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.10.1681/ASN.2015020157Thu, 24 Sep 2015 06:26:03 GMT-07:00Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in PreeclampsiaPreeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20–38 years of age) with very preterm preeclampsia (23–32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%–28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2–11) and 15 days (range 11–21) in women treated once and multiple times, respectively, compared with 3 days (range 0–14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.Thadhani, RaviHagmann, HenningSchaarschmidt, WiebkeRoth, BernhardCingoez, TuelayKarumanchi, S. AnanthWenger, JuliaLucchesi, Kathryn J.Tamez, HectorLindner, TomFridman, AlexanderThome, UlrichKribs, AngelaDanner, MarcoHamacher, StefanieMallmann, PeterStepan, HolgerBenzing, Thomas2015-09-24T06:26:03-07:00doi:10.1681/ASN.2015020157hwp:resource-id:jnephrol;27/3/903American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical trial, preeclampsia, pregnancy, vascular endothelial growth factor, sFlt-1, therapeutic apheresisClinical ResearchClinical Researchresearch-article20162016-03-01March 201610.1681/ASN.20150201571046-66731533-34502015-09-24T06:26:03-07:002016-03Journal of the American Society of NephrologyClinical Research2733903663913665
- Masked Uncontrolled Hypertension in CKDMasked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75–78% (κ coefficient for agreement, 0.44–0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a κ coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90–110 mmHg group, 17% in the 110–119 mmHg group, 34% in the 120–129 mmHg group, and 66% in the 130–139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76–0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring.10.1681/ASN.2015030243Fri, 10 Jul 2015 05:54:43 GMT-07:00Masked Uncontrolled Hypertension in CKDMasked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.7% by daytime ambulatory BP, 32.8% by 24-hour ambulatory BP, 56.1% by daytime or night-time ambulatory BP, and 50.8% by home BP. To assess the reproducibility of the diagnosis, we repeated these measurements after 4 weeks. Agreement in MUCH diagnosis by ambulatory BP was 75–78% (κ coefficient for agreement, 0.44–0.51), depending on the definition used. In contrast, home BP showed an agreement of only 63% and a κ coefficient of 0.25. Prevalence of MUCH increased with increasing clinic systolic BP: 2% in the 90–110 mmHg group, 17% in the 110–119 mmHg group, 34% in the 120–129 mmHg group, and 66% in the 130–139 mmHg group. Clinic BP was a good determinant of MUCH (receiver operating characteristic area under the curve 0.82; 95% confidence interval 0.76–0.87). In diagnosing MUCH, home BP was not different from clinic BP. In conclusion, among people with CKD, MUCH is common and reproducible, and should be suspected when clinic BP is in the prehypertensive range. Confirmation of MUCH diagnosis should rely on ambulatory BP monitoring.Agarwal, RajivPappas, Maria K.Sinha, Arjun D.2015-07-10T05:54:43-07:00doi:10.1681/ASN.2015030243hwp:resource-id:jnephrol;27/3/924American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, chronic kidney disease, blood pressureClinical ResearchClinical Researchresearch-article20162016-03-01March 201610.1681/ASN.20150302431046-66731533-34502015-07-10T05:54:43-07:002016-03Journal of the American Society of NephrologyClinical Research273924932
- PGE2, Kidney Disease, and Cardiovascular Risk: Beyond Hypertension and DiabetesAn important measure of cardiovascular health is obtained by evaluating the global cardiovascular risk, which comprises a number of factors, including hypertension and type 2 diabetes, the leading causes of illness and death in the world, as well as the metabolic syndrome. Altered immunity, inflammation, and oxidative stress underlie many of the changes associated with cardiovascular disease, diabetes, and the metabolic syndrome, and recent efforts have begun to elucidate the contribution of PGE2 in these events. This review summarizes the role of PGE2 in kidney disease outcomes that accelerate cardiovascular disease, highlights the role of cyclooxygenase-2/microsomal PGE synthase 1/PGE2 signaling in hypertension and diabetes, and outlines the contribution of PGE2 to other aspects of the metabolic syndrome, particularly abdominal adiposity, dyslipidemia, and atherogenesis. A clearer understanding of the role of PGE2 could lead to new avenues to improve therapeutic options and disease management strategies.10.1681/ASN.2015050528Fri, 28 Aug 2015 08:24:03 GMT-07:00PGE2, Kidney Disease, and Cardiovascular Risk: Beyond Hypertension and DiabetesAn important measure of cardiovascular health is obtained by evaluating the global cardiovascular risk, which comprises a number of factors, including hypertension and type 2 diabetes, the leading causes of illness and death in the world, as well as the metabolic syndrome. Altered immunity, inflammation, and oxidative stress underlie many of the changes associated with cardiovascular disease, diabetes, and the metabolic syndrome, and recent efforts have begun to elucidate the contribution of PGE2 in these events. This review summarizes the role of PGE2 in kidney disease outcomes that accelerate cardiovascular disease, highlights the role of cyclooxygenase-2/microsomal PGE synthase 1/PGE2 signaling in hypertension and diabetes, and outlines the contribution of PGE2 to other aspects of the metabolic syndrome, particularly abdominal adiposity, dyslipidemia, and atherogenesis. A clearer understanding of the role of PGE2 could lead to new avenues to improve therapeutic options and disease management strategies.Nasrallah, RaniaHassouneh, RamziHébert, Richard L.2015-08-28T08:24:03-07:00doi:10.1681/ASN.2015050528hwp:resource-id:jnephrol;27/3/666American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyBP, cardiovascular disease, diabetes, kidney disease, chronic renal failure, chronic renal insufficiencyUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-03-01March 201610.1681/ASN.20150505281046-66731533-34502015-08-28T08:24:03-07:002016-03Journal of the American Society of NephrologyUp Front Matters273666676
- Immune Mechanisms in Arterial HypertensionTraditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.10.1681/ASN.2015050562Fri, 28 Aug 2015 08:24:05 GMT-07:00Immune Mechanisms in Arterial HypertensionTraditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.Wenzel, UlrichTurner, Jan EricKrebs, ChristianKurts, ChristianHarrison, David G.Ehmke, Heimo2015-08-28T08:24:05-07:00doi:10.1681/ASN.2015050562hwp:resource-id:jnephrol;27/3/677American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, innate immunity, adaptive immunity, dendritic cellsUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-03-01March 201610.1681/ASN.20150505621046-66731533-34502015-08-28T08:24:05-07:002016-03Journal of the American Society of NephrologyUp Front Matters273677686
- Regression of Renal Disease by Angiotensin II Antagonism Is Caused by Regeneration of Kidney VasculatureChronic renal insufficiency inexorably progresses in patients, such as it does after partial renal ablation in rats. However, the progression of renal diseases can be delayed by angiotensin II blockers that stabilize renal function or increase GFR, even in advanced phases of the disease. Regression of glomerulosclerosis can be induced by angiotensin II antagonism, but the effect of these treatments on the entire vascular tree is unclear. Here, using microcomputed tomography and scanning electron microscopy, we compared the size and extension of kidney blood vessels in untreated Wistar rats with those in untreated and angiotensin II antagonist–treated Munich Wistar Frömter (MWF) rats that spontaneously develop kidney disease with age. The kidney vasculature underwent progressive rarefaction in untreated MWF rats, substantially affecting intermediate and small vessels. Microarray analysis showed increased Tgf-β and endothelin-1 gene expression with age. Notably, 10-week inhibition of the renin-angiotensin system regenerated kidney vasculature and normalized Tgf-β and endothelin-1 gene expression in aged MWF rats. These changes were associated with reduced apoptosis, increased endothelial cell proliferation, and restoration of Nrf2 expression, suggesting mechanisms by which angiotensin II antagonism mediates regeneration of capillary segments. These results have important implications in the clinical setting of chronic renal insufficiency.10.1681/ASN.2014100971Fri, 26 Jun 2015 05:45:29 GMT-07:00Regression of Renal Disease by Angiotensin II Antagonism Is Caused by Regeneration of Kidney VasculatureChronic renal insufficiency inexorably progresses in patients, such as it does after partial renal ablation in rats. However, the progression of renal diseases can be delayed by angiotensin II blockers that stabilize renal function or increase GFR, even in advanced phases of the disease. Regression of glomerulosclerosis can be induced by angiotensin II antagonism, but the effect of these treatments on the entire vascular tree is unclear. Here, using microcomputed tomography and scanning electron microscopy, we compared the size and extension of kidney blood vessels in untreated Wistar rats with those in untreated and angiotensin II antagonist–treated Munich Wistar Frömter (MWF) rats that spontaneously develop kidney disease with age. The kidney vasculature underwent progressive rarefaction in untreated MWF rats, substantially affecting intermediate and small vessels. Microarray analysis showed increased Tgf-β and endothelin-1 gene expression with age. Notably, 10-week inhibition of the renin-angiotensin system regenerated kidney vasculature and normalized Tgf-β and endothelin-1 gene expression in aged MWF rats. These changes were associated with reduced apoptosis, increased endothelial cell proliferation, and restoration of Nrf2 expression, suggesting mechanisms by which angiotensin II antagonism mediates regeneration of capillary segments. These results have important implications in the clinical setting of chronic renal insufficiency.Remuzzi, AndreaSangalli, FabioMacconi, DanielaTomasoni, SusannaCattaneo, IreneRizzo, PaolaBonandrini, BarbaraBresciani, ElenaLongaretti, LorenaGagliardini, ElenaConti, SaraBenigni, ArielaRemuzzi, Giuseppe2015-06-26T05:45:29-07:00doi:10.1681/ASN.2014100971hwp:resource-id:jnephrol;27/3/699American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyangiotensin–converting enzyme inhibitors, renal progression, vascular diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-03-01March 201610.1681/ASN.20141009711046-66731533-34502015-06-26T05:45:29-07:002016-03Journal of the American Society of NephrologyBrief Communications273699705
- Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney DiseasePrenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.10.1681/ASN.2014101051Thu, 02 Jul 2015 08:13:57 GMT-07:00Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney DiseasePrenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.Audrézet, Marie-PierreCorbiere, ChristineLebbah, SaidMorinière, VincentBroux, FrançoiseLouillet, FerielleFischbach, MichelZaloszyc, ArianeCloarec, SylvieMerieau, ElodieBaudouin, VéroniqueDeschênes, GeorgesRoussey, GwenaelleMaestri, SandrineVisconti, ChiaraBoyer, OliviaAbel, CarineLahoche, AnnieRandrianaivo, HanitraBessenay, LucieMekahli, DjalilaOuertani, InesDecramer, StéphaneRyckenwaert, AmélieCornec-Le Gall, EmilieSalomon, RémiFerec, ClaudeHeidet, Laurence2015-07-02T08:13:57-07:00doi:10.1681/ASN.2014101051hwp:resource-id:jnephrol;27/3/722American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypediatrics, polycystic kidney disease, human genetics, cystic kidneyBrief CommunicationsBrief Communicationsbrief-report20162016-03-01March 201610.1681/ASN.20141010511046-66731533-34502015-07-02T08:13:57-07:002016-03Journal of the American Society of NephrologyBrief Communications273722729
- Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-UpBecause of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.10.1681/ASN.2015030337Thu, 16 Jul 2015 06:29:57 GMT-07:00Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch–2-Year Follow-UpBecause of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3–0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C–based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.Lenders, MalteCanaan-Kühl, SimaKrämer, JohannesDuning, ThomasReiermann, StefanieSommer, ClaudiaStypmann, JörgBlaschke, DanielaÜçeyler, NurcanHense, Hans-WernerBrand, Stefan-MartinWanner, ChristophWeidemann, FrankBrand, Eva2015-07-16T06:29:57-07:00doi:10.1681/ASN.2015030337hwp:resource-id:jnephrol;27/3/952American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, creatinine clearance, Fabry’s disease, enzyme, replacement therapy, outcomes, cystatin C clearanceClinical ResearchClinical Researchresearch-article20162016-03-01March 201610.1681/ASN.20150303371046-66731533-34502015-07-16T06:29:57-07:002016-03Journal of the American Society of NephrologyClinical Research273952962
- This Month's Highlights10.1681/ASN.2015111278Mon, 29 Feb 2016 10:01:07 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2016-02-29T10:01:07-08:00doi:10.1681/ASN.2015111278hwp:resource-id:jnephrol;27/3/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-03-01March 201610.1681/ASN.20151112781046-66731533-34502016-02-29T10:01:07-08:002016-03Journal of the American Society of NephrologyThis Month's Highlights273ii
- Endogenous Toll-Like Receptor 9 Regulates AKI by Promoting Regulatory T Cell RecruitmentToll-like receptor 9 (TLR9) enhances proinflammatory responses, but whether it can act in a regulatory capacity remains to be established. In experimental murine AKI induced by cisplatin, Tlr9−/− mice developed enhanced renal injury and exhibited fewer intrarenal regulatory T cells (Tregs) compared with genetically intact mice. A series of reconstitution and depletion studies defined a role for TLR9 in maintaining Treg-mediated homeostasis in cisplatin-induced AKI. When Rag1−/− mice were reconstituted with nonregulatory CD25− splenocytes from wild-type (WT) or Tlr9−/− mice, AKI was similarly enhanced. However, when Rag1−/− mice were reconstituted with CD4+CD25+ regulatory cells, WT CD4+CD25+ cells were more renoprotective and localized to the kidney more efficiently than Tlr9−/− CD4+CD25+ cells. In Treg-depleted Foxp3DTR mice, reconstitution with naive WT CD4+CD25+ cells resulted in less severe AKI than did reconstitution with Tlr9−/− Tregs. Tlr9−/− mice were not deficient in CD4+CD25+ cells, and WT and TLR9-deficient Tregs had similar suppressive function ex vivo. However, expression of adhesion molecules important in Treg trafficking was reduced on peripheral CD4+CD25+ cells from Tlr9−/− mice. In conclusion, we identified a pathway by which TLR9 promotes renal Treg accumulation in AKI.10.1681/ASN.2014090927Fri, 26 Jun 2015 05:45:28 GMT-07:00Endogenous Toll-Like Receptor 9 Regulates AKI by Promoting Regulatory T Cell RecruitmentToll-like receptor 9 (TLR9) enhances proinflammatory responses, but whether it can act in a regulatory capacity remains to be established. In experimental murine AKI induced by cisplatin, Tlr9−/− mice developed enhanced renal injury and exhibited fewer intrarenal regulatory T cells (Tregs) compared with genetically intact mice. A series of reconstitution and depletion studies defined a role for TLR9 in maintaining Treg-mediated homeostasis in cisplatin-induced AKI. When Rag1−/− mice were reconstituted with nonregulatory CD25− splenocytes from wild-type (WT) or Tlr9−/− mice, AKI was similarly enhanced. However, when Rag1−/− mice were reconstituted with CD4+CD25+ regulatory cells, WT CD4+CD25+ cells were more renoprotective and localized to the kidney more efficiently than Tlr9−/− CD4+CD25+ cells. In Treg-depleted Foxp3DTR mice, reconstitution with naive WT CD4+CD25+ cells resulted in less severe AKI than did reconstitution with Tlr9−/− Tregs. Tlr9−/− mice were not deficient in CD4+CD25+ cells, and WT and TLR9-deficient Tregs had similar suppressive function ex vivo. However, expression of adhesion molecules important in Treg trafficking was reduced on peripheral CD4+CD25+ cells from Tlr9−/− mice. In conclusion, we identified a pathway by which TLR9 promotes renal Treg accumulation in AKI.Alikhan, Maliha A.Summers, Shaun A.Gan, Poh Y.Chan, Amy J.Khouri, Mary B.Ooi, Joshua D.Ghali, Joanna R.Odobasic, DraganaHickey, Michael J.Kitching, A. RichardHoldsworth, Stephen R.2015-06-26T05:45:28-07:00doi:10.1681/ASN.2014090927hwp:resource-id:jnephrol;27/3/706American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycisplatin nephrotoxicity, Toll-like receptor 9, Regulatory T cells, acute renal failureBrief CommunicationsBrief Communicationsbrief-report20162016-03-01March 201610.1681/ASN.20140909271046-66731533-34502015-06-26T05:45:28-07:002016-03Journal of the American Society of NephrologyBrief Communications273706714
- Kidney Function and Cerebral Blood Flow: The Rotterdam StudyCKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined. This study was performed in the framework of the population–based Rotterdam Study and included 2645 participants with mean age of 56.6 years (45% men). We used eGFR and albumin-to-creatinine ratio to assess kidney function and performed phase–contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow. Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m2 and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2–6.1) mg/g. In age- and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, −0.31; 95% confidence interval, −0.58 to −0.03). The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors. Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow.10.1681/ASN.2014111118Thu, 06 Aug 2015 06:48:17 GMT-07:00Kidney Function and Cerebral Blood Flow: The Rotterdam StudyCKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined. This study was performed in the framework of the population–based Rotterdam Study and included 2645 participants with mean age of 56.6 years (45% men). We used eGFR and albumin-to-creatinine ratio to assess kidney function and performed phase–contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow. Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m2 and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2–6.1) mg/g. In age- and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, −0.31; 95% confidence interval, −0.58 to −0.03). The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors. Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow.Sedaghat, SanazVernooij, Meike W.Loehrer, ElizabethMattace-Raso, Francesco U.S.Hofman, Albertvan der Lugt, AadFranco, Oscar H.Dehghan, AbbasIkram, M. Arfan2015-08-06T06:48:17-07:00doi:10.1681/ASN.2014111118hwp:resource-id:jnephrol;27/3/715American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical epidemiology, GFR, cerebral blood flow, albuminuriaBrief CommunicationsBrief Communicationsbrief-report20162016-03-01March 201610.1681/ASN.20141111181046-66731533-34502015-08-06T06:48:17-07:002016-03Journal of the American Society of NephrologyBrief Communications273715721
- Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE SubjectsAPOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria ≥0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m2 lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.10.1681/ASN.2014111131Mon, 06 Jul 2015 07:55:59 GMT-07:00Integrative Genomics Identifies Novel Associations with APOL1 Risk Genotypes in Black NEPTUNE SubjectsAPOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed clinical and genomic datasets derived from 90 black subjects in the Nephrotic Syndrome Study Network (NEPTUNE), stratified by APOL1 risk genotype. Ninety subjects with proteinuria ≥0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome and followed. Clinical outcomes were determined, and renal histomorphometry and sequencing of Mendelian nephrotic syndrome genes were performed. APOL1 variants were genotyped, and glomerular and tubulointerstitial transcriptomes from protocol renal biopsy cores were analyzed for differential and correlative gene expression. Analyses were performed under the recessive model (high-risk genotype defined by two risk alleles). APOL1 high-risk genotype was significantly associated with a 17 ml/min per 1.73 m2 lower eGFR and a 69% reduction in the probability of complete remission at any time, independent of histologic diagnosis. Neither APOL1 risk group was enriched for Mendelian mutations. On renal biopsy, high-risk genotype was associated with increased fractional interstitial area, interstitial fibrosis, and tubular atrophy. Risk genotype was not associated with intrarenal APOL1 mRNA expression levels. Differential expression analysis demonstrated an increased steady-state level of five genes associated with the high-risk genotype (CXCL9, CXCL11, and UBD in glomerulus; SNOR14B and MUC13 in tubulointerstitium). APOL1 tubulointerstitial coexpression analysis showed coexpression of APOL1 mRNA levels with a group of intrarenal transcripts that together were associated with increased interstitial fibrosis and tubular atrophy. These data indicate the high-risk APOL1 genotype confers renal risk across histopathologic diagnoses.Sampson, Matthew G.Robertson, Catherine C.Martini, SebastianMariani, Laura H.Lemley, Kevin V.Gillies, Christopher E.Otto, Edgar A.Kopp, Jeffrey B.Randolph, AnneVega-Warner, VirginiaEichinger, FelixNair, VijiGipson, Debbie S.Cattran, Daniel C.Johnstone, Duncan B.O’Toole, John F.Bagnasco, Serena M.Song, Peter X.Barisoni, LauraTroost, Jonathan P.Kretzler, MatthiasSedor, John R.,2015-07-06T07:55:59-07:00doi:10.1681/ASN.2014111131hwp:resource-id:jnephrol;27/3/814American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, nephrotic syndrome, genetic renal disease, epidemiology and outcomes, transcriptional profiling, APOL1Basic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141111311046-66731533-34502015-07-06T07:55:59-07:002016-03Journal of the American Society of NephrologyBasic Research273814823
- Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKDPulmonary hypertension (PH) is associated with poor outcomes in the dialysis and general populations, but its effect in CKD is unclear. We evaluated the prevalence and predictors of PH measures and their associations with long–term clinical outcomes in patients with nondialysis-dependent CKD. Chronic Renal Insufficiency Cohort (CRIC) Study participants who had Doppler echocardiography performed were considered for inclusion. PH was defined as the presence of estimated pulmonary artery systolic pressure (PASP) >35 mmHg and/or tricuspid regurgitant velocity (TRV) >2.5 m/s. Associations between PH, PASP, and TRV and cardiovascular events, renal events, and all-cause mortality were examined using Cox proportional hazards models. Of 2959 eligible participants, 21% (n=625) had PH, with higher rates among those with lower levels of kidney function. In the multivariate model, older age, anemia, lower left ventricular ejection fraction, and presence of left ventricular hypertrophy were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with higher risk for death (hazard ratio, 1.38; 95% confidence interval, 1.10 to 1.72) and cardiovascular events (hazard ratio, 1.23; 95% confidence interval, 1.00 to 1.52) but not renal events. Similarly, TRV and PASP were associated with death and cardiovascular events but not renal events. In this study of patients with CKD and preserved left ventricular systolic function, we report a high prevalence of PH. PH and higher TRV and PASP (echocardiographic measures of PH) are associated with adverse outcomes in CKD. Future studies may explain the mechanisms that underlie these findings.10.1681/ASN.2014111111Fri, 18 Sep 2015 07:01:11 GMT-07:00Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in CKDPulmonary hypertension (PH) is associated with poor outcomes in the dialysis and general populations, but its effect in CKD is unclear. We evaluated the prevalence and predictors of PH measures and their associations with long–term clinical outcomes in patients with nondialysis-dependent CKD. Chronic Renal Insufficiency Cohort (CRIC) Study participants who had Doppler echocardiography performed were considered for inclusion. PH was defined as the presence of estimated pulmonary artery systolic pressure (PASP) >35 mmHg and/or tricuspid regurgitant velocity (TRV) >2.5 m/s. Associations between PH, PASP, and TRV and cardiovascular events, renal events, and all-cause mortality were examined using Cox proportional hazards models. Of 2959 eligible participants, 21% (n=625) had PH, with higher rates among those with lower levels of kidney function. In the multivariate model, older age, anemia, lower left ventricular ejection fraction, and presence of left ventricular hypertrophy were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with higher risk for death (hazard ratio, 1.38; 95% confidence interval, 1.10 to 1.72) and cardiovascular events (hazard ratio, 1.23; 95% confidence interval, 1.00 to 1.52) but not renal events. Similarly, TRV and PASP were associated with death and cardiovascular events but not renal events. In this study of patients with CKD and preserved left ventricular systolic function, we report a high prevalence of PH. PH and higher TRV and PASP (echocardiographic measures of PH) are associated with adverse outcomes in CKD. Future studies may explain the mechanisms that underlie these findings.Navaneethan, Sankar D.Roy, JasonTao, KelvinBrecklin, Carolyn S.Chen, JingDeo, RajatFlack, John M.Ojo, Akinlolu O.Plappert, Theodore JRaj, Dominic S.Saydain, GhulamSondheimer, James H.Sood, RuchiSteigerwalt, Susan P.Townsend, Raymond R.Dweik, Raed A.Rahman, Mahboob2015-09-18T07:01:11-07:00doi:10.1681/ASN.2014111111hwp:resource-id:jnephrol;27/3/877American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, pulmonary hypertension, mortality, heart failureClinical EpidemiologyClinical Epidemiologyresearch-article20162016-03-01March 201610.1681/ASN.20141111111046-66731533-34502015-09-18T07:01:11-07:002016-03Journal of the American Society of NephrologyClinical Epidemiology2733877661886663
- APOL1 Genotype and Race Differences in Incident Albuminuria and Renal Function DeclineVariants in the APOL1 gene are associated with kidney disease in blacks. We examined associations of APOL1 with incident albuminuria and kidney function decline among 3030 young adults with preserved GFR in the Coronary Artery Risk Development in Young Adults (CARDIA) study. eGFR by cystatin C (eGFRcys) and albumin-to-creatinine ratio were measured at scheduled examinations. Participants were white (n=1700), high-risk black (two APOL1 risk alleles, n=176), and low-risk black (zero/one risk allele, n=1154). Mean age was 35 years, mean eGFRcys was 107 ml/min per 1.73 m2, and 13.2% of blacks had two APOL1 alleles. The incidence rate per 1000 person-years (95% confidence interval) for albuminuria over 15 years was 15.6 (10.6–22.1) for high-risk blacks, 7.8 (6.4–9.4) for low-risk blacks, and 3.9 (3.1–4.8) for whites. Compared with whites, the odds ratio (95% confidence interval) for incident albuminuria was 5.71 (3.64–8.94) for high-risk blacks and 2.32 (1.73–3.13) for low-risk blacks. Adjustment for risk factors attenuated the difference between low-risk blacks and whites (odds ratio 1.21, 95% confidence interval 0.86–1.71). After adjustment, high-risk blacks had a 0.45% faster yearly eGFRcys decline over 9.3 years compared with whites. Low-risk blacks also had a faster yearly eGFRcys decline compared with whites, but this difference was attenuated after adjustment for risk factors and socioeconomic position. In conclusion, blacks with two APOL1 risk alleles had the highest risk for albuminuria and eGFRcys decline in young adulthood, whereas disparities between low-risk blacks and whites were related to differences in traditional risk factors.10.1681/ASN.2015020124Wed, 15 Jul 2015 04:42:14 GMT-07:00APOL1 Genotype and Race Differences in Incident Albuminuria and Renal Function DeclineVariants in the APOL1 gene are associated with kidney disease in blacks. We examined associations of APOL1 with incident albuminuria and kidney function decline among 3030 young adults with preserved GFR in the Coronary Artery Risk Development in Young Adults (CARDIA) study. eGFR by cystatin C (eGFRcys) and albumin-to-creatinine ratio were measured at scheduled examinations. Participants were white (n=1700), high-risk black (two APOL1 risk alleles, n=176), and low-risk black (zero/one risk allele, n=1154). Mean age was 35 years, mean eGFRcys was 107 ml/min per 1.73 m2, and 13.2% of blacks had two APOL1 alleles. The incidence rate per 1000 person-years (95% confidence interval) for albuminuria over 15 years was 15.6 (10.6–22.1) for high-risk blacks, 7.8 (6.4–9.4) for low-risk blacks, and 3.9 (3.1–4.8) for whites. Compared with whites, the odds ratio (95% confidence interval) for incident albuminuria was 5.71 (3.64–8.94) for high-risk blacks and 2.32 (1.73–3.13) for low-risk blacks. Adjustment for risk factors attenuated the difference between low-risk blacks and whites (odds ratio 1.21, 95% confidence interval 0.86–1.71). After adjustment, high-risk blacks had a 0.45% faster yearly eGFRcys decline over 9.3 years compared with whites. Low-risk blacks also had a faster yearly eGFRcys decline compared with whites, but this difference was attenuated after adjustment for risk factors and socioeconomic position. In conclusion, blacks with two APOL1 risk alleles had the highest risk for albuminuria and eGFRcys decline in young adulthood, whereas disparities between low-risk blacks and whites were related to differences in traditional risk factors.Peralta, Carmen A.Bibbins-Domingo, KirstenVittinghoff, EricLin, FengFornage, MyriamKopp, Jeffrey B.Winkler, Cheryl A.2015-07-15T04:42:14-07:00doi:10.1681/ASN.2015020124hwp:resource-id:jnephrol;27/3/887American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyapol1, kidney function decline, albumin to creatinine ratio, socioeconomic position (SEP), APOL1, incident albuminuriaClinical EpidemiologyClinical Epidemiologyresearch-article20162016-03-01March 201610.1681/ASN.20150201241046-66731533-34502015-07-15T04:42:14-07:002016-03Journal of the American Society of NephrologyClinical Epidemiology273887893
- Hypertension in Pregnancy and Future Cardiovascular Event Risk in SiblingsHypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan–Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27–2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension.10.1681/ASN.2015010086Thu, 27 Aug 2015 12:11:08 GMT-07:00Hypertension in Pregnancy and Future Cardiovascular Event Risk in SiblingsHypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan–Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27–2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension.Weissgerber, Tracey L.Turner, Stephen T.Mosley, Thomas H.Kardia, Sharon L.R.Hanis, Craig L.Milic, Natasa M.Garovic, Vesna D.2015-08-27T12:11:08-07:00doi:10.1681/ASN.2015010086hwp:resource-id:jnephrol;27/3/894American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, cardiovascular disease, pregnancy hypertension, stroke, familial predispositionClinical EpidemiologyClinical Epidemiologyresearch-article20162016-03-01March 201610.1681/ASN.20150100861046-66731533-34502015-08-27T12:11:08-07:002016-03Journal of the American Society of NephrologyClinical Epidemiology273894902
- The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney DiseaseThe course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.10.1681/ASN.2015010016Mon, 06 Jul 2015 07:55:57 GMT-07:00The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney DiseaseThe course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.Cornec-Le Gall, EmilieAudrézet, Marie-PierreRousseau, AnnickHourmant, MaryvonneRenaudineau, EricCharasse, ChristopheMorin, Marie-PascaleMoal, Marie-ChristineDantal, JacquesWehbe, BassemPerrichot, RégineFrouget, ThierryVigneau, CécilePotier, JérômeJousset, PhilippeGuillodo, Marie-PauleSiohan, PascaleTerki, NazimSawadogo, ThéophileLegrand, DidierMenoyo-Calonge, VictorioBenarbia, SeddikBesnier, DominiqueLonguet, HélèneFérec, ClaudeLe Meur, Yannick2015-07-06T07:55:57-07:00doi:10.1681/ASN.2015010016hwp:resource-id:jnephrol;27/3/942American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyend-stage renal disease, ADPKD, risk factors, genetic renal disease, progression of renal failureClinical ResearchClinical Researchresearch-article20162016-03-01March 201610.1681/ASN.20150100161046-66731533-34502015-07-06T07:55:57-07:002016-03Journal of the American Society of NephrologyClinical Research273942951
- MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High PhosphorusVascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or high-phosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and high–calcium and –phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.10.1681/ASN.2014050520Fri, 17 Jul 2015 04:33:19 GMT-07:00MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High PhosphorusVascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or high-phosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and high–calcium and –phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.Panizo, SaraNaves-Díaz, ManuelCarrillo-López, NataliaMartínez-Arias, LauraFernández-Martín, José LuisRuiz-Torres, María PiedadCannata-Andía, Jorge B.Rodríguez, Isabel2015-07-17T04:33:19-07:00doi:10.1681/ASN.2014050520hwp:resource-id:jnephrol;27/3/824American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologymicroRNAs, vascular calcification, nephrectomy, uremia, primary cell culture, cell differentiationBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20140505201046-66731533-34502015-07-17T04:33:19-07:002016-03Journal of the American Society of NephrologyBasic Research273824834
- Hepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coliThe iron-regulatory peptide hepcidin exhibits antimicrobial activity. Having previously shown hepcidin expression in the kidney, we addressed its role in urinary tract infection (UTI), which remains largely unknown. Experimental UTI was induced in wild-type (WT) and hepcidin-knockout (Hepc−/−) mice using the uropathogenic Escherichia coli CFT073 strain. Compared with infected WT mice, infected Hepc−/− mice showed a dramatic increase in renal bacterial load. Moreover, bacterial invasion was significantly dampened by the pretreatment of WT mice with hepcidin. Infected Hepc−/− mice exhibited decreased iron accumulation in the renal medulla and significant attenuation of the renal inflammatory response. Notably, we demonstrated in vitro bacteriostatic activity of hepcidin against CFT073. Furthermore, CFT073 repressed renal hepcidin, both in vivo and in cultured renal cells, and reduced phosphorylation of SMAD kinase in vivo, suggesting a bacterial strategy to escape the antimicrobial activities of hepcidin. In conclusion, we provide new mechanisms by which hepcidin contributes to renal host defense and suggest that targeting hepcidin offers a strategy to prevent bacterial invasion.10.1681/ASN.2014101035Thu, 20 Aug 2015 10:14:16 GMT-07:00Hepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coliThe iron-regulatory peptide hepcidin exhibits antimicrobial activity. Having previously shown hepcidin expression in the kidney, we addressed its role in urinary tract infection (UTI), which remains largely unknown. Experimental UTI was induced in wild-type (WT) and hepcidin-knockout (Hepc−/−) mice using the uropathogenic Escherichia coli CFT073 strain. Compared with infected WT mice, infected Hepc−/− mice showed a dramatic increase in renal bacterial load. Moreover, bacterial invasion was significantly dampened by the pretreatment of WT mice with hepcidin. Infected Hepc−/− mice exhibited decreased iron accumulation in the renal medulla and significant attenuation of the renal inflammatory response. Notably, we demonstrated in vitro bacteriostatic activity of hepcidin against CFT073. Furthermore, CFT073 repressed renal hepcidin, both in vivo and in cultured renal cells, and reduced phosphorylation of SMAD kinase in vivo, suggesting a bacterial strategy to escape the antimicrobial activities of hepcidin. In conclusion, we provide new mechanisms by which hepcidin contributes to renal host defense and suggest that targeting hepcidin offers a strategy to prevent bacterial invasion.Houamel, DouniaDucrot, NicolasLefebvre, ThibaudDaher, RaedMoulouel, BoualemSari, Marie-AgnesLetteron, PhilippeLyoumi, SaidMillot, SarahTourret, JeromeBouvet, OdileVaulont, SophieVandewalle, AlainDenamur, ErickPuy, HervéBeaumont, CaroleGouya, LaurentKarim, Zoubida2015-08-20T10:14:16-07:00doi:10.1681/ASN.2014101035hwp:resource-id:jnephrol;27/3/835American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypyelonephritis, renal epithelial cell, renal protection, cell and transport physiology, cell signaling, kidney diseaseBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141010351046-66731533-34502015-08-20T10:14:16-07:002016-03Journal of the American Society of NephrologyBasic Research273835846
- Modeling the Neurologic and Cognitive Effects of Hyponatremia10.1681/ASN.2015060714Wed, 16 Sep 2015 09:16:48 GMT-07:00Modeling the Neurologic and Cognitive Effects of HyponatremiaCohen, David M.2015-09-16T09:16:48-07:00doi:10.1681/ASN.2015060714hwp:resource-id:jnephrol;27/3/659American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhyponatremia, cell volume regulation, electrolytesUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-03-01March 201610.1681/ASN.20150607141046-66731533-34502015-09-16T09:16:48-07:002016-03Journal of the American Society of NephrologyUp Front Matters2733659766661780
- Apheresis to Treat Preeclampsia: Insights, Opportunities and Challenges10.1681/ASN.2015070794Thu, 24 Sep 2015 06:26:02 GMT-07:00Apheresis to Treat Preeclampsia: Insights, Opportunities and ChallengesEasterling, Thomas R.2015-09-24T06:26:02-07:00doi:10.1681/ASN.2015070794hwp:resource-id:jnephrol;27/3/663American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypreeclampsia, sFlt-1, VEGFUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-03-01March 201610.1681/ASN.20150707941046-66731533-34502015-09-24T06:26:02-07:002016-03Journal of the American Society of NephrologyUp Front Matters2733663903665913
- Pulmonary Hypertension in CKD: Some Answers, Yet More Questions10.1681/ASN.2015070819Fri, 18 Sep 2015 07:01:10 GMT-07:00Pulmonary Hypertension in CKD: Some Answers, Yet More QuestionsSarnak, Mark J.Roberts, Kari E.2015-09-18T07:01:10-07:00doi:10.1681/ASN.2015070819hwp:resource-id:jnephrol;27/3/661American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, pulmonary hypertension, mortalityUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-03-01March 201610.1681/ASN.20150708191046-66731533-34502015-09-18T07:01:10-07:002016-03Journal of the American Society of NephrologyUp Front Matters2733661877663886
- Paradoxical Role of IL-17 in Progression of Diabetic Nephropathy10.1681/ASN.2015070813Wed, 02 Sep 2015 10:48:53 GMT-07:00Paradoxical Role of IL-17 in Progression of Diabetic NephropathyGalvan, Daniel L.Danesh, Farhad R.2015-09-02T10:48:53-07:00doi:10.1681/ASN.2015070813hwp:resource-id:jnephrol;27/3/657American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycytokines, diabetic nephropathy, glomerular epithelial cells, kidneyUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-03-01March 201610.1681/ASN.20150708131046-66731533-34502015-09-02T10:48:53-07:002016-03Journal of the American Society of NephrologyUp Front Matters2733657745658765
- Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ FibrosisDiabetes is the leading cause of kidney failure, accounting for >45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator of chronic inflammatory diseases, but recent studies dispute these findings and suggest that IL-17A can favorably modulate inflammation. Here, we examined the role of IL-17A in diabetic nephropathy. We observed that IL-17A levels in plasma and urine were reduced in patients with advanced diabetic nephropathy. Type 1 diabetic mice that are genetically deficient in IL-17A developed more severe nephropathy, whereas administration of low-dose IL-17A prevented diabetic nephropathy in models of type 1 and type 2 diabetes. Moreover, IL-17A administration effectively treated, prevented, and reversed established nephropathy in genetic models of diabetes. Protective effects were also observed after administration of IL-17F but not IL-17C or IL-17E. Notably, tubular epithelial cell-specific overexpression of IL-17A was sufficient to suppress diabetic nephropathy. Mechanistically, IL-17A administration suppressed phosphorylation of signal transducer and activator of transcription 3, a central mediator of fibrosis, upregulated anti-inflammatory microglia/macrophage WAP domain protein in an AMP-activated protein kinase–dependent manner and favorably modulated renal oxidative stress and AMP-activated protein kinase activation. Administration of recombinant microglia/macrophage WAP domain protein suppressed diabetes-induced albuminuria and enhanced M2 marker expression. These observations suggest that the beneficial effects of IL-17 are isoform-specific and identify low-dose IL-17A administration as a promising therapeutic approach in diabetic kidney disease.10.1681/ASN.2014111136Wed, 02 Sep 2015 10:48:54 GMT-07:00Low-Dose IL-17 Therapy Prevents and Reverses Diabetic Nephropathy, Metabolic Syndrome, and Associated Organ FibrosisDiabetes is the leading cause of kidney failure, accounting for >45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator of chronic inflammatory diseases, but recent studies dispute these findings and suggest that IL-17A can favorably modulate inflammation. Here, we examined the role of IL-17A in diabetic nephropathy. We observed that IL-17A levels in plasma and urine were reduced in patients with advanced diabetic nephropathy. Type 1 diabetic mice that are genetically deficient in IL-17A developed more severe nephropathy, whereas administration of low-dose IL-17A prevented diabetic nephropathy in models of type 1 and type 2 diabetes. Moreover, IL-17A administration effectively treated, prevented, and reversed established nephropathy in genetic models of diabetes. Protective effects were also observed after administration of IL-17F but not IL-17C or IL-17E. Notably, tubular epithelial cell-specific overexpression of IL-17A was sufficient to suppress diabetic nephropathy. Mechanistically, IL-17A administration suppressed phosphorylation of signal transducer and activator of transcription 3, a central mediator of fibrosis, upregulated anti-inflammatory microglia/macrophage WAP domain protein in an AMP-activated protein kinase–dependent manner and favorably modulated renal oxidative stress and AMP-activated protein kinase activation. Administration of recombinant microglia/macrophage WAP domain protein suppressed diabetes-induced albuminuria and enhanced M2 marker expression. These observations suggest that the beneficial effects of IL-17 are isoform-specific and identify low-dose IL-17A administration as a promising therapeutic approach in diabetic kidney disease.Mohamed, RiyazJayakumar, CalpurniaChen, FengFulton, DavidStepp, DavidGansevoort, Ron T.Ramesh, Ganesan2015-09-02T10:48:54-07:00doi:10.1681/ASN.2014111136hwp:resource-id:jnephrol;27/3/745American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, cytokines, diabetic nephropathy, diabetic, glomerulopathyBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141111361046-66731533-34502015-09-02T10:48:54-07:002016-03Journal of the American Society of NephrologyBasic Research2733745657765658
- Chronic Hyponatremia Causes Neurologic and Psychologic ImpairmentsHyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3–CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.10.1681/ASN.2014121196Wed, 16 Sep 2015 09:16:48 GMT-07:00Chronic Hyponatremia Causes Neurologic and Psychologic ImpairmentsHyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3–CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.Fujisawa, HarukiSugimura, YoshihisaTakagi, HiroshiMizoguchi, HiroyukiTakeuchi, HideyukiIzumida, HisakazuNakashima, KohtaroOchiai, HiroshiTakeuchi, SeijiKiyota, AtsushiFukumoto, KazuyaIwama, ShintaroTakagishi, YoshikoHayashi, YoshitakaArima, HiroshiKomatsu, YukioMurata, YoshiharuOiso, Yutaka2015-09-16T09:16:48-07:00doi:10.1681/ASN.2014121196hwp:resource-id:jnephrol;27/3/766American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhyponatremia, dementia, electrolytes, vasopressin, water-electrolyte balance, osmolalityBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141211961046-66731533-34502015-09-16T09:16:48-07:002016-03Journal of the American Society of NephrologyBasic Research2733766659780661
- Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by Tubulointerstitial Cross-TalkAKI with incomplete epithelial repair is a major contributor to CKD characterized by tubulointerstitial fibrosis. Injury–induced epithelial secretion of profibrotic factors is hypothesized to underlie this link, but the identity of these factors and whether epithelial injury is required remain undefined. We previously showed that activation of the canonical Wnt signaling pathway in interstitial pericytes cell autonomously drives myofibroblast activation in vivo. Here, we show that inhibition of canonical Wnt signaling also substantially prevented TGFβ–dependent myofibroblast activation in vitro. To investigate whether Wnt ligand derived from proximal tubule is sufficient for renal fibrogenesis, we generated a novel mouse strain with inducible proximal tubule Wnt1 secretion. Adult mice were treated with vehicle or tamoxifen and euthanized at 12 or 24 weeks postinjection. Compared with vehicle-treated controls, kidneys with tamoxifen–induced Wnt1 expression from proximal tubules displayed interstitial myofibroblast activation and proliferation and increased matrix protein production. PDGF receptor β–positive myofibroblasts isolated from these kidneys exhibited increased canonical Wnt target gene expression compared with controls. Notably, fibrotic kidneys had no evidence of inflammatory cytokine expression, leukocyte infiltration, or epithelial injury, despite the close histologic correlation of each with CKD. These results provide the first example of noninflammatory renal fibrosis. The fact that epithelial–derived Wnt ligand is sufficient to drive interstitial fibrosis provides strong support for the maladaptive repair hypothesis in the AKI to CKD transition.10.1681/ASN.2014121188Thu, 23 Jul 2015 06:46:19 GMT-07:00Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by Tubulointerstitial Cross-TalkAKI with incomplete epithelial repair is a major contributor to CKD characterized by tubulointerstitial fibrosis. Injury–induced epithelial secretion of profibrotic factors is hypothesized to underlie this link, but the identity of these factors and whether epithelial injury is required remain undefined. We previously showed that activation of the canonical Wnt signaling pathway in interstitial pericytes cell autonomously drives myofibroblast activation in vivo. Here, we show that inhibition of canonical Wnt signaling also substantially prevented TGFβ–dependent myofibroblast activation in vitro. To investigate whether Wnt ligand derived from proximal tubule is sufficient for renal fibrogenesis, we generated a novel mouse strain with inducible proximal tubule Wnt1 secretion. Adult mice were treated with vehicle or tamoxifen and euthanized at 12 or 24 weeks postinjection. Compared with vehicle-treated controls, kidneys with tamoxifen–induced Wnt1 expression from proximal tubules displayed interstitial myofibroblast activation and proliferation and increased matrix protein production. PDGF receptor β–positive myofibroblasts isolated from these kidneys exhibited increased canonical Wnt target gene expression compared with controls. Notably, fibrotic kidneys had no evidence of inflammatory cytokine expression, leukocyte infiltration, or epithelial injury, despite the close histologic correlation of each with CKD. These results provide the first example of noninflammatory renal fibrosis. The fact that epithelial–derived Wnt ligand is sufficient to drive interstitial fibrosis provides strong support for the maladaptive repair hypothesis in the AKI to CKD transition.Maarouf, Omar H.Aravamudhan, AnushaRangarajan, DeepikaKusaba, TetsuroZhang, VictorWelborn, JeremyGauvin, DanielHou, XiuyunKramann, RafaelHumphreys, Benjamin D.2015-07-23T06:46:19-07:00doi:10.1681/ASN.2014121188hwp:resource-id:jnephrol;27/3/781American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20141211881046-66731533-34502015-07-23T06:46:19-07:002016-03Journal of the American Society of NephrologyBasic Research273781790
- Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion MechanismMonocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6Chigh monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.10.1681/ASN.2015010009Thu, 09 Jul 2015 08:44:16 GMT-07:00Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion MechanismMonocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6Chigh monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.Chousterman, Benjamin G.Boissonnas, AlexandrePoupel, LucieBaudesson de Chanville, CamilleAdam, JulienTabibzadeh, NahidLicata, FabriceLukaszewicz, Anne-ClaireLombès, AmélieDeterre, PhilippePayen, DidierCombadière, Christophe2015-07-09T08:44:16-07:00doi:10.1681/ASN.2015010009hwp:resource-id:jnephrol;27/3/792American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunology, chemokine receptor, kidney dysfunctionBasic ResearchBasic Researchresearch-article20162016-03-01March 201610.1681/ASN.20150100091046-66731533-34502015-07-09T08:44:16-07:002016-03Journal of the American Society of NephrologyBasic Research273792803
- CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb Ischemia10.2215/CJN.05600515Mon, 14 Dec 2015 07:39:46 GMT-08:00CKD and Acute and Long-Term Outcome of Patients with Peripheral Artery Disease and Critical Limb IschemiaLüders, FlorianBunzemeier, HolgerEngelbertz, ChristianeMalyar, Nasser M.Meyborg, MatthiasRoeder, NorbertBerger, KlausReinecke, Holger2015-12-14T07:39:46-08:00doi:10.2215/CJN.05600515hwp:resource-id:clinjasn;11/2/216American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, peripheral arterial disease, outcome, acute kidney injury, amputation, cohort studies, hospital mortality, hospitalization, humans, length of stayOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-02-05February 05, 201610.2215/CJN.056005151555-90411555-905X2015-12-14T07:39:46-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112216222
- Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial10.2215/CJN.05240515Fri, 15 Jan 2016 06:24:54 GMT-08:00Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized TrialRossi, MeganJohnson, David W.Morrison, MarkPascoe, Elaine M.Coombes, Jeff S.Forbes, Josephine M.Szeto, Cheuk-ChunMcWhinney, Brett C.Ungerer, Jacobus P.J.Campbell, Katrina L.2016-01-15T06:24:54-08:00doi:10.2215/CJN.05240515hwp:resource-id:clinjasn;11/2/223American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, indoxyl sulphate, probiotics, synbiotics, uremic toxins, p-cresyl sulphate, glomerular filtration rate, humans, microbiota, renal insufficiency, chronicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-02-05February 05, 201610.2215/CJN.052405151555-90411555-905X2016-01-15T06:24:54-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles1122223199231201
- Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SC10.2215/CJN.03940415Tue, 15 Dec 2015 06:55:10 GMT-08:00Kidney Disease among Patients with Sickle Cell Disease, Hemoglobin SS and SCDrawz, PaulAyyappan, SabarishNouraie, MehdiSaraf, SantoshGordeuk, VictorHostetter, ThomasGladwin, Mark T.Little, Jane2015-12-15T06:55:10-08:00doi:10.2215/CJN.03940415hwp:resource-id:clinjasn;11/2/207American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacidosis, albuminuria, chronic kidney disease, anemia, sickle cell, blood pressure, glomerular filtration rate, humans, hydroxyurea, hypertension, pulmonaryOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-02-05February 05, 201610.2215/CJN.039404151555-90411555-905X2015-12-15T06:55:10-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112207215
- Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy10.2215/CJN.07490715Mon, 14 Dec 2015 07:39:47 GMT-08:00Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney BiopsyAtta, Mohamed G.Estrella, Michelle M.Skorecki, Karl L.Kopp, Jeffrey B.Winkler, Cheryl A.Wasser, Walter G.Shemer, RevitalRacusen, Lorraine C.Kuperman, MichaelFoy, Matthew C.Lucas, Gregory M.Fine, Derek M.2015-12-14T07:39:47-08:00doi:10.2215/CJN.07490715hwp:resource-id:clinjasn;11/2/262American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHIV, APOL1, AIDS-associated nephropathy, African Americans, alleles, biopsy, genotype, glomerulosclerosis, focal segmental, humans, kidney diseasesOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-02-05February 05, 201610.2215/CJN.074907151555-90411555-905X2015-12-14T07:39:47-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112262270
- Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and Hypertension10.2215/CJN.06980615Mon, 14 Dec 2015 07:39:45 GMT-08:00Associations of Left Ventricular Hypertrophy and Geometry with Adverse Outcomes in Patients with CKD and HypertensionPaoletti, ErnestoDe Nicola, LucaGabbai, Francis B.Chiodini, PaoloRavera, MauraPieracci, LauraMarre, SoniaCassottana, PaoloLucà, SergioVettoretti, SimoneBorrelli, SilvioConte, GiuseppeMinutolo, Roberto2015-12-14T07:39:45-08:00doi:10.2215/CJN.06980615hwp:resource-id:clinjasn;11/2/271American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, left ventricular geometry, blood pressure monitoring, ambulatory, echocardiography, female, follow-up studies, humans, hypertension, hypertrophy, left ventricularOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-02-05February 05, 201610.2215/CJN.069806151555-90411555-905X2015-12-14T07:39:45-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112271279
- Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD10.2215/CJN.07360715Mon, 14 Dec 2015 07:39:43 GMT-08:00Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKDSchei, JørgenStefansson, Vidar T.N.Mathisen, Ulla DorteEriksen, Bjørn O.Solbu, Marit D.Jenssen, Trond G.Melsom, Toralf2015-12-14T07:39:43-08:00doi:10.2215/CJN.07360715hwp:resource-id:clinjasn;11/2/280American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, cardiovascular disease, cystatin C, tumor necrosis factor, fibrinogen, C-reactive protein, humans, kidney function testsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-02-05February 05, 201610.2215/CJN.073607151555-90411555-905X2015-12-14T07:39:43-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112280286
- Predictors of Subclinical Atheromatosis Progression over 2 Years in Patients with Different Stages of CKD10.2215/CJN.01240215Mon, 14 Dec 2015 07:39:45 GMT-08:00Predictors of Subclinical Atheromatosis Progression over 2 Years in Patients with Different Stages of CKDGracia, MartaBetriu, ÀngelsMartínez-Alonso, MontserratArroyo, DavidAbajo, MaríaFernández, ElviraValdivielso, José M.2015-12-14T07:39:45-08:00doi:10.2215/CJN.01240215hwp:resource-id:clinjasn;11/2/287American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyatherosclerosis, chronic kidney disease, cardiovascular disease, blood pressure, carotid intima-media thickness, follow-up studies, humans, renal insufficiency, chronic, smoking, vitamin DOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-02-05February 05, 201610.2215/CJN.012402151555-90411555-905X2015-12-14T07:39:45-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112287296
- Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid–Resistant Nephrotic Syndrome10.2215/CJN.07370715Mon, 14 Dec 2015 07:39:48 GMT-08:00Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid–Resistant Nephrotic SyndromeBüscher, Anja K.Beck, Bodo B.Melk, AnetteHoefele, JuliaKranz, BirgittaBamborschke, DanielBaig, SabrinaLange-Sperandio, BärbelJungraithmayr, TheresaWeber, Lutz T.Kemper, Markus J.Tönshoff, BurkhardHoyer, Peter F.Konrad, MartinWeber, Stefanie2015-12-14T07:39:48-08:00doi:10.2215/CJN.07370715hwp:resource-id:clinjasn;11/2/245American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyNPHS1, NPHS2, WT1, FSGS, steroid resistant nephrotic syndrome, cyclosporine A, humans, kidney failure, chronic, mutationOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-02-05February 05, 201610.2215/CJN.073707151555-90411555-905X2015-12-14T07:39:48-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112245253
- Effect of Synbiotic Therapy on Gut–Derived Uremic Toxins and the Intestinal Microbiome in Patients with CKD10.2215/CJN.13631215Fri, 15 Jan 2016 06:24:53 GMT-08:00Effect of Synbiotic Therapy on Gut–Derived Uremic Toxins and the Intestinal Microbiome in Patients with CKDVaziri, Nosratola D.2016-01-15T06:24:53-08:00doi:10.2215/CJN.13631215hwp:resource-id:clinjasn;11/2/199American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, intestine, oxidative stress, pathophysiology of renal disease and progression, gastrointestinal microbiome, humans, synbiotics, toxins, biologicalEditorialsEditorialseditorial20162016-02-05February 05, 201610.2215/CJN.136312151555-90411555-905X2016-01-15T06:24:53-08:002016-02-05Clinical Journal of the American Society of NephrologyEditorials1122199223201231
- Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials10.2215/CJN.06800615Mon, 14 Dec 2015 07:39:46 GMT-08:00Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled TrialsPatel, LeenaBernard, Lisa M.Elder, Grahame J.2015-12-14T07:39:46-08:00doi:10.2215/CJN.06800615hwp:resource-id:clinjasn;11/2/232American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, mortality, phosphate binders, calcium, sevelamer, meta-analysis, hospitalization, humans, randomized controlled trials as topicOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-02-05February 05, 201610.2215/CJN.068006151555-90411555-905X2015-12-14T07:39:46-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112232244
- Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants10.2215/CJN.06950615Mon, 14 Dec 2015 07:39:48 GMT-08:00Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney TransplantsPotluri, Vishnu S.Parikh, Chirag R.Hall, Isaac E.Ficek, JosephDoshi, Mona D.Butrymowicz, IsabelWeng, Francis L.Schröppel, BerndThiessen-Philbrook, HeatherReese, Peter P.2015-12-14T07:39:48-08:00doi:10.2215/CJN.06950615hwp:resource-id:clinjasn;11/2/324American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydeceased donors, validation studies, acute rejection, adult, allografts, delayed graft function, humans, kidney transplantation, tissue donors, tissue and organ procurementOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-02-05February 05, 201610.2215/CJN.069506151555-90411555-905X2015-12-14T07:39:48-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112324331
- Immunosuppressive MedicationsImmunosuppressive agents are commonly used in the nephrologist’s practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.10.2215/CJN.08570814Mon, 13 Jul 2015 08:04:00 GMT-07:00Immunosuppressive MedicationsImmunosuppressive agents are commonly used in the nephrologist’s practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.Wiseman, Alexander C.2015-07-13T08:04:00-07:00doi:10.2215/CJN.08570814hwp:resource-id:clinjasn;11/2/332American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyGN, kidney transplantation, immunology, cytokines, cell, activationRenal ImmunologyRenal Immunologyresearch-article20162016-02-05February 05, 201610.2215/CJN.085708141555-90411555-905X2015-07-13T08:04:00-07:002016-02-05Clinical Journal of the American Society of NephrologyRenal Immunology112332343
- The Native Kidney Biopsy: Update and Evidence for Best PracticeThe kidney biopsy is the gold standard in the diagnosis and management of many diseases. Since its introduction in the 1950s, advancements have been made in biopsy technique to improve diagnostic yield while minimizing complications. Here, we review kidney biopsy indications, techniques, and complications in the modern era. We also discuss patient populations in whom special consideration must be given when considering a kidney biopsy and the important role that the kidney biopsy plays in nephrology training. These data are presented to develop best practice strategies for this essential procedure.10.2215/CJN.05750515Wed, 02 Sep 2015 10:29:54 GMT-07:00The Native Kidney Biopsy: Update and Evidence for Best PracticeThe kidney biopsy is the gold standard in the diagnosis and management of many diseases. Since its introduction in the 1950s, advancements have been made in biopsy technique to improve diagnostic yield while minimizing complications. Here, we review kidney biopsy indications, techniques, and complications in the modern era. We also discuss patient populations in whom special consideration must be given when considering a kidney biopsy and the important role that the kidney biopsy plays in nephrology training. These data are presented to develop best practice strategies for this essential procedure.Hogan, Jonathan J.Mocanu, MichaelaBerns, Jeffrey S.2015-09-02T10:29:54-07:00doi:10.2215/CJN.05750515hwp:resource-id:clinjasn;11/2/354American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney biopsy, kidney disease, glomerular disease, biopsy, disease management, humans, kidney, nephrectomy, nephrologyMini-ReviewMini-Reviewreview-article20162016-02-05February 05, 201610.2215/CJN.057505151555-90411555-905X2015-09-02T10:29:54-07:002016-02-05Clinical Journal of the American Society of NephrologyMini-Review112354362
- The Role of Time–Limited Trials in Dialysis Decision Making in Critically Ill PatientsTechnologic advances, such as continuous RRT, provide lifesaving therapy for many patients. AKI in the critically ill patient, a fatal diagnosis in the past, is now often a survivable condition. Dialysis decision making for the critically ill patient with AKI is complex. What was once a question solely of survival now is nuanced by an individual’s definition of quality of life, personal values, and short– and long–term prognoses. Clinical evaluation of AKI in the critically ill is multifaceted. Treatment decision making requires consideration of the natural evolution of the patient’s AKI within the context of the global prognosis. Situations are often marked by prognostic uncertainty and clinical unknowns. In the face of these uncertainties, establishment of patient-directed therapies is imperative. A time–limited trial of continuous RRT in this setting is often appropriate but difficult to execute. Using patient preferences as a clinical guide, a proper time–limited trial requires assessment of prognosis, elicitation of patient values, strong communication skills, clear documentation, and often, appropriate integration of palliative care services. A well conducted time–limited trial can avoid interprofessional conflict and provide support for the patient, family, and staff.10.2215/CJN.03550315Thu, 08 Oct 2015 09:09:46 GMT-07:00The Role of Time–Limited Trials in Dialysis Decision Making in Critically Ill PatientsTechnologic advances, such as continuous RRT, provide lifesaving therapy for many patients. AKI in the critically ill patient, a fatal diagnosis in the past, is now often a survivable condition. Dialysis decision making for the critically ill patient with AKI is complex. What was once a question solely of survival now is nuanced by an individual’s definition of quality of life, personal values, and short– and long–term prognoses. Clinical evaluation of AKI in the critically ill is multifaceted. Treatment decision making requires consideration of the natural evolution of the patient’s AKI within the context of the global prognosis. Situations are often marked by prognostic uncertainty and clinical unknowns. In the face of these uncertainties, establishment of patient-directed therapies is imperative. A time–limited trial of continuous RRT in this setting is often appropriate but difficult to execute. Using patient preferences as a clinical guide, a proper time–limited trial requires assessment of prognosis, elicitation of patient values, strong communication skills, clear documentation, and often, appropriate integration of palliative care services. A well conducted time–limited trial can avoid interprofessional conflict and provide support for the patient, family, and staff.Scherer, Jennifer S.Holley, Jean L.2015-10-08T09:09:46-07:00doi:10.2215/CJN.03550315hwp:resource-id:clinjasn;11/2/344American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyintensive care unit, communication, time-limited trials, acute kidney injury, decision making, humans, palliative care, quality of life, renal dialysis, renal replacement therapyEthics SeriesEthics Seriesresearch-article20162016-02-05February 05, 201610.2215/CJN.035503151555-90411555-905X2015-10-08T09:09:46-07:002016-02-05Clinical Journal of the American Society of NephrologyEthics Series112344353
- Structural Predictors of Renal Function Decline10.2215/CJN.13431215Wed, 20 Jan 2016 07:24:36 GMT-08:00Structural Predictors of Renal Function DeclineNicholas, Susanne B.2016-01-20T07:24:36-08:00doi:10.2215/CJN.13431215hwp:resource-id:clinjasn;11/2/202American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, renal biopsy, morphometry, prognosisEditorialsEditorialseditorial20162016-02-05February 05, 201610.2215/CJN.134312151555-90411555-905X2016-01-20T07:24:36-08:002016-02-05Clinical Journal of the American Society of NephrologyEditorials1122202254204261
- The Burden of Harm—What Is the Ideal Vascular Access for Home Hemodialysis?10.2215/CJN.12681115Mon, 04 Jan 2016 06:37:20 GMT-08:00The Burden of Harm—What Is the Ideal Vascular Access for Home Hemodialysis?Trinh, EmilieChan, Christopher T.2016-01-04T06:37:20-08:00doi:10.2215/CJN.12681115hwp:resource-id:clinjasn;11/2/205American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, home hemodialysis, central venous catheter, arteriovenous shunt, surgical, hemodialysis, home, humans, renal dialysisEditorialsEditorialseditorial20162016-02-05February 05, 201610.2215/CJN.126811151555-90411555-905X2016-01-04T06:37:20-08:002016-02-05Clinical Journal of the American Society of NephrologyEditorials1122205298206307
- Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory Death10.2215/CJN.07190715Mon, 14 Dec 2015 07:39:49 GMT-08:00Epidemiology of Kidney Discard from Expanded Criteria Donors Undergoing Donation after Circulatory DeathSingh, Sunita K.Kim, S. Joseph2015-12-14T07:39:49-08:00doi:10.2215/CJN.07190715hwp:resource-id:clinjasn;11/2/317American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyepidemiology and outcomes, kidney transplantation, cadaver organ transplantation, expanded criteria donor, donation after circulatory death, kidney, registries, risk factors, tissue donors, transplant recipientsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-02-05February 05, 201610.2215/CJN.071907151555-90411555-905X2015-12-14T07:39:49-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112317323
- Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition Study10.2215/CJN.06200615Thu, 14 Jan 2016 07:03:05 GMT-08:00Bicarbonate Concentration, Acid-Base Status, and Mortality in the Health, Aging, and Body Composition StudyRaphael, Kalani L.Murphy, Rachel A.Shlipak, Michael G.Satterfield, SuzanneHuston, Hunter K.Sebastian, AnthonySellmeyer, Deborah E.Patel, Kushang V.Newman, Anne B.Sarnak, Mark J.Ix, Joachim H.Fried, Linda F.2016-01-14T07:03:05-08:00doi:10.2215/CJN.06200615hwp:resource-id:clinjasn;11/2/308American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologybicarbonate, acid-base equilibrium, mortality, acidosis, body composition, follow-up studies, glomerular filtration rate, humans, prospective studies, renal insufficiency, chronicOriginal ArticlesGeriatric NephrologyOriginal ArticlesGeriatric Nephrologyresearch-article20162016-02-05February 05, 201610.2215/CJN.062006151555-90411555-905X2016-01-14T07:03:05-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles112308316
- Quality Measures for Dialysis: Time for a Balanced ScorecardRecent federal legislation establishes a merit-based incentive payment system for physicians, with a scorecard for each professional. The Centers for Medicare and Medicaid Services evaluate quality of care with clinical performance measures and have used these metrics for public reporting and payment to dialysis facilities. Similar metrics may be used for the future merit-based incentive payment system. In nephrology, most clinical performance measures measure processes and intermediate outcomes of care. These metrics were developed from population studies of best practice and do not identify opportunities for individualizing care on the basis of patient characteristics and individual goals of treatment. The In-Center Hemodialysis (ICH) Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey examines patients' perception of care and has entered the arena to evaluate quality of care. A balanced scorecard of quality performance should include three elements: population-based best clinical practice, patient perceptions, and individually crafted patient goals of care.10.2215/CJN.06010615Thu, 27 Aug 2015 07:11:44 GMT-07:00Quality Measures for Dialysis: Time for a Balanced ScorecardRecent federal legislation establishes a merit-based incentive payment system for physicians, with a scorecard for each professional. The Centers for Medicare and Medicaid Services evaluate quality of care with clinical performance measures and have used these metrics for public reporting and payment to dialysis facilities. Similar metrics may be used for the future merit-based incentive payment system. In nephrology, most clinical performance measures measure processes and intermediate outcomes of care. These metrics were developed from population studies of best practice and do not identify opportunities for individualizing care on the basis of patient characteristics and individual goals of treatment. The In-Center Hemodialysis (ICH) Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey examines patients' perception of care and has entered the arena to evaluate quality of care. A balanced scorecard of quality performance should include three elements: population-based best clinical practice, patient perceptions, and individually crafted patient goals of care.Kliger, Alan S.2015-08-27T07:11:44-07:00doi:10.2215/CJN.06010615hwp:resource-id:clinjasn;11/2/363American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, quality of life, clinical performance measuresSpecial FeatureSpecial Featureresearch-article20162016-02-05February 05, 201610.2215/CJN.060106151555-90411555-905X2015-08-27T07:11:44-07:002016-02-05Clinical Journal of the American Society of NephrologySpecial Feature112363368
- Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes10.2215/CJN.05760515Wed, 20 Jan 2016 07:24:36 GMT-08:00Structural Predictors of Loss of Renal Function in American Indians with Type 2 DiabetesFufaa, Gudeta D.Weil, E. JenniferLemley, Kevin V.Knowler, William C.Brosius, Frank C.Yee, BerneMauer, MichaelNelson, Robert G.2016-01-20T07:24:36-08:00doi:10.2215/CJN.05760515hwp:resource-id:clinjasn;11/2/254American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetic nephropathy, epidemiology and outcomes, glomerular filtration rate, kidney biopsy, renal morphology, diabetes mellitus, type 2, humans, Indians, North American, kidney diseasesOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20162016-02-05February 05, 201610.2215/CJN.057605151555-90411555-905X2016-01-20T07:24:36-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles1122254202261204
- Association of Vascular Access Type with Mortality, Hospitalization, and Transfer to In-Center Hemodialysis in Patients Undergoing Home Hemodialysis10.2215/CJN.06570615Mon, 04 Jan 2016 06:37:21 GMT-08:00Association of Vascular Access Type with Mortality, Hospitalization, and Transfer to In-Center Hemodialysis in Patients Undergoing Home HemodialysisRivara, Matthew B.Soohoo, MelissaStreja, ElaniMolnar, Miklos Z.Rhee, Connie M.Cheung, Alfred K.Katz, RonitArah, Onyebuchi A.Nissenson, Allen R.Himmelfarb, JonathanKalantar-Zadeh, KamyarMehrotra, Rajnish2016-01-04T06:37:21-08:00doi:10.2215/CJN.06570615hwp:resource-id:clinjasn;11/2/298American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvascular access, end-stage renal disease, home hemodialysis, arteriovenous fistula, arteriovenous graft, mortality risk, hospitalization, central venous catheters, follow-up studies, humansOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-02-05February 05, 201610.2215/CJN.065706151555-90411555-905X2016-01-04T06:37:21-08:002016-02-05Clinical Journal of the American Society of NephrologyOriginal Articles1122298205307206
- Urine Metabolite Profiles Predictive of Human Kidney Allograft StatusNoninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite–mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.10.1681/ASN.2015010107Fri, 05 Jun 2015 11:13:43 GMT-07:00Urine Metabolite Profiles Predictive of Human Kidney Allograft StatusNoninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite–mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.Suhre, KarstenSchwartz, Joseph E.Sharma, Vijay K.Chen, QiuyingLee, John R.Muthukumar, ThangamaniDadhania, Darshana M.Ding, RuchuangIkle, David N.Bridges, Nancy D.Williams, Nikki M.Kastenmüller, GabiKaroly, Edward D.Mohney, Robert P.Abecassis, MichaelFriedewald, JohnKnechtle, Stuart J.Becker, Yolanda T.Samstein, BenjaminShaked, AbrahamGross, Steven S.Suthanthiran, Manikkam2015-06-05T11:13:43-07:00doi:10.1681/ASN.2015010107hwp:resource-id:jnephrol;27/2/626American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, acute rejection, kidney biopsy, transplant outcomesClinical ResearchClinical Researchresearch-article20162016-02-01February 201610.1681/ASN.20150101071046-66731533-34502015-06-05T11:13:43-07:002016-02Journal of the American Society of NephrologyClinical Research272626636
- Association of Height with Elevated Mortality Risk in ESRD: Variation by Race and GenderThe association of adult height with mortality has been extensively investigated in the general population, but little is known about this relationship among dialysis patients. We explored the relationship between height and mortality in a retrospective cohort study of 1,171,842 adults who began dialysis in the United States from 1995 to 2008 and were followed until December 31, 2010. We evaluated height-mortality associations in sex-specific quintiles of increasing height (Q1–Q5) using multivariable Cox regression models adjusted for demographics, comorbid conditions, lifestyle and disability indicators, socioeconomic status, and body weight. For men, compared with the referent quintile (Q1 <167 cm), successive height quintiles had significantly increased hazard ratios (HRs [95% confidence interval]) for mortality: 1.04 (1.02–1.06), 1.08 (1.06–1.10), 1.12 (1.11–1.14), and 1.18 (1.16–1.20) for Q2–Q5, respectively. For women (referent Q1 <155 cm), HRs for mortality were 1.00 (0.99–1.02), 1.05 (1.03–1.06), 1.05 (1.03–1.07), and 1.08 (1.06–1.10) for Q2–Q5, respectively. However, stratification by race showed the pattern of association differed significantly by race (P<0.001 for interaction). For black men, unlike other race groups, height only associated with mortality in Q5, with an HR of 1.06 (1.02–1.09). For black women, HRs for mortality were 0.94 (0.91–0.97), 0.98 (0.95–1.02), 0.96 (0.93–0.99), and 0.99 (0.96–1.02) for Q2–Q5, respectively. These results indicate tallness is associated with higher mortality risks for adults starting dialysis, but this association did not extend to black patients.10.1681/ASN.2014080821Thu, 01 Oct 2015 07:40:20 GMT-07:00Association of Height with Elevated Mortality Risk in ESRD: Variation by Race and GenderThe association of adult height with mortality has been extensively investigated in the general population, but little is known about this relationship among dialysis patients. We explored the relationship between height and mortality in a retrospective cohort study of 1,171,842 adults who began dialysis in the United States from 1995 to 2008 and were followed until December 31, 2010. We evaluated height-mortality associations in sex-specific quintiles of increasing height (Q1–Q5) using multivariable Cox regression models adjusted for demographics, comorbid conditions, lifestyle and disability indicators, socioeconomic status, and body weight. For men, compared with the referent quintile (Q1 <167 cm), successive height quintiles had significantly increased hazard ratios (HRs [95% confidence interval]) for mortality: 1.04 (1.02–1.06), 1.08 (1.06–1.10), 1.12 (1.11–1.14), and 1.18 (1.16–1.20) for Q2–Q5, respectively. For women (referent Q1 <155 cm), HRs for mortality were 1.00 (0.99–1.02), 1.05 (1.03–1.06), 1.05 (1.03–1.07), and 1.08 (1.06–1.10) for Q2–Q5, respectively. However, stratification by race showed the pattern of association differed significantly by race (P<0.001 for interaction). For black men, unlike other race groups, height only associated with mortality in Q5, with an HR of 1.06 (1.02–1.09). For black women, HRs for mortality were 0.94 (0.91–0.97), 0.98 (0.95–1.02), 0.96 (0.93–0.99), and 0.99 (0.96–1.02) for Q2–Q5, respectively. These results indicate tallness is associated with higher mortality risks for adults starting dialysis, but this association did not extend to black patients.Elsayed, Mohamed E.Ferguson, John P.Stack, Austin G.2015-10-01T07:40:20-07:00doi:10.1681/ASN.2014080821hwp:resource-id:jnephrol;27/2/580American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney failure, mortality, epidemiology and outcomes, renal dialysisClinical EpidemiologyClinical Epidemiologyresearch-article20162016-02-01February 201610.1681/ASN.20140808211046-66731533-34502015-10-01T07:40:20-07:002016-02Journal of the American Society of NephrologyClinical Epidemiology2722580339593341
- Efficacy of Targeted Complement Inhibition in Experimental C3 GlomerulopathyC3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). There is no effective treatment for C3 glomerulopathy. We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy.10.1681/ASN.2014121195Fri, 05 Jun 2015 11:13:43 GMT-07:00Efficacy of Targeted Complement Inhibition in Experimental C3 GlomerulopathyC3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). There is no effective treatment for C3 glomerulopathy. We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. CR2-FH partially restored plasma C3 levels in FH-deficient mice 2 hours after intravenous injection. CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. Reduction in glomerular C3d and C9/C5b-9 reactivity was observed after daily administration of CR2-FH for 1 week. In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy.Ruseva, Marieta M.Peng, TaoLasaro, Melissa A.Bouchard, KeithLiu-Chen, SusanSun, FangYu, Zhao-XueMarozsan, AndreWang, YiPickering, Matthew C.2015-06-05T11:13:43-07:00doi:10.1681/ASN.2014121195hwp:resource-id:jnephrol;27/2/405American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, glomerulopathy, therapyBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141211951046-66731533-34502015-06-05T11:13:43-07:002016-02Journal of the American Society of NephrologyBasic Research272405416
- Inflammation in AKI: Current Understanding, Key Questions, and Knowledge GapsInflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.10.1681/ASN.2015030261Wed, 11 Nov 2015 05:22:28 GMT-08:00Inflammation in AKI: Current Understanding, Key Questions, and Knowledge GapsInflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.Rabb, HamidGriffin, Matthew D.McKay, Dianne B.Swaminathan, SundararamanPickkers, PeterRosner, Mitchell H.Kellum, John A.Ronco, Claudio2015-11-11T05:22:28-08:00doi:10.1681/ASN.2015030261hwp:resource-id:jnephrol;27/2/371American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, immunology, pathophysiology of, renal disease and progressionUp Front MattersSpecial ArticleUp Front MattersSpecial Articleresearch-article20162016-02-01February 201610.1681/ASN.20150302611046-66731533-34502015-11-11T05:22:28-08:002016-02Journal of the American Society of NephrologyUp Front Matters272371379
- Immune Sensitization and Mortality in Wait-Listed Kidney Transplant CandidatesCardiovascular mortality is the leading cause of death in ESRD. Whereas innate and adaptive immunity have established roles in cardiovascular disease, the role of humoral immunity is unknown. We conducted a retrospective cohort study in first-time adult kidney transplant candidates (N=161,308) using data from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services to evaluate whether anti–human leukocyte antigen antibodies, measured as panel reactive antibodies (PRAs), are related to mortality in ESRD. Relationships between time-varying PRAs and all-cause or cardiovascular mortality were assessed using Cox proportional hazards models. The analysis was repeated in subcohorts of candidates at lower risk for significant comorbidities, activated on the waiting list after 2007, or unsensitized at activation. Competing risks analyses were also conducted. Fully adjusted models showed increased hazard ratios (HRs [95% confidence intervals]) for all-cause mortality (HR, 1.02 [95% CI, 0.99 to 1.06]; HR, 1.11 [95% CI,1.07 to 1.16]; and HR,1.21 [95% CI,1.15 to 1.27]) and cardiovascular mortality (HR, 1.05 [95% CI,1.00 to 1.10]; HR,1.11 [95% CI,1.05 to 1.18]; and HR,1.21 [95% CI,1.12 to 1.31]) in PRA 1%–19%, PRA 20%–79%, and PRA 80%–100% categories compared with PRA 0%, respectively. Associations between PRA and the study outcomes were accentuated in competing risks models and in lower-risk patients and persisted in other subcohorts. Our findings suggest that PRA is an independent predictor of mortality in wait-listed kidney transplant candidates. The mechanisms by which PRA confers an incremental mortality risk in sensitized patients, and the role of transplantation in modifying this risk, warrant further study.10.1681/ASN.2014090894Mon, 08 Jun 2015 06:52:44 GMT-07:00Immune Sensitization and Mortality in Wait-Listed Kidney Transplant CandidatesCardiovascular mortality is the leading cause of death in ESRD. Whereas innate and adaptive immunity have established roles in cardiovascular disease, the role of humoral immunity is unknown. We conducted a retrospective cohort study in first-time adult kidney transplant candidates (N=161,308) using data from the Scientific Registry of Transplant Recipients and the Centers for Medicare and Medicaid Services to evaluate whether anti–human leukocyte antigen antibodies, measured as panel reactive antibodies (PRAs), are related to mortality in ESRD. Relationships between time-varying PRAs and all-cause or cardiovascular mortality were assessed using Cox proportional hazards models. The analysis was repeated in subcohorts of candidates at lower risk for significant comorbidities, activated on the waiting list after 2007, or unsensitized at activation. Competing risks analyses were also conducted. Fully adjusted models showed increased hazard ratios (HRs [95% confidence intervals]) for all-cause mortality (HR, 1.02 [95% CI, 0.99 to 1.06]; HR, 1.11 [95% CI,1.07 to 1.16]; and HR,1.21 [95% CI,1.15 to 1.27]) and cardiovascular mortality (HR, 1.05 [95% CI,1.00 to 1.10]; HR,1.11 [95% CI,1.05 to 1.18]; and HR,1.21 [95% CI,1.12 to 1.31]) in PRA 1%–19%, PRA 20%–79%, and PRA 80%–100% categories compared with PRA 0%, respectively. Associations between PRA and the study outcomes were accentuated in competing risks models and in lower-risk patients and persisted in other subcohorts. Our findings suggest that PRA is an independent predictor of mortality in wait-listed kidney transplant candidates. The mechanisms by which PRA confers an incremental mortality risk in sensitized patients, and the role of transplantation in modifying this risk, warrant further study.Sapir-Pichhadze, RuthTinckam, Kathryn J.Laupacis, AndreasLogan, Alexander G.Beyene, JosephKim, S. Joseph2015-06-08T06:52:44-07:00doi:10.1681/ASN.2014090894hwp:resource-id:jnephrol;27/2/570American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, immunology, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20162016-02-01February 201610.1681/ASN.20140908941046-66731533-34502015-06-08T06:52:44-07:002016-02Journal of the American Society of NephrologyClinical Epidemiology272570578
- Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney TransplantsCytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.10.1681/ASN.2014100985Mon, 08 Jun 2015 06:52:45 GMT-07:00Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney TransplantsCytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.Kaminski, HannahGarrigue, IsabelleCouzi, LionelTaton, BenjaminBachelet, ThomasMoreau, Jean-FrançoisDéchanet-Merville, JulieThiébaut, RodolpheMerville, Pierre2015-06-08T06:52:45-07:00doi:10.1681/ASN.2014100985hwp:resource-id:jnephrol;27/2/637American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycytomegalovirus, kidney transplantation, immunology, immunosuppressionClinical ResearchClinical Researchresearch-article20162016-02-01February 201610.1681/ASN.20141009851046-66731533-34502015-06-08T06:52:45-07:002016-02Journal of the American Society of NephrologyClinical Research272637645
- HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant RecipientsHigh-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B–depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan–Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.10.1681/ASN.2014090857Fri, 28 Aug 2015 08:24:04 GMT-07:00HDL Cholesterol Efflux Predicts Graft Failure in Renal Transplant RecipientsHigh-density lipoprotein (HDL) particles are involved in the protection against cardiovascular disease by promoting cholesterol efflux, in which accumulated cholesterol is removed from macrophage foam cells. We investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in a cohort of renal transplant recipients (n=495, median follow-up 7.0 years). Cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B–depleted plasma. Baseline efflux capacity was not different in deceased patients and survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan–Meier analysis demonstrated a lower risk for graft failure (P=0.004) but not cardiovascular (P=0.30) or all-cause mortality (P=0.31) with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR], 0.89; 95% confidence interval [95% CI], 0.67 to 1.19; P=0.43). Furthermore, the association between efflux capacity and all-cause mortality (HR, .79; 95% CI, 0.63 to 0.98; P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR, 0.43; 95% CI, 0.29 to 0.64; P<0.001) independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. In conclusion, this prospective study shows that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.Annema, WijtskeDikkers, ArneFreark de Boer, JanDullaart, Robin P. F.Sanders, Jan-Stephan F.Bakker, Stephan J. L.Tietge, Uwe J. F.2015-08-28T08:24:04-07:00doi:10.1681/ASN.2014090857hwp:resource-id:jnephrol;27/2/595American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyarteriosclerosis, chronic allograft failure, lipids, mortality, transplant outcomesClinical ResearchClinical Researchresearch-article20162016-02-01February 201610.1681/ASN.20140908571046-66731533-34502015-08-28T08:24:04-07:002016-02Journal of the American Society of NephrologyClinical Research2722595341603344
- Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney DiseaseThe NADPH oxidase (NOX) isoform NOX4 has been linked with diabetic kidney disease (DKD). However, a mechanistic understanding of the downstream effects of NOX4 remains to be established. We report that podocyte-specific induction of NOX4 in vivo was sufficient to recapitulate the characteristic glomerular changes noted with DKD, including glomerular hypertrophy, mesangial matrix accumulation, glomerular basement membrane thickening, albuminuria, and podocyte dropout. Intervention with a NOX1/NOX4 inhibitor reduced albuminuria, glomerular hypertrophy, and mesangial matrix accumulation in the F1 Akita model of DKD. Metabolomic analyses from these mouse studies revealed that tricarboxylic acid (TCA) cycle–related urinary metabolites were increased in DKD, but fumarate levels were uniquely reduced by the NOX1/NOX4 inhibitor. Expression of fumarate hydratase (FH), which regulates urine fumarate accumulation, was reduced in the diabetic kidney (in mouse and human tissue), and administration of the NOX1/NOX4 inhibitor increased glomerular FH levels in diabetic mice. Induction of Nox4 in vitro and in the podocyte-specific NOX4 transgenic mouse led to reduced FH levels. In vitro, fumarate stimulated endoplasmic reticulum stress, matrix gene expression, and expression of hypoxia-inducible factor-1α (HIF-1α) and TGF-β. Similar upregulation of renal HIF-1α and TGF-β expression was observed in NOX4 transgenic mice and diabetic mice and was attenuated by NOX1/NOX4 inhibition in diabetic mice. In conclusion, NOX4 is a major mediator of diabetes-associated glomerular dysfunction through targeting of renal FH, which increases fumarate levels. Fumarate is therefore a key link connecting metabolic pathways to DKD pathogenesis, and measuring urinary fumarate levels may have application for monitoring renal NOX4 activity.10.1681/ASN.2015030302Wed, 22 Jul 2015 06:07:14 GMT-07:00Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH Oxidase 4 in Diabetic Kidney DiseaseThe NADPH oxidase (NOX) isoform NOX4 has been linked with diabetic kidney disease (DKD). However, a mechanistic understanding of the downstream effects of NOX4 remains to be established. We report that podocyte-specific induction of NOX4 in vivo was sufficient to recapitulate the characteristic glomerular changes noted with DKD, including glomerular hypertrophy, mesangial matrix accumulation, glomerular basement membrane thickening, albuminuria, and podocyte dropout. Intervention with a NOX1/NOX4 inhibitor reduced albuminuria, glomerular hypertrophy, and mesangial matrix accumulation in the F1 Akita model of DKD. Metabolomic analyses from these mouse studies revealed that tricarboxylic acid (TCA) cycle–related urinary metabolites were increased in DKD, but fumarate levels were uniquely reduced by the NOX1/NOX4 inhibitor. Expression of fumarate hydratase (FH), which regulates urine fumarate accumulation, was reduced in the diabetic kidney (in mouse and human tissue), and administration of the NOX1/NOX4 inhibitor increased glomerular FH levels in diabetic mice. Induction of Nox4 in vitro and in the podocyte-specific NOX4 transgenic mouse led to reduced FH levels. In vitro, fumarate stimulated endoplasmic reticulum stress, matrix gene expression, and expression of hypoxia-inducible factor-1α (HIF-1α) and TGF-β. Similar upregulation of renal HIF-1α and TGF-β expression was observed in NOX4 transgenic mice and diabetic mice and was attenuated by NOX1/NOX4 inhibition in diabetic mice. In conclusion, NOX4 is a major mediator of diabetes-associated glomerular dysfunction through targeting of renal FH, which increases fumarate levels. Fumarate is therefore a key link connecting metabolic pathways to DKD pathogenesis, and measuring urinary fumarate levels may have application for monitoring renal NOX4 activity.You, Young-HyunQuach, TammySaito, RintaroPham, JessicaSharma, Kumar2015-07-22T06:07:14-07:00doi:10.1681/ASN.2015030302hwp:resource-id:jnephrol;27/2/466American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, NADPH oxidase, fibrosis, reactive oxygen species, podocyte, mitochondriaBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20150303021046-66731533-34502015-07-22T06:07:14-07:002016-02Journal of the American Society of NephrologyBasic Research2722466337481339
- Proximal Tubules Have the Capacity to Regulate Uptake of AlbuminEvidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level.10.1681/ASN.2014111107Mon, 08 Jun 2015 06:52:49 GMT-07:00Proximal Tubules Have the Capacity to Regulate Uptake of AlbuminEvidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level.Wagner, Mark C.Campos-Bilderback, Silvia B.Chowdhury, MahboobFlores, BrittanyLai, XianyinMyslinski, JeredPandit, SweekarSandoval, Ruben M.Wean, Sarah E.Wei, YuanSatlin, Lisa M.Wiggins, Roger C.Witzmann, Frank A.Molitoris, Bruce A.2015-06-08T06:52:49-07:00doi:10.1681/ASN.2014111107hwp:resource-id:jnephrol;27/2/482American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, renal proximal tubule cell, tubular epithelium, glomerulus, glomerular diseaseBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141111071046-66731533-34502015-06-08T06:52:49-07:002016-02Journal of the American Society of NephrologyBasic Research272482494
- Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia SignalingErythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. However, the hypoxic response of these transformed myofibroblasts remains unclear. Here, we used complementary in vivo transgenic and live imaging approaches to better understand the importance of hypoxia signaling in Epo production. Live imaging of REPs in transgenic mice expressing green fluorescent protein from a modified Epo-gene locus revealed that healthy REPs tightly associated with endothelium by wrapping processes around capillaries. However, this association was hampered in states of renal injury-induced inflammation previously shown to correlate with the transition to myofibroblast-transformed renal Epo-producing cells (MF-REPs). Furthermore, activation of hypoxia-inducible factors (HIFs) by genetic inactivation of HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) selectively in Epo-producing cells reactivated Epo production in MF-REPs. Loss of PHD2 in REPs restored Epo-gene expression in injured kidneys but caused polycythemia. Notably, combined deletions of PHD1 and PHD3 prevented loss of Epo expression without provoking polycythemia. Mice with PHD-deficient REPs also showed resistance to LPS-induced Epo repression in kidneys, suggesting that augmented HIF signaling counterbalances inflammatory stimuli in regulation of Epo production. Thus, augmentation of HIF signaling may be an attractive therapeutic strategy for treating renal anemia by reactivating Epo synthesis in MF-REPs.10.1681/ASN.2014121184Mon, 08 Jun 2015 06:52:48 GMT-07:00Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia SignalingErythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. However, the hypoxic response of these transformed myofibroblasts remains unclear. Here, we used complementary in vivo transgenic and live imaging approaches to better understand the importance of hypoxia signaling in Epo production. Live imaging of REPs in transgenic mice expressing green fluorescent protein from a modified Epo-gene locus revealed that healthy REPs tightly associated with endothelium by wrapping processes around capillaries. However, this association was hampered in states of renal injury-induced inflammation previously shown to correlate with the transition to myofibroblast-transformed renal Epo-producing cells (MF-REPs). Furthermore, activation of hypoxia-inducible factors (HIFs) by genetic inactivation of HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) selectively in Epo-producing cells reactivated Epo production in MF-REPs. Loss of PHD2 in REPs restored Epo-gene expression in injured kidneys but caused polycythemia. Notably, combined deletions of PHD1 and PHD3 prevented loss of Epo expression without provoking polycythemia. Mice with PHD-deficient REPs also showed resistance to LPS-induced Epo repression in kidneys, suggesting that augmented HIF signaling counterbalances inflammatory stimuli in regulation of Epo production. Thus, augmentation of HIF signaling may be an attractive therapeutic strategy for treating renal anemia by reactivating Epo synthesis in MF-REPs.Souma, TomokazuNezu, MasahiroNakano, DaisukeYamazaki, ShunHirano, IkuoSekine, HirokiDan, TakashiTakeda, KotaroFong, Guo-HuaNishiyama, AkiraIto, SadayoshiMiyata, ToshioYamamoto, MasayukiSuzuki, Norio2015-06-08T06:52:48-07:00doi:10.1681/ASN.2014121184hwp:resource-id:jnephrol;27/2/428American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, chronic kidney disease, erythropoietin, fibrosis, hypoxia, Pathophysiology of Renal Disease and ProgressionBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141211841046-66731533-34502015-06-08T06:52:48-07:002016-02Journal of the American Society of NephrologyBasic Research272428438
- Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort StudyChildhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293–533) and 323 (95% CI, 216–481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged ≥15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P≤0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15–0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21–10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.10.1681/ASN.2015020152Thu, 02 Jul 2015 08:13:56 GMT-07:00Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort StudyChildhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293–533) and 323 (95% CI, 216–481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged ≥15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P≤0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15–0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21–10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.Denburg, Michelle R.Kumar, JuhiJemielita, ThomasBrooks, Ellen R.Skversky, AmyPortale, Anthony A.Salusky, Isidro B.Warady, Bradley A.Furth, Susan L.Leonard, Mary B.2015-07-02T08:13:56-07:00doi:10.1681/ASN.2015020152hwp:resource-id:jnephrol;27/2/543American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, children, clinical epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20162016-02-01February 201610.1681/ASN.20150201521046-66731533-34502015-07-02T08:13:56-07:002016-02Journal of the American Society of NephrologyClinical Epidemiology272543550
- Hepatocyte Nuclear Factor 1β–Associated Kidney Disease: More than Renal Cysts and DiabetesHepatocyte nuclear factor 1β (HNF1β)–associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1β transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1β-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1β-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1β-associated disease for the nephrologist.10.1681/ASN.2015050544Fri, 28 Aug 2015 08:24:02 GMT-07:00Hepatocyte Nuclear Factor 1β–Associated Kidney Disease: More than Renal Cysts and DiabetesHepatocyte nuclear factor 1β (HNF1β)–associated disease is a recently recognized clinical entity with a variable multisystem phenotype. Early reports described an association between HNF1B mutations and maturity-onset diabetes of the young. These patients often presented with renal cysts and renal function decline that preceded the diabetes, hence it was initially referred to as renal cysts and diabetes syndrome. However, it is now evident that many more symptoms occur, and diabetes and renal cysts are not always present. The multisystem phenotype is probably attributable to functional promiscuity of the HNF1β transcription factor, involved in the development of the kidney, urogenital tract, pancreas, liver, brain, and parathyroid gland. Nephrologists might diagnose HNF1β-associated kidney disease in patients referred with a suspected diagnosis of autosomal dominant polycystic kidney disease, medullary cystic kidney disease, diabetic nephropathy, or CKD of unknown cause. Associated renal or extrarenal symptoms should alert the nephrologist to HNF1β-associated kidney disease. A considerable proportion of these patients display hypomagnesemia, which sometimes mimics Gitelman syndrome. Other signs include early onset diabetes, gout and hyperparathyroidism, elevated liver enzymes, and congenital anomalies of the urogenital tract. Because many cases of this disease are probably undiagnosed, this review emphasizes the clinical manifestations of HNF1β-associated disease for the nephrologist.Verhave, Jacobien C.Bech, Anneke P.Wetzels, Jack F.M.Nijenhuis, Tom2015-08-28T08:24:02-07:00doi:10.1681/ASN.2015050544hwp:resource-id:jnephrol;27/2/345American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, clinical nephrology, CKD, cystic kidney, diabetes mellitus, electrolytesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-02-01February 201610.1681/ASN.20150505441046-66731533-34502015-08-28T08:24:02-07:002016-02Journal of the American Society of NephrologyUp Front Matters272345353
- Uremic Toxicity of Advanced Glycation End Products in CKDAdvanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product–specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD.10.1681/ASN.2014101047Wed, 26 Aug 2015 06:22:19 GMT-07:00Uremic Toxicity of Advanced Glycation End Products in CKDAdvanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product–specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD.Stinghen, Andréa E.M.Massy, Ziad A.Vlassara, HelenStriker, Gary E.Boullier, Agnès2015-08-26T06:22:19-07:00doi:10.1681/ASN.2014101047hwp:resource-id:jnephrol;27/2/354American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyadvanced glycation end product, uremia, CKDUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-02-01February 201610.1681/ASN.20141010471046-66731533-34502015-08-26T06:22:19-07:002016-02Journal of the American Society of NephrologyUp Front Matters272354370
- Myeloperoxidase Peptide–Based Nasal Tolerance in Experimental ANCA–Associated GNLess toxic treatment options for patients with myeloperoxidase (MPO)-ANCA–associated GN are needed. Using an established murine model of focal necrotizing GN mediated by autoimmunity to MPO (autoimmune anti–MPO GN), we assessed the capacity for nasal tolerance induced by nasal insufflation of the immunodominant nephritogenic MPO peptide (MPO409–428) to attenuate this disease. Compared with mice that received an irrelevant immunodominant ovalbumin (OVA) peptide, OVA323–339, mice that received MPO409–428 were protected from the development of humoral and cell-mediated autoimmunity to full-length MPO and the development of GN. In mice with established anti–MPO autoimmunity, nasal insufflation of MPO409–428 as a therapeutic attenuated anti–MPO GN. To investigate the nature of this induced tolerance, we isolated CD4+ T cells from the upper airway draining lymph nodes of both OVA323–339- and MPO409–428-tolerized mice. Adoptive transfer of CD4+ T cells from MPO409–428- but not OVA323–339-tolerized mice to animals with established anti–MPO autoimmunity attenuated the subsequent development of GN, confirming that the immunosuppression induced by these T cells is antigen specific. Ex vivo studies showed that nasal tolerance to MPO is mediated by both conventional and induced T regulatory cells. The strong homology between the pathogenic human MPO B cell epitope recognized by ANCA in patients with acute vasculitis and the nephritogenic murine T cell MPO epitope emphasizes the clinical relevance of this study.10.1681/ASN.2015010089Fri, 05 Jun 2015 11:13:45 GMT-07:00Myeloperoxidase Peptide–Based Nasal Tolerance in Experimental ANCA–Associated GNLess toxic treatment options for patients with myeloperoxidase (MPO)-ANCA–associated GN are needed. Using an established murine model of focal necrotizing GN mediated by autoimmunity to MPO (autoimmune anti–MPO GN), we assessed the capacity for nasal tolerance induced by nasal insufflation of the immunodominant nephritogenic MPO peptide (MPO409–428) to attenuate this disease. Compared with mice that received an irrelevant immunodominant ovalbumin (OVA) peptide, OVA323–339, mice that received MPO409–428 were protected from the development of humoral and cell-mediated autoimmunity to full-length MPO and the development of GN. In mice with established anti–MPO autoimmunity, nasal insufflation of MPO409–428 as a therapeutic attenuated anti–MPO GN. To investigate the nature of this induced tolerance, we isolated CD4+ T cells from the upper airway draining lymph nodes of both OVA323–339- and MPO409–428-tolerized mice. Adoptive transfer of CD4+ T cells from MPO409–428- but not OVA323–339-tolerized mice to animals with established anti–MPO autoimmunity attenuated the subsequent development of GN, confirming that the immunosuppression induced by these T cells is antigen specific. Ex vivo studies showed that nasal tolerance to MPO is mediated by both conventional and induced T regulatory cells. The strong homology between the pathogenic human MPO B cell epitope recognized by ANCA in patients with acute vasculitis and the nephritogenic murine T cell MPO epitope emphasizes the clinical relevance of this study.Gan, Poh-YiTan, Diana S.Y.Ooi, Joshua D.Alikhan, Maliha A.Kitching, A. RichardHoldsworth, Stephen R.2015-06-05T11:13:45-07:00doi:10.1681/ASN.2015010089hwp:resource-id:jnephrol;27/2/385American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, GN, toleranceBrief CommunicationsBrief Communicationsbrief-report20162016-02-01February 201610.1681/ASN.20150100891046-66731533-34502015-06-05T11:13:45-07:002016-02Journal of the American Society of NephrologyBrief Communications272385391
- Renal Clearance of Mineral Metabolism BiomarkersCKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD.10.1681/ASN.2014121253Fri, 05 Jun 2015 11:13:44 GMT-07:00Renal Clearance of Mineral Metabolism BiomarkersCKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD.van Ballegooijen, Adriana J.Rhee, Eugene P.Elmariah, Sammyde Boer, Ian H.Kestenbaum, Bryan2015-06-05T11:13:44-07:00doi:10.1681/ASN.2014121253hwp:resource-id:jnephrol;27/2/392American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal clearance, extraction, mineral metabolism biomarkersBrief CommunicationsBrief Communicationsbrief-report20162016-02-01February 201610.1681/ASN.20141212531046-66731533-34502015-06-05T11:13:44-07:002016-02Journal of the American Society of NephrologyBrief Communications272392397
- Sulfenic Acid Modification of Endothelin B Receptor is Responsible for the Benefit of a Nonsteroidal Mineralocorticoid Receptor Antagonist in Renal IschemiaAKI is associated with high mortality rates and the development of CKD. Ischemia/reperfusion (IR) is an important cause of AKI. Unfortunately, there is no available pharmacologic approach to prevent or limit renal IR injury in common clinical practice. Renal IR is characterized by diminished nitric oxide bioavailability and reduced renal blood flow; however, the mechanisms leading to these alterations are poorly understood. In a rat model of renal IR, we investigated whether the administration of the novel nonsteroidal mineralocorticoid receptor (MR) antagonist BR-4628 can prevent or treat the renal dysfunction and tubular injury induced by IR. Renal injury induced by ischemia was associated with increased oxidant damage, which led to a cysteine sulfenic acid modification in endothelin B receptor and consequently decreased endothelial nitric oxide synthase activation. These modifications were efficiently prevented by nonsteroidal MR antagonism. Furthermore, we demonstrated that the protective effect of BR-4628 against IR was lost when a selective endothelin B receptor antagonist was coadministered. These data describe a new mechanism for reduced endothelial nitric oxide synthase activation during renal IR that can be blocked by MR antagonism with BR-4628.10.1681/ASN.2014121216Fri, 11 Sep 2015 06:24:43 GMT-07:00Sulfenic Acid Modification of Endothelin B Receptor is Responsible for the Benefit of a Nonsteroidal Mineralocorticoid Receptor Antagonist in Renal IschemiaAKI is associated with high mortality rates and the development of CKD. Ischemia/reperfusion (IR) is an important cause of AKI. Unfortunately, there is no available pharmacologic approach to prevent or limit renal IR injury in common clinical practice. Renal IR is characterized by diminished nitric oxide bioavailability and reduced renal blood flow; however, the mechanisms leading to these alterations are poorly understood. In a rat model of renal IR, we investigated whether the administration of the novel nonsteroidal mineralocorticoid receptor (MR) antagonist BR-4628 can prevent or treat the renal dysfunction and tubular injury induced by IR. Renal injury induced by ischemia was associated with increased oxidant damage, which led to a cysteine sulfenic acid modification in endothelin B receptor and consequently decreased endothelial nitric oxide synthase activation. These modifications were efficiently prevented by nonsteroidal MR antagonism. Furthermore, we demonstrated that the protective effect of BR-4628 against IR was lost when a selective endothelin B receptor antagonist was coadministered. These data describe a new mechanism for reduced endothelial nitric oxide synthase activation during renal IR that can be blocked by MR antagonism with BR-4628.Barrera-Chimal, JonatanPrince, SoniaFadel, FouadEl Moghrabi, SoumayaWarnock, David G.Kolkhof, PeterJaisser, Frédéric2015-09-11T06:24:43-07:00doi:10.1681/ASN.2014121216hwp:resource-id:jnephrol;27/2/398American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, aldosterone, ischemia-reperfusion, nitric oxideBrief CommunicationsBrief Communicationsbrief-report20162016-02-01February 201610.1681/ASN.20141212161046-66731533-34502015-09-11T06:24:43-07:002016-02Journal of the American Society of NephrologyBrief Communications2722398335404337
- Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel ExcretionUrinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.10.1681/ASN.2014111137Thu, 25 Jun 2015 07:06:19 GMT-07:00Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel ExcretionUrinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.Qi, YingWang, XiaojingRose, Kristie L.MacDonald, W. HayesZhang, BingSchey, Kevin L.Luther, James M.2015-06-25T07:06:19-07:00doi:10.1681/ASN.2014111137hwp:resource-id:jnephrol;27/2/646American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenin angiotensin system, epithelial sodium channel, aldosterone, exosome, clinical nephrology, hypertensionClinical ResearchClinical Researchresearch-article20162016-02-01February 201610.1681/ASN.20141111371046-66731533-34502015-06-25T07:06:19-07:002016-02Journal of the American Society of NephrologyClinical Research272646656
- This Month's Highlights10.1681/ASN.2015111236Fri, 29 Jan 2016 10:01:33 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2016-01-29T10:01:33-08:00doi:10.1681/ASN.2015111236hwp:resource-id:jnephrol;27/2/iAmerican Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20162016-02-01February 201610.1681/ASN.20151112361046-66731533-34502016-01-29T10:01:33-08:002016-02Journal of the American Society of NephrologyThis Month's Highlights272ii
- Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in Progressive Kidney DiseasesProgressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1–56), unilateral ureteral obstruction (UUO, days 1–10), and Alport mice (6–8 weeks old). Contrast-enhanced in vivo µCT enabled robust, noninvasive, and longitudinal monitoring of vessel functionality and revealed a progressive decline of the renal relative blood volume in all models. This reduction ranged from −20% in early disease stages to −61% in late disease stages and preceded fibrosis. Upon Microfil perfusion, high-resolution ex vivo µCT allowed quantitative analyses of three-dimensional vascular networks in all three models. These analyses revealed significant and previously unrecognized alterations of preglomerular arteries: a reduction in vessel diameter, a prominent reduction in vessel branching, and increased vessel tortuosity. In summary, using µCT methodology, we revealed insights into macro-to-microvascular alterations in progressive renal disease and provide a platform that may serve as the basis to evaluate vascular therapeutics in renal disease.10.1681/ASN.2015020204Mon, 20 Jul 2015 09:15:10 GMT-07:00Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in Progressive Kidney DiseasesProgressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1–56), unilateral ureteral obstruction (UUO, days 1–10), and Alport mice (6–8 weeks old). Contrast-enhanced in vivo µCT enabled robust, noninvasive, and longitudinal monitoring of vessel functionality and revealed a progressive decline of the renal relative blood volume in all models. This reduction ranged from −20% in early disease stages to −61% in late disease stages and preceded fibrosis. Upon Microfil perfusion, high-resolution ex vivo µCT allowed quantitative analyses of three-dimensional vascular networks in all three models. These analyses revealed significant and previously unrecognized alterations of preglomerular arteries: a reduction in vessel diameter, a prominent reduction in vessel branching, and increased vessel tortuosity. In summary, using µCT methodology, we revealed insights into macro-to-microvascular alterations in progressive renal disease and provide a platform that may serve as the basis to evaluate vascular therapeutics in renal disease.Ehling, JosefBábíčková, JankaGremse, FelixKlinkhammer, Barbara M.Baetke, SarahKnuechel, RuthKiessling, FabianFloege, JürgenLammers, TwanBoor, Peter2015-07-20T09:15:10-07:00doi:10.1681/ASN.2015020204hwp:resource-id:jnephrol;27/2/520American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, fibrosis, imaging, capillary rarefaction, computed tomography, noninvasiveBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20150202041046-66731533-34502015-07-20T09:15:10-07:002016-02Journal of the American Society of NephrologyBasic Research272520532
- Electrocardiographic Measures and Prediction of Cardiovascular and Noncardiovascular Death in CKDLimited studies have assessed the resting 12-lead electrocardiogram (ECG) as a screening test in intermediate risk populations. We evaluated whether a panel of common ECG parameters are independent predictors of mortality risk in a prospective cohort of participants with CKD. The Chronic Renal Insufficiency Cohort (CRIC) study enrolled 3939 participants with eGFR<70 ml/min per 1.73 m2 from June 2003 to September 2008. Over a median follow-up of 7.5 years, 750 participants died. After adjudicating the initial 497 deaths, we identified 256 cardiovascular and 241 noncardiovascular deaths. ECG metrics were independent risk markers for cardiovascular death (hazard ratio, 95% confidence interval): PR interval ≥200 ms (1.62, 1.19–2.19); QRS interval 100–119 ms (1.64, 1.20–2.25) and ≥120 ms (1.75, 1.17–2.62); corrected QT (QTc) interval ≥450 ms in men or ≥460 ms in women (1.72, 1.19–2.49); and heart rate 60–90 beats per minute (1.21, 0.89–1.63) and ≥90 beats per minute (2.35, 1.03–5.33). Most ECG measures were stronger markers of risk for cardiovascular death than for all-cause mortality or noncardiovascular death. Adding these intervals to a comprehensive model of cardiorenal risk factors increased the C-statistic for cardiovascular death from 0.77 to 0.81 (P<0.001). Furthermore, adding ECG metrics to the model adjusted for standard risk factors resulted in a net reclassification of 12.1% (95% confidence interval 8.1%–16.0%). These data suggest common ECG metrics are independent risk factors for cardiovascular death and enhance the ability to predict death events in a population with CKD.10.1681/ASN.2014101045Thu, 09 Jul 2015 08:44:15 GMT-07:00Electrocardiographic Measures and Prediction of Cardiovascular and Noncardiovascular Death in CKDLimited studies have assessed the resting 12-lead electrocardiogram (ECG) as a screening test in intermediate risk populations. We evaluated whether a panel of common ECG parameters are independent predictors of mortality risk in a prospective cohort of participants with CKD. The Chronic Renal Insufficiency Cohort (CRIC) study enrolled 3939 participants with eGFR<70 ml/min per 1.73 m2 from June 2003 to September 2008. Over a median follow-up of 7.5 years, 750 participants died. After adjudicating the initial 497 deaths, we identified 256 cardiovascular and 241 noncardiovascular deaths. ECG metrics were independent risk markers for cardiovascular death (hazard ratio, 95% confidence interval): PR interval ≥200 ms (1.62, 1.19–2.19); QRS interval 100–119 ms (1.64, 1.20–2.25) and ≥120 ms (1.75, 1.17–2.62); corrected QT (QTc) interval ≥450 ms in men or ≥460 ms in women (1.72, 1.19–2.49); and heart rate 60–90 beats per minute (1.21, 0.89–1.63) and ≥90 beats per minute (2.35, 1.03–5.33). Most ECG measures were stronger markers of risk for cardiovascular death than for all-cause mortality or noncardiovascular death. Adding these intervals to a comprehensive model of cardiorenal risk factors increased the C-statistic for cardiovascular death from 0.77 to 0.81 (P<0.001). Furthermore, adding ECG metrics to the model adjusted for standard risk factors resulted in a net reclassification of 12.1% (95% confidence interval 8.1%–16.0%). These data suggest common ECG metrics are independent risk factors for cardiovascular death and enhance the ability to predict death events in a population with CKD.Deo, RajatShou, HaochangSoliman, Elsayed Z.Yang, WeiArkin, Joshua M.Zhang, XiaomingTownsend, Raymond R.Go, Alan S.Shlipak, Michael G.Feldman, Harold I.2015-07-09T08:44:15-07:00doi:10.1681/ASN.2014101045hwp:resource-id:jnephrol;27/2/559American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, electrophysiology, epidemiology and outcomes, mortality risk, risk factorsClinical EpidemiologyClinical Epidemiologyresearch-article20162016-02-01February 201610.1681/ASN.20141010451046-66731533-34502015-07-09T08:44:15-07:002016-02Journal of the American Society of NephrologyClinical Epidemiology272559569
- You’re Not Big—You’re Just Tall, That’s All!10.1681/ASN.2015070816Thu, 01 Oct 2015 07:40:19 GMT-07:00You’re Not Big—You’re Just Tall, That’s All!Daugirdas, John T.2015-10-01T07:40:19-07:00doi:10.1681/ASN.2015070816hwp:resource-id:jnephrol;27/2/339American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhemodialysis, hemodialysis adequacy, obesity, nutritionUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-02-01February 201610.1681/ASN.20150708161046-66731533-34502015-10-01T07:40:19-07:002016-02Journal of the American Society of NephrologyUp Front Matters2722339580341593
- Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush BorderImmune complex tubulointerstitial nephritis due to antibodies to brush border antigens of the proximal tubule has been demonstrated experimentally and rarely in humans. Our patient developed ESRD and early recurrence after transplantation. IgG and C3 deposits were conspicuous in the tubular basement membrane of proximal tubules, corresponding to deposits observed by electron microscopy. Rare subepithelial deposits were found in the glomeruli. The patient had no evidence of SLE and had normal complement levels. Serum samples from the patient reacted with the brush border of normal human kidney, in contrast with the negative results with 20 control serum samples. Preliminary characterization of the brush border target antigen excluded megalin, CD10, and maltase. We postulate that antibodies to brush border antigens cause direct epithelial injury, accumulate in the tubular basement membrane, and elicit an interstitial inflammatory response.10.1681/ASN.2015030334Wed, 02 Sep 2015 10:48:53 GMT-07:00Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush BorderImmune complex tubulointerstitial nephritis due to antibodies to brush border antigens of the proximal tubule has been demonstrated experimentally and rarely in humans. Our patient developed ESRD and early recurrence after transplantation. IgG and C3 deposits were conspicuous in the tubular basement membrane of proximal tubules, corresponding to deposits observed by electron microscopy. Rare subepithelial deposits were found in the glomeruli. The patient had no evidence of SLE and had normal complement levels. Serum samples from the patient reacted with the brush border of normal human kidney, in contrast with the negative results with 20 control serum samples. Preliminary characterization of the brush border target antigen excluded megalin, CD10, and maltase. We postulate that antibodies to brush border antigens cause direct epithelial injury, accumulate in the tubular basement membrane, and elicit an interstitial inflammatory response.Rosales, Ivy A.Collins, A. Bernarddo Carmo, Paula Alves S.Tolkoff-Rubin, NinaSmith, R. NealColvin, Robert B.2015-09-02T10:48:53-07:00doi:10.1681/ASN.2015030334hwp:resource-id:jnephrol;27/2/380American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyimmune complex, tubulointerstitial, brush borderUp Front MattersPathophysiology of the Renal BiopsyUp Front MattersPathophysiology of the Renal Biopsyresearch-article20162016-02-01February 201610.1681/ASN.20150303341046-66731533-34502015-09-02T10:48:53-07:002016-02Journal of the American Society of NephrologyUp Front Matters272380384
- LDL Receptor–Related Protein 6 Modulates Ret Proto-Oncogene Signaling in Renal Development and Cystic DysplasiaHypoplastic and/or cystic kidneys have been found in both LDL receptor–related protein 6 (Lrp6)- and β-catenin–mutant mouse embryos, and these proteins are key molecules for Wnt signaling. However, the underlying mechanisms of Lrp6/β-catenin signaling in renal development and cystic formation remain poorly understood. In this study, we found evidence that diminished cell proliferation and increased apoptosis occur before cystic dysplasia in the renal primordia of Lrp6-deficient mouse embryos. The expression of Ret proto-oncogene (Ret), a critical receptor for the growth factor glial cell line–derived neurotrophic factor (GDNF), which is required for early nephrogenesis, was dramatically diminished in the mutant renal primordia. The activities of other representative nephrogenic genes, including Lim1, Pax2, Pax8, GDNF, and Wnt11, were subsequently diminished in the mutant renal primordia. Molecular biology experiments demonstrated that Ret is a novel transcriptional target of Wnt/β-catenin signaling. Wnt agonist lithium promoted Ret expression in vitro and in vivo. Furthermore, Lrp6-knockdown or lithium treatment in vitro led to downregulation or upregulation, respectively, of the phosphorylated mitogen-activated protein kinases 1 and 3, which act downstream of GDNF/Ret signaling. Mice with single and double mutations of Lrp6 and Ret were perinatal lethal and demonstrated gene dosage–dependent effects on the severity of renal hypoplasia during embryogenesis. Taken together, these results suggest that Lrp6-mediated Wnt/β-catenin signaling modulates or interacts with a signaling network consisting of Ret cascades and related nephrogenic factors for renal development, and the disruption of these genes or signaling activities may cause a spectrum of hypoplastic and cystic kidney disorders.10.1681/ASN.2014100998Fri, 05 Jun 2015 11:13:47 GMT-07:00LDL Receptor–Related Protein 6 Modulates Ret Proto-Oncogene Signaling in Renal Development and Cystic DysplasiaHypoplastic and/or cystic kidneys have been found in both LDL receptor–related protein 6 (Lrp6)- and β-catenin–mutant mouse embryos, and these proteins are key molecules for Wnt signaling. However, the underlying mechanisms of Lrp6/β-catenin signaling in renal development and cystic formation remain poorly understood. In this study, we found evidence that diminished cell proliferation and increased apoptosis occur before cystic dysplasia in the renal primordia of Lrp6-deficient mouse embryos. The expression of Ret proto-oncogene (Ret), a critical receptor for the growth factor glial cell line–derived neurotrophic factor (GDNF), which is required for early nephrogenesis, was dramatically diminished in the mutant renal primordia. The activities of other representative nephrogenic genes, including Lim1, Pax2, Pax8, GDNF, and Wnt11, were subsequently diminished in the mutant renal primordia. Molecular biology experiments demonstrated that Ret is a novel transcriptional target of Wnt/β-catenin signaling. Wnt agonist lithium promoted Ret expression in vitro and in vivo. Furthermore, Lrp6-knockdown or lithium treatment in vitro led to downregulation or upregulation, respectively, of the phosphorylated mitogen-activated protein kinases 1 and 3, which act downstream of GDNF/Ret signaling. Mice with single and double mutations of Lrp6 and Ret were perinatal lethal and demonstrated gene dosage–dependent effects on the severity of renal hypoplasia during embryogenesis. Taken together, these results suggest that Lrp6-mediated Wnt/β-catenin signaling modulates or interacts with a signaling network consisting of Ret cascades and related nephrogenic factors for renal development, and the disruption of these genes or signaling activities may cause a spectrum of hypoplastic and cystic kidney disorders.Wang, YongpingStokes, ArjunDuan, ZhijianHui, JordanXu, YingChen, YiPingChen, Hong-WuLam, KitZhou, Chengji J.2015-06-05T11:13:47-07:00doi:10.1681/ASN.2014100998hwp:resource-id:jnephrol;27/2/417American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell signaling, cystic kidney, renal agenesisBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141009981046-66731533-34502015-06-05T11:13:47-07:002016-02Journal of the American Society of NephrologyBasic Research272417427
- Deletion of Lkb1 in Renal Tubular Epithelial Cells Leads to CKD by Altering MetabolismRenal tubule epithelial cells are high-energy demanding polarized epithelial cells. Liver kinase B1 (LKB1) is a key regulator of polarity, proliferation, and cell metabolism in epithelial cells, but the function of LKB1 in the kidney is unclear. Our unbiased gene expression studies of human control and CKD kidney samples identified lower expression of LKB1 and regulatory proteins in CKD. Mice with distal tubule epithelial-specific Lkb1 deletion (Ksp-Cre/Lkb1flox/flox) exhibited progressive kidney disease characterized by flattened dedifferentiated tubule epithelial cells, interstitial matrix accumulation, and dilated cystic-appearing tubules. Expression of epithelial polarity markers β-catenin and E-cadherin was not altered even at later stages. However, expression levels of key regulators of metabolism, AMP-activated protein kinase (Ampk), peroxisome proliferative activated receptor gamma coactivator 1-α (Ppargc1a), and Ppara, were significantly lower than those in controls and correlated with fibrosis development. Loss of Lkb1 in cultured epithelial cells resulted in energy depletion, apoptosis, less fatty acid oxidation and glycolysis, and a profibrotic phenotype. Treatment of Lkb1-deficient cells with an AMP-activated protein kinase (AMPK) agonist (A769662) or a peroxisome proliferative activated receptor alpha agonist (fenofibrate) restored the fatty oxidation defect and reduced apoptosis. In conclusion, we show that loss of LKB1 in renal tubular epithelial cells has an important role in kidney disease development by influencing intracellular metabolism.10.1681/ASN.2014121181Mon, 08 Jun 2015 06:52:48 GMT-07:00Deletion of Lkb1 in Renal Tubular Epithelial Cells Leads to CKD by Altering MetabolismRenal tubule epithelial cells are high-energy demanding polarized epithelial cells. Liver kinase B1 (LKB1) is a key regulator of polarity, proliferation, and cell metabolism in epithelial cells, but the function of LKB1 in the kidney is unclear. Our unbiased gene expression studies of human control and CKD kidney samples identified lower expression of LKB1 and regulatory proteins in CKD. Mice with distal tubule epithelial-specific Lkb1 deletion (Ksp-Cre/Lkb1flox/flox) exhibited progressive kidney disease characterized by flattened dedifferentiated tubule epithelial cells, interstitial matrix accumulation, and dilated cystic-appearing tubules. Expression of epithelial polarity markers β-catenin and E-cadherin was not altered even at later stages. However, expression levels of key regulators of metabolism, AMP-activated protein kinase (Ampk), peroxisome proliferative activated receptor gamma coactivator 1-α (Ppargc1a), and Ppara, were significantly lower than those in controls and correlated with fibrosis development. Loss of Lkb1 in cultured epithelial cells resulted in energy depletion, apoptosis, less fatty acid oxidation and glycolysis, and a profibrotic phenotype. Treatment of Lkb1-deficient cells with an AMP-activated protein kinase (AMPK) agonist (A769662) or a peroxisome proliferative activated receptor alpha agonist (fenofibrate) restored the fatty oxidation defect and reduced apoptosis. In conclusion, we show that loss of LKB1 in renal tubular epithelial cells has an important role in kidney disease development by influencing intracellular metabolism.Han, Seung HyeokMalaga-Dieguez, LauraChinga, FrankKang, Hyun MiTao, JianlingReidy, KimberlySusztak, Katalin2015-06-08T06:52:48-07:00doi:10.1681/ASN.2014121181hwp:resource-id:jnephrol;27/2/439American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, metabolism, renal cell biology, apoptosisBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141211811046-66731533-34502015-06-08T06:52:48-07:002016-02Journal of the American Society of NephrologyBasic Research272439453
- RORγt+Foxp3+ Cells are an Independent Bifunctional Regulatory T Cell Lineage and Mediate Crescentic GNCells expressing both the regulatory T cell (Treg)-inducing transcription factor Foxp3 and the Th17 transcription factor RORγt have been identified (biTregs). It is unclear whether RORγt+Foxp3+ biTregs belong to the Th17-specific Treg17 cells, represent intermediates during Treg/Th17 transdifferentiation, or constitute a distinct cell lineage. Because the role of biTregs in inflammatory renal disease is also unknown, we studied these cells in the nephrotoxic nephritis (NTN) model of acute crescentic GN. Induction of NTN resulted in rapid renal and systemic expansion of biTregs. Notably, analyses of the biTreg expression profile revealed production of both anti-inflammatory (IL-10, IL-35) and proinflammatory (IL-17) cytokines. Additionally, biTregs expressed a signature of surface molecules and transcription factors distinct from those of Th17 cells and conventional Tregs (cTregs), and biTregs were identified in Treg17-deficient mice. Finally, fate reporter and cell transfer studies confirmed that biTregs are not Treg/Th17 transdifferentiating cells. Therapeutic transfer of biTregs suppressed the development of nephritis to an extent similar to that observed with transferred cTregs, but in vitro studies indicated different mechanisms of immunosuppression for biTregs and cTregs. Intriguingely, as predicted from their cytokine profile, endogenous biTregs displayed additional proinflammatory functions in NTN that were abrogated by cell-specific deletion of RORγt. In summary, we provide evidence that RORγt+Foxp3+ biTregs are a novel and independent bifunctional regulatory T cell lineage distinct from cTregs, Treg17 cells, and Th17 cells. Furthermore, biTregs appear to contribute to crescentic GN and hence may be novel therapeutic targets.10.1681/ASN.2014090880Mon, 08 Jun 2015 06:52:47 GMT-07:00RORγt+Foxp3+ Cells are an Independent Bifunctional Regulatory T Cell Lineage and Mediate Crescentic GNCells expressing both the regulatory T cell (Treg)-inducing transcription factor Foxp3 and the Th17 transcription factor RORγt have been identified (biTregs). It is unclear whether RORγt+Foxp3+ biTregs belong to the Th17-specific Treg17 cells, represent intermediates during Treg/Th17 transdifferentiation, or constitute a distinct cell lineage. Because the role of biTregs in inflammatory renal disease is also unknown, we studied these cells in the nephrotoxic nephritis (NTN) model of acute crescentic GN. Induction of NTN resulted in rapid renal and systemic expansion of biTregs. Notably, analyses of the biTreg expression profile revealed production of both anti-inflammatory (IL-10, IL-35) and proinflammatory (IL-17) cytokines. Additionally, biTregs expressed a signature of surface molecules and transcription factors distinct from those of Th17 cells and conventional Tregs (cTregs), and biTregs were identified in Treg17-deficient mice. Finally, fate reporter and cell transfer studies confirmed that biTregs are not Treg/Th17 transdifferentiating cells. Therapeutic transfer of biTregs suppressed the development of nephritis to an extent similar to that observed with transferred cTregs, but in vitro studies indicated different mechanisms of immunosuppression for biTregs and cTregs. Intriguingely, as predicted from their cytokine profile, endogenous biTregs displayed additional proinflammatory functions in NTN that were abrogated by cell-specific deletion of RORγt. In summary, we provide evidence that RORγt+Foxp3+ biTregs are a novel and independent bifunctional regulatory T cell lineage distinct from cTregs, Treg17 cells, and Th17 cells. Furthermore, biTregs appear to contribute to crescentic GN and hence may be novel therapeutic targets.Kluger, Malte A.Meyer, Matthias C.Nosko, AnnaGoerke, BoerenLuig, MichaelWegscheid, ClaudiaTiegs, GisaStahl, Rolf A. K.Panzer, UlfSteinmetz, Oliver M.2015-06-08T06:52:47-07:00doi:10.1681/ASN.2014090880hwp:resource-id:jnephrol;27/2/454American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, immunology and pathology, T cellsBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20140908801046-66731533-34502015-06-08T06:52:47-07:002016-02Journal of the American Society of NephrologyBasic Research272454465
- Association of Body Mass Index with Patient-Centered Outcomes in Children with ESRDObesity is associated with less access to transplantation among adults with ESRD. To examine the association between body mass index at ESRD onset and survival and transplantation in children, we performed a retrospective analysis of children ages 2–19 years old beginning RRT from 1995 to 2011 using the US Renal Data System. Among 13,172 children, prevalence of obesity increased from 14% to 18%, whereas prevalence of underweight decreased from 12% to 9% during this period. Over a median follow-up of 7.0 years, 10,004 children had at least one kidney transplant, and 1675 deaths occurred. Risk of death was higher in obese (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.03 to 1.32) and underweight (HR, 1.26; 95% CI, 1.09 to 1.47) children than children with normal body mass indices. Obese and underweight children were less likely to receive a kidney transplant (HR, 0.92; 95% CI, 0.87 to 0.97; HR, 0.83; 95% CI, 0.78 to 0.89, respectively). Obese children had lower odds of receiving a living donor transplant (odds ratio, 0.85; 95% CI, 0.74 to 0.98) if the transplant occurred within 18 months of ESRD onset. Adjustment for transplant in a time–dependent Cox model attenuated the higher risk of death in obese but not underweight children (HR, 1.09; 95% CI, 0.96 to 1.24). Lower rates of kidney transplantation may, therefore, mediate the higher risk of death in obese children with ESRD. The increasing prevalence of obesity among children starting RRT may impede kidney transplantation, especially from living donors.10.1681/ASN.2015010008Mon, 08 Jun 2015 06:52:46 GMT-07:00Association of Body Mass Index with Patient-Centered Outcomes in Children with ESRDObesity is associated with less access to transplantation among adults with ESRD. To examine the association between body mass index at ESRD onset and survival and transplantation in children, we performed a retrospective analysis of children ages 2–19 years old beginning RRT from 1995 to 2011 using the US Renal Data System. Among 13,172 children, prevalence of obesity increased from 14% to 18%, whereas prevalence of underweight decreased from 12% to 9% during this period. Over a median follow-up of 7.0 years, 10,004 children had at least one kidney transplant, and 1675 deaths occurred. Risk of death was higher in obese (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.03 to 1.32) and underweight (HR, 1.26; 95% CI, 1.09 to 1.47) children than children with normal body mass indices. Obese and underweight children were less likely to receive a kidney transplant (HR, 0.92; 95% CI, 0.87 to 0.97; HR, 0.83; 95% CI, 0.78 to 0.89, respectively). Obese children had lower odds of receiving a living donor transplant (odds ratio, 0.85; 95% CI, 0.74 to 0.98) if the transplant occurred within 18 months of ESRD onset. Adjustment for transplant in a time–dependent Cox model attenuated the higher risk of death in obese but not underweight children (HR, 1.09; 95% CI, 0.96 to 1.24). Lower rates of kidney transplantation may, therefore, mediate the higher risk of death in obese children with ESRD. The increasing prevalence of obesity among children starting RRT may impede kidney transplantation, especially from living donors.Ku, ElaineGlidden, David V.Hsu, Chi-yuanPortale, Anthony A.Grimes, BarbaraJohansen, Kirsten L.2015-06-08T06:52:46-07:00doi:10.1681/ASN.2015010008hwp:resource-id:jnephrol;27/2/551American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, obesity, pediatrics, transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20162016-02-01February 201610.1681/ASN.20150100081046-66731533-34502015-06-08T06:52:46-07:002016-02Journal of the American Society of NephrologyClinical Epidemiology272551558
- Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKIRetinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.10.1681/ASN.2014111108Wed, 24 Jun 2015 01:05:56 GMT-07:00Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKIRetinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.Chiba, TakutoSkrypnyk, Nataliya I.Skvarca, Lauren BrilliPenchev, RadostinZhang, Ke XinRochon, Elizabeth R.Fall, Jessica L.Paueksakon, PaisitYang, HaichunAlford, Catherine E.Roman, Beth L.Zhang, Ming-ZhiHarris, RaymondHukriede, Neil A.de Caestecker, Mark P.2015-06-24T13:05:56-07:00doi:10.1681/ASN.2014111108hwp:resource-id:jnephrol;27/2/495American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, signaling, macrophages, tubular epithelium, renal injury, renal proximal tubule cellBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141111081046-66731533-34502015-06-24T13:05:56-07:002016-02Journal of the American Society of NephrologyBasic Research272495508
- HDL: Beyond Atheroprotection10.1681/ASN.2015070793Fri, 28 Aug 2015 08:24:03 GMT-07:00HDL: Beyond AtheroprotectionKon, ValentinaLinton, MacRae F.2015-08-28T08:24:03-07:00doi:10.1681/ASN.2015070793hwp:resource-id:jnephrol;27/2/341American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, lipids, kidney transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-02-01February 201610.1681/ASN.20150707931046-66731533-34502015-08-28T08:24:03-07:002016-02Journal of the American Society of NephrologyUp Front Matters2722341595344603
- Mineralocorticoid Receptor Antagonism in AKI: A New Hope?10.1681/ASN.2015080866Fri, 11 Sep 2015 06:24:43 GMT-07:00Mineralocorticoid Receptor Antagonism in AKI: A New Hope?Juncos, Luis A.Juncos, Luis I.2015-09-11T06:24:43-07:00doi:10.1681/ASN.2015080866hwp:resource-id:jnephrol;27/2/335American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyaldosterone, acute renal failure, nitric oxideUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-02-01February 201610.1681/ASN.20150808661046-66731533-34502015-09-11T06:24:43-07:002016-02Journal of the American Society of NephrologyUp Front Matters2722335398337404
- NADPH Oxidase 4 at the Nexus of Diabetes, Reactive Oxygen Species, and Renal Metabolism10.1681/ASN.2015060698Wed, 22 Jul 2015 06:07:13 GMT-07:00NADPH Oxidase 4 at the Nexus of Diabetes, Reactive Oxygen Species, and Renal MetabolismRhee, Eugene P.2015-07-22T06:07:13-07:00doi:10.1681/ASN.2015060698hwp:resource-id:jnephrol;27/2/337American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetic nephropathy, oxidative stress, NADPH oxidase, metabolismUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-02-01February 201610.1681/ASN.20150606981046-66731533-34502015-07-22T06:07:13-07:002016-02Journal of the American Society of NephrologyUp Front Matters2722337466339481
- CKD Stimulates Muscle Protein Loss Via Rho-associated Protein Kinase 1 ActivationIn patients with CKD, muscle wasting is common and is associated with morbidity and mortality. Mechanisms leading to loss of muscle proteins include insulin resistance, which suppresses Akt activity and thus stimulates protein degradation via the ubiquitin-proteasome system. However, the specific factors controlling CKD-induced suppression of Akt activity in muscle remain undefined. In mice with CKD, the reduction in Akt activity in muscle exceeded the decrease in upstream insulin receptor substrate-1–associated phosphatidylinositol 3–kinase activity, suggesting that CKD activates other pathways that suppress Akt. Furthermore, a CKD-induced increase uncovered caspase-3 activity in muscle in these mice. In C2C12 muscle cells, activated caspase-3 cleaves and activates Rho-associated protein kinase 1 (ROCK1), which enhances the activity of phosphatase and tensin homolog (PTEN) and reduces Akt activity. Notably, constitutive activation of ROCK1 also led to increased caspase-3 activity in vitro. In mice with either global ROCK1 knockout or muscle-specific PTEN knockout, CKD-associated muscle proteolysis was blunted. These results suggest ROCK1 activation in CKD and perhaps in other catabolic conditions can promote loss of muscle protein via a negative feedback loop.10.1681/ASN.2014121208Mon, 08 Jun 2015 06:52:45 GMT-07:00CKD Stimulates Muscle Protein Loss Via Rho-associated Protein Kinase 1 ActivationIn patients with CKD, muscle wasting is common and is associated with morbidity and mortality. Mechanisms leading to loss of muscle proteins include insulin resistance, which suppresses Akt activity and thus stimulates protein degradation via the ubiquitin-proteasome system. However, the specific factors controlling CKD-induced suppression of Akt activity in muscle remain undefined. In mice with CKD, the reduction in Akt activity in muscle exceeded the decrease in upstream insulin receptor substrate-1–associated phosphatidylinositol 3–kinase activity, suggesting that CKD activates other pathways that suppress Akt. Furthermore, a CKD-induced increase uncovered caspase-3 activity in muscle in these mice. In C2C12 muscle cells, activated caspase-3 cleaves and activates Rho-associated protein kinase 1 (ROCK1), which enhances the activity of phosphatase and tensin homolog (PTEN) and reduces Akt activity. Notably, constitutive activation of ROCK1 also led to increased caspase-3 activity in vitro. In mice with either global ROCK1 knockout or muscle-specific PTEN knockout, CKD-associated muscle proteolysis was blunted. These results suggest ROCK1 activation in CKD and perhaps in other catabolic conditions can promote loss of muscle protein via a negative feedback loop.Peng, HuiCao, JinYu, RizhenDanesh, FarhadWang, YanlinMitch, William E.Xu, JingHu, Zhaoyong2015-06-08T06:52:45-07:00doi:10.1681/ASN.2014121208hwp:resource-id:jnephrol;27/2/509American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, metabolism, cell signalingBasic ResearchBasic Researchresearch-article20162016-02-01February 201610.1681/ASN.20141212081046-66731533-34502015-06-08T06:52:45-07:002016-02Journal of the American Society of NephrologyBasic Research272509519
- N-Acetyl-β-d-Glucosaminidase Does Not Enhance Prediction of Cardiovascular or All-Cause Mortality by Albuminuria in a Low-Risk PopulationAlbuminuria is a well known risk factor for cardiovascular disease and mortality, but focus on renal tubular dysfunction as a potential risk factor is growing also. The association between the urinary activity of N-acetyl-β-d-glucosaminidase (NAG) and cardiovascular risk has been assessed mostly in cross-sectional studies. We studied the cross-sectional associations between urinary NAG and cardiovascular risk factors and the longitudinal associations between NAG, cardiovascular disease, and all-cause mortality in a general population. Urinary NAG/creatinine ratio (NAG ratio) and albumin/creatinine ratio (ACR) were measured in 6834 participants of the Tromsø Study in 1994–1995. During the median 17.5 years of follow-up, 958 myocardial infarctions, 726 ischemic strokes, and 2358 deaths were registered. In multivariable analyses adjusted for albuminuria and cardiovascular risk factors, a baseline NAG ratio in the highest quartile was associated with an increased risk of myocardial infarction (hazard ratio [HR], 1.43; 95% confidence interval [95% CI], 1.16 to 1.76), ischemic stroke (HR, 1.41; 95% CI, 1.10 to 1.80), and all-cause mortality (HR, 1.60; 95% CI, 1.39 to 1.84). Combined, ACR and NAG ratio above median associated with a 48%–80% increased risk for the three end points. However, the NAG ratio did not add significantly to the baseline risk-prediction models when assessed by area under the receiver operating characteristics curve or net reclassification improvement. In conclusion, the nonsignificant improvement of risk prediction does not support the clinical use of NAG ratio in cardiovascular risk assessment in a low-risk group.10.1681/ASN.2014100960Fri, 05 Jun 2015 11:13:44 GMT-07:00N-Acetyl-β-d-Glucosaminidase Does Not Enhance Prediction of Cardiovascular or All-Cause Mortality by Albuminuria in a Low-Risk PopulationAlbuminuria is a well known risk factor for cardiovascular disease and mortality, but focus on renal tubular dysfunction as a potential risk factor is growing also. The association between the urinary activity of N-acetyl-β-d-glucosaminidase (NAG) and cardiovascular risk has been assessed mostly in cross-sectional studies. We studied the cross-sectional associations between urinary NAG and cardiovascular risk factors and the longitudinal associations between NAG, cardiovascular disease, and all-cause mortality in a general population. Urinary NAG/creatinine ratio (NAG ratio) and albumin/creatinine ratio (ACR) were measured in 6834 participants of the Tromsø Study in 1994–1995. During the median 17.5 years of follow-up, 958 myocardial infarctions, 726 ischemic strokes, and 2358 deaths were registered. In multivariable analyses adjusted for albuminuria and cardiovascular risk factors, a baseline NAG ratio in the highest quartile was associated with an increased risk of myocardial infarction (hazard ratio [HR], 1.43; 95% confidence interval [95% CI], 1.16 to 1.76), ischemic stroke (HR, 1.41; 95% CI, 1.10 to 1.80), and all-cause mortality (HR, 1.60; 95% CI, 1.39 to 1.84). Combined, ACR and NAG ratio above median associated with a 48%–80% increased risk for the three end points. However, the NAG ratio did not add significantly to the baseline risk-prediction models when assessed by area under the receiver operating characteristics curve or net reclassification improvement. In conclusion, the nonsignificant improvement of risk prediction does not support the clinical use of NAG ratio in cardiovascular risk assessment in a low-risk group.Solbu, Marit D.Toft, IngridLøchen, Maja-LisaMathiesen, Ellisiv B.Eriksen, Bjørn O.Melsom, ToralfNjølstad, IngerWilsgaard, TomJenssen, Trond G.2015-06-05T11:13:44-07:00doi:10.1681/ASN.2014100960hwp:resource-id:jnephrol;27/2/533American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyalbuminuria, cardiovascular disease, clinical epidemiology, mortality risk, proximal tubule, renal dysfunctionClinical EpidemiologyClinical Epidemiologyresearch-article20162016-02-01February 201610.1681/ASN.20141009601046-66731533-34502015-06-05T11:13:44-07:002016-02Journal of the American Society of NephrologyClinical Epidemiology272533542
- Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile HypercalcemiaIdiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH.10.1681/ASN.2014101025Fri, 05 Jun 2015 11:13:46 GMT-07:00Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile HypercalcemiaIdiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH.Schlingmann, Karl P.Ruminska, JustynaKaufmann, MartinDursun, IsmailPatti, MonicaKranz, BirgittaPronicka, EwaCiara, ElzbietaAkcay, TeomanBulus, DeryaCornelissen, Elisabeth A.M.Gawlik, AnetaSikora, PrzemysławPatzer, LudwigGaliano, MatthiasBoyadzhiev, VeselinDumic, MiroslavVivante, AsafKleta, RobertDekel, BenjaminLevtchenko, ElenaBindels, René J.Rust, StephanForster, Ian C.Hernando, NatiJones, GlenvilleWagner, Carsten A.Konrad, Martin2015-06-05T11:13:46-07:00doi:10.1681/ASN.2014101025hwp:resource-id:jnephrol;27/2/604American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, molecular genetics, mineral metabolism, activated Vitamin D, hypercalciuriaClinical ResearchClinical Researchresearch-article20162016-02-01February 201610.1681/ASN.20141010251046-66731533-34502015-06-05T11:13:46-07:002016-02Journal of the American Society of NephrologyClinical Research272604614
- Non-Complement–Binding De Novo Donor-Specific Anti-HLA Antibodies and Kidney Allograft SurvivalC1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity >6237 and >10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P<0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.10.1681/ASN.2014040326Fri, 05 Jun 2015 11:13:46 GMT-07:00Non-Complement–Binding De Novo Donor-Specific Anti-HLA Antibodies and Kidney Allograft SurvivalC1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity >6237 and >10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P<0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.Guidicelli, GwendalineGuerville, FlorentLepreux, SébastienWiebe, ChrisThaunat, OlivierDubois, ValérieVisentin, JonathanBachelet, ThomasMorelon, EmmanuelNickerson, PeterMerville, PierreTaupin, Jean-LucCouzi, Lionel2015-06-05T11:13:46-07:00doi:10.1681/ASN.2014040326hwp:resource-id:jnephrol;27/2/615American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, de novo donor specific antibodies, C1q, complement, graft survivalClinical ResearchClinical Researchresearch-article20162016-02-01February 201610.1681/ASN.20140403261046-66731533-34502015-06-05T11:13:46-07:002016-02Journal of the American Society of NephrologyClinical Research272615625
- Exploration of Association of 1,25-OH2D3 with Augmentation Index, a Composite Measure of Arterial StiffnessBackground and objectives: Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness. Design, setting, participants, and measurements: In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx. Results: The median eGFR was significantly different between clinics (range 25–81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant. Conclusion: This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.10.2215/CJN.00900208Wed, 15 Oct 2008 07:55:28 GMT-07:00Exploration of Association of 1,25-OH2D3 with Augmentation Index, a Composite Measure of Arterial StiffnessBackground and objectives: Abnormalities in mineral metabolism [calcium, phosphate, and immunoreactive parathyroid hormone (PTH)] and vitamin D have been linked to increases in central arterial stiffness. Central arterial stiffness can be measured using noninvasive technologies, including augmentation index (AIx), a composite measure of arterial stiffness. Design, setting, participants, and measurements: In 131 outpatients identified from individual cardiac or kidney disease clinics, we examined conventional demographic and laboratory risk factors, vitamin D levels (1,25-OH2D3 and 25-OHD3), and markers of inflammation or endothelial function [C-reactive peptide (hsCRP), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and IL-6] in relationship to AIx. Results: The median eGFR was significantly different between clinics (range 25–81 ml/min). Subjects with higher phosphate or MMP-9 levels were found to have a higher AIx (P = 0.02 and 0.07, respectively). Lower 1,25-OH2D3 levels or reduced eGFR were associated with higher AIx (P = 0.002 and 0.005, respectively). The associations between 1,25-OH2D3 and phosphate levels and AIx were observed for values within the normal range. No association was noted for calcium, iPTH, 25-OHD3, or hsCRP and AIx. Adjusting for potential confounders [eGFR, calcium, phosphate, and (log) iPTH] the association of lower 1,25-OH2D3 with AIx remained statistically significant. Conclusion: This exploratory study demonstrates a significant association between AIx and 1,25-OH2D3 in a diverse group with cardiac, kidney disease, or both. These increasing understanding of the role of vitamin D in vascular health lends a context to these findings and raises questions as to additional modifiable risk factors in complex patients. Further studies are required.Andrade, JasonEr, LeeIgnaszewski, AndrewLevin, Adeera2008-10-15T07:55:28-07:00doi:10.2215/CJN.00900208hwp:resource-id:clinjasn;3/6/1800American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMineral Metabolism and Bone DiseaseMineral Metabolism and Bone Diseaseresearch-article20082008-11-01November 200810.2215/CJN.009002081555-90411555-905X2008-10-15T07:55:28-07:002008-11Clinical Journal of the American Society of NephrologyMineral Metabolism and Bone Disease3618001806
- Spirituality, Social Support, and Survival in Hemodialysis PatientsBackground and objectives: No studies have evaluated the relationship among spirituality, social support, and survival in patients with ESRD. This study assessed whether spirituality was an independent predictor of survival in dialysis patients with ESRD after controlling for age, diabetes, albumin, and social support. Design, setting, participants, & measurements: A total of 166 patients who had ESRD and were treated with hemodialysis completed questionnaires on psychosocial variables, quality of life, and religious and spiritual beliefs. The religious variables were categorized into three scores on a 0 to 20 scale (low to high levels): Spirituality, religious involvement, and religion as coping. Social support was assessed using the Multidimensional Scale for Perceived Social Support. Analyses were also performed including and excluding patients with HIV infection. Religious variables were categorized on the basis of means, medians, and tertiles. Results: In analyses that used religious variables, only the responses on the spirituality scale split at the mean were associated with survival. The association of other religious variables with survival did not reach significance. Social support correlated with spirituality, religion as coping, and religious involvement measures. Only social support and age were associated with survival when controlling for diabetes, albumin concentration, HIV infection, and spirituality. Conclusions: These data suggest that the effects of spirituality may be mediated by social support. Larger, multicenter, prospective studies that use well-validated tools to measure religiosity and spirituality are needed to determine whether there is an independent association of spirituality variables with survival in patients with ESRD.10.2215/CJN.01790408Wed, 15 Oct 2008 07:55:37 GMT-07:00Spirituality, Social Support, and Survival in Hemodialysis PatientsBackground and objectives: No studies have evaluated the relationship among spirituality, social support, and survival in patients with ESRD. This study assessed whether spirituality was an independent predictor of survival in dialysis patients with ESRD after controlling for age, diabetes, albumin, and social support. Design, setting, participants, & measurements: A total of 166 patients who had ESRD and were treated with hemodialysis completed questionnaires on psychosocial variables, quality of life, and religious and spiritual beliefs. The religious variables were categorized into three scores on a 0 to 20 scale (low to high levels): Spirituality, religious involvement, and religion as coping. Social support was assessed using the Multidimensional Scale for Perceived Social Support. Analyses were also performed including and excluding patients with HIV infection. Religious variables were categorized on the basis of means, medians, and tertiles. Results: In analyses that used religious variables, only the responses on the spirituality scale split at the mean were associated with survival. The association of other religious variables with survival did not reach significance. Social support correlated with spirituality, religion as coping, and religious involvement measures. Only social support and age were associated with survival when controlling for diabetes, albumin concentration, HIV infection, and spirituality. Conclusions: These data suggest that the effects of spirituality may be mediated by social support. Larger, multicenter, prospective studies that use well-validated tools to measure religiosity and spirituality are needed to determine whether there is an independent association of spirituality variables with survival in patients with ESRD.Spinale, JoannCohen, Scott D.Khetpal, PrashantPeterson, Rolf A.Clougherty, BrennaPuchalski, Christina M.Patel, Samir S.Kimmel, Paul L.2008-10-15T07:55:37-07:00doi:10.2215/CJN.01790408hwp:resource-id:clinjasn;3/6/1620American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyChronic Kidney DiseaseChronic Kidney Diseaseresearch-article20082008-11-01November 200810.2215/CJN.017904081555-90411555-905X2008-10-15T07:55:37-07:002008-11Clinical Journal of the American Society of NephrologyChronic Kidney Disease3616201627
- Transplant Tourism in the United States: A Single-Center ExperienceBackground and objectives: Transplant “tourism” typically refers to the practice of traveling outside the country of residence to obtain organ transplantation. This study describes the characteristics and outcomes of 33 kidney transplant recipients who traveled abroad for transplant and returned to University of California, Los Angeles (UCLA) for follow-up. Design, settings, participants, & measurements: Posttransplantation outcomes were compared between tourists and a matched cohort of patients who underwent transplantation at UCLA (matched for age, race, transplant year, dialysis time, previous transplantation, and donor type). Median follow-up time was 487 d (range 68 to 3056). Results: Compared with all patients who underwent transplantation at UCLA, tourists included more Asians and had shorter dialysis times. Most patients traveled to their region of ethnicity with the majority undergoing transplantation in China (44%), Iran (16%), and the Philippines (13%). Living unrelated transplants were most common. Tourists presented to UCLA a median of 35 d after transplantation. Four patients required urgent hospitalization, three of whom lost their grafts. Seventeen (52%) patients had infections, with nine requiring hospitalization. One patient lost her graft and subsequently died from complications related to donor-contracted hepatitis B. One-year graft survival was 89% for tourists and 98% for the matched UCLA cohort (P = 0.75). The rate of acute rejection at 1 yr was 30% in tourists and 12% in the matched cohort. Conclusions: Tourists had a more complex posttransplantation course with a higher incidence of acute rejection and severe infectious complications.10.2215/CJN.02180508Wed, 15 Oct 2008 07:55:45 GMT-07:00Transplant Tourism in the United States: A Single-Center ExperienceBackground and objectives: Transplant “tourism” typically refers to the practice of traveling outside the country of residence to obtain organ transplantation. This study describes the characteristics and outcomes of 33 kidney transplant recipients who traveled abroad for transplant and returned to University of California, Los Angeles (UCLA) for follow-up. Design, settings, participants, & measurements: Posttransplantation outcomes were compared between tourists and a matched cohort of patients who underwent transplantation at UCLA (matched for age, race, transplant year, dialysis time, previous transplantation, and donor type). Median follow-up time was 487 d (range 68 to 3056). Results: Compared with all patients who underwent transplantation at UCLA, tourists included more Asians and had shorter dialysis times. Most patients traveled to their region of ethnicity with the majority undergoing transplantation in China (44%), Iran (16%), and the Philippines (13%). Living unrelated transplants were most common. Tourists presented to UCLA a median of 35 d after transplantation. Four patients required urgent hospitalization, three of whom lost their grafts. Seventeen (52%) patients had infections, with nine requiring hospitalization. One patient lost her graft and subsequently died from complications related to donor-contracted hepatitis B. One-year graft survival was 89% for tourists and 98% for the matched UCLA cohort (P = 0.75). The rate of acute rejection at 1 yr was 30% in tourists and 12% in the matched cohort. Conclusions: Tourists had a more complex posttransplantation course with a higher incidence of acute rejection and severe infectious complications.Gill, JagbirMadhira, Bhaskara R.Gjertson, DavidLipshutz, GeraldCecka, J. MichaelPham, Phuong-ThuWilkinson, AlanBunnapradist, SuphamaiDanovitch, Gabriel M.2008-10-15T07:55:45-07:00doi:10.2215/CJN.02180508hwp:resource-id:clinjasn;3/6/1820American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal TransplantationRenal Transplantationresearch-article20082008-11-01November 200810.2215/CJN.021805081555-90411555-905X2008-10-15T07:55:45-07:002008-11Clinical Journal of the American Society of NephrologyRenal Transplantation36218202491828250
- Recovery of Hyperphosphatoninism and Renal Phosphorus Wasting One Year after Successful Renal TransplantationBackground and objectives: In the first months after successful kidney transplantation, hypophosphatemia and renal phosphorus wasting are common and related to inappropriately high parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) levels. Little is known about the long-term natural history of renal phosphorus homeostasis in renal transplant recipients. Design, setting, participants: We prospectively followed parameters of mineral metabolism (including full-length PTH and FGF-23) in 50 renal transplant recipients at the time of transplantation (Tx), at month 3 (M3) and at month 12 (M12). Transplant recipients were (1:1) matched for estimated GFR with chronic kidney disease (CKD) patients. Results: FGF-23 levels (Tx: 2816 [641 to 10665] versus M3: 73 [43 to 111] versus M12: 56 [34 to 78] ng/L, median [interquartile range]) and fractional phosphorus excretion (FEphos; M3: 45 ± 19% versus M12: 37 ± 13%) significantly declined over time after renal transplantation. Levels 1 yr after transplantation were similar to those in CKD patients (FGF-23: 47 [34 to 77] ng/L; FEphos 35 ± 16%). Calcium (9.1 ± 0.5 versus 8.9 ± 0.3 mg/dl) and PTH (27.2 [17.0 to 46.0] versus 17.5 [11.7 to 24.4] ng/L) levels were significantly higher, whereas phosphorus (3.0 ± 0.6 versus 3.3 ± 0.6 mg/dl) levels were significantly lower 1 yr after renal transplantation as compared with CKD patients. Conclusions: Data indicate that hyperphosphatoninism and renal phosphorus wasting regress by 1 yr after successful renal transplantation.10.2215/CJN.01310308Wed, 15 Oct 2008 07:55:35 GMT-07:00Recovery of Hyperphosphatoninism and Renal Phosphorus Wasting One Year after Successful Renal TransplantationBackground and objectives: In the first months after successful kidney transplantation, hypophosphatemia and renal phosphorus wasting are common and related to inappropriately high parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) levels. Little is known about the long-term natural history of renal phosphorus homeostasis in renal transplant recipients. Design, setting, participants: We prospectively followed parameters of mineral metabolism (including full-length PTH and FGF-23) in 50 renal transplant recipients at the time of transplantation (Tx), at month 3 (M3) and at month 12 (M12). Transplant recipients were (1:1) matched for estimated GFR with chronic kidney disease (CKD) patients. Results: FGF-23 levels (Tx: 2816 [641 to 10665] versus M3: 73 [43 to 111] versus M12: 56 [34 to 78] ng/L, median [interquartile range]) and fractional phosphorus excretion (FEphos; M3: 45 ± 19% versus M12: 37 ± 13%) significantly declined over time after renal transplantation. Levels 1 yr after transplantation were similar to those in CKD patients (FGF-23: 47 [34 to 77] ng/L; FEphos 35 ± 16%). Calcium (9.1 ± 0.5 versus 8.9 ± 0.3 mg/dl) and PTH (27.2 [17.0 to 46.0] versus 17.5 [11.7 to 24.4] ng/L) levels were significantly higher, whereas phosphorus (3.0 ± 0.6 versus 3.3 ± 0.6 mg/dl) levels were significantly lower 1 yr after renal transplantation as compared with CKD patients. Conclusions: Data indicate that hyperphosphatoninism and renal phosphorus wasting regress by 1 yr after successful renal transplantation.Evenepoel, PieterMeijers, Bjorn K.I.de Jonge, HylkeNaesens, MaartenBammens, BertClaes, KathleenKuypers, DirkVanrenterghem, Yves2008-10-15T07:55:35-07:00doi:10.2215/CJN.01310308hwp:resource-id:clinjasn;3/6/1829American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal TransplantationRenal Transplantationresearch-article20082008-11-01November 200810.2215/CJN.013103081555-90411555-905X2008-10-15T07:55:35-07:002008-11Clinical Journal of the American Society of NephrologyRenal Transplantation3618291836
- A Survey of Nephrologists’ Views on Preemptive TransplantationBackground and objectives: Despite emerging evidence that preemptive transplantation is the best treatment modality for patients reaching end-stage renal disease (ESRD), it is underutilized. Nephrologists’ views on preemptive transplantation are explored herein. Design, setting, participants, & measurements: A web-based survey elicited barriers to preemptive transplantation as perceived by nephrologists as well as demographic and practice variables associated with a favorable attitude toward preemptive transplantation. Results: Four hundred seventy-six of 5,901 eligible nephrologists responded (8% participation rate). Seventy-one percent of respondents agreed that preemptive transplantation is the best treatment modality for eligible chronic kidney disease (CKD) patients reaching ESRD, 69% reported that late referrals did not allow enough time for patients to be evaluated for preemptive transplantation, and 50% stated that there was too much delay between a patient's referral and the time the patient was seen at the transplant center. Nephrologists agreed to a lesser extent that they should be held accountable for CKD patients’ education (26%) and preemptive transplant referrals (23%). The most important patient factors considered when deciding not to discuss preemptive transplant were poor health status (70%), lack of compliance (69%), other medical problems (51%), being too old (40%), lack of prescription coverage (37%), and lack of health insurance to cover the costs of the procedure (36%). Conclusions: Surveyed nephrologists consider preemptive transplantation as the optimal treatment modality for eligible patients. Late referral, patient health and insurance status, and delayed transplant center evaluation are perceived as major barriers to preemptive transplantation.10.2215/CJN.00150108Wed, 01 Oct 2008 11:43:14 GMT-07:00A Survey of Nephrologists’ Views on Preemptive TransplantationBackground and objectives: Despite emerging evidence that preemptive transplantation is the best treatment modality for patients reaching end-stage renal disease (ESRD), it is underutilized. Nephrologists’ views on preemptive transplantation are explored herein. Design, setting, participants, & measurements: A web-based survey elicited barriers to preemptive transplantation as perceived by nephrologists as well as demographic and practice variables associated with a favorable attitude toward preemptive transplantation. Results: Four hundred seventy-six of 5,901 eligible nephrologists responded (8% participation rate). Seventy-one percent of respondents agreed that preemptive transplantation is the best treatment modality for eligible chronic kidney disease (CKD) patients reaching ESRD, 69% reported that late referrals did not allow enough time for patients to be evaluated for preemptive transplantation, and 50% stated that there was too much delay between a patient's referral and the time the patient was seen at the transplant center. Nephrologists agreed to a lesser extent that they should be held accountable for CKD patients’ education (26%) and preemptive transplant referrals (23%). The most important patient factors considered when deciding not to discuss preemptive transplant were poor health status (70%), lack of compliance (69%), other medical problems (51%), being too old (40%), lack of prescription coverage (37%), and lack of health insurance to cover the costs of the procedure (36%). Conclusions: Surveyed nephrologists consider preemptive transplantation as the optimal treatment modality for eligible patients. Late referral, patient health and insurance status, and delayed transplant center evaluation are perceived as major barriers to preemptive transplantation.Pradel, Françoise G.Jain, RahulMullins, C. DanielVassalotti, Joseph A.Bartlett, Stephen T.2008-10-01T11:43:14-07:00doi:10.2215/CJN.00150108hwp:resource-id:clinjasn;3/6/1837American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal TransplantationRenal Transplantationresearch-article20082008-11-01November 200810.2215/CJN.001501081555-90411555-905X2008-10-01T11:43:14-07:002008-11Clinical Journal of the American Society of NephrologyRenal Transplantation3618371845
- Renal Transplantation Is Not Associated with Regression of Left Ventricular Hypertrophy: A Magnetic Resonance StudyBackground and objectives: Patients with end-stage renal failure (ESRD) have an increased risk of premature cardiovascular (CV) disease. Left ventricular hypertrophy is an independent risk factor for CV events and death in ESRD. Renal transplantation has been associated with reduction in CV risk and echocardiographic regression of left ventricular hypertrophy. However, echocardiography overestimates LV mass in ESRD patients. Cardiac magnetic resonance (CMR) provides more detailed, volume-independent, measures of cardiac structure. Changes in LV mass measured by CMR after renal transplantation were studied. Design, setting, participants, & measurements: Fifty patients underwent CMR on two occasions. Twenty-five were transplanted before the second scan. CMR was performed to measure LV mass index (LVMI), ejection fraction, end-diastolic and end-systolic volumes. Changes were expressed as percentage change over time. Patients with CV events between scans (e.g., acute coronary syndrome, myocardial infarction) were excluded. All transplant patients had serum creatinine <150 μmol/L. Results: There was no significant change in LVMI between patients who underwent renal transplantation and those who remained on dialysis (transplanted mean, 2.75%/yr, ± 9.1 versus dialysis, −3.6%/yr ± 16.7). In addition, there were no significant changes in end-diastolic volume (transplant, 0.1%/yr ± 19.5 versus not transplanted, −3.4%/yr ± 31.5), end-systolic volume (transplanted mean, 15.2%/yr ± 65.2 versus not transplanted, 3.0%/yr ± 55.5), or ejection fraction (transplant, 2.1%/yr ± 11.9 versus not transplanted, −0.4%/yr ± 5.3). Conclusions: Renal transplantation is not associated with significant regression of LVMI on CMR compared with patients who remain on the transplant waiting list.10.2215/CJN.01400308Wed, 23 Jul 2008 11:05:39 GMT-07:00Renal Transplantation Is Not Associated with Regression of Left Ventricular Hypertrophy: A Magnetic Resonance StudyBackground and objectives: Patients with end-stage renal failure (ESRD) have an increased risk of premature cardiovascular (CV) disease. Left ventricular hypertrophy is an independent risk factor for CV events and death in ESRD. Renal transplantation has been associated with reduction in CV risk and echocardiographic regression of left ventricular hypertrophy. However, echocardiography overestimates LV mass in ESRD patients. Cardiac magnetic resonance (CMR) provides more detailed, volume-independent, measures of cardiac structure. Changes in LV mass measured by CMR after renal transplantation were studied. Design, setting, participants, & measurements: Fifty patients underwent CMR on two occasions. Twenty-five were transplanted before the second scan. CMR was performed to measure LV mass index (LVMI), ejection fraction, end-diastolic and end-systolic volumes. Changes were expressed as percentage change over time. Patients with CV events between scans (e.g., acute coronary syndrome, myocardial infarction) were excluded. All transplant patients had serum creatinine <150 μmol/L. Results: There was no significant change in LVMI between patients who underwent renal transplantation and those who remained on dialysis (transplanted mean, 2.75%/yr, ± 9.1 versus dialysis, −3.6%/yr ± 16.7). In addition, there were no significant changes in end-diastolic volume (transplant, 0.1%/yr ± 19.5 versus not transplanted, −3.4%/yr ± 31.5), end-systolic volume (transplanted mean, 15.2%/yr ± 65.2 versus not transplanted, 3.0%/yr ± 55.5), or ejection fraction (transplant, 2.1%/yr ± 11.9 versus not transplanted, −0.4%/yr ± 5.3). Conclusions: Renal transplantation is not associated with significant regression of LVMI on CMR compared with patients who remain on the transplant waiting list.Patel, Rajan K.Mark, Patrick B.Johnston, NicolaMcGregor, EllonDargie, Henry J.Jardine, Alan G.2008-07-23T11:05:39-07:00doi:10.2215/CJN.01400308hwp:resource-id:clinjasn;3/6/1807American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyRenal TransplantationRenal Transplantationresearch-article20082008-11-01November 200810.2215/CJN.014003081555-90411555-905X2008-07-23T11:05:39-07:002008-11Clinical Journal of the American Society of NephrologyRenal Transplantation3618071811
- Ratio of Paricalcitol Dosage to Serum Parathyroid Hormone Level and Survival in Maintenance Hemodialysis PatientsBackground and objectives: Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients; however, patients with higher serum parathyroid hormone (PTH), indicative of a more severe secondary hyperparathyroidism and higher death risk, are usually given higher VDRA dosages, which can lead to confounding by medical indication and attenuated survival advantage of high VDRA dosages. It was hypothesized that the ratio of the administered paricalcitol dosage to serum PTH level discloses better the underlying dosage–survival association. Design, setting, participants, & measurements: The 3-yr mortality predictability of the administered paricalcitol during the first 3 mo of the cohort divided by averaged serum intact PTH during the same period was examined in 34,307 MHD patients from all DaVita dialysis clinics across the United States using Cox regression. Results: MHD patients were 60.8 ± 15.4 yr of age and included 47% women, 34% black patients, and 47% patients with diabetes. Initially, the ratio of paricalcitol (μg/wk) to PTH (pg/ml) was divided into four groups: 0 (reference), 1 to <30, 30 to <60, and >60 × 10−3. Unadjusted, case mix–adjusted (demographics, comorbidity, and Kt/V), and malnutrition-inflammation complex syndrome–adjusted models, the death rate ratio for the paricalcitol/PTH index groups, were 0.99, 0.95, and 0.92. Restricted cubic splines analyses were consistent with a linear relation. Conclusions: Higher weekly paricalcitol dosage per each unit of serum PTH seems to have an incremental association with greater survival in MHD patients. The observed dosage-response phenomenon needs to be confirmed in clinical trials.10.2215/CJN.01760408Wed, 13 Aug 2008 06:42:44 GMT-07:00Ratio of Paricalcitol Dosage to Serum Parathyroid Hormone Level and Survival in Maintenance Hemodialysis PatientsBackground and objectives: Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients; however, patients with higher serum parathyroid hormone (PTH), indicative of a more severe secondary hyperparathyroidism and higher death risk, are usually given higher VDRA dosages, which can lead to confounding by medical indication and attenuated survival advantage of high VDRA dosages. It was hypothesized that the ratio of the administered paricalcitol dosage to serum PTH level discloses better the underlying dosage–survival association. Design, setting, participants, & measurements: The 3-yr mortality predictability of the administered paricalcitol during the first 3 mo of the cohort divided by averaged serum intact PTH during the same period was examined in 34,307 MHD patients from all DaVita dialysis clinics across the United States using Cox regression. Results: MHD patients were 60.8 ± 15.4 yr of age and included 47% women, 34% black patients, and 47% patients with diabetes. Initially, the ratio of paricalcitol (μg/wk) to PTH (pg/ml) was divided into four groups: 0 (reference), 1 to <30, 30 to <60, and >60 × 10−3. Unadjusted, case mix–adjusted (demographics, comorbidity, and Kt/V), and malnutrition-inflammation complex syndrome–adjusted models, the death rate ratio for the paricalcitol/PTH index groups, were 0.99, 0.95, and 0.92. Restricted cubic splines analyses were consistent with a linear relation. Conclusions: Higher weekly paricalcitol dosage per each unit of serum PTH seems to have an incremental association with greater survival in MHD patients. The observed dosage-response phenomenon needs to be confirmed in clinical trials.Shinaberger, Christian S.Kopple, Joel D.Kovesdy, Csaba P.McAllister, Charles J.van Wyck, DavidGreenland, SanderKalantar-Zadeh, Kamyar2008-08-13T06:42:44-07:00doi:10.2215/CJN.01760408hwp:resource-id:clinjasn;3/6/1769American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and OutcomesEpidemiology and Outcomesresearch-article20082008-11-01November 200810.2215/CJN.017604081555-90411555-905X2008-08-13T06:42:44-07:002008-11Clinical Journal of the American Society of NephrologyEpidemiology and Outcomes3617691776
- Age, Gender, and Race Effects on Cystatin C Levels in US AdolescentsBackground and objectives: The objective of this study was to describe the normal range of serum cystatin C and identify factors associated with variability in serum cystatin C contrasting with factors that are known to influence creatinine levels in the general US adolescent population. Design, setting, participants, & measurements: Serum cystatin C and creatinine were measured in 719 participants aged 12 to 19 yr in the Third National Health and Nutrition Examination Survey, a national cross-sectional survey conducted in 1988 through 1994. We calculated gender- and race/ethnicity-specific cystatin C and creatinine ranges and conducted multivariable linear regression analyses to assess factors that contribute to variability in cystatin C and creatinine levels. Results: Overall, the mean serum cystatin C level was 0.84 mg/L and was higher in male than female individuals and higher in non-Hispanic white versus non-Hispanic black and Mexican American individuals. The mean serum creatinine was 0.71 mg/dl and was higher in male than in female individuals but lower in non-Hispanic white and Mexican American compared with non-Hispanic black individuals. Unlike creatinine, which increases with age from 12 to 19 yr, cystatin C levels decrease, particularly in female individuals. After adjustment for age, gender, and race/ethnicity, uric acid and blood urea nitrogen were significantly associated with cystatin C levels. Conclusions: Serum cystatin C is significantly related to gender, age, race/ethnicity, uric acid, and blood urea nitrogen in adolescents.10.2215/CJN.00840208Wed, 24 Sep 2008 09:00:45 GMT-07:00Age, Gender, and Race Effects on Cystatin C Levels in US AdolescentsBackground and objectives: The objective of this study was to describe the normal range of serum cystatin C and identify factors associated with variability in serum cystatin C contrasting with factors that are known to influence creatinine levels in the general US adolescent population. Design, setting, participants, & measurements: Serum cystatin C and creatinine were measured in 719 participants aged 12 to 19 yr in the Third National Health and Nutrition Examination Survey, a national cross-sectional survey conducted in 1988 through 1994. We calculated gender- and race/ethnicity-specific cystatin C and creatinine ranges and conducted multivariable linear regression analyses to assess factors that contribute to variability in cystatin C and creatinine levels. Results: Overall, the mean serum cystatin C level was 0.84 mg/L and was higher in male than female individuals and higher in non-Hispanic white versus non-Hispanic black and Mexican American individuals. The mean serum creatinine was 0.71 mg/dl and was higher in male than in female individuals but lower in non-Hispanic white and Mexican American compared with non-Hispanic black individuals. Unlike creatinine, which increases with age from 12 to 19 yr, cystatin C levels decrease, particularly in female individuals. After adjustment for age, gender, and race/ethnicity, uric acid and blood urea nitrogen were significantly associated with cystatin C levels. Conclusions: Serum cystatin C is significantly related to gender, age, race/ethnicity, uric acid, and blood urea nitrogen in adolescents.Groesbeck, DarcyKöttgen, AnnaParekh, RulanSelvin, ElizabethSchwartz, George J.Coresh, JosefFurth, Susan2008-09-24T09:00:45-07:00doi:10.2215/CJN.00840208hwp:resource-id:clinjasn;3/6/1777American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and OutcomesEpidemiology and Outcomesresearch-article20082008-11-01November 200810.2215/CJN.008402081555-90411555-905X2008-09-24T09:00:45-07:002008-11Clinical Journal of the American Society of NephrologyEpidemiology and Outcomes3617771785
- Association of Visceral and Subcutaneous Adiposity with Kidney FunctionBackground and objectives: Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations. Design, setting, participants, & measurements: Participants from the Framingham Offspring Study who underwent abdominal computed tomography for VAT and SAT quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was defined as estimated GFR <60 ml/min per 1.73 m2, as estimated using creatinine (n = 89) in the Modification of Diet in Renal Disease (MDRD) formula or by cystatin C (n = 136). Regression models evaluated the cross-sectional relations between VAT and SAT with CKD and cystatin C, with age and gender adjustment and cardiovascular risk factor adjustment. Results: Neither VAT nor SAT was associated with CKD as estimated by the MDRD equation. In contrast, both VAT and SAT were associated with CKD when defined using cystatin-based equations. The estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was 1.9 ml/min per 1.73 m2 and for SAT was 2.6 ml/min per 1.73 m2 in a multivariable-adjusted model. Conclusions: VAT and SAT were associated with CKD when defined using cystatin C estimating equations but not when using a creatinine-based estimating equation. Mechanisms linking adipose tissue to cystatin C warrant further research.10.2215/CJN.02490508Wed, 24 Sep 2008 09:00:50 GMT-07:00Association of Visceral and Subcutaneous Adiposity with Kidney FunctionBackground and objectives: Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations. Design, setting, participants, & measurements: Participants from the Framingham Offspring Study who underwent abdominal computed tomography for VAT and SAT quantification were included (n = 1299; 53% women; mean age 60 yr). CKD was defined as estimated GFR <60 ml/min per 1.73 m2, as estimated using creatinine (n = 89) in the Modification of Diet in Renal Disease (MDRD) formula or by cystatin C (n = 136). Regression models evaluated the cross-sectional relations between VAT and SAT with CKD and cystatin C, with age and gender adjustment and cardiovascular risk factor adjustment. Results: Neither VAT nor SAT was associated with CKD as estimated by the MDRD equation. In contrast, both VAT and SAT were associated with CKD when defined using cystatin-based equations. The estimated decrease in estimated GFR by cystatin C per 1-SD increase of VAT was 1.9 ml/min per 1.73 m2 and for SAT was 2.6 ml/min per 1.73 m2 in a multivariable-adjusted model. Conclusions: VAT and SAT were associated with CKD when defined using cystatin C estimating equations but not when using a creatinine-based estimating equation. Mechanisms linking adipose tissue to cystatin C warrant further research.Young, Jill A.Hwang, Shih-JenSarnak, Mark J.Hoffmann, UdoMassaro, Joseph M.Levy, DanielBenjamin, Emelia J.Larson, Martin G.Vasan, Ramachandran S.O’Donnell, Christopher J.Fox, Caroline S.2008-09-24T09:00:50-07:00doi:10.2215/CJN.02490508hwp:resource-id:clinjasn;3/6/1786American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and OutcomesEpidemiology and Outcomesresearch-article20082008-11-01November 200810.2215/CJN.024905081555-90411555-905X2008-09-24T09:00:50-07:002008-11Clinical Journal of the American Society of NephrologyEpidemiology and Outcomes3617861791
- Screening for Chronic Kidney Disease Complications in US Adults: Racial Implications of a Single GFR ThresholdBackground and objectives: An ideal and effective screening tool should perform equally across ethnic groups. The objective of this study was to determine whether the widely advocated creatinine-based estimated GFR (eGFR) threshold of 60 ml/min per 1.73 m2 identifies the typical metabolic abnormalities related to chronic kidney disease equally well in minority and nonminority adults. Design, setting, participants, & measurements: This objective was addressed using data for 8918 minority and nonminority adult participants in the National Health and Nutrition Examination Survey 2003 through 2006, which used stratified, multistage, probability sampling methods to assemble a nationwide probability sample of the noninstitutionalized population of the United States. Metabolic abnormalities including BP, potassium, hemoglobin, bicarbonate, uric acid, calcium, phosphorus, and parathyroid hormone were defined by fifth or 95th percentile values. Results: Among participants with eGFR <60 ml/min per 1.73 m2, black individuals were more likely than white individuals to have low hemoglobin (adjusted odds ratio [aOR] 3.76; 95% confidence interval [CI] 1.94 to 7.28), elevated uric acid (aOR 2.15; 95% CI 1.26 to 3.68), and elevated parathyroid hormone (aOR 3.93; 95% CI 2.33 to 6.66). Conclusions: Metabolic consequences of reduced eGFR are more common in black individuals and seem to be present at levels well above 60 ml/min per 1.73 m2; thus, black individuals should be screened for the metabolic complications of chronic kidney at higher GFR levels.10.2215/CJN.01890408Wed, 10 Sep 2008 06:29:57 GMT-07:00Screening for Chronic Kidney Disease Complications in US Adults: Racial Implications of a Single GFR ThresholdBackground and objectives: An ideal and effective screening tool should perform equally across ethnic groups. The objective of this study was to determine whether the widely advocated creatinine-based estimated GFR (eGFR) threshold of 60 ml/min per 1.73 m2 identifies the typical metabolic abnormalities related to chronic kidney disease equally well in minority and nonminority adults. Design, setting, participants, & measurements: This objective was addressed using data for 8918 minority and nonminority adult participants in the National Health and Nutrition Examination Survey 2003 through 2006, which used stratified, multistage, probability sampling methods to assemble a nationwide probability sample of the noninstitutionalized population of the United States. Metabolic abnormalities including BP, potassium, hemoglobin, bicarbonate, uric acid, calcium, phosphorus, and parathyroid hormone were defined by fifth or 95th percentile values. Results: Among participants with eGFR <60 ml/min per 1.73 m2, black individuals were more likely than white individuals to have low hemoglobin (adjusted odds ratio [aOR] 3.76; 95% confidence interval [CI] 1.94 to 7.28), elevated uric acid (aOR 2.15; 95% CI 1.26 to 3.68), and elevated parathyroid hormone (aOR 3.93; 95% CI 2.33 to 6.66). Conclusions: Metabolic consequences of reduced eGFR are more common in black individuals and seem to be present at levels well above 60 ml/min per 1.73 m2; thus, black individuals should be screened for the metabolic complications of chronic kidney at higher GFR levels.Ibrahim, Hassan N.Wang, ChangchunIshani, AreefCollins, Allan J.Foley, Robert N.2008-09-10T06:29:57-07:00doi:10.2215/CJN.01890408hwp:resource-id:clinjasn;3/6/1792American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and OutcomesEpidemiology and Outcomesresearch-article20082008-11-01November 200810.2215/CJN.018904081555-90411555-905X2008-09-10T06:29:57-07:002008-11Clinical Journal of the American Society of NephrologyEpidemiology and Outcomes36217922511799253
- Course of Depression and Anxiety Diagnosis in Patients Treated with Hemodialysis: A 16-month Follow-upBackground and objectives: There is growing identification of the need to seriously study the psychiatric presentations of end-stage renal disease patients treated with hemodialysis. This study reports on the course of depression and anxiety diagnoses and their impact on quality of life and health status. Design, setting, participants, & measurements: The 16-mo course of psychiatric diagnoses in 50 end-stage renal disease patients treated with hemodialysis was measured by structured clinical interview. Results: Three different pathways were identified: one subset of patients not having a psychiatric diagnosis at either baseline or 16-mo follow-up (68% for depression, 51% for anxiety), one group having an intermittent course (21% for depression, 34% for anxiety), and one group having a persistent course (11% for depression, 15% for anxiety), with diagnoses at both time 1 and time 2. For depression, the people with the persistent course showed marked decreases in quality of life and self-reported health status compared with the nondepressed and intermittently depressed cohorts. The most powerful predictor of depression at time 2 is degree of depressive affect at time 1(P < 0.05). Conclusions: Patients at risk for short- and long-term complications of depression can be potentially identified by high levels of depressive affect even at a single time point. As nearly 20% of the sample had chronic depression or anxiety, identifying a psychiatric diagnosis in hemodialysis patients and then offering treatment are important because, in the absence of intervention, psychiatric disorders are likely to persist in a substantial proportion of patients.10.2215/CJN.01120308Wed, 06 Aug 2008 07:46:07 GMT-07:00Course of Depression and Anxiety Diagnosis in Patients Treated with Hemodialysis: A 16-month Follow-upBackground and objectives: There is growing identification of the need to seriously study the psychiatric presentations of end-stage renal disease patients treated with hemodialysis. This study reports on the course of depression and anxiety diagnoses and their impact on quality of life and health status. Design, setting, participants, & measurements: The 16-mo course of psychiatric diagnoses in 50 end-stage renal disease patients treated with hemodialysis was measured by structured clinical interview. Results: Three different pathways were identified: one subset of patients not having a psychiatric diagnosis at either baseline or 16-mo follow-up (68% for depression, 51% for anxiety), one group having an intermittent course (21% for depression, 34% for anxiety), and one group having a persistent course (11% for depression, 15% for anxiety), with diagnoses at both time 1 and time 2. For depression, the people with the persistent course showed marked decreases in quality of life and self-reported health status compared with the nondepressed and intermittently depressed cohorts. The most powerful predictor of depression at time 2 is degree of depressive affect at time 1(P < 0.05). Conclusions: Patients at risk for short- and long-term complications of depression can be potentially identified by high levels of depressive affect even at a single time point. As nearly 20% of the sample had chronic depression or anxiety, identifying a psychiatric diagnosis in hemodialysis patients and then offering treatment are important because, in the absence of intervention, psychiatric disorders are likely to persist in a substantial proportion of patients.Cukor, DanielCoplan, JeremyBrown, ClintonPeterson, Rolf A.Kimmel, Paul L.2008-08-06T07:46:07-07:00doi:10.2215/CJN.01120308hwp:resource-id:clinjasn;3/6/1752American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and OutcomesEpidemiology and Outcomesresearch-article20082008-11-01November 200810.2215/CJN.011203081555-90411555-905X2008-08-06T07:46:07-07:002008-11Clinical Journal of the American Society of NephrologyEpidemiology and Outcomes3617521758
- Biomarkers and Health-Related Quality of Life in End-Stage Renal Disease: A Systematic ReviewBackground and objectives: Health-related quality of life (HRQOL) predicts mortality in ESRD, yet adoption of HRQOL monitoring is not widespread, and regulatory authorities remain predominantly concerned with monitoring traditional biologic parameters. To assist with future efforts to adopt HRQOL monitoring while acknowledging the importance of biomarkers, this study sought to establish which domains of HRQOL are most affected by ESRD and to measure the strength of evidence linking common biomarkers to HRQOL in ESRD. Design, setting, participants, & measurements: A systematic review was performed to identify studies that measured HRQOL in ESRD. Data were abstracted according to a conceptual model regarding the measurement of HRQOL differences, and HRQOL data were converted to weighted mean effect sizes and correlation coefficients. Results: The impact of ESRD was largest in the Short Form 36 domains of physical functioning (e.g., role-physical, vitality) and smallest in mental functioning (e.g., mental health, role-emotional). Dialysis adequacy, as measured by Kt/V, was a poor correlate for Short Form 36 scores. Similarly, mineral metabolism (e.g., calcium × phosphorous, parathyroid hormone) and inflammatory (e.g., C-reactive protein, TNF) biomarkers had small effect sizes and correlations with HRQOL. In contrast, hematocrit demonstrated small to moderate relationships with mental and physical HRQOL, and nutritional biomarkers (e.g., albumin, creatinine, body mass index) demonstrated moderate to large relationships. Conclusions: HRQOL in ESRD is most affected in the physical domains, and nutritional biomarkers are most closely associated with these domains. In contrast, Kt/V, mineral metabolism indices, and inflammatory markers are poor HRQOL correlates.10.2215/CJN.00820208Wed, 01 Oct 2008 11:43:16 GMT-07:00Biomarkers and Health-Related Quality of Life in End-Stage Renal Disease: A Systematic ReviewBackground and objectives: Health-related quality of life (HRQOL) predicts mortality in ESRD, yet adoption of HRQOL monitoring is not widespread, and regulatory authorities remain predominantly concerned with monitoring traditional biologic parameters. To assist with future efforts to adopt HRQOL monitoring while acknowledging the importance of biomarkers, this study sought to establish which domains of HRQOL are most affected by ESRD and to measure the strength of evidence linking common biomarkers to HRQOL in ESRD. Design, setting, participants, & measurements: A systematic review was performed to identify studies that measured HRQOL in ESRD. Data were abstracted according to a conceptual model regarding the measurement of HRQOL differences, and HRQOL data were converted to weighted mean effect sizes and correlation coefficients. Results: The impact of ESRD was largest in the Short Form 36 domains of physical functioning (e.g., role-physical, vitality) and smallest in mental functioning (e.g., mental health, role-emotional). Dialysis adequacy, as measured by Kt/V, was a poor correlate for Short Form 36 scores. Similarly, mineral metabolism (e.g., calcium × phosphorous, parathyroid hormone) and inflammatory (e.g., C-reactive protein, TNF) biomarkers had small effect sizes and correlations with HRQOL. In contrast, hematocrit demonstrated small to moderate relationships with mental and physical HRQOL, and nutritional biomarkers (e.g., albumin, creatinine, body mass index) demonstrated moderate to large relationships. Conclusions: HRQOL in ESRD is most affected in the physical domains, and nutritional biomarkers are most closely associated with these domains. In contrast, Kt/V, mineral metabolism indices, and inflammatory markers are poor HRQOL correlates.Spiegel, Brennan M.R.Melmed, GilRobbins, SeanEsrailian, Eric2008-10-01T11:43:16-07:00doi:10.2215/CJN.00820208hwp:resource-id:clinjasn;3/6/1759American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyEpidemiology and OutcomesEpidemiology and Outcomesresearch-article20082008-11-01November 200810.2215/CJN.008202081555-90411555-905X2008-10-01T11:43:16-07:002008-11Clinical Journal of the American Society of NephrologyEpidemiology and Outcomes3617591768
- The Agony of Ecstasy: MDMA (3,4-Methylenedioxymethamphetamine) and the KidneyEcstasy (MDMA, 3,4-methylenedioxymethamphetamine) is commonly used by college-aged individuals. Ecstasy leads to feelings of euphoria, emotional empathy, and increased energy. These effects come at a significant risk for complications. Ecstasy has been associated with acute kidney injury that is most commonly secondary to nontraumatic rhabdomyolysis but also has been reported in the setting of drug-induced liver failure and drug-induced vasculitis. More common, ecstasy has led to serious hyponatremia and hyponatremia-associated deaths. Hyponatremia in these cases is due to a “perfect storm” of ecstasy-induced effects on water balance. Ecstasy leads to secretion of arginine vasopressin as well as polydipsia as a result of its effects on the serotonergic nervous pathways. Compounding these effects are the ready availability of fluids and the recommendation to drink copiously at rave parties where ecstasy is used. The effects of ecstasy on the kidney as well as therapeutic measures for the treatment of ecstasy-induced hyponatremia are presented.10.2215/CJN.02080508Wed, 06 Aug 2008 07:46:11 GMT-07:00The Agony of Ecstasy: MDMA (3,4-Methylenedioxymethamphetamine) and the KidneyEcstasy (MDMA, 3,4-methylenedioxymethamphetamine) is commonly used by college-aged individuals. Ecstasy leads to feelings of euphoria, emotional empathy, and increased energy. These effects come at a significant risk for complications. Ecstasy has been associated with acute kidney injury that is most commonly secondary to nontraumatic rhabdomyolysis but also has been reported in the setting of drug-induced liver failure and drug-induced vasculitis. More common, ecstasy has led to serious hyponatremia and hyponatremia-associated deaths. Hyponatremia in these cases is due to a “perfect storm” of ecstasy-induced effects on water balance. Ecstasy leads to secretion of arginine vasopressin as well as polydipsia as a result of its effects on the serotonergic nervous pathways. Compounding these effects are the ready availability of fluids and the recommendation to drink copiously at rave parties where ecstasy is used. The effects of ecstasy on the kidney as well as therapeutic measures for the treatment of ecstasy-induced hyponatremia are presented.Campbell, Garland A.Rosner, Mitchell H.2008-08-06T07:46:11-07:00doi:10.2215/CJN.02080508hwp:resource-id:clinjasn;3/6/1852American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIn-Depth ReviewsIn-Depth Reviewsother20082008-11-01November 200810.2215/CJN.020805081555-90411555-905X2008-08-06T07:46:11-07:002008-11Clinical Journal of the American Society of NephrologyIn-Depth Reviews3618521860
- Acid-Base Disturbances in Gastrointestinal DiseaseDisruption of normal gastrointestinal function as a result of infection, hereditary or acquired diseases, or complications of surgical procedures uncovers its important role in acid-base homeostasis. Metabolic acidosis or alkalosis may occur, depending on the nature and volume of the unregulated losses that occur. Investigation into the specific pathophysiology of gastrointestinal disorders has provided important new insights into the normal physiology of ion transport along the gut and has also provided new avenues for treatment. This review provides a brief overview of normal ion transport along the gut and then discusses the pathophysiology and treatment of the metabolic acid-base disorders that occur when normal gut function is disrupted.10.2215/CJN.02450508Wed, 15 Oct 2008 07:55:51 GMT-07:00Acid-Base Disturbances in Gastrointestinal DiseaseDisruption of normal gastrointestinal function as a result of infection, hereditary or acquired diseases, or complications of surgical procedures uncovers its important role in acid-base homeostasis. Metabolic acidosis or alkalosis may occur, depending on the nature and volume of the unregulated losses that occur. Investigation into the specific pathophysiology of gastrointestinal disorders has provided important new insights into the normal physiology of ion transport along the gut and has also provided new avenues for treatment. This review provides a brief overview of normal ion transport along the gut and then discusses the pathophysiology and treatment of the metabolic acid-base disorders that occur when normal gut function is disrupted.Gennari, F. JohnWeise, Wolfgang J.2008-10-15T07:55:51-07:00doi:10.2215/CJN.02450508hwp:resource-id:clinjasn;3/6/1861American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyIn-Depth ReviewsIn-Depth Reviewsother20082008-11-01November 200810.2215/CJN.024505081555-90411555-905X2008-10-15T07:55:51-07:002008-11Clinical Journal of the American Society of NephrologyIn-Depth Reviews3618611868
- Nurturing Passion in a Time of Academic Climate Change: The Modern-Day Challenge of Junior Faculty Development10.2215/CJN.04240808Wed, 22 Oct 2008 12:41:58 GMT-07:00Nurturing Passion in a Time of Academic Climate Change: The Modern-Day Challenge of Junior Faculty DevelopmentChapman, Arlene B.Guay-Woodford, Lisa M.2008-10-22T12:41:58-07:00doi:10.2215/CJN.04240808hwp:resource-id:clinjasn;3/6/1878American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMoving Points in NephrologyMoving Points in Nephrologyother20082008-11-01November 200810.2215/CJN.042408081555-90411555-905X2008-10-22T12:41:58-07:002008-11Clinical Journal of the American Society of NephrologyMoving Points in Nephrology3618781883
- Academic Internal Medicine in the United States: Current Trends, Future Implications for Academic Nephrology10.2215/CJN.02110508Wed, 30 Jul 2008 11:41:51 GMT-07:00Academic Internal Medicine in the United States: Current Trends, Future Implications for Academic NephrologyIbrahim, Tod2008-07-30T11:41:51-07:00doi:10.2215/CJN.02110508hwp:resource-id:clinjasn;3/6/1887American Society of NephrologyCopyright © 2008 by the American Society of NephrologyClinical Journal of the American Society of NephrologyMoving Points in NephrologyMoving Points in Nephrologyother20082008-11-01November 200810.2215/CJN.021105081555-90411555-905X2008-07-30T11:41:51-07:002008-11Clinical Journal of the American Society of NephrologyMoving Points in Nephrology3618871894
- Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria Donors10.2215/CJN.03760415Thu, 17 Dec 2015 06:39:20 GMT-08:00Mortality among Younger and Older Recipients of Kidney Transplants from Expanded Criteria Donors Compared with Standard Criteria DonorsMa, Maggie K.M.Lim, Wai H.Craig, Jonathan C.Russ, Graeme R.Chapman, Jeremy R.Wong, Germaine2015-12-17T06:39:20-08:00doi:10.2215/CJN.03760415hwp:resource-id:clinjasn;11/1/128American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal transplantation, mortality, kidney donation, cardiovascular diseases, death, follow-up studies, humans, renal dialysis, risk, tissue donorsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20162016-01-07January 07, 201610.2215/CJN.037604151555-90411555-905X2015-12-17T06:39:20-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles11111281213613
- Waiting for a Deceased Kidney Donor Transplant: Better a Small Fish Than an Empty Dish?10.2215/CJN.12291115Thu, 17 Dec 2015 06:39:18 GMT-08:00Waiting for a Deceased Kidney Donor Transplant: Better a Small Fish Than an Empty Dish?Young, AnnGarg, Amit X.2015-12-17T06:39:18-08:00doi:10.2215/CJN.12291115hwp:resource-id:clinjasn;11/1/12American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal transplantation, kidney donation, mortality risk, death, tissue donorsEditorialsEditorialseditorial20162016-01-07January 07, 201610.2215/CJN.122911151555-90411555-905X2015-12-17T06:39:18-08:002016-01-07Clinical Journal of the American Society of NephrologyEditorials11111212813136
- Factors Associated with Recovery of Renal Function following Radical Nephrectomy for Kidney Neoplasms10.2215/CJN.04070415Fri, 23 Oct 2015 07:32:25 GMT-07:00Factors Associated with Recovery of Renal Function following Radical Nephrectomy for Kidney NeoplasmsZabor, Emily C.Furberg, HelenaMashni, JosephLee, ByronJaimes, Edgar A.Russo, Paul2015-10-23T07:32:25-07:00doi:10.2215/CJN.04070415hwp:resource-id:clinjasn;11/1/101American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrectomy, kidney cancer, chronic kidney disease, renal function, follow-up studies, glomerular filtration rate, humans, kidney, postoperative period, risk factorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-01-07January 07, 201610.2215/CJN.040704151555-90411555-905X2015-10-23T07:32:25-07:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles111101107
- Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function10.2215/CJN.01730215Fri, 23 Oct 2015 07:32:23 GMT-07:00Association between Serum Potassium and Outcomes in Patients with Reduced Kidney FunctionLuo, JiacongBrunelli, Steven M.Jensen, Donna E.Yang, Alex2015-10-23T07:32:23-07:00doi:10.2215/CJN.01730215hwp:resource-id:clinjasn;11/1/90American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, glomerular filtration rate, hospitalization, mortality, ACE inhibitors, follow-up studies, humans, hyperkalemia, hypokalemia, potassiumOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-01-07January 07, 201610.2215/CJN.017302151555-90411555-905X2015-10-23T07:32:23-07:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles11190100
- Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population10.2215/CJN.04230415Fri, 18 Dec 2015 07:18:57 GMT-08:00Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General PopulationPruijm, MennoPonte, BelenAckermann, DanielPaccaud, FredGuessous, IdrisEhret, GeorgPechère-Bertschi, AntoinetteVogt, BrunoMohaupt, Markus G.Martin, Pierre-YvesYouhanna, Sonia C.Nägele, NadineVollenweider, PeterWaeber, GérardBurnier, MichelDevuyst, OlivierBochud, Murielle2015-12-18T07:18:57-08:00doi:10.2215/CJN.04230415hwp:resource-id:clinjasn;11/1/70American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyosmolality, renal tubular cells, electrolytes, glomerular filtration rate, humans, hypertension, renal, potassium, renal insufficiency, chronic, sodium, uromodulinOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-01-07January 07, 201610.2215/CJN.042304151555-90411555-905X2015-12-18T07:18:57-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1111706808
- Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge10.2215/CJN.01290215Thu, 17 Dec 2015 06:39:19 GMT-08:00Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital DischargeLiang, Kelly V.Sileanu, Florentina E.Clermont, GillesMurugan, RaghavanPike, FrancisPalevsky, Paul M.Kellum, John A.2015-12-17T06:39:19-08:00doi:10.2215/CJN.01290215hwp:resource-id:clinjasn;11/1/30American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyHemodialysis, acute kidney injury, cohort studies, critical illness, hemodynamics, humans, intensive care units, kidney failure, chronic, renal replacement therapyOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-01-07January 07, 201610.2215/CJN.012902151555-90411555-905X2015-12-17T06:39:19-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1113038
- Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)10.2215/CJN.04240415Tue, 17 Nov 2015 06:31:03 GMT-08:00Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)Cooper, David S.Claes, DonnaGoldstein, Stuart L.Bennett, Michael R.Ma, QingDevarajan, PrasadKrawczeski, Catherine D.2015-11-17T06:31:03-08:00doi:10.2215/CJN.04240415hwp:resource-id:clinjasn;11/1/21American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, biomarkers, children, acute kidney injury, follow-up studies, humans, kidney, proteinuria, renal insufficiency, chronicOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-01-07January 07, 201610.2215/CJN.042404151555-90411555-905X2015-11-17T06:31:03-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1112129
- B Cells, Antibodies, and MoreB cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell–targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum. However, much remains to be understood about B-cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell–targeted approaches. In this review, we discuss the multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation.10.2215/CJN.09430915Wed, 23 Dec 2015 08:37:21 GMT-08:00B Cells, Antibodies, and MoreB cells play a central role in the immunopathogenesis of glomerulonephritides and transplant rejection. B cells secrete antibodies that contribute to tissue injury via multiple mechanisms. In addition, B cells contribute to disease pathogenesis in autoimmunity and alloimmunity by presenting antigens as well as providing costimulation and cytokines to T cells. B cells also play an immunomodulatory role in regulating the immune response by secreting cytokines that inhibit disease onset and/or progression. B cell–targeted approaches for treating immune diseases of the kidney and other organs have gained significant momentum. However, much remains to be understood about B-cell biology in order to determine the timing, duration, and context of optimal therapeutic response to B cell–targeted approaches. In this review, we discuss the multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation.Hoffman, WilliamLakkis, Fadi G.Chalasani, Geetha2015-12-23T08:37:21-08:00doi:10.2215/CJN.09430915hwp:resource-id:clinjasn;11/1/137American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAntibodies, plasma cells, B regulatory cells, autoimmunity, B-Lymphocytes, cytokines, glomerulonephritis, graft rejection, immune system diseases, T-LymphocytesRenal ImmunologyRenal Immunologyresearch-article20162016-01-07January 07, 201610.2215/CJN.094309151555-90411555-905X2015-12-23T08:37:21-08:002016-01-07Clinical Journal of the American Society of NephrologyRenal Immunology111137154
- A Patient on Peritoneal Dialysis with Refractory Volume OverloadThe management of volume in patients with diabetes on peritoneal dialysis is affected by several factors, including the degree of residual renal function, peritoneal membrane small-solute transport, salt and water intake, blood sugar control, comorbidity, and nutritional status. It requires sequential evaluation of volume status and adjustment of the peritoneal dialysis prescription on the basis of assessments of membrane function and alterations in urine volume. Steps should be taken to preserve residual renal function for as long as possible. Ultimately, in patients who have become anuric and have developed ultrafiltration failure, timely transfer to hemodialysis may be necessary, requiring discussion and planning with the patient.10.2215/CJN.02920315Thu, 16 Jul 2015 07:22:27 GMT-07:00A Patient on Peritoneal Dialysis with Refractory Volume OverloadThe management of volume in patients with diabetes on peritoneal dialysis is affected by several factors, including the degree of residual renal function, peritoneal membrane small-solute transport, salt and water intake, blood sugar control, comorbidity, and nutritional status. It requires sequential evaluation of volume status and adjustment of the peritoneal dialysis prescription on the basis of assessments of membrane function and alterations in urine volume. Steps should be taken to preserve residual renal function for as long as possible. Ultimately, in patients who have become anuric and have developed ultrafiltration failure, timely transfer to hemodialysis may be necessary, requiring discussion and planning with the patient.Wilkie, Martin2015-07-16T07:22:27-07:00doi:10.2215/CJN.02920315hwp:resource-id:clinjasn;11/1/155American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal membrane, diabetic nephropathy, dialysis volume, icodextrin, peritoneal dialysisAttending RoundsAttending Roundsresearch-article20162016-01-07January 07, 201610.2215/CJN.029203151555-90411555-905X2015-07-16T07:22:27-07:002016-01-07Clinical Journal of the American Society of NephrologyAttending Rounds111155160
- Tamm Horsfall Glycoprotein and Uromodulin: It Is All about the Tubules!10.2215/CJN.12201115Fri, 18 Dec 2015 07:18:58 GMT-08:00Tamm Horsfall Glycoprotein and Uromodulin: It Is All about the Tubules!Bleyer, Anthony J.Kmoch, Stanislav2015-12-18T07:18:58-08:00doi:10.2215/CJN.12201115hwp:resource-id:clinjasn;11/1/6American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuromodulin, urine, Tamm Horsfall, chronic kidney disease, genetic renal disease, kidney, mucoproteinsEditorialsEditorialseditorial20162016-01-07January 07, 201610.2215/CJN.122011151555-90411555-905X2015-12-18T07:18:58-08:002016-01-07Clinical Journal of the American Society of NephrologyEditorials111116706288069
- Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion10.2215/CJN.04770415Fri, 18 Dec 2015 07:18:56 GMT-08:00Clinical, Genetic, and Urinary Factors Associated with Uromodulin ExcretionTroyanov, StéphanDelmas-Frenette, CatherineBollée, GuillaumeYouhanna, SoniaBruat, VanessaAwadalla, PhilipDevuyst, OlivierMadore, François2015-12-18T07:18:56-08:00doi:10.2215/CJN.04770415hwp:resource-id:clinjasn;11/1/62American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyuric acid, chronic kidney disease, uromodulin, sodium, hypertension, creatinine, electrolytes, genotype, humansOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-01-07January 07, 201610.2215/CJN.047704151555-90411555-905X2015-12-18T07:18:56-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1111626698
- Complete Remission in the Nephrotic Syndrome Study Network10.2215/CJN.02560315Thu, 10 Dec 2015 12:38:23 GMT-08:00Complete Remission in the Nephrotic Syndrome Study NetworkGipson, Debbie S.Troost, Jonathan P.Lafayette, Richard A.Hladunewich, Michelle A.Trachtman, HowardGadegbeku, Crystal A.Sedor, John R.Holzman, Lawrence B.Moxey-Mims, Marva M.Perumal, KalyaniKaskel, Frederick J.Nelson, Peter J.Tuttle, Katherine R.Bagnasco, Serena M.Hogan, Marie C.Dell, Katherine M.Appel, Gerald B.Lieske, John C.Ilori, Titilayo O.Sethna, Christine B.Fervenza, Fernando C.Hogan, Susan L.Nachman, Patrick H.Rosenberg, Avi Z.Greenbaum, Larry A.Meyers, Kevin E.C.Hewitt, Stephen M.Choi, Michael J.Kopp, Jeffrey B.Zhdanova, OlgaHodgin, Jeffrey B.Johnstone, Duncan B.Adler, Sharon G.Avila-Casado, CarmenNeu, Alicia M.Hingorani, Sangeeta R.Lemley, Kevin V.Nast, Cynthia C.Brady, Tammy M.Barisoni-Thomas, LauraFornoni, AlessiaJennette, J. CharlesCattran, Daniel C.Palmer, Matthew B.Gibson, Keisha L.Reich, Heather N.Mokrzycki, Michele H.Sambandam, Kamalanathan K.Zilleruelo, Gaston E.Licht, ChristophSampson, Matthew G.Song, PeterMariani, Laura H.Kretzler, Matthias2015-12-10T12:38:23-08:00doi:10.2215/CJN.02560315hwp:resource-id:clinjasn;11/1/81American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, focal segmental glomerulosclerosis, membranous nephropathy, minimal change disease, kidney biopsy, cohort studies, glomerular filtration rate, humans, kidney failure chronic, proteinuriaOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20162016-01-07January 07, 201610.2215/CJN.025603151555-90411555-905X2015-12-10T12:38:23-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1118189
- Nephrologists as Educators: Clarifying Roles, Seizing OpportunitiesNephrologists play an important role in providing medical education in a variety of settings, including the medical school classroom, nephrology consult service, outpatient clinic, and dialysis unit. Therefore, nephrologists interact with a variety of learners. In this article the current state of published literature in medical education in nephrology is reviewed. Eight attending roles are identified of the nephrologist as a medical educator in the academic settings: inpatient internal medicine service, nephrology inpatient consult service, inpatient ESRD service, outpatient nephrology clinic, kidney transplantation, dialysis unit, classroom teacher, and research mentor. Defining each of these distinct settings could help to promote positive faculty development and encourage more rigorous education scholarship in nephrology.10.2215/CJN.12151214Fri, 14 Aug 2015 01:28:50 GMT-07:00Nephrologists as Educators: Clarifying Roles, Seizing OpportunitiesNephrologists play an important role in providing medical education in a variety of settings, including the medical school classroom, nephrology consult service, outpatient clinic, and dialysis unit. Therefore, nephrologists interact with a variety of learners. In this article the current state of published literature in medical education in nephrology is reviewed. Eight attending roles are identified of the nephrologist as a medical educator in the academic settings: inpatient internal medicine service, nephrology inpatient consult service, inpatient ESRD service, outpatient nephrology clinic, kidney transplantation, dialysis unit, classroom teacher, and research mentor. Defining each of these distinct settings could help to promote positive faculty development and encourage more rigorous education scholarship in nephrology.Jhaveri, Kenar D.Perazella, Mark A.2015-08-14T13:28:50-07:00doi:10.2215/CJN.12151214hwp:resource-id:clinjasn;11/1/176American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephropathy, ESRD, transplantationEducation SeriesEducation Seriesresearch-article20162016-01-07January 07, 201610.2215/CJN.121512141555-90411555-905X2015-08-14T13:28:50-07:002016-01-07Clinical Journal of the American Society of NephrologyEducation Series111176189
- Quality Measurement in Wonderland: The Curious Case of a Dialysis Readmissions MeasureThe standardized readmission ratio is a new quality measure for dialysis facilities that will affect public reporting and payment beginning in 2017. Like all quality measures affecting public reporting and payment, the standardized readmission ratio was vetted by a process that included a technical expert panel convened by the US Centers for Medicare and Medicaid Services, and, then, the National Quality Forum. Unlike previous measures, standardized readmission ratio followed a tortuous path that exposed problems in the development and endorsement process. Although it is acknowledged that processes in the dialysis facility can be improved to decrease readmissions, multiple objections to the implementation of the standardized readmission ratio measure existed. This review discusses the standardized readmission ratio measure and issues related to quality metric development that are important for the nephrology community to consider.10.2215/CJN.02770315Thu, 16 Jul 2015 07:22:26 GMT-07:00Quality Measurement in Wonderland: The Curious Case of a Dialysis Readmissions MeasureThe standardized readmission ratio is a new quality measure for dialysis facilities that will affect public reporting and payment beginning in 2017. Like all quality measures affecting public reporting and payment, the standardized readmission ratio was vetted by a process that included a technical expert panel convened by the US Centers for Medicare and Medicaid Services, and, then, the National Quality Forum. Unlike previous measures, standardized readmission ratio followed a tortuous path that exposed problems in the development and endorsement process. Although it is acknowledged that processes in the dialysis facility can be improved to decrease readmissions, multiple objections to the implementation of the standardized readmission ratio measure existed. This review discusses the standardized readmission ratio measure and issues related to quality metric development that are important for the nephrology community to consider.Fishbane, StevenWish, Jay B.2015-07-16T07:22:26-07:00doi:10.2215/CJN.02770315hwp:resource-id:clinjasn;11/1/190American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhospitalization, economic effect, ESRDPublic Policy SeriesPublic Policy Seriesresearch-article20162016-01-07January 07, 201610.2215/CJN.027703151555-90411555-905X2015-07-16T07:22:26-07:002016-01-07Clinical Journal of the American Society of NephrologyPublic Policy Series1111190195194197
- Exploring Potential Reasons for the Temporal Trend in Dialysis-Requiring AKI in the United States10.2215/CJN.04520415Fri, 18 Dec 2015 07:18:58 GMT-08:00Exploring Potential Reasons for the Temporal Trend in Dialysis-Requiring AKI in the United StatesHsu, Raymond K.McCulloch, Charles E.Heung, MichaelSaran, RajivShahinian, Vahakn B.Pavkov, Meda E.Burrows, Nilka RíosPowe, Neil R.Hsu, Chi-yuan2015-12-18T07:18:58-08:00doi:10.2215/CJN.04520415hwp:resource-id:clinjasn;11/1/14American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute kidney injury, temporal trend, dialysis, epidemiology, cohort studies, humans, incidence, renal dialysis, retrospective studies, sepsisOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20162016-01-07January 07, 201610.2215/CJN.045204151555-90411555-905X2015-12-18T07:18:58-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1111141203
- Evaluation of Neurocognition in Youth with CKD Using a Novel Computerized Neurocognitive Battery10.2215/CJN.02110215Fri, 23 Oct 2015 07:32:24 GMT-07:00Evaluation of Neurocognition in Youth with CKD Using a Novel Computerized Neurocognitive BatteryHartung, Erum A.Kim, Ji YoungLaney, NinaHooper, Stephen R.Radcliffe, JerilynnPort, Allison M.Gur, Ruben C.Furth, Susan L.2015-10-23T07:32:24-07:00doi:10.2215/CJN.02110215hwp:resource-id:clinjasn;11/1/39American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, psychological tests, attention, executive function, memory, neuropsychological, children, adolescents, cognition, humansOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20162016-01-07January 07, 201610.2215/CJN.021102151555-90411555-905X2015-10-23T07:32:24-07:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1113946
- Cocoa Flavanols: A Magic Potion for Protecting the Endothelium in Kidney Failure?10.2215/CJN.12141115Thu, 17 Dec 2015 06:39:18 GMT-08:00Cocoa Flavanols: A Magic Potion for Protecting the Endothelium in Kidney Failure?Zoccali, CarmineMallamaci, Francesca2015-12-17T06:39:18-08:00doi:10.2215/CJN.12141115hwp:resource-id:clinjasn;11/1/9American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyflavanols, flavonoids, ESRD, flow mediated vasodilatation, endothelial dysfunction, cardiovascular risk, cacao, endothelium, polyphenols, renal insufficiencyEditorialsEditorialseditorial20162016-01-07January 07, 201610.2215/CJN.121411151555-90411555-905X2015-12-17T06:39:18-08:002016-01-07Clinical Journal of the American Society of NephrologyEditorials1111910811118
- Brokering Compromise to Achieve Consensus10.2215/CJN.09250815Mon, 07 Dec 2015 05:53:39 GMT-08:00Brokering Compromise to Achieve ConsensusBurstin, HelenAmin, Taroon2015-12-07T05:53:39-08:00doi:10.2215/CJN.09250815hwp:resource-id:clinjasn;11/1/195American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis, end-stage renal disease, outcomes, Centers for Medicare and Medicaid Services, consensus, humans, kidney, kidney failure, chronic, patient readmission, renal dialysisPublic Policy SeriesPublic Policy Seriesresearch-article20162016-01-07January 07, 201610.2215/CJN.092508151555-90411555-905X2015-12-07T05:53:39-08:002016-01-07Clinical Journal of the American Society of NephrologyPublic Policy Series1111195190197194
- Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary HyperparathyroidismCKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD–related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions.10.2215/CJN.01760215Wed, 29 Jul 2015 06:53:30 GMT-07:00Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary HyperparathyroidismCKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD–related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions.Bover, JordiUreña, PabloRuiz-García, CésardaSilva, IaraLescano, Patriciadel Carpio, JacquelineBallarín, JoséCozzolino, Mario2015-07-29T06:53:30-07:00doi:10.2215/CJN.01760215hwp:resource-id:clinjasn;11/1/161American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, mineral metabolism, calcium receptor, hyperparathyroidism, vascular calcificationIn-Depth ReviewIn-Depth Reviewreview-article20162016-01-07January 07, 201610.2215/CJN.017602151555-90411555-905X2015-07-29T06:53:30-07:002016-01-07Clinical Journal of the American Society of NephrologyIn-Depth Review111161174
- Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial10.2215/CJN.05210515Tue, 10 Nov 2015 08:28:34 GMT-08:00Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) TrialMattoo, Tej K.Chesney, Russell W.Greenfield, Saul P.Hoberman, AlejandroKeren, RonMathews, RanjivGravens-Mueller, LisaIvanova, AnastasiaCarpenter, Myra A.Moxey-Mims, MarvaMajd, MassoudZiessman, Harvey A.2015-11-10T08:28:34-08:00doi:10.2215/CJN.05210515hwp:resource-id:clinjasn;11/1/54American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyvesico-ureteral reflux, renal scarring, reflux nephropathy, anti-infective agents, child, humans, kidney, random allocation, trimethoprim-sulfamethoxazole combination urinary tract infectionsOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-01-07January 07, 201610.2215/CJN.052105151555-90411555-905X2015-11-10T08:28:34-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1115461
- Lupus Nephritis in the Era of Biomarkers10.2215/CJN.12371115Wed, 23 Dec 2015 08:37:19 GMT-08:00Lupus Nephritis in the Era of BiomarkersMonroy Trujillo, Jose ManuelFine, Derek Michael2015-12-23T08:37:19-08:00doi:10.2215/CJN.12371115hwp:resource-id:clinjasn;11/1/4American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologylupus nephritis, biomarkers, systemic lupus erythematosusEditorialsEditorialseditorial20162016-01-07January 07, 201610.2215/CJN.123711151555-90411555-905X2015-12-23T08:37:19-08:002016-01-07Clinical Journal of the American Society of NephrologyEditorials1111447553
- Predictors of Incident ESRD among Patients with Primary Hyperoxaluria Presenting Prior to Kidney Failure10.2215/CJN.02810315Thu, 10 Dec 2015 12:38:22 GMT-08:00Predictors of Incident ESRD among Patients with Primary Hyperoxaluria Presenting Prior to Kidney FailureZhao, FangBergstralh, Eric J.Mehta, Ramila A.Vaughan, Lisa E.Olson, Julie B.Seide, Barbara M.Meek, Alicia M.Cogal, Andrea G.Lieske, John C.Milliner, Dawn S.2015-12-10T12:38:22-08:00doi:10.2215/CJN.02810315hwp:resource-id:clinjasn;11/1/119American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologygenetic renal disease, kidney stones, mineral metabolism, calcium oxalate, follow-up studies, humans, hyperoxaluria, primary, kidney failure, chronic, oxalates, registriesOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20162016-01-07January 07, 201610.2215/CJN.028103151555-90411555-905X2015-12-10T12:38:22-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles111119126
- Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare10.2215/CJN.03990415Wed, 23 Dec 2015 08:37:20 GMT-08:00Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its FlareBirmingham, Daniel J.Bitter, Joshua E.Ndukwe, Ezinne G.Dials, SarahGullo, Terese R.Conroy, SaraNagaraja, Haikady N.Rovin, Brad H.Hebert, Lee A.2015-12-23T08:37:20-08:00doi:10.2215/CJN.03990415hwp:resource-id:clinjasn;11/1/47American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanti-C1q, anti-C3b, lupus nephritis, flare, autoantibodies, complement C1q, cross-sectional studies, humans, immunoglobulin G, prospective studiesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20162016-01-07January 07, 201610.2215/CJN.039904151555-90411555-905X2015-12-23T08:37:20-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1111474535
- Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double–Blind, Randomized, Placebo–Controlled Trial10.2215/CJN.05560515Thu, 17 Dec 2015 06:39:18 GMT-08:00Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double–Blind, Randomized, Placebo–Controlled TrialRassaf, TienushRammos, ChristosHendgen-Cotta, Ulrike B.Heiss, ChristianKleophas, WernerDellanna, FrankFloege, JürgenHetzel, Gerd R.Kelm, Malte2015-12-17T06:39:18-08:00doi:10.2215/CJN.05560515hwp:resource-id:clinjasn;11/1/108American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycocoa-flavanols, endothelial function, hemodialysis, vascular functions, nutrition, blood pressure, double-blind method, heart rate, hemodynamics, humans, kidney failure, chronicOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20162016-01-07January 07, 201610.2215/CJN.055605151555-90411555-905X2015-12-17T06:39:18-08:002016-01-07Clinical Journal of the American Society of NephrologyOriginal Articles1111108911811
- Temporal Trends in AKI: Insights from Big Data10.2215/CJN.12351115Fri, 18 Dec 2015 07:18:58 GMT-08:00Temporal Trends in AKI: Insights from Big DataNadkarni, Girish N.Coca, Steven G.2015-12-18T07:18:58-08:00doi:10.2215/CJN.12351115hwp:resource-id:clinjasn;11/1/1American Society of NephrologyCopyright © 2016 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, dialysis, end stage kidney disease, acute kidney injury, creatinine, problem solvingEditorialsEditorialseditorial20162016-01-07January 07, 201610.2215/CJN.123511151555-90411555-905X2015-12-18T07:18:58-08:002016-01-07Clinical Journal of the American Society of NephrologyEditorials1111114320
- Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINTIn this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.10.1681/ASN.2015101125Mon, 09 Nov 2015 08:28:57 GMT-08:00Managing Hypertension in Patients with CKD: A Marathon, Not a SPRINTIn this manuscript, nephrologist-investigators from one of five Clinical Center Networks of the Systolic Blood Pressure Intervention Trial (SPRINT) provide background information and context on the intensity of anti-hypertensive therapy in conjunction with the release of detailed results from SPRINT's primary analysis. The authors highlight published evidence on the safety and efficacy of differing intensities of anti-hypertensive therapy in mild to moderate CKD, where SPRINT will help to inform practice, as well as where gaps in evidence will remain. The authors also challenge the nephrology community to renew its attention and efforts on hypertension clinical care and research.Chertow, Glenn M.Beddhu, SrinivasanLewis, Julia B.Toto, Robert D.Cheung, Alfred K.2015-11-09T08:28:57-08:00doi:10.1681/ASN.2015101125hwp:resource-id:jnephrol;27/1/40American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, clinical trial, chronic kidney diseaseUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20162016-01-01January 201610.1681/ASN.20151011251046-66731533-34502015-11-09T08:28:57-08:002016-01Journal of the American Society of NephrologyUp Front Matters2714043
- Calcification Propensity and Survival among Renal Transplant RecipientsCalciprotein particle maturation time (T50) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T50 in renal transplantation, baseline serum T50 was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T50 with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T50 was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T50, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T50 values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T50 improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T50 was also associated with increased graft failure risk. The associations of T50 with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T50 was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.10.1681/ASN.2014070670Wed, 29 Apr 2015 10:30:12 GMT-07:00Calcification Propensity and Survival among Renal Transplant RecipientsCalciprotein particle maturation time (T50) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T50 in renal transplantation, baseline serum T50 was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T50 with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T50 was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T50, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T50 values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T50 improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T50 was also associated with increased graft failure risk. The associations of T50 with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T50 was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.Keyzer, Charlotte A.de Borst, Martin H.van den Berg, ElseJahnen-Dechent, WilliArampatzis, SpyridonFarese, StefanBergmann, Ivo P.Floege, JürgenNavis, GerjanBakker, Stephan J.L.van Goor, HarryEisenberger, UtePasch, Andreas2015-04-29T10:30:12-07:00doi:10.1681/ASN.2014070670hwp:resource-id:jnephrol;27/1/239American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, mortality risk, graft failure, calcification propensity, serum T50, calciprotein particlesClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20140706701046-66731533-34502015-04-29T10:30:12-07:002016-01Journal of the American Society of NephrologyClinical Research271239248
- Dense Deposit Disease Mimicking a Renal Small Vessel VasculitisDense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0–3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature.10.1681/ASN.2015020187Fri, 11 Sep 2015 06:24:43 GMT-07:00Dense Deposit Disease Mimicking a Renal Small Vessel VasculitisDense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0–3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature.Singh, LavleenSingh, GeetikaBhardwaj, SwatiSinha, AditiBagga, ArvindDinda, Amit2015-09-11T06:24:43-07:00doi:10.1681/ASN.2015020187hwp:resource-id:jnephrol;27/1/59American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyC3 glomerulopathy, dense deposit disease, C3GN, necrotizing crescentic GNUp Front MattersPathophysiology of the Renal BiopsyUp Front MattersPathophysiology of the Renal Biopsyresearch-article20162016-01-01January 201610.1681/ASN.20150201871046-66731533-34502015-09-11T06:24:43-07:002016-01Journal of the American Society of NephrologyUp Front Matters2715962
- ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic MicroangiopathyThrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor–related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor–related TMA. ADAMTS13−/− mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor–related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13−/− mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.10.1681/ASN.2014121165Tue, 02 Jun 2015 11:31:54 GMT-07:00ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic MicroangiopathyThrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor–related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor–related TMA. ADAMTS13−/− mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor–related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13−/− mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.Erpenbeck, LuiseDemers, MelanieZsengellér, Zsuzsanna K.Gallant, MaureenCifuni, Stephen M.Stillman, Isaac E.Karumanchi, S. AnanthWagner, Denisa D.2015-06-02T11:31:54-07:00doi:10.1681/ASN.2014121165hwp:resource-id:jnephrol;27/1/120American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyVEGF, thrombosis, von Willebrand FactorBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141211651046-66731533-34502015-06-02T11:31:54-07:002016-01Journal of the American Society of NephrologyBasic Research271112031315
- Nuclear Factor Erythroid 2-Related Factor 2 Drives Podocyte-Specific Expression of Peroxisome Proliferator-Activated Receptor γ Essential for Resistance to Crescentic GNNecrotizing and crescentic rapidly progressive GN (RPGN) is a life-threatening syndrome characterized by a rapid loss of renal function. Evidence suggests that podocyte expression of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) may prevent podocyte injury, but the function of glomerular PPARγ in acute, severe inflammatory GN is unknown. Here, we observed marked loss of PPARγ abundance and transcriptional activity in glomerular podocytes in experimental RPGN. Blunted expression of PPARγ in podocyte nuclei was also found in kidneys from patients diagnosed with crescentic GN. Podocyte-specific Pparγ gene targeting accentuated glomerular damage, with increased urinary loss of albumin and severe kidney failure. Furthermore, a PPARγ gain-of-function approach achieved by systemic administration of thiazolidinedione (TZD) failed to prevent severe RPGN in mice with podocyte-specific Pparγ gene deficiency. In nuclear factor erythroid 2-related factor 2 (NRF2)–deficient mice, loss of podocyte PPARγ was observed at baseline. NRF2 deficiency markedly aggravated the course of RPGN, an effect that was partially prevented by TZD administration. Furthermore, delayed administration of TZD, initiated after the onset of RPGN, still alleviated the severity of experimental RPGN. These findings establish a requirement for the NRF2–PPARγ cascade in podocytes, and we suggest that these transcription factors have a role in augmenting the tolerance of glomeruli to severe immune-complex mediated injury. The NRF2–PPARγ pathway may be a therapeutic target for RPGN.10.1681/ASN.2014111080Thu, 21 May 2015 10:56:38 GMT-07:00Nuclear Factor Erythroid 2-Related Factor 2 Drives Podocyte-Specific Expression of Peroxisome Proliferator-Activated Receptor γ Essential for Resistance to Crescentic GNNecrotizing and crescentic rapidly progressive GN (RPGN) is a life-threatening syndrome characterized by a rapid loss of renal function. Evidence suggests that podocyte expression of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) may prevent podocyte injury, but the function of glomerular PPARγ in acute, severe inflammatory GN is unknown. Here, we observed marked loss of PPARγ abundance and transcriptional activity in glomerular podocytes in experimental RPGN. Blunted expression of PPARγ in podocyte nuclei was also found in kidneys from patients diagnosed with crescentic GN. Podocyte-specific Pparγ gene targeting accentuated glomerular damage, with increased urinary loss of albumin and severe kidney failure. Furthermore, a PPARγ gain-of-function approach achieved by systemic administration of thiazolidinedione (TZD) failed to prevent severe RPGN in mice with podocyte-specific Pparγ gene deficiency. In nuclear factor erythroid 2-related factor 2 (NRF2)–deficient mice, loss of podocyte PPARγ was observed at baseline. NRF2 deficiency markedly aggravated the course of RPGN, an effect that was partially prevented by TZD administration. Furthermore, delayed administration of TZD, initiated after the onset of RPGN, still alleviated the severity of experimental RPGN. These findings establish a requirement for the NRF2–PPARγ cascade in podocytes, and we suggest that these transcription factors have a role in augmenting the tolerance of glomeruli to severe immune-complex mediated injury. The NRF2–PPARγ pathway may be a therapeutic target for RPGN.Henique, CaroleBollee, GuillaumeLenoir, OliviaDhaun, NeerajCamus, MarineChipont, AnnaFlosseau, KathleenMandet, ChantalYamamoto, MasayukiKarras, AlexandreThervet, EricBruneval, PatrickNochy, DominiqueMesnard, LaurentTharaux, Pierre-Louis2015-05-21T10:56:38-07:00doi:10.1681/ASN.2014111080hwp:resource-id:jnephrol;27/1/172American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, glomerulonephritis, podocyte, focal segmental glomerulosclerosis, metabolism, renal protectionBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141110801046-66731533-34502015-05-21T10:56:38-07:002016-01Journal of the American Society of NephrologyBasic Research271172188
- Podocyte-Specific Deletion of Yes-Associated Protein Causes FSGS and Progressive Renal FailureFSGS is the most common primary glomerular disease underlying ESRD in the United States and is increasing in incidence globally. FSGS results from podocyte injury, yet the mechanistic details of disease pathogenesis remain unclear. This has resulted in an unmet clinical need for cell-specific therapy in the treatment of FSGS and other proteinuric kidney diseases. We previously identified Yes-associated protein (YAP) as a prosurvival signaling molecule, the in vitro silencing of which increases podocyte susceptibility to apoptotic stimulus. YAP is a potent oncogene that is a prominent target for chemotherapeutic drug development. In this study, we tested the hypothesis that podocyte-specific deletion of Yap leads to proteinuric kidney disease through increased podocyte apoptosis. Yap was selectively silenced in podocytes using Cre-mediated recombination controlled by the podocin promoter. Yap silencing in podocytes resulted in podocyte apoptosis, podocyte depletion, proteinuria, and an increase in serum creatinine. Histologically, features characteristic of FSGS, including mesangial sclerosis, podocyte foot process effacement, tubular atrophy, interstitial fibrosis, and casts, were observed. In human primary FSGS, we noted reduced glomerular expression of YAP. Taken together, these results suggest a role for YAP as a physiologic antagonist of podocyte apoptosis, the signaling of which is essential for maintaining the integrity of the glomerular filtration barrier. These data suggest potential nephrotoxicity with strategies directed toward inhibition of YAP function. Further studies should evaluate the role of YAP in proteinuric glomerular disease pathogenesis and its potential utility as a therapeutic target.10.1681/ASN.2014090916Tue, 26 May 2015 08:19:22 GMT-07:00Podocyte-Specific Deletion of Yes-Associated Protein Causes FSGS and Progressive Renal FailureFSGS is the most common primary glomerular disease underlying ESRD in the United States and is increasing in incidence globally. FSGS results from podocyte injury, yet the mechanistic details of disease pathogenesis remain unclear. This has resulted in an unmet clinical need for cell-specific therapy in the treatment of FSGS and other proteinuric kidney diseases. We previously identified Yes-associated protein (YAP) as a prosurvival signaling molecule, the in vitro silencing of which increases podocyte susceptibility to apoptotic stimulus. YAP is a potent oncogene that is a prominent target for chemotherapeutic drug development. In this study, we tested the hypothesis that podocyte-specific deletion of Yap leads to proteinuric kidney disease through increased podocyte apoptosis. Yap was selectively silenced in podocytes using Cre-mediated recombination controlled by the podocin promoter. Yap silencing in podocytes resulted in podocyte apoptosis, podocyte depletion, proteinuria, and an increase in serum creatinine. Histologically, features characteristic of FSGS, including mesangial sclerosis, podocyte foot process effacement, tubular atrophy, interstitial fibrosis, and casts, were observed. In human primary FSGS, we noted reduced glomerular expression of YAP. Taken together, these results suggest a role for YAP as a physiologic antagonist of podocyte apoptosis, the signaling of which is essential for maintaining the integrity of the glomerular filtration barrier. These data suggest potential nephrotoxicity with strategies directed toward inhibition of YAP function. Further studies should evaluate the role of YAP in proteinuric glomerular disease pathogenesis and its potential utility as a therapeutic target.Schwartzman, MonicaReginensi, AntoineWong, Jenny S.Basgen, John M.Meliambro, KristinNicholas, Susanne B.D'Agati, VivetteMcNeill, HelenCampbell, Kirk N.2015-05-26T08:19:22-07:00doi:10.1681/ASN.2014090916hwp:resource-id:jnephrol;27/1/216American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyfocal segmental glomerulosclerosis, glomerular disease, podocyteBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20140909161046-66731533-34502015-05-26T08:19:22-07:002016-01Journal of the American Society of NephrologyBasic Research271216226
- Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort StudyProteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3–1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0–3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.10.1681/ASN.2015010062Tue, 07 Jul 2015 12:05:37 GMT-07:00Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort StudyProteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3–1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0–3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.Naesens, MaartenLerut, EvelyneEmonds, Marie-PauleHerelixka, AlbertEvenepoel, PieterClaes, KathleenBammens, BertSprangers, BenMeijers, BjörnJochmans, InaMonbaliu, DiethardPirenne, JacquesKuypers, Dirk R.J.2015-07-07T12:05:37-07:00doi:10.1681/ASN.2015010062hwp:resource-id:jnephrol;27/1/281American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, kidney transplantation, survival, histopathologyClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20150100621046-66731533-34502015-07-07T12:05:37-07:002016-01Journal of the American Society of NephrologyClinical Research271281292
- Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKIThe opportunity to make advances in the prevention and treatment of AKI has never been greater than it is today. Major advances have been made in the understanding of the biology of AKI, the design of clinical trials, and the use of diagnostic and prognostic biomarkers. These advances have been supplemented by the coordinated effort of societies, federal agencies, and industry, such that we are poised in the ensuing years to positively address the unrelenting harm that this disorder has created. Over the past decade, major advances have been made in understanding the pathophysiology of AKI, mainly through the study of small animal models. However, translating these findings to human AKI remains a barrier, which is typified by the absence of effective therapeutic agents. The purpose of the Acute Dialysis Quality Initiative (ADQI) XIII was to harmonize human and animal studies and determine what is known about potential therapeutic targets and what gaps in knowledge remain. A series of invited reviews will distill key concepts from this initiative that focus on different pathogenic features of AKI, including hemodynamics, immunity and inflammation, cellular and molecular pathways, progression, and regeneration and repair. This series will convey the status of our knowledge of the pathophysiology of human AKI and propose therapeutic targets for further investigation.10.1681/ASN.2015030233Fri, 30 Oct 2015 07:47:15 GMT-07:00Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKIThe opportunity to make advances in the prevention and treatment of AKI has never been greater than it is today. Major advances have been made in the understanding of the biology of AKI, the design of clinical trials, and the use of diagnostic and prognostic biomarkers. These advances have been supplemented by the coordinated effort of societies, federal agencies, and industry, such that we are poised in the ensuing years to positively address the unrelenting harm that this disorder has created. Over the past decade, major advances have been made in understanding the pathophysiology of AKI, mainly through the study of small animal models. However, translating these findings to human AKI remains a barrier, which is typified by the absence of effective therapeutic agents. The purpose of the Acute Dialysis Quality Initiative (ADQI) XIII was to harmonize human and animal studies and determine what is known about potential therapeutic targets and what gaps in knowledge remain. A series of invited reviews will distill key concepts from this initiative that focus on different pathogenic features of AKI, including hemodynamics, immunity and inflammation, cellular and molecular pathways, progression, and regeneration and repair. This series will convey the status of our knowledge of the pathophysiology of human AKI and propose therapeutic targets for further investigation.Okusa, Mark D.Rosner, Mitchell H.Kellum, John A.Ronco, Claudio2015-10-30T07:47:15-07:00doi:10.1681/ASN.2015030233hwp:resource-id:jnephrol;27/1/44American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, pathophysiology of renal disease, and progressionUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20162016-01-01January 201610.1681/ASN.20150302331046-66731533-34502015-10-30T07:47:15-07:002016-01Journal of the American Society of NephrologyUp Front Matters2714448
- Renal Hemodynamics in AKI: In Search of New Treatment TargetsNovel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies.10.1681/ASN.2015030234Wed, 28 Oct 2015 07:03:12 GMT-07:00Renal Hemodynamics in AKI: In Search of New Treatment TargetsNovel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies.Matejovic, MartinInce, CanChawla, Lakhmir S.Blantz, RolandMolitoris, Bruce A.Rosner, Mitchell H.Okusa, Mark D.Kellum, John A.Ronco, Claudio2015-10-28T07:03:12-07:00doi:10.1681/ASN.2015030234hwp:resource-id:jnephrol;27/1/49American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, clinical nephrology, hemodynamics and vascular, regulationUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20162016-01-01January 201610.1681/ASN.20150302341046-66731533-34502015-10-28T07:03:12-07:002016-01Journal of the American Society of NephrologyUp Front Matters2714958
- Vascular Endothelial Growth Factor C for Polycystic Kidney DiseasesPolycystic kidney diseases (PKD) are genetic disorders characterized by progressive epithelial cyst growth leading to destruction of normally functioning renal tissue. Current therapies have focused on the cyst epithelium, and little is known about how the blood and lymphatic microvasculature modulates cystogenesis. Hypomorphic Pkd1nl/nl mice were examined, showing that cystogenesis was associated with a disorganized pericystic network of vessels expressing platelet/endothelial cell adhesion molecule 1 and vascular endothelial growth factor receptor 3 (VEGFR3). The major ligand for VEGFR3 is VEGFC, and there were lower levels of Vegfc mRNA within the kidneys during the early stages of cystogenesis in 7-day-old Pkd1nl/nl mice. Seven-day-old mice were treated with exogenous VEGFC for 2 weeks on the premise that this would remodel both the VEGFR3+ pericystic vascular network and larger renal lymphatics that may also affect the severity of PKD. Treatment with VEGFC enhanced VEGFR3 phosphorylation in the kidney, normalized the pattern of the pericystic network of vessels, and widened the large lymphatics in Pkd1nl/nl mice. These effects were associated with significant reductions in cystic disease, BUN and serum creatinine levels. Furthermore, VEGFC administration reduced M2 macrophage pericystic infiltrate, which has been implicated in the progression of PKD. VEGFC administration also improved cystic disease in Cys1cpk/cpk mice, a model of autosomal recessive PKD, leading to a modest but significant increase in lifespan. Overall, this study highlights VEGFC as a potential new treatment for some aspects of PKD, with the possibility for synergy with current epithelially targeted approaches.10.1681/ASN.2014090856Tue, 02 Jun 2015 11:31:55 GMT-07:00Vascular Endothelial Growth Factor C for Polycystic Kidney DiseasesPolycystic kidney diseases (PKD) are genetic disorders characterized by progressive epithelial cyst growth leading to destruction of normally functioning renal tissue. Current therapies have focused on the cyst epithelium, and little is known about how the blood and lymphatic microvasculature modulates cystogenesis. Hypomorphic Pkd1nl/nl mice were examined, showing that cystogenesis was associated with a disorganized pericystic network of vessels expressing platelet/endothelial cell adhesion molecule 1 and vascular endothelial growth factor receptor 3 (VEGFR3). The major ligand for VEGFR3 is VEGFC, and there were lower levels of Vegfc mRNA within the kidneys during the early stages of cystogenesis in 7-day-old Pkd1nl/nl mice. Seven-day-old mice were treated with exogenous VEGFC for 2 weeks on the premise that this would remodel both the VEGFR3+ pericystic vascular network and larger renal lymphatics that may also affect the severity of PKD. Treatment with VEGFC enhanced VEGFR3 phosphorylation in the kidney, normalized the pattern of the pericystic network of vessels, and widened the large lymphatics in Pkd1nl/nl mice. These effects were associated with significant reductions in cystic disease, BUN and serum creatinine levels. Furthermore, VEGFC administration reduced M2 macrophage pericystic infiltrate, which has been implicated in the progression of PKD. VEGFC administration also improved cystic disease in Cys1cpk/cpk mice, a model of autosomal recessive PKD, leading to a modest but significant increase in lifespan. Overall, this study highlights VEGFC as a potential new treatment for some aspects of PKD, with the possibility for synergy with current epithelially targeted approaches.Huang, Jennifer L.Woolf, Adrian S.Kolatsi-Joannou, MariaBaluk, PeterSandford, Richard N.Peters, Dorien J.M.McDonald, Donald M.Price, Karen L.Winyard, Paul J.D.Long, David A.2015-06-02T11:31:55-07:00doi:10.1681/ASN.2014090856hwp:resource-id:jnephrol;27/1/69American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvascular endothelial growth factor, endothelium, polycystic kidney diseaseBrief CommunicationsBrief Communicationsbrief-report20162016-01-01January 201610.1681/ASN.20140908561046-66731533-34502015-06-02T11:31:55-07:002016-01Journal of the American Society of NephrologyBrief Communications2711691773
- Renal Production, Uptake, and Handling of Circulating αKlothoαKlotho is a multifunctional protein highly expressed in the kidney. Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance. The role of the kidney in circulating αKlotho production and handling is incompletely understood, however. Here, we found higher αKlotho concentration in suprarenal compared with infrarenal inferior vena cava in both rats and humans. In rats, serum αKlotho concentration dropped precipitously after bilateral nephrectomy or upon treatment with inhibitors of αKlotho extracellular domain shedding. Furthermore, the serum half-life of exogenous αKlotho in anephric rats was four- to five-fold longer than that in normal rats, and exogenously injected labeled recombinant αKlotho was detected in the kidney and in urine of rats. Both in vivo (micropuncture) and in vitro (proximal tubule cell line) studies showed that αKlotho traffics from the basal to the apical side of the proximal tubule via transcytosis. Thus, we conclude that the kidney has dual roles in αKlotho homeostasis, producing and releasing αKlotho into the circulation and clearing αKlotho from the blood into the urinary lumen.10.1681/ASN.2014101030Thu, 14 May 2015 08:07:09 GMT-07:00Renal Production, Uptake, and Handling of Circulating αKlothoαKlotho is a multifunctional protein highly expressed in the kidney. Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance. The role of the kidney in circulating αKlotho production and handling is incompletely understood, however. Here, we found higher αKlotho concentration in suprarenal compared with infrarenal inferior vena cava in both rats and humans. In rats, serum αKlotho concentration dropped precipitously after bilateral nephrectomy or upon treatment with inhibitors of αKlotho extracellular domain shedding. Furthermore, the serum half-life of exogenous αKlotho in anephric rats was four- to five-fold longer than that in normal rats, and exogenously injected labeled recombinant αKlotho was detected in the kidney and in urine of rats. Both in vivo (micropuncture) and in vitro (proximal tubule cell line) studies showed that αKlotho traffics from the basal to the apical side of the proximal tubule via transcytosis. Thus, we conclude that the kidney has dual roles in αKlotho homeostasis, producing and releasing αKlotho into the circulation and clearing αKlotho from the blood into the urinary lumen.Hu, Ming ChangShi, MingjunZhang, JianningAddo, TayoCho, Han JuBarker, Sarah L.Ravikumar, PriyaGillings, NancyBian, AoSidhu, Sachdev S.Kuro-o, MakotoMoe, Orson W.2015-05-14T08:07:09-07:00doi:10.1681/ASN.2014101030hwp:resource-id:jnephrol;27/1/79American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrology[REMOVED HYPERLINK FIELD]Klotho, Transcytosis, Nephrectomy, Cell & Transport Physiology, renal proximal tubule cell, distal tubuleBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141010301046-66731533-34502015-05-14T08:07:09-07:002016-01Journal of the American Society of NephrologyBasic Research2717990
- IL-6 Trans-Signaling Drives Murine Crescentic GNThe role of IL-6 signaling in renal diseases remains controversial, with data describing both anti-inflammatory and proinflammatory effects. IL-6 can act via classic signaling, engaging its two membrane receptors gp130 and IL-6 receptor (IL-6R). Alternatively, IL-6 trans-signaling requires soluble IL-6R (sIL-6R) to act on IL-6R-negative cells that express gp130. Here, we characterize the role of both pathways in crescentic nephritis. Patients with crescentic nephritis had significantly elevated levels of IL-6 in both serum and urine. Similarly, nephrotoxic serum-induced nephritis (NTN) in BALB/c mice was associated with elevated serum IL-6 levels. Levels of serum sIL-6R and renal downstream signals of IL-6 (phosphorylated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3) increased over time in this model. Simultaneous inhibition of both IL-6 signaling pathways using anti–IL-6 antibody did not have a significant impact on NTN severity. In contrast, specific inhibition of trans-signaling using recombinant sgp130Fc resulted in milder disease. Vice versa, specific activation of trans-signaling using a recombinant IL-6–sIL-6R fusion molecule (Hyper-IL-6) significantly aggravated NTN and led to increased systolic BP in NTN mice. This correlated with increased renal mRNA synthesis of the Th17 cell cytokine IL-17A and decreased synthesis of resistin-like alpha (RELMalpha)-encoding mRNA, a surrogate marker of lesion-mitigating M2 macrophage subtypes. Collectively, our data suggest a central role for IL-6 trans-signaling in crescentic nephritis and offer options for more effective and specific therapeutic interventions in the IL-6 system.10.1681/ASN.2014111147Wed, 03 Jun 2015 08:15:31 GMT-07:00IL-6 Trans-Signaling Drives Murine Crescentic GNThe role of IL-6 signaling in renal diseases remains controversial, with data describing both anti-inflammatory and proinflammatory effects. IL-6 can act via classic signaling, engaging its two membrane receptors gp130 and IL-6 receptor (IL-6R). Alternatively, IL-6 trans-signaling requires soluble IL-6R (sIL-6R) to act on IL-6R-negative cells that express gp130. Here, we characterize the role of both pathways in crescentic nephritis. Patients with crescentic nephritis had significantly elevated levels of IL-6 in both serum and urine. Similarly, nephrotoxic serum-induced nephritis (NTN) in BALB/c mice was associated with elevated serum IL-6 levels. Levels of serum sIL-6R and renal downstream signals of IL-6 (phosphorylated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3) increased over time in this model. Simultaneous inhibition of both IL-6 signaling pathways using anti–IL-6 antibody did not have a significant impact on NTN severity. In contrast, specific inhibition of trans-signaling using recombinant sgp130Fc resulted in milder disease. Vice versa, specific activation of trans-signaling using a recombinant IL-6–sIL-6R fusion molecule (Hyper-IL-6) significantly aggravated NTN and led to increased systolic BP in NTN mice. This correlated with increased renal mRNA synthesis of the Th17 cell cytokine IL-17A and decreased synthesis of resistin-like alpha (RELMalpha)-encoding mRNA, a surrogate marker of lesion-mitigating M2 macrophage subtypes. Collectively, our data suggest a central role for IL-6 trans-signaling in crescentic nephritis and offer options for more effective and specific therapeutic interventions in the IL-6 system.Braun, Gerald S.Nagayama, YoshikuniMaruta, YuichiHeymann, Felixvan Roeyen, Claudia R.Klinkhammer, Barbara M.Boor, PeterVilla, LuigiSalant, David J.Raffetseder, UteRose-John, StefanOstendorf, TammoFloege, Jürgen2015-06-03T08:15:31-07:00doi:10.1681/ASN.2014111147hwp:resource-id:jnephrol;27/1/132American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, albuminuria, proteinuria, nephritisBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141111471046-66731533-34502015-06-03T08:15:31-07:002016-01Journal of the American Society of NephrologyBasic Research271132142
- IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated InjuryAntibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1–4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury.10.1681/ASN.2014111120Thu, 20 Aug 2015 10:14:17 GMT-07:00IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated InjuryAntibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1–4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury.Lefaucheur, CarmenViglietti, DenisBentlejewski, CarolDuong van Huyen, Jean-PaulVernerey, DewiAubert, OlivierVerine, JérômeJouven, XavierLegendre, ChristopheGlotz, DenisLoupy, AlexandreZeevi, Adriana2015-08-20T10:14:17-07:00doi:10.1681/ASN.2014111120hwp:resource-id:jnephrol;27/1/293American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, immunology and pathology, acute allograft, rejectionClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20141111201046-66731533-34502015-08-20T10:14:17-07:002016-01Journal of the American Society of NephrologyClinical Research271129363048
- ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGSHereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.10.1681/ASN.2014121240Tue, 12 May 2015 08:28:06 GMT-07:00ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGSHereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.Korkmaz, EmineLipska-Ziętkiewicz, Beata S.Boyer, OliviaGribouval, OlivierFourrage, CecileTabatabaei, MansourehSchnaidt, SvenGucer, SafakKaymaz, FigenArici, MustafaDinckan, AyhanMir, SevgiBayazit, Aysun K.Emre, SevincBalat, AyseRees, LesleyShroff, RukshanaBergmann, CarstenMourani, CheblAntignac, CorinneOzaltin, FatihSchaefer, Franz,2015-05-12T08:28:06-07:00doi:10.1681/ASN.2014121240hwp:resource-id:jnephrol;27/1/63American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulopathy, genetic renal disease, focal segmental glomerulosclerosis, familial nephropathy, mitochondriaBrief CommunicationsBrief Communicationsbrief-report20162016-01-01January 201610.1681/ASN.20141212401046-66731533-34502015-05-12T08:28:06-07:002016-01Journal of the American Society of NephrologyBrief Communications2716368
- Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract CancersLithium induces proliferation in the epithelium of renal collecting ducts. A recent small-scale cohort study reported a strong association between use of lithium and increased risk of renal neoplasia. We therefore conducted a large-scale pharmacoepidemiologic study of the association between long-term use of lithium and risk of upper urinary tract cancer, including renal cell cancer and cancers of the renal pelvis or ureter. We identified all histologically verified upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish Cancer Registry. A total of 6477 cases were matched by age and sex to 259,080 cancer-free controls. Data on lithium use from 1995 to 2012 were obtained from the Danish Prescription Registry. We estimated the association between long-term use of lithium (≥5 years) and risk of upper urinary tract cancer using conditional logistic regression with adjustment for potential confounders. Long-term use of lithium was observed among 0.22% of cases and 0.17% of controls. This yielded an overall nonsignificant adjusted odds ratio (OR) of 1.3 (95% confidence interval [95% CI], 0.8–2.2) for upper urinary tract cancer associated with long-term use of lithium. Analyses stratified by stage and subtype of upper urinary tract cancer revealed slight but nonsignificant increases in the ORs for localized disease (OR, 1.6; 95% CI, 0.8–3.0) and for renal pelvis/ureter cancers (OR, 1.7; 95% CI, 0.5–5.4). In conclusion, in our nationwide case-control study, use of lithium was not associated with an increased risk of upper urinary tract cancer.10.1681/ASN.2015010061Mon, 04 May 2015 07:11:17 GMT-07:00Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract CancersLithium induces proliferation in the epithelium of renal collecting ducts. A recent small-scale cohort study reported a strong association between use of lithium and increased risk of renal neoplasia. We therefore conducted a large-scale pharmacoepidemiologic study of the association between long-term use of lithium and risk of upper urinary tract cancer, including renal cell cancer and cancers of the renal pelvis or ureter. We identified all histologically verified upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish Cancer Registry. A total of 6477 cases were matched by age and sex to 259,080 cancer-free controls. Data on lithium use from 1995 to 2012 were obtained from the Danish Prescription Registry. We estimated the association between long-term use of lithium (≥5 years) and risk of upper urinary tract cancer using conditional logistic regression with adjustment for potential confounders. Long-term use of lithium was observed among 0.22% of cases and 0.17% of controls. This yielded an overall nonsignificant adjusted odds ratio (OR) of 1.3 (95% confidence interval [95% CI], 0.8–2.2) for upper urinary tract cancer associated with long-term use of lithium. Analyses stratified by stage and subtype of upper urinary tract cancer revealed slight but nonsignificant increases in the ORs for localized disease (OR, 1.6; 95% CI, 0.8–3.0) and for renal pelvis/ureter cancers (OR, 1.7; 95% CI, 0.5–5.4). In conclusion, in our nationwide case-control study, use of lithium was not associated with an increased risk of upper urinary tract cancer.Pottegård, AntonHallas, JesperJensen, Boye L.Madsen, KirstenFriis, Søren2015-05-04T07:11:17-07:00doi:10.1681/ASN.2015010061hwp:resource-id:jnephrol;27/1/249American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologykidney cancer, lithium, pharmacoepidemiologyClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20150100611046-66731533-34502015-05-04T07:11:17-07:002016-01Journal of the American Society of NephrologyClinical Research271249255
- Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers?Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles.10.1681/ASN.2015010074Thu, 06 Aug 2015 06:48:16 GMT-07:00Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers?Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles.Erdbrügger, UtaLe, Thu H.2015-08-06T06:48:16-07:00doi:10.1681/ASN.2015010074hwp:resource-id:jnephrol;27/1/12American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyextracellular vesicles, kidney disease, biomarker, exosomes, microparticlesUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-01-01January 201610.1681/ASN.20150100741046-66731533-34502015-08-06T06:48:16-07:002016-01Journal of the American Society of NephrologyUp Front Matters2711226
- Necroinflammation in Kidney DiseaseThe bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury–related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.10.1681/ASN.2015040405Wed, 02 Sep 2015 10:48:55 GMT-07:00Necroinflammation in Kidney DiseaseThe bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury–related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.Mulay, Shrikant R.Linkermann, AndreasAnders, Hans-Joachim2015-09-02T10:48:55-07:00doi:10.1681/ASN.2015040405hwp:resource-id:jnephrol;27/1/27American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, Immunology and pathology, kidney failureUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20162016-01-01January 201610.1681/ASN.20150404051046-66731533-34502015-09-02T10:48:55-07:002016-01Journal of the American Society of NephrologyUp Front Matters2712739
- Vascular Endothelial Growth Factor Therapy for the Kidney: Are We There Yet?10.1681/ASN.2015050491Tue, 02 Jun 2015 11:31:55 GMT-07:00Vascular Endothelial Growth Factor Therapy for the Kidney: Are We There Yet?Chade, Alejandro R.2015-06-02T11:31:55-07:00doi:10.1681/ASN.2015050491hwp:resource-id:jnephrol;27/1/1American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycystic kidney, vascular endothelial growth factor, renal injury, lymphatics, vesselsUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-01-01January 201610.1681/ASN.20150504911046-66731533-34502015-06-02T11:31:55-07:002016-01Journal of the American Society of NephrologyUp Front Matters2711169377
- The Aryl Hydrocarbon Receptor is a Critical Regulator of Tissue Factor Stability and an Antithrombotic Target in UremiaPatients with CKD suffer high rates of thrombosis, particularly after endovascular interventions, yet few options are available to improve management and reduce thrombotic risk. We recently demonstrated that indoxyl sulfate (IS) is a potent CKD-specific prothrombotic metabolite that induces tissue factor (TF) in vascular smooth muscle cells (vSMCs), although the precise mechanism and treatment implications remain unclear. Because IS is an agonist of the aryl hydrocarbon receptor (AHR), we first examined the relationship between IS levels and AHR-inducing activity in sera of patients with ESRD. IS levels correlated significantly with both vSMC AHR activity and TF activity. Mechanistically, we demonstrated that IS activates the AHR pathway in primary human aortic vSMCs, and further, that AHR interacts directly with and stabilizes functional TF. Antagonists directly targeting AHR enhanced TF ubiquitination and degradation and suppressed thrombosis in a postinterventional model of CKD and endovascular injury. Furthermore, AHR antagonists inhibited TF in a manner dependent on circulating IS levels. In conclusion, we demonstrated that IS regulates TF stability through AHR signaling and uncovered AHR as an antithrombotic target and AHR antagonists as a novel class of antithrombotics. Together, IS and AHR have potential as uremia-specific biomarkers and targets that may be leveraged as a promising theranostic platform to better manage the elevated thrombosis rates in patients with CKD.10.1681/ASN.2014121241Wed, 27 May 2015 11:20:14 GMT-07:00The Aryl Hydrocarbon Receptor is a Critical Regulator of Tissue Factor Stability and an Antithrombotic Target in UremiaPatients with CKD suffer high rates of thrombosis, particularly after endovascular interventions, yet few options are available to improve management and reduce thrombotic risk. We recently demonstrated that indoxyl sulfate (IS) is a potent CKD-specific prothrombotic metabolite that induces tissue factor (TF) in vascular smooth muscle cells (vSMCs), although the precise mechanism and treatment implications remain unclear. Because IS is an agonist of the aryl hydrocarbon receptor (AHR), we first examined the relationship between IS levels and AHR-inducing activity in sera of patients with ESRD. IS levels correlated significantly with both vSMC AHR activity and TF activity. Mechanistically, we demonstrated that IS activates the AHR pathway in primary human aortic vSMCs, and further, that AHR interacts directly with and stabilizes functional TF. Antagonists directly targeting AHR enhanced TF ubiquitination and degradation and suppressed thrombosis in a postinterventional model of CKD and endovascular injury. Furthermore, AHR antagonists inhibited TF in a manner dependent on circulating IS levels. In conclusion, we demonstrated that IS regulates TF stability through AHR signaling and uncovered AHR as an antithrombotic target and AHR antagonists as a novel class of antithrombotics. Together, IS and AHR have potential as uremia-specific biomarkers and targets that may be leveraged as a promising theranostic platform to better manage the elevated thrombosis rates in patients with CKD.Shivanna, SowmyaKolandaivelu, KumaranShashar, MosheBelghasim, MostafaAl-Rabadi, LaithBalcells, MercedesZhang, AnqiWeinberg, JaniceFrancis, JeanPollastri, Michael P.Edelman, Elazer R.Sherr, David H.Chitalia, Vipul C.2015-05-27T11:20:14-07:00doi:10.1681/ASN.2014121241hwp:resource-id:jnephrol;27/1/189American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, thrombosis, uremiaBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141212411046-66731533-34502015-05-27T11:20:14-07:002016-01Journal of the American Society of NephrologyBasic Research271189201
- Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKDAngiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and vitamin D-fibroblast growth factor-23 (FGF-23)-Klotho pathways. To determine whether vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort. In 167 children (median eGFR 51 ml/min per 1.73 m2), serum 25-hydroxyvitamin D (25(OH)D), FGF-23, and Klotho levels were measured at baseline and after a median 8 months on ACEi. Children with lower 25(OH)D levels had higher urinary protein/creatinine ratios at baseline (P=0.03) and at follow-up (P=0.006). Levels of 25(OH)D and serum vitamin D-binding protein were not associated, but 25(OH)D ≤50 nmol/L associated with higher diastolic BP (P=0.004). ACEi therapy also associated with increased Klotho levels (P<0.001). The annualized loss of eGFR was inversely associated with baseline 25(OH)D level (P<0.001, r=0.32). Five-year renal survival was 75% in patients with baseline 25(OH)D ≥50 nmol/L and 50% in those with lower 25(OH)D levels (P<0.001). This renoprotective effect remained significant but attenuated with ACEi therapy (P=0.05). Renal survival increased 8.2% per 10 nmol/L increase in 25(OH)D (P=0.03), independent of eGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis. In children with CKD, 25(OH)D ≥50 nmol/L was associated with greater preservation of renal function. This effect was present but attenuated with concomitant ACEi therapy.10.1681/ASN.2014090947Thu, 11 Jun 2015 06:59:48 GMT-07:00Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKDAngiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and vitamin D-fibroblast growth factor-23 (FGF-23)-Klotho pathways. To determine whether vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort. In 167 children (median eGFR 51 ml/min per 1.73 m2), serum 25-hydroxyvitamin D (25(OH)D), FGF-23, and Klotho levels were measured at baseline and after a median 8 months on ACEi. Children with lower 25(OH)D levels had higher urinary protein/creatinine ratios at baseline (P=0.03) and at follow-up (P=0.006). Levels of 25(OH)D and serum vitamin D-binding protein were not associated, but 25(OH)D ≤50 nmol/L associated with higher diastolic BP (P=0.004). ACEi therapy also associated with increased Klotho levels (P<0.001). The annualized loss of eGFR was inversely associated with baseline 25(OH)D level (P<0.001, r=0.32). Five-year renal survival was 75% in patients with baseline 25(OH)D ≥50 nmol/L and 50% in those with lower 25(OH)D levels (P<0.001). This renoprotective effect remained significant but attenuated with ACEi therapy (P=0.05). Renal survival increased 8.2% per 10 nmol/L increase in 25(OH)D (P=0.03), independent of eGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis. In children with CKD, 25(OH)D ≥50 nmol/L was associated with greater preservation of renal function. This effect was present but attenuated with concomitant ACEi therapy.Shroff, RukshanaAitkenhead, HelenCosta, NikolaTrivelli, AntonellaLitwin, MieczyslawPicca, StefanoAnarat, AliSallay, PeterOzaltin, FatihZurowska, AleksandraJankauskiene, AugustinaMontini, GiovanniCharbit, MarinaSchaefer, FranzWühl, Elke2015-06-11T06:59:48-07:00doi:10.1681/ASN.2014090947hwp:resource-id:jnephrol;27/1/314American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyvitamin D, chronic kidney disease, proteinuria, children, glomerular filtration rate, ACE inhibitorsClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20140909471046-66731533-34502015-06-11T06:59:48-07:002016-01Journal of the American Society of NephrologyClinical Research271314322
- Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO StudyLongitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49–0.89), cardiac events (HR, 0.71; 95% CI, 0.53–0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34–0.62) in time-dependent analyses. No significant associations of 1,25(OH)2D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13–2.18), cardiac events (HR, 1.49; 95% CI, 1.06–2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07–2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.10.1681/ASN.2014101009Wed, 13 May 2015 06:08:08 GMT-07:00Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO StudyLongitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49–0.89), cardiac events (HR, 0.71; 95% CI, 0.53–0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34–0.62) in time-dependent analyses. No significant associations of 1,25(OH)2D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13–2.18), cardiac events (HR, 1.49; 95% CI, 1.06–2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07–2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.Chonchol, MichelGreene, TomZhang, YingyingHoofnagle, Andrew N.Cheung, Alfred K.2015-05-13T06:08:08-07:00doi:10.1681/ASN.2014101009hwp:resource-id:jnephrol;27/1/227American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologychronic hemodialysis, chronic inflammation, epidemiology and outcomes, fibroblast, vitamin DClinical EpidemiologyClinical Epidemiologyresearch-article20162016-01-01January 201610.1681/ASN.20141010091046-66731533-34502015-05-13T06:08:08-07:002016-01Journal of the American Society of NephrologyClinical Epidemiology271227237
- Trimethylamine N-Oxide as a Novel Therapeutic Target in CKD10.1681/ASN.2015050576Thu, 30 Jul 2015 06:30:25 GMT-07:00Trimethylamine N-Oxide as a Novel Therapeutic Target in CKDTang, W.H. Wilson2015-07-30T06:30:25-07:00doi:10.1681/ASN.2015050576hwp:resource-id:jnephrol;27/1/8American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytrimethylamine N-oxide, coronary artery disease, CKDUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-01-01January 201610.1681/ASN.20150505761046-66731533-34502015-07-30T06:30:25-07:002016-01Journal of the American Society of NephrologyUp Front Matters2711830510313
- Endothelial Dysfunction: The Secret Agent Driving Kidney Disease10.1681/ASN.2015050502Tue, 02 Jun 2015 11:31:56 GMT-07:00Endothelial Dysfunction: The Secret Agent Driving Kidney DiseaseJohnson, Richard J.Nangaku, Masaomi2015-06-02T11:31:56-07:00doi:10.1681/ASN.2015050502hwp:resource-id:jnephrol;27/1/3American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical nephrology, endothelium, pathologyUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-01-01January 201610.1681/ASN.20150505021046-66731533-34502015-06-02T11:31:56-07:002016-01Journal of the American Society of NephrologyUp Front Matters271131205131
- Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion InjuryNatural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2α in T/NKT cells and found that HIF-2α knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2α knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1+ cell depletion or Fas ligand blockade. Compared with wild-type NKT cells, HIF-2α−/− NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2α-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2α−/− NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2α in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2α-knockout mice. Taken together, our results reveal a hypoxia/HIF-2α/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.10.1681/ASN.2014121248Fri, 08 May 2015 07:44:15 GMT-07:00Hypoxia-Inducible Factor-2α Limits Natural Killer T Cell Cytotoxicity in Renal Ischemia/Reperfusion InjuryNatural killer T (NKT) cells are the major early-acting immune cell type and fundamental immune modulators in ischemia-reperfusion injury (IRI). Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2α in T/NKT cells and found that HIF-2α knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. HIF-2α knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1+ cell depletion or Fas ligand blockade. Compared with wild-type NKT cells, HIF-2α−/− NKT cells adoptively transferred to Rag1-knockout mice elicited more severe renal injury, and these mice were not protected by CGS21680, an adenosine A2A receptor agonist. Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2α-dependent. Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2α−/− NKT cells. Finally, CGS21680 and LPS, an inducer of HIF-2α in endothelium, synergistically reduced renal IRI substantially, but this effect was absent in Mx1-Cre-induced global HIF-2α-knockout mice. Taken together, our results reveal a hypoxia/HIF-2α/adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI.Zhang, JianjunHan, ConghuiDai, HuijuanHou, JianquanDong, YangCui, XiaolanXu, LongmeiZhang, MingXia, Qiang2015-05-08T07:44:15-07:00doi:10.1681/ASN.2014121248hwp:resource-id:jnephrol;27/1/92American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyischemic renal failure, hypoxia, immunology, ischemia-reperfusionBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141212481046-66731533-34502015-05-08T07:44:15-07:002016-01Journal of the American Society of NephrologyBasic Research27192106
- Markers of Endothelial-to-Mesenchymal Transition: Evidence for Antibody-Endothelium Interaction during Antibody-Mediated Rejection in Kidney RecipientsAntibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.10.1681/ASN.2014070679Wed, 20 May 2015 07:59:59 GMT-07:00Markers of Endothelial-to-Mesenchymal Transition: Evidence for Antibody-Endothelium Interaction during Antibody-Mediated Rejection in Kidney RecipientsAntibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.Xu-Dubois, Yi-ChunPeltier, JulieBrocheriou, IsabelleSuberbielle-Boissel, CarolineDjamali, ArjangReese, ShannonMooney, NualaKeuylian, ZelaLion, JulienOuali, NacéraLevy, Pierre P.Jouanneau, ChantalRondeau, EricHertig, Alexandre2015-05-20T07:59:59-07:00doi:10.1681/ASN.2014070679hwp:resource-id:jnephrol;27/1/324American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant pathology, endothelium, rejection, antibody-mediated rejectionClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20140706791046-66731533-34502015-05-20T07:59:59-07:002016-01Journal of the American Society of NephrologyClinical Research271324332
- Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage PopulationsMacrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear. In this study, we used a renal bilateral ischemia-reperfusion injury mouse model to identify unique monocyte/macrophage populations by differential expression of Ly6C in CD11b+ cells and to define the function of these cells in the pathophysiology of disease on the basis of microarray gene signatures and reduction strategies. Macrophage populations were isolated from kidney homogenates by fluorescence-activated cell sorting for whole genome microarray analysis. The CD11b+/Ly6Chigh population associated with the onset of renal injury and increase in proinflammatory cytokines, whereas the CD11b+/Ly6Cintermediate population peaked during kidney repair. The CD11b+/Ly6Clow population emerged with developing renal fibrosis. Principal component and hierarchical cluster analyses identified gene signatures unique to each population. The CD11b+/Ly6Cintermediate population had a distinct phenotype of wound healing, confirmed by results of studies inhibiting the macrophage colony-stimulating factor 1 receptor,whereas the CD11b+/Ly6Clow population had a profibrotic phenotype. All populations, including the CD11b+/Ly6Chigh population, carried differential inflammatory signatures. The expression of M2-specific markers was detected in both the CD11b+/Ly6Cintermediate and CD11b+/Ly6Clow populations, suggesting these in vivo populations do not fit into the traditional classifications defined by in vitro systems. Results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b+/Ly6C+ monocyte/macrophage populations in the pathophysiology of disease after AKI.10.1681/ASN.2014111138Tue, 26 May 2015 08:19:21 GMT-07:00Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage PopulationsMacrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear. In this study, we used a renal bilateral ischemia-reperfusion injury mouse model to identify unique monocyte/macrophage populations by differential expression of Ly6C in CD11b+ cells and to define the function of these cells in the pathophysiology of disease on the basis of microarray gene signatures and reduction strategies. Macrophage populations were isolated from kidney homogenates by fluorescence-activated cell sorting for whole genome microarray analysis. The CD11b+/Ly6Chigh population associated with the onset of renal injury and increase in proinflammatory cytokines, whereas the CD11b+/Ly6Cintermediate population peaked during kidney repair. The CD11b+/Ly6Clow population emerged with developing renal fibrosis. Principal component and hierarchical cluster analyses identified gene signatures unique to each population. The CD11b+/Ly6Cintermediate population had a distinct phenotype of wound healing, confirmed by results of studies inhibiting the macrophage colony-stimulating factor 1 receptor,whereas the CD11b+/Ly6Clow population had a profibrotic phenotype. All populations, including the CD11b+/Ly6Chigh population, carried differential inflammatory signatures. The expression of M2-specific markers was detected in both the CD11b+/Ly6Cintermediate and CD11b+/Ly6Clow populations, suggesting these in vivo populations do not fit into the traditional classifications defined by in vitro systems. Results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b+/Ly6C+ monocyte/macrophage populations in the pathophysiology of disease after AKI.Clements, MeghanGershenovich, MichaelChaber, ChristopherCampos-Rivera, JuanitaDu, PanZhang, MindyLedbetter, SteveZuk, Anna2015-05-26T08:19:21-07:00doi:10.1681/ASN.2014111138hwp:resource-id:jnephrol;27/1/159American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologypathophysiology of renal disease and progression, ischemia-reperfusion, macrophages, gene expression, fibrosis, transcriptional profilingBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141111381046-66731533-34502015-05-26T08:19:21-07:002016-01Journal of the American Society of NephrologyBasic Research271159170
- The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive HumansThe renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D1-like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na+/day) and high (300 mmol Na+/day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D1-like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D1-like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions.10.1681/ASN.2014100958Thu, 14 May 2015 08:07:10 GMT-07:00The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive HumansThe renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D1-like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design. All subjects attained sodium balance on low (50 mmol Na+/day) and high (300 mmol Na+/day) NaCl diets, administered 4 weeks apart. Sodium, potassium, lithium, para-aminohippurate, and creatinine clearances were measured before, during, and after a 3-hour infusion of fenoldopam, a D1-like receptor agonist, with and without pretreatment with enalapril, an angiotensin converting enzyme inhibitor. On the high NaCl diet, fenoldopam-induced natriuresis was associated with the inhibition of renal proximal and distal tubule sodium transport. On the low NaCl diet, fenoldopam decreased renal distal tubule sodium transport but did not cause natriuresis. The addition of enalapril to fenoldopam restored the natriuretic effect of fenoldopam and its inhibitory effect on proximal tubule sodium transport. Thus, on a high NaCl diet fenoldopam causes natriuresis by inhibiting renal proximal and distal tubule transport, but on a low NaCl diet the increased RAAS activity prevents the D1-like receptor from inhibiting renal proximal tubule sodium transport, neutralizing the natriuretic effect of fenoldopam. These results demonstrate an interaction between the renin-angiotensin and renal dopaminergic systems in humans and highlight the influence of dietary NaCl on these interactions.Natarajan, Aruna R.Eisner, Gilbert M.Armando, InesBrowning, ShaunaghPezzullo, John C.Rhee, LaurenDajani, MustafaCarey, Robert M.Jose, Pedro A.2015-05-14T08:07:10-07:00doi:10.1681/ASN.2014100958hwp:resource-id:jnephrol;27/1/265American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologyhypertension, dopamine, enalapril, salt, natriuresisClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20141009581046-66731533-34502015-05-14T08:07:10-07:002016-01Journal of the American Society of NephrologyClinical Research271265279
- Donor-Specific HLA Antibody IgG Subclasses Are Associated with Phenotypes of Antibody-Mediated Rejection in Sensitized Renal Allograft Recipients10.1681/ASN.2015060608Thu, 20 Aug 2015 10:14:17 GMT-07:00Donor-Specific HLA Antibody IgG Subclasses Are Associated with Phenotypes of Antibody-Mediated Rejection in Sensitized Renal Allograft RecipientsJordan, Stanley C.2015-08-20T10:14:17-07:00doi:10.1681/ASN.2015060608hwp:resource-id:jnephrol;27/1/6American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyHLA, antibody, allograftUp Front MattersEditorialsUp Front MattersEditorialseditorial20162016-01-01January 201610.1681/ASN.20150606081046-66731533-34502015-08-20T10:14:17-07:002016-01Journal of the American Society of NephrologyUp Front Matters271162938304
- Podocyte p53 Limits the Severity of Experimental Alport SyndromeAlport syndrome (AS) is one of the most common types of inherited nephritis caused by mutation in one of the glomerular basement membrane components. AS is characterized by proteinuria at early stage of the disease and glomerular hyperplastic phenotype and renal fibrosis at late stage. Here, we show that global deficiency of tumor suppressor p53 significantly accelerated AS progression in X-linked AS mice and decreased the lifespan of these mice. p53 protein expression was detected in 21-week-old wild-type mice but not in age-matched AS mice. Expression of proinflammatory cytokines and profibrotic genes was higher in p53+/− AS mice than in p53+/+ AS mice. In vitro experiments revealed that p53 modulates podocyte migration and positively regulates the expression of podocyte-specific genes. We established podocyte-specific p53 (pod-p53)-deficient AS mice, and determined that pod-p53 deficiency enhanced the AS-induced renal dysfunction, foot process effacement, and alteration of gene-expression pattern in glomeruli. These results reveal a protective role of p53 in the progression of AS and in maintaining glomerular homeostasis by modulating the hyperplastic phenotype of podocytes in AS.10.1681/ASN.2014111109Tue, 12 May 2015 08:28:08 GMT-07:00Podocyte p53 Limits the Severity of Experimental Alport SyndromeAlport syndrome (AS) is one of the most common types of inherited nephritis caused by mutation in one of the glomerular basement membrane components. AS is characterized by proteinuria at early stage of the disease and glomerular hyperplastic phenotype and renal fibrosis at late stage. Here, we show that global deficiency of tumor suppressor p53 significantly accelerated AS progression in X-linked AS mice and decreased the lifespan of these mice. p53 protein expression was detected in 21-week-old wild-type mice but not in age-matched AS mice. Expression of proinflammatory cytokines and profibrotic genes was higher in p53+/− AS mice than in p53+/+ AS mice. In vitro experiments revealed that p53 modulates podocyte migration and positively regulates the expression of podocyte-specific genes. We established podocyte-specific p53 (pod-p53)-deficient AS mice, and determined that pod-p53 deficiency enhanced the AS-induced renal dysfunction, foot process effacement, and alteration of gene-expression pattern in glomeruli. These results reveal a protective role of p53 in the progression of AS and in maintaining glomerular homeostasis by modulating the hyperplastic phenotype of podocytes in AS.Fukuda, RyosukeSuico, Mary AnnKai, YukariOmachi, KoheiMotomura, KeishiKoga, TomoakiKomohara, YoshihiroKoyama, KosukeYokota, TsubasaTaura, ManabuShuto, TsuyoshiKai, Hirofumi2015-05-12T08:28:08-07:00doi:10.1681/ASN.2014111109hwp:resource-id:jnephrol;27/1/144American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyAlport-s syndrome, p53, podocyte, renal progression, p53 knockout, mouseBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20141111091046-66731533-34502015-05-12T08:28:08-07:002016-01Journal of the American Society of NephrologyBasic Research271144157
- Inhibition of SET Domain–Containing Lysine Methyltransferase 7/9 Ameliorates Renal FibrosisTGF-β1 activity results in methylation of lysine 4 of histone H3 (H3K4) through SET domain–containing lysine methyltransferase 7/9 (SET7/9) induction, which is important for the transcriptional activation of fibrotic genes in vitro. However, in vivo studies utilizing an experimental model of renal fibrosis are required to develop therapeutic interventions that target SET7/9. In this study, we investigated the signaling pathway of TGF-β1-induced SET7/9 expression and whether inhibition of SET7/9 suppresses renal fibrosis in unilateral ureteral obstruction (UUO) mice and kidney cell lines. Among the SET family, SET7/9 was upregulated on days 3 and 7 in UUO mice, and the upregulation was suppressed by TGF-β1 neutralizing antibody. TGF-β1 induced SET7/9 expression via Smad3 in normal rat kidney (NRK)-52E cells. In human kidney biopsy specimens from patients diagnosed with IgA nephropathy and membranous nephropathy, SET7/9 expression was positively correlated with the degree of interstitial fibrosis (r=0.59, P=0.001 in patients with IgA nephropathy; and r=0.58, P<0.05 in patients with membranous nephropathy). In addition, small interfering RNA-mediated knockdown of SET7/9 expression significantly attenuated renal fibrosis in UUO mice. Sinefungin, an inhibitor of SET7/9, also suppressed the expression of mesenchymal markers and extracellular matrix proteins and inhibited H3K4 mono-methylation (H3K4me1) in kidneys of UUO mice. Moreover, sinefungin had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and H3K4me1 in both NRK-52E and NRK-49F cells. In conclusion, sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4me1 and may be a candidate therapeutic agent.10.1681/ASN.2014090850Thu, 04 Jun 2015 07:24:17 GMT-07:00Inhibition of SET Domain–Containing Lysine Methyltransferase 7/9 Ameliorates Renal FibrosisTGF-β1 activity results in methylation of lysine 4 of histone H3 (H3K4) through SET domain–containing lysine methyltransferase 7/9 (SET7/9) induction, which is important for the transcriptional activation of fibrotic genes in vitro. However, in vivo studies utilizing an experimental model of renal fibrosis are required to develop therapeutic interventions that target SET7/9. In this study, we investigated the signaling pathway of TGF-β1-induced SET7/9 expression and whether inhibition of SET7/9 suppresses renal fibrosis in unilateral ureteral obstruction (UUO) mice and kidney cell lines. Among the SET family, SET7/9 was upregulated on days 3 and 7 in UUO mice, and the upregulation was suppressed by TGF-β1 neutralizing antibody. TGF-β1 induced SET7/9 expression via Smad3 in normal rat kidney (NRK)-52E cells. In human kidney biopsy specimens from patients diagnosed with IgA nephropathy and membranous nephropathy, SET7/9 expression was positively correlated with the degree of interstitial fibrosis (r=0.59, P=0.001 in patients with IgA nephropathy; and r=0.58, P<0.05 in patients with membranous nephropathy). In addition, small interfering RNA-mediated knockdown of SET7/9 expression significantly attenuated renal fibrosis in UUO mice. Sinefungin, an inhibitor of SET7/9, also suppressed the expression of mesenchymal markers and extracellular matrix proteins and inhibited H3K4 mono-methylation (H3K4me1) in kidneys of UUO mice. Moreover, sinefungin had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and H3K4me1 in both NRK-52E and NRK-49F cells. In conclusion, sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4me1 and may be a candidate therapeutic agent.Sasaki, KensukeDoi, ShigehiroNakashima, AyumuIrifuku, TaisukeYamada, KyokoKokoroishi, KeikoUeno, ToshinoriDoi, ToshikiHida, EisukeArihiro, KojiKohno, NobuokiMasaki, Takao2015-06-04T07:24:17-07:00doi:10.1681/ASN.2014090850hwp:resource-id:jnephrol;27/1/203American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycell signaling, obstructive nephropathy, renal fibrosis, TGF-βBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20140908501046-66731533-34502015-06-04T07:24:17-07:002016-01Journal of the American Society of NephrologyBasic Research271203215
- Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis BurdenTrimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r2=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.10.1681/ASN.2014111063Thu, 30 Jul 2015 06:30:25 GMT-07:00Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis BurdenTrimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r2=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.Stubbs, Jason R.House, John A.Ocque, A. JacobZhang, ShiqinJohnson, CassandraKimber, CassandraSchmidt, KyleGupta, AditiWetmore, James B.Nolin, Thomas D.Spertus, John A.Yu, Alan S.2015-07-30T06:30:25-07:00doi:10.1681/ASN.2014111063hwp:resource-id:jnephrol;27/1/305American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, CKD, coronary artery disease, ESRD, atherosclerosis, mortalityClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20141110631046-66731533-34502015-07-30T06:30:25-07:002016-01Journal of the American Society of NephrologyClinical Research2711305831310
- Serum-Mediated Inhibition of Enzyme Replacement Therapy in Fabry DiseaseFabry disease (FD) is a progressive multisystemic disorder, treatable with recombinant enzyme replacement therapy (agalsidase). However, recent studies suggest an endogenous inhibition of agalsidase in patients with FD, as reported for other lysosomal storage diseases. To assess the clinical consequences of serum-mediated agalsidase inhibition in affected patients, we determined the agalsidase inhibition status of 168 patients (68 male) with FD and compared outcomes of inhibition-positive patients with those of inhibition-negative patients. The assessment included clinical events during time on agalsidase, determination of renal and cardiac function, and evaluation of FD-related symptoms. The frequency of serum-mediated agalsidase inhibition was 40% in agalsidase-treated males. Inhibition did not depend on the compound initially used (agalsidase-α or -β). Agalsidase inhibition was associated with higher lyso-globotriaosylceramide levels and worse disease severity scores in patients. Compared with agalsidase inhibition-negative men, agalsidase inhibition-positive men showed greater left ventricular mass (P=0.02) and substantially lower renal function (difference in eGFR of about –30 ml/min per 1.73 m2; P=0.04), which was confirmed by a longitudinal 5-year retrospective analysis. Additionally, affected patients presented more often with FD-typical symptoms, such as diarrhea, fatigue, and neuropathic pain, among others. Therefore, patients with poor clinical outcome on agalsidase should be tested for agalsidase inhibition. Future studies are warranted to determine if affected patients with FD benefit from acute reduction of anti-agalsidase antibodies or long-term immune modulation therapies to suppress agalsidase inhibition and to identify mechanisms that minimize antibody generation against agalsidase.10.1681/ASN.2014121226Thu, 30 Apr 2015 07:36:48 GMT-07:00Serum-Mediated Inhibition of Enzyme Replacement Therapy in Fabry DiseaseFabry disease (FD) is a progressive multisystemic disorder, treatable with recombinant enzyme replacement therapy (agalsidase). However, recent studies suggest an endogenous inhibition of agalsidase in patients with FD, as reported for other lysosomal storage diseases. To assess the clinical consequences of serum-mediated agalsidase inhibition in affected patients, we determined the agalsidase inhibition status of 168 patients (68 male) with FD and compared outcomes of inhibition-positive patients with those of inhibition-negative patients. The assessment included clinical events during time on agalsidase, determination of renal and cardiac function, and evaluation of FD-related symptoms. The frequency of serum-mediated agalsidase inhibition was 40% in agalsidase-treated males. Inhibition did not depend on the compound initially used (agalsidase-α or -β). Agalsidase inhibition was associated with higher lyso-globotriaosylceramide levels and worse disease severity scores in patients. Compared with agalsidase inhibition-negative men, agalsidase inhibition-positive men showed greater left ventricular mass (P=0.02) and substantially lower renal function (difference in eGFR of about –30 ml/min per 1.73 m2; P=0.04), which was confirmed by a longitudinal 5-year retrospective analysis. Additionally, affected patients presented more often with FD-typical symptoms, such as diarrhea, fatigue, and neuropathic pain, among others. Therefore, patients with poor clinical outcome on agalsidase should be tested for agalsidase inhibition. Future studies are warranted to determine if affected patients with FD benefit from acute reduction of anti-agalsidase antibodies or long-term immune modulation therapies to suppress agalsidase inhibition and to identify mechanisms that minimize antibody generation against agalsidase.Lenders, MalteStypmann, JörgDuning, ThomasSchmitz, BorisBrand, Stefan-MartinBrand, Eva2015-04-30T19:36:48-07:00doi:10.1681/ASN.2014121226hwp:resource-id:jnephrol;27/1/256American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of NephrologyFabry disease, glomerular filtration rate, left ventricular mass, enzyme, replacement therapyClinical ResearchClinical Researchresearch-article20162016-01-01January 201610.1681/ASN.20141212261046-66731533-34502015-04-30T19:36:48-07:002016-01Journal of the American Society of NephrologyClinical Research271256264
- Calcineurin and Sorting-Related Receptor with A-Type Repeats Interact to Regulate the Renal Na+-K+-2Cl− CotransporterThe furosemide-sensitive Na+-K+-2Cl−-cotransporter (NKCC2) is crucial for NaCl reabsorption in kidney thick ascending limb (TAL) and drives the urine concentrating mechanism. NKCC2 activity is modulated by N-terminal phosphorylation and dephosphorylation. Serine-threonine kinases that activate NKCC2 have been identified, but less is known about phosphatases that deactivate NKCC2. Inhibition of calcineurin phosphatase has been shown to stimulate transport in the TAL and the distal convoluted tubule. Here, we identified NKCC2 as a target of the calcineurin Aβ isoform. Short-term cyclosporine administration in mice augmented the abundance of phospho-NKCC2, and treatment of isolated TAL with cyclosporine increased the chloride affinity and transport activity of NKCC2. Because sorting-related receptor with A-type repeats (SORLA) may affect NKCC2 phosphoregulation, we used SORLA-knockout mice to test whether SORLA is involved in calcineurin-dependent modulation of NKCC2. SORLA-deficient mice showed more calcineurin Aβ in the apical region of TAL cells and less NKCC2 phosphorylation and activity compared with littermate controls. In contrast, overexpression of SORLA in cultured cells reduced the abundance of endogenous calcineurin Aβ. Cyclosporine administration rapidly normalized the abundance of phospho-NKCC2 in SORLA-deficient mice, and a functional interaction between calcineurin Aβ and SORLA was further corroborated by binding assays in rat kidney extracts. In summary, we have shown that calcineurin Aβ and SORLA are key components in the phosphoregulation of NKCC2. These results may have clinical implications for immunosuppressive therapy using calcineurin inhibitors.10.1681/ASN.2014070728Tue, 12 May 2015 08:28:07 GMT-07:00Calcineurin and Sorting-Related Receptor with A-Type Repeats Interact to Regulate the Renal Na+-K+-2Cl− CotransporterThe furosemide-sensitive Na+-K+-2Cl−-cotransporter (NKCC2) is crucial for NaCl reabsorption in kidney thick ascending limb (TAL) and drives the urine concentrating mechanism. NKCC2 activity is modulated by N-terminal phosphorylation and dephosphorylation. Serine-threonine kinases that activate NKCC2 have been identified, but less is known about phosphatases that deactivate NKCC2. Inhibition of calcineurin phosphatase has been shown to stimulate transport in the TAL and the distal convoluted tubule. Here, we identified NKCC2 as a target of the calcineurin Aβ isoform. Short-term cyclosporine administration in mice augmented the abundance of phospho-NKCC2, and treatment of isolated TAL with cyclosporine increased the chloride affinity and transport activity of NKCC2. Because sorting-related receptor with A-type repeats (SORLA) may affect NKCC2 phosphoregulation, we used SORLA-knockout mice to test whether SORLA is involved in calcineurin-dependent modulation of NKCC2. SORLA-deficient mice showed more calcineurin Aβ in the apical region of TAL cells and less NKCC2 phosphorylation and activity compared with littermate controls. In contrast, overexpression of SORLA in cultured cells reduced the abundance of endogenous calcineurin Aβ. Cyclosporine administration rapidly normalized the abundance of phospho-NKCC2 in SORLA-deficient mice, and a functional interaction between calcineurin Aβ and SORLA was further corroborated by binding assays in rat kidney extracts. In summary, we have shown that calcineurin Aβ and SORLA are key components in the phosphoregulation of NKCC2. These results may have clinical implications for immunosuppressive therapy using calcineurin inhibitors.Borschewski, AljonaHimmerkus, NinaBoldt, ChristinBlankenstein, Katharina I.McCormick, James A.Lazelle, RebeccaWillnow, Thomas E.Jankowski, VeraPlain, AlleinBleich, MarkusEllison, David H.Bachmann, SebastianMutig, Kerim2015-05-12T08:28:07-07:00doi:10.1681/ASN.2014070728hwp:resource-id:jnephrol;27/1/107American Society of NephrologyCopyright © 2016 by the American Society of NephrologyJournal of the American Society of Nephrologycyclosporine, epithelial sodium transport, cell signalingBasic ResearchBasic Researchresearch-article20162016-01-01January 201610.1681/ASN.20140707281046-66731533-34502015-05-12T08:28:07-07:002016-01Journal of the American Society of NephrologyBasic Research271107119
- Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake10.2215/CJN.03830415Thu, 08 Oct 2015 09:09:44 GMT-07:00Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium IntakeKeyzer, Charlotte A.Lambers-Heerspink, Hiddo J.Joosten, Michel M.Deetman, Petronella E.Gansevoort, Ron T.Navis, GerjanKema, Ido P.de Zeeuw, DickBakker, Stephan J.L.de Borst, Martin H.2015-10-08T09:09:44-07:00doi:10.2215/CJN.03830415hwp:resource-id:clinjasn;10/12/2119American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrology25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, vitamin D, sodium, diet, chronic kidney disease, albuminuria, eGFR, creatinine, cystatin C, follow-up studies, humansOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-12-07December 07, 201510.2215/CJN.038304151555-90411555-905X2015-10-08T09:09:44-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221192127
- Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression10.2215/CJN.05220515Thu, 01 Oct 2015 06:28:58 GMT-07:00Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD ProgressionChen, Teresa K.Choi, Michael J.Kao, W.H. LindaAstor, Brad C.Scialla, Julia J.Appel, Lawrence J.Li, LiangLipkowitz, Michael S.Wolf, MylesParekh, Rulan S.Winkler, Cheryl A.Estrella, Michelle M.Crews, Deidra C.2015-10-01T06:28:58-07:00doi:10.2215/CJN.05220515hwp:resource-id:clinjasn;10/12/2128American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAASK (African American Study of Kidney Disease and Hypertension), chronic kidney disease, hypertension, apolipoprotein L1, 25-hydroxyvitamin D2, African Americans, blood pressure, body mass index, genotype kidney failure, chronic, fibroblast growth factor 23Original ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-12-07December 07, 201510.2215/CJN.052205151555-90411555-905X2015-10-01T06:28:58-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221282135
- Risk Stratification for Rejection and Infection after Kidney Transplantation10.2215/CJN.01790215Thu, 01 Oct 2015 06:28:59 GMT-07:00Risk Stratification for Rejection and Infection after Kidney TransplantationCippà, Pietro E.Schiesser, MarcEkberg, Henrikvan Gelder, TeunMueller, Nicolas J.Cao, Claude A.Fehr, ThomasBernasconi, Corrado2015-10-01T06:28:59-07:00doi:10.2215/CJN.01790215hwp:resource-id:clinjasn;10/12/2213American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologytransplant outcomes, transplant infectious disease, cause of death, cyclosporin, death, humans, immunosuppression, kidney transplantation, tacrolimus, transplant recipientsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20152015-12-07December 07, 201510.2215/CJN.017902151555-90411555-905X2015-10-01T06:28:59-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101222132220
- Risk Factors for Infection-Related Hospitalization in In-Center Hemodialysis10.2215/CJN.03050315Fri, 13 Nov 2015 09:02:25 GMT-08:00Risk Factors for Infection-Related Hospitalization in In-Center HemodialysisDalrymple, Lorien S.Mu, YiNguyen, Danh V.Romano, Patrick S.Chertow, Glenn M.Grimes, BarbaraKaysen, George A.Johansen, Kirsten L.2015-11-13T09:02:25-08:00doi:10.2215/CJN.03050315hwp:resource-id:clinjasn;10/12/2170American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, hemodialysis, epidemiology and outcomes, hospitalization, humans, kidney failure, chronic, renal dialysis, risk factors, serum albumin, social classOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-12-07December 07, 201510.2215/CJN.030503151555-90411555-905X2015-11-13T09:02:25-08:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1012122170210121802103
- Frailty and Cognitive Function in Incident Hemodialysis Patients10.2215/CJN.01960215Mon, 16 Nov 2015 01:48:34 GMT-08:00Frailty and Cognitive Function in Incident Hemodialysis PatientsMcAdams-DeMarco, Mara A.Tan, JingwenSalter, Megan L.Gross, AldenMeoni, Lucy A.Jaar, Bernard G.Kao, Wen-Hong LindaParekh, Rulan S.Segev, Dorry L.Sozio, Stephen M.2015-11-16T13:48:34-08:00doi:10.2215/CJN.01960215hwp:resource-id:clinjasn;10/12/2181American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyafrican american, black, hemodialysis, ESRD, epidemiology and outcomes, frailty, cognition, dementia, depression, kidney failure, chronic, renal dialysisOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-12-07December 07, 201510.2215/CJN.019602151555-90411555-905X2015-11-16T13:48:34-08:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1012122181210421892106
- Arterial Stiffness and Decline in Kidney Function10.2215/CJN.03000315Thu, 12 Nov 2015 07:15:14 GMT-08:00Arterial Stiffness and Decline in Kidney FunctionSedaghat, SanazMattace-Raso, Francesco U.S.Hoorn, Ewout J.Uitterlinden, Andre G.Hofman, AlbertIkram, M. ArfanFranco, Oscar H.Dehghan, Abbas2015-11-12T07:15:14-08:00doi:10.2215/CJN.03000315hwp:resource-id:clinjasn;10/12/2190American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymeta-analysis, chronic kidney disease, genetic risk score, arterial stiffness, pulse pressure, carotid stiffness, blood pressure, follow-up studies, pulse wave analysis, vascular stiffnessOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-12-07December 07, 201510.2215/CJN.030003151555-90411555-905X2015-11-12T07:15:14-08:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles1012122190210721972109
- Long-Term Risk of Cancer in Survivors of Pediatric ESRD10.2215/CJN.03630415Thu, 01 Oct 2015 06:28:59 GMT-07:00Long-Term Risk of Cancer in Survivors of Pediatric ESRDPloos van Amstel, SophieVogelzang, Judith L.Starink, Marcus V.Jager, Kitty J.Groothoff, Jaap W.2015-10-01T06:28:59-07:00doi:10.2215/CJN.03630415hwp:resource-id:clinjasn;10/12/2198American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal transplantation, end-stage renal disease, cancer, carcinoma, squamous cell, child, follow-up studies, kidney failure, chronic, neoplasms, renal insufficiency, chronic, survivorsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-12-07December 07, 201510.2215/CJN.036304151555-90411555-905X2015-10-01T06:28:59-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221982204
- AKI in Children Hospitalized with Nephrotic Syndrome10.2215/CJN.06620615Thu, 08 Oct 2015 09:09:43 GMT-07:00AKI in Children Hospitalized with Nephrotic SyndromeRheault, Michelle N.Zhang, LeiSelewski, David T.Kallash, MahmoudTran, Cheryl L.Seamon, MeredithKatsoufis, ChrysoAshoor, IsaHernandez, JoelSupe-Markovina, KatarinaD'Alessandri-Silva, CynthiaDeJesus-Gonzalez, NilkaVasylyeva, Tetyana L.Formeck, CassandraWoll, ChristopherGbadegesin, RasheedGeier, PavelDevarajan, PrasadCarpenter, Shannon L.Kerlin, Bryce A.Smoyer, William E.2015-10-08T09:09:43-07:00doi:10.2215/CJN.06620615hwp:resource-id:clinjasn;10/12/2110American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynephrotic syndrome, nephrotoxicity, length of stay, dialysis, acute kidney injury, child, hospitalization, humans, incidence, risk factorsOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20152015-12-07December 07, 201510.2215/CJN.066206151555-90411555-905X2015-10-08T09:09:43-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221102118
- Cytokines: Names and Numbers You Should Care AboutCytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.10.2215/CJN.07590714Mon, 04 May 2015 11:07:43 GMT-07:00Cytokines: Names and Numbers You Should Care AboutCytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.Holdsworth, Stephen R.Gan, Poh-Yi2015-05-04T11:07:43-07:00doi:10.2215/CJN.07590714hwp:resource-id:clinjasn;10/12/2243American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycytokines, clinical trial, nephrologyRenal ImmunologyRenal Immunologyresearch-article20152015-12-07December 07, 201510.2215/CJN.075907141555-90411555-905X2015-05-04T11:07:43-07:002015-12-07Clinical Journal of the American Society of NephrologyRenal Immunology101222432254
- Acid-Base HomeostasisAcid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.10.2215/CJN.07400715Mon, 23 Nov 2015 06:23:46 GMT-08:00Acid-Base HomeostasisAcid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.Hamm, L. LeeNakhoul, NazihHering-Smith, Kathleen S.2015-11-23T06:23:46-08:00doi:10.2215/CJN.07400715hwp:resource-id:clinjasn;10/12/2232American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal physiology, acid-base homeostasis, homeostasis, pH regulation, acid-base equilibrium, acidosis, bone density, kidney, nephrolithiasis, renal insufficiency, chronicRenal PhysiologyRenal Physiologyresearch-article20152015-12-07December 07, 201510.2215/CJN.074007151555-90411555-905X2015-11-23T06:23:46-08:002015-12-07Clinical Journal of the American Society of NephrologyRenal Physiology101222322242
- A Patient with Recurrent Arteriovenous Graft ThrombosisArteriovenous grafts (AVGs) are prone to frequent thrombosis that is superimposed on underlying hemodynamically significant stenosis, most commonly at the graft-vein anastomosis. There has been great interest in detecting AVG stenosis in a timely fashion and performing preemptive angioplasty, in the belief that this will prevent AVG thrombosis. Three surveillance methods (static dialysis venous pressure, flow monitoring, and duplex ultrasound) can detect AVG stenosis. Whereas observational studies have reported that surveillance with preemptive angioplasty substantially reduces AVG thrombosis, randomized clinical trials have failed to confirm such a benefit. There is a high frequency of early AVG restenosis after angioplasty caused by aggressive neointimal hyperplasia resulting from vascular injury. Stent grafts prevent AVG restenosis better than balloon angioplasty, but they do not prevent AVG thrombosis. Several pharmacologic interventions to prevent AVG failure have been evaluated in randomized clinical trials. Anticoagulation or aspirin plus clopidogrel do not prevent AVG thrombosis, but increase hemorrhagic events. Treatment of hyperhomocysteinemia does not prevent AVG thrombosis. Dipyridamole plus aspirin modestly decreases AVG stenosis or thrombosis. Fish oil substantially decreases the frequency of AVG stenosis and thrombosis. In patients who have exhausted all options for vascular access in the upper extremities, thigh AVGs are a superior option to tunneled internal jugular vein central vein catheters (CVCs). An immediate-use AVG is a reasonable option in patients with recurrent CVC dysfunction or infection. Tunneled femoral CVCs have much worse survival than internal jugular CVCs.10.2215/CJN.00190115Thu, 16 Apr 2015 09:12:56 GMT-07:00A Patient with Recurrent Arteriovenous Graft ThrombosisArteriovenous grafts (AVGs) are prone to frequent thrombosis that is superimposed on underlying hemodynamically significant stenosis, most commonly at the graft-vein anastomosis. There has been great interest in detecting AVG stenosis in a timely fashion and performing preemptive angioplasty, in the belief that this will prevent AVG thrombosis. Three surveillance methods (static dialysis venous pressure, flow monitoring, and duplex ultrasound) can detect AVG stenosis. Whereas observational studies have reported that surveillance with preemptive angioplasty substantially reduces AVG thrombosis, randomized clinical trials have failed to confirm such a benefit. There is a high frequency of early AVG restenosis after angioplasty caused by aggressive neointimal hyperplasia resulting from vascular injury. Stent grafts prevent AVG restenosis better than balloon angioplasty, but they do not prevent AVG thrombosis. Several pharmacologic interventions to prevent AVG failure have been evaluated in randomized clinical trials. Anticoagulation or aspirin plus clopidogrel do not prevent AVG thrombosis, but increase hemorrhagic events. Treatment of hyperhomocysteinemia does not prevent AVG thrombosis. Dipyridamole plus aspirin modestly decreases AVG stenosis or thrombosis. Fish oil substantially decreases the frequency of AVG stenosis and thrombosis. In patients who have exhausted all options for vascular access in the upper extremities, thigh AVGs are a superior option to tunneled internal jugular vein central vein catheters (CVCs). An immediate-use AVG is a reasonable option in patients with recurrent CVC dysfunction or infection. Tunneled femoral CVCs have much worse survival than internal jugular CVCs.Allon, Michael2015-04-16T09:12:56-07:00doi:10.2215/CJN.00190115hwp:resource-id:clinjasn;10/12/2255American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydialysis access, vascular access, arteriovenous graftAttending RoundsAttending Roundsresearch-article20152015-12-07December 07, 201510.2215/CJN.001901151555-90411555-905X2015-04-16T09:12:56-07:002015-12-07Clinical Journal of the American Society of NephrologyAttending Rounds101222552262
- Frailty and Cognitive Impairment in ESRD: Brain-Body Connections10.2215/CJN.11321015Mon, 16 Nov 2015 01:48:33 GMT-08:00Frailty and Cognitive Impairment in ESRD: Brain-Body ConnectionsSeliger, Stephen L.2015-11-16T13:48:33-08:00doi:10.2215/CJN.11321015hwp:resource-id:clinjasn;10/12/2104American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, hemodialysis, dementia, brain, cognition, cognition disordersEditorialsEditorialseditorial20152015-12-07December 07, 201510.2215/CJN.113210151555-90411555-905X2015-11-16T13:48:33-08:002015-12-07Clinical Journal of the American Society of NephrologyEditorials1012122104218121062189
- Targeting Blood Vessel Stiffness to Protect Kidney Function10.2215/CJN.11331015Thu, 12 Nov 2015 07:15:13 GMT-08:00Targeting Blood Vessel Stiffness to Protect Kidney FunctionDhaun, NeerajWebb, David J.2015-11-12T07:15:13-08:00doi:10.2215/CJN.11331015hwp:resource-id:clinjasn;10/12/2107American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarterial stiffness, glomerular filtration rate, renal function decline, chronic kidney diseaseEditorialsEditorialseditorial20152015-12-07December 07, 201510.2215/CJN.113310151555-90411555-905X2015-11-12T07:15:13-08:002015-12-07Clinical Journal of the American Society of NephrologyEditorials10121112210719792190210919882197
- BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes Trial10.2215/CJN.02850315Mon, 19 Oct 2015 06:56:00 GMT-07:00BP and Renal Outcomes in Diabetic Kidney Disease: The Veterans Affairs Nephropathy in Diabetes TrialLeehey, David J.Zhang, Jane H.Emanuele, Nicholas V.Whaley-Connell, AdamPalevsky, Paul M.Reilly, Robert F.Guarino, PeterFried, Linda F.2015-10-19T06:56:00-07:00doi:10.2215/CJN.02850315hwp:resource-id:clinjasn;10/12/2159American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, proteinuria, end-stage renal disease, progression of chronic kidney disease, blood pressure, diabetic nephropathies, follow-up studies, glomerular filtration rate, humans, kidney failure, chronicOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20152015-12-07December 07, 201510.2215/CJN.028503151555-90411555-905X2015-10-19T06:56:00-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221592169
- Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan AfricaCKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa.10.2215/CJN.11951214Thu, 02 Jul 2015 09:52:04 GMT-07:00Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan AfricaCKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa.Osafo, CharlotteRaji, Yemi RaheemBurke, DavidTayo, Bamidele O.Tiffin, NickiMoxey-Mims, Marva M.Rasooly, Rebekah S.Kimmel, Paul L.Ojo, AkinloluAdu, DwomoaParekh, Rulan S.,2015-07-02T09:52:04-07:00doi:10.2215/CJN.11951214hwp:resource-id:clinjasn;10/12/2279American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, APOL1, genes, ESRD, AfricansSpecial FeatureSpecial Featureresearch-article20152015-12-07December 07, 201510.2215/CJN.119512141555-90411555-905X2015-07-02T09:52:04-07:002015-12-07Clinical Journal of the American Society of NephrologySpecial Feature101222792287
- Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD10.2215/CJN.03640415Tue, 17 Nov 2015 06:31:04 GMT-08:00Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKDLepage, LaurenceDufour, Anne-ClaudeDoiron, JessicaHandfield, KatiaDesforges, KatherineBell, RobertVallée, MichelSavoie, MichelPerreault, SylvieLaurin, Louis-PhilippePichette, VincentLafrance, Jean-Philippe2015-11-17T06:31:04-08:00doi:10.2215/CJN.03640415hwp:resource-id:clinjasn;10/12/2136American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyperkalemia, randomized controlled trial, polystyrene sulfonic acid, kidney failure, chronic, double-blind method, humans, outpatients, polystyrenes, potassium, renal insufficiency, chronicOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20152015-12-07December 07, 201510.2215/CJN.036404151555-90411555-905X2015-11-17T06:31:04-08:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221362142
- Mild Chronic Hyponatremia in the Ambulatory Setting: Significance and ManagementMild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.10.2215/CJN.00170115Wed, 24 Jun 2015 12:39:22 GMT-07:00Mild Chronic Hyponatremia in the Ambulatory Setting: Significance and ManagementMild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.Rondon-Berrios, HelbertBerl, Tomas2015-06-24T12:39:22-07:00doi:10.2215/CJN.00170115hwp:resource-id:clinjasn;10/12/2268American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhyponatremia, mortality, morbidity, tolvaptan, ureaIn-Depth ReviewIn-Depth Reviewresearch-article20152015-12-07December 07, 201510.2215/CJN.001701151555-90411555-905X2015-06-24T12:39:22-07:002015-12-07Clinical Journal of the American Society of NephrologyIn-Depth Review101222682278
- Infections Requiring Hospitalization in Patients on Hemodialysis10.2215/CJN.10891015Fri, 13 Nov 2015 09:02:25 GMT-08:00Infections Requiring Hospitalization in Patients on HemodialysisGilbertson, David T.Wetmore, James B.2015-11-13T09:02:25-08:00doi:10.2215/CJN.10891015hwp:resource-id:clinjasn;10/12/2101American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhumans, renal dialysis, hemodialysis, hemodialysis access, hospitalizationEditorialsEditorialseditorial20152015-12-07December 07, 201510.2215/CJN.108910151555-90411555-905X2015-11-13T09:02:25-08:002015-12-07Clinical Journal of the American Society of NephrologyEditorials1012122101217021032180
- Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function10.2215/CJN.00980115Thu, 12 Nov 2015 07:15:13 GMT-08:00Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal FunctionAraki, Shin-ichiHaneda, MasakazuKoya, DaisukeKondo, KeikoTanaka, SachikoArima, HisatomiKume, ShinjiNakazawa, JunChin-Kanasaki, MasamiUgi, SatoshiKawai, HiromichiAraki, HisazumiUzu, TakashiMaegawa, Hiroshi2015-11-12T07:15:13-08:00doi:10.2215/CJN.00980115hwp:resource-id:clinjasn;10/12/2152American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycardiovascular disease, electrolytes, nutrition, diabetes mellitus, type 2, follow-up studies, myocardial infarction, peripheral vascular diseases, potassium, potassium, dietary, renal insufficiencyOriginal ArticlesDiabetes and the KidneyOriginal ArticlesDiabetes and the Kidneyresearch-article20152015-12-07December 07, 201510.2215/CJN.009801151555-90411555-905X2015-11-12T07:15:13-08:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221522158
- Emotional and Financial Experiences of Kidney Donors over the Past 50 Years: The RELIVE Study10.2215/CJN.07120714Tue, 13 Oct 2015 05:51:09 GMT-07:00Emotional and Financial Experiences of Kidney Donors over the Past 50 Years: The RELIVE StudyJacobs, Cheryl L.Gross, Cynthia R.Messersmith, Emily E.Hong, Barry A.Gillespie, Brenda W.Hill-Callahan, PegTaler, Sandra J.Jowsey, Sheila G.Beebe, Tim J.Matas, Arthur J.Odim, JonahIbrahim, Hassan N.2015-10-13T05:51:09-07:00doi:10.2215/CJN.07120714hwp:resource-id:clinjasn;10/12/2221American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologykidney donation, quality of life, renal transplantation, cost of illness, emotions, living donors, motivation, social support, tissue donors, vulnerable populationsOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20152015-12-07December 07, 201510.2215/CJN.071207141555-90411555-905X2015-10-13T05:51:09-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101222212231
- Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis10.2215/CJN.00120115Thu, 05 Nov 2015 07:20:15 GMT-08:00Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal VasculitisManenti, LucioVaglio, AugustoGnappi, ElisaMaggiore, UmbertoAllegri, LandinoAllinovi, MarcoUrban, Maria L.Delsante, MarcoGaletti, MariclaNicastro, MariaPilato, Francesco P.Buzio, Carlo2015-11-05T07:20:15-08:00doi:10.2215/CJN.00120115hwp:resource-id:clinjasn;10/12/2143American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycomplement, CKD progression, vasculitis, anti-neutrophil cytoplasmic antibody-associated vasculitis antibodies, antineutrophil cytoplasmic biopsy kidney failure, chronic thrombotic microangiopathiesOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20152015-12-07December 07, 201510.2215/CJN.001201151555-90411555-905X2015-11-05T07:20:15-08:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101221432151
- Balancing the Duty to Treat Patients with Ebola Virus Disease with the Risks to Dialysis PersonnelIn 2014, the author was invited to present at the American Society for Nephrology’s annual conference in Philadelphia on the ethics of treating patients with Ebola virus disease. The argument was made that the status of health care workers, including nephrologists, was the dominant ethical standard that generated both the duty to treat and the conflicts between this commitment and other ethical commitments that arise in public health emergencies. Conflicts between duty to treat and personal safety, duty to community, and duty to colleagues were illustrated, and suggestions for designing ethics into medical practice were given. This article is a summary of that presentation.10.2215/CJN.03730415Thu, 06 Aug 2015 06:47:46 GMT-07:00Balancing the Duty to Treat Patients with Ebola Virus Disease with the Risks to Dialysis PersonnelIn 2014, the author was invited to present at the American Society for Nephrology’s annual conference in Philadelphia on the ethics of treating patients with Ebola virus disease. The argument was made that the status of health care workers, including nephrologists, was the dominant ethical standard that generated both the duty to treat and the conflicts between this commitment and other ethical commitments that arise in public health emergencies. Conflicts between duty to treat and personal safety, duty to community, and duty to colleagues were illustrated, and suggestions for designing ethics into medical practice were given. This article is a summary of that presentation.Evans, Nicholas G.2015-08-06T06:47:46-07:00doi:10.2215/CJN.03730415hwp:resource-id:clinjasn;10/12/2263American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyprofessional ethics, duty to treat, Ebola virus diseaseEthics SeriesEthics Seriesresearch-article20152015-12-07December 07, 201510.2215/CJN.037304151555-90411555-905X2015-08-06T06:47:46-07:002015-12-07Clinical Journal of the American Society of NephrologyEthics Series101222632267
- Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption10.2215/CJN.03170315Tue, 27 Oct 2015 11:54:45 GMT-07:00Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose AbsorptionBernardo, Ana PaulaOliveira, Jose C.Santos, OliviaCarvalho, Maria J.Cabrita, AntonioRodrigues, Anabela2015-10-27T11:54:45-07:00doi:10.2215/CJN.03170315hwp:resource-id:clinjasn;10/12/2205American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologynutrition, insulin resistance, peritoneal glucose absorption, Adiponectin, Body Mass Index, diabetes mellitus, Insulin-Like Growth Factor Binding Protein 1 Leptin obesity peritoneal dialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-12-07December 07, 201510.2215/CJN.031703151555-90411555-905X2015-10-27T11:54:45-07:002015-12-07Clinical Journal of the American Society of NephrologyOriginal Articles101222052212
- Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and OrganizationGlomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein–protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.10.1681/ASN.2014040419Mon, 20 Apr 2015 09:27:21 GMT-07:00Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and OrganizationGlomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein–protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.Randles, Michael J.Woolf, Adrian S.Huang, Jennifer L.Byron, AdamHumphries, Jonathan D.Price, Karen L.Kolatsi-Joannou, MariaCollinson, SophieDenny, ThomasKnight, DavidMironov, AleksandrStarborg, TobyKorstanje, RonHumphries, Martin J.Long, David A.Lennon, Rachel2015-04-20T09:27:21-07:00doi:10.1681/ASN.2014040419hwp:resource-id:jnephrol;26/12/3021American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyextracellular matrix, cell-matrix-interactions, albuminuriaBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140404191046-66731533-34502015-04-20T09:27:21-07:002015-12Journal of the American Society of NephrologyBasic Research261230213034
- Complete and Partial Remission as Surrogate End Points in Membranous NephropathyAbsent a remission of proteinuria, primary membranous nephropathy (MN) can lead to ESRD over many years. Therefore, use of an earlier end point could facilitate the conduct of clinical trials. This manuscript evaluates complete remission (CR) and partial remission (PR) of proteinuria as surrogate end points for a treatment effect on ESRD in patients with primary MN with heavy proteinuria. CR is associated with a low relapse rate and excellent long–term renal survival, and it plausibly reflects remission of the disease process that leads to ESRD. Patients who achieve PR have better renal outcomes than those who do not but may have elevated relapse rates. How long PR must be maintained to yield a benefit on renal outcomes is also unknown. Hence, available data suggest that CR could be used as a surrogate end point in primary MN, whereas PR seems reasonably likely to predict clinical benefit. In the United States, surrogate end points that are reasonably likely to predict clinical benefit can be used as a basis for accelerated approval; treatments approved under this program must verify the clinical benefit in postmarketing trials. Additional analyses of the relationship between treatment effects on CR and PR and subsequent renal outcomes would inform the design of future clinical trials in primary MN.10.1681/ASN.2015010091Mon, 15 Jun 2015 07:15:00 GMT-07:00Complete and Partial Remission as Surrogate End Points in Membranous NephropathyAbsent a remission of proteinuria, primary membranous nephropathy (MN) can lead to ESRD over many years. Therefore, use of an earlier end point could facilitate the conduct of clinical trials. This manuscript evaluates complete remission (CR) and partial remission (PR) of proteinuria as surrogate end points for a treatment effect on ESRD in patients with primary MN with heavy proteinuria. CR is associated with a low relapse rate and excellent long–term renal survival, and it plausibly reflects remission of the disease process that leads to ESRD. Patients who achieve PR have better renal outcomes than those who do not but may have elevated relapse rates. How long PR must be maintained to yield a benefit on renal outcomes is also unknown. Hence, available data suggest that CR could be used as a surrogate end point in primary MN, whereas PR seems reasonably likely to predict clinical benefit. In the United States, surrogate end points that are reasonably likely to predict clinical benefit can be used as a basis for accelerated approval; treatments approved under this program must verify the clinical benefit in postmarketing trials. Additional analyses of the relationship between treatment effects on CR and PR and subsequent renal outcomes would inform the design of future clinical trials in primary MN.Thompson, AlizaCattran, Daniel C.Blank, MelanieNachman, Patrick H.2015-06-15T07:15:00-07:00doi:10.1681/ASN.2015010091hwp:resource-id:jnephrol;26/12/2930American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular disease, membranous nephropathy, nephrotic syndrome, outcomes, surrogate outcomesUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20152015-12-01December 201510.1681/ASN.20150100911046-66731533-34502015-06-15T07:15:00-07:002015-12Journal of the American Society of NephrologyUp Front Matters261229302937
- The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic LesionsOver 10 years have passed since the latest revision of the histopathologic classification of lupus nephritis. This revision was a significant improvement compared with the previous version, mainly because of clearer and more concise definitions and the elimination of mixed subclasses. Despite these improvements, there are still some difficulties in the classification for lupus nephritis, many of which are in the definitions provided. In this review, we focus on the difficulties surrounding the evaluation of classes III and IV lesions, particularly the definitions of endocapillary and extracapillary proliferation, the use of the terms endocapillary proliferation and hypercellularity, the clinical relevance of segmental and global subdivision in class IV, and the value of distinguishing lesions that indicate activity and chronicity. Vascular and tubulointerstitial lesions are also discussed. Furthermore, we give an overview of the history of the classification to provide background on the origin and development of the definitions in lupus nephritis. The issues raised in this review as well as the suggestions for improvements may assist with a revision of the lupus nephritis classification in the near future.10.1681/ASN.2015040384Tue, 07 Jul 2015 12:05:37 GMT-07:00The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic LesionsOver 10 years have passed since the latest revision of the histopathologic classification of lupus nephritis. This revision was a significant improvement compared with the previous version, mainly because of clearer and more concise definitions and the elimination of mixed subclasses. Despite these improvements, there are still some difficulties in the classification for lupus nephritis, many of which are in the definitions provided. In this review, we focus on the difficulties surrounding the evaluation of classes III and IV lesions, particularly the definitions of endocapillary and extracapillary proliferation, the use of the terms endocapillary proliferation and hypercellularity, the clinical relevance of segmental and global subdivision in class IV, and the value of distinguishing lesions that indicate activity and chronicity. Vascular and tubulointerstitial lesions are also discussed. Furthermore, we give an overview of the history of the classification to provide background on the origin and development of the definitions in lupus nephritis. The issues raised in this review as well as the suggestions for improvements may assist with a revision of the lupus nephritis classification in the near future.Wilhelmus, SuzanneAlpers, Charles E.Cook, H. TerenceFerrario, FrancoFogo, Agnes B.Haas, MarkJoh, KensukeNoël, Laure-HélèneSeshan, Surya V.Bruijn, Jan A.Bajema, Ingeborg M.2015-07-07T12:05:37-07:00doi:10.1681/ASN.2015040384hwp:resource-id:jnephrol;26/12/2938American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologylupus nephritis, renal biopsy, renal pathology, systemic lupus, erythematosusUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20152015-12-01December 201510.1681/ASN.20150403841046-66731533-34502015-07-07T12:05:37-07:002015-12Journal of the American Society of NephrologyUp Front Matters261229382946
- Reassessing the Significance of Intimal Arteritis in Kidney Transplant Biopsy SpecimensIntimal arteritis (the presence of v-lesions) in kidney transplant biopsy specimens is believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis in 703 indication biopsy specimens and used microarray-based molecular tests to re-examine the relationship of v-lesions to rejection. v-Lesions were noted in 49 specimens (7%) and were usually mild (v1). The presence of v-lesions had no effect on graft survival compared with the absence of v-lesions. Pathologists using current conventions almost always interpreted v-lesions as reflecting T cell–mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). The molecular scores questioned the conventional diagnoses in 29 of 49 specimens (59%), including ten that were conventional TCMR with no molecular rejection and nine that were conventional TCMR mixed with pure ABMR molecularly. The presence of tubulointerstitial inflammation (i-t) meeting TCMR criteria allowed subclassification of v-lesion specimens into 21 i-t-v-lesion specimens and 28 isolated v-lesion specimens. Molecular TCMR scores were positive in 95% of i-t-v-lesion specimens but only 21% of isolated v-lesion specimens. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%). Time of biopsy after transplantation was critical for understanding isolated v-lesions: most early isolated v-lesion specimens had no molecular rejection and were DSA negative, whereas most isolated >1 year after transplantation had positive DSA and ABMR scores. Therefore, v-lesions in indication biopsy specimens do not affect prognosis and can reflect TCMR, ABMR, or no rejection. Time after transplantation, DSA, and accompanying inflammation provide probabilistic basis for interpreting v-lesions.10.1681/ASN.2014111064Mon, 27 Apr 2015 05:08:41 GMT-07:00Reassessing the Significance of Intimal Arteritis in Kidney Transplant Biopsy SpecimensIntimal arteritis (the presence of v-lesions) in kidney transplant biopsy specimens is believed to have major prognostic and diagnostic significance. We assessed the relationship of v-lesions to prognosis in 703 indication biopsy specimens and used microarray-based molecular tests to re-examine the relationship of v-lesions to rejection. v-Lesions were noted in 49 specimens (7%) and were usually mild (v1). The presence of v-lesions had no effect on graft survival compared with the absence of v-lesions. Pathologists using current conventions almost always interpreted v-lesions as reflecting T cell–mediated rejection (TCMR), either pure or mixed with antibody-mediated rejection (ABMR). The molecular scores questioned the conventional diagnoses in 29 of 49 specimens (59%), including ten that were conventional TCMR with no molecular rejection and nine that were conventional TCMR mixed with pure ABMR molecularly. The presence of tubulointerstitial inflammation (i-t) meeting TCMR criteria allowed subclassification of v-lesion specimens into 21 i-t-v-lesion specimens and 28 isolated v-lesion specimens. Molecular TCMR scores were positive in 95% of i-t-v-lesion specimens but only 21% of isolated v-lesion specimens. Molecular ABMR scores were often positive in isolated v-lesion biopsies (46%). Time of biopsy after transplantation was critical for understanding isolated v-lesions: most early isolated v-lesion specimens had no molecular rejection and were DSA negative, whereas most isolated >1 year after transplantation had positive DSA and ABMR scores. Therefore, v-lesions in indication biopsy specimens do not affect prognosis and can reflect TCMR, ABMR, or no rejection. Time after transplantation, DSA, and accompanying inflammation provide probabilistic basis for interpreting v-lesions.Salazar, Israel D.R.López, Maribel MerinoChang, JessicaHalloran, Philip F.2015-04-27T05:08:41-07:00doi:10.1681/ASN.2014111064hwp:resource-id:jnephrol;26/12/3190American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologykidney biopsy, kidney, kidney transplantationClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20141110641046-66731533-34502015-04-27T05:08:41-07:002015-12Journal of the American Society of NephrologyClinical Research261231903198
- Moving Beyond Minimization Trials in Kidney Transplantation10.1681/ASN.2015030245Wed, 29 Apr 2015 10:30:10 GMT-07:00Moving Beyond Minimization Trials in Kidney TransplantationMatas, Arthur J.Gaston, Robert S.2015-04-29T10:30:10-07:00doi:10.1681/ASN.2015030245hwp:resource-id:jnephrol;26/12/2898American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyimmunosuppression, drug minimization, renal transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-12-01December 201510.1681/ASN.20150302451046-66731533-34502015-04-29T10:30:10-07:002015-12Journal of the American Society of NephrologyUp Front Matters2612122898311429013122
- Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft SurvivalProgress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.10.1681/ASN.2014080804Wed, 08 Apr 2015 01:17:14 GMT-07:00Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft SurvivalProgress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival.Batal, IbrahimDe Serres, Sacha A.Safa, KassemBijol, VanesaUeno, TakuyaOnozato, Maristela L.Iafrate, A. JohnHerter, Jan M.Lichtman, Andrew H.Mayadas, Tanya N.Guleria, IndiraRennke, Helmut G.Najafian, NaderChandraker, Anil2015-04-08T13:17:14-07:00doi:10.1681/ASN.2014080804hwp:resource-id:jnephrol;26/12/3102American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologytransplant pathology, chronic inflammation, chronic graft deteriorationClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140808041046-66731533-34502015-04-08T13:17:14-07:002015-12Journal of the American Society of NephrologyClinical Research261231023113
- Adverse Outcomes of Tacrolimus Withdrawal in Immune–Quiescent Kidney Transplant RecipientsConcerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor–reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.10.1681/ASN.2014121234Wed, 29 Apr 2015 10:30:11 GMT-07:00Adverse Outcomes of Tacrolimus Withdrawal in Immune–Quiescent Kidney Transplant RecipientsConcerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor–reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.Hricik, Donald E.Formica, Richard N.Nickerson, PeterRush, DavidFairchild, Robert L.Poggio, Emilio D.Gibson, Ian W.Wiebe, ChrisTinckam, KathrynBunnapradist, SuphamaiSamaniego-Picota, MilagrosBrennan, Daniel C.Schröppel, BerndGaber, OsamaArmstrong, BrianIkle, DavidDiop, HelenaBridges, Nancy D.Heeger, Peter S.2015-04-29T10:30:11-07:00doi:10.1681/ASN.2014121234hwp:resource-id:jnephrol;26/12/3114American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal transplantation, rejection, immunosuppressionClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20141212341046-66731533-34502015-04-29T10:30:11-07:002015-12Journal of the American Society of NephrologyClinical Research2612123114289831222901
- Bridging Translation by Improving Preclinical Study Design in AKIDespite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.10.1681/ASN.2015070832Wed, 04 Nov 2015 10:27:55 GMT-08:00Bridging Translation by Improving Preclinical Study Design in AKIDespite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.de Caestecker, MarkHumphreys, Ben D.Liu, Kathleen D.Fissell, William H.Cerda, JorgeNolin, Thomas D.Askenazi, DavidMour, GirishHarrell, Frank E.Pullen, NickOkusa, Mark D.Faubel, Sarah2015-11-04T10:27:55-08:00doi:10.1681/ASN.2015070832hwp:resource-id:jnephrol;26/12/2905American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute kidney injury, preclinical research, reproducibilityUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20152015-12-01December 201510.1681/ASN.20150708321046-66731533-34502015-11-04T10:27:55-08:002015-12Journal of the American Society of NephrologyUp Front Matters2612122905289129162893
- Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway: An Etiologic ApproachKidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway (AP) are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage. The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. Nevertheless, we contend that these diseases should be grouped as disorders of the AP and classified on an etiologic basis. In this review, we define different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.10.1681/ASN.2015020184Thu, 16 Jul 2015 06:29:58 GMT-07:00Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway: An Etiologic ApproachKidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway (AP) are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage. The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. Nevertheless, we contend that these diseases should be grouped as disorders of the AP and classified on an etiologic basis. In this review, we define different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.De Vriese, An S.Sethi, SanjeevVan Praet, JensNath, Karl A.Fervenza, Fernando C.2015-07-16T06:29:58-07:00doi:10.1681/ASN.2015020184hwp:resource-id:jnephrol;26/12/2917American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, GN, hemolytic uremic syndromeUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20152015-12-01December 201510.1681/ASN.20150201841046-66731533-34502015-07-16T06:29:58-07:002015-12Journal of the American Society of NephrologyUp Front Matters261229172929
- Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac SurgeryAdministration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m2. In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.10.1681/ASN.2014080840Thu, 07 May 2015 06:59:17 GMT-07:00Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac SurgeryAdministration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m2. In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.Jacob, Kirolos A.Leaf, David E.Dieleman, Jan M.van Dijk, DiederikNierich, Arno P.Rosseel, Peter M.van der Maaten, Joost M.Hofland, JanDiephuis, Jan C.de Lange, FelleryBoer, ChristineKluin, JolandaWaikar, Sushrut S.2015-05-07T06:59:17-07:00doi:10.1681/ASN.2014080840hwp:resource-id:jnephrol;26/12/2947American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, dialysis, clinical trial, cardiovascular, creatinine, ischemia–reperfusionBrief CommunicationBrief Communicationbrief-report20152015-12-01December 201510.1681/ASN.20140808401046-66731533-34502015-05-07T06:59:17-07:002015-12Journal of the American Society of NephrologyBrief Communication261229472951
- Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic SyndromeThrombotic disease, a major life–threatening complication of nephrotic syndrome, has been associated with proteinuria and hypoalbuminemia severity. However, it is not fully understood how disease severity correlates with severity of the acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk remains limited. Here, we show that two well established ex vivo hypercoagulopathy assays, thrombin generation and rotational thromboelastometry, are highly correlated with proteinuria and hypoalbuminemia in the puromycin aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the puromycin aminonucleoside model, hyperfibrinogenemia and antithrombin deficiency were also correlated with proteinuria severity, consistent with reports in human nephrotic syndrome. Importantly, although coagulation was not spontaneously activated in vivo with increasing proteinuria, vascular injury induced a more robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy is highly correlated with nephrotic disease severity, but overt thrombosis may require an initiating insult, such as vascular injury. Our results suggest that proteinuria and/or hypoalbuminemia could be developed as clinically meaningful surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic syndrome at highest risk for thrombotic disease and potentially target them for anticoagulant pharmacoprophylaxis.10.1681/ASN.2014111097Wed, 08 Apr 2015 01:17:15 GMT-07:00Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic SyndromeThrombotic disease, a major life–threatening complication of nephrotic syndrome, has been associated with proteinuria and hypoalbuminemia severity. However, it is not fully understood how disease severity correlates with severity of the acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk remains limited. Here, we show that two well established ex vivo hypercoagulopathy assays, thrombin generation and rotational thromboelastometry, are highly correlated with proteinuria and hypoalbuminemia in the puromycin aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the puromycin aminonucleoside model, hyperfibrinogenemia and antithrombin deficiency were also correlated with proteinuria severity, consistent with reports in human nephrotic syndrome. Importantly, although coagulation was not spontaneously activated in vivo with increasing proteinuria, vascular injury induced a more robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy is highly correlated with nephrotic disease severity, but overt thrombosis may require an initiating insult, such as vascular injury. Our results suggest that proteinuria and/or hypoalbuminemia could be developed as clinically meaningful surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic syndrome at highest risk for thrombotic disease and potentially target them for anticoagulant pharmacoprophylaxis.Kerlin, Bryce A.Waller, Amanda P.Sharma, RuchikaChanley, Melinda A.Nieman, Marvin T.Smoyer, William E.2015-04-08T13:17:15-07:00doi:10.1681/ASN.2014111097hwp:resource-id:jnephrol;26/12/3009American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, hypoalbuminemia, nephrotic syndrome, thrombosis, vascular, disease, cardiovascular diseaseBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20141110971046-66731533-34502015-04-08T13:17:15-07:002015-12Journal of the American Society of NephrologyBasic Research261230093019
- APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy StudyAPOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (Nglom) and mean glomerular volume (Vglom) were measured by the dissector/fractionator method in kidneys of African-American and non–African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in Nglom and increases in Vglom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥30 kg/m2, enhanced the expression of age-related changes in Nglom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.10.1681/ASN.2014080768Tue, 02 Jun 2015 11:31:55 GMT-07:00APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy StudyAPOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (Nglom) and mean glomerular volume (Vglom) were measured by the dissector/fractionator method in kidneys of African-American and non–African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in Nglom and increases in Vglom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥30 kg/m2, enhanced the expression of age-related changes in Nglom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.Hoy, Wendy E.Hughson, Michael D.Kopp, Jeffrey B.Mott, Susan A.Bertram, John F.Winkler, Cheryl A.2015-06-02T11:31:55-07:00doi:10.1681/ASN.2014080768hwp:resource-id:jnephrol;26/12/3179American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyAPOL1 risk alleles, glomerular number, glomerular enlargement, African AmericansClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140807681046-66731533-34502015-06-02T11:31:55-07:002015-12Journal of the American Society of NephrologyClinical Research2612123179290131892903
- This Month's Highlights10.1681/ASN.2015080970Mon, 30 Nov 2015 10:01:19 GMT-08:00This Month's HighlightsAmerican Society of Nephrology2015-11-30T10:01:19-08:00doi:10.1681/ASN.2015080970hwp:resource-id:jnephrol;26/12/iAmerican Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20152015-12-01December 201510.1681/ASN.20150809701046-66731533-34502015-11-30T10:01:19-08:002015-12Journal of the American Society of NephrologyThis Month's Highlights2612ii
- Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac SurgeryInflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a ≥50% or ≥0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.10.1681/ASN.2014080764Wed, 08 Apr 2015 01:17:15 GMT-07:00Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac SurgeryInflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a ≥50% or ≥0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.Zhang, William R.Garg, Amit X.Coca, Steven G.Devereaux, Philip J.Eikelboom, JohnKavsak, PeterMcArthur, EricThiessen-Philbrook, HeatherShortt, ColleenShlipak, MichaelWhitlock, RichardParikh, Chirag R.2015-04-08T13:17:15-07:00doi:10.1681/ASN.2014080764hwp:resource-id:jnephrol;26/12/3123American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycytokines, mortality, Epidemiology and outcomes, clinical epidemiologyClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140807641046-66731533-34502015-04-08T13:17:15-07:002015-12Journal of the American Society of NephrologyClinical Research261231233132
- Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood PressureThe fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10−5) and diastolic BP (P=7.61×10−3) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10−3). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.10.1681/ASN.2014121211Mon, 27 Apr 2015 05:08:41 GMT-07:00Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood PressureThe fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10−5) and diastolic BP (P=7.61×10−3) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10−3). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.Tomaszewski, MaciejEales, JamesDenniff, MatthewMyers, StephenChew, Guat SiewNelson, Christopher P.Christofidou, ParaskeviDesai, AishwaryaBüsst, CaraWojnar, LukaszMusialik, KatarzynaJozwiak, JacekDebiec, RadoslawDominiczak, Anna F.Navis, Gerjanvan Gilst, Wiek H.van der Harst, PimSamani, Nilesh J.Harrap, StephenBogdanski, PawelZukowska-Szczechowska, EwaCharchar, Fadi J.2015-04-27T05:08:41-07:00doi:10.1681/ASN.2014121211hwp:resource-id:jnephrol;26/12/3151American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologygene expression, gene transcription, hypertension, blood pressure, glomerulus, kidneyClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20141212111046-66731533-34502015-04-27T05:08:41-07:002015-12Journal of the American Society of NephrologyClinical Research261231513160
- Glomerular Aging and Focal Global Glomerulosclerosis: A Podometric PerspectiveKidney aging is associated with an increasing proportion of globally scarred glomeruli, decreasing renal function, and exponentially increasing ESRD prevalence. In model systems, podocyte depletion causes glomerulosclerosis, suggesting age-associated glomerulosclerosis could be caused by a similar mechanism. We measured podocyte number, size, density, and glomerular volume in 89 normal kidney samples from living and deceased kidney donors and normal poles of nephrectomies. Podocyte nuclear density decreased with age due to a combination of decreased podocyte number per glomerulus and increased glomerular volume. Compensatory podocyte cell hypertrophy prevented a change in the proportion of tuft volume occupied by podocytes. Young kidneys had high podocyte reserve (podocyte density >300 per 106 µm3), but by 70–80 years of age, average podocyte nuclear density decreased to, <100 per 106 µm3, with corresponding podocyte hypertrophy. In older age podocyte detachment rate (urine podocin mRNA-to-creatinine ratio) was higher than at younger ages and podocytes were stressed (increased urine podocin-to-nephrin mRNA ratio). Moreover, in older kidneys, proteinaceous material accumulated in the Bowman space of glomeruli with low podocyte density. In a subset of these glomeruli, mass podocyte detachment events occurred in association with podocytes becoming binucleate (mitotic podocyte catastrophe) and subsequent wrinkling of glomerular capillaries, tuft collapse, and periglomerular fibrosis. In kidneys of young patients with underlying glomerular diseases similar pathologic events were identified in association with focal global glomerulosclerosis. Podocyte density reduction with age may therefore directly lead to focal global glomerulosclerosis, and all progressive glomerular diseases can be considered superimposed accelerators of this underlying process.10.1681/ASN.2014080752Tue, 02 Jun 2015 11:31:53 GMT-07:00Glomerular Aging and Focal Global Glomerulosclerosis: A Podometric PerspectiveKidney aging is associated with an increasing proportion of globally scarred glomeruli, decreasing renal function, and exponentially increasing ESRD prevalence. In model systems, podocyte depletion causes glomerulosclerosis, suggesting age-associated glomerulosclerosis could be caused by a similar mechanism. We measured podocyte number, size, density, and glomerular volume in 89 normal kidney samples from living and deceased kidney donors and normal poles of nephrectomies. Podocyte nuclear density decreased with age due to a combination of decreased podocyte number per glomerulus and increased glomerular volume. Compensatory podocyte cell hypertrophy prevented a change in the proportion of tuft volume occupied by podocytes. Young kidneys had high podocyte reserve (podocyte density >300 per 106 µm3), but by 70–80 years of age, average podocyte nuclear density decreased to, <100 per 106 µm3, with corresponding podocyte hypertrophy. In older age podocyte detachment rate (urine podocin mRNA-to-creatinine ratio) was higher than at younger ages and podocytes were stressed (increased urine podocin-to-nephrin mRNA ratio). Moreover, in older kidneys, proteinaceous material accumulated in the Bowman space of glomeruli with low podocyte density. In a subset of these glomeruli, mass podocyte detachment events occurred in association with podocytes becoming binucleate (mitotic podocyte catastrophe) and subsequent wrinkling of glomerular capillaries, tuft collapse, and periglomerular fibrosis. In kidneys of young patients with underlying glomerular diseases similar pathologic events were identified in association with focal global glomerulosclerosis. Podocyte density reduction with age may therefore directly lead to focal global glomerulosclerosis, and all progressive glomerular diseases can be considered superimposed accelerators of this underlying process.Hodgin, Jeffrey B.Bitzer, MarkusWickman, LarysaAfshinnia, FarsadWang, Su QO’Connor, ChristopherYang, YanMeadowbrooke, ChrystaChowdhury, MahboobKikuchi, MasaoWiggins, Jocelyn E.Wiggins, Roger C.2015-06-02T11:31:53-07:00doi:10.1681/ASN.2014080752hwp:resource-id:jnephrol;26/12/3162American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyaging, podocyte, glomerulosclerosisClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140807521046-66731533-34502015-06-02T11:31:53-07:002015-12Journal of the American Society of NephrologyClinical Research2612123162290131782903
- Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of HypercalciuriaPotassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.10.1681/ASN.2014121223Wed, 08 Apr 2015 01:17:18 GMT-07:00Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of HypercalciuriaPotassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.Krieger, Nancy S.Asplin, John R.Frick, Kevin K.Granja, IgnacioCulbertson, Christopher D.Ng, AdelineGrynpas, Marc D.Bushinsky, David A.2015-04-08T13:17:18-07:00doi:10.1681/ASN.2014121223hwp:resource-id:jnephrol;26/12/3001American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyhypercalciuria, kidney stones, mineral metabolismBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20141212231046-66731533-34502015-04-08T13:17:18-07:002015-12Journal of the American Society of NephrologyBasic Research261230013008
- Oxidative Stress and Metabolism: The NF–Erythroid 2 p45–Related Factor 2:Kelch–like ECH–Associated Protein 1 System and Regulatory T Lymphocytes in Ischemic AKI10.1681/ASN.2015060720Thu, 20 Aug 2015 10:14:14 GMT-07:00Oxidative Stress and Metabolism: The NF–Erythroid 2 p45–Related Factor 2:Kelch–like ECH–Associated Protein 1 System and Regulatory T Lymphocytes in Ischemic AKILu, Christopher Y.de Albuquerque Rocha, Natalia2015-08-20T10:14:14-07:00doi:10.1681/ASN.2015060720hwp:resource-id:jnephrol;26/12/2893American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyoxidative stress, metabolism, AKIUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-12-01December 201510.1681/ASN.20150607201046-66731533-34502015-08-20T10:14:14-07:002015-12Journal of the American Society of NephrologyUp Front Matters2612122893298928953000
- Models of Human AKI: Resemblance, Reproducibility, and Return on Investment10.1681/ASN.2015101109Wed, 04 Nov 2015 10:27:51 GMT-08:00Models of Human AKI: Resemblance, Reproducibility, and Return on InvestmentNath, Karl A.2015-11-04T10:27:51-08:00doi:10.1681/ASN.2015101109hwp:resource-id:jnephrol;26/12/2891American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologypreclinical studies, contrast dye, erythropoietin, acute kidney injury, translational studiesUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-12-01December 201510.1681/ASN.20151011091046-66731533-34502015-11-04T10:27:51-08:002015-12Journal of the American Society of NephrologyUp Front Matters2612122891290528932916
- T Lymphocyte–Specific Activation of Nrf2 Protects from AKIT lymphocytes are established mediators of ischemia reperfusion (IR)–induced AKI, but traditional immune principles do not explain their mechanism of early action in the absence of alloantigen. Nrf2 is a transcription factor that is crucial for cytoprotective gene expression and is generally thought to have a key role in dampening IR-induced AKI through protective effects on epithelial cells. We proposed an alternative hypothesis that augmentation of Nrf2 in T cells is essential to mitigate oxidative stress during IR-induced AKI. We therefore generated mice with genetically amplified levels of Nrf2 specifically in T cells and examined the effect on antioxidant gene expression, T cell activation, cytokine production, and IR-induced AKI. T cell–specific augmentation of Nrf2 significantly increased baseline antioxidant gene expression. These mice had a high frequency of intrarenal CD25+Foxp3+ regulatory T cells and decreased frequencies of CD11b+CD11c+ and F4/80+ cells. Intracellular levels of TNF-α, IFN-γ, and IL-17 were significantly lower in CD4+ T cells with high Nrf2 expression. Mice with increased T cell expression of Nrf2 were significantly protected from functional and histologic consequences of AKI. Furthermore, adoptive transfer of high-Nrf2 T cells protected wild-type mice from IR injury and significantly improved their survival. These data demonstrate that T cell–specific activation of Nrf2 protects from IR-induced AKI, revealing a novel mechanism of tissue protection during acute injury responses.10.1681/ASN.2014100978Thu, 20 Aug 2015 10:14:15 GMT-07:00T Lymphocyte–Specific Activation of Nrf2 Protects from AKIT lymphocytes are established mediators of ischemia reperfusion (IR)–induced AKI, but traditional immune principles do not explain their mechanism of early action in the absence of alloantigen. Nrf2 is a transcription factor that is crucial for cytoprotective gene expression and is generally thought to have a key role in dampening IR-induced AKI through protective effects on epithelial cells. We proposed an alternative hypothesis that augmentation of Nrf2 in T cells is essential to mitigate oxidative stress during IR-induced AKI. We therefore generated mice with genetically amplified levels of Nrf2 specifically in T cells and examined the effect on antioxidant gene expression, T cell activation, cytokine production, and IR-induced AKI. T cell–specific augmentation of Nrf2 significantly increased baseline antioxidant gene expression. These mice had a high frequency of intrarenal CD25+Foxp3+ regulatory T cells and decreased frequencies of CD11b+CD11c+ and F4/80+ cells. Intracellular levels of TNF-α, IFN-γ, and IL-17 were significantly lower in CD4+ T cells with high Nrf2 expression. Mice with increased T cell expression of Nrf2 were significantly protected from functional and histologic consequences of AKI. Furthermore, adoptive transfer of high-Nrf2 T cells protected wild-type mice from IR injury and significantly improved their survival. These data demonstrate that T cell–specific activation of Nrf2 protects from IR-induced AKI, revealing a novel mechanism of tissue protection during acute injury responses.Noel, SanjeevMartina, Maria N.Bandapalle, SamathaRacusen, Lorraine C.Potteti, Haranatha R.Hamad, Abdel R.A.Reddy, Sekhar P.Rabb, Hamid2015-08-20T10:14:15-07:00doi:10.1681/ASN.2014100978hwp:resource-id:jnephrol;26/12/2989American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, Nrf2-Keap1, T cell, oxidative stress, inflammationBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20141009781046-66731533-34502015-08-20T10:14:15-07:002015-12Journal of the American Society of NephrologyBasic Research2612122989289330002895
- JAK3/STAT6 Stimulates Bone Marrow–Derived Fibroblast Activation in Renal FibrosisRenal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow–derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow–derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow–derived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of α-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow–derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow–derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6−/− bone marrow cells displayed fewer bone marrow–derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6+/+ bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow–derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development.10.1681/ASN.2014070717Mon, 01 Jun 2015 07:57:32 GMT-07:00JAK3/STAT6 Stimulates Bone Marrow–Derived Fibroblast Activation in Renal FibrosisRenal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow–derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow–derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow–derived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of α-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow–derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow–derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6−/− bone marrow cells displayed fewer bone marrow–derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6+/+ bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow–derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development.Yan, JingyinZhang, ZhengmaoYang, JunMitch, William E.Wang, Yanlin2015-06-01T07:57:32-07:00doi:10.1681/ASN.2014070717hwp:resource-id:jnephrol;26/12/3060American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal fibrosis, fibroblast, extracellular matrix, cell signaling, cytokinesBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140707171046-66731533-34502015-06-01T07:57:32-07:002015-12Journal of the American Society of NephrologyBasic Research2612123060289630712898
- Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in Diabetic Kidney DiseaseDiabetic kidney disease (DKD) is a microvascular complication that leads to kidney dysfunction and ESRD, but the underlying mechanisms remain unclear. Podocyte Wnt-pathway activation has been demonstrated to be a trigger mechanism for various proteinuric diseases. Notably, four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in urogenital systems and has been implicated in Wnt/β-catenin signaling. Here, we used in vitro podocyte culture experiments and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine the possible role of FHL2 in DKD and to clarify its association with the Wnt pathway. In human and mouse kidney tissues, FHL2 protein was abundantly expressed in podocytes but not in renal tubular cells. Treatment with high glucose or diabetes-related cytokines, including angiotensin II and TGF-β1, activated FHL2 protein and Wnt/β-catenin signaling in cultured podocytes. This activation also upregulated FHL2 expression and promoted FHL2 translocation from cytosol to nucleus. Genetic deletion of the FHL2 gene mitigated the podocyte dedifferentiation caused by activated Wnt/β-catenin signaling under Wnt-On, but not under Wnt-Off, conditions. Diabetic FHL2+/+ mice developed markedly increased albuminuria and thickening of the glomerular basement membrane compared with nondiabetic FHL2+/+ mice. However, FHL2 knockout significantly attenuated these DKD-induced changes. Furthermore, kidney samples from patients with diabetes had a higher degree of FHL2 podocyte nuclear translocation, which was positively associated with albuminuria and progressive renal function deterioration. Therefore, we conclude that FHL2 has both structural and functional protein-protein interactions with β-catenin in the podocyte nucleus and that FHL2 protein inhibition can mitigate Wnt/β-catenin–induced podocytopathy.10.1681/ASN.2014100989Wed, 08 Apr 2015 01:17:16 GMT-07:00Four-and-a-Half LIM Domains Protein 2 Is a Coactivator of Wnt Signaling in Diabetic Kidney DiseaseDiabetic kidney disease (DKD) is a microvascular complication that leads to kidney dysfunction and ESRD, but the underlying mechanisms remain unclear. Podocyte Wnt-pathway activation has been demonstrated to be a trigger mechanism for various proteinuric diseases. Notably, four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in urogenital systems and has been implicated in Wnt/β-catenin signaling. Here, we used in vitro podocyte culture experiments and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine the possible role of FHL2 in DKD and to clarify its association with the Wnt pathway. In human and mouse kidney tissues, FHL2 protein was abundantly expressed in podocytes but not in renal tubular cells. Treatment with high glucose or diabetes-related cytokines, including angiotensin II and TGF-β1, activated FHL2 protein and Wnt/β-catenin signaling in cultured podocytes. This activation also upregulated FHL2 expression and promoted FHL2 translocation from cytosol to nucleus. Genetic deletion of the FHL2 gene mitigated the podocyte dedifferentiation caused by activated Wnt/β-catenin signaling under Wnt-On, but not under Wnt-Off, conditions. Diabetic FHL2+/+ mice developed markedly increased albuminuria and thickening of the glomerular basement membrane compared with nondiabetic FHL2+/+ mice. However, FHL2 knockout significantly attenuated these DKD-induced changes. Furthermore, kidney samples from patients with diabetes had a higher degree of FHL2 podocyte nuclear translocation, which was positively associated with albuminuria and progressive renal function deterioration. Therefore, we conclude that FHL2 has both structural and functional protein-protein interactions with β-catenin in the podocyte nucleus and that FHL2 protein inhibition can mitigate Wnt/β-catenin–induced podocytopathy.Li, Szu-YuanHuang, Po-HsunTarng, Der-CherngLin, Tzu-PingYang, Wu-ChangChang, Yen-HwaYang, An-HangLin, Chih-ChingYang, Muh-HwaChen, Jaw-WenSchmid-Schönbein, Geert W.Chien, ShuChu, Pao-HsienLin, Shing-Jong2015-04-08T13:17:16-07:00doi:10.1681/ASN.2014100989hwp:resource-id:jnephrol;26/12/3072American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologypodocyte, diabetes, proteinuriaBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20141009891046-66731533-34502015-04-08T13:17:16-07:002015-12Journal of the American Society of NephrologyBasic Research261230723084
- T Helper 2 Cytokine Signaling in Bone Marrow–Derived Fibroblasts: A Target for Renal Fibrosis10.1681/ASN.2015040469Mon, 01 Jun 2015 07:57:10 GMT-07:00T Helper 2 Cytokine Signaling in Bone Marrow–Derived Fibroblasts: A Target for Renal FibrosisSakai, NorihikoWada, Takashi2015-06-01T07:57:10-07:00doi:10.1681/ASN.2015040469hwp:resource-id:jnephrol;26/12/2896American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, signaling, cytokinesUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-12-01December 201510.1681/ASN.20150404691046-66731533-34502015-06-01T07:57:10-07:002015-12Journal of the American Society of NephrologyUp Front Matters2612122896306028983071
- Characteristics and Outcomes of AKI Treated with Dialysis during Pregnancy and the Postpartum PeriodAcute kidney injury (AKI) is a rare complication of pregnancy, but may be associated with significant morbidity and mortality in young and often otherwise healthy women. We conducted a retrospective population-based cohort study of all consecutive pregnancies over a 15-year period (1997–2011) in Ontario, Canada, and describe the incidence and outcomes of AKI treated with dialysis during pregnancy or within 12 weeks of delivery. Of 1,918,789 pregnancies, 188 were complicated by AKI treated with dialysis (incidence: 1 per 10,000 [95% confidence interval, 0.8 to 1.1]). Only 21 of 188 (11.2%) women had record of a preexisting medical condition; however, 130 (69.2%) women experienced a major pregnancy-related complication, including preeclampsia, thrombotic microangiopathy, heart failure, sepsis, or postpartum hemorrhage. Eight women died (4.3% versus 0.01% in the general population), and seven (3.9%) women remained dialysis dependent 4 months after delivery. Low birth weight (<2500 g), small for gestational age, or preterm birth (<37 weeks’ gestation) were more common in pregnancies in which dialysis was initiated (35.6% versus 14.0%; relative risk, 3.40; 95% confidence interval, 2.52 to 4.58). There were no stillbirths and fewer than five neonatal deaths (<2.7%) in affected pregnancies compared with 0.1% and 0.8%, respectively, in the general population. In conclusion, AKI treated with dialysis during pregnancy is rare and typically occurs in healthy women who acquire a major pregnancy-related medical condition such as preeclampsia. Many affected women and their babies have good short-term outcomes.10.1681/ASN.2014100954Thu, 14 May 2015 08:07:08 GMT-07:00Characteristics and Outcomes of AKI Treated with Dialysis during Pregnancy and the Postpartum PeriodAcute kidney injury (AKI) is a rare complication of pregnancy, but may be associated with significant morbidity and mortality in young and often otherwise healthy women. We conducted a retrospective population-based cohort study of all consecutive pregnancies over a 15-year period (1997–2011) in Ontario, Canada, and describe the incidence and outcomes of AKI treated with dialysis during pregnancy or within 12 weeks of delivery. Of 1,918,789 pregnancies, 188 were complicated by AKI treated with dialysis (incidence: 1 per 10,000 [95% confidence interval, 0.8 to 1.1]). Only 21 of 188 (11.2%) women had record of a preexisting medical condition; however, 130 (69.2%) women experienced a major pregnancy-related complication, including preeclampsia, thrombotic microangiopathy, heart failure, sepsis, or postpartum hemorrhage. Eight women died (4.3% versus 0.01% in the general population), and seven (3.9%) women remained dialysis dependent 4 months after delivery. Low birth weight (<2500 g), small for gestational age, or preterm birth (<37 weeks’ gestation) were more common in pregnancies in which dialysis was initiated (35.6% versus 14.0%; relative risk, 3.40; 95% confidence interval, 2.52 to 4.58). There were no stillbirths and fewer than five neonatal deaths (<2.7%) in affected pregnancies compared with 0.1% and 0.8%, respectively, in the general population. In conclusion, AKI treated with dialysis during pregnancy is rare and typically occurs in healthy women who acquire a major pregnancy-related medical condition such as preeclampsia. Many affected women and their babies have good short-term outcomes.Hildebrand, Ainslie M.Liu, KuanShariff, Salimah Z.Ray, Joel G.Sontrop, Jessica M.Clark, William F.Hladunewich, Michelle A.Garg, Amit X.2015-05-14T08:07:08-07:00doi:10.1681/ASN.2014100954hwp:resource-id:jnephrol;26/12/3085American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, dialysis, clinical epidemiologyClinical EpidemiologyClinical Epidemiologyresearch-article20152015-12-01December 201510.1681/ASN.20141009541046-66731533-34502015-05-14T08:07:08-07:002015-12Journal of the American Society of NephrologyClinical Epidemiology261230853091
- Thioredoxin-Interacting Protein Deficiency Protects against Diabetic NephropathyExpression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP−/−, and TxNIP+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O2− generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.10.1681/ASN.2014050528Wed, 08 Apr 2015 01:17:11 GMT-07:00Thioredoxin-Interacting Protein Deficiency Protects against Diabetic NephropathyExpression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP−/−, and TxNIP+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O2− generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.Shah, AnuXia, LingMasson, Elodie A.Y.Gui, ChloeMomen, AbdulShikatani, Eric A.Husain, MansoorQuaggin, SusanJohn, RohanFantus, I.G.2015-04-08T13:17:11-07:00doi:10.1681/ASN.2014050528hwp:resource-id:jnephrol;26/12/2963American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes mellitus, diabetic nephropathy, oxidative stressBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140505281046-66731533-34502015-04-08T13:17:11-07:002015-12Journal of the American Society of NephrologyBasic Research261229632977
- P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes InsipidusP2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague–Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.10.1681/ASN.2014010118Wed, 08 Apr 2015 01:17:08 GMT-07:00P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes InsipidusP2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. Administration of clopidogrel bisulfate, an irreversible inhibitor of P2Y12-R, significantly increased urine concentration and AQP2 protein in the kidneys of Sprague–Dawley rats. Notably, clopidogrel did not alter urine concentration in Brattleboro rats that lack AVP. Clopidogrel administration also significantly ameliorated lithium-induced polyuria, improved urine concentrating ability and AQP2 protein abundance, and reversed the lithium-induced increase in free-water excretion, without decreasing blood or kidney tissue lithium levels. Clopidogrel administration also augmented the lithium-induced increase in urinary AVP excretion and suppressed the lithium-induced increase in urinary nitrates/nitrites (nitric oxide production) and 8-isoprostane (oxidative stress). Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.Zhang, YuePeti-Peterdi, JanosMüller, Christa E.Carlson, Noel G.Baqi, YounisStrasburg, David L.Heiney, Kristina M.Villanueva, KarieKohan, Donald E.Kishore, Bellamkonda K.2015-04-08T13:17:08-07:00doi:10.1681/ASN.2014010118hwp:resource-id:jnephrol;26/12/2978American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycollecting ducts, cyclic AMP, diabetes insipidus, vasopressin, extracellular, nucleotides, hypothalamusBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140101181046-66731533-34502015-04-08T13:17:08-07:002015-12Journal of the American Society of NephrologyBasic Research261229782987
- Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance HemodialysisClinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.10.1681/ASN.2014060614Wed, 08 Apr 2015 01:17:12 GMT-07:00Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance HemodialysisClinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.Harel, ZivWald, RonMcArthur, EricChertow, Glenn M.Harel, ShaiGruneir, AndreaFischer, Hadas D.Garg, Amit X.Perl, JeffreyNash, Danielle M.Silver, SamuelBell, Chaim M.2015-04-08T13:17:12-07:00doi:10.1681/ASN.2014060614hwp:resource-id:jnephrol;26/12/3141American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyclinical epidemiology, hemodialysis, hospitalizationClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140606141046-66731533-34502015-04-08T13:17:12-07:002015-12Journal of the American Society of NephrologyClinical Research261231413150
- Outcomes of In-Hospital Cardiopulmonary Resuscitation in Maintenance Dialysis PatientsOutcomes of cardiopulmonary resuscitation (CPR) in hospitalized patients with ESRD requiring maintenance dialysis are unknown. Outcomes of in-hospital CPR in these patients were compared with outcomes in the general population using data from the Nationwide Inpatient Sample (NIS; 2005–2011). The study population included all adults (≥18years old) from the general population and those with a history of ESRD. Baseline characteristics, in-hospital complications, and discharge outcomes were compared between the two groups. The effects of in-hospital CPR on mortality, length of stay, hospitalization charges, and discharge destination were analyzed. Yearly national trends in survival, discharge to home, and length of stay were also examined using the Cochran–Armitage trend test. During the study period, 56,069 patients with ESRD underwent in-hospital CPR compared with 323,620 patients from the general population. Unadjusted in-hospital mortality rates were higher in patients with ESRD (73.9% versus 71.8%, P<0.001) on univariate analysis. After adjusting for age, gender, and potential confounders, patients with ESRD had higher odds of mortality (odds ratio, 1.24; 95% confidence interval, 1.11 to 1.3; P<0.001). Survival after CPR improved in the year 2011 compared with 2005 (31% versus 21%, P<0.001). Multivariate analysis also revealed that a greater proportion of patients with ESRD who survived were discharged to skilled nursing facilities. In conclusion, outcomes after in-hospital CPR are improving in patients with ESRD but remain worse than outcomes in the general population. Patients with ESRD who survive are more likely to be discharged to nursing homes.10.1681/ASN.2014080766Thu, 23 Apr 2015 06:36:47 GMT-07:00Outcomes of In-Hospital Cardiopulmonary Resuscitation in Maintenance Dialysis PatientsOutcomes of cardiopulmonary resuscitation (CPR) in hospitalized patients with ESRD requiring maintenance dialysis are unknown. Outcomes of in-hospital CPR in these patients were compared with outcomes in the general population using data from the Nationwide Inpatient Sample (NIS; 2005–2011). The study population included all adults (≥18years old) from the general population and those with a history of ESRD. Baseline characteristics, in-hospital complications, and discharge outcomes were compared between the two groups. The effects of in-hospital CPR on mortality, length of stay, hospitalization charges, and discharge destination were analyzed. Yearly national trends in survival, discharge to home, and length of stay were also examined using the Cochran–Armitage trend test. During the study period, 56,069 patients with ESRD underwent in-hospital CPR compared with 323,620 patients from the general population. Unadjusted in-hospital mortality rates were higher in patients with ESRD (73.9% versus 71.8%, P<0.001) on univariate analysis. After adjusting for age, gender, and potential confounders, patients with ESRD had higher odds of mortality (odds ratio, 1.24; 95% confidence interval, 1.11 to 1.3; P<0.001). Survival after CPR improved in the year 2011 compared with 2005 (31% versus 21%, P<0.001). Multivariate analysis also revealed that a greater proportion of patients with ESRD who survived were discharged to skilled nursing facilities. In conclusion, outcomes after in-hospital CPR are improving in patients with ESRD but remain worse than outcomes in the general population. Patients with ESRD who survive are more likely to be discharged to nursing homes.Saeed, FahadAdil, Malik MMalik, Ahmed A.Schold, Jesse D.Holley, Jean L.2015-04-23T06:36:47-07:00doi:10.1681/ASN.2014080766hwp:resource-id:jnephrol;26/12/3093American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular, chronic dialysis, epidemiology and outcomesClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140807661046-66731533-34502015-04-23T06:36:47-07:002015-12Journal of the American Society of NephrologyClinical Research261230933101
- Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium ExcretionInappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)–dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II–dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%–10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II–dependent vascular responses in the kidney to effect natriuresis and BP control.10.1681/ASN.2014080816Wed, 08 Apr 2015 01:17:19 GMT-07:00Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium ExcretionInappropriate activation of the type 1A angiotensin (AT1A) receptor contributes to the pathogenesis of hypertension and its associated complications. To define the role for actions of vascular AT1A receptors in BP regulation and hypertension pathogenesis, we generated mice with cell-specific deletion of AT1A receptors in smooth muscle cells (SMKO mice) using Loxp technology and Cre transgenes with robust expression in both conductance and resistance arteries. We found that elimination of AT1A receptors from vascular smooth muscle cells (VSMCs) caused a modest (approximately 7 mmHg) yet significant reduction in baseline BP and exaggerated sodium sensitivity in mice. Additionally, the severity of angiotensin II (Ang II)–dependent hypertension was dramatically attenuated in SMKO mice, and this protection against hypertension was associated with enhanced urinary excretion of sodium. Despite the lower BP, acute vasoconstrictor responses to Ang II in the systemic vasculature were largely preserved (approximately 80% of control levels) in SMKO mice because of exaggerated activity of the sympathetic nervous system rather than residual actions of AT1B receptors. In contrast, Ang II–dependent responses in the renal circulation were almost completely eliminated in SMKO mice (approximately 5%–10% of control levels). These findings suggest that direct actions of AT1A receptors in VSMCs are essential for regulation of renal blood flow by Ang II and highlight the capacity of Ang II–dependent vascular responses in the kidney to effect natriuresis and BP control.Sparks, Matthew A.Stegbauer, JohannesChen, DaianGomez, Jose A.Griffiths, Robert C.Azad, Hooman A.Herrera, MarcelaGurley, Susan B.Coffman, Thomas M.2015-04-08T13:17:19-07:00doi:10.1681/ASN.2014080816hwp:resource-id:jnephrol;26/12/2953American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyangiotensin, blood pressure, renal hemodynamics, vascularBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140808161046-66731533-34502015-04-08T13:17:19-07:002015-12Journal of the American Society of NephrologyBasic Research261229532962
- Outcomes of Elderly Patients after Predialysis Vascular Access CreationUniform vascular access guidelines for elderly patients may be inappropriate because of the competing risk of death, high rate of arteriovenous fistula (AVF) maturation failure, and poor vascular access outcomes in this population. However, the outcomes in elderly patients with advanced CKD who receive permanent vascular access before dialysis initiation are unclear. We identified a large nationally representative cohort of 3418 elderly patients (aged ≥70 years) with CKD undergoing predialysis AVF or arteriovenous graft (AVG) creation from 2004 to 2009, and assessed the frequencies of dialysis initiation, death before dialysis initiation, and dialysis-free survival for 2 years after vascular access creation. In all, 67% of patients with predialysis AVF and 71% of patients with predialysis AVG creation initiated dialysis within 2 years of access placement, but the overall risk of dialysis initiation was modified by patient age and race. Only one half of patients initiated dialysis with a functioning AVF or AVG; 46.8% of AVFs were created <90 days before dialysis initiation. Catheter dependence at dialysis initiation was more common in patients receiving predialysis AVF than in patients receiving AVG (46.0% versus 28.5%; P<0.001). In conclusion, most elderly patients with advanced CKD who received predialysis vascular access creation initiated dialysis within 2 years. As a consequence of late predialysis placement or maturation failure, almost one half of patients receiving AVFs initiated dialysis with a catheter. Insertion of an AVG closer to dialysis initiation may serve as a “catheter-sparing” approach and allow delay of permanent access placement in selected elderly patients with CKD.10.1681/ASN.2014090938Wed, 08 Apr 2015 01:17:10 GMT-07:00Outcomes of Elderly Patients after Predialysis Vascular Access CreationUniform vascular access guidelines for elderly patients may be inappropriate because of the competing risk of death, high rate of arteriovenous fistula (AVF) maturation failure, and poor vascular access outcomes in this population. However, the outcomes in elderly patients with advanced CKD who receive permanent vascular access before dialysis initiation are unclear. We identified a large nationally representative cohort of 3418 elderly patients (aged ≥70 years) with CKD undergoing predialysis AVF or arteriovenous graft (AVG) creation from 2004 to 2009, and assessed the frequencies of dialysis initiation, death before dialysis initiation, and dialysis-free survival for 2 years after vascular access creation. In all, 67% of patients with predialysis AVF and 71% of patients with predialysis AVG creation initiated dialysis within 2 years of access placement, but the overall risk of dialysis initiation was modified by patient age and race. Only one half of patients initiated dialysis with a functioning AVF or AVG; 46.8% of AVFs were created <90 days before dialysis initiation. Catheter dependence at dialysis initiation was more common in patients receiving predialysis AVF than in patients receiving AVG (46.0% versus 28.5%; P<0.001). In conclusion, most elderly patients with advanced CKD who received predialysis vascular access creation initiated dialysis within 2 years. As a consequence of late predialysis placement or maturation failure, almost one half of patients receiving AVFs initiated dialysis with a catheter. Insertion of an AVG closer to dialysis initiation may serve as a “catheter-sparing” approach and allow delay of permanent access placement in selected elderly patients with CKD.Lee, TimmyThamer, MaeZhang, YiZhang, QianAllon, Michael2015-04-08T13:17:10-07:00doi:10.1681/ASN.2014090938hwp:resource-id:jnephrol;26/12/3133American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyvascular access, arteriovenous fistula, arteriovenous graftClinical ResearchClinical Researchresearch-article20152015-12-01December 201510.1681/ASN.20140909381046-66731533-34502015-04-08T13:17:10-07:002015-12Journal of the American Society of NephrologyClinical Research261231333140
- Glomerular Effects of Age and APOL110.1681/ASN.2015040459Tue, 02 Jun 2015 11:31:53 GMT-07:00Glomerular Effects of Age and APOL1Meyer, Timothy W.Lenihan, Colin R.2015-06-02T11:31:53-07:00doi:10.1681/ASN.2015040459hwp:resource-id:jnephrol;26/12/2901American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycell survival, podocyte, glomerulusUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-12-01December 201510.1681/ASN.20150404591046-66731533-34502015-06-02T11:31:53-07:002015-12Journal of the American Society of NephrologyUp Front Matters26121212290131623179290331783189
- Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney DamageNitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function.10.1681/ASN.2014030280Wed, 08 Apr 2015 01:17:07 GMT-07:00Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney DamageNitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function.Tomlinson, James A.P.Caplin, BenBoruc, OlgaBruce-Cobbold, ClaireCutillas, PedroDormann, DirkFaull, PeterGrossman, Rebecca C.Khadayate, SanjayMas, Valeria R.Nitsch, Dorothea D.Wang, ZhenNorman, Jill T.Wilcox, Christopher S.Wheeler, David C.Leiper, James2015-04-08T13:17:07-07:00doi:10.1681/ASN.2014030280hwp:resource-id:jnephrol;26/12/3045American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologynitric oxide, chronic renal failure, fibrosis, pathophysiology of renal disease and progression, proximal tubule, transgenic mouseBasic ResearchBasic Researchresearch-article20152015-12-01December 201510.1681/ASN.20140302801046-66731533-34502015-04-08T13:17:07-07:002015-12Journal of the American Society of NephrologyBasic Research261230453059
- Serum Uric Acid and Risk of CKD in Type 2 Diabetes10.2215/CJN.03140315Fri, 04 Sep 2015 06:30:54 GMT-07:00Serum Uric Acid and Risk of CKD in Type 2 DiabetesDe Cosmo, SalvatoreViazzi, FrancescaPacilli, AntonioGiorda, CarloCeriello, AntonioGentile, SandroRusso, GiuseppinaRossi, Maria C.Nicolucci, AntonioGuida, PietroFeig, DanielJohnson, Richard J.Pontremoli, Roberto,2015-09-04T06:30:54-07:00doi:10.2215/CJN.03140315hwp:resource-id:clinjasn;10/11/1921American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologydiabetes mellitus, glomerular filtration rate, albuminuriaOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-11-06November 06, 201510.2215/CJN.031403151555-90411555-905X2015-09-04T06:30:54-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119211929
- Long-Term Renal Function after Endovascular Aneurysm Repair10.2215/CJN.04870515Tue, 20 Oct 2015 08:13:58 GMT-07:00Long-Term Renal Function after Endovascular Aneurysm RepairSaratzis, AthanasiosBath, Michael F.Harrison, SeamusSayers, Robert D.Mahmood, AsifSarafidis, PantelisBown, Matthew J.2015-10-20T08:13:58-07:00doi:10.2215/CJN.04870515hwp:resource-id:clinjasn;10/11/1930American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, endovascular aneurysm repair, renal injury, aortic aneurysm, abdominal, endarterectomy, carotid, endovascular procedures, glomerular filtration rate, humansOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-11-06November 06, 201510.2215/CJN.048705151555-90411555-905X2015-10-20T08:13:58-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles1011111930188919361891
- Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients10.2215/CJN.12161214Fri, 04 Sep 2015 06:30:53 GMT-07:00Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant RecipientsSerrano, Oscar K.Friedmann, PatriciaAhsanuddin, SayeedaMillan, CarlosBen-Yaacov, AlmogKayler, Liise K.2015-09-04T06:30:53-07:00doi:10.2215/CJN.12161214hwp:resource-id:clinjasn;10/11/2030American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal transplantation, acute allograft rejection, chronic graft deteriorationOriginal ArticlesRenal TransplantationOriginal ArticlesRenal Transplantationresearch-article20152015-11-06November 06, 201510.2215/CJN.121612141555-90411555-905X2015-09-04T06:30:53-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101120302038
- Rate of Kidney Function Decline and Risk of Hospitalizations in Stage 3A CKD10.2215/CJN.04480415Tue, 08 Sep 2015 09:19:18 GMT-07:00Rate of Kidney Function Decline and Risk of Hospitalizations in Stage 3A CKDXie, YanBowe, BenjaminXian, HongBalasubramanian, SumitraAl-Aly, Ziyad2015-09-08T09:19:18-07:00doi:10.2215/CJN.04480415hwp:resource-id:clinjasn;10/11/1946American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhospitalization, chronic kidney disease, eGFR slope, glomerular filtration rate, length of stay, patient readmission, renal insufficiency, chronic, risk, united states, veteransOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-11-06November 06, 201510.2215/CJN.044804151555-90411555-905X2015-09-08T09:19:18-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119461955
- Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study10.2215/CJN.02590315Tue, 08 Sep 2015 09:19:18 GMT-07:00Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities StudyFoster, Meredith C.Coresh, JosefBonventre, Joseph V.Sabbisetti, Venkata S.Waikar, Sushrut S.Mifflin, Theodore E.Nelson, Robert G.Grams, MorganFeldman, Harold I.Vasan, Ramachandran S.Kimmel, Paul L.Hsu, Chi-yuanLiu, Kathleen D.,2015-09-08T09:19:18-07:00doi:10.2215/CJN.02590315hwp:resource-id:clinjasn;10/11/1956American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyalbuminuria, chronic kidney disease, end-stage renal disease, acetylglucosaminidase, diabetes mellitus, fatty acid-binding proteins, kidney failure, chronic, lipocalins, renal insufficiency, chronicOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-11-06November 06, 201510.2215/CJN.025903151555-90411555-905X2015-09-08T09:19:18-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119561963
- Interstate Variation in Receipt of Nephrologist Care in US Patients Approaching ESRD: Race, Age, and State Characteristics10.2215/CJN.02800315Thu, 08 Oct 2015 09:09:45 GMT-07:00Interstate Variation in Receipt of Nephrologist Care in US Patients Approaching ESRD: Race, Age, and State CharacteristicsYan, GuofenCheung, Alfred K.Greene, TomYu, Alison J.Oliver, M. NormanYu, WeiMa, Jennie Z.Norris, Keith C.2015-10-08T09:09:45-07:00doi:10.2215/CJN.02800315hwp:resource-id:clinjasn;10/11/1979American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, racial difference, US Renal Data System, pre-ESRD care, state characteristicsOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-11-06November 06, 201510.2215/CJN.028003151555-90411555-905X2015-10-08T09:09:45-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles10111112197918922107198818942109
- Kinetic eGFR and Novel AKI Biomarkers to Predict Renal Recovery10.2215/CJN.12651214Fri, 04 Sep 2015 06:30:52 GMT-07:00Kinetic eGFR and Novel AKI Biomarkers to Predict Renal RecoveryDewitte, AntoineJoannès-Boyau, OlivierSidobre, CaroleFleureau, CatherineBats, Marie-LiseDerache, PhilippeLeuillet, SébastienRipoche, JeanCombe, ChristianOuattara, Alexandre2015-09-04T06:30:52-07:00doi:10.2215/CJN.12651214hwp:resource-id:clinjasn;10/11/1900American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAKI, biomarkers, neutrophil gelatinase–associated lipocalin, NGAL, [TIMP-2]*[IGFBP7], Doppler ultrasonographyOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20152015-11-06November 06, 201510.2215/CJN.126512141555-90411555-905X2015-09-04T06:30:52-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119001910
- The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis10.2215/CJN.12201214Fri, 04 Sep 2015 06:30:53 GMT-07:00The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or SepsisReilly, John P.Anderson, Brian J.Mangalmurti, Nilam S.Nguyen, Tam D.Holena, Daniel N.Wu, QufeiNguyen, Ethan T.Reilly, Muredach P.Lanken, Paul N.Christie, Jason D.Meyer, Nuala J.Shashaty, Michael G.S.2015-09-04T06:30:53-07:00doi:10.2215/CJN.12201214hwp:resource-id:clinjasn;10/11/1911American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyABO histoblood group system, AKI, sepsis, trauma, critical illnessOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20152015-11-06November 06, 201510.2215/CJN.122012141555-90411555-905X2015-09-04T06:30:53-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119111920
- T Cells: Soldiers and Spies—The Surveillance and Control of Effector T Cells by Regulatory T CellsTraditionally, T cells were CD4+ helper or CD8+ cytotoxic T cells, and with antibodies, they were the soldiers of immunity. Now, many functionally distinct subsets of activated CD4+ and CD8+ T cells have been described, each with distinct cytokine and transcription factor expression. For CD4+ T cells, these include Th1 cells expressing the transcription factor T-bet and cytokines IL-2, IFN-γ, and TNF-β; Th2 cells expressing GATA-3 and the cytokines IL-4, IL-5, and IL-13; and Th17 cells expressing RORγt and cytokines IL-17A, IL-17F, IL-21, and IL-22. The cytokines produced determine the immune inflammation that they mediate. T cells of the effector lineage can be naïve T cells, recently activated T cells, or memory T cells that can be distinguished by cell surface markers. T regulatory cells or spies were characterized as CD8+ T cells expressing I-J in the 1970s. In the 1980s, suppressor cells fell into disrepute when the gene for I-J was not present in the mouse MHC I region. At that time, a CD4+ T cell expressing CD25, the IL-2 receptor-α, was identified to transfer transplant tolerance. This was the same phenotype of activated CD4+CD25+ T cells that mediated rejection. Thus, the cells that could induce tolerance and undermine rejection had similar badges and uniforms as the cells effecting rejection. Later, FOXP3, a transcription factor that confers suppressor function, was described and distinguishes T regulatory cells from effector T cells. Many subtypes of T regulatory cells can be characterized by different expressions of cytokines and receptors for cytokines or chemokines. In intense immune inflammation, T regulatory cells express cytokines characteristic of effector cells; for example, Th1-like T regulatory cells express T-bet, and IFN-γ–like Th1 cells and effector T cells can change sides by converting to T regulatory cells. Effector T cells and T regulatory cells use similar molecules to be activated and mediate their function, and thus, it can be very difficult to distinguish soldiers from spies.10.2215/CJN.06620714Wed, 15 Apr 2015 07:05:41 GMT-07:00T Cells: Soldiers and Spies—The Surveillance and Control of Effector T Cells by Regulatory T CellsTraditionally, T cells were CD4+ helper or CD8+ cytotoxic T cells, and with antibodies, they were the soldiers of immunity. Now, many functionally distinct subsets of activated CD4+ and CD8+ T cells have been described, each with distinct cytokine and transcription factor expression. For CD4+ T cells, these include Th1 cells expressing the transcription factor T-bet and cytokines IL-2, IFN-γ, and TNF-β; Th2 cells expressing GATA-3 and the cytokines IL-4, IL-5, and IL-13; and Th17 cells expressing RORγt and cytokines IL-17A, IL-17F, IL-21, and IL-22. The cytokines produced determine the immune inflammation that they mediate. T cells of the effector lineage can be naïve T cells, recently activated T cells, or memory T cells that can be distinguished by cell surface markers. T regulatory cells or spies were characterized as CD8+ T cells expressing I-J in the 1970s. In the 1980s, suppressor cells fell into disrepute when the gene for I-J was not present in the mouse MHC I region. At that time, a CD4+ T cell expressing CD25, the IL-2 receptor-α, was identified to transfer transplant tolerance. This was the same phenotype of activated CD4+CD25+ T cells that mediated rejection. Thus, the cells that could induce tolerance and undermine rejection had similar badges and uniforms as the cells effecting rejection. Later, FOXP3, a transcription factor that confers suppressor function, was described and distinguishes T regulatory cells from effector T cells. Many subtypes of T regulatory cells can be characterized by different expressions of cytokines and receptors for cytokines or chemokines. In intense immune inflammation, T regulatory cells express cytokines characteristic of effector cells; for example, Th1-like T regulatory cells express T-bet, and IFN-γ–like Th1 cells and effector T cells can change sides by converting to T regulatory cells. Effector T cells and T regulatory cells use similar molecules to be activated and mediate their function, and thus, it can be very difficult to distinguish soldiers from spies.Hall, Bruce M.2015-04-15T07:05:41-07:00doi:10.2215/CJN.06620714hwp:resource-id:clinjasn;10/11/2050American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyTreg, T cell, cytokine, transplantation, GNRenal ImmunologyRenal Immunologyresearch-article20152015-11-06November 06, 201510.2215/CJN.066207141555-90411555-905X2015-04-15T07:05:41-07:002015-11-06Clinical Journal of the American Society of NephrologyRenal Immunology101120502064
- Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug TransportersThe proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily. We review the basic physiology of these SLC and ABC transporters, many of which are often called drug transporters. With an emphasis on OAT1 (SLC22A6), the closely related OAT3 (SLC22A8), and OCT2 (SLC22A2), we explore the implications of recent in vitro, in vivo, and clinical data pertinent to the kidney. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liver-derived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. These transporters may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD.10.2215/CJN.02440314Wed, 21 Oct 2015 06:22:20 GMT-07:00Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug TransportersThe proximal tubule of the kidney plays a crucial role in the renal handling of drugs (e.g., diuretics), uremic toxins (e.g., indoxyl sulfate), environmental toxins (e.g., mercury, aristolochic acid), metabolites (e.g., uric acid), dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters of the solute carrier (SLC) superfamily, including organic anion transporter (OAT) and organic cation transporter (OCT) subfamilies, and the ATP-binding cassette (ABC) superfamily. We review the basic physiology of these SLC and ABC transporters, many of which are often called drug transporters. With an emphasis on OAT1 (SLC22A6), the closely related OAT3 (SLC22A8), and OCT2 (SLC22A2), we explore the implications of recent in vitro, in vivo, and clinical data pertinent to the kidney. The analysis of murine knockouts has revealed a key role for these transporters in the renal handling not only of drugs and toxins but also of gut microbiome products, as well as liver-derived phase 1 and phase 2 metabolites, including putative uremic toxins (among other molecules of metabolic and clinical importance). Functional activity of these transporters (and polymorphisms affecting it) plays a key role in drug handling and nephrotoxicity. These transporters may also play a role in remote sensing and signaling, as part of a versatile small molecule communication network operative throughout the body in normal and diseased states, such as AKI and CKD.Nigam, Sanjay K.Wu, WeiBush, Kevin T.Hoenig, Melanie P.Blantz, Roland C.Bhatnagar, Vibha2015-10-21T06:22:20-07:00doi:10.2215/CJN.02440314hwp:resource-id:clinjasn;10/11/2039American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal physiology, drug transporter, nephrotoxicity, ATP-Binding Cassette Transporters, Acute Kidney Injury, Anti-Bacterial Agents, Cations, Diuretics, Organic Anion Transporters, Renal Insufficiency, ChronicRenal PhysiologyRenal Physiologyresearch-article20152015-11-06November 06, 201510.2215/CJN.024403141555-90411555-905X2015-10-21T06:22:20-07:002015-11-06Clinical Journal of the American Society of NephrologyRenal Physiology101120392049
- Clinical Decision Making in a Patient with Stage 5 CKD—Is eGFR Good Enough?The development and widespread use of serum creatinine concentration–based prediction equations to calculate eGFR have been major advances for detection of patients with CKD and the epidemiologic study of CKD and its outcomes. However, these equations as well as those that also incorporate serum cystatin C concentration provide GFR estimates that, although reasonably precise on average, can differ markedly and in clinically important ways from actual GFR. Thus, it is important that clinicians who use these equations for clinical decision-making be familiar with their strengths and weaknesses and have an appreciation of their potential for error. More precise knowledge of actual GFR is important in certain clinical circumstances, including, as presented in this Attending Rounds, patients with stage 5 CKD, in whom decisions regarding dialysis initiation are necessary. Nephrologists should have the ability to accurately determine GFR when needed if clinical circumstances suggest inaccuracy of the calculated eGFR reported by the clinical laboratory.10.2215/CJN.00340115Thu, 16 Apr 2015 09:12:52 GMT-07:00Clinical Decision Making in a Patient with Stage 5 CKD—Is eGFR Good Enough?The development and widespread use of serum creatinine concentration–based prediction equations to calculate eGFR have been major advances for detection of patients with CKD and the epidemiologic study of CKD and its outcomes. However, these equations as well as those that also incorporate serum cystatin C concentration provide GFR estimates that, although reasonably precise on average, can differ markedly and in clinically important ways from actual GFR. Thus, it is important that clinicians who use these equations for clinical decision-making be familiar with their strengths and weaknesses and have an appreciation of their potential for error. More precise knowledge of actual GFR is important in certain clinical circumstances, including, as presented in this Attending Rounds, patients with stage 5 CKD, in whom decisions regarding dialysis initiation are necessary. Nephrologists should have the ability to accurately determine GFR when needed if clinical circumstances suggest inaccuracy of the calculated eGFR reported by the clinical laboratory.Berns, Jeffrey S.2015-04-16T09:12:52-07:00doi:10.2215/CJN.00340115hwp:resource-id:clinjasn;10/11/2065American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, GFR, ESRD, Cockcroft–GaultAttending RoundsAttending Roundsresearch-article20152015-11-06November 06, 201510.2215/CJN.003401151555-90411555-905X2015-04-16T09:12:52-07:002015-11-06Clinical Journal of the American Society of NephrologyAttending Rounds101120652072
- Electronic Health Record Patient Portals in CKD and Hypertension Management: Meaningfully Used?10.2215/CJN.10070915Thu, 22 Oct 2015 07:05:22 GMT-07:00Electronic Health Record Patient Portals in CKD and Hypertension Management: Meaningfully Used?Mendu, Mallika L.Waikar, Sushrut S.2015-10-22T07:05:22-07:00doi:10.2215/CJN.10070915hwp:resource-id:clinjasn;10/11/1897American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyblood pressure, chronic kidney disease, hypertension, disease management, electronic health records, health records, personal, humansEditorialsEditorialseditorial20152015-11-06November 06, 201510.2215/CJN.100709151555-90411555-905X2015-10-22T07:05:22-07:002015-11-06Clinical Journal of the American Society of NephrologyEditorials1011111897201318992022
- A Systematic Review and Meta-Analysis of Outcomes of Pregnancy in CKD and CKD Outcomes in Pregnancy10.2215/CJN.09250914Tue, 20 Oct 2015 08:13:58 GMT-07:00A Systematic Review and Meta-Analysis of Outcomes of Pregnancy in CKD and CKD Outcomes in PregnancyZhang, Jing-JingMa, Xin-XinHao, LiLiu, Li-JunLv, Ji-ChengZhang, Hong2015-10-20T08:13:58-07:00doi:10.2215/CJN.09250914hwp:resource-id:clinjasn;10/11/1964American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, renal function, pregnancy, cesarean section, follow-up studies, gestational age, humans, infant, low birth weight, pre-eclampsia, premature birthOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-11-06November 06, 201510.2215/CJN.092509141555-90411555-905X2015-10-20T08:13:58-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119641978
- Nephrolithiasis as a Risk Factor for CKD: The Atherosclerosis Risk in Communities Study10.2215/CJN.10111014Fri, 04 Sep 2015 06:30:55 GMT-07:00Nephrolithiasis as a Risk Factor for CKD: The Atherosclerosis Risk in Communities StudyKummer, Andrew E.Grams, MorganLutsey, PamelaChen, YuanMatsushita, KunihiroKöttgen, AnnaFolsom, Aaron R.Coresh, Josef2015-09-04T06:30:55-07:00doi:10.2215/CJN.10111014hwp:resource-id:clinjasn;10/11/2023American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, follow-up studies, hospitalization, kidney calculi, nephrolithiasis, renal insufficiency, chronic, risk factors, uric acidOriginal ArticlesNephrolithiasisOriginal ArticlesNephrolithiasisresearch-article20152015-11-06November 06, 201510.2215/CJN.101110141555-90411555-905X2015-09-04T06:30:55-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101120232029
- Long–Term Renal Function after Abdominal Aortic Aneurysm Repair10.2215/CJN.09850915Tue, 20 Oct 2015 08:13:56 GMT-07:00Long–Term Renal Function after Abdominal Aortic Aneurysm RepairBahia, Sandeep SinghDe Bruin, Jorg Lucas2015-10-20T08:13:56-07:00doi:10.2215/CJN.09850915hwp:resource-id:clinjasn;10/11/1889American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal function decline, glomerular filtration rate, vascular, arteries, aortic aneurysm, abdominal, reconstructive surgical procedures, urinary tract physiological phenomena, vascular surgical proceduresEditorialsEditorialseditorial20152015-11-06November 06, 201510.2215/CJN.098509151555-90411555-905X2015-10-20T08:13:56-07:002015-11-06Clinical Journal of the American Society of NephrologyEditorials1011111889193018911936
- Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam10.2215/CJN.02330315Fri, 04 Sep 2015 06:30:55 GMT-07:00Renal Outcomes in Critically Ill Patients Receiving Propofol or MidazolamLeite, Tacyano TavaresMacedo, EtienneMartins, Izanio da SilvaNeves, Fernanda Macedo de OliveiraLibório, Alexandre Braga2015-09-04T06:30:55-07:00doi:10.2215/CJN.02330315hwp:resource-id:clinjasn;10/11/1937American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyARF, renal protection, renal dialysisOriginal ArticlesCritical Care NephrologyOriginal ArticlesCritical Care Nephrologyresearch-article20152015-11-06November 06, 201510.2215/CJN.023303151555-90411555-905X2015-09-04T06:30:55-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101119371945
- Peritoneal Equilibration Test and Patient Outcomes10.2215/CJN.03470315Tue, 13 Oct 2015 05:51:09 GMT-07:00Peritoneal Equilibration Test and Patient OutcomesMehrotra, RajnishRavel, VanessaStreja, ElaniKuttykrishnan, SoorajAdams, Scott V.Katz, RonitMolnar, Miklos Z.Kalantar-Zadeh, Kamyar2015-10-13T05:51:09-07:00doi:10.2215/CJN.03470315hwp:resource-id:clinjasn;10/11/1990American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, mortality, creatinine, dialysis solutions, follow-up studies, hospitalization, humans, renal dialysis, ultrafiltrationOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-11-06November 06, 201510.2215/CJN.034703151555-90411555-905X2015-10-13T05:51:09-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles1011111990189520011896
- Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected FindingsThe Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among nearly 4000 individuals with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >90 published scientific articles, promoted many young investigative careers in nephrology, and fostered international collaborations focused on understanding the global burden of CKD. The third phase of the CRIC Study will complete enrollment of 1500 additional study participants in 2015 and is designed to answer questions regarding morbidity and mortality in mild-to-moderate CKD and to assess the burden of CKD in older persons. This review highlights some of the salient findings of the CRIC Study in the areas of race and ethnicity, CKD progression, CKD and cognition, and cardiovascular disease outcomes; it also outlines the ongoing and forthcoming opportunities for the global nephrology community to enhance its understanding of CKD and related complications through the study.10.2215/CJN.04260415Tue, 11 Aug 2015 06:35:11 GMT-07:00Chronic Renal Insufficiency Cohort Study (CRIC): Overview and Summary of Selected FindingsThe Chronic Renal Insufficiency Cohort (CRIC) Study is a United States multicenter, prospective study of racially and ethnically diverse patients with CKD. Although the original aims of the study were to identify novel predictors of CKD progression and to elucidate the risk and manifestations of cardiovascular disease among nearly 4000 individuals with CKD, the CRIC Study has evolved into a national resource for investigation of a broad spectrum of CKD-related topics. The study has produced >90 published scientific articles, promoted many young investigative careers in nephrology, and fostered international collaborations focused on understanding the global burden of CKD. The third phase of the CRIC Study will complete enrollment of 1500 additional study participants in 2015 and is designed to answer questions regarding morbidity and mortality in mild-to-moderate CKD and to assess the burden of CKD in older persons. This review highlights some of the salient findings of the CRIC Study in the areas of race and ethnicity, CKD progression, CKD and cognition, and cardiovascular disease outcomes; it also outlines the ongoing and forthcoming opportunities for the global nephrology community to enhance its understanding of CKD and related complications through the study.Denker, MatthewBoyle, SuzanneAnderson, Amanda H.Appel, Lawrence J.Chen, JingFink, Jeffrey C.Flack, JohnGo, Alan S.Horwitz, EdwardHsu, Chi-yuanKusek, John W.Lash, James P.Navaneethan, SankarOjo, Akinlolu O.Rahman, MahboobSteigerwalt, Susan P.Townsend, Raymond R.Feldman, Harold I.2015-08-11T06:35:11-07:00doi:10.2215/CJN.04260415hwp:resource-id:clinjasn;10/11/2073American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, cohort study, chronic renal insufficiencySpecial FeatureSpecial Featureresearch-article20152015-11-06November 06, 201510.2215/CJN.042604151555-90411555-905X2015-08-11T06:35:11-07:002015-11-06Clinical Journal of the American Society of NephrologySpecial Feature101120732083
- Border Health: State-Level Variation in Predialysis Nephrology Care10.2215/CJN.09440915Thu, 08 Oct 2015 09:09:43 GMT-07:00Border Health: State-Level Variation in Predialysis Nephrology CareHall, Yoshio N.Himmelfarb, Jonathan2015-10-08T09:09:43-07:00doi:10.2215/CJN.09440915hwp:resource-id:clinjasn;10/11/1892American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyend-stage renal disease, United States Renal Data System, progression of chronic renal failure, ethnicity, clinical epidemiology, chronic kidney diseaseEditorialsEditorialseditorial20152015-11-06November 06, 201510.2215/CJN.094409151555-90411555-905X2015-10-08T09:09:43-07:002015-11-06Clinical Journal of the American Society of NephrologyEditorials1011111892197918941988
- The Ethics of Chronic Dialysis for the Older Patient: Time to Reevaluate the NormsRecent research highlights the potential burdens of hemodialysis for older patients with significant comorbidities, for whom there is clinical equipoise regarding the net benefits. With the advent of accountable care and bundled payment, previous incentives to offer hemodialysis to as many patients as possible are being replaced with a disincentive to dialyze high-risk patients. While this may offset the harm of overtreatment for some elderly patients, some voice concerns that the pendulum will swing too far back, with a return to ageist rationing of hemodialysis. Nephrologists should ensure that the patient’s rights to be informed about the potential benefits and burdens of hemodialysis are respected, particularly because age, functional status, nutritional status, and comorbidities affect the net balance between benefits and burdens. Nephrologists are also called on to help patients make a decision, for which the patient's goals of care guide determination of potential benefit from hemodialysis. This article addresses concerns about present overtreatment and future risk of undertreatment of older adults with ESRD. It also discusses ways in which providers can ethically approach the question of initiation of hemodialysis in the elderly patient by including patient-specific estimates of prognosis, shared decision-making, and the use of specialist palliative care clinicians or ethics consultants for complex cases.10.2215/CJN.09761014Tue, 14 Apr 2015 10:56:34 GMT-07:00The Ethics of Chronic Dialysis for the Older Patient: Time to Reevaluate the NormsRecent research highlights the potential burdens of hemodialysis for older patients with significant comorbidities, for whom there is clinical equipoise regarding the net benefits. With the advent of accountable care and bundled payment, previous incentives to offer hemodialysis to as many patients as possible are being replaced with a disincentive to dialyze high-risk patients. While this may offset the harm of overtreatment for some elderly patients, some voice concerns that the pendulum will swing too far back, with a return to ageist rationing of hemodialysis. Nephrologists should ensure that the patient’s rights to be informed about the potential benefits and burdens of hemodialysis are respected, particularly because age, functional status, nutritional status, and comorbidities affect the net balance between benefits and burdens. Nephrologists are also called on to help patients make a decision, for which the patient's goals of care guide determination of potential benefit from hemodialysis. This article addresses concerns about present overtreatment and future risk of undertreatment of older adults with ESRD. It also discusses ways in which providers can ethically approach the question of initiation of hemodialysis in the elderly patient by including patient-specific estimates of prognosis, shared decision-making, and the use of specialist palliative care clinicians or ethics consultants for complex cases.Thorsteinsdottir, BjorgSwetz, Keith M.Albright, Robert C.2015-04-14T10:56:34-07:00doi:10.2215/CJN.09761014hwp:resource-id:clinjasn;10/11/2094American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyESRD, hemodialysis, geriatric nephrology, ethics, shared decision-makingEthics SeriesEthics Seriesresearch-article20152015-11-06November 06, 201510.2215/CJN.097610141555-90411555-905X2015-04-14T10:56:34-07:002015-11-06Clinical Journal of the American Society of NephrologyEthics Series101120942099
- ADAMTS13 Secretion and Residual Activity among Patients with Congenital Thrombotic Thrombocytopenic Purpura with and without Renal Impairment10.2215/CJN.01700215Fri, 04 Sep 2015 06:30:51 GMT-07:00ADAMTS13 Secretion and Residual Activity among Patients with Congenital Thrombotic Thrombocytopenic Purpura with and without Renal ImpairmentRurali, EricaBanterla, FedericaDonadelli, RobertaBresin, ElenaGalbusera, MiriamGastoldi, SaraPeyvandi, FloraUnderwood, MaryRemuzzi, GiuseppeNoris, Marina2015-09-04T06:30:51-07:00doi:10.2215/CJN.01700215hwp:resource-id:clinjasn;10/11/2002American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycongenital TTP, ADAMTS13 mutations, ADAMTS13 secretion levels, ADAMTS13 activity, acute renal impairmentOriginal ArticlesGeneticsOriginal ArticlesGeneticsresearch-article20152015-11-06November 06, 201510.2215/CJN.017002151555-90411555-905X2015-09-04T06:30:51-07:002015-11-06Clinical Journal of the American Society of NephrologyOriginal Articles101120022012
- Predicting Risk in Peritoneal Dialysis: Is Membrane Biology Destiny?10.2215/CJN.10100915Tue, 13 Oct 2015 05:51:10 GMT-07:00Predicting Risk in Peritoneal Dialysis: Is Membrane Biology Destiny?Ramirez, Maria ErikaBargman, Joanne2015-10-13T05:51:10-07:00doi:10.2215/CJN.10100915hwp:resource-id:clinjasn;10/11/1895American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, peritoneum, risk, peritoneal membrane, epidemiology and outcomes, survival, chronic infmalationEditorialsEditorialseditorial20152015-11-06November 06, 201510.2215/CJN.101009151555-90411555-905X2015-10-13T05:51:10-07:002015-11-06Clinical Journal of the American Society of NephrologyEditorials1011111895199018962001
- A Podocyte-Based Automated Screening Assay Identifies Protective Small MoleculesPodocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell–based high–throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high–content screening–based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quantitatively measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z′ value >0.44, making it suitable for compound screening. On screening with >2100 pharmacologically active agents, we identified 24 small molecules that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an β1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active β1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS–induced podocyte foot process effacement and proteinuria. Analysis of the murine glomeruli showed that LPS administration reduced the levels of active β1 integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside–induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte–based screening assays for identifying novel therapeutics for proteinuric kidney diseases.10.1681/ASN.2014090859Thu, 09 Apr 2015 07:35:57 GMT-07:00A Podocyte-Based Automated Screening Assay Identifies Protective Small MoleculesPodocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell–based high–throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high–content screening–based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quantitatively measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z′ value >0.44, making it suitable for compound screening. On screening with >2100 pharmacologically active agents, we identified 24 small molecules that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an β1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active β1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS–induced podocyte foot process effacement and proteinuria. Analysis of the murine glomeruli showed that LPS administration reduced the levels of active β1 integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside–induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte–based screening assays for identifying novel therapeutics for proteinuric kidney diseases.Lee, Ha WonKhan, Samia Q.Faridi, Mohd HafeezWei, ChangliTardi, Nicholas J.Altintas, Mehmet M.Elshabrawy, Hatem A.Mangos, SteveQuick, Kevin L.Sever, SanjaReiser, JochenGupta, Vineet2015-04-09T07:35:57-07:00doi:10.1681/ASN.2014090859hwp:resource-id:jnephrol;26/11/2741American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerular epithelial cells, glomerular disease, adhesion moleculeBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140908591046-66731533-34502015-04-09T07:35:57-07:002015-11Journal of the American Society of NephrologyBasic Research261127412752
- Uric Acid and Cardiovascular Events: A Mendelian Randomization StudyObesity and diets rich in uric acid–raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid–regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.10.1681/ASN.2014070660Wed, 18 Mar 2015 11:44:28 GMT-07:00Uric Acid and Cardiovascular Events: A Mendelian Randomization StudyObesity and diets rich in uric acid–raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiovascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid–regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.Kleber, Marcus E.Delgado, GracielaGrammer, Tanja B.Silbernagel, GüntherHuang, JieKrämer, Bernhard K.Ritz, EberhardMärz, Winfried2015-03-18T11:44:28-07:00doi:10.1681/ASN.2014070660hwp:resource-id:jnephrol;26/11/2831American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, cardiovascular events, mortality risk, genetics, developmentClinical ResearchClinical Researchresearch-article20152015-11-01November 201510.1681/ASN.20140706601046-66731533-34502015-03-18T11:44:28-07:002015-11Journal of the American Society of NephrologyClinical Research261128312838
- Maintenance Dialysis throughout the World in Years 1990 and 2010Rapidly rising global rates of chronic diseases portend a consequent rise in ESRD. Despite this, kidney disease is not included in the list of noncommunicable diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In an effort to accurately report the trajectory and pattern of global growth of maintenance dialysis, we present the change in prevalence and incidence from 1990 to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic database. The results are on the basis of an analysis of data from worldwide national and regional renal disease registries and detailed systematic literature review for years 1980–2010. Incidence and prevalence estimates of provision of maintenance dialysis from this database were updated using a negative binomial Bayesian meta-regression tool for 187 countries. Results indicate substantial growth in utilization of maintenance dialysis in almost all world regions. Changes in population structure, changes in aging, and the worldwide increase in diabetes mellitus and hypertension explain a significant portion, but not all, of the increase because increased dialysis provision also accounts for a portion of the rise. These findings argue for the importance of inclusion of kidney disease among NCD targets for reducing premature death throughout the world.10.1681/ASN.2014101017Fri, 24 Jul 2015 12:01:23 GMT-07:00Maintenance Dialysis throughout the World in Years 1990 and 2010Rapidly rising global rates of chronic diseases portend a consequent rise in ESRD. Despite this, kidney disease is not included in the list of noncommunicable diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In an effort to accurately report the trajectory and pattern of global growth of maintenance dialysis, we present the change in prevalence and incidence from 1990 to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic database. The results are on the basis of an analysis of data from worldwide national and regional renal disease registries and detailed systematic literature review for years 1980–2010. Incidence and prevalence estimates of provision of maintenance dialysis from this database were updated using a negative binomial Bayesian meta-regression tool for 187 countries. Results indicate substantial growth in utilization of maintenance dialysis in almost all world regions. Changes in population structure, changes in aging, and the worldwide increase in diabetes mellitus and hypertension explain a significant portion, but not all, of the increase because increased dialysis provision also accounts for a portion of the rise. These findings argue for the importance of inclusion of kidney disease among NCD targets for reducing premature death throughout the world.Thomas, BernadetteWulf, SarahBikbov, BorisPerico, NorbertoCortinovis, MonicaCourville de Vaccaro, KarenFlaxman, AbrahamPeterson, HannahDelossantos, AllyneHaring, DianaMehrotra, RajnishHimmelfarb, JonathanRemuzzi, GiuseppeMurray, ChristopherNaghavi, Mohsen2015-07-24T12:01:23-07:00doi:10.1681/ASN.2014101017hwp:resource-id:jnephrol;26/11/2621American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologychronic dialysis, diabetes mellitus, ESRDUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20152015-11-01November 201510.1681/ASN.20141010171046-66731533-34502015-07-24T12:01:23-07:002015-11Journal of the American Society of NephrologyUp Front Matters2611112621260126332603
- Improving the Nephrology Match: the Path ForwardThe Fellowship Match process was designed to provide applicants and program directors with an opportunity to consider all their options before making decisions about post-residency training. In a Match, applicants can choose the programs that best suit their career goals, and program directors can consider all candidates before preparing a rank order list. The Match is a contract, requiring obligations of both programs and applicants to achieve success, ensure uniformity, and standardize participation.10.1681/ASN.2015040420Fri, 04 Sep 2015 11:58:27 GMT-07:00Improving the Nephrology Match: the Path ForwardThe Fellowship Match process was designed to provide applicants and program directors with an opportunity to consider all their options before making decisions about post-residency training. In a Match, applicants can choose the programs that best suit their career goals, and program directors can consider all candidates before preparing a rank order list. The Match is a contract, requiring obligations of both programs and applicants to achieve success, ensure uniformity, and standardize participation.Hsu, Chi-yuanParker, Mark G.Ross, Michael J.Schmidt, Rebecca J.Harris, Raymond C.2015-09-04T11:58:27-07:00doi:10.1681/ASN.2015040420hwp:resource-id:jnephrol;26/11/2634American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyNephrology training, Match, NRMPUp Front MattersSpecial ArticlesUp Front MattersSpecial Articlesresearch-article20152015-11-01November 201510.1681/ASN.20150404201046-66731533-34502015-09-04T11:58:27-07:002015-11Journal of the American Society of NephrologyUp Front Matters261126342639
- Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated VasculitisANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease.10.1681/ASN.2014050477Wed, 18 Mar 2015 11:44:30 GMT-07:00Circulating ADAM17 Level Reflects Disease Activity in Proteinase-3 ANCA-Associated VasculitisANCA-associated vasculitides are characterized by inflammatory destruction of small vessels accompanied by enhanced cleavage of membrane-bound proteins. One of the main proteases responsible for ectodomain shedding is disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Given its potential role in aggravating vascular dysfunction, we examined the role of ADAM17 in active proteinase-3 (PR3)-positive ANCA-associated vasculitis (AAV). ADAM17 concentration was significantly increased in plasma samples from patients with active PR3-AAV compared with samples from patients in remission or from other controls with renal nonvascular diseases. Comparably, plasma levels of the ADAM17 substrate syndecan-1 were significantly enhanced in active AAV. We also observed that plasma-derived ADAM17 retained its specific proteolytic activity and was partly located on extracellular microparticles. Transcript levels of ADAM17 were increased in blood samples of patients with active AAV, but those of ADAM10 or tissue inhibitor of metalloproteinases 3, which inhibits ADAMs, were not. We also performed a microRNA (miR) screen and identified miR-634 as significantly upregulated in blood samples from patients with active AAV. In vitro, miR-634 mimics induced a proinflammatory phenotype in monocyte-derived macrophages, with enhanced expression and release of ADAM17 and IL-6. These data suggest that ADAM17 has a prominent role in AAV and might account for the vascular complications associated with this disease.Bertram, AnnaLovric, SvjetlanaEngel, AlissaBeese, MichaelaWyss, KristinHertel, BarbaraPark, Joon-KeunBecker, Jan U.Kegel, JohannaHaller, HermannHaubitz, MarionKirsch, Torsten2015-03-18T11:44:30-07:00doi:10.1681/ASN.2014050477hwp:resource-id:jnephrol;26/11/2860American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, cardiovascular disease, cytokines, endothelium, macrophages, vasculitisClinical ResearchClinical Researchresearch-article20152015-11-01November 201510.1681/ASN.20140504771046-66731533-34502015-03-18T11:44:30-07:002015-11Journal of the American Society of NephrologyClinical Research261128602870
- The Labile Side of Iron Supplementation in CKDThe practice of intravenous iron supplementation has grown as nephrologists have gradually moved away from the liberal use of erythropoiesis-stimulating agents as the main treatment for the anemia of CKD. This approach, together with the introduction of large-dose iron preparations, raises the future specter of inadvertent iatrogenic iron toxicity. Concerns have been raised in original studies and reviews about cardiac complications and severe infections that result from long-term intravenous iron supplementation. Regarding the iron preparations specifically, even though all the currently available preparations appear to be relatively safe in the short term, little is known regarding their long-term safety. In this review we summarize current knowledge of iron metabolism with an emphasis on the sources and potentially harmful effects of labile iron, highlight the approaches to identifying labile iron in pharmaceutical preparations and body fluids and its potential toxic role as a pathogenic factor in the complications of CKD, and propose methods for its early detection in at-risk patients.10.1681/ASN.2015010052Thu, 21 May 2015 10:56:37 GMT-07:00The Labile Side of Iron Supplementation in CKDThe practice of intravenous iron supplementation has grown as nephrologists have gradually moved away from the liberal use of erythropoiesis-stimulating agents as the main treatment for the anemia of CKD. This approach, together with the introduction of large-dose iron preparations, raises the future specter of inadvertent iatrogenic iron toxicity. Concerns have been raised in original studies and reviews about cardiac complications and severe infections that result from long-term intravenous iron supplementation. Regarding the iron preparations specifically, even though all the currently available preparations appear to be relatively safe in the short term, little is known regarding their long-term safety. In this review we summarize current knowledge of iron metabolism with an emphasis on the sources and potentially harmful effects of labile iron, highlight the approaches to identifying labile iron in pharmaceutical preparations and body fluids and its potential toxic role as a pathogenic factor in the complications of CKD, and propose methods for its early detection in at-risk patients.Slotki, ItzchakCabantchik, Zvi Ioav2015-05-21T10:56:37-07:00doi:10.1681/ASN.2015010052hwp:resource-id:jnephrol;26/11/2612American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, anemia, mortality risk, labile iron, inflammationUp Front MattersBrief ReviewUp Front MattersBrief Reviewbrief-report20152015-11-01November 201510.1681/ASN.20150100521046-66731533-34502015-05-21T10:56:37-07:002015-11Journal of the American Society of NephrologyUp Front Matters261126122619
- Risk Adjustment and the Assessment of Disparities in Dialysis Mortality OutcomesStandardized mortality ratios (SMRs) reported by Medicare compare mortality at individual dialysis facilities with the national average, and are currently adjusted for race. However, whether the adjustment for race obscures or clarifies disparities in quality of care for minority groups is unknown. Cox model-based SMRs were computed with and without adjustment for patient race for 5920 facilities in the United States during 2010. The study population included virtually all patients treated with dialysis during this period. Without race adjustment, facilities with higher proportions of black patients had better survival outcomes; facilities with the highest percentage of black patients (top 10%) had overall mortality rates approximately 7% lower than expected. After adjusting for within-facility racial differences, facilities with higher proportions of black patients had poorer survival outcomes among black and non-black patients; facilities with the highest percentage of black patients (top 10%) had mortality rates approximately 6% worse than expected. In conclusion, accounting for within-facility racial differences in the computation of SMR helps to clarify disparities in quality of health care among patients with ESRD. The adjustment that accommodates within-facility comparisons is key, because it could also clarify relationships between patient characteristics and health care provider outcomes in other settings.10.1681/ASN.2014050512Thu, 16 Apr 2015 08:54:05 GMT-07:00Risk Adjustment and the Assessment of Disparities in Dialysis Mortality OutcomesStandardized mortality ratios (SMRs) reported by Medicare compare mortality at individual dialysis facilities with the national average, and are currently adjusted for race. However, whether the adjustment for race obscures or clarifies disparities in quality of care for minority groups is unknown. Cox model-based SMRs were computed with and without adjustment for patient race for 5920 facilities in the United States during 2010. The study population included virtually all patients treated with dialysis during this period. Without race adjustment, facilities with higher proportions of black patients had better survival outcomes; facilities with the highest percentage of black patients (top 10%) had overall mortality rates approximately 7% lower than expected. After adjusting for within-facility racial differences, facilities with higher proportions of black patients had poorer survival outcomes among black and non-black patients; facilities with the highest percentage of black patients (top 10%) had mortality rates approximately 6% worse than expected. In conclusion, accounting for within-facility racial differences in the computation of SMR helps to clarify disparities in quality of health care among patients with ESRD. The adjustment that accommodates within-facility comparisons is key, because it could also clarify relationships between patient characteristics and health care provider outcomes in other settings.Kalbfleisch, JohnWolfe, RobertBell, SarahSun, RenaMessana, JosephShearon, TempieAshby, ValariePadilla, RobinZhang, MinTurenne, MarcPearson, JeffreyDahlerus, ClaudiaLi, Yi2015-04-16T08:54:05-07:00doi:10.1681/ASN.2014050512hwp:resource-id:jnephrol;26/11/2641American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, end-stage renal disease, mortality, outcomes, risk factorsBrief CommunicationBrief Communicationbrief-report20152015-11-01November 201510.1681/ASN.20140505121046-66731533-34502015-04-16T08:54:05-07:002015-11Journal of the American Society of NephrologyBrief Communication261126412645
- This Month's Highlights10.1681/ASN.2015060721Fri, 30 Oct 2015 10:01:01 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2015-10-30T10:01:01-07:00doi:10.1681/ASN.2015060721hwp:resource-id:jnephrol;26/11/iAmerican Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20152015-11-01November 201510.1681/ASN.20150607211046-66731533-34502015-10-30T10:01:01-07:002015-11Journal of the American Society of NephrologyThis Month's Highlights2611ii
- Zinc-α2-Glycoprotein Exerts Antifibrotic Effects in Kidney and HeartZinc-α2-glycoprotein (AZGP1) is a secreted protein synthesized by epithelial cells and adipocytes that has roles in lipid metabolism, cell cycling, and cancer progression. Our previous findings in AKI indicated a new role for AZGP1 in the regulation of fibrosis, which is a unifying feature of CKD. Using two models of chronic kidney injury, we now show that mice with genetic AZGP1 deletion develop significantly more kidney fibrosis. This destructive phenotype was rescued by injection of recombinant AZGP1. Exposure of AZGP1-deficient mice to cardiac stress by thoracic aortic constriction revealed that antifibrotic effects were not restricted to the kidney but were cardioprotective. In vitro, recombinant AZGP1 inhibited kidney epithelial dedifferentiation and antagonized fibroblast activation by negatively regulating TGF-β signaling. Patient sera with high levels of AZGP1 similarly attenuated TGF-β signaling in fibroblasts. Taken together, these findings indicate a novel role for AZGP1 as a negative regulator of fibrosis progression, suggesting that recombinant AZGP1 may have translational effect for treating fibrotic disease.10.1681/ASN.2014050485Wed, 18 Mar 2015 11:44:26 GMT-07:00Zinc-α2-Glycoprotein Exerts Antifibrotic Effects in Kidney and HeartZinc-α2-glycoprotein (AZGP1) is a secreted protein synthesized by epithelial cells and adipocytes that has roles in lipid metabolism, cell cycling, and cancer progression. Our previous findings in AKI indicated a new role for AZGP1 in the regulation of fibrosis, which is a unifying feature of CKD. Using two models of chronic kidney injury, we now show that mice with genetic AZGP1 deletion develop significantly more kidney fibrosis. This destructive phenotype was rescued by injection of recombinant AZGP1. Exposure of AZGP1-deficient mice to cardiac stress by thoracic aortic constriction revealed that antifibrotic effects were not restricted to the kidney but were cardioprotective. In vitro, recombinant AZGP1 inhibited kidney epithelial dedifferentiation and antagonized fibroblast activation by negatively regulating TGF-β signaling. Patient sera with high levels of AZGP1 similarly attenuated TGF-β signaling in fibroblasts. Taken together, these findings indicate a novel role for AZGP1 as a negative regulator of fibrosis progression, suggesting that recombinant AZGP1 may have translational effect for treating fibrotic disease.Sörensen-Zender, IngaBhayana, SagarSusnik, NathanRolli, VeroniqueBatkai, SandorBaisantry, ArpitaBahram, SiamakSen, PayelTeng, BeinaLindner, RobertSchiffer, MarioThum, ThomasMelk, AnetteHaller, HermannSchmitt, Roland2015-03-18T11:44:26-07:00doi:10.1681/ASN.2014050485hwp:resource-id:jnephrol;26/11/2659American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, epithelial, fibroblast, renal fibrosis, renal tubular epithelial cells, GF-βBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140504851046-66731533-34502015-03-18T11:44:26-07:002015-11Journal of the American Society of NephrologyBasic Research261126592668
- Placental Growth Factor as a Predictor of Cardiovascular Events in Patients with CKD from the NARA-CKD StudyPlacental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals [95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile (≥19.6 pg/ml) and the lowest eGFR tertile (<30 ml/min per 1.73 m2). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD.10.1681/ASN.2014080772Wed, 18 Mar 2015 11:44:39 GMT-07:00Placental Growth Factor as a Predictor of Cardiovascular Events in Patients with CKD from the NARA-CKD StudyPlacental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals [95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile (≥19.6 pg/ml) and the lowest eGFR tertile (<30 ml/min per 1.73 m2). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD.Matsui, MasaruUemura, ShiroTakeda, YukijiSamejima, Ken-ichiMatsumoto, TakakiHasegawa, AyakoTsushima, HideoHoshino, EiUeda, TomoyaMorimoto, KatsuhikoOkamoto, KeisukeOkada, SadanoriOnoue, KenjiOkayama, SatoshiKawata, HiroyukiKawakami, RikaMaruyama, NaokiAkai, YasuhiroIwano, MasayukiShiiki, HideoSaito, Yoshihiko,2015-03-18T11:44:39-07:00doi:10.1681/ASN.2014080772hwp:resource-id:jnephrol;26/11/2871American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, VEGF, cardiovascular eventsClinical ResearchClinical Researchresearch-article20152015-11-01November 201510.1681/ASN.20140807721046-66731533-34502015-03-18T11:44:39-07:002015-11Journal of the American Society of NephrologyClinical Research261128712881
- Akt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal IschemiaRenal ischemia and reperfusion injury causes loss of renal epithelial cell polarity and perturbations in tubular solute and fluid transport. Na+,K+-ATPase, which is normally found at the basolateral plasma membrane of renal epithelial cells, is internalized and accumulates in intracellular compartments after renal ischemic injury. We previously reported that the subcellular distribution of Na+,K+-ATPase is modulated by direct binding to Akt substrate of 160 kD (AS160), a Rab GTPase-activating protein that regulates the trafficking of glucose transporter 4 in response to insulin and muscle contraction. Here, we investigated the effect of AS160 on Na+,K+-ATPase trafficking in response to energy depletion. We found that AS160 is required for the intracellular accumulation of Na+,K+-ATPase that occurs in response to energy depletion in cultured epithelial cells. Energy depletion led to dephosphorylation of AS160 at S588, which was required for the energy depletion–induced accumulation of Na,K-ATPase in intracellular compartments. In AS160-knockout mice, the effects of renal ischemia on the distribution of Na+,K+-ATPase were substantially reduced in the epithelial cells of distal segments of the renal tubules. These data demonstrate that AS160 has a direct role in linking the trafficking of Na+,K+-ATPase to the energy state of renal epithelial cells.10.1681/ASN.2013101040Wed, 18 Mar 2015 11:44:33 GMT-07:00Akt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal IschemiaRenal ischemia and reperfusion injury causes loss of renal epithelial cell polarity and perturbations in tubular solute and fluid transport. Na+,K+-ATPase, which is normally found at the basolateral plasma membrane of renal epithelial cells, is internalized and accumulates in intracellular compartments after renal ischemic injury. We previously reported that the subcellular distribution of Na+,K+-ATPase is modulated by direct binding to Akt substrate of 160 kD (AS160), a Rab GTPase-activating protein that regulates the trafficking of glucose transporter 4 in response to insulin and muscle contraction. Here, we investigated the effect of AS160 on Na+,K+-ATPase trafficking in response to energy depletion. We found that AS160 is required for the intracellular accumulation of Na+,K+-ATPase that occurs in response to energy depletion in cultured epithelial cells. Energy depletion led to dephosphorylation of AS160 at S588, which was required for the energy depletion–induced accumulation of Na,K-ATPase in intracellular compartments. In AS160-knockout mice, the effects of renal ischemia on the distribution of Na+,K+-ATPase were substantially reduced in the epithelial cells of distal segments of the renal tubules. These data demonstrate that AS160 has a direct role in linking the trafficking of Na+,K+-ATPase to the energy state of renal epithelial cells.Alves, Daiane S.Thulin, GunillaLoffing, JohannesKashgarian, MichaelCaplan, Michael J.2015-03-18T11:44:33-07:00doi:10.1681/ASN.2013101040hwp:resource-id:jnephrol;26/11/2765American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycell physiology, transport physiology, cell biology, cell structure, cell signaling, epithelial, ischemia-reperfusion, MDCKBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20131010401046-66731533-34502015-03-18T11:44:33-07:002015-11Journal of the American Society of NephrologyBasic Research261127652776
- Combined Deletion of Vhl and Kif3a Accelerates Renal Cyst FormationA subset of familial and sporadic clear cell renal cell carcinomas (ccRCCs) is believed to develop from cystic precursor lesions. Loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the primary cilium in response to specific signals. Because the primary cilium suppresses renal cyst formation, loss of the cilium may be an initiating event in the formation of ccRCC. To test this hypothesis, we analyzed the consequences of inducible renal epithelium–specific deletion of Vhl together with ablation of the primary cilium via deletion of the kinesin family member 3A (Kif3a) gene. We developed a microcomputed tomography–based imaging approach to allow quantitative longitudinal monitoring of cystic burden, revealing that combined loss of Vhl and Kif3a shortened the latency of cyst initiation, increased the number of cysts per kidney, and increased the total cystic burden. In contrast with findings in other cystic models, cysts in Kif3a mutant mice did not display accumulation of hypoxia-inducible factor 1-α (HIF1α), and deletion of both Hif1a and Kif3a did not affect cyst development or progression. Vhl/Kif3a double mutation also increased the frequency of cysts that displayed multilayered epithelial growth, which correlated with an increased frequency of misoriented cystic epithelial cell divisions. These results argue against the involvement of HIF1α in promoting renal cyst growth and suggest that the formation of simple and atypical renal cysts that resemble ccRCC precursor lesions is greatly accelerated by the combined loss of Vhl and the primary cilium.10.1681/ASN.2014090875Wed, 18 Mar 2015 11:44:27 GMT-07:00Combined Deletion of Vhl and Kif3a Accelerates Renal Cyst FormationA subset of familial and sporadic clear cell renal cell carcinomas (ccRCCs) is believed to develop from cystic precursor lesions. Loss of function of the von Hippel-Lindau tumor suppressor gene (VHL) predisposes renal epithelial cells to loss of the primary cilium in response to specific signals. Because the primary cilium suppresses renal cyst formation, loss of the cilium may be an initiating event in the formation of ccRCC. To test this hypothesis, we analyzed the consequences of inducible renal epithelium–specific deletion of Vhl together with ablation of the primary cilium via deletion of the kinesin family member 3A (Kif3a) gene. We developed a microcomputed tomography–based imaging approach to allow quantitative longitudinal monitoring of cystic burden, revealing that combined loss of Vhl and Kif3a shortened the latency of cyst initiation, increased the number of cysts per kidney, and increased the total cystic burden. In contrast with findings in other cystic models, cysts in Kif3a mutant mice did not display accumulation of hypoxia-inducible factor 1-α (HIF1α), and deletion of both Hif1a and Kif3a did not affect cyst development or progression. Vhl/Kif3a double mutation also increased the frequency of cysts that displayed multilayered epithelial growth, which correlated with an increased frequency of misoriented cystic epithelial cell divisions. These results argue against the involvement of HIF1α in promoting renal cyst growth and suggest that the formation of simple and atypical renal cysts that resemble ccRCC precursor lesions is greatly accelerated by the combined loss of Vhl and the primary cilium.Lehmann, HolgerVicari, DanieleWild, Peter J.Frew, Ian J.2015-03-18T11:44:27-07:00doi:10.1681/ASN.2014090875hwp:resource-id:jnephrol;26/11/2778American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyrenal carcinoma, cystic kidney, cell biology and structureBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140908751046-66731533-34502015-03-18T11:44:27-07:002015-11Journal of the American Society of NephrologyBasic Research261127782788
- Hepcidin Mitigates Renal Ischemia-Reperfusion Injury by Modulating Systemic Iron HomeostasisIron-mediated oxidative stress is implicated in the pathogenesis of renal ischemia–reperfusion injury. Hepcidin is an endogenous acute phase hepatic hormone that prevents iron export from cells by inducing degradation of the only known iron export protein, ferroportin. In this study, we used a mouse model to investigate the effect of renal ischemia–reperfusion injury on systemic iron homeostasis and determine if dynamic modulation of iron homeostasis with hepcidin has therapeutic benefit in the treatment of AKI. Renal ischemia–reperfusion injury induced hepatosplenic iron export through increased ferroportin expression, which resulted in hepatosplenic iron depletion and an increase in serum and kidney nonheme iron levels. Exogenous hepcidin treatment prevented renal ischemia-reperfusion–induced changes in iron homeostasis. Hepcidin also decreased kidney ferroportin expression and increased the expression of cytoprotective H-ferritin. Hepcidin-induced restoration of iron homeostasis was accompanied by a significant reduction in ischemia-reperfusion–induced tubular injury, apoptosis, renal oxidative stress, and inflammatory cell infiltration. Hepcidin–deficient mice demonstrated increased susceptibility to ischemia-reperfusion injury compared with wild-type mice. Reconstituting hepcidin-deficient mice with exogenous hepcidin induced hepatic iron sequestration, attenuated the reduction in renal H-ferritin and reduced renal oxidative stress, apoptosis, inflammation, and tubular injury. Hepcidin-mediated protection was associated with reduced serum IL-6 levels. In summary, renal ischemia–reperfusion injury results in profound alterations in systemic iron homeostasis. Hepcidin treatment restores iron homeostasis and reduces inflammation to mediate protection in renal ischemia–reperfusion injury, suggesting that hepcidin-ferroportin pathway holds promise as a novel therapeutic target in the treatment of AKI.10.1681/ASN.2014101037Wed, 18 Mar 2015 11:44:29 GMT-07:00Hepcidin Mitigates Renal Ischemia-Reperfusion Injury by Modulating Systemic Iron HomeostasisIron-mediated oxidative stress is implicated in the pathogenesis of renal ischemia–reperfusion injury. Hepcidin is an endogenous acute phase hepatic hormone that prevents iron export from cells by inducing degradation of the only known iron export protein, ferroportin. In this study, we used a mouse model to investigate the effect of renal ischemia–reperfusion injury on systemic iron homeostasis and determine if dynamic modulation of iron homeostasis with hepcidin has therapeutic benefit in the treatment of AKI. Renal ischemia–reperfusion injury induced hepatosplenic iron export through increased ferroportin expression, which resulted in hepatosplenic iron depletion and an increase in serum and kidney nonheme iron levels. Exogenous hepcidin treatment prevented renal ischemia-reperfusion–induced changes in iron homeostasis. Hepcidin also decreased kidney ferroportin expression and increased the expression of cytoprotective H-ferritin. Hepcidin-induced restoration of iron homeostasis was accompanied by a significant reduction in ischemia-reperfusion–induced tubular injury, apoptosis, renal oxidative stress, and inflammatory cell infiltration. Hepcidin–deficient mice demonstrated increased susceptibility to ischemia-reperfusion injury compared with wild-type mice. Reconstituting hepcidin-deficient mice with exogenous hepcidin induced hepatic iron sequestration, attenuated the reduction in renal H-ferritin and reduced renal oxidative stress, apoptosis, inflammation, and tubular injury. Hepcidin-mediated protection was associated with reduced serum IL-6 levels. In summary, renal ischemia–reperfusion injury results in profound alterations in systemic iron homeostasis. Hepcidin treatment restores iron homeostasis and reduces inflammation to mediate protection in renal ischemia–reperfusion injury, suggesting that hepcidin-ferroportin pathway holds promise as a novel therapeutic target in the treatment of AKI.Scindia, YogeshDey, ParomitaThirunagari, AbhinavLiping, HuangRosin, Diane L.Floris, MatteoOkusa, Mark D.Swaminathan, Sundararaman2015-03-18T11:44:29-07:00doi:10.1681/ASN.2014101037hwp:resource-id:jnephrol;26/11/2800American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyischemia-reperfusion, iron homeostasis, hepcidin, acute kidney injury, acute renal failure, oxidative stressBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20141010371046-66731533-34502015-03-18T11:44:29-07:002015-11Journal of the American Society of NephrologyBasic Research261128002814
- Ambient Melamine Exposure and Urinary Biomarkers of Early Renal InjuryInformation about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August–December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday–Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (P<0.001). Urinary melamine levels were positively associated with urinary N-acetyl β-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable β2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting.10.1681/ASN.2014121233Thu, 04 Jun 2015 07:24:16 GMT-07:00Ambient Melamine Exposure and Urinary Biomarkers of Early Renal InjuryInformation about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August–December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday–Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (P<0.001). Urinary melamine levels were positively associated with urinary N-acetyl β-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable β2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting.Wu, Chia-FangPeng, Chiung-YuLiu, Chia-ChuLin, Wen-YiPan, Chih-HongCheng, Ching-MeiHsieh, Hui-MinHsieh, Tusty-JiuanChen, Bai-HsiunWu, Ming-Tsang2015-06-04T07:24:16-07:00doi:10.1681/ASN.2014121233hwp:resource-id:jnephrol;26/11/2821American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, chronic renal failure, clinical epidemiology, nephrotoxicity, biomarkers of renal tubular injuryClinical EpidemiologyClinical Epidemiologyresearch-article20152015-11-01November 201510.1681/ASN.20141212331046-66731533-34502015-06-04T07:24:16-07:002015-11Journal of the American Society of NephrologyClinical Epidemiology261128212829
- Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody–Mediated Kidney Allograft RejectionUrinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively diagnose T cell–mediated rejection (TCMR) of renal allografts. However, performance of these molecules as diagnostic/prognostic markers of antibody-mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10 levels in a highly sensitized cohort of 244 renal allograft recipients (67 with preformed donor–specific antibodies [DSAs]) with 281 indication biopsy samples. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the extent of tubulointerstitial (i+t score; all P<0.001) and microvascular (g+ptc score; all P<0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P<0.001) and ABMR (AUC=0.76; 95% CI, 0.69 to 0.82; P<0.001) with high accuracy, even in the absence of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P<0.001). Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR (AUC=0.75; 95% CI, 0.68 to 0.82; P<0.001), combining urinary CXCL10:Cr with immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77 to 0.89; P<0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr ratio associates with tubulointerstitial and microvascular inflammation of the renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring significantly improves the noninvasive diagnosis of ABMR and the stratification of patients at high risk for graft loss.10.1681/ASN.2014080797Wed, 06 May 2015 06:11:16 GMT-07:00Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody–Mediated Kidney Allograft RejectionUrinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively diagnose T cell–mediated rejection (TCMR) of renal allografts. However, performance of these molecules as diagnostic/prognostic markers of antibody-mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10 levels in a highly sensitized cohort of 244 renal allograft recipients (67 with preformed donor–specific antibodies [DSAs]) with 281 indication biopsy samples. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the extent of tubulointerstitial (i+t score; all P<0.001) and microvascular (g+ptc score; all P<0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P<0.001) and ABMR (AUC=0.76; 95% CI, 0.69 to 0.82; P<0.001) with high accuracy, even in the absence of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P<0.001). Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR (AUC=0.75; 95% CI, 0.68 to 0.82; P<0.001), combining urinary CXCL10:Cr with immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77 to 0.89; P<0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr ratio associates with tubulointerstitial and microvascular inflammation of the renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring significantly improves the noninvasive diagnosis of ABMR and the stratification of patients at high risk for graft loss.Rabant, MarionAmrouche, LucileLebreton, XavierAulagnon, FlorenceBenon, AurélienSauvaget, VirginiaBonifay, RajaMorin, LiseScemla, AnneDelville, MarianneMartinez, FrankTimsit, Marc OlivierDuong Van Huyen, Jean-PaulLegendre, ChristopheTerzi, FabiolaAnglicheau, Dany2015-05-06T06:11:16-07:00doi:10.1681/ASN.2014080797hwp:resource-id:jnephrol;26/11/2840American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologykidney transplantation, noninvasive diagnosis, biomarker, antibody-mediated rejectionClinical ResearchClinical Researchresearch-article20152015-11-01November 201510.1681/ASN.20140807971046-66731533-34502015-05-06T06:11:16-07:002015-11Journal of the American Society of NephrologyClinical Research2611112840260728512609
- C4d as a Diagnostic Tool in Proliferative GNProliferative GN is classified as immune complex-mediated or complement-mediated (C3 glomerulopathy). Immune complex-mediated GN results from glomerular deposition of immune-complexes/Ig and C3; the C3 is derived from activation of the classical and/or lectin pathways of complement. C3 glomerulopathy results from deposition of C3 and other complement fragments with minimal or no deposition of immune complexes/Ig; the C3 is derived from activation of the alternative pathway of complement. C4d is a byproduct of activation of the classic and lectin pathways. Although widely used as a marker for antibody-mediated rejection, the significance of C4d in C3 glomerulopathy is undetermined. We studied glomerular C4d staining in 18 biopsy specimens of immune-complex GN, 30 biopsy specimens of C3 GN, and 13 biopsy specimens of postinfectious GN. All specimens of immune complex-mediated GN, except two specimens of IgA nephropathy and one specimen of sclerosing membranoproliferative GN, showed bright (2–3+) C4d staining. The staining pattern of C4d mirrored the staining patterns of Ig and C3. Conversely, C4d staining was completely negative in 24 (80%) of 30 specimens of C3 glomerulopathy, and only trace/1+ C4d staining was detected in six (20%) specimens. With regard to postinfectious GN, C4d staining was negative in six (46%) of 13 specimens, suggesting an abnormality in the alternative pathway, and it was positive in seven (54%) specimens. To summarize, C4d serves as a positive marker for immune complex-mediated GN but is absent or minimally detected in C3 glomerulopathy.10.1681/ASN.2014040406Tue, 19 May 2015 05:07:21 GMT-07:00C4d as a Diagnostic Tool in Proliferative GNProliferative GN is classified as immune complex-mediated or complement-mediated (C3 glomerulopathy). Immune complex-mediated GN results from glomerular deposition of immune-complexes/Ig and C3; the C3 is derived from activation of the classical and/or lectin pathways of complement. C3 glomerulopathy results from deposition of C3 and other complement fragments with minimal or no deposition of immune complexes/Ig; the C3 is derived from activation of the alternative pathway of complement. C4d is a byproduct of activation of the classic and lectin pathways. Although widely used as a marker for antibody-mediated rejection, the significance of C4d in C3 glomerulopathy is undetermined. We studied glomerular C4d staining in 18 biopsy specimens of immune-complex GN, 30 biopsy specimens of C3 GN, and 13 biopsy specimens of postinfectious GN. All specimens of immune complex-mediated GN, except two specimens of IgA nephropathy and one specimen of sclerosing membranoproliferative GN, showed bright (2–3+) C4d staining. The staining pattern of C4d mirrored the staining patterns of Ig and C3. Conversely, C4d staining was completely negative in 24 (80%) of 30 specimens of C3 glomerulopathy, and only trace/1+ C4d staining was detected in six (20%) specimens. With regard to postinfectious GN, C4d staining was negative in six (46%) of 13 specimens, suggesting an abnormality in the alternative pathway, and it was positive in seven (54%) specimens. To summarize, C4d serves as a positive marker for immune complex-mediated GN but is absent or minimally detected in C3 glomerulopathy.Sethi, SanjeevNasr, Samih HDe Vriese, An S.Fervenza, Fernando C.2015-05-19T05:07:21-07:00doi:10.1681/ASN.2014040406hwp:resource-id:jnephrol;26/11/2852American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyglomerulonephritis, immunology and pathology, kidney biopsy, membranoproliferative glomerulonephritis (MPGN), renal pathologyClinical ResearchClinical Researchresearch-article20152015-11-01November 201510.1681/ASN.20140404061046-66731533-34502015-05-19T05:07:21-07:002015-11Journal of the American Society of NephrologyClinical Research2611112852260928592611
- Visualization of Calcium Dynamics in Kidney Proximal TubulesIntrarenal changes in cytoplasmic calcium levels have a key role in determining pathologic and pharmacologic responses in major kidney diseases. However, cell-specific delivery of calcium-sensitive probes in vivo remains problematic. We generated a transgenic rat stably expressing the green fluorescent protein-calmodulin–based genetically encoded calcium indicator (GCaMP2) predominantly in the kidney proximal tubules. The transposon-based method used allowed the generation of homozygous transgenic rats containing one copy of the transgene per allele with a defined insertion pattern, without genetic or phenotypic alterations. We applied in vitro confocal and in vivo two-photon microscopy to examine basal calcium levels and ligand- and drug-induced alterations in these levels in proximal tubular epithelial cells. Notably, renal ischemia induced a transient increase in cellular calcium, and reperfusion resulted in a secondary calcium load, which was significantly decreased by systemic administration of specific blockers of the angiotensin receptor and the Na-Ca exchanger. The parallel examination of in vivo cellular calcium dynamics and renal circulation by fluorescent probes opens new possibilities for physiologic and pharmacologic investigations.10.1681/ASN.2014070705Wed, 18 Mar 2015 11:44:38 GMT-07:00Visualization of Calcium Dynamics in Kidney Proximal TubulesIntrarenal changes in cytoplasmic calcium levels have a key role in determining pathologic and pharmacologic responses in major kidney diseases. However, cell-specific delivery of calcium-sensitive probes in vivo remains problematic. We generated a transgenic rat stably expressing the green fluorescent protein-calmodulin–based genetically encoded calcium indicator (GCaMP2) predominantly in the kidney proximal tubules. The transposon-based method used allowed the generation of homozygous transgenic rats containing one copy of the transgene per allele with a defined insertion pattern, without genetic or phenotypic alterations. We applied in vitro confocal and in vivo two-photon microscopy to examine basal calcium levels and ligand- and drug-induced alterations in these levels in proximal tubular epithelial cells. Notably, renal ischemia induced a transient increase in cellular calcium, and reperfusion resulted in a secondary calcium load, which was significantly decreased by systemic administration of specific blockers of the angiotensin receptor and the Na-Ca exchanger. The parallel examination of in vivo cellular calcium dynamics and renal circulation by fluorescent probes opens new possibilities for physiologic and pharmacologic investigations.Szebényi, KornéliaFüredi, AndrásKolacsek, OrsolyaCsohány, RózsaPrókai, ÁgnesKis-Petik, KatalinSzabó, AttilaBősze, ZsuzsannaBender, BalázsTóvári, JózsefEnyedi, ÁgnesOrbán, Tamás I.Apáti, ÁgotaSarkadi, Balázs2015-03-18T11:44:38-07:00doi:10.1681/ASN.2014070705hwp:resource-id:jnephrol;26/11/2731American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, renal ischemia, renal proximal tubule cell, ischemia-reperfusion, hypoxiaBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140707051046-66731533-34502015-03-18T11:44:38-07:002015-11Journal of the American Society of NephrologyBasic Research261127312740
- Activated Protein C Ameliorates Renal Ischemia-Reperfusion Injury by Restricting Y-Box Binding Protein-1 UbiquitinationIschemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role of the coagulation system in renal IRI has been established, but the functional relevance of thrombomodulin (TM)-dependent activated protein C (aPC) generation and the intracellular targets of aPC remain undefined. Here, we investigated the role of TM-dependent aPC generation and therapeutic aPC application in a murine renal IRI model and in an in vitro hypoxia and reoxygenation (HR) model using proximal tubular cells. In renal IRI, endogenous aPC levels were reduced. Genetic or therapeutic reconstitution of aPC efficiently ameliorated renal IRI independently of its anticoagulant properties. In tubular cells, cytoprotective aPC signaling was mediated through protease activated receptor-1- and endothelial protein C receptor-dependent regulation of the cold-shock protein Y-box binding protein-1 (YB-1). The mature 50 kD form of YB-1 was required for the nephro- and cytoprotective effects of aPC in vivo and in vitro, respectively. Reduction of mature YB-1 and K48-linked ubiquitination of YB-1 was prevented by aPC after renal IRI or tubular HR injury. aPC preserved the interaction of YB-1 with the deubiquitinating enzyme otubain-1 and maintained expression of otubain-1, which was required to reduce K48-linked YB-1 ubiquitination and to stabilize the 50 kD form of YB-1 after renal IRI and tubular HR injury. These data link the cyto- and nephroprotective effects of aPC with the ubiquitin-proteasome system and identify YB-1 as a novel intracellular target of aPC. These insights may provide new impetus for translational efforts aiming to restrict renal IRI.10.1681/ASN.2014080846Tue, 26 May 2015 08:19:23 GMT-07:00Activated Protein C Ameliorates Renal Ischemia-Reperfusion Injury by Restricting Y-Box Binding Protein-1 UbiquitinationIschemia-reperfusion injury (IRI) is the leading cause of ARF. A pathophysiologic role of the coagulation system in renal IRI has been established, but the functional relevance of thrombomodulin (TM)-dependent activated protein C (aPC) generation and the intracellular targets of aPC remain undefined. Here, we investigated the role of TM-dependent aPC generation and therapeutic aPC application in a murine renal IRI model and in an in vitro hypoxia and reoxygenation (HR) model using proximal tubular cells. In renal IRI, endogenous aPC levels were reduced. Genetic or therapeutic reconstitution of aPC efficiently ameliorated renal IRI independently of its anticoagulant properties. In tubular cells, cytoprotective aPC signaling was mediated through protease activated receptor-1- and endothelial protein C receptor-dependent regulation of the cold-shock protein Y-box binding protein-1 (YB-1). The mature 50 kD form of YB-1 was required for the nephro- and cytoprotective effects of aPC in vivo and in vitro, respectively. Reduction of mature YB-1 and K48-linked ubiquitination of YB-1 was prevented by aPC after renal IRI or tubular HR injury. aPC preserved the interaction of YB-1 with the deubiquitinating enzyme otubain-1 and maintained expression of otubain-1, which was required to reduce K48-linked YB-1 ubiquitination and to stabilize the 50 kD form of YB-1 after renal IRI and tubular HR injury. These data link the cyto- and nephroprotective effects of aPC with the ubiquitin-proteasome system and identify YB-1 as a novel intracellular target of aPC. These insights may provide new impetus for translational efforts aiming to restrict renal IRI.Dong, WeiWang, HongjieShahzad, KhurrumBock, FabianAl-Dabet, Moh'd MohanadRanjan, SatishWolter, JulianeKohli, ShreyHoffmann, JulianeDhople, Vishnu MukundZhu, ChengLindquist, Jonathan A.Esmon, Charles T.Gröne, ElisabethGröne, Herman-JosefMadhusudhan, ThatiMertens, Peter R.Schlüter, DirkIsermann, Berend2015-05-26T08:19:23-07:00doi:10.1681/ASN.2014080846hwp:resource-id:jnephrol;26/11/2789American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycell signaling, ischemic renal failure, renal proximal tubule cell, acute renal, failure, ischemia-reperfusion, thrombosisBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140808461046-66731533-34502015-05-26T08:19:23-07:002015-11Journal of the American Society of NephrologyBasic Research2611112789260527992607
- A Role for Tubular Necroptosis in Cisplatin-Induced AKICell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis, a type of programmed necrosis, has a role in cisplatin-induced AKI. We found that inhibition of any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination of cytokines (TNF-α, TNF-related weak inducer of apoptosis, and IFN-γ) that were upregulated in proximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatin-treated mice was partially diminished in RIP3- or MLKL-deficient mice, suggesting a positive feedback loop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI.10.1681/ASN.2014080741Wed, 18 Mar 2015 11:44:36 GMT-07:00A Role for Tubular Necroptosis in Cisplatin-Induced AKICell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis, a type of programmed necrosis, has a role in cisplatin-induced AKI. We found that inhibition of any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination of cytokines (TNF-α, TNF-related weak inducer of apoptosis, and IFN-γ) that were upregulated in proximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatin-treated mice was partially diminished in RIP3- or MLKL-deficient mice, suggesting a positive feedback loop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI.Xu, YanfangMa, HuabinShao, JingWu, JianfengZhou, LinyingZhang, ZhirongWang, YuzeHuang, ZheRen, JunmingLiu, SuhuanChen, XiangmeiHan, Jiahuai2015-03-18T11:44:36-07:00doi:10.1681/ASN.2014080741hwp:resource-id:jnephrol;26/11/2647American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologynecroptosis, renal proximal tubule cell, cisplatin nephrotoxicityBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140807411046-66731533-34502015-03-18T11:44:36-07:002015-11Journal of the American Society of NephrologyBasic Research261126472658
- Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific TranscriptomesThe function of each renal tubule segment depends on the genes expressed therein. High-throughput methods used for global profiling of gene expression in unique cell types have shown low sensitivity and high false positivity, thereby limiting the usefulness of these methods in transcriptomic research. However, deep sequencing of RNA species (RNA-seq) achieves highly sensitive and quantitative transcriptomic profiling by sequencing RNAs in a massive, parallel manner. Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys. Polyadenylated mRNAs were captured by oligo-dT primers and processed into adapter–ligated cDNA libraries that were sequenced using an Illumina platform. Transcriptomes were identified to a median depth of 8261 genes in microdissected renal tubule samples (105 replicates in total) and glomeruli (5 replicates). Manual microdissection allowed a high degree of sample purity, which was evidenced by the observed distributions of well established cell–specific markers. The main product of this work is an extensive database of gene expression along the nephron provided as a publicly accessible webpage (https://helixweb.nih.gov/ESBL/Database/NephronRNAseq/index.html). The data also provide genome-wide maps of alternative exon usage and polyadenylation sites in the kidney. We illustrate the use of the data by profiling transcription factor expression along the renal tubule and mapping metabolic pathways.10.1681/ASN.2014111067Fri, 27 Mar 2015 12:56:03 GMT-07:00Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific TranscriptomesThe function of each renal tubule segment depends on the genes expressed therein. High-throughput methods used for global profiling of gene expression in unique cell types have shown low sensitivity and high false positivity, thereby limiting the usefulness of these methods in transcriptomic research. However, deep sequencing of RNA species (RNA-seq) achieves highly sensitive and quantitative transcriptomic profiling by sequencing RNAs in a massive, parallel manner. Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys. Polyadenylated mRNAs were captured by oligo-dT primers and processed into adapter–ligated cDNA libraries that were sequenced using an Illumina platform. Transcriptomes were identified to a median depth of 8261 genes in microdissected renal tubule samples (105 replicates in total) and glomeruli (5 replicates). Manual microdissection allowed a high degree of sample purity, which was evidenced by the observed distributions of well established cell–specific markers. The main product of this work is an extensive database of gene expression along the nephron provided as a publicly accessible webpage (https://helixweb.nih.gov/ESBL/Database/NephronRNAseq/index.html). The data also provide genome-wide maps of alternative exon usage and polyadenylation sites in the kidney. We illustrate the use of the data by profiling transcription factor expression along the renal tubule and mapping metabolic pathways.Lee, Jae WookChou, Chung-LinKnepper, Mark A.2015-03-27T12:56:03-07:00doi:10.1681/ASN.2014111067hwp:resource-id:jnephrol;26/11/2669American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologynephron, transcriptional profiling, transcription factors, collecting ductsBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20141110671046-66731533-34502015-03-27T12:56:03-07:002015-11Journal of the American Society of NephrologyBasic Research2611112669260326772605
- Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ TransportKcnj10 encodes the inwardly rectifying K+ channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K+ channel are incompletely characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells demonstrated that c-Src–induced stimulation of Kcnj10 requires coexpression of caveolin-1 (cav-1), and immunostaining showed expression of cav-1 in the basolateral membrane of parvalbumin-positive DCT. Patch-clamp experiments detected a 40-pS inwardly rectifying K+ channel, a heterotetramer of Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild-type (WT) and cav-1-knockout (KO) mice. However, the activity of this basolateral 40-pS K+ channel was lower in KO mice than in WT mice. Moreover, the K+ reversal potential (an indication of membrane potential) was less negative in the DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated that cav-1 deficiency decreased the expression of the Na+/Cl– cotransporter and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of epithelial Na+ channel-α. Furthermore, the urinary excretion of Mg2+ and K+ was significantly higher in KO mice than in WT mice, and KO mice developed hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav-1 decreases basolateral K+ channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na+/Cl– cotransporter expression induced by cav-1 deficiency may underlie the compromised renal transport of Mg2+, Ca2+, and K+.10.1681/ASN.2014070658Mon, 06 Apr 2015 05:57:44 GMT-07:00Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ TransportKcnj10 encodes the inwardly rectifying K+ channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K+ channel are incompletely characterized. Here, patch-clamp experiments in Kcnj10-transfected HEK293 cells demonstrated that c-Src–induced stimulation of Kcnj10 requires coexpression of caveolin-1 (cav-1), and immunostaining showed expression of cav-1 in the basolateral membrane of parvalbumin-positive DCT. Patch-clamp experiments detected a 40-pS inwardly rectifying K+ channel, a heterotetramer of Kir4.1/Kir5.1, in the basolateral membrane of the early DCT (DCT1) in both wild-type (WT) and cav-1-knockout (KO) mice. However, the activity of this basolateral 40-pS K+ channel was lower in KO mice than in WT mice. Moreover, the K+ reversal potential (an indication of membrane potential) was less negative in the DCT1 of KO mice than in the DCT1 of WT mice. Western blot analysis demonstrated that cav-1 deficiency decreased the expression of the Na+/Cl– cotransporter and Ste20-proline-alanine-rich kinase (SPAK) but increased the expression of epithelial Na+ channel-α. Furthermore, the urinary excretion of Mg2+ and K+ was significantly higher in KO mice than in WT mice, and KO mice developed hypomagnesemia, hypocalcemia, and hypokalemia. We conclude that disruption of cav-1 decreases basolateral K+ channel activity and depolarizes the cell membrane potential in the DCT1 at least in part by suppressing the stimulatory effect of c-Src on Kcnj10. Furthermore, the decrease in Kcnj10 and Na+/Cl– cotransporter expression induced by cav-1 deficiency may underlie the compromised renal transport of Mg2+, Ca2+, and K+.Wang, LijunZhang, ChengbiaoSu, XiaotongLin, Dao-HongWang, Wenhui2015-04-06T05:57:44-07:00doi:10.1681/ASN.2014070658hwp:resource-id:jnephrol;26/11/2678American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyK channels, hypokalemia, Gitelman’s syndromeBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140706581046-66731533-34502015-04-06T05:57:44-07:002015-11Journal of the American Society of NephrologyBasic Research261126782690
- Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein ExpressionAccumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca2+ signals mediated by store–operated Ca2+ channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store–operated Ca2+ channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store–operated Ca2+ channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium release–activated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II–induced fibronectin protein expression, whereas thapsigargin abrogated high glucose– and TGF-β1–stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno–associated virus–encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store–operated Ca2+ channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes.10.1681/ASN.2014090853Wed, 18 Mar 2015 11:44:24 GMT-07:00Store–Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein ExpressionAccumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca2+ signals mediated by store–operated Ca2+ channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store–operated Ca2+ channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store–operated Ca2+ channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium release–activated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II–induced fibronectin protein expression, whereas thapsigargin abrogated high glucose– and TGF-β1–stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno–associated virus–encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store–operated Ca2+ channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes.Wu, PeiwenWang, YanxiaDavis, Mark E.Zuckerman, Jonathan E.Chaudhari, SarikaBegg, MalcolmMa, Rong2015-03-18T11:44:24-07:00doi:10.1681/ASN.2014090853hwp:resource-id:jnephrol;26/11/2691American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycalcium, diabetic nephropathy, extracellular matrix, fibronectin, ion, channel, mesangial cellsBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140908531046-66731533-34502015-03-18T11:44:24-07:002015-11Journal of the American Society of NephrologyBasic Research261126912702
- A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen ExpansionGrainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells. Hence, we identified a Grhl2/Ovol2 network controlling Cldn4 and Rab25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia.10.1681/ASN.2014080759Wed, 18 Mar 2015 11:44:37 GMT-07:00A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen ExpansionGrainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells. Hence, we identified a Grhl2/Ovol2 network controlling Cldn4 and Rab25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia.Aue, AnnekatrinHinze, ChristianWalentin, KatharinaRuffert, JanettYurtdas, YesimWerth, MaxChen, WeiRabien, AnjaKilic, ErginSchulzke, Jörg-DieterSchumann, MichaelSchmidt-Ott, Kai M.2015-03-18T11:44:37-07:00doi:10.1681/ASN.2014080759hwp:resource-id:jnephrol;26/11/2704American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyGrainyhead transcription factors, collecting duct, lumen expansion, barrier, formation, nephric duct, Grainyhead-like 2Basic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140807591046-66731533-34502015-03-18T11:44:37-07:002015-11Journal of the American Society of NephrologyBasic Research261127042715
- EGF Receptor Inhibition Alleviates Hyperuricemic NephropathyHyperuricemia is an independent risk factor for CKD and contributes to kidney fibrosis. In this study, we investigated the effect of EGF receptor (EGFR) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN induced by feeding a mixture of adenine and potassium oxonate, increased EGFR phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of gefitinib, a highly selective EGFR inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. Gefitinib treatment also inhibited hyperuricemia-induced activation of the TGF-β1 and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, gefitinib treatment suppressed xanthine oxidase activity, which mediates uric acid production, and preserved expression of organic anion transporters 1 and 3, which promotes uric acid excretion in the kidney of hyperuricemic rats. Thus, blocking EGFR can attenuate development of HN via suppression of TGF-β1 signaling and inflammation and promotion of the molecular processes that reduce uric acid accumulation in the body.10.1681/ASN.2014080793Wed, 18 Mar 2015 11:44:35 GMT-07:00EGF Receptor Inhibition Alleviates Hyperuricemic NephropathyHyperuricemia is an independent risk factor for CKD and contributes to kidney fibrosis. In this study, we investigated the effect of EGF receptor (EGFR) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN induced by feeding a mixture of adenine and potassium oxonate, increased EGFR phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of gefitinib, a highly selective EGFR inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. Gefitinib treatment also inhibited hyperuricemia-induced activation of the TGF-β1 and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, gefitinib treatment suppressed xanthine oxidase activity, which mediates uric acid production, and preserved expression of organic anion transporters 1 and 3, which promotes uric acid excretion in the kidney of hyperuricemic rats. Thus, blocking EGFR can attenuate development of HN via suppression of TGF-β1 signaling and inflammation and promotion of the molecular processes that reduce uric acid accumulation in the body.Liu, NaWang, LiYang, TaoXiong, ChongxiangXu, LiuqingShi, YingfengBao, WenfangChin, Y. EugeneCheng, Shi-BinYan, HaidongQiu, AndongZhuang, Shougang2015-03-18T11:44:35-07:00doi:10.1681/ASN.2014080793hwp:resource-id:jnephrol;26/11/2716American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyCell signaling, chronic kidney disease, interstitial fibrosis, fibroblast, TGF-betaBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140807931046-66731533-34502015-03-18T11:44:35-07:002015-11Journal of the American Society of NephrologyBasic Research261127162729
- Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft RejectionThe myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.10.1681/ASN.2014080813Wed, 18 Mar 2015 11:44:32 GMT-07:00Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft RejectionThe myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection.Lerret, Nadine M.Li, TingWang, Jiao-JingKang, Hee-KapWang, ShengWang, XueqiongJie, ChunfaKanwar, Yashpal S.Abecassis, Michael M.Luo, XunrongZhang, Zheng2015-03-18T11:44:32-07:00doi:10.1681/ASN.2014080813hwp:resource-id:jnephrol;26/11/2753American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, kidney transplantation, lymphocytes, renal, function, transgenic mouseBasic ResearchBasic Researchresearch-article20152015-11-01November 201510.1681/ASN.20140808131046-66731533-34502015-03-18T11:44:32-07:002015-11Journal of the American Society of NephrologyBasic Research261127532764
- Heritability of Risk for Sudden Cardiac Arrest in ESRDPatients on dialysis are 20 times more likely to have a cardiac arrest compared with the general population. We considered whether inherited factors associate with cardiac arrest among patients on dialysis. From a sample of 647,457 patients on chronic dialysis, we identified 5117 pairs of patients who came from the same family. These patients were each matched to a control subject from the same population. McNemar’s tests were used to compare the risk of cardiac arrest between the familial related and unrelated pairs. Genetically related family members who did not cohabitate had an odds ratio of 1.88 (95% confidence interval [95% CI], 1.25 to 2.84) for cardiac arrest compared with their phenotypically matched unrelated controls. Genetically related family members who lived together in the same environment had an odds ratio of 1.66 (95% CI, 1.20 to 2.28). Spouses, who are genetically unrelated but live together in the same environment, had an odds ratio of 0.95 (95% CI, 0.60 to 1.59) for cardiac arrest. The risk of cardiac arrest in patients on dialysis may be attributable to inherited factors. Additional studies are needed to identify such candidate genes that modify cardiovascular risk in ESRD.10.1681/ASN.2014090881Thu, 16 Apr 2015 08:54:06 GMT-07:00Heritability of Risk for Sudden Cardiac Arrest in ESRDPatients on dialysis are 20 times more likely to have a cardiac arrest compared with the general population. We considered whether inherited factors associate with cardiac arrest among patients on dialysis. From a sample of 647,457 patients on chronic dialysis, we identified 5117 pairs of patients who came from the same family. These patients were each matched to a control subject from the same population. McNemar’s tests were used to compare the risk of cardiac arrest between the familial related and unrelated pairs. Genetically related family members who did not cohabitate had an odds ratio of 1.88 (95% confidence interval [95% CI], 1.25 to 2.84) for cardiac arrest compared with their phenotypically matched unrelated controls. Genetically related family members who lived together in the same environment had an odds ratio of 1.66 (95% CI, 1.20 to 2.28). Spouses, who are genetically unrelated but live together in the same environment, had an odds ratio of 0.95 (95% CI, 0.60 to 1.59) for cardiac arrest. The risk of cardiac arrest in patients on dialysis may be attributable to inherited factors. Additional studies are needed to identify such candidate genes that modify cardiovascular risk in ESRD.Chan, Kevin E.Newton-Cheh, ChristopherGusella, James F.Maddux, Franklin W.2015-04-16T08:54:06-07:00doi:10.1681/ASN.2014090881hwp:resource-id:jnephrol;26/11/2815American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular, dialysis, epidemiology and outcomesClinical EpidemiologyClinical Epidemiologyresearch-article20152015-11-01November 201510.1681/ASN.20140908811046-66731533-34502015-04-16T08:54:06-07:002015-11Journal of the American Society of NephrologyClinical Epidemiology261128152820
- APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South AfricansAPOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a South-African black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polymorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy–naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.10.1681/ASN.2014050469Wed, 18 Mar 2015 11:44:23 GMT-07:00APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South AfricansAPOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a South-African black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polymorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy–naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.Kasembeli, Alex N.Duarte, RaquelRamsay, MichèleMosiane, PulaneDickens, CarolineDix-Peek, ThérèseLimou, SophieSezgin, EfeNelson, George W.Fogo, Agnes B.Goetsch, StewartKopp, Jeffrey B.Winkler, Cheryl A.Naicker, Saraladevi2015-03-18T11:44:23-07:00doi:10.1681/ASN.2014050469hwp:resource-id:jnephrol;26/11/2882American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, collapsing glomerulopathy, HIV nephropathy, genetics, developmentClinical ResearchClinical Researchresearch-article20152015-11-01November 201510.1681/ASN.20140504691046-66731533-34502015-03-18T11:44:23-07:002015-11Journal of the American Society of NephrologyClinical Research261128822890
- Urine CXCL10/IP-10 Fingers Ongoing Antibody-Mediated Kidney Graft Rejection10.1681/ASN.2015040353Wed, 06 May 2015 06:11:16 GMT-07:00Urine CXCL10/IP-10 Fingers Ongoing Antibody-Mediated Kidney Graft RejectionFairchild, Robert L.Suthanthiran, Manikkam2015-05-06T06:11:16-07:00doi:10.1681/ASN.2015040353hwp:resource-id:jnephrol;26/11/2607American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute allograft rejection, chemokine, transplantationUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-11-01November 201510.1681/ASN.20150403531046-66731533-34502015-05-06T06:11:16-07:002015-11Journal of the American Society of NephrologyUp Front Matters2611112607284026092851
- C4d Staining in the Diagnosis of C3 Glomerulopathy10.1681/ASN.2015040433Tue, 19 May 2015 05:07:21 GMT-07:00C4d Staining in the Diagnosis of C3 GlomerulopathyCook, H. Terence2015-05-19T05:07:21-07:00doi:10.1681/ASN.2015040433hwp:resource-id:jnephrol;26/11/2609American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycomplement, glomerulonephritis, immunohistochemistryUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-11-01November 201510.1681/ASN.20150404331046-66731533-34502015-05-19T05:07:21-07:002015-11Journal of the American Society of NephrologyUp Front Matters2611112609285226112859
- A Friend in Need: Activated Protein C Stabilizes YB-1 during Renal Ischemia Reperfusion Injury10.1681/ASN.2015040351Tue, 26 May 2015 08:19:22 GMT-07:00A Friend in Need: Activated Protein C Stabilizes YB-1 during Renal Ischemia Reperfusion InjuryGriffin, BrendaMurphy, Madeline2015-05-26T08:19:22-07:00doi:10.1681/ASN.2015040351hwp:resource-id:jnephrol;26/11/2605American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, epithelial, ischemia reperfusionUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-11-01November 201510.1681/ASN.20150403511046-66731533-34502015-05-26T08:19:22-07:002015-11Journal of the American Society of NephrologyUp Front Matters2611112605278926072799
- Meeting the World’s Need for Maintenance Dialysis10.1681/ASN.2015060660Fri, 24 Jul 2015 12:01:23 GMT-07:00Meeting the World’s Need for Maintenance DialysisWetmore, James B.Collins, Allan J.2015-07-24T12:01:23-07:00doi:10.1681/ASN.2015060660hwp:resource-id:jnephrol;26/11/2601American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyESRD, dialysis, worldUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-11-01November 201510.1681/ASN.20150606601046-66731533-34502015-07-24T12:01:23-07:002015-11Journal of the American Society of NephrologyUp Front Matters2611112601262126032633
- A Transcriptional Map of the Renal Tubule: Linking Structure to Function10.1681/ASN.2015030242Fri, 27 Mar 2015 12:56:02 GMT-07:00A Transcriptional Map of the Renal Tubule: Linking Structure to FunctionKretzler, MatthiasJu, Wenjun2015-03-27T12:56:02-07:00doi:10.1681/ASN.2015030242hwp:resource-id:jnephrol;26/11/2603American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologynephron, transcriptional profiling, gene expressionUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-11-01November 201510.1681/ASN.20150302421046-66731533-34502015-03-27T12:56:02-07:002015-11Journal of the American Society of NephrologyUp Front Matters2611112603266926052677
- Cardiac Resynchronization Therapy in CKD Stage 4 Patients10.2215/CJN.00620115Fri, 25 Sep 2015 01:16:23 GMT-07:00Cardiac Resynchronization Therapy in CKD Stage 4 PatientsHöke, UlasKhidir, Mand J.H.van der Velde, Enno T.Schalij, Martin J.Bax, Jeroen J.Delgado, VictoriaMarsan, Nina Ajmone2015-09-25T13:16:23-07:00doi:10.2215/CJN.00620115hwp:resource-id:clinjasn;10/10/1740American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyrenal function, chronic kidney disease, congestive heart failure, chronic, heart failure, survivalOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-10-07October 07, 201510.2215/CJN.006201151555-90411555-905X2015-09-25T13:16:23-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1010101740170517481707
- Urinary EGF Receptor Ligand Excretion in Patients with Autosomal Dominant Polycystic Kidney Disease and Response to Tolvaptan10.2215/CJN.09941014Fri, 31 Jul 2015 10:25:44 GMT-07:00Urinary EGF Receptor Ligand Excretion in Patients with Autosomal Dominant Polycystic Kidney Disease and Response to TolvaptanHarskamp, Laura R.Gansevoort, Ron T.Boertien, Wendy E.van Oeveren, WimEngels, Gerwin E.van Goor, HarryMeijer, Esther2015-07-31T10:25:44-07:00doi:10.2215/CJN.09941014hwp:resource-id:clinjasn;10/10/1749American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyADPKD, HB-EGF, V2 receptor antagonist, EGF receptorOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-10-07October 07, 201510.2215/CJN.099410141555-90411555-905X2015-07-31T10:25:44-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017491756
- Prevalence and Correlates of CKD in Hispanics/Latinos in the United States10.2215/CJN.02020215Mon, 28 Sep 2015 08:28:01 GMT-07:00Prevalence and Correlates of CKD in Hispanics/Latinos in the United StatesRicardo, Ana C.Flessner, Michael F.Eckfeldt, John H.Eggers, Paul W.Franceschini, NoraGo, Alan S.Gotman, Nathan M.Kramer, Holly J.Kusek, John W.Loehr, Laura R.Melamed, Michal L.Peralta, Carmen A.Raij, LeopoldoRosas, Sylvia E.Talavera, Gregory A.Lash, James P.2015-09-28T08:28:01-07:00doi:10.2215/CJN.02020215hwp:resource-id:clinjasn;10/10/1757American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCKD, prevalence, HispanicsOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-10-07October 07, 201510.2215/CJN.020202151555-90411555-905X2015-09-28T08:28:01-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1010101757170817661710
- Early Failure of Dialysis Access among the Elderly in the Era of Fistula First10.2215/CJN.09040914Fri, 07 Aug 2015 07:04:59 GMT-07:00Early Failure of Dialysis Access among the Elderly in the Era of Fistula FirstWoo, KarenGoldman, Dana P.Romley, John A.2015-08-07T07:04:59-07:00doi:10.2215/CJN.09040914hwp:resource-id:clinjasn;10/10/1791American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyarteriovenous shunt, ESRD, geriatric nephrology, Medicare claims, surgical failureOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-10-07October 07, 201510.2215/CJN.090409141555-90411555-905X2015-08-07T07:04:59-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017911798
- Receipt of Intravenous Iron and Clinical Outcomes among Hemodialysis Patients Hospitalized for Infection10.2215/CJN.01090115Mon, 28 Sep 2015 08:28:02 GMT-07:00Receipt of Intravenous Iron and Clinical Outcomes among Hemodialysis Patients Hospitalized for InfectionIshida, Julie H.Marafino, Ben J.McCulloch, Charles E.Dalrymple, Lorien S.Dudley, R. AdamsGrimes, Barbara A.Johansen, Kirsten L.2015-09-28T08:28:02-07:00doi:10.2215/CJN.01090115hwp:resource-id:clinjasn;10/10/1799American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, iron, infectionOriginal ArticlesEpidemiology and OutcomesOriginal ArticlesEpidemiology and Outcomesresearch-article20152015-10-07October 07, 201510.2215/CJN.010901151555-90411555-905X2015-09-28T08:28:02-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1010101799171418051715
- Serotonin-Norepinephrine Reuptake Inhibitors and the Risk of AKI: A Cohort Study of Eight Administrative Databases and Meta-Analysis10.2215/CJN.11271114Fri, 31 Jul 2015 10:25:45 GMT-07:00Serotonin-Norepinephrine Reuptake Inhibitors and the Risk of AKI: A Cohort Study of Eight Administrative Databases and Meta-AnalysisRenoux, ChristelLix, Lisa M.Patenaude, ValérieBresee, Lauren C.Paterson, J. MichaelLafrance, Jean-PhilippeTamim, HalaMahmud, Salaheddin M.Alsabbagh, Mhd. WasemHemmelgarn, BrendaDormuth, Colin R.Ernst, Pierre,2015-07-31T10:25:45-07:00doi:10.2215/CJN.11271114hwp:resource-id:clinjasn;10/10/1716American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyARF, risk factors, drug nephrotoxicity, clinical epidemiology, depressionOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20152015-10-07October 07, 201510.2215/CJN.112711141555-90411555-905X2015-07-31T10:25:45-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017161722
- False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria10.2215/CJN.02430315Thu, 03 Sep 2015 06:25:37 GMT-07:00False-Positive Rate of AKI Using Consensus Creatinine–Based CriteriaLin, JennieFernandez, HildaShashaty, Michael G.S.Negoianu, DanTestani, Jeffrey M.Berns, Jeffrey S.Parikh, Chirag R.Wilson, F. Perry2015-09-03T06:25:37-07:00doi:10.2215/CJN.02430315hwp:resource-id:clinjasn;10/10/1723American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, epidemiology and outcomes, survival, creatinine, misdiagnosisOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20152015-10-07October 07, 201510.2215/CJN.024303151555-90411555-905X2015-09-03T06:25:37-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017231731
- Outcomes After Post-Traumatic AKI Requiring RRT in United States Military Service Members10.2215/CJN.00890115Thu, 03 Sep 2015 06:25:36 GMT-07:00Outcomes After Post-Traumatic AKI Requiring RRT in United States Military Service MembersBolanos, Jonathan A.Yuan, Christina M.Little, Dustin J.Oliver, David K.Howard, Steven R.Abbott, Kevin C.Olson, Stephen W.2015-09-03T06:25:36-07:00doi:10.2215/CJN.00890115hwp:resource-id:clinjasn;10/10/1732American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyacute renal failure, chronic kidney disease, dialysis, mortality risk, military casualtiesOriginal ArticlesAcute Kidney InjuryOriginal ArticlesAcute Kidney Injuryresearch-article20152015-10-07October 07, 201510.2215/CJN.008901151555-90411555-905X2015-09-03T06:25:36-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017321739
- Is Intravenous Iron Supplementation Safe to Administer to Patients on Hemodialysis with Active Infection—What Do We Know, and What More Do We Need to Know?10.2215/CJN.08060715Mon, 28 Sep 2015 08:28:02 GMT-07:00Is Intravenous Iron Supplementation Safe to Administer to Patients on Hemodialysis with Active Infection—What Do We Know, and What More Do We Need to Know?Bennett, Charles LeeHermanson, Terhi2015-09-28T08:28:02-07:00doi:10.2215/CJN.08060715hwp:resource-id:clinjasn;10/10/1714American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyhemodialysis, chronic kidney disease, cardiovascular diseaseEditorialsEditorialseditorial20152015-10-07October 07, 201510.2215/CJN.080607151555-90411555-905X2015-09-28T08:28:02-07:002015-10-07Clinical Journal of the American Society of NephrologyEditorials1010101714179917151805
- Hyponatremia and Cognitive Impairment in Patients Treated with Peritoneal Dialysis10.2215/CJN.02240215Fri, 31 Jul 2015 10:25:44 GMT-07:00Hyponatremia and Cognitive Impairment in Patients Treated with Peritoneal DialysisXu, RongPi, Hai-chenXiong, Zu-yingLiao, Jin-lanHao, LiLiu, Gui-lingRen, Ye-PingWang, QinZheng, Zhao-xiaDuan, Li-pingDong, Jie2015-07-31T10:25:44-07:00doi:10.2215/CJN.02240215hwp:resource-id:clinjasn;10/10/1806American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyperitoneal dialysis, hyponatremia, executive dysfunction, cognitive impairmentOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-10-07October 07, 201510.2215/CJN.022402151555-90411555-905X2015-07-31T10:25:44-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101018061813
- Physiology of the Renal InterstitiumLong overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial renin- and erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium.10.2215/CJN.00640114Thu, 26 Mar 2015 09:03:50 GMT-07:00Physiology of the Renal InterstitiumLong overlooked as the virtual compartment and then strictly characterized through descriptive morphologic analysis, the renal interstitium has finally been associated with function. With identification of interstitial renin- and erythropoietin-producing cells, the most prominent endocrine functions of the kidney have now been attributed to the renal interstitium. This article reviews the functional role of renal interstitium.Zeisberg, MichaelKalluri, Raghu2015-03-26T09:03:50-07:00doi:10.2215/CJN.00640114hwp:resource-id:clinjasn;10/10/1831American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyfibrosis, renal interstitium, renin angiotensin system, erythropoietin, fibroblastRenal PhysiologyRenal Physiologyresearch-article20152015-10-07October 07, 201510.2215/CJN.006401141555-90411555-905X2015-03-26T09:03:50-07:002015-10-07Clinical Journal of the American Society of NephrologyRenal Physiology101018311840
- Dendritic Cells and Macrophages: Sentinels in the KidneyThe mononuclear phagocytes (dendritic cells and macrophages) are closely related immune cells with central roles in anti-infectious defense and maintenance of organ integrity. The canonical function of dendritic cells is the activation of T cells, whereas macrophages remove apoptotic cells and microbes by phagocytosis. In the kidney, these cell types form an intricate system of mononuclear phagocytes that surveys against injury and infection and contributes to organ homeostasis and tissue repair but may also promote progression of CKD. This review summarizes the general functions and classification of dendritic cells and macrophages in the immune system and recapitulates why overlapping definitions and historically separate research have created controversy about their tasks. Their roles in acute kidney disease, CKD, and renal transplantation are described, and therapeutic strategy to modify these cells for therapeutic purposes is discussed.10.2215/CJN.07100714Wed, 07 Jan 2015 07:50:02 GMT-08:00Dendritic Cells and Macrophages: Sentinels in the KidneyThe mononuclear phagocytes (dendritic cells and macrophages) are closely related immune cells with central roles in anti-infectious defense and maintenance of organ integrity. The canonical function of dendritic cells is the activation of T cells, whereas macrophages remove apoptotic cells and microbes by phagocytosis. In the kidney, these cell types form an intricate system of mononuclear phagocytes that surveys against injury and infection and contributes to organ homeostasis and tissue repair but may also promote progression of CKD. This review summarizes the general functions and classification of dendritic cells and macrophages in the immune system and recapitulates why overlapping definitions and historically separate research have created controversy about their tasks. Their roles in acute kidney disease, CKD, and renal transplantation are described, and therapeutic strategy to modify these cells for therapeutic purposes is discussed.Weisheit, Christina K.Engel, Daniel R.Kurts, Christian2015-01-07T07:50:02-08:00doi:10.2215/CJN.07100714hwp:resource-id:clinjasn;10/10/1841American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologymacrophages, kidney disease, immunology, immunology and pathology, immunosuppressionRenal ImmunologyRenal Immunologyresearch-article20152015-10-07October 07, 201510.2215/CJN.071007141555-90411555-905X2015-01-07T07:50:02-08:002015-10-07Clinical Journal of the American Society of NephrologyRenal Immunology101018411851
- Promoting Kidney Function Recovery in Patients with AKI Requiring RRTAKI requiring RRT is associated with high mortality, morbidity, and long-term consequences, including CKD and ESRD. Many patients never recover kidney function; in others, kidney function improves over a period of many weeks or months. Methodologic constraints of the available literature limit our understanding of the recovery process and hamper adequate intervention. Current management strategies have focused on acute care and short-term mortality, but new data indicate that long-term consequences of AKI requiring RRT are substantial. Promotion of kidney function recovery is a neglected focus of research and intervention. This lack of emphasis on recovery is illustrated by the relative paucity of research in this area and by the lack of demonstrated effective management strategies. In this article the epidemiologic implications of kidney recovery after AKI requiring RRT are discussed, the available literature and its methodologic constraints are reviewed, and strategies to improve the understanding of factors that affect kidney function recovery are proposed. Measures to promote kidney function recovery are a serious unmet need, with a great potential to improve short- and long-term patient outcomes.10.2215/CJN.01170215Thu, 02 Jul 2015 09:52:03 GMT-07:00Promoting Kidney Function Recovery in Patients with AKI Requiring RRTAKI requiring RRT is associated with high mortality, morbidity, and long-term consequences, including CKD and ESRD. Many patients never recover kidney function; in others, kidney function improves over a period of many weeks or months. Methodologic constraints of the available literature limit our understanding of the recovery process and hamper adequate intervention. Current management strategies have focused on acute care and short-term mortality, but new data indicate that long-term consequences of AKI requiring RRT are substantial. Promotion of kidney function recovery is a neglected focus of research and intervention. This lack of emphasis on recovery is illustrated by the relative paucity of research in this area and by the lack of demonstrated effective management strategies. In this article the epidemiologic implications of kidney recovery after AKI requiring RRT are discussed, the available literature and its methodologic constraints are reviewed, and strategies to improve the understanding of factors that affect kidney function recovery are proposed. Measures to promote kidney function recovery are a serious unmet need, with a great potential to improve short- and long-term patient outcomes.Cerdá, JorgeLiu, Kathleen D.Cruz, Dinna N.Jaber, Bertrand L.Koyner, Jay L.Heung, MichaelOkusa, Mark D.Faubel, Sarah2015-07-02T09:52:03-07:00doi:10.2215/CJN.01170215hwp:resource-id:clinjasn;10/10/1859American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyAKI, kidney function recovery, survival, RRT, progression of renal failureCommentaryCommentaryarticle-commentary20152015-10-07October 07, 201510.2215/CJN.011702151555-90411555-905X2015-07-02T09:52:03-07:002015-10-07Clinical Journal of the American Society of NephrologyCommentary101018591867
- Outpatient Dialysis for Patients with AKI: A Policy Approach to Improving CareThe rate of AKI requiring dialysis has increased significantly over the past decade in the United States. At the same time, survival from AKI seems to be improving, and thus, more patients with AKI are surviving to discharge while still requiring dialysis. Currently, the options for providing outpatient dialysis in patients with AKI are limited, particularly after a 2012 revised interpretation of the Centers for Medicare and Medicaid Services guidelines, which prohibited Medicare reimbursement for acute dialysis at ESRD facilities. This article provides a historical perspective on outpatient dialysis management of patients with AKI, reviews the current clinical landscape of care for these patients, and highlights key areas of knowledge deficit. Lastly, policy changes that have the opportunity to significantly improve the care of this at-risk population are suggested.10.2215/CJN.02290215Tue, 28 Jul 2015 09:20:43 GMT-07:00Outpatient Dialysis for Patients with AKI: A Policy Approach to Improving CareThe rate of AKI requiring dialysis has increased significantly over the past decade in the United States. At the same time, survival from AKI seems to be improving, and thus, more patients with AKI are surviving to discharge while still requiring dialysis. Currently, the options for providing outpatient dialysis in patients with AKI are limited, particularly after a 2012 revised interpretation of the Centers for Medicare and Medicaid Services guidelines, which prohibited Medicare reimbursement for acute dialysis at ESRD facilities. This article provides a historical perspective on outpatient dialysis management of patients with AKI, reviews the current clinical landscape of care for these patients, and highlights key areas of knowledge deficit. Lastly, policy changes that have the opportunity to significantly improve the care of this at-risk population are suggested.Heung, MichaelFaubel, SarahWatnick, SuzanneCruz, Dinna N.Koyner, Jay L.Mour, GirishLiu, Kathleen D.Cerda, JorgeOkusa, Mark D.Lukaszewski, MarkVijayan, Anitha2015-07-28T09:20:43-07:00doi:10.2215/CJN.02290215hwp:resource-id:clinjasn;10/10/1868American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyCenters for Medicare and Medicaid Services, dialysis, acute dialysis, ESRDCommentaryCommentaryarticle-commentary20152015-10-07October 07, 201510.2215/CJN.022902151555-90411555-905X2015-07-28T09:20:43-07:002015-10-07Clinical Journal of the American Society of NephrologyCommentary101018681874
- Correction10.2215/CJN.08840815Thu, 17 Sep 2015 06:22:37 GMT-07:00CorrectionAmerican Society of Nephrology2015-09-17T18:22:37-07:00doi:10.2215/CJN.08840815hwp:resource-id:clinjasn;10/10/1886American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologycalcium, phosphate, magnesium homeostasis, erratumErratumErratumcorrection20152015-10-07October 07, 201510.2215/CJN.088408151555-90411555-905X2015-09-17T18:22:37-07:002015-10-07Clinical Journal of the American Society of NephrologyErratum10101071886125718871272
- Mineral (Mal)Adaptation to Kidney Disease—Young Investigator Award Address: American Society of Nephrology Kidney Week 2014In the short time since its initial discovery as the cause of rare hypophosphatemic disorders, fibroblast growth factor-23 (FGF-23) has emerged as a major regulator of mineral metabolism and critical component of the bone and mineral adaptation to CKD. However, because elevated FGF-23 levels are also a novel biomarker and possible molecular mediator of increased risks of cardiovascular disease and death in CKD, the initially adaptive response to increase FGF-23 levels to maintain neutral phosphate balance in CKD may ultimately become maladaptive. Incorporating FGF-23 into understanding the complex physiology that governs normal bone and mineral metabolism and its alterations in CKD has filled critical knowledge gaps and opened a new landscape of exciting hypotheses and novel therapeutic strategies to be tested in the continued quest to alleviate the burden of CKD.10.2215/CJN.04430415Tue, 08 Sep 2015 09:19:17 GMT-07:00Mineral (Mal)Adaptation to Kidney Disease—Young Investigator Award Address: American Society of Nephrology Kidney Week 2014In the short time since its initial discovery as the cause of rare hypophosphatemic disorders, fibroblast growth factor-23 (FGF-23) has emerged as a major regulator of mineral metabolism and critical component of the bone and mineral adaptation to CKD. However, because elevated FGF-23 levels are also a novel biomarker and possible molecular mediator of increased risks of cardiovascular disease and death in CKD, the initially adaptive response to increase FGF-23 levels to maintain neutral phosphate balance in CKD may ultimately become maladaptive. Incorporating FGF-23 into understanding the complex physiology that governs normal bone and mineral metabolism and its alterations in CKD has filled critical knowledge gaps and opened a new landscape of exciting hypotheses and novel therapeutic strategies to be tested in the continued quest to alleviate the burden of CKD.Wolf, Myles2015-09-08T09:19:17-07:00doi:10.2215/CJN.04430415hwp:resource-id:clinjasn;10/10/1875American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyphosphate, FGF-23, calciumSpecial FeatureSpecial Featureresearch-article20152015-10-07October 07, 201510.2215/CJN.044304151555-90411555-905X2015-09-08T09:19:17-07:002015-10-07Clinical Journal of the American Society of NephrologySpecial Feature101018751885
- Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States10.2215/CJN.01590215Thu, 10 Sep 2015 06:36:59 GMT-07:00Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United StatesWright, Daniel G.Wright, Elizabeth C.Narva, Andrew S.Noguchi, Constance T.Eggers, Paul W.2015-09-10T06:36:59-07:00doi:10.2215/CJN.01590215hwp:resource-id:clinjasn;10/10/1822American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, ESRD, erythropoietin, epoetin, hemodialysisOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-10-07October 07, 201510.2215/CJN.015902151555-90411555-905X2015-09-10T06:36:59-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101018221830
- A New Grading System for the Management of Antenatal Hydronephrosis10.2215/CJN.12861214Fri, 31 Jul 2015 10:25:47 GMT-07:00A New Grading System for the Management of Antenatal HydronephrosisDos Santos, JoanaParekh, Rulan S.Piscione, Tino D.Hassouna, TarekFigueroa, VictorGonima, PaulaVargas, IsisFarhat, WalidRosenblum, Norman D.2015-07-31T10:25:47-07:00doi:10.2215/CJN.12861214hwp:resource-id:clinjasn;10/10/1783American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyantenatal hydronephrosis, congenital hydronephrosis, grading system, pelviectasis, ureteropelvic junction obstructionOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20152015-10-07October 07, 201510.2215/CJN.128612141555-90411555-905X2015-07-31T10:25:47-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017831790
- The Role of Ethnic Variation and CKD10.2215/CJN.09100815Mon, 28 Sep 2015 08:28:02 GMT-07:00The Role of Ethnic Variation and CKDHarawa, Nina T.Norris, Keith C.2015-09-28T08:28:02-07:00doi:10.2215/CJN.09100815hwp:resource-id:clinjasn;10/10/1708American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologychronic kidney disease, ethnicity, epidemiology and outcomesEditorialsEditorialseditorial20152015-10-07October 07, 201510.2215/CJN.091008151555-90411555-905X2015-09-28T08:28:02-07:002015-10-07Clinical Journal of the American Society of NephrologyEditorials1010101708175717101766
- Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing10.2215/CJN.02600315Tue, 18 Aug 2015 07:10:20 GMT-07:00Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent DosingKaraboyas, AngeloZee, JarcyMorgenstern, HalNolen, Jacqueline G.Hakim, RaymondKalantar-Zadeh, KamyarZager, PhilipPisoni, Ronald L.Port, Friedrich K.Robinson, Bruce M.2015-08-18T07:10:20-07:00doi:10.2215/CJN.02600315hwp:resource-id:clinjasn;10/10/1814American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyanemia, chronic kidney disease, dialysis, erythropoietin, epoetinOriginal ArticlesESRD and Chronic DialysisOriginal ArticlesESRD and Chronic Dialysisresearch-article20152015-10-07October 07, 201510.2215/CJN.026003151555-90411555-905X2015-08-18T07:10:20-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101018141821
- Cardiorenal Resynchronization Therapy: Strengthening the Heart and Kidneys10.2215/CJN.09120815Fri, 25 Sep 2015 01:16:22 GMT-07:00Cardiorenal Resynchronization Therapy: Strengthening the Heart and KidneysObeng-Gyimah, Edmond K.Deo, Rajat2015-09-25T13:16:22-07:00doi:10.2215/CJN.09120815hwp:resource-id:clinjasn;10/10/1705American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyheart failure, electrophysiology, echocardiography, chronic kidney diseaseEditorialsEditorialseditorial20152015-10-07October 07, 201510.2215/CJN.091208151555-90411555-905X2015-09-25T13:16:22-07:002015-10-07Clinical Journal of the American Society of NephrologyEditorials1010101705174017071748
- Performance of Temporary Hemodialysis Catheter Insertion by Nephrology Fellows and Attending Nephrologists10.2215/CJN.01720215Fri, 25 Sep 2015 01:16:23 GMT-07:00Performance of Temporary Hemodialysis Catheter Insertion by Nephrology Fellows and Attending NephrologistsMcQuillan, Rory F.Clark, EdwardZahirieh, AlirezaCohen, Elaine R.Paparello, James J.Wayne, Diane B.Barsuk, Jeffrey H.2015-09-25T13:16:23-07:00doi:10.2215/CJN.01720215hwp:resource-id:clinjasn;10/10/1767American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysimulation, mastery learning, nephrology training, central venous catheter insertion, competencyOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20152015-10-07October 07, 201510.2215/CJN.017202151555-90411555-905X2015-09-25T13:16:23-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles1010101767171117721713
- Eculizumab in Pediatric Dense Deposit Disease10.2215/CJN.01360215Thu, 27 Aug 2015 07:11:44 GMT-07:00Eculizumab in Pediatric Dense Deposit DiseaseOosterveld, Michiel J.S.Garrelfs, Mark R.Hoppe, BerndFlorquin, SandrineRoelofs, Joris J.T.H.van den Heuvel, L.P.Amann, KerstinDavin, Jean-ClaudeBouts, Antonia H.M.Schriemer, Pietrik J.Groothoff, Jaap W.2015-08-27T07:11:44-07:00doi:10.2215/CJN.01360215hwp:resource-id:clinjasn;10/10/1773American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of NephrologyC3 glomerulopathy, dense deposit disease, glomerulonephritis, membranoproliferative, C3 nephritic factor, complementOriginal ArticlesClinical NephrologyOriginal ArticlesClinical Nephrologyresearch-article20152015-10-07October 07, 201510.2215/CJN.013602151555-90411555-905X2015-08-27T07:11:44-07:002015-10-07Clinical Journal of the American Society of NephrologyOriginal Articles101017731782
- We Need to Train the Trainers10.2215/CJN.08650815Fri, 25 Sep 2015 01:16:22 GMT-07:00We Need to Train the TrainersAsif, ArifBeathard, Gerald A.2015-09-25T13:16:22-07:00doi:10.2215/CJN.08650815hwp:resource-id:clinjasn;10/10/1711American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologyinterventional nephrology, dialysis access, dialysisEditorialsEditorialseditorial20152015-10-07October 07, 201510.2215/CJN.086508151555-90411555-905X2015-09-25T13:16:22-07:002015-10-07Clinical Journal of the American Society of NephrologyEditorials1010101711176717131772
- Tolerant Kidney Transplant Patients Produce B Cells with Regulatory PropertiesWhereas a B cell–transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells have in this tolerance has not been reported. In this study, we analyzed the role of B cells from operationally tolerant patients, healthy volunteers, and kidney transplant recipients with stable graft function on T cell suppression. Proliferation, apoptosis, and type I proinflammatory cytokine production by effector CD4+CD25− T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells inhibit CD4+CD25− effector T cell response in a dose-dependent manner. This effect required B cells to interact with T-cell targets and was achieved through a granzyme B (GzmB)–dependent pathway. Tolerant recipients harbored a higher number of B cells expressing GzmB and displaying a plasma cell phenotype. Finally, GzmB+ B-cell number was dependent on IL-21 production, and B cells from tolerant recipients but not from other patients positively regulated both the number of IL-21+ T cells and IL-21 production, suggesting a feedback loop in tolerant recipients that increases excessive B cell activation and allows regulation to take place. These data provide insights into the characterization of B cell–mediated immunoregulation in clinical tolerance and show a potential regulatory effect of B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.10.1681/ASN.2014040404Mon, 02 Feb 2015 08:01:16 GMT-08:00Tolerant Kidney Transplant Patients Produce B Cells with Regulatory PropertiesWhereas a B cell–transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells have in this tolerance has not been reported. In this study, we analyzed the role of B cells from operationally tolerant patients, healthy volunteers, and kidney transplant recipients with stable graft function on T cell suppression. Proliferation, apoptosis, and type I proinflammatory cytokine production by effector CD4+CD25− T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells inhibit CD4+CD25− effector T cell response in a dose-dependent manner. This effect required B cells to interact with T-cell targets and was achieved through a granzyme B (GzmB)–dependent pathway. Tolerant recipients harbored a higher number of B cells expressing GzmB and displaying a plasma cell phenotype. Finally, GzmB+ B-cell number was dependent on IL-21 production, and B cells from tolerant recipients but not from other patients positively regulated both the number of IL-21+ T cells and IL-21 production, suggesting a feedback loop in tolerant recipients that increases excessive B cell activation and allows regulation to take place. These data provide insights into the characterization of B cell–mediated immunoregulation in clinical tolerance and show a potential regulatory effect of B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.Chesneau, MélanieMichel, LaureDugast, EmilieChenouard, AlexisBaron, DanielPallier, AnnaïckDurand, JustineBraza, FaouziGuerif, PierrickLaplaud, David-AxelSoulillou, Jean-PaulGiral, MagaliDegauque, NicolasChiffoleau, EliseBrouard, Sophie2015-02-02T08:01:16-08:00doi:10.1681/ASN.2014040404hwp:resource-id:jnephrol;26/10/2588American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyB cells, regulation, apoptosis, granzyme B, kidney transplantation, toleranceClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140404041046-66731533-34502015-02-02T08:01:16-08:002015-10Journal of the American Society of NephrologyClinical Research261025882598
- This Month's Highlights10.1681/ASN.2015060682Wed, 30 Sep 2015 10:01:07 GMT-07:00This Month's HighlightsAmerican Society of Nephrology2015-09-30T10:01:07-07:00doi:10.1681/ASN.2015060682hwp:resource-id:jnephrol;26/10/iAmerican Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyThis Month's HighlightsThis Month's Highlightsin-brief20152015-10-01October 201510.1681/ASN.20150606821046-66731533-34502015-09-30T10:01:07-07:002015-10Journal of the American Society of NephrologyThis Month's Highlights2610ii
- Salt Accelerates Allograft Rejection through Serum- and Glucocorticoid-Regulated Kinase-1–Dependent Inhibition of Regulatory T CellsA high-salt diet (HSD) in humans is linked to a number of complications, including hypertension and cardiovascular events. Whether a HSD affects the immune response in transplantation is unknown. Using a murine transplantation model, we investigated the effect of NaCl on the alloimmune response in vitro and in vivo. Incremental NaCl concentrations in vitro augmented T cell proliferation in the settings of both polyclonal and allospecific stimulation. Feeding a HSD to C57BL/6 wild-type recipients of bm12 allografts led to accelerated cardiac allograft rejection, despite similar mean BP and serum sodium levels in HSD and normal salt diet (NSD) groups. The accelerated rejection was associated with a reduction in the proportion of CD4+Foxp3+ regulatory T cells (Tregs) and a significant decrease in Treg proliferation, leading to an increased ratio of antigen-experienced CD4+ T cells to Tregs in mice recipients of a HSD compared with mice recipients of a NSD. Because serum- and glucocorticoid-regulated kinase-1 (SGK1) has been proposed as a potential target of salt in immune cells, we fed a HSD to CD4CreSGK1fl/fl B6-transplanted recipients and observed abrogation of the deleterious effect of a HSD in the absence of SGK1 on CD4+ cells. In summary, we show that NaCl negatively affects the regulatory balance of T cells in transplantation and precipitates rejection in an SGK1-dependent manner.10.1681/ASN.2014090914Wed, 01 Apr 2015 04:59:19 GMT-07:00Salt Accelerates Allograft Rejection through Serum- and Glucocorticoid-Regulated Kinase-1–Dependent Inhibition of Regulatory T CellsA high-salt diet (HSD) in humans is linked to a number of complications, including hypertension and cardiovascular events. Whether a HSD affects the immune response in transplantation is unknown. Using a murine transplantation model, we investigated the effect of NaCl on the alloimmune response in vitro and in vivo. Incremental NaCl concentrations in vitro augmented T cell proliferation in the settings of both polyclonal and allospecific stimulation. Feeding a HSD to C57BL/6 wild-type recipients of bm12 allografts led to accelerated cardiac allograft rejection, despite similar mean BP and serum sodium levels in HSD and normal salt diet (NSD) groups. The accelerated rejection was associated with a reduction in the proportion of CD4+Foxp3+ regulatory T cells (Tregs) and a significant decrease in Treg proliferation, leading to an increased ratio of antigen-experienced CD4+ T cells to Tregs in mice recipients of a HSD compared with mice recipients of a NSD. Because serum- and glucocorticoid-regulated kinase-1 (SGK1) has been proposed as a potential target of salt in immune cells, we fed a HSD to CD4CreSGK1fl/fl B6-transplanted recipients and observed abrogation of the deleterious effect of a HSD in the absence of SGK1 on CD4+ cells. In summary, we show that NaCl negatively affects the regulatory balance of T cells in transplantation and precipitates rejection in an SGK1-dependent manner.Safa, KassemOhori, ShunsukeBorges, Thiago J.Uehara, MayukoBatal, IbrahimShimizu, TetsunosukeMagee, Ciara N.Belizaire, RogerAbdi, RezaWu, ChuanChandraker, AnilRiella, Leonardo V.2015-04-01T04:59:19-07:00doi:10.1681/ASN.2014090914hwp:resource-id:jnephrol;26/10/2341American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologysalt, Tregs, rejectionBrief CommunicationBrief Communicationbrief-report20152015-10-01October 201510.1681/ASN.20140909141046-66731533-34502015-04-01T04:59:19-07:002015-10Journal of the American Society of NephrologyBrief Communication261023412347
- Urine Collagen Fragments and CKD Progression—The Cardiovascular Health StudyTubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m2, and median urine PIIINP was 2.6 (interquartile range, 1.4–4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.10.1681/ASN.2014070696Thu, 05 Feb 2015 05:58:39 GMT-08:00Urine Collagen Fragments and CKD Progression—The Cardiovascular Health StudyTubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged ≥65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m2, and median urine PIIINP was 2.6 (interquartile range, 1.4–4.2) μg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.Ix, Joachim H.Biggs, Mary L.Mukamal, KennethDjousse, LucSiscovick, DavidTracy, RussellKatz, RonitDelaney, Joseph A.Chaves, PauloRifkin, Dena E.Hughes-Austin, Jan M.Garimella, Pranav S.Sarnak, Mark J.Shlipak, Michael G.Kizer, Jorge R.2015-02-05T05:58:39-08:00doi:10.1681/ASN.2014070696hwp:resource-id:jnephrol;26/10/2494American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyfibrosis, geriatric nephrology, progression of chronic renal failure, tubule, cellsClinical EpidemiologyClinical Epidemiologyresearch-article20152015-10-01October 201510.1681/ASN.20140706961046-66731533-34502015-02-05T05:58:39-08:002015-10Journal of the American Society of NephrologyClinical Epidemiology261024942503
- Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA VasculitisIn patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification.10.1681/ASN.2014090903Fri, 08 May 2015 07:44:14 GMT-07:00Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA VasculitisIn patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification.Hilhorst, Marcvan Paassen, PieterTervaert, Jan Willem Cohen2015-05-08T07:44:14-07:00doi:10.1681/ASN.2014090903hwp:resource-id:jnephrol;26/10/2314American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyANCA, vasculitis, glomerulonephritisUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20152015-10-01October 201510.1681/ASN.20140909031046-66731533-34502015-05-08T07:44:14-07:002015-10Journal of the American Society of NephrologyUp Front Matters261023142327
- Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKDPatients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3–4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.10.1681/ASN.2015020117Tue, 12 May 2015 08:28:09 GMT-07:00Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKDPatients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3–4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.Isakova, TamaraIx, Joachim H.Sprague, Stuart M.Raphael, Kalani L.Fried, LindaGassman, Jennifer J.Raj, DominicCheung, Alfred K.Kusek, John W.Flessner, Michael F.Wolf, MylesBlock, Geoffrey A.2015-05-12T08:28:09-07:00doi:10.1681/ASN.2015020117hwp:resource-id:jnephrol;26/10/2328American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyphosphate uptake, phosphate binders, chronic kidney diseaseUp Front MattersBrief ReviewsUp Front MattersBrief Reviewsbrief-report20152015-10-01October 201510.1681/ASN.20150201171046-66731533-34502015-05-12T08:28:09-07:002015-10Journal of the American Society of NephrologyUp Front Matters261023282339
- Deficiency in the Formation of 20-Hydroxyeicosatetraenoic Acid Enhances Renal Ischemia-Reperfusion InjuryIschemia-reperfusion (IR) injury is the most common cause of AKI. The susceptibility to develop AKI varies widely among patients. However, little is known about the genes involved. 20-Hydroxyeicosatetraenoic acid (20-HETE) has an important role in the regulation of renal tubular and vascular function and has been implicated in IR injury. In this study, we examined whether a deficiency in the renal formation of 20-HETE enhances the susceptibility of Dahl salt-sensitive (SS) rats to ischemic AKI. Transfer of chromosome 5 containing the CYP4A genes responsible for the formation of 20-HETE from the Brown Norway (BN) rat onto the SS genetic background increased renal 20-HETE levels after ischemia and reduced plasma creatinine levels (±SEM) 24 hours after IR from 3.7±0.1 to 2.0±0.2 mg/dl in an SS.5BN-consomic strain. Transfer of this chromosome also prevented the secondary decline in medullary blood flow and ischemia that develops 2 hours after IR in the susceptible SS strain. Blockade of the synthesis of 20-HETE with HET0016 reversed the renoprotective effects in SS.5BN rats. Similar results were observed in an SS.5Lew-congenic strain, in which a smaller region of chromosome 5 containing the CYP4A genes from a Lewis rat was introgressed onto the SS genetic background. These results indicate that 20-HETE has a protective role in renal IR injury by maintaining medullary blood flow and that a genetic deficiency in the formation of 20-HETE increases the susceptibility of SS rats to ischemic AKI.10.1681/ASN.2014090868Mon, 02 Feb 2015 08:01:06 GMT-08:00Deficiency in the Formation of 20-Hydroxyeicosatetraenoic Acid Enhances Renal Ischemia-Reperfusion InjuryIschemia-reperfusion (IR) injury is the most common cause of AKI. The susceptibility to develop AKI varies widely among patients. However, little is known about the genes involved. 20-Hydroxyeicosatetraenoic acid (20-HETE) has an important role in the regulation of renal tubular and vascular function and has been implicated in IR injury. In this study, we examined whether a deficiency in the renal formation of 20-HETE enhances the susceptibility of Dahl salt-sensitive (SS) rats to ischemic AKI. Transfer of chromosome 5 containing the CYP4A genes responsible for the formation of 20-HETE from the Brown Norway (BN) rat onto the SS genetic background increased renal 20-HETE levels after ischemia and reduced plasma creatinine levels (±SEM) 24 hours after IR from 3.7±0.1 to 2.0±0.2 mg/dl in an SS.5BN-consomic strain. Transfer of this chromosome also prevented the secondary decline in medullary blood flow and ischemia that develops 2 hours after IR in the susceptible SS strain. Blockade of the synthesis of 20-HETE with HET0016 reversed the renoprotective effects in SS.5BN rats. Similar results were observed in an SS.5Lew-congenic strain, in which a smaller region of chromosome 5 containing the CYP4A genes from a Lewis rat was introgressed onto the SS genetic background. These results indicate that 20-HETE has a protective role in renal IR injury by maintaining medullary blood flow and that a genetic deficiency in the formation of 20-HETE increases the susceptibility of SS rats to ischemic AKI.Muroya, YoshikazuFan, FanRegner, Kevin R.Falck, John R.Garrett, Michael R.Juncos, Luis A.Roman, Richard J.2015-02-02T08:01:06-08:00doi:10.1681/ASN.2014090868hwp:resource-id:jnephrol;26/10/2460American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, 20-HETE, genetics, intrarenal blood flowBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140908681046-66731533-34502015-02-02T08:01:06-08:002015-10Journal of the American Society of NephrologyBasic Research261024602469
- Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous NephropathyRituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m2) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0–145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P<0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P<0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.10.1681/ASN.2014070640Tue, 24 Mar 2015 08:34:22 GMT-07:00Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous NephropathyRituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m2) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0–145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P<0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P<0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.Ruggenenti, PieroDebiec, HannaRuggiero, BarbaraChianca, AntoniettaPellé, TimotheeGaspari, FlavioSuardi, FlavioGagliardini, ElenaOrisio, SilviaBenigni, ArielaRonco, PierreRemuzzi, Giuseppe2015-03-24T08:34:22-07:00doi:10.1681/ASN.2014070640hwp:resource-id:jnephrol;26/10/2545American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, nephrotic syndrome, primary, glomerulonephritis, proteinuria, polymorphismsClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140706401046-66731533-34502015-03-24T08:34:22-07:002015-10Journal of the American Society of NephrologyClinical Research2610102545230825582311
- Cause of Death in Patients with Reduced Kidney FunctionInformation on common causes of death in people with CKD is limited. We hypothesized that, as eGFR declines, cardiovascular mortality and mortality from infection account for increasing proportions of deaths. We calculated eGFR using the CKD Epidemiology Collaboration equation for residents of Alberta, Canada who died between 2002 and 2009. We used multinomial logistic regression to estimate unadjusted and age- and sex-adjusted differences in the proportions of deaths from each cause according to the severity of CKD. Cause of death was classified as cardiovascular, infection, cancer, other, or not reported using International Classification of Diseases codes. Among 81,064 deaths, the most common cause was cancer (31.9%) followed by cardiovascular disease (30.2%). The most common cause of death for those with eGFR≥60 ml/min per 1.73 m2 and no proteinuria was cancer (38.1%); the most common cause of death for those with eGFR<60 ml/min per 1.73 m2 was cardiovascular disease. The unadjusted proportion of patients who died from cardiovascular disease increased as eGFR decreased (20.7%, 36.8%, 41.2%, and 43.7% of patients with eGFR≥60 [with proteinuria], 45–59.9, 30–44.9, and 15–29.9 ml/min per 1.73 m2, respectively). The proportions of deaths from heart failure and valvular disease specifically increased with declining eGFR along with the proportions of deaths from infectious and other causes, whereas the proportion of deaths from cancer decreased. In conclusion, we found an inverse association between eGFR and specific causes of death, including specific types of cardiovascular disease, infection, and other causes, in this cohort.10.1681/ASN.2014070714Mon, 02 Mar 2015 07:28:23 GMT-08:00Cause of Death in Patients with Reduced Kidney FunctionInformation on common causes of death in people with CKD is limited. We hypothesized that, as eGFR declines, cardiovascular mortality and mortality from infection account for increasing proportions of deaths. We calculated eGFR using the CKD Epidemiology Collaboration equation for residents of Alberta, Canada who died between 2002 and 2009. We used multinomial logistic regression to estimate unadjusted and age- and sex-adjusted differences in the proportions of deaths from each cause according to the severity of CKD. Cause of death was classified as cardiovascular, infection, cancer, other, or not reported using International Classification of Diseases codes. Among 81,064 deaths, the most common cause was cancer (31.9%) followed by cardiovascular disease (30.2%). The most common cause of death for those with eGFR≥60 ml/min per 1.73 m2 and no proteinuria was cancer (38.1%); the most common cause of death for those with eGFR<60 ml/min per 1.73 m2 was cardiovascular disease. The unadjusted proportion of patients who died from cardiovascular disease increased as eGFR decreased (20.7%, 36.8%, 41.2%, and 43.7% of patients with eGFR≥60 [with proteinuria], 45–59.9, 30–44.9, and 15–29.9 ml/min per 1.73 m2, respectively). The proportions of deaths from heart failure and valvular disease specifically increased with declining eGFR along with the proportions of deaths from infectious and other causes, whereas the proportion of deaths from cancer decreased. In conclusion, we found an inverse association between eGFR and specific causes of death, including specific types of cardiovascular disease, infection, and other causes, in this cohort.Thompson, StephanieJames, MatthewWiebe, NatashaHemmelgarn, BrendaManns, BradenKlarenbach, ScottTonelli, Marcello2015-03-02T07:28:23-08:00doi:10.1681/ASN.2014070714hwp:resource-id:jnephrol;26/10/2504American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, epidemiology and outcomes, mortality, GFR, cardiovascular diseaseClinical EpidemiologyClinical Epidemiologyresearch-article20152015-10-01October 201510.1681/ASN.20140707141046-66731533-34502015-03-02T07:28:23-08:002015-10Journal of the American Society of NephrologyClinical Epidemiology2610102504230725112308
- Cause-Specific Deaths in Non–Dialysis-Dependent CKDCKD is associated with higher risk of death, but details regarding differences in cause-specific death in CKD are unclear. We examined the leading causes of death among a non–dialysis-dependent CKD population using an electronic medical record-based CKD registry in a large healthcare system and the Ohio Department of Health mortality files. We included 33,478 white and 5042 black patients with CKD who resided in Ohio between January 2005 and September 2009 and had two measurements of eGFR<60 ml/min per 1.73 m2 obtained 90 days apart. Causes of death (before ESRD) were classified into cardiovascular, malignancy, and non-cardiovascular/non-malignancy diseases and non–disease-related causes. During a median follow-up of 2.3 years, 6661 of 38,520 patients (17%) with CKD died. Cardiovascular diseases (34.7%) and malignant neoplasms (31.8%) were the leading causes of death, with malignancy-related deaths more common among those with earlier stages of kidney disease. After adjusting for covariates, each 5 ml/min per 1.73 m2 decline in eGFR was associated with higher risk of death due to cardiovascular disease (hazard ratio [HR], 1.10; 95% confidence interval [95% CI], 1.08 to 1.12) and non-cardiovascular/non-malignancy diseases (HR, 1.12; 95% CI, 1.09 to 1.14) but not to malignancy. In the adjusted models, blacks had overall-mortality hazard ratios similar to those of whites but higher hazard ratios for cardiovascular deaths. Further studies to confirm these findings and explain the mechanisms for differences are warranted. In addition to lowering cardiovascular burden in CKD, efforts to target known risk factors for cancer at the population level are needed.10.1681/ASN.2014101034Thu, 04 Jun 2015 07:24:16 GMT-07:00Cause-Specific Deaths in Non–Dialysis-Dependent CKDCKD is associated with higher risk of death, but details regarding differences in cause-specific death in CKD are unclear. We examined the leading causes of death among a non–dialysis-dependent CKD population using an electronic medical record-based CKD registry in a large healthcare system and the Ohio Department of Health mortality files. We included 33,478 white and 5042 black patients with CKD who resided in Ohio between January 2005 and September 2009 and had two measurements of eGFR<60 ml/min per 1.73 m2 obtained 90 days apart. Causes of death (before ESRD) were classified into cardiovascular, malignancy, and non-cardiovascular/non-malignancy diseases and non–disease-related causes. During a median follow-up of 2.3 years, 6661 of 38,520 patients (17%) with CKD died. Cardiovascular diseases (34.7%) and malignant neoplasms (31.8%) were the leading causes of death, with malignancy-related deaths more common among those with earlier stages of kidney disease. After adjusting for covariates, each 5 ml/min per 1.73 m2 decline in eGFR was associated with higher risk of death due to cardiovascular disease (hazard ratio [HR], 1.10; 95% confidence interval [95% CI], 1.08 to 1.12) and non-cardiovascular/non-malignancy diseases (HR, 1.12; 95% CI, 1.09 to 1.14) but not to malignancy. In the adjusted models, blacks had overall-mortality hazard ratios similar to those of whites but higher hazard ratios for cardiovascular deaths. Further studies to confirm these findings and explain the mechanisms for differences are warranted. In addition to lowering cardiovascular burden in CKD, efforts to target known risk factors for cancer at the population level are needed.Navaneethan, Sankar D.Schold, Jesse D.Arrigain, SusanaJolly, Stacey E.Nally, Joseph V.2015-06-04T07:24:16-07:00doi:10.1681/ASN.2014101034hwp:resource-id:jnephrol;26/10/2512American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologychronic kidney disease, cardiovascular disease, malignancy, mortalityClinical EpidemiologyClinical Epidemiologyresearch-article20152015-10-01October 201510.1681/ASN.20141010341046-66731533-34502015-06-04T07:24:16-07:002015-10Journal of the American Society of NephrologyClinical Epidemiology2610102512230725202308
- Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal SclerosisEncapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.10.1681/ASN.2014090939Fri, 30 Jan 2015 07:47:18 GMT-08:00Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal SclerosisEncapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.Morelle, JohannSow, AmadouHautem, NicolasBouzin, CarolineCrott, RalphDevuyst, OlivierGoffin, Eric2015-01-30T07:47:18-08:00doi:10.1681/ASN.2014090939hwp:resource-id:jnephrol;26/10/2521American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyperitoneal dialysis, water channels, ultrafiltration, vascular endothelial growth factorClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140909391046-66731533-34502015-01-30T07:47:18-08:002015-10Journal of the American Society of NephrologyClinical Research261025212533
- Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary HyperoxaluriaPrimary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.10.1681/ASN.2014070698Mon, 02 Feb 2015 08:01:18 GMT-08:00Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary HyperoxaluriaPrimary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial.Hopp, KatharinaCogal, Andrea G.Bergstralh, Eric J.Seide, Barbara M.Olson, Julie B.Meek, Alicia M.Lieske, John C.Milliner, Dawn S.Harris, Peter C.2015-02-02T08:01:18-08:00doi:10.1681/ASN.2014070698hwp:resource-id:jnephrol;26/10/2559American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologygenetic renal disease, kidney stones, molecular geneticsClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140706981046-66731533-34502015-02-02T08:01:18-08:002015-10Journal of the American Society of NephrologyClinical Research261025592570
- AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAsPhenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.10.1681/ASN.2014070710Tue, 21 Apr 2015 08:31:37 GMT-07:00AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAsPhenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.Collino, FedericaBruno, StefaniaIncarnato, DannyDettori, DanielaNeri, FrancescoProvero, PaoloPomatto, MargheritaOliviero, SalvatoreTetta, CiroQuesenberry, Peter J.Camussi, Giovanni2015-04-21T08:31:37-07:00doi:10.1681/ASN.2014070710hwp:resource-id:jnephrol;26/10/2349American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, gene expression, stem cellBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140707101046-66731533-34502015-04-21T08:31:37-07:002015-10Journal of the American Society of NephrologyBasic Research2610102349230323602304
- Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult KidneysNephrin is required during kidney development for the maturation of podocytes and formation of the slit diaphragm junctional complex. Because nephrin expression is downregulated in acquired glomerular diseases, nephrin deficiency is considered a pathologic feature of glomerular injury. However, whether nephrin deficiency exacerbates glomerular injury in glomerular diseases has not been experimentally confirmed. Here, we generated mice with inducible RNA interference–mediated nephrin knockdown. Short-term nephrin knockdown (6 weeks), starting after the completion of kidney development at 5 weeks of age, did not affect glomerular structure or function. In contrast, mice with long-term nephrin knockdown (20 weeks) developed mild proteinuria, foot process effacement, filtration slit narrowing, mesangial hypercellularity and sclerosis, glomerular basement membrane thickening, subendothelial zone widening, and podocyte apoptosis. When subjected to an acquired glomerular insult induced by unilateral nephrectomy or doxorubicin, mice with short-term nephrin knockdown developed more severe glomerular injury compared with mice without nephrin knockdown. Additionally, nephrin-knockdown mice developed more exaggerated glomerular enlargement when subjected to unilateral nephrectomy and more podocyte apoptosis and depletion after doxorubicin challenge. AKT phosphorylation, which is a slit diaphragm–mediated and nephrin-dependent pathway in the podocyte, was markedly reduced in mice with long-term or short-term nephrin knockdown challenged with uninephrectomy or doxorubicin. Taken together, our data establish that under the basal condition and in acquired glomerular diseases, nephrin is required to maintain slit diaphragm integrity and slit diaphragm–mediated signaling to preserve glomerular function and podocyte viability in adult mice.10.1681/ASN.2014040405Mon, 02 Feb 2015 08:01:07 GMT-08:00Nephrin Preserves Podocyte Viability and Glomerular Structure and Function in Adult KidneysNephrin is required during kidney development for the maturation of podocytes and formation of the slit diaphragm junctional complex. Because nephrin expression is downregulated in acquired glomerular diseases, nephrin deficiency is considered a pathologic feature of glomerular injury. However, whether nephrin deficiency exacerbates glomerular injury in glomerular diseases has not been experimentally confirmed. Here, we generated mice with inducible RNA interference–mediated nephrin knockdown. Short-term nephrin knockdown (6 weeks), starting after the completion of kidney development at 5 weeks of age, did not affect glomerular structure or function. In contrast, mice with long-term nephrin knockdown (20 weeks) developed mild proteinuria, foot process effacement, filtration slit narrowing, mesangial hypercellularity and sclerosis, glomerular basement membrane thickening, subendothelial zone widening, and podocyte apoptosis. When subjected to an acquired glomerular insult induced by unilateral nephrectomy or doxorubicin, mice with short-term nephrin knockdown developed more severe glomerular injury compared with mice without nephrin knockdown. Additionally, nephrin-knockdown mice developed more exaggerated glomerular enlargement when subjected to unilateral nephrectomy and more podocyte apoptosis and depletion after doxorubicin challenge. AKT phosphorylation, which is a slit diaphragm–mediated and nephrin-dependent pathway in the podocyte, was markedly reduced in mice with long-term or short-term nephrin knockdown challenged with uninephrectomy or doxorubicin. Taken together, our data establish that under the basal condition and in acquired glomerular diseases, nephrin is required to maintain slit diaphragm integrity and slit diaphragm–mediated signaling to preserve glomerular function and podocyte viability in adult mice.Li, XuezhuChuang, Peter Y.D’Agati, Vivette D.Dai, YanYacoub, RabiFu, JiaXu, JinTaku, OltjonPremsrirut, Prem K.Holzman, Lawrence B.He, John Cijiang2015-02-02T08:01:07-08:00doi:10.1681/ASN.2014040405hwp:resource-id:jnephrol;26/10/2361American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologynephrin, podocyte, glomerulopathy, slit diaphragm, kidney disease, animal modelBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140404051046-66731533-34502015-02-02T08:01:07-08:002015-10Journal of the American Society of NephrologyBasic Research261023612377
- Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the KidneyEpigenetic mechanisms may underlie the progression of diabetic kidney disease. Because the kidney is a heterogeneous organ with different cell types, we investigated DNA methylation status of the kidney in a cell type–specific manner. We first identified genes specifically demethylated in the normal proximal tubules obtained from control db/m mice, and next delineated the candidate disease-modifying genes bearing aberrant DNA methylation induced by diabetes using db/db mice. Genes involved in glucose metabolism, including Sglt2, Pck1, and G6pc, were selectively hypomethylated in the proximal tubules in control mice. Hnf4a, a transcription factor regulating transporters for reabsorption, was also selectively demethylated. In diabetic mice, aberrant hypomethylation of Agt, Abcc4, Cyp4a10, Glut5, and Met and hypermethylation of Kif20b, Cldn18, and Slco1a1 were observed. Time-dependent demethylation of Agt, a marker of diabetic kidney disease, was accompanied by histone modification changes. Furthermore, inhibition of DNA methyltransferase or histone deacetylase increased Agt mRNA in cultured human proximal tubular cells. Aberrant DNA methylation and concomitant changes in histone modifications and mRNA expression in the diabetic kidney were resistant to antidiabetic treatment with pioglitazone. These results suggest that an epigenetic switch involving aberrant DNA methylation causes persistent mRNA expression of select genes that may lead to phenotype changes of the proximal tubules in diabetic kidney disease.10.1681/ASN.2014070665Wed, 04 Feb 2015 10:52:56 GMT-08:00Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the KidneyEpigenetic mechanisms may underlie the progression of diabetic kidney disease. Because the kidney is a heterogeneous organ with different cell types, we investigated DNA methylation status of the kidney in a cell type–specific manner. We first identified genes specifically demethylated in the normal proximal tubules obtained from control db/m mice, and next delineated the candidate disease-modifying genes bearing aberrant DNA methylation induced by diabetes using db/db mice. Genes involved in glucose metabolism, including Sglt2, Pck1, and G6pc, were selectively hypomethylated in the proximal tubules in control mice. Hnf4a, a transcription factor regulating transporters for reabsorption, was also selectively demethylated. In diabetic mice, aberrant hypomethylation of Agt, Abcc4, Cyp4a10, Glut5, and Met and hypermethylation of Kif20b, Cldn18, and Slco1a1 were observed. Time-dependent demethylation of Agt, a marker of diabetic kidney disease, was accompanied by histone modification changes. Furthermore, inhibition of DNA methyltransferase or histone deacetylase increased Agt mRNA in cultured human proximal tubular cells. Aberrant DNA methylation and concomitant changes in histone modifications and mRNA expression in the diabetic kidney were resistant to antidiabetic treatment with pioglitazone. These results suggest that an epigenetic switch involving aberrant DNA methylation causes persistent mRNA expression of select genes that may lead to phenotype changes of the proximal tubules in diabetic kidney disease.Marumo, TakeshiYagi, ShintaroKawarazaki, WakakoNishimoto, MitsuhiroAyuzawa, NobuhiroWatanabe, AtsushiUeda, KoheiHirahashi, JunichiHishikawa, KeiichiSakurai, HiroyukiShiota, KunioFujita, Toshiro2015-02-04T10:52:56-08:00doi:10.1681/ASN.2014070665hwp:resource-id:jnephrol;26/10/2388American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologydiabetes, angiotensin, renal proximal tubule cellBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140706651046-66731533-34502015-02-04T10:52:56-08:002015-10Journal of the American Society of NephrologyBasic Research261023882397
- Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GNSevere GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti–glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN.10.1681/ASN.2014070673Mon, 02 Feb 2015 08:01:11 GMT-08:00Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GNSevere GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti–glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN.Kumar, Santhosh V.R.Kulkarni, Onkar P.Mulay, Shrikant R.Darisipudi, Murthy N.Romoli, SimoneThomasova, DanaScherbaum, Christina R.Hohenstein, BerndHugo, ChristianMüller, SusannaLiapis, HelenAnders, Hans-Joachim2015-02-02T08:01:11-08:00doi:10.1681/ASN.2014070673hwp:resource-id:jnephrol;26/10/2399American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyARF, glomerular endothelial cells, immunology, pathologyBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140706731046-66731533-34502015-02-02T08:01:11-08:002015-10Journal of the American Society of NephrologyBasic Research261023992413
- Developmental Programming of Branching Morphogenesis in the KidneyThe kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases.10.1681/ASN.2014090886Mon, 02 Feb 2015 08:01:09 GMT-08:00Developmental Programming of Branching Morphogenesis in the KidneyThe kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases.Sampogna, Rosemary V.Schneider, LauraAl-Awqati, Qais2015-02-02T08:01:09-08:00doi:10.1681/ASN.2014090886hwp:resource-id:jnephrol;26/10/2414American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologykidney development, branching morphogenesis, variability, nephron numberBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140908861046-66731533-34502015-02-02T08:01:09-08:002015-10Journal of the American Society of NephrologyBasic Research261024142422
- NH4Cl Treatment Prevents Tissue Calcification in Klotho DeficiencyKlotho, a cofactor in suppressing 1,25(OH)2D3 formation, is a powerful regulator of mineral metabolism. Klotho-hypomorphic mice (kl/kl) exhibit excessive plasma 1,25(OH)2D3, Ca2+, and phosphate concentrations, severe tissue calcification, volume depletion with hyperaldosteronism, and early death. Calcification is paralleled by overexpression of osteoinductive transcription factor Runx2/Cbfa1, Alpl, and senescence-associated molecules Tgfb1, Pai-1, p21, and Glb1. Here, we show that NH4Cl treatment in drinking water (0.28 M) prevented soft tissue and vascular calcification and increased the life span of kl/kl mice >12-fold in males and >4-fold in females without significantly affecting extracellular pH or plasma concentrations of 1,25(OH)2D3, Ca2+, and phosphate. NH4Cl treatment significantly decreased plasma aldosterone and antidiuretic hormone concentrations and reversed the increase of Runx2/Cbfa1, Alpl, Tgfb1, Pai-1, p21, and Glb1 expression in aorta of kl/kl mice. Similarly, in primary human aortic smooth muscle cells (HAoSMCs), NH4Cl treatment reduced phosphate-induced mRNA expression of RUNX2/CBFA1, ALPL, and senescence-associated molecules. In both kl/kl mice and phosphate-treated HAoSMCs, levels of osmosensitive transcription factor NFAT5 and NFAT5-downstream mediator SOX9 were higher than in controls and decreased after NH4Cl treatment. Overexpression of NFAT5 in HAoSMCs mimicked the effect of phosphate and abrogated the effect of NH4Cl on SOX9, RUNX2/CBFA1, and ALPL mRNA expression. TGFB1 treatment of HAoSMCs upregulated NFAT5 expression and prevented the decrease of phosphate-induced NFAT5 expression after NH4Cl treatment. In conclusion, NH4Cl treatment prevents tissue calcification, reduces vascular senescence, and extends survival of klotho-hypomorphic mice. The effects of NH4Cl on vascular osteoinduction involve decrease of TGFB1 and inhibition of NFAT5-dependent osteochondrogenic signaling.10.1681/ASN.2014030230Mon, 02 Feb 2015 08:01:15 GMT-08:00NH4Cl Treatment Prevents Tissue Calcification in Klotho DeficiencyKlotho, a cofactor in suppressing 1,25(OH)2D3 formation, is a powerful regulator of mineral metabolism. Klotho-hypomorphic mice (kl/kl) exhibit excessive plasma 1,25(OH)2D3, Ca2+, and phosphate concentrations, severe tissue calcification, volume depletion with hyperaldosteronism, and early death. Calcification is paralleled by overexpression of osteoinductive transcription factor Runx2/Cbfa1, Alpl, and senescence-associated molecules Tgfb1, Pai-1, p21, and Glb1. Here, we show that NH4Cl treatment in drinking water (0.28 M) prevented soft tissue and vascular calcification and increased the life span of kl/kl mice >12-fold in males and >4-fold in females without significantly affecting extracellular pH or plasma concentrations of 1,25(OH)2D3, Ca2+, and phosphate. NH4Cl treatment significantly decreased plasma aldosterone and antidiuretic hormone concentrations and reversed the increase of Runx2/Cbfa1, Alpl, Tgfb1, Pai-1, p21, and Glb1 expression in aorta of kl/kl mice. Similarly, in primary human aortic smooth muscle cells (HAoSMCs), NH4Cl treatment reduced phosphate-induced mRNA expression of RUNX2/CBFA1, ALPL, and senescence-associated molecules. In both kl/kl mice and phosphate-treated HAoSMCs, levels of osmosensitive transcription factor NFAT5 and NFAT5-downstream mediator SOX9 were higher than in controls and decreased after NH4Cl treatment. Overexpression of NFAT5 in HAoSMCs mimicked the effect of phosphate and abrogated the effect of NH4Cl on SOX9, RUNX2/CBFA1, and ALPL mRNA expression. TGFB1 treatment of HAoSMCs upregulated NFAT5 expression and prevented the decrease of phosphate-induced NFAT5 expression after NH4Cl treatment. In conclusion, NH4Cl treatment prevents tissue calcification, reduces vascular senescence, and extends survival of klotho-hypomorphic mice. The effects of NH4Cl on vascular osteoinduction involve decrease of TGFB1 and inhibition of NFAT5-dependent osteochondrogenic signaling.Leibrock, Christina B.Alesutan, IoanaVoelkl, JakobPakladok, TatsianaMichael, DianaSchleicher, ErwinKamyabi-Moghaddam, ZahraQuintanilla-Martinez, LeticiaKuro-o, MakotoLang, Florian2015-02-02T08:01:15-08:00doi:10.1681/ASN.2014030230hwp:resource-id:jnephrol;26/10/2423American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, mineral metabolism, vascular calcification, aldosteroneBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140302301046-66731533-34502015-02-02T08:01:15-08:002015-10Journal of the American Society of NephrologyBasic Research261024232433
- Klotho Protects Against Indoxyl Sulphate-Induced Myocardial HypertrophyLeft ventricular hypertrophy (LVH) is a common complication in patients with CKD and an independent risk factor for death. Changes in the levels of uremic solutes or Klotho have been reported to be related to CKD, whereas the relationships between these factors and CKD-associated LVH remain unclear. Here, we investigated the interaction between Klotho and indoxyl sulfate (IS), a typical uremic solute, in CKD-associated LVH. In a survey of 86 patients with CKD, a negative relationship was found between serum levels of IS and Klotho (r=−0.59, P<0.001). Furthermore, serum levels of IS and Klotho were independently associated with LVH (for IS: r=0.69, P<0.001; for Klotho: r=−0.49, P<0.001). In normal mice, intraperitoneal injection of IS for 8 weeks induced LVH accompanied by substantial downregulation of renal Klotho. Notably, IS-induced LVH was more severe in heterozygous Klotho-deficient (kl/+) mice. In vitro, treatment with Klotho strongly inhibited IS-induced cardiomyocyte hypertrophy by blocking oxidative stress and inhibiting p38 and extracellular signal–regulated protein kinase 1/2 signaling pathways. In a mouse model of CKD-associated LVH, the renal expression of Klotho was lower and the level of serum IS was higher than in healthy controls. Moreover, treatment of CKD mice with Klotho protein significantly restrained the development of LVH. Taken together, these results suggest that Klotho is an endogenous protector against IS-induced LVH, and the imbalance between Klotho and IS may contribute to the development of LVH in CKD.10.1681/ASN.2014060543Tue, 24 Mar 2015 08:34:28 GMT-07:00Klotho Protects Against Indoxyl Sulphate-Induced Myocardial HypertrophyLeft ventricular hypertrophy (LVH) is a common complication in patients with CKD and an independent risk factor for death. Changes in the levels of uremic solutes or Klotho have been reported to be related to CKD, whereas the relationships between these factors and CKD-associated LVH remain unclear. Here, we investigated the interaction between Klotho and indoxyl sulfate (IS), a typical uremic solute, in CKD-associated LVH. In a survey of 86 patients with CKD, a negative relationship was found between serum levels of IS and Klotho (r=−0.59, P<0.001). Furthermore, serum levels of IS and Klotho were independently associated with LVH (for IS: r=0.69, P<0.001; for Klotho: r=−0.49, P<0.001). In normal mice, intraperitoneal injection of IS for 8 weeks induced LVH accompanied by substantial downregulation of renal Klotho. Notably, IS-induced LVH was more severe in heterozygous Klotho-deficient (kl/+) mice. In vitro, treatment with Klotho strongly inhibited IS-induced cardiomyocyte hypertrophy by blocking oxidative stress and inhibiting p38 and extracellular signal–regulated protein kinase 1/2 signaling pathways. In a mouse model of CKD-associated LVH, the renal expression of Klotho was lower and the level of serum IS was higher than in healthy controls. Moreover, treatment of CKD mice with Klotho protein significantly restrained the development of LVH. Taken together, these results suggest that Klotho is an endogenous protector against IS-induced LVH, and the imbalance between Klotho and IS may contribute to the development of LVH in CKD.Yang, KeWang, ChengNie, LingZhao, XiaohuiGu, JunGuan, XuWang, SongXiao, TangliXu, XinliHe, TingXia, XuefengWang, JunpingZhao, Jinghong2015-03-24T08:34:28-07:00doi:10.1681/ASN.2014060543hwp:resource-id:jnephrol;26/10/2434American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyuremia, left ventricular hypertrophy, CKDBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140605431046-66731533-34502015-03-24T08:34:28-07:002015-10Journal of the American Society of NephrologyBasic Research2610102434230524462307
- Extracellular Superoxide Dismutase Protects against Proteinuric Kidney DiseaseExtracellular superoxide dismutase (EC-SOD), also known as SOD3, is an antioxidant expressed at high levels in normal adult kidneys. Because oxidative stress contributes to a variety of kidney injuries, we hypothesized that EC-SOD may be protective in CKD progression. To study this hypothesis, we used a murine model of ADR nephropathy characterized by albuminuria and renal dysfunction. We found that levels of EC-SOD diminished throughout the course of disease progression and were associated with increased levels of NADPH oxidase and oxidative stress markers. EC-SOD null mice were sensitized to ADR injury, as evidenced by increases in albuminuria, serum creatinine, histologic damage, and oxidative stress. The absence of EC-SOD led to increased levels of NADPH oxidase and an increase in β-catenin signaling, which has been shown to be pathologic in a variety of kidney injuries. Exposure of EC-SOD null mice to either chronic angiotensin II infusion or to daily albumin injections also caused increased proteinuria. In contrast, EC-SOD null mice subjected to nonproteinuric CKD induced by unilateral ureteral obstruction exhibited no differences compared with wild-type mice. Finally, we also found a decrease in EC-SOD in human CKD biopsy samples, similar to our findings in mice. Therefore, we conclude that EC-SOD is protective in CKDs characterized by proteinuria.10.1681/ASN.2014060613Mon, 02 Feb 2015 08:01:04 GMT-08:00Extracellular Superoxide Dismutase Protects against Proteinuric Kidney DiseaseExtracellular superoxide dismutase (EC-SOD), also known as SOD3, is an antioxidant expressed at high levels in normal adult kidneys. Because oxidative stress contributes to a variety of kidney injuries, we hypothesized that EC-SOD may be protective in CKD progression. To study this hypothesis, we used a murine model of ADR nephropathy characterized by albuminuria and renal dysfunction. We found that levels of EC-SOD diminished throughout the course of disease progression and were associated with increased levels of NADPH oxidase and oxidative stress markers. EC-SOD null mice were sensitized to ADR injury, as evidenced by increases in albuminuria, serum creatinine, histologic damage, and oxidative stress. The absence of EC-SOD led to increased levels of NADPH oxidase and an increase in β-catenin signaling, which has been shown to be pathologic in a variety of kidney injuries. Exposure of EC-SOD null mice to either chronic angiotensin II infusion or to daily albumin injections also caused increased proteinuria. In contrast, EC-SOD null mice subjected to nonproteinuric CKD induced by unilateral ureteral obstruction exhibited no differences compared with wild-type mice. Finally, we also found a decrease in EC-SOD in human CKD biopsy samples, similar to our findings in mice. Therefore, we conclude that EC-SOD is protective in CKDs characterized by proteinuria.Tan, Roderick J.Zhou, DongXiao, LiangxiangZhou, LiliLi, YingjianBastacky, Sheldon I.Oury, Tim D.Liu, Youhua2015-02-02T08:01:04-08:00doi:10.1681/ASN.2014060613hwp:resource-id:jnephrol;26/10/2447American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyproteinuria, podocyte, oxidative stress, kidney diseaseBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140606131046-66731533-34502015-02-02T08:01:04-08:002015-10Journal of the American Society of NephrologyBasic Research261024472459
- Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKIWe showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemia-reperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and α7 nicotinic acetylcholine receptors (α7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (–7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; –14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA–induced splenic denervation also prevented ultrasound-induced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal α7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and α7nAChR–/– mice. Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture–induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.10.1681/ASN.2014080769Mon, 02 Feb 2015 08:01:02 GMT-08:00Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKIWe showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemia-reperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and α7 nicotinic acetylcholine receptors (α7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (–7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; –14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA–induced splenic denervation also prevented ultrasound-induced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal α7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and α7nAChR–/– mice. Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture–induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.Gigliotti, Joseph C.Huang, LipingBajwa, AmandeepYe, HongMace, Eric H.Hossack, John A.Kalantari, KambizInoue, TsuyoshiRosin, Diane L.Okusa, Mark D.2015-02-02T08:01:02-08:00doi:10.1681/ASN.2014080769hwp:resource-id:jnephrol;26/10/2470American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, cholinergic anti-inflammatory pathway, neuroimmune, spleen, inflammationBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140807691046-66731533-34502015-02-02T08:01:02-08:002015-10Journal of the American Society of NephrologyBasic Research261024702481
- A Lifetime of Allograft Function with Kidneys from Older DonorsStrategies to increase expanded criteria donor (ECD) transplantation are needed. We quantified the extent to which ECD kidneys provide recipients with a lifetime of allograft function by determining the difference between patient survival and death-censored allograft survival (graft survival). Initial analyses compared 5-year outcomes in the Eurotransplant Senior Program (European) and the United States Renal Data System. Among European recipients ≥65 years, patient survival exceeded graft survival, and ECD recipients returned to dialysis for an average of 5.2 months after transplant failure. Among United States recipients ≥60 years, graft survival exceeded patient survival. Although patient survival in elderly recipients in the United States was low (49% at 5 years), the average difference in patient survival at 10 years in elderly recipients in the United States with an ECD versus non-ECD transplant was only 7 months. The probability of patient survival with a functioning allograft at 5 years was higher with ECD transplantation within 1 year after activation to the waiting list than with delayed non-ECD transplantation ≥3 years after activation to the waiting list. Subsequent analyses demonstrated that ECD transplants do not provide a lifetime of allograft function in recipients <50 years in the United States. These findings should encourage ECD transplantation in patients ≥60 years, demonstrate that rapid ECD transplantation is superior to delayed non-ECD transplantation, and challenge the policy in the United States of allowing patients <50 years to receive an ECD transplant.10.1681/ASN.2014080771Thu, 26 Mar 2015 08:34:39 GMT-07:00A Lifetime of Allograft Function with Kidneys from Older DonorsStrategies to increase expanded criteria donor (ECD) transplantation are needed. We quantified the extent to which ECD kidneys provide recipients with a lifetime of allograft function by determining the difference between patient survival and death-censored allograft survival (graft survival). Initial analyses compared 5-year outcomes in the Eurotransplant Senior Program (European) and the United States Renal Data System. Among European recipients ≥65 years, patient survival exceeded graft survival, and ECD recipients returned to dialysis for an average of 5.2 months after transplant failure. Among United States recipients ≥60 years, graft survival exceeded patient survival. Although patient survival in elderly recipients in the United States was low (49% at 5 years), the average difference in patient survival at 10 years in elderly recipients in the United States with an ECD versus non-ECD transplant was only 7 months. The probability of patient survival with a functioning allograft at 5 years was higher with ECD transplantation within 1 year after activation to the waiting list than with delayed non-ECD transplantation ≥3 years after activation to the waiting list. Subsequent analyses demonstrated that ECD transplants do not provide a lifetime of allograft function in recipients <50 years in the United States. These findings should encourage ECD transplantation in patients ≥60 years, demonstrate that rapid ECD transplantation is superior to delayed non-ECD transplantation, and challenge the policy in the United States of allowing patients <50 years to receive an ECD transplant.Rose, CarenSchaeffner, ElkeFrei, UlrichGill, JagbirGill, John S.2015-03-26T08:34:39-07:00doi:10.1681/ASN.2014080771hwp:resource-id:jnephrol;26/10/2483American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologytransplantation, survival, expanded criteria donors, health policy, cadaver organ transplantationClinical EpidemiologyClinical Epidemiologyresearch-article20152015-10-01October 201510.1681/ASN.20140807711046-66731533-34502015-03-26T08:34:39-07:002015-10Journal of the American Society of NephrologyClinical Epidemiology261024832493
- Kidney Function Alters the Relationship between Postoperative Troponin T Level and DeathCardiac troponin T (cTnT), even at low concentrations, is a risk factor for 30-day mortality in patients undergoing noncardiac surgery, but it is uncertain whether that risk is generalizable to patients with poor kidney function. We, therefore, evaluated the relationship between cTnT concentration and kidney function on the outcome of 30-day mortality in a post hoc analysis of a prospective cohort study of patients undergoing noncardiac surgery. cTnT was measured for 3 days after surgery and considered abnormal if the peak was ≥0.02 ng/ml. Of the included 14,037 patients, 267 (1.9%) patients died within 30 days of surgery. The adjusted hazard ratios for death with an abnormal cTnT concentration were 4.37 (95% confidence intervals [95% CI], 3.21 to 6.22), 6.15 (95% CI, 2.95 to 140.9), 6.30 (95% CI, 3.12 to 21.23), 1.33 (95% CI, 0.56 to 4.85), and 1.46 (95% CI, 0.46 to 9.21) for eGFR≥60, 45 to <60, 30 to <45, 15 to <30, and <15 ml/min per 1.73 m2 or on dialysis, respectively. Compared with patients with eGFR≥60 ml/min per 1.73 m2, the adjusted hazard ratio was significantly lower for patients with eGFR=15 to <30 ml/min per 1.73 m2 (interaction P value=0.02). Redefining abnormal cTnT concentration as ≥0.03 ng/ml or a change of ≥0.02 ng/ml did not alter results. Because the risk associated with postoperative cTnT levels may be different for patients with eGFR<30 ml/min per 1.73 m2, additional research is required to determine how to interpret perioperative cTnT values for patients with low kidney function.10.1681/ASN.2014060536Mon, 23 Feb 2015 07:52:24 GMT-08:00Kidney Function Alters the Relationship between Postoperative Troponin T Level and DeathCardiac troponin T (cTnT), even at low concentrations, is a risk factor for 30-day mortality in patients undergoing noncardiac surgery, but it is uncertain whether that risk is generalizable to patients with poor kidney function. We, therefore, evaluated the relationship between cTnT concentration and kidney function on the outcome of 30-day mortality in a post hoc analysis of a prospective cohort study of patients undergoing noncardiac surgery. cTnT was measured for 3 days after surgery and considered abnormal if the peak was ≥0.02 ng/ml. Of the included 14,037 patients, 267 (1.9%) patients died within 30 days of surgery. The adjusted hazard ratios for death with an abnormal cTnT concentration were 4.37 (95% confidence intervals [95% CI], 3.21 to 6.22), 6.15 (95% CI, 2.95 to 140.9), 6.30 (95% CI, 3.12 to 21.23), 1.33 (95% CI, 0.56 to 4.85), and 1.46 (95% CI, 0.46 to 9.21) for eGFR≥60, 45 to <60, 30 to <45, 15 to <30, and <15 ml/min per 1.73 m2 or on dialysis, respectively. Compared with patients with eGFR≥60 ml/min per 1.73 m2, the adjusted hazard ratio was significantly lower for patients with eGFR=15 to <30 ml/min per 1.73 m2 (interaction P value=0.02). Redefining abnormal cTnT concentration as ≥0.03 ng/ml or a change of ≥0.02 ng/ml did not alter results. Because the risk associated with postoperative cTnT levels may be different for patients with eGFR<30 ml/min per 1.73 m2, additional research is required to determine how to interpret perioperative cTnT values for patients with low kidney function.Walsh, MichaelWang, Chew-YinOng, Gracie S.Y.Tan, Alvin S.B.Mansor, MarzidaShariffuddin, Ina I.Hashim, Noorjahan H.M.Lai, Hou YeeUndok, A. WahabKolandaivel, Ushananthini N.Vajiravelu, VasanthanGarg, Amit X.Cuerden, MeaghanGuyatt, GordonThabane, LehanaMooney, JohnLee, VincentChow, ClaraDevereaux, Phillip J.2015-02-23T07:52:24-08:00doi:10.1681/ASN.2014060536hwp:resource-id:jnephrol;26/10/2571American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycardiovascular disease, CKD, survival, risk factors, epidemiology and outcomesClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140605361046-66731533-34502015-02-23T07:52:24-08:002015-10Journal of the American Society of NephrologyClinical Research261025712577
- Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRDFerric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0–28.9] versus 26.8 [13.4–47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023–9695] versus 6954 [2664–12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.10.1681/ASN.2014080842Tue, 03 Mar 2015 07:53:52 GMT-08:00Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRDFerric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0–28.9] versus 26.8 [13.4–47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023–9695] versus 6954 [2664–12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.Umanath, KausikJalal, Diana I.Greco, Barbara A.Umeukeje, Ebele M.Reisin, EfrainManley, JohnZeig, StevenNegoi, Dana G.Hiremath, Anand N.Blumenthal, Samuel S.Sika, MohammedNiecestro, RobertKoury, Mark J.Ma, Khe-NiGreene, TomLewis, Julia B.Dwyer, Jamie P.2015-03-03T07:53:52-08:00doi:10.1681/ASN.2014080842hwp:resource-id:jnephrol;26/10/2578American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologydialysis, anemia, erythropoietin, ESRD, iron, phosphate binder, ferric citrate, ESAClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140808421046-66731533-34502015-03-03T07:53:52-08:002015-10Journal of the American Society of NephrologyClinical Research2610102578231125872313
- Erratum10.1681/ASN.2015050575Wed, 30 Sep 2015 10:01:08 GMT-07:00ErratumAmerican Society of Nephrology2015-09-30T10:01:08-07:00doi:10.1681/ASN.2015050575hwp:resource-id:jnephrol;26/10/2599American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologychronic renal disease, cardiovascular disease, hospitalizationErrataErratacorrection20152015-10-01October 201510.1681/ASN.20150505751046-66731533-34502015-09-30T10:01:08-07:002015-10Journal of the American Society of NephrologyErrata262610425999462599956
- Erratum10.1681/ASN.2015070789Wed, 30 Sep 2015 10:01:08 GMT-07:00ErratumAmerican Society of Nephrology2015-09-30T10:01:08-07:00doi:10.1681/ASN.2015070789hwp:resource-id:jnephrol;26/10/2600American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyErrataErratacorrection20152015-10-01October 201510.1681/ASN.20150707891046-66731533-34502015-09-30T10:01:08-07:002015-10Journal of the American Society of NephrologyErrata26262510611260014762445260014762457
- Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal SyndromeExperimental evidence has clarified distant organ dysfunctions induced by AKI. Crosstalk between the kidney and heart, which has been recognized recently as cardiorenal syndrome, appears to have an important role in clinical settings, but the mechanisms by which AKI causes cardiac injury remain poorly understood. Both the kidney and heart are highly energy-demanding organs that are rich in mitochondria. Therefore, we investigated the role of mitochondrial dynamics in kidney–heart organ crosstalk. Renal ischemia reperfusion (IR) injury was induced by bilateral renal artery clamping for 30 min in 8-week-old male C57BL/6 mice. Electron microscopy showed a significant increase of mitochondrial fragmentation in the heart at 24 h. Cardiomyocyte apoptosis and cardiac dysfunction, evaluated by echocardiography, were observed at 72 h. Among the mitochondrial dynamics regulating molecules, dynamin-related protein 1 (Drp1), which regulates fission, and mitofusin 1, mitofusin 2, and optic atrophy 1, which regulate fusion, only Drp1 was increased in the mitochondrial fraction of the heart. A Drp1 inhibitor, mdivi-1, administered before IR decreased mitochondrial fragmentation and cardiomyocyte apoptosis significantly and improved cardiac dysfunction induced by renal IR. This study showed that renal IR injury induced fragmentation of mitochondria in a fission-dominant manner with Drp1 activation and subsequent cardiomyocyte apoptosis in the heart. Furthermore, cardiac dysfunction induced by renal IR was improved by Drp1 inhibition. These data suggest that mitochondrial fragmentation by fission machinery may be a new therapeutic target in cardiac dysfunction induced by AKI.10.1681/ASN.2014080750Mon, 02 Feb 2015 08:01:13 GMT-08:00Regulation of Mitochondrial Dynamics by Dynamin-Related Protein-1 in Acute Cardiorenal SyndromeExperimental evidence has clarified distant organ dysfunctions induced by AKI. Crosstalk between the kidney and heart, which has been recognized recently as cardiorenal syndrome, appears to have an important role in clinical settings, but the mechanisms by which AKI causes cardiac injury remain poorly understood. Both the kidney and heart are highly energy-demanding organs that are rich in mitochondria. Therefore, we investigated the role of mitochondrial dynamics in kidney–heart organ crosstalk. Renal ischemia reperfusion (IR) injury was induced by bilateral renal artery clamping for 30 min in 8-week-old male C57BL/6 mice. Electron microscopy showed a significant increase of mitochondrial fragmentation in the heart at 24 h. Cardiomyocyte apoptosis and cardiac dysfunction, evaluated by echocardiography, were observed at 72 h. Among the mitochondrial dynamics regulating molecules, dynamin-related protein 1 (Drp1), which regulates fission, and mitofusin 1, mitofusin 2, and optic atrophy 1, which regulate fusion, only Drp1 was increased in the mitochondrial fraction of the heart. A Drp1 inhibitor, mdivi-1, administered before IR decreased mitochondrial fragmentation and cardiomyocyte apoptosis significantly and improved cardiac dysfunction induced by renal IR. This study showed that renal IR injury induced fragmentation of mitochondria in a fission-dominant manner with Drp1 activation and subsequent cardiomyocyte apoptosis in the heart. Furthermore, cardiac dysfunction induced by renal IR was improved by Drp1 inhibition. These data suggest that mitochondrial fragmentation by fission machinery may be a new therapeutic target in cardiac dysfunction induced by AKI.Sumida, MakiDoi, KentOgasawara, EmiYamashita, TetsushiHamasaki, YoshifumiKariya, TaroTakimoto, EikiYahagi, NaokiNangaku, MasaomiNoiri, Eisei2015-02-02T08:01:13-08:00doi:10.1681/ASN.2014080750hwp:resource-id:jnephrol;26/10/2378American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyacute renal failure, apoptosis, cardiovascular, mitochondriaBasic ResearchBasic Researchresearch-article20152015-10-01October 201510.1681/ASN.20140807501046-66731533-34502015-02-02T08:01:13-08:002015-10Journal of the American Society of NephrologyBasic Research261023782387
- High Parathyroid Hormone Level and Osteoporosis Predict Progression of Coronary Artery Calcification in Patients on DialysisCoronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bone markers. A total of 213 patients received baseline measurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores>400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD–associated CAC prevalence and progression.10.1681/ASN.2014070686Thu, 02 Apr 2015 06:42:40 GMT-07:00High Parathyroid Hormone Level and Osteoporosis Predict Progression of Coronary Artery Calcification in Patients on DialysisCoronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bone markers. A total of 213 patients received baseline measurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores>400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD–associated CAC prevalence and progression.Malluche, Hartmut H.Blomquist, GustavMonier-Faugere, Marie-ClaudeCantor, Thomas L.Davenport, Daniel L.2015-04-02T06:42:40-07:00doi:10.1681/ASN.2014070686hwp:resource-id:jnephrol;26/10/2534American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologycoronary calcification, parathyroid hormone, renal osteodystrophyClinical ResearchClinical Researchresearch-article20152015-10-01October 201510.1681/ASN.20140706861046-66731533-34502015-04-02T06:42:40-07:002015-10Journal of the American Society of NephrologyClinical Research261025342544
- Loss of Klotho in CKD Breaks One’s Heart10.1681/ASN.2015020200Tue, 24 Mar 2015 08:34:29 GMT-07:00Loss of Klotho in CKD Breaks One’s HeartFu, HaiyanLiu, Youhua2015-03-24T08:34:29-07:00doi:10.1681/ASN.2015020200hwp:resource-id:jnephrol;26/10/2305American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, cardiovascular disease, left ventricular hypertrophyUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-10-01October 201510.1681/ASN.20150202001046-66731533-34502015-03-24T08:34:29-07:002015-10Journal of the American Society of NephrologyUp Front Matters2610102305243423072446
- Not All Deaths in CKD Are from a Broken Heart10.1681/ASN.2015050531Thu, 04 Jun 2015 07:24:14 GMT-07:00Not All Deaths in CKD Are from a Broken HeartWong, GermaineGarg, Amit X.2015-06-04T07:24:14-07:00doi:10.1681/ASN.2015050531hwp:resource-id:jnephrol;26/10/2307American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyCKD, mortality, cancerUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-10-01October 201510.1681/ASN.20150505311046-66731533-34502015-06-04T07:24:14-07:002015-10Journal of the American Society of NephrologyUp Front Matters26101010230725042512230825112520
- Is It Too Much of a Good Thing? A New Era in Phosphate Binder Therapy in ESRD10.1681/ASN.2015020135Tue, 03 Mar 2015 07:53:53 GMT-08:00Is It Too Much of a Good Thing? A New Era in Phosphate Binder Therapy in ESRDQunibi, Wajeh Y.2015-03-03T07:53:53-08:00doi:10.1681/ASN.2015020135hwp:resource-id:jnephrol;26/10/2311American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologyanemia, phosphate binders, hemodialysisUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-10-01October 201510.1681/ASN.20150201351046-66731533-34502015-03-03T07:53:53-08:002015-10Journal of the American Society of NephrologyUp Front Matters2610102311257823132587
- Anti-phospholipase A2 Receptor Antibody and Immunosuppression in Membranous Nephropathy: More Evidence for Pathogenicity of Anti-phospholipase A2 Receptor Autoantibodies10.1681/ASN.2015020181Tue, 24 Mar 2015 08:34:31 GMT-07:00Anti-phospholipase A2 Receptor Antibody and Immunosuppression in Membranous Nephropathy: More Evidence for Pathogenicity of Anti-phospholipase A2 Receptor AutoantibodiesBrenchley, Paul E.C.2015-03-24T08:34:31-07:00doi:10.1681/ASN.2015020181hwp:resource-id:jnephrol;26/10/2308American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of Nephrologymembranous nephropathy, anti-PLA2R, rituximab, immunosuppressionUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-10-01October 201510.1681/ASN.20150201811046-66731533-34502015-03-24T08:34:31-07:002015-10Journal of the American Society of NephrologyUp Front Matters2610102308254523112558
- Exosomes to the Rescue10.1681/ASN.2015030254Tue, 21 Apr 2015 08:31:36 GMT-07:00Exosomes to the RescueRossol-Allison, JessicaWard, Christopher J.2015-04-21T08:31:36-07:00doi:10.1681/ASN.2015030254hwp:resource-id:jnephrol;26/10/2303American Society of NephrologyCopyright © 2015 by the American Society of NephrologyJournal of the American Society of NephrologyAKI, mesenchymal, stem cellsUp Front MattersEditorialsUp Front MattersEditorialseditorial20152015-10-01October 201510.1681/ASN.20150302541046-66731533-34502015-04-21T08:31:36-07:002015-10Journal of the American Society of NephrologyUp Front Matters2610102303234923042360
- Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD10.2215/CJN.03100315Tue, 07 Jul 2015 07:33:53 GMT-07:00Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKDPoesen, RubenRamezani, AliClaes, KathleenAugustijns, PatrickKuypers, DirkBarrows, Ian R.Muralidharan, JagadeesanEvenepoel, PieterMeijers, BjörnRaj, Dominic S.2015-07-07T07:33:53-07:00doi:10.2215/CJN.03100315hwp:resource-id:clinjasn;10/9/1525American Society of NephrologyCopyright © 2015 by the American Society of NephrologyClinical Journal of the American Society of Nephrologysoluble CD14, endotoxin, inflammation, microbiome, CKDOriginal ArticlesChronic Kidney DiseaseOriginal ArticlesChronic Kidney Diseaseresearch-article20152015-09-04September 04, 201510.2215/CJN.031003151555-90411555-905X2015-07-07T07:33:53-07:002015-09-04Clinical Journal of the American Society of NephrologyOriginal Articles10915251533